A Trial of Metformin in Individuals With Fragile X Syndrome

Science.gov (United States)

2018-04-10

Fragile X Syndrome; Fragile X Mental Retardation Syndrome; Mental Retardation, X Linked; Genetic Diseases, X-Linked; Trinucleotide Repeat Expansion; Fra(X) Syndrome; Intellectual Disability; FXS; Neurobehavioral Manifestations; Sex Chromosome Disorders

Cytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder

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Reddy Kavita S

2005-01-01

Full Text Available Abstract Background Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5–10 % of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. Methods Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH and/or molecular testing for fragile X syndrome by Southern and PCR methods. Results The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs abnormality was found in 14/421 [3.33 %] cases. The aberrations were: 4/14 [28%] supernumerary markers; 4/14 [28%] deletions; 1/14 [7%] duplication; 3/14 [21%] inversions; 2/14 [14%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 %] with an abnormal result. The mutations detected were: a full mutation (fM and abnormal methylation in 3 [43 %], mosaic mutations with partial methylation of variable clinical significance in 3 [43%] and a permutation carrier [14%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7%, FRAX 2–4%. Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. Conclusions Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23

Fragile X syndrome in two siblings with major congenital malformations

Energy Technology Data Exchange (ETDEWEB)

Giampietro, P.F.; Haas, B.R.; Lipper, E. [Cornell Univ. Medical Center, New York, NY (United States)] [and others

1996-05-17

We report on 2 brothers with both fragile X and VACTERL-H syndrome. The first sibling, age 5, had bilateral cleft lip and palate, ventricular septal defect, and a hypoplastic thumb. The second sibling, age 2{1/2}, had a trachesophageal fistula, esophageal atresia, and vertebral abnormality. High-resolution chromosome analysis showed a 46,XY chromosome constitution in both siblings. By PCR and Southern blot analysis, the siblings were found to have large triplet repeat expansions in the fragile X gene (FMR 1) and both had methylation mosaicism. Enzyme kinetic studies of iduronate sulfatase demonstrated a two-fold increase in activity in the first sib as compared to the second. Possible mechanisms through which the fragile X mutation can cause down-regulation of adjacent loci are discussed. 24 refs., 4 figs.

Autism Is Associated with the Fragile-X Syndrome.

Science.gov (United States)

Brown, W. Ted.; And Others

1982-01-01

The authors describe their methods for establishing the presence or absence of the fragile-X chromosome and discuss some of the clinical implications of their findings in relation to the clinical diagnosis of autism. (SW)

Ocular Motor Indicators of Executive Dysfunction in Fragile X and Turner Syndromes

Science.gov (United States)

Lasker, Adrian G.; Mazzocco, Michele M. M.; Zee, David S.

2007-01-01

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner…

Chromosomal abnormalities in a psychiatric population

Energy Technology Data Exchange (ETDEWEB)

Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

1995-02-27

Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

The Report on 2 Cases of Fragile X Syndrome Comorbid with Attention Deficit/Hyperactivity Disorder

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Katayoun Khoushabi

2000-07-01

Full Text Available The term “fragile X syndrome” is named after a constriction recognizable on chromosome (at Xq 27.3 cultured at chromosome media without folic acid. The unstable part includes repetition of 3 nucleotides which is intensified at subsequent generation (DNA amplification and gives rise to a more severe phenotype in the individual. About 20% of males have normal fragile X syndrome. The daughters of these individuals have abnormal chromosomes (carrier and their grandchildren will be marked. In typical syndrome, the boys will suffer from mental retardation, macrocephalia, large or protruding ears, elongated face, and macroorchidism. In terms of behavioral comorbidity, symptoms are similar to pervasive developmental disorder such as autism and attention deficit/hyperactivity disorder. The impairments in cognitive abilities are manifested as learning difficulties to severe problems. Our patients were 2 boys (6 and 7 years old referred due to their hyperactivity. In physical examination, attention deficit/hyperactivity disorder as well as fragile X syndrome were confirmed. In chromosome culture test, the constriction at Xq 27.3 was specified.

Fragile X founder effect and distribution of CGG repeats among the mentally retarded population of Andalusia, South Spain

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Yolanda de Diego

2002-01-01

Full Text Available Fragile X syndrome is the most common inherited form of mental retardation. We investigated the prevalence of the Fragile X syndrome in the population with mental retardation of unknown etiology in Andalusia, South Spain. We analyzed 322 unrelated patients (280 males and 42 females, and found a fragile X syndrome frequency of 6.5%. Among the non-fragile X chromosomes, the 29 CGG repeat was the most common allele. At the linked microsatellite DXS548 locus, we found a new allele which we called "allele 10" (17 CA. Similar to other south European populations, allele 2 (25 CA at the DXS548 locus and the fragile X allele were in linkage disequilibrium supporting the idea of a common founder chromosome predisposing to the CGG expansion.

Fragile X-associated tremor/ataxia syndrome.

Science.gov (United States)

Hoem, Gry; Koht, Jeanette

2017-10-31

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a hereditary neurodegenerative disorder caused by a mutation on the X chromosome. The major signs and symptoms are tremor, ataxia and parkinsonism. Up to one in 2 000 persons over 50 years of age will develop the syndrome. There is reason to believe that too few individuals in Norway undergo testing for this condition.

FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells

DEFF Research Database (Denmark)

Pentzold, Constanze; Shah, Shiraz Ali; Hansen, Niels Richard

2018-01-01

Common Chromosomal Fragile Sites (CFSs) are specific genomic regions prone to form breaks on metaphase chromosomes in response to replication stress. Moreover, CFSs are mutational hotspots in cancer genomes, showing that the mutational mechanisms that operate at CFSs are highly active in cancer c...

The Neuroanatomy and Neuroendocrinology of Fragile X Syndrome

Science.gov (United States)

Hessl, David; Rivera, Susan M.; Reiss, Allan L.

2004-01-01

Fragile X syndrome (FXS), caused by a single gene mutation on the X chromosome, offers a unique opportunity for investigation of gene-brain-behavior relationships. Recent advances in molecular genetics, human brain imaging, and behavioral studies have started to unravel the complex pathways leading to the cognitive, psychiatric, and physical…

Common chromosomal fragile sites (CFS) may be involved in normal and traumatic cognitive stress memory consolidation and altered nervous system immunity.

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Gericke, G S

2010-05-01

Previous reports of specific patterns of increased fragility at common chromosomal fragile sites (CFS) found in association with certain neurobehavioural disorders did not attract attention at the time due to a shift towards molecular approaches to delineate neuropsychiatric disorder candidate genes. Links with miRNA, altered methylation and the origin of copy number variation indicate that CFS region characteristics may be part of chromatinomic mechanisms that are increasingly linked with neuroplasticity and memory. Current reports of large-scale double-stranded DNA breaks in differentiating neurons and evidence of ongoing DNA demethylation of specific gene promoters in adult hippocampus may shed new light on the dynamic epigenetic changes that are increasingly appreciated as contributing to long-term memory consolidation. The expression of immune recombination activating genes in key stress-induced memory regions suggests the adoption by the brain of this ancient pattern recognition and memory system to establish a structural basis for long-term memory through controlled chromosomal breakage at highly specific genomic regions. It is furthermore considered that these mechanisms for management of epigenetic information related to stress memory could be linked, in some instances, with the transfer of the somatically acquired information to the germline. Here, rearranged sequences can be subjected to further selection and possible eventual retrotranscription to become part of the more stable coding machinery if proven to be crucial for survival and reproduction. While linkage of cognitive memory with stress and fear circuitry and memory establishment through structural DNA modification is proposed as a normal process, inappropriate activation of immune-like genomic rearrangement processes through traumatic stress memory may have the potential to lead to undesirable activation of neuro-inflammatory processes. These theories could have a significant impact on the

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

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Aisling Frizzell

2014-03-01

Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

Human Chromosome 7: DNA Sequence and Biology

OpenAIRE

Scherer, Stephen W.; Cheung, Joseph; MacDonald, Jeffrey R.; Osborne, Lucy R.; Nakabayashi, Kazuhiko; Herbrick, Jo-Anne; Carson, Andrew R.; Parker-Katiraee, Layla; Skaug, Jennifer; Khaja, Razi; Zhang, Junjun; Hudek, Alexander K.; Li, Martin; Haddad, May; Duggan, Gavin E.

2003-01-01

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate gene...

High chromosomal instability in workers occupationally exposed to solvents and paint removers.

Science.gov (United States)

Villalba-Campos, Mónica; Chuaire-Noack, Lilian; Sánchez-Corredor, Magda Carolina; Rondón-Lagos, Milena

2016-01-01

Painters are exposed to an extensive variety of harmful substances like aromatic hydrocarbons used as solvents and paint removers, some of which have shown clastogenic activity. These substances constitute a complex mixture of chemicals which contain well-known genotoxicants, such as Benzene, Toluene and Xylene. Thus, chronic occupational exposure to such substances may be considered to possess genotoxic risk. In Colombia the information available around the genotoxic damage (Chromosomal and DNA damage) in car paint shop workers is limited and the knowledge of this damage could contribute not only to a better understanding of the carcinogenic effect of this kind of substances but also could be used as biomarkers of occupational exposure to genotoxic agents. In this study, the genotoxic effect of aromatic hydrocarbons was assessed in peripheral blood lymphocytes of 24 workers occupationally exposed and 24 unexposed donors, by using Cytogenetic analysis and comet assay. A high frequency of Chromosomal alterations was found in the exposed group in comparison with those observed in the unexposed group. Among the total of CAs observed in the exposed group, fragilities were most frequently found (100 %), followed by chromosomal breaks (58 %), structural (41.2 %) and numerical chromosomal alterations (21 %). Numerical chromosomal alterations, fragilities and chromosomal breaks showed significant differences between exposed and unexposed groups. Among the fragilities, fra(9)(q12) was the most frequently observed. DNA damage index was also significantly higher in the exposed group compared to the unexposed group (p car paint shops workers and are also indicative of high chromosomal instability. The high frequency of both Chromosomal Alterations and DNA Damage Index observed in this study indicates an urgent need of intervention not only to prevent the increased risk of developing cancer but also to the application of strict health control and motivation to the use of

RTEL1 inhibits trinucleotide repeat expansions and fragility.

Science.gov (United States)

Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

2014-03-13

Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

Science.gov (United States)

Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

2014-01-01

The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

Molecular approach of the fragile chromosomal region Xq31-34 in cattle (Bos taurus by microdissection and DOP-PCR Aproximação molecular da região cromossômica frágil Xq31-34 em bovinos (Bos taurus utilizando microdissecação cromossômica e DOP-PCR

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S. Llambí

2008-08-01

Full Text Available Fragile sites (FS are chromosomal regions where the normal compactation of chromatine is not observed. FRAXA (Fra Xq27.3, X sexual chromosome is one of the most studied FS in humans. FRAXA is an expansion of the trinucleotide CGG located in the gene FMR-1. In cattle, sites of chromosomal fragility were reported in BTAX, associated with different pathologies and fertility impairment. Chromosomal microdissection has became a valuable tool for isolating chromatine fragments. In this work, it was combined the chromosomal microdissection technique with DOP-PCR in order to carry out a molecular analysis of the fragile chromosomal region BTAXq31-34. In that region, polymorphic DNA-RAPD sequences (GC rich are present and sequences of the gene FMR-1 are missing. The results showed the usefulness of the microdissection-DOP-PCR technique for molecular characterization of fragile chromosomal sites in cattle.Os sítios frágeis (FS são regiões de cromossomo onde a compactação normal da cromatina não é realizada. O FRAXA (Fra Xq27.3, cromossomo sexual X é um dos FS mais estudados em seres humanos. O FRAXA apresenta expansão do trinucleotídeo CGG localizado no gene FMR-1. Em bovinos, existem estudos informando sobre fragilidade cromossômica em BTAX associada com diversas patologias e alterações na fertilidade. A microdissecação cromossômica é uma valiosa técnica para isolar fragmentos de cromatina. Neste trabalho, combinou-se a técnica de microdissecação de cromossomo com DOP-PCR para executar a análise molecular da região do sitio frágil cromossômico BTAXq31-34. Naquela região estão presentes seqüências do polimorfo DNA-RAPD (rico em GC, em que as seqüências do gene FMR-1 estão ausentes. Os resultados mostram a utilidade da técnica de microdissecação-DOP-PCR para a caracterização molecular de sítios frágeis cromossômicos em bovinos.

Screening Children with Autism for Fragile-X Syndrome and Phenylketonuria. Brief Report.

Science.gov (United States)

Pueschel, Siegfried M.; And Others

1985-01-01

Family histories, comprehensive physical examinations, and chromosome analyses of 35 males with autism were performed. Results indicated that the fragile X syndrome may be present in less than 16 percent of persons whose family history or physical features suggest the condition's possible presence. Screening 42 autistic children for…

EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders

Science.gov (United States)

Biancalana, Valérie; Glaeser, Dieter; McQuaid, Shirley; Steinbach, Peter

2015-01-01

Different mutations occurring in the unstable CGG repeat in 5' untranslated region of FMR1 gene are responsible for three fragile X-associated disorders. An expansion of over ∼200 CGG repeats when associated with abnormal methylation and inactivation of the promoter is the mutation termed ‘full mutation' and is responsible for fragile X syndrome (FXS), a neurodevelopmental disorder described as the most common cause of inherited intellectual impairment. The term ‘abnormal methylation' is used here to distinguish the DNA methylation induced by the expanded repeat from the ‘normal methylation' occurring on the inactive X chromosomes in females with normal, premutation, and full mutation alleles. All male and roughly half of the female full mutation carriers have FXS. Another anomaly termed ‘premutation' is characterized by the presence of 55 to ∼200 CGGs without abnormal methylation, and is the cause of two other diseases with incomplete penetrance. One is fragile X-associated primary ovarian insufficiency (FXPOI), which is characterized by a large spectrum of ovarian dysfunction phenotypes and possible early menopause as the end stage. The other is fragile X-associated tremor/ataxia syndrome (FXTAS), which is a late onset neurodegenerative disorder affecting males and females. Because of the particular pattern and transmission of the CGG repeat, appropriate molecular testing and reporting is very important for the optimal genetic counselling in the three fragile X-associated disorders. Here, we describe best practice guidelines for genetic analysis and reporting in FXS, FXPOI, and FXTAS, including carrier and prenatal testing. PMID:25227148

Prevalence of carriers of premutation-size alleles of the FMR1 gene-and implications for the population genetics of the fragile X syndrome

Energy Technology Data Exchange (ETDEWEB)

Rousseau, F.; Rouillard, P.; Morel, M.L. [Universite Laval, Quebec City (Canada)] [and others

1995-11-01

The fragile X syndrome is the second leading cause of mental retardation after Down syndrome. Fragile X premutations are not associated with any clinical phenotype but are at high risk of expanding to full mutations causing the disease when they are transmitted by a carrier woman. There is no reliable estimate of the prevalence of women who are carriers of fragile X premutations. We have screened 10,624 unselected women by Southern blot for the presence of FMR1 premutation alleles and have confirmed their size by PCR analysis. We found 41 carriers of alleles with 55-101 CGG repeats, a prevalence of 1/259 women (95% confidence interval 1/373-1/198). Thirty percent of these alleles carry an inferred haplotype that corresponds to the most frequent haplotype found in fragile X males and may indeed constitute premutations associated with a significant risk of expansion on transmission by carrier women. We identified another inferred haplotype that is rare in both normal and fragile X chromosomes but that is present on 13 (57%) of 23 chromosomes carrying FMR1 alleles with 53-64 CGG repeats. This suggests either (1) that this haplotype may be stable or (2) that the associated premutation-size alleles have not yet reached equilibrium in this population and that the incidence of fragile X syndrome may increase in the future. 42 refs., 3 figs., 4 tabs.

Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

Science.gov (United States)

Collins, D T; Mannina, E M; Mendonca, M

2015-10-01

Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed. © 2015 Wiley Periodicals, Inc.

Effects of hyperoxia and caffeine on the expression of fragile site at Xq27.3

Energy Technology Data Exchange (ETDEWEB)

Rafi, S.K.; Surana, R.B.; Christopher, K.L. [Armed Forces Institute of Pathology, Washington, DC (United States)] [and others

1996-02-02

To enhance the cytogenetic expression of the fragile X chromosome, we studied the effects of hyperoxia and caffeine on the induction of fragile Xq27.3. A lymphoblastoid cell line (GM 06912) derived from a fragile X male proband was cultured in RPMI 1640 containing 16% dialyzed fetal calf serum. The cells were synchronously subjected to one of 3 different atmospheric oxygen tensions (21%, 21.3 kPa, hyperoxic) during the last 24 hours of the 72 hour culture, immediately after the addition of 2{prime}-deoxy-5-fluorouridine (FUdR) at 25 ng/ml. To study the enhancing effect of caffeine, with or without hyperoxia, a second set of cultures was additionally subjected to caffeine (2.5 mM) during the last 6 hours of the culture. When the fragility of hyperoxic cells (38.1 kPa dissolved oxygen) was compared to that of normoxic control cells (13.3 kPa dissolved oxygen), the difference was significant (P < 0.05). These data suggest that there is a mean increase in the fragile Xq27.3 expressivity as the dissolved oxygen tension increases. Additionally, we observed that caffeine, with or without hyperoxia, significantly (P <0.05) suppressed the expression of the fragile X site in this lymphoblastoid cell line. 34 refs., 2 tabs.

Abnormalities of chromosome No. 1: significance in malignant transformation

Energy Technology Data Exchange (ETDEWEB)

Rowley, J D

1978-01-01

Studies of human hematologic malignancies have provided sufficient data not only for the identification of nonrandom abnormalities of whole chromosomes, but also for determination of the specific chromosome regions involved. In clonal aberrations leading to an excess of chromosome No. 1, or a partial excess of No. 1, trisomy for bands 1q25 to 1q32 was noted in the myeloid cells obtained from every one of 35 patients who had various disorders, such as acute leukemia, polycythemia vera, or myelofibrosis. Similar chromosome changes were a consistent finding in various solid tumors as well. This rearrangement was not the result of a particularly fragile site in that region of the chromosome, since the break points in reciprocal translocations that involve No. 1 occurred almost exclusively in the short arm. The nonrandom chromosome changes found in neoplastic cells can now be correlated with the gene loci on these chromosomes or chromosome segments as an attempt is made to identify specific genes that might be related to malignancy.

Cytogenetic evaluation of chromosomal disorders in Down Syndrome

International Nuclear Information System (INIS)

Shafik, H.M.

1987-01-01

Down Syndrome (DS) patients are at high risk to develop leukemia. They are also highly sensitive to the induction of chromosomal aberrations when their GO lymphocytes are irradiated in vitro. The objective of this study was to further investigate the differential radiosensitivity of DS lymphocytes at the different stages of the cell cycle, as damage to proliferating cells is more relevant to health problems than damage to non-dividing cells. In addition, the proliferation kinetics and stage of differentiation of circulating DS lymphocytes was studied in an attempt to understand the mechanism for the enhanced chromosomal radiosensitivity. Moreover, the x-ray induced specific chromosomal breakpoints were identified and correlated with the locations of oncogene and fragile sites in order to investigate cytogenetically the early stages of leukemogenesis

Fragile X syndrome and fragile X-associated tremor ataxia syndrome.

Science.gov (United States)

Hall, Deborah A; Berry-Kravis, Elizabeth

2018-01-01

Fragile X-associated disorders encompass several conditions, which are caused by expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or >200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures. Fragile X-associated tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy. Fragile X-associated primary ovarian insufficiency also occurs in premutation carrier women and manifests with infertility and early menopause. The diseases constituting fragile X-associated disorders differ mechanistically, due to the distinct molecular properties of premutation versus full mutations. Fragile X syndrome occurs when there is a lack of fragile X mental retardation protein (FMRP) due to FMR1 methylation and silencing. In fragile X-associated tremor ataxia syndrome, a toxic gain of function is postulated with the production of excess CGG repeat-containing FMR1 mRNA, abnormal translation of the repeat sequence leading to production of polyglycine, polyalanine, and other polypeptides and to outright deficits in translation leading to reduced FMRP at larger premutation sizes. The changes in underlying brain chemistry due to FMR1 mutations have led to therapeutic studies in these disorders, with some progress being made in fragile X syndrome. This paper also summarizes indications for testing, genetic counseling issues, and what the future holds for these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Deletion of PTEN Produces Deficits in Conditioned Fear and Increases Fragile X Mental Retardation Protein

Science.gov (United States)

Lugo, Joaquin N.; Smith, Gregory D.; Morrison, Jessica B.; White, Jessika

2013-01-01

The phosphatase and tensin homolog detected on chromosome 10 (PTEN) gene product modulates activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. The PI3K pathway has been found to be involved in the regulation of the fragile X mental retardation protein, which is important for long-term depression and in the formation of new…

Equipment fragility testing

International Nuclear Information System (INIS)

Holman, G.S.; Chou, C.K.; Cummings, G.E.

1985-01-01

Current probabilistic risk assessment (PRA) methods for nuclear power plants utilize component fragilities which are for the most part based on a limited data base and engineering judgement. The seismic design of components is based on code limits and NRC requirements that do not reflect the actual capacity of a component to resist failure. In order to improve the present component fragility data base and establish component seismic design margins, the NRC has commissioned a projected three-year program to compile existing fragilities data and at the same time independently perform fragilities tests on selected mechanical and electrical components. This paper presents the planning and technical approach being taken by LLNL in the NRC Component Fragility Program

A Female Patient with FMR1 Premutation and Mosaic X Chromosome Aneuploidy and Two Sons with Intellectual Disability.

Science.gov (United States)

Galanina, Ekaterina M; Tulupov, Andrey A; Lemskaya, Natalya A; Korostyshevskaya, Aleksandra M; Maksimova, Yuliya V; Shorina, Asia R; Savelov, Andrey A; Sergeeva, Irina G; Isanova, Evgeniya R; Grishchenko, Irina V; Yudkin, Dmitry V

2017-03-01

In this report, we describe a molecular cytogenetic study of a family burdened with intellectual disability (ID) and suicide. Our study revealed that the mother has a heterozygous premutation in the FMR1 gene and supernumerary X chromosomes as well as X-derived marker chromosomes. Both of her sons have ID and a normal chromosome number. One of the sons has fragile X syndrome, and the other has ID of an unclear nature.

A clinical study of mentally retarded children with fragile X syndrome inSaudi Arabia

International Nuclear Information System (INIS)

Al-Husain, M.; Salih, Mustafa A.M.; Zaki, Osama K.; Al-Othman, L.; Al-Nasser, Mohammed N.

2000-01-01

Studies on fragile X syndrome are scarce in Saudi Arabia and othercountries of the Arabian Peninsula. The few studies previously done haveeither been in the form of case reports or those performed oninstitutionalized mentally retarded patients. The aim of this study was todetermine the prevalence of fragile X syndrome among cases with mentalretardation who have been referred to the pediatric neurology clinics of KingKhalid University Hospital (KKUH) in Riyadh. Cytogenetic studies wereperformed in 94 cases that were referred to the pediatric neurology clinicsof KKUH because of mental retardation and/or delayed milestones ofdevelopment, from July 1995 to December 1997. Six male probands (6.4%) showedthe classic fragile X chromosome and another six (including a four year oldgirl) were detected, following extension of the cytogenetic studies to all 32first-degree relatives. Affection of more than one sibling was ascertained infour families. One family had four brothers with fragile X syndrome, whereasanother formed part of a large kindred with twelve males and five females whowere mentally retarded. A clinical, physical and psychological screeningchecklist was applied to the eleven affected males. Large testicular size,long face and short attention span were the most frequent features and eachwas detected in nine patients (82%). Pes planus and history of delayed speechwere found in eight patients (73%). The study showed that the fragile Xsyndrome clinical screening checklist has been applied in other populationsmight equally valuable and applicable among the population of Saudi Arabia.However, the presence of pale blue eyes can be excluded and more weight givento positive family history of mental to the most common clinical diagnosticfeatures of fragile X syndrome. (author)

Differential effects of treatment with UV-light (365 nm) and 8-methoxypsoralen on chromosomes of healthy persons and psoriatic patients

International Nuclear Information System (INIS)

Loeber, G.; Kittler, L.

1986-01-01

The effect of 8-methoxypsoralen (8-MOP, 5 x 10 -5 M), near UV-light of 365 nm wavelength (UVA, 1.5 J/cm 2 ) and the combination of both (PUVA treatment) were studied on lymphocytes in vitro taken from healthy persons and patients with psoriasis vulgaris and psoriasis arthritis (psoriasis arthropathica). Chromosomes isolated from cell nuclei were visualized by means of Giemsa staining technique and analyzed for induction of chromosomal defects, i.e. premature centromere division (PCD), major coiling (MC), and formation of gaps and fragile sites. Exposure of nonpsoriatic lymphocytes to 8-MOP, UVA or PUVA increased the rate of PCD or MC generation. In experiments with psoriatic lymphocytes a much weaker effect was found, with a moderate increase of PCD and MC after UVA or PUVA treatment in the case of psoriasis vulgaris, and of MC after UVA treatment of psoriasis arthritis. On the average the number of chromosomes per metaphase plate displaying PCD did not exceed 10. No indication was obtained for the preference of certain chromosome groups or the appearance of 'fragile sites'. Under all experimental conditions the number of chromosome gaps ranged in the order of their spontaneous induction. The findings suggest PCD and MC investigations as possible sensitive tools for diagnosing latent psoriasis and for refined analysis of psoriatic cells or chromosomes. (author)

Seismic fragility of nuclear power plant components (Phase 2): A fragility handbook on eighteen components

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.; Kassir, M.K.; Shteyngart, S.

1991-06-01

Fragility estimates of seven equipment classes were published in earlier reports. This report presents fragility analysis results from eleven additional equipment categories. The fragility levels are expressed in probabilistic terms. For users' convenience, this concluding report includes a summary of fragility results of all eighteen equipment classes. A set of conversion factors based on judgment is recommended for use of the information for early vintage equipment. The knowledge gained in conducting the Component Fragility Program and similar other programs is expected to provide a new direction for seismic verification and qualification of equipment. 15 refs., 12 tabs

Distribution of X-ray-induced chromosome breakpoints in Down syndrome lymphocytes

International Nuclear Information System (INIS)

Shafik, H.M.; Au, W.W.; Whorton, E.B. Jr.; Legator, M.S.

1990-01-01

Down syndrome (DS) individuals are known to be predisposed to develop leukemia and their lymphocytes are highly sensitive to the induction of chromosome aberrations by X-rays. A study was conducted to identify the chromosome breakpoints and to evaluate whether site specificity for chromosome breakage and rearrangement may exist which may explain the predisposition phenomenon. DS lymphocytes at the G1 phase of the cell cycle were irradiated with 300, 450, and 600 rad of X-rays. Cells were harvested after 3 days in culture and 193 G-banded karyotypes were analyzed to identify the induced chromosome abnormalities. Out of 273 breakpoints identified, 122 were involved in the formation of stable chromosome rearrangements and 151 in the formation of unstable abnormalities. The Poisson analysis of these breakpoints demonstrated that 16 chromosome bands located in chromosomes 1, 3, 7, 12, 17, 19 and X were preferentially involved in breakage and rearrangement (P less than 0.05). These 16 bands are also found to be locations of cancer breakpoints, oncogenes, or fragile sites. Many abnormal cells were observed to carry stable chromosome rearrangements only. Therefore, these cells are presumed to be compatible with survival and to be initiated in the transformation process. We propose that similar stable and site-specific chromosome rearrangements may exist in proliferating cells in DS individuals after exposure to clastogens and that this abnormality predisposes them to develop leukemia

Location of a High-Lysine Gene and the DDT-Resistance Gene on Barley Chromosome 7

DEFF Research Database (Denmark)

Jensen, J.

1979-01-01

mutants, nos 1508.18, and 19. Linkage studies with translocations locate the Lys3 locus in the centromere region ofchromosome 7. A linkage study involving the loci lys3 and ddt (resistance to DDT) together with the marker locifi (fragile stem), s(short rachilla hairs), and r (smooth awn) show...... that the order of the five loci on chromosome 7 from the long to the short chromosome arm is Y, s,fi, lys3, ddt. The distance from locus I to locus ddt is about 100 centimorgans....

Fragile X-associated tremor/ataxia syndrome: another phenotype of the fragile X gene.

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Hessl, David; Grigsby, Jim

2016-08-01

Neuropsychologists have an important role in evaluating patients with fragile X-associated disorders, but most practitioners are unaware of the recently identified neurodegenerative movement disorder known as fragile X-associated tremor ataxia syndrome (FXTAS). The objective of this editorial is to orient the reader to FXTAS and highlight the importance of clinical neuropsychology in describing the fragile X premutation phenotype and the role practitioners may have in assessing and monitoring patients with or at risk for neurodegeneration. We issued a call for papers for the special issue, highlighting the primary objective of familiarizing clinical neuropsychologists with FXTAS, and with the neuropsychological phenotype of both male and female asymptomatic carriers. Eight papers are included, including an overview of the fragile X-associated disorders (Grigsby), a review of the neuroradiological and neurological aspects of FXTAS and how the disorder compares to other movement disorders (O'Keefe et al.), a perspective on the prominence of white matter disease and dementia in FXTAS (Filley), and a review of mouse models of FXTAS (Foote). There are four research papers, including one on self-reported memory problems in FXTAS (Birch et al.), and three papers focused on the neuropsychiatric aspects of the fragile X premutation, a review (Bourgeois), an examination of autism-related traits (Schneider), and a research paper on executive functioning and psychopathology (Grigsby). The issue highlights the importance of awareness of fragile X-associated disorders for neuropsychologists, an awareness that must reach beyond neurodevelopmental aspects related to fragile X syndrome into the realm of neurodegenerative disease and aging.

Diagnostic Yield of Chromosomal Microarray Analysis in an Autism Primary Care Practice: Which Guidelines to Implement?

Science.gov (United States)

McGrew, Susan G.; Peters, Brittany R.; Crittendon, Julie A.; Veenstra-VanderWeele, Jeremy

2012-01-01

Genetic testing is recommended for patients with ASD; however specific recommendations vary by specialty. American Academy of Pediatrics and American Academy of Neurology guidelines recommend G-banded karyotype and Fragile X DNA. The American College of Medical Genetics recommends Chromosomal Microarray Analysis (CMA). We determined the yield of…

Role of the diet in ontogenesis and induction of chromosomal aberrations in population living in the area exposed to radioactive contamination

International Nuclear Information System (INIS)

Ilyinskikh, N.N.; Ilyinskikh, I.N.; Ilyinskikh, E.N.; Semenov, A.G.; Kozlova, S.B.

2005-01-01

The objective of this work is to investigate a role of diet in oncogenesis and induction of chromosomal aberrations in fragility sites in the peripheral blood lymphocytes of people in some areas exposed to radionuclides as a result of an accident in the Siberian Chemical Combine (SCP). The purpose of the present study was to investigate the level of aberrations at fragile sites of chromosomes in peripheral blood lymphocytes of population residing area contaminated with radionuclides following an accident at the Siberian Chemical Plant (SCP). We carried out micronucleus test to screen people with radiation-related cytogenetic effects. Of 1246 examined inhabitants of Samus settlement, 148 showed significantly increased frequency of micronucleated erythrocytes and were selected for chromosome analysis as a radiation-exposed group. Additional analysis was carried out for 40 patients with gastric cancer and atrophic gastritis with stage II-III epithelial dysplasia. Eighty six individuals from non-contaminated area were used as a control group. Chromosomal breaks and exchanges occurred preferentially in chromosomes 3 and 6 among radiation-exposed persons and patients. The regions 3pl4-3p25 and 6p23 were damaged most often. There was a tendency towards preferential involvement at q21-q25 of chromosome 6 in patients with gastric cancer and atrophic gastritis. Specific damage at certain chromosome sites was observed in radiation-exposed population as well as in patients with gastric cancer. Most often this damage was located near oncogene loci which could imply that chromosome damage induced by radiation is likely to be a predisposing factor to the expression of oncogenes and malignant transformation of cells in exposed individuals. (author)

Axonal neuropathy in female carriers of the fragile X premutation with fragile x-associated tremor ataxia syndrome.

Science.gov (United States)

Ram, Suresh; Devapriya, Inoka A; Fenton, Grace; Mcvay, Lindsey; Nguyen, Danh V; Tassone, Flora; Maselli, Ricardo A; Hagerman, Randi J

2015-08-01

In this study we examined whether females with the fragile X-associated tremor ataxia syndrome (FXTAS) and non-FXTAS premutation carriers have electrophysiological signs of underlying peripheral neuropathy. Nerve conduction studies (NCS) were performed on 19 women with FXTAS, 20 non-FXTAS carriers, and 26 age-matched controls. The results were compared with existing data on corresponding male carriers. Women with FXTAS and non-FXTAS carriers had reduced sensory nerve action potential amplitudes. Also, there was a strong trend for reduced compound muscle action potential amplitudes in women with FXTAS, but not in non-FXTAS carriers. No significant slowing of nerve conduction velocities, prolongation of F-wave latencies, or associations with molecular measures was observed. This study suggests an underlying axonal neuropathy in women with FXTAS. However, in comparison to men with FXTAS, the NCS abnormalities in women were less severe, possibly due to the effect of a normal X chromosome. © 2014 Wiley Periodicals, Inc.

Formation of radiation induced chromosome aberrations: involvement of telomeric sequences and telomerase

International Nuclear Information System (INIS)

Pirzio, L.

2004-07-01

As telomeres are crucial for chromosome integrity; we investigated the role played by telomeric sequences in the formation and in the transmission of radio-induced chromosome rearrangements in human cells. Starting from interstitial telomeric sequences (ITS) as putative region of breakage, we showed that the radiation sensitivity is not equally distributed along chromosomes and. is not affected by ITS. On the contrary, plasmid integration sites are prone to radio-induced breaks, suggesting a possible integration at sites already characterized by fragility. However plasmids do not preferentially insert at radio-induced breaks in human cells immortalized by telomerase. These cells showed remarkable karyotype stability even after irradiation, suggesting a role of telomerase in the genome maintenance despite functional telomeres. Finally, we showed that the presence of more breaks in a cell favors the repair, leading to an increase of transmissible rearrangements. (author)

Genetics Home Reference: fragile X syndrome

Science.gov (United States)

... Facebook Twitter Home Health Conditions Fragile X syndrome Fragile X syndrome Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Fragile X syndrome is a genetic condition that causes a ...

Altered structural brain connectome in young adult fragile X premutation carriers.

Science.gov (United States)

Leow, Alex; Harvey, Danielle; Goodrich-Hunsaker, Naomi J; Gadelkarim, Johnson; Kumar, Anand; Zhan, Liang; Rivera, Susan M; Simon, Tony J

2014-09-01

Fragile X premutation carriers (fXPC) are characterized by 55-200 CGG trinucleotide repeats in the 5' untranslated region on the Xq27.3 site of the X chromosome. Clinically, they are associated with the fragile X-Associated Tremor/Ataxia Syndrome, a late-onset neurodegenerative disorder with diffuse white matter neuropathology. Here, we conducted first-ever graph theoretical network analyses in fXPCs using 30-direction diffusion-weighted magnetic resonance images acquired from 42 healthy controls aged 18-44 years (HC; 22 male and 20 female) and 46 fXPCs (16 male and 30 female). Globally, we found no differences between the fXPCs and HCs within each gender for all global graph theoretical measures. In male fXPCs, global efficiency was significantly negatively associated with the number of CGG repeats. For nodal measures, significant group differences were found between male fXPCs and male HCs in the right fusiform and the right ventral diencephalon (for nodal efficiency), and in the left hippocampus [for nodal clustering coefficient (CC)]. In female fXPCs, CC in the left superior parietal cortex correlated with counting performance in an enumeration task. Copyright © 2014 Wiley Periodicals, Inc.

Systems fragility: The sociology of chaos.

Science.gov (United States)

Hodges, Lori R

2016-01-01

This article examines the concept of community fragility in emergency management from a systems perspective. Using literature that addresses fragility in four areas of complex systems, including ecosystems, social systems, sociotechnical systems, and complex adaptive systems, a theoretical framework focused on the emergency management field is created. These findings illustrate how community fragility factors can be used in the emergency management field to not only improve overall outcomes after disaster but also build less fragile systems and communities in preparation for future disasters.

Neighborhood Disadvantage and Telomere Length: Results from the Fragile Families Study

Directory of Open Access Journals (Sweden)

Douglas S. Massey

2018-04-01

Full Text Available Telomeres are repetitive nucleotide sequences located at the ends of chromosomes that protect genetic material. We use data from the Fragile Families and Child Wellbeing Study to analyze the relationship between exposure to spatially concentrated disadvantage and telomere length for white and black mothers. We find that neighborhood disadvantage is associated with shorter telomere length for mothers of both races. This finding highlights a potential mechanism through which the unique spatially concentrated disadvantage faced by African Americans contributes to racial health disparities. We conclude that equalizing the health and socioeconomic status of black and white Americans will be very difficult without reducing levels of residential segregation in the United States.

Fragile X syndrome and fragile X-associated disorders [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Akash Rajaratnam

2017-12-01

Full Text Available Fragile X syndrome (FXS is caused by a full mutation on the FMR1 gene and a subsequent lack of FMRP, the protein product of FMR1. FMRP plays a key role in regulating the translation of many proteins involved in maintaining neuronal synaptic connections; its deficiency may result in a range of intellectual disabilities, social deficits, psychiatric problems, and dysmorphic physical features. A range of clinical involvement is also associated with the FMR1 premutation, including fragile X-associated tremor ataxia syndrome, fragile X-associated primary ovarian insufficiency, psychiatric problems, hypertension, migraines, and autoimmune problems. Over the past few years, there have been a number of advances in our knowledge of FXS and fragile X-associated disorders, and each of these advances offers significant clinical implications. Among these developments are a better understanding of the clinical impact of the phenomenon known as mosaicism, the revelation that various types of mutations can cause FXS, and improvements in treatment for FXS.

Three Faces of Fragile X.

Science.gov (United States)

Lieb-Lundell, Cornelia C E

2016-11-01

Fragile X syndrome (FXS) is the first of 3 syndromes identified as a health condition related to fragile X mental retardation (FMR1) gene dysfunction. The other 2 syndromes are fragile X-associated primary ovarian insufficiency syndrome (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS), which together are referred to as fragile X-associated disorders (FXDs). Collectively, this group comprises the 3 faces of fragile X. Even though the 3 conditions share a common genetic defect, each one is a separate health condition that results in a variety of body function impairments such as motor delay, musculoskeletal issues related to low muscle tone, coordination limitations, ataxia, tremor, undefined muscle aches and pains, and, for FXTAS, a late-onset neurodegeneration. Although each FXD condition may benefit from physical therapy intervention, available evidence as to the efficacy of intervention appropriate to FXDs is lacking. This perspective article will discuss the genetic basis of FMR1 gene dysfunction and describe health conditions related to this mutation, which have a range of expressions within a family. Physical therapy concerns and possible assessment and intervention strategies will be introduced. Understanding the intergenerational effect of the FMR1 mutation with potential life-span expression is a key component to identifying and treating the health conditions related to this specific genetic condition. © 2016 American Physical Therapy Association.

Chromosomes of older humans are more prone to aminopterine-induced breakage

International Nuclear Information System (INIS)

Esposito, D.; Fassina, G.; Szabo, P.; Weksler, M.; De Angelis, P.; Siniscalco, M.; Rodgers, L.

1989-01-01

The authors have adopted a simplified version of the cell hybrid cotransfer method to test the hypothesis that human lymphocytes derived from elderly individuals have a higher chromosome instability. Peripheral blood lymphocytes from old male individuals and young controls were fused with a Chinese hamster cell line (CHO-YH21), yielding 10 HAT-resistant rodent-human clones from the old propositi and 22 from the young controls. Both series of hybrid clones were analyzed with respect to the retention of the enzyme glucose-6-phosphate dehydrogenase and the surface antigen MIC2 identified by monoclonal antibody 12E7, two human X chromosome-linked markers located at opposite ends of the X chromosome. Cell hybrid clones with an X chromosome from a young control retained both markers in about 70% of the cells. In contrast, cell hybrid clones with an X chromosome from an old donor retained the MIC2 marker in only 30% of their cells. Slot-blot hybridization studies have established that the observed loss of the MIC2 marker is due to loss of the coding gene, not to suppression of its expression. T lymphocytes from old donors were also found to have an LD 50 for aminopterine significantly lower than the concentration of this drug in the HAT medium used to grow the hybrids. They speculate that the higher rate of chromosomal breakage and of marker loss observed along the old-age X chromosomes could be the result of molecular scars accumulated with aging at sites of constitutive chromosomal fragility

Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile X syndrome reveals limited, call type specific deficits.

Directory of Open Access Journals (Sweden)

Snigdha Roy

Full Text Available Fragile X syndrome (FXS is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1 gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP. Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.

Inhibition of colorectal cancer genomic copy number alterations and chromosomal fragile site tumor suppressor FHIT and WWOX deletions by DNA mismatch repair

Science.gov (United States)

Gelincik, Ozkan; Blecua, Pedro; Edelmann, Winfried; Kucherlapati, Raju; Zhou, Kathy; Jasin, Maria; Gümüş, Zeynep H.; Lipkin, Steven M.

2017-01-01

Homologous recombination (HR) enables precise DNA repair after DNA double strand breaks (DSBs) using identical sequence templates, whereas homeologous recombination (HeR) uses only partially homologous sequences. Homeologous recombination introduces mutations through gene conversion and genomic deletions through single-strand annealing (SSA). DNA mismatch repair (MMR) inhibits HeR, but the roles of mammalian MMR MutL homologues (MLH1, PMS2 and MLH3) proteins in HeR suppression are poorly characterized. Here, we demonstrate that mouse embryonic fibroblasts (MEFs) carrying Mlh1, Pms2, and Mlh3 mutations have higher HeR rates, by using 7,863 uniquely mapping paired direct repeat sequences (DRs) in the mouse genome as endogenous gene conversion and SSA reporters. Additionally, when DSBs are induced by gamma-radiation, Mlh1, Pms2 and Mlh3 mutant MEFs have higher DR copy number alterations (CNAs), including DR CNA hotspots previously identified in mouse MMR-deficient colorectal cancer (dMMR CRC). Analysis of The Cancer Genome Atlas CRC data revealed that dMMR CRCs have higher genome-wide DR HeR rates than MMR proficient CRCs, and that dMMR CRCs have deletion hotspots in tumor suppressors FHIT/WWOX at chromosomal fragile sites FRA3B and FRA16D (which have elevated DSB rates) flanked by paired homologous DRs and inverted repeats (IR). Overall, these data provide novel insights into the MMR-dependent HeR inhibition mechanism and its role in tumor suppression. PMID:29069730

Chromosomal radiosensitivity of prostate cancer patients

International Nuclear Information System (INIS)

McRobbie, M.L.; Riches, A.; Baxby, K.

2003-01-01

Full text: Radiosensitivity of peripheral blood lymphocytes from prostate cancer patients is being investigated using the G2 assay and the Cytokinesis Block Micronucleus(CBMN)assay. The G2 assay evaluates chromosomal damage caused by irradiating cells in the G2 phase of the cell cycle. The CBMN assay quantifies the post mitotic micronuclei, which are the expression of damage incurred during G0. An association between hypersensitivity to the chromosome damaging effects of ionising radiation and cancer predispostion has been demonstrated in a number of heritable conditions by using the aforementioned techniques. Recently, increased chromosomal radiosensitivity has been demonstrated in a significant proportion of patients with no obvious family history of malignancy. The aim of this study is to establish whether a group of prostatic carcinoma patients exists and if so whether there are any correlations between their G2 and G0 sensitivities. The study has shown there is no correlation between G2 and G0 sensitivity, confirming the general trend that individuals exhibiting chromosomal radiosensitivity are defective in only one mechanism and G2 and G0 sensitivity are largely independent. Current data indicates that there is an identifiable group of men within the prostate cancer population with increased chromosomal radiosensitivity. Using the G2 assay and the 90th percentile of the controls as a cut off point for sensitivity, no significant difference between the controls and the patient population has been found. However, using the CBMN assay and again the 90th percentile, approximately 11% of the control group are sensitive compared with approximately 40% of the carcinoma cases. The implications of this increased radiosensitivity are as yet unclear, but it is indicative of increased chromosomal fragility and therefore, possibly associated with malignant transformation. Hence, it may prove a useful tool in identifying individuals at increased risk of developing

Flooding Fragility Experiments and Prediction

Energy Technology Data Exchange (ETDEWEB)

Smith, Curtis L. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Tahhan, Antonio [Idaho National Lab. (INL), Idaho Falls, ID (United States); Muchmore, Cody [Idaho National Lab. (INL), Idaho Falls, ID (United States); Nichols, Larinda [Idaho National Lab. (INL), Idaho Falls, ID (United States); Bhandari, Bishwo [Idaho National Lab. (INL), Idaho Falls, ID (United States); Pope, Chad [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2016-09-01

This report describes the work that has been performed on flooding fragility, both the experimental tests being carried out and the probabilistic fragility predictive models being produced in order to use the text results. Flooding experiments involving full-scale doors have commenced in the Portal Evaluation Tank. The goal of these experiments is to develop a full-scale component flooding experiment protocol and to acquire data that can be used to create Bayesian regression models representing the fragility of these components. This work is in support of the Risk-Informed Safety Margin Characterization (RISMC) Pathway external hazards evaluation research and development.

Mechanisms of telomere loss and their consequences for chromosome instability

International Nuclear Information System (INIS)

Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P.

2012-01-01

The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Mechanisms of telomere loss and their consequences for chromosome instability

Directory of Open Access Journals (Sweden)

Keiko eMuraki

2012-10-01

Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Mechanisms of telomere loss and their consequences for chromosome instability

Energy Technology Data Exchange (ETDEWEB)

Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA (United States)

2012-10-04

The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.

Investigation of X-ray-induced chromosome aberrations in 'preleukaemic' mammalian cells

International Nuclear Information System (INIS)

Szollar, J.

1977-01-01

A study was done on the frequency of numerical and structural aberrations induced by different doses of X-ray irradiation in spontaneously leukaemic AKR mice, compared with the values of healthy control CBA/H-T 6 T 6 mice. Both were irradiated under the same conditions, but their chromosomes were affected in a different way. The number of cells containing aneuploid sets, rings, fragments, or metacentric chromosomes was significantly higher in the 2-month-old AKR mice than in the control CBA group. The increased chromosomal fragility found in AKR bone marrow cells 5-7 months before the manifestation of lymphoid leukaemia might be an important factor in the development of malignant condition. This genetic imbalance could provide a possible reason for an increase of spontaneous malfunction of the cellular system, as well as for an increased sensitivity to external factors. Thus it might be connected directly with the predisposition to malignant growth, or it has an indirect role helping virus activation, or acting together with the immune deficiency, by creating a weaker system that is more sensitive to carcinogenic agents

Fragile X-associated disorders: Don't miss them.

Science.gov (United States)

Birch, Rachael C; Cohen, Jonathan; Trollor, Julian N

2017-01-01

Fragile X-associated disorders are a family of inherited disorders caused by expansions in the Fragile X Mental Retardation 1 (FMR1) gene. Premutation expansions of the FMR1 gene confer risk for fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome, as well as other medical and psychiatric comorbidities. Premutation expansions of the FMR1 gene are common in the general population. However, fragile X-associated disorders are frequently under-recognised and often misdiagnosed. The aim of this article is to describe fragile X-associated disorders and identify specific considerations for general practitioners (GPs) during identification and management of these disorders. GPs have a critical role in the identification of fragile X-associated disorders, as well as coordination of complex care needs. Prompt recognition and appropriate management of these disorders and potential medical and psychiatric comorbidities will have important implications not only for the affected patient, but also other family members who may be at risk.

Component fragilities - data collection, analysis and interpretation

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1986-01-01

As part of the component fragility research program sponsored by the US Nuclear Regulatory Commission, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment with emphasis on electrical equipment, by identifying, collecting and analyzing existing test data from various sources. BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical and control devices of various manufacturers and models. Through a cooperative agreement, BNL has also obtained test data from EPRI/ANCO. An analysis of the collected data reveals that fragility levels can best be described by a group of curves corresponding to various failure modes. The lower bound curve indicates the initiation of malfunctioning or structural damage, whereas the upper bound curve corresponds to overall failure of the equipment based on known failure modes occurring separately or interactively. For some components, the upper and lower bound fragility levels are observed to vary appreciably depending upon the manufacturers and models. An extensive amount of additional fragility or high level test data exists. If completely collected and properly analyzed, the entire data bank is expected to greatly reduce the need for additional testing to establish fragility levels for most equipment

Component fragility research program

International Nuclear Information System (INIS)

Tsai, N.C.; Mochizuki, G.L.; Holman, G.S.

1989-11-01

To demonstrate how ''high-level'' qualification test data can be used to estimate the ultimate seismic capacity of nuclear power plant equipment, we assessed in detail various electrical components tested by the Pacific Gas ampersand Electric Company for its Diablo Canyon plant. As part of our Phase I Component Fragility Research Program, we evaluated seismic fragility for five Diablo Canyon components: medium-voltage (4kV) switchgear; safeguard relay board; emergency light battery pack; potential transformer; and station battery and racks. This report discusses our Phase II fragility evaluation of a single Westinghouse Type W motor control center column, a fan cooler motor controller, and three local starters at the Diablo Canyon nuclear power plant. These components were seismically qualified by means of biaxial random motion tests on a shaker table, and the test response spectra formed the basis for the estimate of the seismic capacity of the components. The seismic capacity of each component is referenced to the zero period acceleration (ZPA) and, in our Phase II study only, to the average spectral acceleration (ASA) of the motion at its base. For the motor control center, the seismic capacity was compared to the capacity of a Westinghouse Five-Star MCC subjected to actual fragility tests by LLNL during the Phase I Component Fragility Research Program, and to generic capacities developed by the Brookhaven National Laboratory for motor control center. Except for the medium-voltage switchgear, all of the components considered in both our Phase I and Phase II evaluations were qualified in their standard commercial configurations or with only relatively minor modifications such as top bracing of cabinets. 8 refs., 67 figs., 7 tabs

Alternative Lengthening of Telomeres: Recurrent Cytogenetic Aberrations and Chromosome Stability under Extreme Telomere Dysfunction

Directory of Open Access Journals (Sweden)

Despoina Sakellariou

2013-11-01

Full Text Available Human tumors using the alternative lengthening of telomeres (ALT exert high rates of telomere dysfunction. Numerical chromosomal aberrations are very frequent, and structural rearrangements are widely scattered among the genome. This challenging context allows the study of telomere dysfunction-driven chromosomal instability in neoplasia (CIN in a massive scale. We used molecular cytogenetics to achieve detailed karyotyping in 10 human ALT neoplastic cell lines.We identified 518 clonal recombinant chromosomes affected by 649 structural rearrangements. While all human chromosomes were involved in random or clonal, terminal, or pericentromeric rearrangements and were capable to undergo telomere healing at broken ends, a differential recombinatorial propensity of specific genomic regions was noted.We show that ALT cells undergo epigenetic modifications rendering polycentric chromosomes functionally monocentric, and because of increased terminal recombinogenicity, they generate clonal recombinant chromosomes with interstitial telomeric repeats. Losses of chromosomes 13, X, and 22, gains of 2, 3, 5, and 20, and translocation/deletion events involving several common chromosomal fragile sites (CFSs were recurrent. Long-term reconstitution of telomerase activity in ALT cells reduced significantly the rates of random ongoing telomeric and pericentromeric CIN. However, the contribution of CFS in overall CIN remained unaffected, suggesting that in ALT cells whole-genome replication stress is not suppressed by telomerase activation. Our results provide novel insights into ALT-driven CIN, unveiling in parallel specific genomic sites that may harbor genes critical for ALT cancerous cell growth.

Seismic component fragility data base for IPEEE

International Nuclear Information System (INIS)

Bandyopadhyay, K.; Hofmayer, C.

1990-01-01

Seismic probabilistic risk assessment or a seismic margin study will require a reliable data base of seismic fragility of various equipment classes. Brookhaven National Laboratory (BNL) has selected a group of equipment and generically evaluated the seismic fragility of each equipment class by use of existing test data. This paper briefly discusses the evaluation methodology and the fragility results. The fragility analysis results when used in the Individual Plant Examination for External Events (IPEEE) Program for nuclear power plants are expected to provide insights into seismic vulnerabilities of equipment for earthquakes beyond the design basis. 3 refs., 1 fig., 1 tab

Uptake and Diagnostic Yield of Chromosomal Microarray in an Australian Child Development Clinic

Directory of Open Access Journals (Sweden)

Dylan Mordaunt

2014-05-01

Full Text Available Autism is an etiologically heterogeneous developmental disorder for which the range of genetic investigations has expanded considerably over the past decade. Introduction of chromosomal microarray (CMA to clinical practice has expanded the range of conditions which pediatricians are able to detect. This study reviewed the utilization, yield and cost of genetic investigations in a sample of children with pervasive developmental disorders (PDD in an Australian metropolitan child development service. Six hundred and ninety eight patients with PDD were identified from the clinic population. One hundred and ten (15.7% of the clinic population had undergone investigation with chromosomal microarray, 140 (20.0% with karyotype (KT, and 167 (23.9% with Fragile X testing (FRGX. Twelve (10.9% CMA findings were reported, of which seven (6.3% were felt to be the likely cause of the child’s clinical features. Five (3.5% KT findings were reported, of which four (2.9% were felt to be the likely cause of the child’s clinical features. Two patients (1.2% were identified with Fragile X expansions. One fifth of the clinic’s recent PDD population had undergone testing with CMA. CMA appears to have increased the diagnostic yield of the genetic investigation of autism, in line with internationally reported levels. Number needed to test (NNT and cost per incremental diagnosis, were also in line with internationally reported levels.

53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress

DEFF Research Database (Denmark)

Lukas, Claudia; Savic, Velibor; Bekker-Jensen, Simon

2011-01-01

stress increases the frequency of chromosomal lesions that are transmitted to daughter cells. Throughout G1, these lesions are sequestered in nuclear compartments marked by p53-binding protein 1 (53BP1) and other chromatin-associated genome caretakers. We show that the number of such 53BP1 nuclear bodies...... increases after genetic ablation of BLM, a DNA helicase associated with dissolution of entangled DNA. Conversely, 53BP1 nuclear bodies are partially suppressed by knocking down SMC2, a condensin subunit required for mechanical stability of mitotic chromosomes. Finally, we provide evidence that 53BP1 nuclear...... bodies shield chromosomal fragile sites sequestered in these compartments against erosion. Together, these data indicate that restoration of DNA or chromatin integrity at loci prone to replication problems requires mitotic transmission to the next cell generations....

Chromosomal break points in irradiated and ethyl methane sulphonate treated leucocytes of patients with Down syndrome

International Nuclear Information System (INIS)

Reeja, T.C.; Chandra, N.; Marimuthu, K.M.

1993-01-01

Frequencies of chromosomal damage in the peripheral leucocytes of patients with Down syndrome, on exposure to gamma rays (2Gy) or ethyl methane sulphonate (EMS, 1 x 10 -4 M), were assessed. Analysis of break points in the chromosomes of irradiated cells revealed a non-random occurrence. Six of the break points observed in EMS-treated cells were found to overlap with those recorded in irradiated cells. Thirteen break points observed were found to correlate with the location of cancer-specific break points and four of these coincided with the bands where oncogenes have been located. Two break points were localised to the same bands as that of known heritable fragile sites. (author). 17 refs., 2 figs., 3 tabs

Determinants of Banking System Fragility : A Regional Perspective

NARCIS (Netherlands)

Degryse, H.A.; Elahi, M.A.; Penas, M.F.

2012-01-01

Abstract: Banking systems are fragile not only within one country but also within and across regions. We study the role of regional banking system characteristics for regional banking system fragility. We find that regional banking system fragility reduces when banks in the region jointly hold more

Employment Impact and Financial Burden for Families of Children with Fragile X Syndrome: Findings from the National Fragile X Survey

Science.gov (United States)

Ouyang, L.; Grosse, S.; Raspa, M.; Bailey, D.

2010-01-01

Background: The employment impact and financial burden experienced by families of children with fragile X syndrome (FXS) has not been quantified in the USA. Method: Using a national fragile X family survey, we analysed data on 1019 families with at least one child who had a full FXS mutation. Out-of-pocket expenditures related to fragile X were…

Financial fragility in the Great Moderation

NARCIS (Netherlands)

Bezemer, Dirk; Grydaki, Maria

2014-01-01

A nascent literature explores the measurement of financial fragility. This paper considers evidence for rising financial fragility during the 1984-2007 Great Moderation in the U.S. The literature suggests that macroeconomic stability combined with strong growth of credit to asset markets, in asset

Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency from Molecular Mechanisms to Clinical Manifestations

Directory of Open Access Journals (Sweden)

Limor Man

2017-09-01

Full Text Available Fragile X syndrome (FXS, is caused by a loss-of-function mutation in the FMR1 gene located on the X-chromosome, which leads to the most common cause of inherited intellectual disability in males and the leading single-gene defect associated with autism. A full mutation (FM is represented by more than 200 CGG repeats within the FMR1 gene, resulting in FXS. A FM is inherited from women carrying a FM or a premutation (PM; 55–200 CGG repeats allele. PM is associated with phenotypes distinct from those associated with FM. Some manifestations of the PM are unique; fragile-X-associated tremor/ataxia syndrome (FXTAS, and fragile-X-associated primary ovarian insufficiency (FXPOI, while others tend to be non-specific such as intellectual disability. In addition, women carrying a PM may suffer from subfertility or infertility. There is a need to elucidate whether the impairment of ovarian function found in PM carriers arises during the primordial germ cell (PGC development stage, or due to a rapidly diminishing oocyte pool throughout life or even both. Due to the possibility of expansion into a FM in the next generation, and other ramifications, carrying a PM can have an enormous impact on one’s life; therefore, preconception counseling for couples carrying the PM is of paramount importance. In this review, we will elaborate on the clinical manifestations in female PM carriers and propose the definition of fragile-X-associated diminished ovarian reserve (FXDOR, then we will review recent scientific findings regarding possible mechanisms leading to FXDOR and FXPOI. Lastly, we will discuss counseling, preventative measures and interventions available for women carrying a PM regarding different aspects of their reproductive life, fertility treatment, pregnancy, prenatal testing, contraception and fertility preservation options.

Fragile X-Associated Diminished Ovarian Reserve and Primary Ovarian Insufficiency from Molecular Mechanisms to Clinical Manifestations.

Science.gov (United States)

Man, Limor; Lekovich, Jovana; Rosenwaks, Zev; Gerhardt, Jeannine

2017-01-01

Fragile X syndrome (FXS), is caused by a loss-of-function mutation in the FMR1 gene located on the X-chromosome, which leads to the most common cause of inherited intellectual disability in males and the leading single-gene defect associated with autism. A full mutation (FM) is represented by more than 200 CGG repeats within the FMR1 gene, resulting in FXS. A FM is inherited from women carrying a FM or a premutation (PM; 55-200 CGG repeats) allele. PM is associated with phenotypes distinct from those associated with FM. Some manifestations of the PM are unique; fragile-X-associated tremor/ataxia syndrome (FXTAS), and fragile-X-associated primary ovarian insufficiency (FXPOI), while others tend to be non-specific such as intellectual disability. In addition, women carrying a PM may suffer from subfertility or infertility. There is a need to elucidate whether the impairment of ovarian function found in PM carriers arises during the primordial germ cell (PGC) development stage, or due to a rapidly diminishing oocyte pool throughout life or even both. Due to the possibility of expansion into a FM in the next generation, and other ramifications, carrying a PM can have an enormous impact on one's life; therefore, preconception counseling for couples carrying the PM is of paramount importance. In this review, we will elaborate on the clinical manifestations in female PM carriers and propose the definition of fragile-X-associated diminished ovarian reserve (FXDOR), then we will review recent scientific findings regarding possible mechanisms leading to FXDOR and FXPOI. Lastly, we will discuss counseling, preventative measures and interventions available for women carrying a PM regarding different aspects of their reproductive life, fertility treatment, pregnancy, prenatal testing, contraception and fertility preservation options.

RECQ5 Helicase Cooperates with MUS81 Endonuclease in Processing Stalled Replication Forks at Common Fragile Sites during Mitosis

DEFF Research Database (Denmark)

Di Marco, Stefano; Hasanova, Zdenka; Kanagaraj, Radhakrishnan

2017-01-01

The MUS81-EME1 endonuclease cleaves late replication intermediates at common fragile sites (CFSs) during early mitosis to trigger DNA-repair synthesis that ensures faithful chromosome segregation. Here, we show that these DNA transactions are promoted by RECQ5 DNA helicase in a manner dependent...... on its Ser727 phosphorylation by CDK1. Upon replication stress, RECQ5 associates with CFSs in early mitosis through its physical interaction with MUS81 and promotes MUS81-dependent mitotic DNA synthesis. RECQ5 depletion or mutational inactivation of its ATP-binding site, RAD51-interacting domain...

Seismic fragility capacity of equipment

International Nuclear Information System (INIS)

Iijima, Toru; Abe, Hiroshi; Suzuki, Kenichi

2006-01-01

Seismic probabilistic safety assessment (PSA) is an available method to evaluate residual risks of nuclear plants that are designed on definitive seismic conditions. From our preliminary seismic PSA analysis, horizontal shaft pumps are important components that have significant influences on the core damage frequency (CDF). An actual horizontal shaft pump and some kinds of elements were tested to evaluate realistic fragility capacities. Our test results showed that the realistic fragility capacity of horizontal shaft pump would be at least four times as high as a current value, 1.6 x 9.8 m/s 2 , used for our seismic PSA. We are going to incorporate the fragility capacity data that were obtained from those tests into our seismic PSA analysis, and we expect that the reliability of seismic PSA should increase. (author)

Seismic fragility analyses

International Nuclear Information System (INIS)

Kostov, Marin

2000-01-01

In the last two decades there is increasing number of probabilistic seismic risk assessments performed. The basic ideas of the procedure for performing a Probabilistic Safety Analysis (PSA) of critical structures (NUREG/CR-2300, 1983) could be used also for normal industrial and residential buildings, dams or other structures. The general formulation of the risk assessment procedure applied in this investigation is presented in Franzini, et al., 1984. The probability of failure of a structure for an expected lifetime (for example 50 years) can be obtained from the annual frequency of failure, β E determined by the relation: β E ∫[d[β(x)]/dx]P(flx)dx. β(x) is the annual frequency of exceedance of load level x (for example, the variable x may be peak ground acceleration), P(fI x) is the conditional probability of structure failure at a given seismic load level x. The problem leads to the assessment of the seismic hazard β(x) and the fragility P(fl x). The seismic hazard curves are obtained by the probabilistic seismic hazard analysis. The fragility curves are obtained after the response of the structure is defined as probabilistic and its capacity and the associated uncertainties are assessed. Finally the fragility curves are combined with the seismic loading to estimate the frequency of failure for each critical scenario. The frequency of failure due to seismic event is presented by the scenario with the highest frequency. The tools usually applied for probabilistic safety analyses of critical structures could relatively easily be adopted to ordinary structures. The key problems are the seismic hazard definitions and the fragility analyses. The fragility could be derived either based on scaling procedures or on the base of generation. Both approaches have been presented in the paper. After the seismic risk (in terms of failure probability) is assessed there are several approaches for risk reduction. Generally the methods could be classified in two groups. The

Fragile X syndrome

Science.gov (United States)

... problems, or intellectual disability may not be present. Symptoms Behavior problems associated with fragile X syndrome include: Autism spectrum disorder Delay in crawling, walking, or twisting Hand flapping ...

Chromosome breakage at sites of oncogenes in a population accidentally exposed to radioactive chemical pollution

International Nuclear Information System (INIS)

Ilyinskikh, N.N.; IIlyinskikh, I.N.; Ilyinskikh, E.N.

2003-01-01

The purpose of the present study was to investigate the level of aberrations at fragile sites of chromosomes in peripheral blood lymphocytes of the population of an area polluted with radionuclides, following an accident at the Siberian Chemical Plant (SCP). We carried out the micro-nucleus test to screen people with radiation-related cytogenetic effects. Of the 1246 examined inhabitants of the settlement of Samus, 148 showed a significantly increased frequency of micro-nucleated erythrocytes and were selected for the chromosome analysis as a radiation-exposed group. Additional analysis was carried out on 40 patients with gastric cancer and atrophic gastritis with stage II-III epithelial dysplasia. Eighty six individuals from a non-polluted area were used as a control group. Chromosomal breaks and exchanges occurred preferentially in chromosomes 3 and 6 among radiation-exposed persons and patients. The regions 3p14-3p25 and 6p23 were damaged most often. There was a tendency towards preferential involvement at q21-q25 of chromosome 6 in patients with gastric cancer and atrophic gastritis. Specific damage at certain chromosome sites was observed in the radiation-exposed population as well as in patients with gastric cancer. Most often this damage were located near oncogene loci which could imply that chromosome damage induced by radiation is likely to be a predisposing factor to the expression of oncogenes and malignant transformation of cells in exposed individuals. (author)

The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities.

Science.gov (United States)

Naim, Valeria; Rosselli, Filippo

2009-06-01

Loss-of-function of caretaker genes characterizes a group of cancer predisposition diseases that feature cellular hypersensitivity to DNA damage and chromosome fragility; this group includes Fanconi anaemia and Bloom syndrome. The products of the 13 FANC genes (mutated in Fanconi anaemia), which constitute the 'FANC' pathway, and BLM (the RecQ helicase mutated in Bloom syndrome) are thought to collaborate during the S phase of the cell cycle, preventing chromosome instability. Recently, BLM has been implicated in the completion of sister chromatid separation during mitosis, a complex process in which precise regulation and execution is crucial to preserve genomic stability. Here we show for the first time a role for the FANC pathway in chromosome segregation during mitotic cell division. FANCD2, a key component of the pathway, localizes to discrete spots on mitotic chromosomes. FANCD2 chromosomal localization is responsive to replicative stress and specifically targets aphidicolin (APH)-induced chromatid gaps and breaks. Our data indicate that the FANC pathway is involved in rescuing abnormal anaphase and telophase (ana-telophase) cells, limiting aneuploidy and reducing chromosome instability in daughter cells. We further address a cooperative role for the FANC pathway and BLM in preventing micronucleation, through FANC-dependent targeting of BLM to non-centromeric abnormal structures induced by replicative stress. We reveal new crosstalk between FANC and BLM proteins, extending their interaction beyond the S-phase rescue of damaged DNA to the safeguarding of chromosome stability during mitosis.

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

Science.gov (United States)

Smith, Leann E.; Barker, Erin T.; Seltzer, Marsha Mailick; Abbeduto, Leonard; Greenberg, Jan S.

2012-01-01

The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n = 30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n = 106) and (b) individuals diagnosed with autism (but not fragile X syndrome;…

Autism Spectrum Disorder and Fragile X Syndrome

Science.gov (United States)

... only after another family member has been diagnosed. Autism Spectrum Disorder and Fragile X Syndrome Fragile X syndrome is ... gene cause of ASD What Is Autism Spectrum Disorder? Autism spectrum disorder (ASD) is a behavioral diagnosis. The range ...

Relay testing parametric investigation of seismic fragility

International Nuclear Information System (INIS)

Bandyopadhyay, K.; Hofmayer, C.; Kassir, M.; Pepper, S.

1989-01-01

The seismic capacity of most electrical equipment is governed by malfunction of relays. An evaluation of the existing relay test data base at Brookhaven National Laboratory (BNL) has indicated that the seismic fragility of a relay may depend on various parameters related to the design or the input motion. In particular, the electrical mode, contact state, adjustment, chatter duration acceptance limit, and the frequency and the direction of the vibration input have been considered to influence the relay fragility level. For a particular relay type, the dynamics of its moving parts depends on the exact model number and vintage and hence, these parameters may also influence the fragility level. In order to investigate the effect of most of these parameters on the seismic fragility level, BNL has conducted a relay test program. The testing has been performed at Wyle Laboratories. Establishing the correlation between the single frequency fragility test input and the corresponding multifrequency response spectrum (TRS) is also an objective of this test program. This paper discusses the methodology used for testing and presents a brief summary of important test results. 1 ref., 10 figs

Seismic fragility of nuclear power plant components (Phase II)

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.; Kassir, M.K.; Pepper, S.E.

1990-02-01

As part of the Component Fragility Program which was initiated in FY 1985, three additional equipment classes have been evaluated. This report contains the fragility results and discussions on these equipment classes which are switchgear, I and C panels and relays. Both low and medium voltage switchgear assemblies have been considered and a separate fragility estimate for each type is provided. Test data on cabinets from the nuclear instrumentation/neutron monitoring system, plant/process protection system, solid state protective system and engineered safeguards test system comprise the BNL data base for I and C panels (NSSS). Fragility levels have been determined for various failure modes of switchgear and I ampersand C panels, and the deterministic results are presented in terms of test response spectra. In addition, the test data have been evaluated for estimating the respective probabilistic fragility levels which are expressed in terms of a median value, an uncertainty coefficient, a randomness coefficient and an HCLPF value. Due to a wide variation of relay design and the fragility level, a generic fragility level cannot be established for relays. 7 refs., 13 figs., 12 tabs

Resilience and the Fragile City

Directory of Open Access Journals (Sweden)

John de Boer

2015-04-01

Full Text Available Humanitarian, security, and development actors are witnessing two distinct but intertwined trends that will have a dramatic impact on their operations. The first relates to the fact that the locus of global poverty and vulnerability to disaster are increasingly concentrated in fragile and conflict affected states. The second trend is associated with the notion that the world has entered a period of unprecedented urbanization. For the first time in history, more people live inside urban centres than outside of them. As the world continues to urbanize, global emergencies will increasingly be concentrated in cities, particularly in lower income and fragile countries where the pace of urbanization is fastest. Yet, despite the growing risks facing urban populations living in fragile and conflict affected countries, there is very little understanding of what can be done to reduce the risks posed to these cities and their populations.

Radiobiological application of atomic force microscopy. Analysis on human chromosomes in culture medium

International Nuclear Information System (INIS)

Watanabe, Makoto; Kinjo, Yasuhito

1995-01-01

We have proposed a 'Heterogeneous Chromatin Target Model' on the regulating mechanisms involved in chromosome mutation due to ionizing radiations. The heterogeneity of chromatin is derived from the highly condensed organization of chromatin segments that consist of hypersensitive and fragile sites in the fluctuating assembly of nucleosome clusters (superbeads). The above consideration is going to be subjected to a new experimental approach applying the atomic force microscope (AFM), one of the most promising members of a family of scanning probe microscope (SPM). The AFM can be operated in liquid as well as in air. A living specimen can be examined without any preparative procedures (for instance, fixation, staining, vecuum evaporation and so on). Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. In the present report, the mitotic metaphase chromosomes released from living cells (human lymphocytes RPMI) were spread on the clean surface of distilled water filled in a trough. The spread surface film, in which the chromosomes were embedded, was picked up and adhered tightly on a specimen substrate made of silicon. The whole-mounted chromosome were submerged in a solution of culture medium and observed within a liquid immersion cell for AFM. We used an AFM system, SPA-300 made by Seiko Instruments. The particulate chromatin segments of nucleosome clusters (superbeads) were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (author)

Seismic fragility levels of nuclear power plant equipment

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1987-01-01

Seismic fragility levels of safety-related electrical and mechanical equipment used in nuclear power plants are discussed. The fragility level is defined as the vibration level corresponding to initiation of equipment malfunctions. The test response spectrum is used as a measure of this vibration level. The fragility phenomenon of an equipment is represented by a number of response spectra corresponding to various failure modes. Analysis methods are described for determination of the fragility level by use of existing test data. Useful conversion factors are tabulated to transform test response spectra from one damping value to another. Results are presented for switch-gears and motor control centers. The capacity levels of these equipment assemblies are observed to be limited by malfunctioning of contactors, motor starters, relays and/or switches. The applicability of the fragility levels, determined in terms of test response spectra, to Seismic Margin Studies and Probabilistic Risk Assessments is discussed and specific recommendations are provided

Study on the Progress of Ecological Fragility Assessment in China

Science.gov (United States)

Chen, Pei; Hou, Kang; Chang, Yue; Li, Xuxiang; Zhang, Yunwei

2018-02-01

The basic elements of human survival are based on the ecological environment. The development of social economic and the security of the ecological environment are closely linked and interact with each other. The fragility of the environment directly affects the stability of the regional ecosystem and the sustainable development of the ecological environment. As part of the division of the national ecological security, the assessment of ecological fragility has become a hot and difficult issue in environmental research, and researchers at home and abroad have systematically studied the causes and states of ecological fragility. The assessment of regional ecological fragility is a qualitative and quantitative analysis of the unbalanced distribution of ecological environment factors caused by human socio-economic activities or changes in ecosystems. At present, researches on ecological fragility has not formed a complete and unified index assessment system, and the unity of the assessment model has a direct impact on the accuracy of the index weights. Therefore, the discussion on selection of ecological fragility indexes and the improvement of ecological fragility assessment model is necessary, which is good for the improvement of ecological fragility assessment system in China.

Component fragilities. Data collection, analysis and interpretation

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1985-01-01

As part of the component fragility research program sponsored by the US NRC, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment with emphasis on electrical equipment. To date, BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical and control devices, e.g., switches, transmitters, potentiometers, indicators, relays, etc., of various manufacturers and models. BNL has also obtained test data from EPRI/ANCO. Analysis of the collected data reveals that fragility levels can best be described by a group of curves corresponding to various failure modes. The lower bound curve indicates the initiation of malfunctioning or structural damage, whereas the upper bound curve corresponds to overall failure of the equipment based on known failure modes occurring separately or interactively. For some components, the upper and lower bound fragility levels are observed to vary appreciably depending upon the manufacturers and models. For some devices, testing even at the shake table vibration limit does not exhibit any failure. Failure of a relay is observed to be a frequent cause of failure of an electrical panel or a system. An extensive amount of additional fregility or high level test data exists

BANKING SYSTEM FRAGILITY: CASE OF THE REPUBLIC OF MOLDOVA

Directory of Open Access Journals (Sweden)

Dorina CLICHICI

2014-04-01

Full Text Available The paper studied the determinants of Moldovan banking system fragility. It underlines the existing researches into the empirical determinants of banking fragility. The analysis revealed that there are numerous channels through which weaknesses within the macroeconomic conditions and structural characteristics might increase banking system fragility. The main macroeconomic determinants which may have an impact on Moldovan banking system fragility are: excessive domestic liquidity, pro-cyclical character of the banking system, dependence on remittances, financial dollarization. There are also several banking characteristics which play a role for Moldovan banking system fragility: the undermined intermediation function, high level of bad loans, uncertainties in the ownership structure, low presence of foreign strategic investors. The paper employed a quantitative, a qualitative and a comparative analysis using the financial soundness and structural indicators of the Moldovan banking system in order to assess the impact of various determinants on Moldovan banking system fragility. The results reveal a high degree of capitalization and liquidity of Moldovan banking system, factors which contribute and maintain the general stability of the entire financial system.

Longitudinal Profiles of Adaptive Behavior in Fragile X Syndrome

Science.gov (United States)

Quintin, Eve-Marie; Jo, Booil; Lightbody, Amy A.; Hazlett, Heather Cody; Piven, Joseph; Hall, Scott S.; Reiss, Allan L.

2014-01-01

OBJECTIVE: To examine longitudinally the adaptive behavior patterns in fragile X syndrome. METHOD: Caregivers of 275 children and adolescents with fragile X syndrome and 225 typically developing children and adolescents (2–18 years) were interviewed with the Vineland Adaptive Behavior Scales every 2 to 4 years as part of a prospective longitudinal study. RESULTS: Standard scores of adaptive behavior in people with fragile X syndrome are marked by a significant decline over time in all domains for males and in communication for females. Socialization skills are a relative strength as compared with the other domains for males with fragile X syndrome. Females with fragile X syndrome did not show a discernible pattern of developmental strengths and weaknesses. CONCLUSIONS: This is the first large-scale longitudinal study to show that the acquisition of adaptive behavior slows as individuals with fragile X syndrome age. It is imperative to ensure that assessments of adaptive behavior skills are part of intervention programs focusing on childhood and adolescence in this condition. PMID:25070318

Fragile Butterfly

DEFF Research Database (Denmark)

2011-01-01

Valg af materiale/medie/form: Med indlevelse og en unik balance af sårbarhed i stemmen synger og fortolker Heidie sine egne sange, hvis lyriske tekster grundlæggende har to temaer: En dyb kærlighed til livet og det at turde kærligheden. Toneuniverset i Fragile Butterfly tager sit afsæt i jazzen...

Tracking development assistance for health to fragile states: 2005-2011.

Science.gov (United States)

Graves, Casey M; Haakenstad, Annie; Dieleman, Joseph L

2015-03-19

Development assistance for health (DAH) has grown substantially, totaling more than $31.3 billion in 2013. However, the degree that countries with high concentrations of armed conflict, ethnic violence, inequality, debt, and corruption have received this health aid and how that assistance might be different from the funding provided to other countries has not been assessed. We combine DAH estimates and a multidimensional fragile states index for 2005 through 2011. We disaggregate and compare total DAH disbursed for fragile states versus stable states. Between 2005 and 2011, DAH per person in fragile countries increased at an annualized rate of 5.4%. In 2011 DAH to fragile countries totaled $6.2 billion, which is $5.05 per person. This is 43% of total DAH that is traced to a country. Comparing low-income countries, funding channeled to fragile countries was $7.22 per person while stable countries received $11.15 per person. Relative to stable countries, donors preferred to provide more funding to low-income fragile countries that have refugees or ongoing external intervention but tended to avoid providing funding to countries with political gridlock, flawed elections, or economic decline. In 2011, Ethiopia received the most health aid of all fragile countries, while the United States provided the most funds to fragile countries. In 2011, 1.2 billion people lived in fragile countries. DAH can bolster health systems and might be especially valuable in providing long-term stability in fragile environments. While external health funding to these countries has increased since 2005, it is, in per person terms, almost half as much as the DAH provided to stable countries of comparable income levels.

A note on families of fragility curves

International Nuclear Information System (INIS)

Kaplan, S.; Bier, V.M.; Bley, D.C.

1989-01-01

In the quantitative assessment of seismic risk, uncertainty in the fragility of a structural component is usually expressed by putting forth a family of fragility curves, with probability serving as the parameter of the family. Commonly, a lognormal shape is used both for the individual curves and for the expression of uncertainty over the family. A so-called composite single curve can also be drawn and used for purposes of approximation. This composite curve is often regarded as equivalent to the mean curve of the family. The equality seems intuitively reasonable, but according to the authors has never been proven. The paper presented proves this equivalence hypothesis mathematically. Moreover, the authors show that this equivalence hypothesis between fragility curves is itself equivalent to an identity property of the standard normal probability curve. Thus, in the course of proving the fragility curve hypothesis, the authors have also proved a rather obscure, but interesting and perhaps previously unrecognized, property of the standard normal curve

21 CFR 864.6600 - Osmotic fragility test.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Osmotic fragility test. 864.6600 Section 864.6600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Manual Hematology Devices § 864.6600 Osmotic fragility...

Fragile X syndrome in females - a familial case report and review of the literature.

Science.gov (United States)

Stembalska, Agnieszka; Łaczmańska, Izabela; Gil, Justyna; Pesz, Karolina A

2016-01-01

Fragile X syndrome (FXS), one of the manifestations of FMR1-related disorders, is one of the most frequent genetic causes of intellectual disability. In over 99% of all cases it results from the expansion of CGG repeats in the 5'-untranslated region of the FMR1 gene and presents in males and in about 50% of the females with an FMR1 full mutation, usually with a milder phenotype. Although the morphologic and behavioral phenotype in males is a well-recognized entity, the presentation in females is variable and not as specific. The objective of this paper is to present a family with quite a severe expression of the disorder in two sisters with a full mutation. We report on a two-generation family where both males and females were found to be affected by FXS. We also present the diagnostic pathway and methods that led to the diagnosis of fragile X syndrome in the two sisters, as well as the method that explained the normal phenotype in their mother. The CGG repeats analysis in the FMR1 gene showed one normal allele and one allele with a full mutation in both sisters (probands) and their mother. A full mutation was also found in three male cousins of the probands. The analysis of the X-chromosome methylation status has shown a random X inactivation in proband 1 and 2 and a non-random one in the proband's mother, with the normal allele predominantly active. The reasons for different clinical presentations are discussed; moreover a review of the literature on females with FXS is presented. We hope that this paper will facilitate the future diagnosis of fragile X syndromes in females.

Usng subjective percentiles and test data for estimating fragility functions

International Nuclear Information System (INIS)

George, L.L.; Mensing, R.W.

1981-01-01

Fragility functions are cumulative distribution functions (cdfs) of strengths at failure. They are needed for reliability analyses of systems such as power generation and transmission systems. Subjective opinions supplement sparse test data for estimating fragility functions. Often the opinions are opinions on the percentiles of the fragility function. Subjective percentiles are likely to be less biased than opinions on parameters of cdfs. Solutions to several problems in the estimation of fragility functions are found for subjective percentiles and test data. How subjective percentiles should be used to estimate subjective fragility functions, how subjective percentiles should be combined with test data, how fragility functions for several failure modes should be combined into a composite fragility function, and how inherent randomness and uncertainty due to lack of knowledge should be represented are considered. Subjective percentiles are treated as independent estimates of percentiles. The following are derived: least-squares parameter estimators for normal and lognormal cdfs, based on subjective percentiles (the method is applicable to any invertible cdf); a composite fragility function for combining several failure modes; estimators of variation within and between groups of experts for nonidentically distributed subjective percentiles; weighted least-squares estimators when subjective percentiles have higher variation at higher percents; and weighted least-squares and Bayes parameter estimators based on combining subjective percentiles and test data. 4 figures, 2 tables

Trio Fragile / Olga Kaljundi

Index Scriptorium Estoniae

Kaljundi, Olga, 1941-2001

1998-01-01

Tallinna Vene Draamateatri galeriis esinenud trupi "Trio Fragile" vernissaazhist. Trio loomingust ja osalejatest : kahe muusiku seltskonnas esineb ka 1984.a. Kunstiülikooli lõpetanud kunstnik Tõnu Talve.

Attentional Set-Shifting in Fragile X Syndrome

Science.gov (United States)

Van der Molen, M. J. W.; Van der Molen, M. W.; Ridderinkhof, K. R.; Hamel, B. C. J.; Curfs, L. M. G.; Ramakers, G. J. A.

2012-01-01

The ability to flexibly adapt to the changing demands of the environment is often reported as a core deficit in fragile X syndrome (FXS). However, the cognitive processes that determine this attentional set-shifting deficit remain elusive. The present study investigated attentional set-shifting ability in fragile X syndrome males with the…

Improved Iris Recognition through Fusion of Hamming Distance and Fragile Bit Distance.

Science.gov (United States)

Hollingsworth, Karen P; Bowyer, Kevin W; Flynn, Patrick J

2011-12-01

The most common iris biometric algorithm represents the texture of an iris using a binary iris code. Not all bits in an iris code are equally consistent. A bit is deemed fragile if its value changes across iris codes created from different images of the same iris. Previous research has shown that iris recognition performance can be improved by masking these fragile bits. Rather than ignoring fragile bits completely, we consider what beneficial information can be obtained from the fragile bits. We find that the locations of fragile bits tend to be consistent across different iris codes of the same eye. We present a metric, called the fragile bit distance, which quantitatively measures the coincidence of the fragile bit patterns in two iris codes. We find that score fusion of fragile bit distance and Hamming distance works better for recognition than Hamming distance alone. To our knowledge, this is the first and only work to use the coincidence of fragile bit locations to improve the accuracy of matches.

High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome.

Science.gov (United States)

Basuta, Kirin; Schneider, Andrea; Gane, Louise; Polussa, Jonathan; Woodruff, Bryan; Pretto, Dalyir; Hagerman, Randi; Tassone, Flora

2015-09-01

Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS. © 2015 Wiley Periodicals, Inc.

Fragility correlates thermodynamic and kinetic properties of glass forming liquids

Energy Technology Data Exchange (ETDEWEB)

Reddy, C.Narayana [Maharani’s Science College for Women, Bangalore 560001 (India); Viswanatha, R.; Chethana, B.K. [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India); Gowda, V.C.Veeranna [Government First Grade College, Jayanagara, Bangalore 560070 (India); Rao, K.J., E-mail: kalyajrao@yahoo.co.in [Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012 (India)

2015-03-15

Graphical abstract: The suggested new fragility parameter correlates viscosity and configurational entropy. - Highlights: • A new fragility function, F=ΔT/ΔC{sub p}×C{sub p}{sup l}/T{sub g} has been proposed. • A three parameter viscosity function using the new F reproduces Angell fragility plot. • A new ΔC{sub p} function is derived which directly relates Adam–Gibbs function with the fragility based viscosity function. - Abstract: In our earlier communication we proposed a simple fragility determining function, ([NBO]/V{sub m}{sup 3}T{sub g}), which we have now used to analyze several glass systems using available thermal data. A comparison with similar fragility determining function, ΔC{sub p}/C{sub p}{sup l}, introduced by Chryssikos et al. in their investigation of lithium borate glasses has also been performed and found to be more convenient quantity for discussing fragilities. We now propose a new function which uses both ΔC{sub p} and ΔT and which gives a numerical fragility parameter, F whose value lies between 0 and 1 for glass forming liquids. F can be calculated through the use of measured thermal parameters ΔC{sub p}, C{sub p}{sup l}, T{sub g} and T{sub m}. Use of the new fragility values in reduced viscosity equation reproduces the whole range of viscosity curves of the Angell plot. The reduced viscosity equation can be directly compared with the Adam–Gibbs viscosity equation and a heat capacity function can be formulated which reproduces satisfactorily the ΔC{sub p} versus ln(T{sub r}) curves and hence the configurational entropy.

Developing empirical collapse fragility functions for global building types

Science.gov (United States)

Jaiswal, K.; Wald, D.; D'Ayala, D.

2011-01-01

Building collapse is the dominant cause of casualties during earthquakes. In order to better predict human fatalities, the U.S. Geological Survey’s Prompt Assessment of Global Earthquakes for Response (PAGER) program requires collapse fragility functions for global building types. The collapse fragility is expressed as the probability of collapse at discrete levels of the input hazard defined in terms of macroseismic intensity. This article provides a simple procedure for quantifying collapse fragility using vulnerability criteria based on the European Macroseismic Scale (1998) for selected European building types. In addition, the collapse fragility functions are developed for global building types by fitting the beta distribution to the multiple experts’ estimates for the same building type (obtained from EERI’s World Housing Encyclopedia (WHE)-PAGER survey). Finally, using the collapse probability distributions at each shaking intensity level as a prior and field-based collapse-rate observations as likelihood, it is possible to update the collapse fragility functions for global building types using the Bayesian procedure.

Treatment of Fragile X Syndrome with a Neuroactive Steroid

Science.gov (United States)

2013-08-01

Fulks JL, O’Bryhim BE et al (2010) Dopamine release and uptake impairments and behavioral alterations observed in mice that model fragile x mental...D2 dopamine receptor agonist. J Cogn Neurosci 4(1):58–68 Luo Y, Shan G et al (2010) Fragile x mental retardation protein regulates proliferation and...AD_________________ Award Number: W81XWH-11-1-0626 TITLE: Treatment of Fragile X Syndrome with a

Nuclear Power Plant Mechanical Component Flooding Fragility Experiments Status

Energy Technology Data Exchange (ETDEWEB)

Pope, C. L. [Idaho State Univ., Pocatello, ID (United States); Savage, B. [Idaho State Univ., Pocatello, ID (United States); Johnson, B. [Idaho State Univ., Pocatello, ID (United States); Muchmore, C. [Idaho State Univ., Pocatello, ID (United States); Nichols, L. [Idaho State Univ., Pocatello, ID (United States); Roberts, G. [Idaho State Univ., Pocatello, ID (United States); Ryan, E. [Idaho State Univ., Pocatello, ID (United States); Suresh, S. [Idaho State Univ., Pocatello, ID (United States); Tahhan, A. [Idaho State Univ., Pocatello, ID (United States); Tuladhar, R. [Idaho State Univ., Pocatello, ID (United States); Wells, A. [Idaho State Univ., Pocatello, ID (United States); Smith, C. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2017-07-24

This report describes progress on Nuclear Power Plant mechanical component flooding fragility experiments and supporting research. The progress includes execution of full scale fragility experiments using hollow-core doors, design of improvements to the Portal Evaluation Tank, equipment procurement and initial installation of PET improvements, designation of experiments exploiting the improved PET capabilities, fragility mathematical model development, Smoothed Particle Hydrodynamic simulations, wave impact simulation device research, and pipe rupture mechanics research.

Seismic fragility of nuclear power plant components. Phase I

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.

1986-06-01

As part of the Component Fragility Research Program, sponsored by the US Nuclear Regulatory Commission, BNL is involved in establishing seismic fragility levels for various nuclear power plant equipment by identifying, collecting and analyzing existing test data from various sources. In Phase I of this program, BNL has reviewed approximately seventy test reports to collect fragility or high level test data for switchgears, motor control centers and similar electrical cabinets, valve actuators and numerous electrical devices of various manufacturers and models. This report provides an assessment and evaluation of the data collected in Phase I. The fragility data for medium voltage and low voltage switchgears and motor control centers are analyzed using the test response spectra (TRS) as a measure of the fragility level. The analysis reveals that fragility levels can best be described by a group of TRS curves corresponding to various failure modes. The lower-bound curve indicates the initiation of malfunctioning or structural damage; whereas, the upper-bound curve corresponds to overall failure of the equipment based on known failure modes. High level test data for some components are included in the report. These data indicate that some components are inherently strong and do not exhibit any failure mode even when tested at the vibration limit of a shake table. The common failure modes are identified in the report. The fragility levels determined in this report have been compared with those used in the PRA and Seismic Margin Studies. It appears that the BNL data better correlate with the HCLPF (High Confidence of a Low Probability of Failure) level used in Seismic Margin Studies and can improve this level as high as 60% for certain applications. Specific recommendations are provided for proper application of BNL fragility data to other studies

Kerr black holes are not fragile

Energy Technology Data Exchange (ETDEWEB)

McInnes, Brett, E-mail: matmcinn@nus.edu.sg [Centro de Estudios Cientificos (CECs), Valdivia (Chile); National University of Singapore (Singapore)

2012-04-21

Certain AdS black holes are 'fragile', in the sense that, if they are deformed excessively, they become unstable to a fundamental non-perturbative stringy effect analogous to Schwinger pair-production [of branes]. Near-extremal topologically spherical AdS-Kerr black holes, which are natural candidates for string-theoretic models of the very rapidly rotating black holes that have actually been observed to exist, do represent a very drastic deformation of the AdS-Schwarzschild geometry. One therefore has strong reason to fear that these objects might be 'fragile', which in turn could mean that asymptotically flat rapidly rotating black holes might be fragile in string theory. Here we show that this does not happen: despite the severe deformation implied by near-extremal angular momenta, brane pair-production around topologically spherical AdS-Kerr-Newman black holes is always suppressed.

Tirilazad mesylate protects stored erythrocytes against osmotic fragility.

Science.gov (United States)

Epps, D E; Knechtel, T J; Bacznskyj, O; Decker, D; Guido, D M; Buxser, S E; Mathews, W R; Buffenbarger, S L; Lutzke, B S; McCall, J M

1994-12-01

The hypoosmotic lysis curve of freshly collected human erythrocytes is consistent with a single Gaussian error function with a mean of 46.5 +/- 0.25 mM NaCl and a standard deviation of 5.0 +/- 0.4 mM NaCl. After extended storage of RBCs under standard blood bank conditions the lysis curve conforms to the sum of two error functions instead of a possible shift in the mean and a broadening of a single error function. Thus, two distinct sub-populations with different fragilities are present instead of a single, broadly distributed population. One population is identical to the freshly collected erythrocytes, whereas the other population consists of osmotically fragile cells. The rate of generation of the new, osmotically fragile, population of cells was used to probe the hypothesis that lipid peroxidation is responsible for the induction of membrane fragility. If it is so, then the antioxidant, tirilazad mesylate (U-74,006f), should protect against this degradation of stored erythrocytes. We found that tirilazad mesylate, at 17 microM (1.5 mol% with respect to membrane lecithin), retards significantly the formation of the osmotically fragile RBCs. Concomitantly, the concentration of free hemoglobin which accumulates during storage is markedly reduced by the drug. Since the presence of the drug also decreases the amount of F2-isoprostanes formed during the storage period, an antioxidant mechanism must be operative. These results demonstrate that tirilazad mesylate significantly decreases the number of fragile erythrocytes formed during storage in the blood bank.

Improved Erythrocyte Osmotic Fragility and Packed Cell Volume ...

African Journals Online (AJOL)

Improved Erythrocyte Osmotic Fragility and Packed Cell Volume following administration of Aloe barbadensis Juice Extract in Rats. ... Abstract. Aloe barbadensis is a popular house plant that has a long history of a multipurpose folk remedy. ... Keywords: osmotic fragility, packed cell volume, haemoglobin, Aloe vera ...

The correlation between fragility, density, and atomic interaction in glass-forming liquids.

Science.gov (United States)

Wang, Lijin; Guan, Pengfei; Wang, W H

2016-07-21

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as RI, RII, and RIII, respectively, with qualitatively disparate dynamic behaviors: RI which can be described by "softness makes strong glasses," RII where fragility is independent of softness and can only be tuned by density, and RIII with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

Component Fragility Research Program: Phase 1 component prioritization

International Nuclear Information System (INIS)

Holman, G.S.; Chou, C.K.

1987-06-01

Current probabilistic risk assessment (PRA) methods for nuclear power plants utilize seismic ''fragilities'' - probabilities of failure conditioned on the severity of seismic input motion - that are based largely on limited test data and on engineering judgment. Under the NRC Component Fragility Research Program (CFRP), the Lawrence Livermore National Laboratory (LLNL) has developed and demonstrated procedures for using test data to derive probabilistic fragility descriptions for mechanical and electrical components. As part of its CFRP activities, LLNL systematically identified and categorized components influencing plant safety in order to identify ''candidate'' components for future NRC testing. Plant systems relevant to safety were first identified; within each system components were then ranked according to their importance to overall system function and their anticipated seismic capacity. Highest priority for future testing was assigned to those ''very important'' components having ''low'' seismic capacity. This report describes the LLNL prioritization effort, which also included application of ''high-level'' qualification data as an alternate means of developing probabilistic fragility descriptions for PRA applications

Structure-specific endonucleases

DEFF Research Database (Denmark)

Minocherhomji, Sheroy; Hickson, Ian D

2014-01-01

Fragile sites are conserved loci predisposed to form breaks in metaphase chromosomes. The inherent instability of these loci is associated with chromosomal rearrangements in cancers and is a feature of cells from patients with chromosomal instability syndromes. One class of fragile sites, the com...

Fragile-to-fragile liquid transition at Tg and stable-glass phase nucleation rate maximum at the Kauzmann temperature TK

International Nuclear Information System (INIS)

Tournier, Robert F.

2014-01-01

An undercooled liquid is unstable. The driving force of the glass transition at T g is a change of the undercooled-liquid Gibbs free energy. The classical Gibbs free energy change for a crystal formation is completed including an enthalpy saving. The crystal growth critical nucleus is used as a probe to observe the Laplace pressure change Δp accompanying the enthalpy change −V m ×Δp at T g where V m is the molar volume. A stable glass–liquid transition model predicts the specific heat jump of fragile liquids at T≤T g , the Kauzmann temperature T K where the liquid entropy excess with regard to crystal goes to zero, the equilibrium enthalpy between T K and T g , the maximum nucleation rate at T K of superclusters containing magic atom numbers, and the equilibrium latent heats at T g and T K . Strong-to-fragile and strong-to-strong liquid transitions at T g are also described and all their thermodynamic parameters are determined from their specific heat jumps. The existence of fragile liquids quenched in the amorphous state, which do not undergo liquid–liquid transition during heating preceding their crystallization, is predicted. Long ageing times leading to the formation at T K of a stable glass composed of superclusters containing up to 147 atom, touching and interpenetrating, are evaluated from nucleation rates. A fragile-to-fragile liquid transition occurs at T g without stable-glass formation while a strong glass is stable after transition

Invertible chaotic fragile watermarking for robust image authentication

International Nuclear Information System (INIS)

Sidiropoulos, Panagiotis; Nikolaidis, Nikos; Pitas, Ioannis

2009-01-01

Fragile watermarking is a popular method for image authentication. In such schemes, a fragile signal that is sensitive to manipulations is embedded in the image, so that it becomes undetectable after any modification of the original work. Most algorithms focus either on the ability to retrieve the original work after watermark detection (invertibility) or on detecting which image parts have been altered (localization). Furthermore, the majority of fragile watermarking schemes suffer from robustness flaws. We propose a new technique that combines localization and invertibility. Moreover, watermark dependency on the original image and the non-linear watermark embedding procedure guarantees that no malicious attacks will manage to create information leaks.

Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome.

Science.gov (United States)

Hall, Deborah A; O'Keefe, Joan A

2013-11-01

This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists. Copyright © 2013. Published by Elsevier Inc.

Genetics Home Reference: fragile X-associated primary ovarian insufficiency

Science.gov (United States)

... Share: Email Facebook Twitter Home Health Conditions FXPOI Fragile X-associated primary ovarian insufficiency Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated primary ovarian insufficiency ( FXPOI ) is a condition ...

Genetics Home Reference: fragile X-associated tremor/ataxia syndrome

Science.gov (United States)

... Share: Email Facebook Twitter Home Health Conditions FXTAS Fragile X-associated tremor/ataxia syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated tremor/ataxia syndrome ( FXTAS ) is characterized by ...

The correlation between fragility, density, and atomic interaction in glass-forming liquids

Energy Technology Data Exchange (ETDEWEB)

Wang, Lijin; Guan, Pengfei, E-mail: pguan@csrc.ac.cn [Beijing Computational Science Research Center, Beijing 100193 (China); Wang, W. H. [Institute of Physics, Chinese Academy of Sciences, Beijing 100190 (China)

2016-07-21

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as R{sub I,} R{sub II}, and R{sub III}, respectively, with qualitatively disparate dynamic behaviors: R{sub I} which can be described by “softness makes strong glasses,” R{sub II} where fragility is independent of softness and can only be tuned by density, and R{sub III} with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

The correlation between fragility, density, and atomic interaction in glass-forming liquids

International Nuclear Information System (INIS)

Wang, Lijin; Guan, Pengfei; Wang, W. H.

2016-01-01

The fragility that controls the temperature-dependent viscous properties of liquids as the glass transition is approached, in various glass-forming liquids with different softness of the repulsive part of atomic interactions at different densities, is investigated by molecular dynamic simulations. We show that the landscape of fragility in purely repulsive systems can be separated into three regions denoted as R I, R II , and R III , respectively, with qualitatively disparate dynamic behaviors: R I which can be described by “softness makes strong glasses,” R II where fragility is independent of softness and can only be tuned by density, and R III with constant fragility, suggesting that density plays an unexpected role for understanding the repulsive softness dependence of fragility. What is more important is that we unify the long-standing inconsistence with respect to the repulsive softness dependence of fragility by observing that a glass former can be tuned more fragile if nonperturbative attraction is added into it. Moreover, we find that the vastly dissimilar influences of attractive interaction on fragility could be estimated from the structural properties of related zero-temperature glasses.

Screening and diagnosis for the fragile X syndrome among the mentally retarded: an epidemiological and psychological survey. Collaborative Fragile X Study Group

NARCIS (Netherlands)

B.B.A. de Vries (Bert); B.A. Oostra (Ben); M.F. Niermeijer (Martinus); A. Tibben (Arend); A.M.W. van den Ouweland (Ans); S. Mohkamsing; H.J. Duivenvoorden (Hugo); E. Mol; K. Gelsema; M. van Rijn; D.J.J. Halley (Dicky); L.A. Sandkuijl (Lodewijk)

1997-01-01

textabstractThe fragile X syndrome is an X-linked mental retardation disorder caused by an expanded CGG repeat in the first exon of the fragile X mental retardation (FMR1) gene. Its frequency, X-linked inheritance, and consequences for relatives all prompt for

Preserved entropy and fragile magnetism.

Science.gov (United States)

Canfield, Paul C; Bud'ko, Sergey L

2016-08-01

A large swath of quantum critical and strongly correlated electron systems can be associated with the phenomena of preserved entropy and fragile magnetism. In this overview we present our thoughts and plans for the discovery and development of lanthanide and transition metal based, strongly correlated systems that are revealed by suppressed, fragile magnetism, quantum criticality, or grow out of preserved entropy. We will present and discuss current examples such as YbBiPt, YbAgGe, YbFe2Zn20, PrAg2In, BaFe2As2, CaFe2As2, LaCrSb3 and LaCrGe3 as part of our motivation and to provide illustrative examples.

Fragility and cooperativity concepts in hydrogen-bonded organic glasses

International Nuclear Information System (INIS)

Delpouve, N.; Vuillequez, A.; Saiter, A.; Youssef, B.; Saiter, J.M.

2012-01-01

Molecular dynamics at the glass transition of three lactose/oil glassy systems have been investigated according to the cooperativity and fragility approaches. From Donth's approach, the cooperativity length is estimated by modulated temperature calorimetric measurements. Results reveal that modification of the disaccharide by oil leads to increase the disorder degree in the lactose, the size of the cooperative domains and the fragility index. These particular hydrogen-bonded organic glasses follow the general tendency observed on organic and inorganic polymers: the higher the cooperativity length, the higher the value of the fragility index at T g .

Finiteness Marking in Boys with Fragile X Syndrome

Science.gov (United States)

Sterling, Audra M.; Rice, Mabel L.; Warren, Steven F.

2012-01-01

Purpose: The current study investigated finiteness marking (e.g., he walk "s", he walk "ed") in boys with fragile X syndrome (FXS); the boys were grouped based on receptive vocabulary (i.e., borderline, impaired). Method: Twenty-one boys with the full mutation of fragile X, between the ages of 8 and 16 years participated. The…

Dilemmas in counselling females with the fragile X syndrome

NARCIS (Netherlands)

B.B.A. de Vries (Bert); H.M. van den Boer-van den Berg; M.F. Niermeijer (Martinus); A. Tibben (Arend)

1999-01-01

textabstractThe dilemmas in counselling a mildly retarded female with the fragile X syndrome and her retarded partner are presented. The fragile X syndrome is an X linked mental retardation disorder that affects males and, often less severely, females. Affected females

Seismic fragilities for nuclear power plant risk studies

International Nuclear Information System (INIS)

Kennedy, R.P.; Ravindra, M.K.

1983-01-01

Seismic fragilities of critical structures and equipment are developed as families of conditional failure frequency curves plotted against peak ground acceleration. The procedure is based on available data combined with judicious extrapolation of design information on plant structures and equipment. Representative values of fragility parameters for typical modern nuclear power plants are provided. Based on the fragility evaluation for about a dozen nuclear power plants, it is proposed that unnecessary conservatism existing in current seismic design practice could be removed by properly accounting for inelastic energy absorption capabilities of structures. The paper discusses the key contributors to seismic risk and the significance of possible correlation between component failures and potential design and construction errors

Effective updating process of seismic fragilities using Bayesian method and information entropy

International Nuclear Information System (INIS)

Kato, Masaaki; Takata, Takashi; Yamaguchi, Akira

2008-01-01

Seismic probabilistic safety assessment (SPSA) is an effective method for evaluating overall performance of seismic safety of a plant. Seismic fragilities are estimated to quantify the seismically induced accident sequences. It is a great concern that the SPSA results involve uncertainties, a part of which comes from the uncertainty in the seismic fragility of equipment and systems. A straightforward approach to reduce the uncertainty is to perform a seismic qualification test and to reflect the results on the seismic fragility estimate. In this paper, we propose a figure-of-merit to find the most cost-effective condition of the seismic qualification tests about the acceleration level and number of components tested. Then a mathematical method to reflect the test results on the fragility update is developed. A Bayesian method is used for the fragility update procedure. Since a lognormal distribution that is used for the fragility model does not have a Bayes conjugate function, a parameterization method is proposed so that the posterior distribution expresses the characteristics of the fragility. The information entropy is used as the figure-of-merit to express importance of obtained evidence. It is found that the information entropy is strongly associated with the uncertainty of the fragility. (author)

Increased expression of aphidicolin-induced common fragile sites in Tourette syndrome: The key to understand the genetics of comorbid phenotypes?

Energy Technology Data Exchange (ETDEWEB)

Gericke, G.S.; Simonic, I.; Cloete, E.; Becker, P.J. [Univ. of Pretoria (South Africa)

1996-02-16

In a comparison of 80 common aphidicolin-induced fragile sites (FS) between 26 DSM-IV Tourette syndrome (TS) and 24 control individuals, the mean of the summed break frequencies following mild aphidicolin pretreatment was significantly higher in TS individuals than in controls (P < 0.001). Other breakpoints encountered during this study, i.e., random breaks, breaks corresponding to rare FS, and breakpoints recorded by others but not listed as common FS according to the Chromosome Coordinating Meeting were listed as category II breakpoints. By using the most significantly different mean FS breakage figures between TS and control individuals, further stepwise discriminant analysis allowed identification of TS individuals from only a few sites in both the common FS and category II breakpoint groups. Future research needs to focus on confirmation of altered common fragile site expression in association with behavioral variation, whether expression of certain discriminatory sites concurs with specific comorbid disorder expression; the nature of the molecular alterations at these FS and the implications of a genomic instability phenotype for the mapping of a primary TS gene or genes. 45 refs., 1 fig., 2 tabs.

Forests, Fragility and Conflict : Overview and Case Studies

OpenAIRE

Harwell, Emily; Farah, Douglas; Blundell, Arthur G.

2011-01-01

This book provides a synthesis of key themes and current knowledge about the links among forests, armed conflict, poverty, and various aspects of state fragility. The main themes addressed are: how predatory, incapable, or absent states are fragile in different ways, and their diverse relationships to forests and conflict; the mechanisms by which forests facilitate or prolong conflict, inc...

Damage of chromosoms under irradiation of human blood lymphocytes and development of bystander effect.

Science.gov (United States)

Shemetun, O V

2016-12-01

the research the distribution of radiation induced damages among chromosomes and their bands in irra diated in vitro human blood lymphocytes and in unirradiated bystander cells.Material and methods of research: cultivation of human peripheral blood lymphocytes by semi micromethod D.A. Hungerford, modeling of radiation induced bystander effect in mixed cultures consisting of irradiated in vitro and non irradiated blood lymphocytes from persons of different gender, GTG staining of metaphase chromosomes and their cytogenetic analysis. Break points in chromosomes under the formation of aberrations were identified in exposed in vitro human peripheral blood lymphocytes in doses 0.25 Gy (95 breaks in 1248 cells) and 1.0 Gy (227 breaks in 726 cells) and in non irradiated bystander cells under their joint cultivation with irradiated in vitro human lymphocytes (51 breaks in 1137 cells at irradiation of adjacent populations of lymphocytes in dose 0.25 Gy and 75 breaks in 1321 cells at irradiation of adjacent population of lymphocytes in a dose 1.0 Gy). The distribution of injuries among the chromo somes and their bands was investigated. in radiation exposed in vitro human peripheral blood lymphocytes as well as in bystander cells the fre quency of damaged bands and number of breaks which localized in them exceeded the control value (p chromosomes were damaged according to their relative length. Location of bands with increasing number of breaks coincided with the «hot spots» of chromosome damage following irradiation and fragile sites. More sensitive to damage were G negative euchromatin chromosome bands, in which were localized 82 88 % breaks. Damageability of telomeric regions in the irradiated cells had no significant difference from the control, while in bystander cells was lower than control value (p < 0.05). O. V. Shemetun.

Data-Driven Decision Making in Fragile Contexts : Evidence from Sudan

OpenAIRE

Hamilton, Alexander; Hammer, Craig

2017-01-01

Data deficiencies contribute to state fragility and exacerbate fragile states’ already limited capacity to provide basic services, public security and rule of law. The lack of robust, good quality data can also have a disabling effect on government efforts to manage political conflict, and indeed can worsen conflict, since violent settings pose substantial challenges to knowledge generation, capture and application. In short, in fragile contexts the need for reliable evidence at all levels ...

Bayesian methodology for generic seismic fragility evaluation of components in nuclear power plants

International Nuclear Information System (INIS)

Yamaguchi, Akira; Campbell, R.D.; Ravindra, M.K.

1991-01-01

Bayesian methodology for updating the seismic fragility of components in nuclear power plants is presented. The generic fragility data which have been evaluated based on the past SPSAs are combined with the seismic experience data. Although the seismic experience is limited to the acceleration range below the median capacity of the components, it has been found that the evidence is effective to update the fragility tail. In other words, the uncertainty of the fragility is reduced although the median capacity itself is not modified to a great extent. The annual frequency of failure is also reduced as a result of the updating of the fragility tail. The PDF of the seismic capacity is handled in discrete form, which enables the use of arbitrary type of prior distribution. Accordingly, the Log-N prior can be used which is consistent with the widely used fragility model. For evaluating posterior fragility parameters (A m and B U ), two methods have been proposed. Furthermore, it has been found that the importance of evidence used in the Bayesian methodology can be quantified by the entropy of the evidence. Only the events with high entropy need to be considered in the Bayesian updating of the fragility. The currently available seismic experience database for typical components can be utilized to develop the fragility tail which is contributive to the seismically-induced failure frequency. The combined use of generic fragility and seismic experience data, with the aid of Bayesian methodology, provides refined generic fragility curves which are useful for SPSA studies. (author)

The highly fragile glass former Decalin

International Nuclear Information System (INIS)

Eibl, Stefan

2009-01-01

Systems exhibiting the glass transition can be classified by fragility. In this work we studied structural and dynamical aspects of highly fragile C 10 H 18 Decalin. Trans Decalin is locked into a pseudo-flat centrosymmetric conformation, while cis Decalin interchanges dynamically between chiral, pseudo-spherical ground states. On investigation of the phase behaviour trans Decalin was found to crystallise rapidly and cleanly; its crystal structure could be determined. From the crystal structure the dynamics of crystalline trans Decalin could be calculated using ab-initio lattice energy calculations and compared to measurements. Using neutron diffraction and molecular dynamics simulations the amorphous structure of Decalin was investigated. The difference in structure to the common molecular liquid Cumene is significant. The features of the amorphous structure of sphere-like cis Decalin show strong resemblance to the ones of Argon and metallic glasses. The dynamics of Decalin were investigated in the slightly supercooled liquid range. Using neutron scattering and optical spectroscopy, data was collected for a wide spectral range and several temperatures. The data suggests high fragility for the generic Decalin mixture, which is in agreement with the reported results. By contrast to previous estimations, an extrapolation of our data indicates cis Decalin to be only slightly less fragile than the generic mixture. Finally a lower limit to the four point susceptibility function χ 4 could be calculated and the number of correlated molecules determined. The evolution of this value as a function of T g /T and relaxation time are in agreement with literature. (author) [fr

Fragility and cooperativity concepts in hydrogen-bonded organic glasses

Energy Technology Data Exchange (ETDEWEB)

Delpouve, N., E-mail: delpouve.nicolas@gmail.com [AMME-LECAP EA 4528 International Laboratory, University of Rouen, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France); Vuillequez, A.; Saiter, A.; Youssef, B.; Saiter, J.M. [AMME-LECAP EA 4528 International Laboratory, University of Rouen, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France)

2012-09-01

Molecular dynamics at the glass transition of three lactose/oil glassy systems have been investigated according to the cooperativity and fragility approaches. From Donth's approach, the cooperativity length is estimated by modulated temperature calorimetric measurements. Results reveal that modification of the disaccharide by oil leads to increase the disorder degree in the lactose, the size of the cooperative domains and the fragility index. These particular hydrogen-bonded organic glasses follow the general tendency observed on organic and inorganic polymers: the higher the cooperativity length, the higher the value of the fragility index at T{sub g}.

Seismic fragility analysis of structural components for HFBR facilities

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.

1992-01-01

The paper presents a summary of recently completed seismic fragility analyses of the HFBR facilities. Based on a detailed review of past PRA studies, various refinements were made regarding the strength and ductility evaluation of structural components. Available laboratory test data were analysed to evaluate the formulations used to predict the ultimate strength and deformation capacities of steel, reinforced concrete and masonry structures. The biasness and uncertainties were evaluated within the framework of the fragility evaluation methods widely accepted in the nuclear industry. A few examples of fragility calculations are also included to illustrate the use of the presented formulations

Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards

Science.gov (United States)

Ham, H. J.; Lee, S.; Choi, S. H.; Yun, W. S.

2015-12-01

Agricultural Fragility Estimates Subjected to Volcanic Ash Fall Hazards Hee Jung Ham1, Seung-Hun Choi1, Woo-Seok Yun1, Sungsu Lee2 1Department of Architectural Engineering, Kangwon National University, Korea 2Division of Civil Engineering, Chungbuk National University, Korea ABSTRACT In this study, fragility functions are developed to estimate expected volcanic ash damages of the agricultural sector in Korea. The fragility functions are derived from two approaches: 1) empirical approach based on field observations of impacts to agriculture from the 2006 eruption of Merapi volcano in Indonesia and 2) the FOSM (first-order second-moment) analytical approach based on distribution and thickness of volcanic ash observed from the 1980 eruption of Mt. Saint Helens and agricultural facility specifications in Korea. Fragility function to each agricultural commodity class is presented by a cumulative distribution function of the generalized extreme value distribution. Different functions are developed to estimate production losses from outdoor and greenhouse farming. Seasonal climate influences vulnerability of each agricultural crop and is found to be a crucial component in determining fragility of agricultural commodities to an ash fall. In the study, the seasonality coefficient is established as a multiplier of fragility function to consider the seasonal vulnerability. Yields of the different agricultural commodities are obtained from Korean Statistical Information Service to create a baseline for future agricultural volcanic loss estimation. Numerically simulated examples of scenario ash fall events at Mt. Baekdu volcano are utilized to illustrate the application of the developed fragility functions. Acknowledgements This research was supported by a grant 'Development of Advanced Volcanic Disaster Response System considering Potential Volcanic Risk around Korea' [MPSS-NH-2015-81] from the Natural Hazard Mitigation Research Group, Ministry of Public Safety and Security of

The Seismic Fragility Evaluation of an Offsite Transformer according to Aging Effects

International Nuclear Information System (INIS)

Kim, Min Kyu; Choi, In Kil

2008-01-01

A seismic fragility analysis was performed, especially for an aged electric power transmission system, in this study. A real electric transformer system for Korean Nuclear Power Plants was selected for the seismic fragility evaluation. In the case of a seismic fragility analysis we should use design material properties and conditions. However material properties and environmental conditions of most structures and equipment are changed according to a lapse of time. Aging conditions greatly affect the integrity of the structures and equipment at NPP sites, but it is very difficult to estimate them qualitatively. Integrity of an anchor bolt system was considered with the aging conditions for an electric transformer system. At first, a seismic fragility analysis was performed for a fine condition for an electric transformer system. After that, a seismic fragility analysis according to the fastener of an anchor bolt system was conducted. This study showed that a looser anchor bolt creates seismic responses and seismic fragility changes of more 10%

Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle

Science.gov (United States)

Sabbagh-Haddad, Aida; Haddad, Denise Sabbagh; Michel-Crosato, Edgard; Arita, Emiko Saito

2016-01-01

ABSTRACT Fragile X syndrome (FXS) is a disorder linked to the chromosome X long arm (Xq27.3), which is identified by a constriction named fragile site. It determines various changes, such as behavioral or emotional problems, learning difficulties, and intellectual disabilities. Craniofacial abnormalities such as elongated and narrow face, prominent forehead, broad nose, large and prominent ear pavilions, strabismus, and myopia are frequent characteristics. Regarding the oral aspects, deep and high-arched palate, mandibular prognathism, and malocclusion are also observed. Objective: The purpose of this study was to evaluate the dental radiographic characteristics as described in 40 records of patients with panoramic radiography. Material and Methods: The patients were in the range of 6–17 years old, and were divided into two groups (20 subjects who were compatible with the normality standard and 20 individuals diagnosed with the FXS), which were matched for gender and age. Analysis of the panoramic radiographic examination involved the evaluation of dental mineralization stage, mandibular angle size, and presence of dental anomalies in both deciduous and permanent dentitions. Results: The results of radiographic evaluation demonstrated that the chronology of tooth eruption of all third and second lower molars is anticipated in individuals with FXS (pdental anomalies. In addition, an increase was observed in the mandibular angle size in the FXS group (pdental radiographic changes is of great importance for dental surgeons to plan the treatment of these individuals. PMID:27812623

Chromosome

Science.gov (United States)

... St Louis, MO: Elsevier; 2017:chap 69. Taber's Medical Dictionary Online. Chromosome. www.tabers.com/tabersonline/view/Tabers-Dictionary/753321/all/chromosome?q=Chromosome&ti=0 . Accessed June 11, 2017.

Diagnostic, carrier and prenatal genetic testing for fragile X ...

African Journals Online (AJOL)

Background. Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene (FMR-1) gene. Objectives. To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders ...

Whole-of-Government Approaches to Fragile States in Africa

DEFF Research Database (Denmark)

Olsen, Gorm Rye

2013-01-01

For a number of years fragile states have been high on the foreign policy agendas of the USA and the EU. Both actors look upon fragile states with great concern and consider them as security threats. Officially they give priority to ‘whole-of-government approaches’ (wga) when addressing the threats...

Cities could hold the key to understanding fragility | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

Cities are engines of economic growth and the primary sites of basic service delivery. Yet weak governance, along with inequalities related to income, social class, religion, and gender, may lead to a breakdown of systems and structures, and eventually to "fragile cities." Although the fragile cities concept is relatively new, ...

Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution.

Science.gov (United States)

Guillén, Yolanda; Ruiz, Alfredo

2012-02-01

Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution.

Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution

Directory of Open Access Journals (Sweden)

Guillén Yolanda

2012-02-01

Full Text Available Abstract Background Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. Results In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. Conclusions D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution.

Gene alterations at Drosophila inversion breakpoints provide prima facie evidence for natural selection as an explanation for rapid chromosomal evolution

Science.gov (United States)

2012-01-01

Background Chromosomal inversions have been pervasive during the evolution of the genus Drosophila, but there is significant variation between lineages in the rate of rearrangement fixation. D. mojavensis, an ecological specialist adapted to a cactophilic niche under extreme desert conditions, is a chromosomally derived species with ten fixed inversions, five of them not present in any other species. Results In order to explore the causes of the rapid chromosomal evolution in D. mojavensis, we identified and characterized all breakpoints of seven inversions fixed in chromosome 2, the most dynamic one. One of the inversions presents unequivocal evidence for its generation by ectopic recombination between transposon copies and another two harbor inverted duplications of non-repetitive DNA at the two breakpoints and were likely generated by staggered single-strand breaks and repair by non-homologous end joining. Four out of 14 breakpoints lay in the intergenic region between preexisting duplicated genes, suggesting an adaptive advantage of separating previously tightly linked duplicates. Four out of 14 breakpoints are associated with transposed genes, suggesting these breakpoints are fragile regions. Finally two inversions contain novel genes at their breakpoints and another three show alterations of genes at breakpoints with potential adaptive significance. Conclusions D. mojavensis chromosomal inversions were generated by multiple mechanisms, an observation that does not provide support for increased mutation rate as explanation for rapid chromosomal evolution. On the other hand, we have found a number of gene alterations at the breakpoints with putative adaptive consequences that directly point to natural selection as the cause of D. mojavensis rapid chromosomal evolution. PMID:22296923

Chromosomal imbalances in four new uterine cervix carcinoma derived cell lines

International Nuclear Information System (INIS)

Hidalgo, Alfredo; Monroy, Alberto; Arana, Rosa Ma; Taja, Lucía; Vázquez, Guelaguetza; Salcedo, Mauricio

2003-01-01

Uterine cervix carcinoma is the second most common female malignancy worldwide and a major health problem in Mexico, representing the primary cause of death among the Mexican female population. High risk human papillomavirus (HPV) infection is considered to be the most important risk factor for the development of this tumor and cervical carcinoma derived cell lines are very useful models for the study of viral carcinogenesis. Comparative Genomic Hybridization (CGH) experiments have detected a specific pattern of chromosomal imbalances during cervical cancer progression, indicating chromosomal regions that might contain genes that are important for cervical transformation. We performed HPV detection and CGH analysis in order to initiate the genomic characterization of four recently established cervical carcinoma derived cell lines from Mexican patients. All the cell lines were HPV18 positive. The most prevalent imbalances in the cell lines were gains in chromosomes 1q23-q32, 3q11.2-q13.1, 3q22-q26.1, 5p15.1-p11.2, this alteration present as a high copy number amplification in three of the cell lines, 7p15-p13, 7q21, 7q31, 11q21, and 12q12, and losses in 2q35-qter, 4p16, 6q26-qter, 9q34 and 19q13.2-qter. Analysis of our present findings and previously reported data suggest that gains at 1q31-q32 and 7p13-p14, as well as losses at 6q26-q27 are alterations that might be unique for HPV18 positive cases. These chromosomal regions, as well as regions with high copy number amplifications, coincide with known fragile sites and known HPV integration sites. The general pattern of chromosomal imbalances detected in the cells resembled that found in invasive cervical tumors, suggesting that the cells represent good models for the study of cervical carcinoma

Fragility and hysteretic creep in frictional granular jamming.

Science.gov (United States)

Bandi, M M; Rivera, M K; Krzakala, F; Ecke, R E

2013-04-01

The granular jamming transition is experimentally investigated in a two-dimensional system of frictional, bidispersed disks subject to quasistatic, uniaxial compression without vibrational disturbances (zero granular temperature). Three primary results are presented in this experimental study. First, using disks with different static friction coefficients (μ), we experimentally verify numerical results that predict jamming onset at progressively lower packing fractions with increasing friction. Second, we show that the first compression cycle measurably differs from subsequent cycles. The first cycle is fragile-a metastable configuration with simultaneous jammed and unjammed clusters-over a small packing fraction interval (φ(1)disk displacements over the same packing fraction interval. This fragile behavior is explained through a percolation mechanism of stressed contacts where cluster growth exhibits spatial correlation with disk displacements and contributes to recent results emphasizing fragility in frictional jamming. Control experiments show that the fragile state results from the experimental incompatibility between the requirements for zero friction and zero granular temperature. Measurements with several disk materials of varying elastic moduli E and friction coefficients μ show that friction directly controls the start of the fragile state but indirectly controls the exponential pressure rise. Finally, under repetitive loading (compression) and unloading (decompression), we find the system exhibits pressure hysteresis, and the critical packing fraction φ(c) increases slowly with repetition number. This friction-induced hysteretic creep is interpreted as the granular pack's evolution from a metastable to an eventual structurally stable configuration. It is shown to depend on the quasistatic step size Δφ, which provides the only perturbative mechanism in the experimental protocol, and the friction coefficient μ, which acts to stabilize the pack.

Obesity, Food Selectivity, and Physical Activity in Individuals with Fragile X Syndrome

Science.gov (United States)

Raspa, Melissa; Bailey, Donald B., Jr.; Bishop, Ellen; Holiday, David; Olmsted, Murrey

2010-01-01

National survey data from 884 families were used to examine the overall health of children and adults with fragile X syndrome. Results indicate the rate of obesity in adults with fragile X syndrome is similar to the general population (30%). Male children with fragile X syndrome, however, had higher rates of obesity (31%) when compared with…

Ectodermal dysplasia-skin fragility syndrome: A rare case report

Directory of Open Access Journals (Sweden)

Subhash Kashyap

2015-01-01

Full Text Available Ectodermal dysplasia/skin fragility syndrome (ED-SFS is a newly described autosomal recessive disorder characterized by skin fragility and blistering, palmoplantar keratoderma, abnormal hair growth, nail dystrophy, and occasionally defective sweating. It results from mutations in the PKP1 gene encoding plakophilin 1 (PKP1, which is an important component of stratifying epithelial desmosomes and a nuclear component of many cell types. Only 12 cases of this rare genodermatosis have been reported so far. We present an unusual case of ED-SFS in a 12-year boy who was normal at birth but subsequently developed skin fragility, hair and nail deformities, abnormal dentition, palmoplantar keratoderma, and abnormal sweating but no systemic abnormality.

Fragility Analysis of Concrete Gravity Dams

Science.gov (United States)

Tekie, Paulos B.; Ellingwood, Bruce R.

2002-09-01

Concrete gravity dams are an important part ofthe nation's infrastructure. Many dams have been in service for over 50 years, during which time important advances in the methodologies for evaluation of natural phenomena hazards have caused the design-basis events to be revised upwards, in some cases significantly. Many existing dams fail to meet these revised safety criteria and structural rehabilitation to meet newly revised criteria may be costly and difficult. A probabilistic safety analysis (PSA) provides a rational safety assessment and decision-making tool managing the various sources of uncertainty that may impact dam performance. Fragility analysis, which depicts fl%e uncertainty in the safety margin above specified hazard levels, is a fundamental tool in a PSA. This study presents a methodology for developing fragilities of concrete gravity dams to assess their performance against hydrologic and seismic hazards. Models of varying degree of complexity and sophistication were considered and compared. The methodology is illustrated using the Bluestone Dam on the New River in West Virginia, which was designed in the late 1930's. The hydrologic fragilities showed that the Eluestone Dam is unlikely to become unstable at the revised probable maximum flood (PMF), but it is likely that there will be significant cracking at the heel ofthe dam. On the other hand, the seismic fragility analysis indicated that sliding is likely, if the dam were to be subjected to a maximum credible earthquake (MCE). Moreover, there will likely be tensile cracking at the neck of the dam at this level of seismic excitation. Probabilities of relatively severe limit states appear to be only marginally affected by extremely rare events (e.g. the PMF and MCE). Moreover, the risks posed by the extreme floods and earthquakes were not balanced for the Bluestone Dam, with seismic hazard posing a relatively higher risk.

Ectodermal Dysplasia Skin Fragility Syndrome

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Ayça Alan Atalay

2014-06-01

Full Text Available Ectodermal dysplasia-skin fragility syndrome (EDSFS is a rare autosomal recessive genodermatosis first described in 1997 by Mc Grath. EDSFS results from loss of function mutations in plakophilin-1 (PKP1. PKP1 is a structural component of desmosomes, cellcell adhesion complexes. It is also found as a nuclear protein in several cell types that are lack of desmosomes. In skin, however, PKP1 expression is confined mainly to suprabasal keratinocytes and the outer root sheath of hair follicules. Loss of function mutation in PKP1 leads to extensive skin fragility, bullae and erosions following minor trauma, focal keratoderma with painful fissures, alopecia, and nail dystrophy. In some patients hypohidrosis may also be seen. EDSFS is now considered as a specific suprabasal form of epidermolysis bullosa simplex. In this report we describe a 20 year old EDSFS case.

International Companies in Fragile States

DEFF Research Database (Denmark)

Patey, Luke; Kragelund, Peter

Denmark must not fail to promote corporate social responsibility in fragile states. International companies remain active in these environments, and often worsen rather than alleviate poor governance. Financial transparency and human rights initiatives offer the first step in ensuring...

Robust-yet-fragile nature of interdependent networks

Science.gov (United States)

Tan, Fei; Xia, Yongxiang; Wei, Zhi

2015-05-01

Interdependent networks have been shown to be extremely vulnerable based on the percolation model. Parshani et al. [Europhys. Lett. 92, 68002 (2010), 10.1209/0295-5075/92/68002] further indicated that the more intersimilar networks are, the more robust they are to random failures. When traffic load is considered, how do the coupling patterns impact cascading failures in interdependent networks? This question has been largely unexplored until now. In this paper, we address this question by investigating the robustness of interdependent Erdös-Rényi random graphs and Barabási-Albert scale-free networks under either random failures or intentional attacks. It is found that interdependent Erdös-Rényi random graphs are robust yet fragile under either random failures or intentional attacks. Interdependent Barabási-Albert scale-free networks, however, are only robust yet fragile under random failures but fragile under intentional attacks. We further analyze the interdependent communication network and power grid and achieve similar results. These results advance our understanding of how interdependency shapes network robustness.

Epidemiology of "fragile skin": results from a survey of different skin types

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Haftek M

2013-12-01

Full Text Available Marek Haftek,1 Christine Coutanceau,2 Charles Taïeb3 1Université Lyon 1, Laboratoire de Recherche Dermatologique, Faculté de Médecine et de Pharmacie, Lyon, 2Département Médical, Laboratoires Dermatologiques A-Derma, Lavaur, 3Public Health, Pierre Fabre SA, Paris, France Background: Epidemiologic information regarding the prevalence of "fragile skin" in different adult populations is currently limited. The objective of the current survey was to assess the occurrence of perceived "fragile skin" across different skin types in the general adult population. Methods: Individuals aged 15–65 years from five representative geographic regions (France, Spain, Sweden, Japan, and the US were interviewed and grouped into the following skin types: Caucasian North skin (n=1,218, Caucasian South skin (n=1,695, Asian skin (n=1,500, and Black skin (n=500. The main survey question was "In your opinion, do you have fragile skin?" Concepts relating to the nature and appearance of an individual's skin were also evaluated. Results: A total of 4,913 individuals were interviewed. Subjects in the Caucasian North, Caucasian South, Asian, and Black skin type groups responded positively to the question "In your opinion, do you have fragile skin?" in the following proportions: 24.44%, 29.71%, 52.67%, and 42.20%, respectively. With the exception of individuals in the Black skin group, "fragile skin" was prevalent in significantly more women than men (P<0.0001. Compared with other age categories, the prevalence of "fragile skin" was significantly higher in individuals aged 15–34 years (P<0.0001, regardless of skin type. In general, individuals reporting "fragile skin" were 2–3-fold more likely to respond positively to a series of questions relating to the nature and appearance of their skin. The prevalence of "fragile skin" was also higher in individuals who experienced dermatosis (skin lesions of any type in the previous 12 months. Conclusion: Whilst these

Rescue of Synaptic Phenotypes and Spatial Memory in Young Fragile X Mice.

Science.gov (United States)

Sun, Miao-Kun; Hongpaisan, Jarin; Alkon, Daniel L

2016-05-01

Fragile X syndrome (FXS) is characterized by synaptic immaturity, cognitive impairment, and behavioral changes. The disorder is caused by transcriptional shutdown in neurons of thefragile X mental retardation 1gene product, fragile X mental retardation protein. Fragile X mental retardation protein is a repressor of dendritic mRNA translation and its silencing leads to dysregulation of synaptically driven protein synthesis and impairments of intellect, cognition, and behavior, and FXS is a disorder that currently has no effective therapeutics. Here, young fragile X mice were treated with chronic bryostatin-1, a relatively selective protein kinase Cεactivator, which induces synaptogenesis and synaptic maturation/repair. Chronic treatment with bryostatin-1 rescues young fragile X mice from the disorder phenotypes, including normalization of most FXS abnormalities in 1) hippocampal brain-derived neurotrophic factor expression, 2) postsynaptic density-95 levels, 3) transformation of immature dendritic spines to mature synapses, 4) densities of the presynaptic and postsynaptic membranes, and 5) spatial learning and memory. The therapeutic effects were achieved without downregulation of metabotropic glutamate receptor (mGluR) 5 in the hippocampus and are more dramatic than those of a late-onset treatment in adult fragile X mice. mGluR5 expression was in fact lower in fragile X mice and its expression was restored with the bryostatin-1 treatment. Our results show that synaptic and cognitive function of young FXS mice can be normalized through pharmacological treatment without downregulation of mGluR5 and that bryostatin-1-like agents may represent a novel class of drugs to treat fragile X mental retardation at a young age and in adults. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Survey of seismic fragilities used in PRA studies of nuclear power plants

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Chokshi, N.C.

1998-01-01

In recent years, seismic PRA studies have been performed on a large number of nuclear power plants in the USA. This paper presents a summary of a survey on fragility databases and the range of evaluated fragility values of various equipment categories based on past PRAs. The survey includes the use of experience data, the interpretations of available test data, and the quantification of uncertainties. The surveyed fragility databases are limited to data available in the public domain such as NUREG reports, conference proceedings and other publicly available reports. The extent of the availability of data as well as limitations are studied and tabulated for various equipment categories. The survey of the fragility values in past PRA studies includes not only the best estimate values, but also the dominant failure modes and the estimated uncertainty levels for each equipment category. The engineering judgments employed in estimating the uncertainty in the fragility values are also studied. This paper provides a perspective on the seismic fragility evaluation procedures for equipment in order to clearly identify the engineering analysis and judgment used in past seismic PRA studies

Prevalence and factors associated with fragility syndrome in older adults attending

Directory of Open Access Journals (Sweden)

Milton Carlos Gonzáles-Mechán

2017-03-01

Full Text Available Objectives: To identify the prevalence and factors associated with fragility syndrome in older adults attending the EsSalud (Peruvian Social Security Health Insurance primary health care service, Chiclayo - Peru. Materials and methods: A descriptive, prospective and cross-sectional study was conducted on a sample consisting of 326 older adults from urban areas and surrounding districts of Chiclayo, who attend the outpatient service at the Hospital Naylamp and Policlínico Chiclayo Oeste. A data collection sheet including social-demographic variables, comorbidity and polypharmacy, and fragility syndrome clinical criteria was filled in. Results: The prevalence of fragility was 17.5% and that of pre-fragility, 40.9%. The most frequent fragility clinical criteria were as follows: self-reported fatigue (42.3% and decreased grip strength (32.8%. The bivariate analysis showed an association with age, level of education, occupation (class IV and V concerning manual work, comorbidity (class II, asymptomatic disease or asymptomatic disease that requires medication but is under control, polypharmacy, anemia, Parkinson’s disease and non-vascular neurological disease. The final prediction model covering the age (1.08, 95% CI: 1.03 to 1.12, higher education level as a preventive variable (0.21, 95% CI: 0.07 to 0.62, type II comorbidity (11 08, 95% CI: 1.45 to 84.38 and polypharmacy (2.49, 95% CI: 1.24 to 5.03 predicts the likelihood of fragility syndrome in 75.6%. Conclusions: There is a high prevalence of fragility in the elderly population attending the primary health care service, and a significant association with age, higher education level, type II comorbidity and polypharmacy

Fragility: The Next Wave in Critical Infrastructure Protection

OpenAIRE

Allan McDougall

2009-01-01

In North America today, we are about to embark on a significant effort to repair, or even upgrade, many aspects of our infrastructure. Many of these efforts are linked to economic recovery packages. Others are based on sheer need. The challenge for decision makers and planners involves ensuring that scarce economic resources are put to their best use. Understanding the concept of fragility plays a pivotal part in reaching that understanding.Fragility, like many other systems—particularly Info...

Mathematical Definition, Mapping, and Detection of (Anti)Fragility

OpenAIRE

Taleb, Nassim N.; Douady, Raphael

2012-01-01

URL des Documents de travail : http://centredeconomiesorbonne.univ-paris1.fr/documents-de-travail/; Documents de travail du Centre d'Economie de la Sorbonne 2014.93 - ISSN : 1955-611X; We provide a mathematical definition of fragility and antifragility as negative or positive sensitivity to a semi-measure of dispersion and volatility (a variant of negative or positive "vega") and examine the link to nonlinear effects. We integrate model error (and biases) into the fragile or antifragile conte...

Fabrication and transfer of fragile 3D PDMS microstructures

International Nuclear Information System (INIS)

Karlsson, J Mikael; Haraldsson, Tommy; Carlborg, Carl Fredrik; Van der Wijngaart, Wouter; Hansson, Jonas; Russom, Aman

2012-01-01

We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors’ knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour. (paper)

Fragility Variation of Lithium Borate Glasses Studied by Temperature-Modulated DSC

Science.gov (United States)

Matsuda, Yu; Fukawa, Yasuteru; Kawashima, Mitsuru; Kojima, Seiji

2008-02-01

The fragility of lithium borate glass system has been investigated by Temperature-Modulated Differential Scanning Calorimetry (TMDSC). The frequency and temperature dependences of dynamic specific heat have been observed in the vicinity of a glass transition temperature Tg. It is shown that the value of the fragility index m can be determined from the temperature dependence of the α-relaxation times observed by TMDSC, when the raw phase angle is properly corrected. The composition dependence of the fragility has been also discussed.

Fragility non-hip fracture patients are at risk.

Science.gov (United States)

Gosch, M; Druml, T; Nicholas, J A; Hoffmann-Weltin, Y; Roth, T; Zegg, M; Blauth, M; Kammerlander, C

2015-01-01

Fragility fractures are a growing worldwide health care problem. Hip fractures have been clearly associated with poor outcomes. Fragility fractures of other bones are common reasons for hospital admission and short-term disability, but specific long-term outcome studies of non-hip fragility fractures are rare. The aim of our trial was to evaluate the 1-year outcomes of non-hip fragility fracture patients. This study is a retrospective cohort review of 307 consecutive older inpatient non-hip fracture patients. Patient data for analysis included fracture location, comorbidity prevalence, pre-fracture functional status, osteoporosis treatments and sociodemographic characteristics. The main outcomes evaluated were 1-year mortality and post-fracture functional status. As compared to the expected mortality, the observed 1-year mortality was increased in the study group (17.6 vs. 12.2 %, P = 0.005). After logistic regression, three variables remained as independent risk factors for 1-year mortality among non-hip fracture patients: malnutrition (OR 3.3, CI 1.5-7.1), Charlson comorbidity index (CCI) (OR 1.3, CI 1.1-1.5) and the Parker Mobility Score (PMS) (OR 0.85, CI 0.74-0.98). CCI and PMS were independent risk factors for a high grade of dependency after 1 year. Management of osteoporosis did not significantly improve after hospitalization due to a non-hip fragility fracture. The outcomes of older non-hip fracture patients are comparable to the poor outcomes of older hip fracture patients, and appear to be primarily related to comorbidities, pre-fracture function and nutritional status. The low rate of patients on osteoporosis medications likely reflects the insufficient recognition of the importance of osteoporosis assessment and treatment in non-hip fracture patients. Increased clinical and academic attention to non-hip fracture patients is needed.

Risk factors for fragility fracture in Seremban district, Malaysia: a comparison of patients with fragility fracture in the orthopedic ward versus those in the outpatient department.

Science.gov (United States)

Keng Yin Loh; King Hock Shong; Soo Nie Lan; Lo, Wan-Yi; Shu Yuen Woon

2008-01-01

Osteoporosis is a silent disease and becomes clinically significant in the presence of fragility fracture. Identifying risk factors that are associated with osteoporosis in the community is important in reducing the incidence of fragility fracture. The aim of this study is to identify risk factors associated with fragility fracture in the Seremban District of Malaysia. This is a population comparison study between orthopedic ward patients and outpatients attending a community health clinic for 6 months. Epidemiological data and the possible risk factors for osteoporosis were collected by direct interview. This study demonstrates that advancing age, low body weight, smoking, lack of regular exercise, low consumption of calcium containing foods, and using bone depleting drugs (steroids, thyroid hormone, and frusemides) are major risk factors for fragility fracture. Most of these risk factors are modifiable through effective lifestyle intervention.

Clinical aspects of the fragile X syndrome.

Science.gov (United States)

Brown, W Ted

2012-01-01

Fragile X syndrome patients express a wide array of cognitive and other gender-specific phenotypic features. These manifestations result not only from molecular mechanisms that are altered as a result of the expansion of a CGG-repeat region in the FMR1 promoter, but also genetic factors such as founder effects and mosaicism. In this chapter, I will summarize the many and varied features of fragile X syndrome as they present themselves in a clinical setting and describe the procedures that are used to diagnose patients. Finally, I will briefly touch on recent developments that will affect patient screening in the future.

The World Bank and Fragile States: Dynamics of Cooperation and Aid Structure

Directory of Open Access Journals (Sweden)

Solomatin A.

2018-03-01

Full Text Available The eradication of extreme poverty in fragile states is one of the central problems of global governance at the present time. Development of these states is hindered by instability, weak public and social institutions or ongoing conflicts and violence. The World Bank is a key partner of fragile states, which account for almost a third of the world’s population. This article is a continuation of research exploring the evolution of conceptual and practical approaches by the World Bank to cooperation with fragile states. Its methodology is based on a multilevel analysis of the securitization of foreign aid as proposed by J. Lind and J. Howell of the London School of Economics. The main focus of this examination is on the dynamics of the change of scale and structure of the World Bank’s aid to fragile states in comparison with global armed trends of providing aid to fragile states as well. This article concludes that statements about the priority of the Bank’s work in fragile states have not yet been realized in practice. The Bank remains committed to the standard approach to working with this group of recipients, which involves serious risks. The World Bank leans toward supporting projects in fragile states which increases volatility and reduces aid predictability. This trend undermines the development potentials of recipient states. Attention is drawn to political factors influencing aid flows to fragile states and particularly to the tendency of increasing the share of aid provided to fragile states through multi donor trust funds rather than through the mechanisms of the International Development Association (IDA. This trend indicates that the Bank is no longer a central point of aid distribution to the recipients, pointing to the lack of trust of donor states in the existing mechanisms and rules of aid distribution. It also reveals the expanding role of donors’ strategic interests in the process of choosing recipients of World Bank aid.

Heart Activity and Autistic Behavior in Infants and Toddlers with Fragile X Syndrome

Science.gov (United States)

Roberts, Jane E.; Tonnsen, Bridgette; Robinson, Ashley; Shinkareva, Svetlana V.

2012-01-01

The present study contrasted physiological arousal in infants and toddlers with fragile X syndrome to typically developing control participants and examined physiological predictors early in development to autism severity later in development in fragile X syndrome. Thirty-one males with fragile X syndrome (ages 8-40 months) and 25 age-matched…

Raman and DSC studies of fragility in tellurium-zinc oxide glass formers

International Nuclear Information System (INIS)

Stavrou, Elissaios; Kripotou, Sotiria; Raptis, Constantine; Turrell, Sylvia; Syassen, Karl

2011-01-01

Raman scattering and differential scanning calorimetry (DSC) measurements have been carried out in four mixed (TeO 2 ) 1-x (ZnO) x (x = 0.1, 0.2, 0.3, 0.4) glasses at high temperatures (Raman and DSC through the glass transition) and high pressures (Raman) with the aim of determining the fragility of these glass forming oxides. Four different criteria, corresponding to four parameters, were applied to assess the fragility of the glasses. From the DSC studies, we have obtained the fragility parameter m which corresponds to the slopes of Arrhenius (lnQ vs. 1/T g , were Q is the heating rate) plots, and the glass transition width ΔT g . Also, from the low-frequency Raman scattering, and in particular the boson peak intensity of the glasses at T g , we have estimated the fragility ratio r R (T g ) = I min /I max whose value serves as another (empirical) fragility criterion. Finally, from high pressure Raman measurements on the glasses, we have estimated the Grueneisen parameter γ T for each glass, which constitutes the fourth fragility parameter adopted in this work. Considering the four parameters ΔT g , m, r (T g ) and γ T and the generally accepted (empirical) fragility criteria, we conclude that the mixed tellurium-zinc oxides constitute strong-to-intermediate glass formers (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Seismic fragility of ventilation stack of nuclear power plant

International Nuclear Information System (INIS)

Nefedov, S.S.; Yugai, T.Z.; Kalinkin, I.V.; Vizir, P.L.

2003-01-01

Fragility study of safety related elements is necessary step in seismic PSA of nuclear power plant (NPP). In present work fragility was analyzed after the example of the ventilation stack of NPP. Ventilation stack, considered in present work, is a separately erected construction with height of 100 m made of cast-in-place reinforced concrete. In accordance with IAEA terminology fragility of element is defined as conditional probability of its failure at given level of seismic loading. Failure of a ventilation stack was considered as development of the plastic hinge in some section of a shaft. Seismic ground acceleration a, which corresponds to failure, could be defined as limit seismic acceleration of ventilation stack [a]. Limit seismic acceleration [a] was considered as random value. Sources of its variation are connected with stochastic nature of factors determining it (properties of construction materials, soils etc.), and also with uncertainties of existing analytical techniques. Random value [a] was assumed to be distributed lognormally. Median m[a] and logarithmically standard deviation β of this distribution were defined by 'scaling method' developed by R.P. Kennedy et al. Using this values fragility curves were plotted for different levels of confidence probability. (author)

The "enemies within"

DEFF Research Database (Denmark)

Bhowmick, Rahul; Hickson, Ian D

2017-01-01

of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent...

Handbook of nuclear power plant seismic fragilities, Seismic Safety Margins Research Program

International Nuclear Information System (INIS)

Cover, L.E.; Bohn, M.P.; Campbell, R.D.; Wesley, D.A.

1983-12-01

The Seismic Safety Margins Research Program (SSMRP) has a gola to develop a complete fully coupled analysis procedure (including methods and computer codes) for estimating the risk of an earthquake-induced radioactive release from a commercial nuclear power plant. As part of this program, calculations of the seismic risk from a typical commercial nuclear reactor were made. These calculations required a knowledge of the probability of failure (fragility) of safety-related components in the reactor system which actively participate in the hypothesized accident scenarios. This report describes the development of the required fragility relations and the data sources and data reduction techniques upon which they are based. Both building and component fragilities are covered. The building fragilities are for the Zion Unit 1 reactor which was the specific plant used for development of methodology in the program. Some of the component fragilities are site-specific also, but most would be usable for other sites as well

Cities could hold the key to understanding fragility | CRDI - Centre ...

International Development Research Centre (IDRC) Digital Library (Canada)

Cities are engines of economic growth and the primary sites of basic service delivery. Yet weak governance, along with inequalities related to income, social class, religion, and gender, may lead to a breakdown of systems and structures, and eventually to "fragile cities." Although the fragile cities concept is relatively new, ...

Research for genetic instability of human genome

International Nuclear Information System (INIS)

Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M.; Murata, M.

1992-01-01

In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author)

Fragile X syndrome: A review of clinical management

Science.gov (United States)

Lozano, Reymundo; Azarang, Atoosa; Wilaisakditipakorn, Tanaporn; Hagerman, Randi J

2016-01-01

Summary The fragile X mental retardation 1 gene, which codes for the fragile X mental retardation 1 protein, usually has 5 to 40 CGG repeats in the 5′ untranslated promoter. The full mutation is the almost always the cause of fragile X syndrome (FXS). The prevalence of FXS is about 1 in 4,000 to 1 in 7,000 in the general population although the prevalence varies in different regions of the world. FXS is the most common inherited cause of intellectual disability and autism. The understanding of the neurobiology of FXS has led to many targeted treatments, but none have cured this disorder. The treatment of the medical problems and associated behaviors remain the most useful intervention for children with FXS. In this review, we focus on the non-pharmacological and pharmacological management of medical and behavioral problems associated with FXS as well as current recommendations for follow-up and surveillance. PMID:27672537

Modeling Fragile X Syndrome in Drosophila

Science.gov (United States)

Drozd, Małgorzata; Bardoni, Barbara; Capovilla, Maria

2018-01-01

Intellectual disability (ID) and autism are hallmarks of Fragile X Syndrome (FXS), a hereditary neurodevelopmental disorder. The gene responsible for FXS is Fragile X Mental Retardation gene 1 (FMR1) encoding the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein involved in RNA metabolism and modulating the expression level of many targets. Most cases of FXS are caused by silencing of FMR1 due to CGG expansions in the 5′-UTR of the gene. Humans also carry the FXR1 and FXR2 paralogs of FMR1 while flies have only one FMR1 gene, here called dFMR1, sharing the same level of sequence homology with all three human genes, but functionally most similar to FMR1. This enables a much easier approach for FMR1 genetic studies. Drosophila has been widely used to investigate FMR1 functions at genetic, cellular, and molecular levels since dFMR1 mutants have many phenotypes in common with the wide spectrum of FMR1 functions that underlay the disease. In this review, we present very recent Drosophila studies investigating FMRP functions at genetic, cellular, molecular, and electrophysiological levels in addition to research on pharmacological treatments in the fly model. These studies have the potential to aid the discovery of pharmacological therapies for FXS. PMID:29713264

Association between change in BMD and fragility fracture in women and men.

Science.gov (United States)

Berger, Claudie; Langsetmo, Lisa; Joseph, Lawrence; Hanley, David A; Davison, K Shawn; Josse, Robert G; Prior, Jerilynn C; Kreiger, Nancy; Tenenhouse, Alan; Goltzman, David

2009-02-01

Our objective was to estimate the relationship between longitudinal change in BMD and fragility fractures. We studied 3635 women and 1417 men 50-85 yr of age in the Canadian Multicentre Osteoporosis Study who had at least two BMD measurements (lumbar spine, femoral neck, total hip, and trochanter) within the first 5 yr of the study and fragility fractures (any, main, forearm/wrist, ribs, hip) within the first 7 yr. Multiple logistic regression was used to model the relationship between baseline BMD, BMD change, and fragility fractures. We found that, among nonusers of antiresorptives, independent of baseline BMD, a decrease of 0.01 g/cm(2)/yr in total hip BMD was associated with an increased risk of fragility fracture with ORs of 1.15 (95% CI: 1.01; 1.32) in women and 1.34 (95% CI: 1.02; 1.78) in men. The risk of fragility fractures in subgroups such as fast losers and those with osteopenia was better estimated by models that included BMD change than by models that included baseline BMD but excluded BMD change. Although the association between baseline BMD and fragility fractures was similar in users and nonusers of antiresorptives, the association was stronger in nonusers compared with users. These results show that BMD change in both men and women is an independent risk factor for fragility fractures and also predicts fracture risk in those with osteopenia. The results suggest that BMD change should be included with other variables in a comprehensive fracture prediction model to capture its contribution to osteoporotic fracture risk.

Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.

Science.gov (United States)

Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H

2013-07-08

The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.

Thermalization as an Invisibility Cloak for Fragile Quantum Superpositions

OpenAIRE

Hahn, Walter; Fine, Boris V.

2017-01-01

We propose a method for protecting fragile quantum superpositions in many-particle systems from dephasing by external classical noise. We call superpositions "fragile" if dephasing occurs particularly fast, because the noise couples very differently to the superposed states. The method consists of letting a quantum superposition evolve under the internal thermalization dynamics of the system, followed by a time reversal manipulation known as Loschmidt echo. The thermalization dynamics makes t...

Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability.

Science.gov (United States)

Schalbetter, Stephanie A; Mansoubi, Sahar; Chambers, Anna L; Downs, Jessica A; Baxter, Jonathan

2015-08-18

Faithful genome duplication and inheritance require the complete resolution of all intertwines within the parental DNA duplex. This is achieved by topoisomerase action ahead of the replication fork or by fork rotation and subsequent resolution of the DNA precatenation formed. Although fork rotation predominates at replication termination, in vitro studies have suggested that it also occurs frequently during elongation. However, the factors that influence fork rotation and how rotation and precatenation may influence other replication-associated processes are unknown. Here we analyze the causes and consequences of fork rotation in budding yeast. We find that fork rotation and precatenation preferentially occur in contexts that inhibit topoisomerase action ahead of the fork, including stable protein-DNA fragile sites and termination. However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3. In the absence of Tof1/Timeless, excessive fork rotation and precatenation cause extensive DNA damage following DNA replication. With Tof1, damage related to precatenation is focused on the fragile protein-DNA sites where fork rotation is induced. We conclude that although fork rotation and precatenation facilitate unwinding in hard-to-replicate contexts, they intrinsically disrupt normal chromosome duplication and are therefore restricted by Timeless/Tipin.

Babies at Double Jeopardy: Medically Fragile Infants and Child Neglect

Science.gov (United States)

Fullar, Suzanne A.

2008-01-01

Medically fragile infants, those born prematurely or with other complex medical or genetic problems, are at risk of long-term health and developmental problems. When a medically fragile infant comes home to a family with significant social problems such as domestic violence, mental illness, or substance abuse, the infant is at double jeopardy--at…

Self-Injurious Behavior and Fragile X Syndrome: Findings from the National Fragile X Survey

Science.gov (United States)

Symons, Frank J.; Byiers, Breanne J.; Raspa, Melissa; Bishop, Ellen; Bailey, Donald B., Jr.

2010-01-01

We used National Fragile X Survey data in order to examine reported self-injurious behavior (SIB) to (a) generate lifetime and point prevalence estimates, (b) document detailed features of SIB (frequency, types, location, severity) in relation to gender, and (c) compare comorbid conditions between matched pairs (SIB vs. no SIB). Results indicate…

Fetal chromosome analysis: screening for chromosome disease?

DEFF Research Database (Denmark)

Philip, J; Tabor, Ann; Bang, J

1983-01-01

The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...

Positron Emission Tomography (PET Quantification of GABAA Receptors in the Brain of Fragile X Patients.

Directory of Open Access Journals (Sweden)

Charlotte D'Hulst

Full Text Available Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS, a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.

Spatial organization of the budding yeast genome in the cell nucleus and identification of specific chromatin interactions from multi-chromosome constrained chromatin model.

Science.gov (United States)

Gürsoy, Gamze; Xu, Yun; Liang, Jie

2017-07-01

Nuclear landmarks and biochemical factors play important roles in the organization of the yeast genome. The interaction pattern of budding yeast as measured from genome-wide 3C studies are largely recapitulated by model polymer genomes subject to landmark constraints. However, the origin of inter-chromosomal interactions, specific roles of individual landmarks, and the roles of biochemical factors in yeast genome organization remain unclear. Here we describe a multi-chromosome constrained self-avoiding chromatin model (mC-SAC) to gain understanding of the budding yeast genome organization. With significantly improved sampling of genome structures, both intra- and inter-chromosomal interaction patterns from genome-wide 3C studies are accurately captured in our model at higher resolution than previous studies. We show that nuclear confinement is a key determinant of the intra-chromosomal interactions, and centromere tethering is responsible for the inter-chromosomal interactions. In addition, important genomic elements such as fragile sites and tRNA genes are found to be clustered spatially, largely due to centromere tethering. We uncovered previously unknown interactions that were not captured by genome-wide 3C studies, which are found to be enriched with tRNA genes, RNAPIII and TFIIS binding. Moreover, we identified specific high-frequency genome-wide 3C interactions that are unaccounted for by polymer effects under landmark constraints. These interactions are enriched with important genes and likely play biological roles.

Fragility curves for bridges under differential support motions

DEFF Research Database (Denmark)

Konakli, Katerina

2012-01-01

This paper employs the notion of fragility to investigate the seismic vulnerability of bridges subjected to spatially varying support motions. Fragility curves are developed for four highway bridges in California with vastly different structural characteristics. The input in this analysis consists...... of simulated ground motion arrays with temporal and spectral nonstationarities, and consistent with prescribed spatial variation patterns. Structural damage is quantified through displacement ductility demands obtained from nonlinear time-history analysis. The potential use of the ‘equal displacement’ rule...... to approximately evaluate displacement demands from analysis of the equivalent linear systems is examined....

Fragility of chalcogenide glass in relation to characteristic temperature T0/Tg

Science.gov (United States)

Shaker, A. M.; Shanker Rao, T.; Lilly Shanker Rao, T.; Venkataraman, K.

2018-03-01

The present study reports the mutual relationship between the fragility index m and the characteristic temperature T0/Tg. The fragility of the chalcogenide amorphous glass of Ge10Se50Te40 is calculated by utilizing glass transition temperature (Tg) measured by DSC (Differential Scanning Calorimetry) at different heating rates (β) in the range 5 to 20 K/min. Vogel-Fulcher-Tammann (VFT) equation is fitted to the data of Tg. In addition to the VFT method, three other methods are also used to evaluate m. The fragility index m of the Ge10Se50Te40 system showed the trend of decrease with increasing heating rate but remained stable around 22 for the heating rate 10 K/min. The value of m for the glass is near the lower limit (m ≈ 16) this indicates the alloy is a strong glass forming material in accordance of Angell’s interpretation of fragility. The calculated values of characteristic temperature T0/Tg is very close to 1 which also indicates that clearly the system is most fragile.

Fragile X premutation carriers: A systematic review of neuroimaging findings.

Science.gov (United States)

Brown, Stephanie S G; Stanfield, Andrew C

2015-05-15

Expansion of the CGG repeat region of the FMR1 gene from less than 45 repeats to between 55 and 200 repeats is known as the fragile X premutation. Carriers of the fragile X premutation may develop a neurodegenerative disease called fragile X-associated tremor/ataxia syndrome (FXTAS). Recent evidence suggests that premutation carriers experience other psychiatric difficulties throughout their lifespan. Medline, EMBASE and PsychINFO were searched for all appropriate English language studies published between January 1990 and December 2013. 419 potentially relevant articles were identified and screened. 19 articles were included in the analysis. We discuss key structural magnetic resonance imaging (MRI) findings such as the MCP sign and white matter atrophy. Additionally, we discuss how functional MRI results have progressed our knowledge of how FXTAS may manifest, including reduced brain activation during social and memory tasks in multiple regions. This systematic review may have been limited by the search for articles on just 3 scientific databases. Differing techniques and methods of analyses between research groups and primary research articles may have caused differences in results between studies. Current MRI studies into the fragile X premutation have been important in the diagnosis of FXTAS and identifying potential pathophysiological mechanisms. Associations with blood based measures have also demonstrated that neurodevelopmental and neurodegenerative aspects of the fragile X premutation could be functionally and pathologically separate. Larger longitudinal studies will be required to investigate these conclusions. Copyright © 2015 Elsevier B.V. All rights reserved.

Fragile Cities: a Critical Perspective on the Repertoire for New Urban Humanitarian Interventions

Directory of Open Access Journals (Sweden)

Manoela Miklos

Full Text Available Abstract At the end of the 1990s, researchers involved in the debate on the new wars introduced discussion about the urban dimension of contemporary conflicts into the International Relations discipline. The innovative debate about urban fragility is one of the many lines of inquiry that emerge within the framework of the relationship between cities and contemporary conflicts. This paper seeks to demonstrate that the concept of ‘fragile city’ offers a new and relevant analytical framework for understanding contemporary urban violence and inequality. Moreover, this same concept could also be instrumental in making fragile cities the new locus of international humanitarianism. The notion of fragile city emerges to describe new emergency situations more closely linked to urban contexts than to national dynamics, as previously described in the literature on fragile states. The concept of fragile city is a groundbreaking tool for understanding the human consequences of inequality in urban settings, but might also be used as a rhetorical vehicle for the reproduction of old dynamics and the inauguration of new intervention practices in urban areas that were previously inaccessible to humanitarian action, especially cities in Latin America.

Component Fragility Research Program: Phase 1, Demonstration tests: Volume 1, Summary report

International Nuclear Information System (INIS)

Holman, G.S.; Chou, C.K.; Shipway, G.D.; Glozman, V.

1987-08-01

This report describes tests performed in Phase I of the NRC Component Fragility Research Program. The purpose of these tests was to demonstrate procedures for characterizing the seismic fragility of a selected component, investigating how various parameters affect fragility, and finally using test data to develop practical fragility descriptions suitable for application in probabilistic risk assessments. A three-column motor control center housing motor controllers of various types and sizes as well as relays of different types and manufacturers was subjected to seismic input motions up to 2.5g zero period acceleration. To investigate the effect of base flexibility on the structural behavior of the MCC and on the functional behavior of the electrical devices, multiple tests were performed on each of four mounting configurations: four bolts per column with top bracking, four bolts per column with no top brace, four bolts per column with internal diagonal bracking, and two bolts per column with no top or internal bracking. Device fragility was characterized by contact chatter correlated to local in-cabinet response at the device location. Seismic capacities were developed for each device on the basis of local input motion required to cause chatter; these results were then applied to develop probabilistic fragility curves for each type of device, including estimates of the ''high-confidence low probability of failure'' capacity of each

The "enemies within": regions of the genome that are inherently difficult to replicate [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Rahul Bhowmick

2017-05-01

Full Text Available An unusual feature of many eukaryotic genomes is the presence of regions that appear intrinsically difficult to copy during the process of DNA replication. Curiously, the location of these difficult-to-replicate regions is often conserved between species, implying a valuable role in some aspect of genome organization or maintenance. The most prominent class of these regions in mammalian cells is defined as chromosome fragile sites, which acquired their name because of a propensity to form visible gaps/breaks on otherwise-condensed chromosomes in mitosis. This fragility is particularly apparent following perturbation of DNA replication—a phenomenon often referred to as “replication stress”. Here, we review recent data on the molecular basis for chromosome fragility and the role of fragile sites in the etiology of cancer. In particular, we highlight how studies on fragile sites have provided unexpected insights into how the DNA repair machinery assists in the completion of DNA replication.

Fragile X mental retardation protein participates in non-coding RNA pathways.

Science.gov (United States)

Li, En-Hui; Zhao, Xin; Zhang, Ce; Liu, Wei

2018-02-20

Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells. Subsequent studies showed that the Drosophila FMRP participates in piRNA pathway by interacting with Aub, Ago1 and Piwi in the maintenance of normal chromatin structures and genomic stability. More recent studies showed that FMRP is associated with lncRNA pathway, suggesting a potential role for the involvement in the clinical manifestations. In this review, we summarize the novel findings and explore the relationship between FMRP and non-coding RNA pathways, particularly the piRNA pathway, thereby providing critical insights on the molecular pathogenesis of Fragile X syndrome, and potential translational applications in clinical management of the disease.

Ethnobotany and Ethnomedicinal Uses, Chromosomal Status and Natural Propagation of Some Plants of Lahaul-Spiti and Adjoining Hills

Directory of Open Access Journals (Sweden)

Puneet Kumar

2013-01-01

Full Text Available The present study documented the ethnobotanical and medicinal uses of plants from an ecologically fragile cold desert area of Lahaul-Spiti (Himachal Pradesh, India. Local people use plants for curing the stomach troubles, pain reliever, cough, gastric disorders, and aphrodisiac and other household purposes. In addition, chromosome numbers, male meiosis, and natural propagation were also investigated in these ethnobotanically used plants. Present investigations also form the basis for exploitation of intraspecific chromosomal variation/new cytotypes recorded in some of the presently studied species to detect biochemical diversity in the medicinally important plants. For documentation of ethnobotanical information, personal observations and interviews were conducted with medicine men, hakims, farmers, shepherds, local healers, and old aged people. This study identified 40 plant species under 33 genera belonging to 17 families which have been used locally for curing various diseases and other purposes. All the chromosome counts are new to the study area. On worldwide basis, meiotic chromosome counts of n=14 and n=8 in Rosularia alpestris and Corydalis govaniana, respectively, are the first ever reports. The present study indicates that the people of the area possess good knowledge about the different uses of plants in the area. It has been noticed that due to the lack of interest among younger generations in the preservation of invaluable ethnic knowledge, there is every possible chance of losing such a rich heritage of knowledge. It is very urgent to conserve such invaluable ethnic knowledge before it gets lost.

Selective Spatial Processing Deficits in an At-Risk Subgroup of the Fragile X Premutation

Science.gov (United States)

Hocking, Darren R.; Kogan, Cary S.; Cornish, Kim M.

2012-01-01

Until a decade ago, it was assumed that males with the fragile X premutation were unaffected by any cognitive phenotype. Here we examined the extent to which CGG repeat toxicity extends to visuospatial functioning in male fragile X premutation carriers who are asymptomatic for a late-onset neurodegenerative disorder, fragile X-associated…

Takagi-Sugeno Fuzzy Systems Non-fragile H-infinity Filtering

CERN Document Server

Chang, Xiao-Heng

2012-01-01

"Takagi-Sugeno Fuzzy Systems Non-fragile H-infinity Filtering" investigates the problem of non-fragile H-infinity filter design for T-S fuzzy systems. The nonlinear plant is represented by a T-S fuzzy model. Given a T-S fuzzy system, the objective of this book is to design an H-infinity filter with the gain variations such that the filtering error system guarantees a prescribed H-infinity performance level. Furthermore, it demonstrates that the solution of non-fragile H-infinity filter design problem can be obtained by solving a set of linear matrix inequalities (LMIs). The intended audiences are graduate students and researchers both from the fields of engineering and mathematics. Dr. Xiao-Heng Chang is an Associate Professor at the College of Engineering, Bohai University, Jinzhou, Liaoning, China. He is also a Postdoctoral Researcher at the College of Information Science and Engineering, Northeastern University, Shenyang, China.

Research for genetic instability of human genome

Energy Technology Data Exchange (ETDEWEB)

Hori, T.; Takahashi, E.; Tsuji, H.; Yamauchi, M. (National Inst. of Radiological Sciences, Chiba (Japan)); Murata, M.

1992-01-01

In the present review paper, the potential relevance of chromosomal fragile sites to carcinogenesis and mutagenesis is discussed based on our own and other's studies. Recent evidence indicate that fragile sites may act as predisposition factors involved in chromosomal instability of the human genome and that the sites may be preferential targets for various DNA damaging agents including ionizing radiation. It is also demonstrated that some critical genomic rearrangements at the fragile sites may contribute towards oncogenesis and that individuals carrying heritable form of fragile site may be at the risk. Although clinical significance of autosomal fragile sites has been a matter of discussion, a fragile site of the X chromosome is known to be associated with an X-linked genetic diseases, called fragile X syndrome. Molecular events leading to the fragile X syndrome have recently been elucidated. The fragile X genotype can be characterized by an increased amount of p(CCG)n repeat DNA sequence in the FMR-1 gene and the repeated sequences are shown to be unstable in both meiosis and mitosis. These repeats might exhibit higher mutation rate than is generally seen in the human genome. Further studies on the fragile sites in molecular biology and radiation biology will yield relevant data to the molecular mechanisms of genetic instability of the human genome as well as to better assessment of genetic effect of ionizing radiation. (author).

Inter-chromosomal heterogeneity in the formation of radiation induced chromosomal aberrations

International Nuclear Information System (INIS)

Natarajan, A.T.; Vermeulen, S.; Boei, J.J.W.A.

1997-01-01

It is generally assumed that radiation induced chromosomal lesions are distributed randomly and repaired randomly among the genome. Recent studies using fluorescent in situ hybridization (FISH) and chromosome specific DNA libraries indicate that some chromosomes are more sensitive for radiation induced aberration formation than others. Chromosome No. 4 in human and chromosome No. 8 in Chinese hamster have been found to involve more in exchange aberrations than others, when calculated on the basis of their DNA content. Painting with arm specific chromosome libraries indicate that the frequencies of radiation induced intra-chromosome exchanges (i.e., between the arms of a chromosome, such as centric rings and inversions) are far in excess than one would expect on the basis of the frequencies of observed inter-chromosomal exchanges. The possible factors leading to the observed heterogeneity will be discussed

Transmission of chromosomal and instability via a chromosome irradiated with ionizing radiation

International Nuclear Information System (INIS)

Kodama, Seiji; Tanabe, Masateru; Shiraishi, Kazunori; Oshimura, Mitsuo

2010-01-01

We examined the stability of the transferred chromosome in 5 and 12 microcell hybrids including unirradiated human chromosomes 6 and 8, respectively, and 6 and 19 microcell hybrids including 4 Gy-irradiated human chromosomes 6 and 8, respectively. The transferred chromosome was structurally stable in most microcell hybrids transferred with the unirradiated chromosomes 6 and 8. In contrast, the 4 Gy-irradiated human chromosomes were unstable in 3 out of 6 hybrids (50%) with chromosome 6 and 3 out of 19 hybrids (16%) with chromosome 8, showing multiple aberrations in high frequencies (35∼98%). To know the cause of delayed chromosomal instability, intrachromosomal rearrangements of the human chromosome is investigated by subtelomere FISH in 17 microcell hybrids transferred with chromosomes 6 and 8. We found frequent intrachromosomal in 7 microcell hybrids (41%). However, no clear correlation was observed between the intrachromosomal rearrangements and the induction of delayed chromosomal instability by ionizing radiation

Family Environment and Behavior Problems in Children, Adolescents, and Adults with Fragile X Syndrome

Science.gov (United States)

Greenberg, Jan S.; Seltzer, Marsha Mailick; Baker, Jason K.; Smith, Leann E.; Warren, Steven F.; Brady, Nancy; Hong, Jinkuk

2012-01-01

We examine how the family environment is associated with aspects of the Fragile X syndrome phenotype during childhood, adolescence, and adulthood. Mothers of children (n = 48), adolescents (n = 85), and adults (n = 34) with Fragile X syndrome participated in a multisite study. For children and adults with Fragile X syndrome, the presence of warmth…

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand*

Science.gov (United States)

Teasley, Daniel C.; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R.; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A.

2015-01-01

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. PMID:25922071

Mitotic chromosome structure

International Nuclear Information System (INIS)

Heermann, Dieter W.

2012-01-01

Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

Mitotic chromosome structure

Energy Technology Data Exchange (ETDEWEB)

Heermann, Dieter W., E-mail: heermann@tphys.uni-heidelberg.de

2012-07-15

Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.

Fragile Elite

DEFF Research Database (Denmark)

Bregnbæk, Susanne

China's One Child Policy and its rigorous national focus on educational testing are well known. But what happens to those "lucky" few at the very top of the pyramid? Fragile Elite explores the contradictions of being an elite student through ethnographic research conducted at two top universities...... in China. It uncovers the intimate psychological strains students suffer under the pressure imposed on them by parents and state, where the state acts as a parent, and the parents sometimes reinforce the state. The book offers insights into the intergenerational tensions as work in relation to the ongoing...... shifts in educational policy and definition of what a "quality" student, child, and citizen is in contemporary China....

Fragile X syndrome: panoramic radiographic evaluation of dental anomalies, dental mineralization stage, and mandibular angle

Directory of Open Access Journals (Sweden)

Aida Sabbagh-Haddad

Full Text Available ABSTRACT Fragile X syndrome (FXS is a disorder linked to the chromosome X long arm (Xq27.3, which is identified by a constriction named fragile site. It determines various changes, such as behavioral or emotional problems, learning difficulties, and intellectual disabilities. Craniofacial abnormalities such as elongated and narrow face, prominent forehead, broad nose, large and prominent ear pavilions, strabismus, and myopia are frequent characteristics. Regarding the oral aspects, deep and high-arched palate, mandibular prognathism, and malocclusion are also observed. Objective: The purpose of this study was to evaluate the dental radiographic characteristics as described in 40 records of patients with panoramic radiography. Material and Methods: The patients were in the range of 6–17 years old, and were divided into two groups (20 subjects who were compatible with the normality standard and 20 individuals diagnosed with the FXS, which were matched for gender and age. Analysis of the panoramic radiographic examination involved the evaluation of dental mineralization stage, mandibular angle size, and presence of dental anomalies in both deciduous and permanent dentitions. Results: The results of radiographic evaluation demonstrated that the chronology of tooth eruption of all third and second lower molars is anticipated in individuals with FXS (p<0.05. In this group, supernumerary deciduous teeth (2.83%, giroversion of permanent teeth (2.31%, and partial anodontia (1.82% were the most frequent dental anomalies. In addition, an increase was observed in the mandibular angle size in the FXS group (p<0.05. Conclusion: We conclude that knowledge of dental radiographic changes is of great importance for dental surgeons to plan the treatment of these individuals.

The Evaluation of Corneal Fragility After UVA/Riboflavin Crosslinking.

Science.gov (United States)

Li, Zhiwei; Wang, Yumeng; Xu, Yanyun; Jhanji, Vishal; Zhang, Chunxiao; Mu, Guoying

2017-03-01

To evaluate the fragility of cornea after UVA/riboflavin crosslinking (CXL). Sixty New Zealand rabbits received UVA/riboflavin crosslinking treatment (wavelength 365 nm, irradiance 3.0 mW/cm, and total dose 5.4 J/cm) on right eyes. Animals were sacrificed before and immediately after treatment (day 0), day 1, 3, 7, and 28 after treatment. A 4×10 mm corneal strip for biomechanical evaluation was harvested after sacrifice. The corneal fragility was evaluated by measurement of elongation rate, whereby the elongation rate equals elongation length/baseline length. The Youngs modulus and maximal stress were 1.41±0.51 MPa and 5.56±1.84 MPa before CXL, and increased to 2.31±0.68 MPa (P=0.008) and 9.25±2.74 MPa (P=0.04), respectively, on day 0, then maintained a stable level within a 28 days follow-up. The elongation rate was 62.04±9.34% before CXL and decreased to 48.95%±8.24% (P=0.02) on day 0, then maintained a stable level within a 28 days follow-up. This study showed an increase in the corneal fragility after UVA/riboflavin crosslinking along with an increase in the corneal stiffness. A long-term follow-up should be taken to evaluate the potential deleterious effect of the increasing corneal fragility after UVA/riboflavin crosslinking.

Manipulations of attention dissociate fragile visual short-term memory from visual working memory.

Science.gov (United States)

Vandenbroucke, Annelinde R E; Sligte, Ilja G; Lamme, Victor A F

2011-05-01

People often rely on information that is no longer in view, but maintained in visual short-term memory (VSTM). Traditionally, VSTM is thought to operate on either a short time-scale with high capacity - iconic memory - or a long time scale with small capacity - visual working memory. Recent research suggests that in addition, an intermediate stage of memory in between iconic memory and visual working memory exists. This intermediate stage has a large capacity and a lifetime of several seconds, but is easily overwritten by new stimulation. We therefore termed it fragile VSTM. In previous studies, fragile VSTM has been dissociated from iconic memory by the characteristics of the memory trace. In the present study, we dissociated fragile VSTM from visual working memory by showing a differentiation in their dependency on attention. A decrease in attention during presentation of the stimulus array greatly reduced the capacity of visual working memory, while this had only a small effect on the capacity of fragile VSTM. We conclude that fragile VSTM is a separate memory store from visual working memory. Thus, a tripartite division of VSTM appears to be in place, comprising iconic memory, fragile VSTM and visual working memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Role of Chain Length in Nonergodicity Factor and Fragility of Polymers

DEFF Research Database (Denmark)

Dalle-Ferrie, Cecile; Niss, Kristine; Sokolov, Alexei

2010-01-01

The mechanism that leads to different fragility values upon approaching the glass transition remains a topic of active discussion. Many researchers are trying to find an answer in the properties of the frozen glassy state. Following this approach, we focus here on a previously proposed relationship...... between the fragility of glass-formers and their nonergodicity factor, determined by inelastic X-ray scattering (IXS) in the glass. We extend this molecular liquid study to two model polymers— polystyrene (PS) and polyisobutylene (PIB)—for which we change the molecular weight. Polymers offer...... the opportunity to change the fragility without altering the chemical structure, just by changing the chain length. Thus, we specifically chose PS and PIB because they exhibit opposite dependences of fragility with molecular weight. Our analysis for these two polymers reveals no unique correlation between...

Influence of carbide precipitation upon hydrogen fragilization of an AISI 304 steel

International Nuclear Information System (INIS)

Hazarabedian, A.E.; Ovejero Garcia, J.

1991-01-01

The present work deals with austenitic stainless steels for a family of steels that is renowned for its high resistance to hydrogen fragilization. Nevertheless, these steels may suffer hydrogen fragilization under severe working conditions. This fact is strongly dependent on many factors -composition, grain size, other phases present, corrosion sensitivity, etc.-. While there are studies that show how intergranular corrosion is influenced by corrosion sensitivity -mainly due to carbide precipitation in grain boundaries-, there are no reports about the effect of the carbide precipitation itself on hydrogen fragilization for these steels. (Author) [es

On the pressure dependence of the fragility of glycerol

Energy Technology Data Exchange (ETDEWEB)

Pawlus, S; Paluch, M; Ziolo, J [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Roland, C M [Naval Research Laboratory, Chemistry Division, Code 6120, Washington, DC 20375-5342 (United States)

2009-08-19

This work was motivated by ostensibly contradictory results from different groups regarding the effect of pressure on the fragility of glycerol. We present new experimental data for an intermediate pressure regime showing that the fragility increases with pressure up to about 1.8 GPa, becoming invariant at higher pressures. There is no discrepancy among the various literature data taken in toto. The behavior of glycerol is quite distinct from that of normal liquids, a result of its substantial hydrogen bonding. (fast track communication)

Behavioral Intervention for Problem Behavior in Children with Fragile X Syndrome

Science.gov (United States)

Moskowitz, Lauren J.; Carr, Edward G.; Durand, V. Mark

2011-01-01

Parents and professionals typically report problem behavior as a significant concern for children with fragile X syndrome. In the present study, the authors explored whether behaviorally based interventions would result in a reduction in problem behavior and an improvement in quality of life for 3 children with fragile X syndrome and their…

Chromosomal aberration

International Nuclear Information System (INIS)

Ishii, Yutaka

1988-01-01

Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G 2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G 2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G 2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G 1 phase. (author)

A novel approach to simultaneously scan genes at fragile sites

International Nuclear Information System (INIS)

Willem, Pascale; Brown, Jacqueline; Schouten, Jan

2006-01-01

Fragile sites are regions of the genome sensitive to replication stress and to exposure to environmental carcinogens. The two most commonly expressed fragile sites FRA3B and FRA16D host the histidine triad (FHIT) and WW domain containing oxidoreductase (WWOX) genes respectively. There is growing evidence that both genes contribute to cancer development and they are frequently altered by allelic and homozygous deletions in a variety of tumors. Their status is linked to prognosis in several malignancies and they are thought to be involved in early tumorigenesis. The loci for FHIT and WWOX both span over a megabase but the genes encode for small transcripts. Thus the screening of intragenic deletion can be difficult and has relied on loss of heterozygosity LOH assays, or genomic arrays. Multiplex ligation dependent probe amplification MLPA, allows for the detection of deletions/duplications and relative quantification of up to 40 specific probes in a single assay. A FHIT/WWOX MLPA assay was designed, applied and validated in five esophageal squamous cell carcinoma ESCC, cell lines established in South Africa where this cancer is of high prevalence. Sixteen probes covered all FHIT exons and 7 probes covered WWOX. Both homozygous and hemizygous deletions were detected in FHIT, in four of the cell lines with a preferential deletion of exons 5 and 4. Chromosome 3 short arm was present in normal copy number indicating that deletions were site specific. In contrast WWOX was not altered in any cell lines. RT-PCR expression pattern paralleled the pattern of deletions. Ten primary ESCC tumor specimens were subsequently screened with this assay. FHIT exon deletions were found in four of them. This method offers an alternative to loss of heterozygosity studies. Simultaneous scanning of FHIT and WWOX exons in the context of early tumorigenesis and tumor progression, may help clarify the mechanistic events related to cancer development which are not revealed by imuno

Essays on financial fragility and regulation

NARCIS (Netherlands)

Ma, K.

2013-01-01

This thesis investigates various issues in regulation, with three chapters on financial fragility and banking regulation, and one chapter on competition policy. Chapter 2 studies banks’ herding driven by their need for market liquidity, highlighting a trade-off between systemic risk and liquidity

Y-chromosome evolution: emerging insights into processes of Y-chromosome degeneration.

Science.gov (United States)

Bachtrog, Doris

2013-02-01

The human Y chromosome is intriguing not only because it harbours the master-switch gene that determines gender but also because of its unusual evolutionary history. The Y chromosome evolved from an autosome, and its evolution has been characterized by massive gene decay. Recent whole-genome and transcriptome analyses of Y chromosomes in humans and other primates, in Drosophila species and in plants have shed light on the current gene content of the Y chromosome, its origins and its long-term fate. Furthermore, comparative analysis of young and old Y chromosomes has given further insights into the evolutionary and molecular forces triggering Y-chromosome degeneration and into the evolutionary destiny of the Y chromosome.

Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.

Science.gov (United States)

Inda, María del Mar; Fan, Xing; Muñoz, Jorge; Perot, Christine; Fauvet, Didier; Danglot, Giselle; Palacio, Ana; Madero, Pilar; Zazpe, Idoya; Portillo, Eduardo; Tuñón, Teresa; Martínez-Peñuela, José María; Alfaro, Jorge; Eiras, José; Bernheim, Alain; Castresana, Javier S

2003-01-01

Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss. Copyright 2002 Wiley-Liss, Inc.

Managing Public Finance and Procurement in Fragile and Conflicted Settings

OpenAIRE

Porter, Doug; Andrews, Matt; Turkewitz, Joel; Wescotttz, Clay

2011-01-01

Discusses ways to enhance the incentives for elites to invest political capital in achieving (1) functional results through the formal public finance management (PFM) system; (2) the effectiveness of agencies responsible for services and regulating activities; and (3) better performance of civil service officials. Using the Public Expenditure and Financial Accountability (PEFA) Performance Measurement Framework, countries affected by conflict and fragility can be compared with non-fragile poo...

Fragility Modeling of Aging Containment Metallic Pressure Boundaries

International Nuclear Information System (INIS)

Cherry, J.L.; Ellingwood, B.R.

1999-01-01

The containment in a nuclear power plant (NPP) provides a barrier against the release of radioactivity in the event of an accident. Corrosion that has been observed in some steel containments and liners of reinforced concrete containments has raised questions about their ability to perform this function. The performance of corroded containments during events at or beyond the design basis is impacted by numerous sources of uncertainty. A fragility model of the containment provides a relatively simple depiction of the impact of uncertainties on structural performance and a basis for decision-making in the presence of uncertainty. Moreover, it is a necessary ingredient of any time-dependent structural reliability analysis. A nonlinear finite element analysis of containment response furnishes the necessary platform to perform numerical experiments to determine containment fragility. A statistically-based sampling plan minimizes the finite element computations required to develop the fragility curve. The -percentile (or other fractile) then gives a statistically based indication of the lower bound on containment capacity, and can be used as a screening tool to determine whether more refined further analysis or tests to support service life evaluations are warranted

Slit scan flow cytometry of isolated chromosomes following fluorescence hybridization: an approach of online screening for specific chromosomes and chromosome translocations

NARCIS (Netherlands)

Hausmann, M.; Dudin, G.; Aten, J. A.; Heilig, R.; Diaz, E.; Cremer, C.

1991-01-01

The recently developed methods of non radioactive in situ hybridization of chromosomes offer new aspects for chromosome analysis. Fluorescent labelling of hybridized chromosomes or chromosomal subregions allows to facilitate considerably the detection of specific chromosomal abnormalities. For many

The Relationship between the (In-)Stability of NORs and Their Chromosomal Location: The Example of Cercopithecidae and a Short Review of Other Primates.

Science.gov (United States)

Gerbault-Seureau, Michèle; Cacheux, Lauriane; Dutrillaux, Bernard

2017-01-01

Amongst Cercopithecidae, the species of the Cercopithecini tribe underwent a very active chromosome evolution, principally by fissions, which increased their chromosome number up to 72. In contrast, all the species of Papionini have fairly similar karyotypes with 42 chromosomes. In animals, nucleolus organizer regions (NORs) are generally considered as instable structures, which frequently vary in size, number, and location at both infra- and interspecific levels. Although in Cercopithecinae the NORs, involved in breaks, exchanges, and translocations, behave like fragile sites in somatic cells, their number and location appear to be very stable between species. Fluorescence in situ hybridization of a 28S rDNA probe on metaphase chromosomes displayed a unique interstitial location in either an acrocentric pair (in 12 species of Cercopithecini) or a metacentric pair (in 6 species of Papionini). A non-exhaustive survey of literature data on NOR location in other primates shows that numerical variations of the NORs principally depend on their location: most multiple NORs are in terminal positions, while almost all unique NORs are in interstitial positions. We propose that this correlation is the consequence of the selection against gametic imbalances involving the chromosomal material distal to the NORs, which is effective when they are interstitially, but not terminally, located. Thus, the consequences of the interstitial NOR instability for reproduction are essentially limited to their size variations, as observed in Cercopithecidae. © 2018 S. Karger AG, Basel.

Flap Endonuclease 1 Limits Telomere Fragility on the Leading Strand.

Science.gov (United States)

Teasley, Daniel C; Parajuli, Shankar; Nguyen, Mai; Moore, Hayley R; Alspach, Elise; Lock, Ying Jie; Honaker, Yuchi; Saharia, Abhishek; Piwnica-Worms, Helen; Stewart, Sheila A

2015-06-12

The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Seismic fragility analysis of the block masonry wall in nuclear power plants

International Nuclear Information System (INIS)

Wang, Z-L.; Pandey, M.D.; Xie, X-C.

2014-01-01

The evaluation of seismic fragility of a structure is an integral part in the Seismic Probabilistic Risk Analysis (SPRA). The block masonry wall, a commonly used barrier in nuclear power plants, is fairly vulnerable to failure under an earthquake. In practice, the seismic fragility of block walls is commonly evaluated using a simple deterministic approach called Conservative Deterministic Failure Margin (CDFM) method. This paper presents a more formal fragility analysis of a block wall based on rigorous probabilistic methods and the accuracy of the CDFM method is evaluated by comparison to the more rigorous FA method. (author)

Fragility and structure of Al-Cu alloy melts

International Nuclear Information System (INIS)

Lv Xiaoqian; Bian Xiufang; Mao Tan; Li Zhenkuan; Guo Jing; Zhao Yan

2007-01-01

The dynamic viscosity measurements are performed for Al-Cu alloy melts with different compositions using an oscillating-cup viscometer. The results show that the viscosities of Al-Cu alloy melts increase with the copper content increasing, and also have a correlation with the correlation radius of clusters, which is measured by the high-temperature X-ray diffractometer. It has also been found that the fragilities of superheated melts (M) of hypereutectic Al-Cu alloys increase with the copper content increasing. There exists a relationship between the fragility and the structure in Al-Cu alloy melts. The value of the M reflects the variation of activation energy for viscous flow

Seismic fragility capacity of equipment--horizontal shaft pump test

International Nuclear Information System (INIS)

Iijima, T.; Abe, H.; Suzuki, K.

2005-01-01

The current seismic fragility capacity of horizontal shaft pump is 1.6 x 9.8 m/s 2 (1.6 g), which was decided from previous vibration tests and we believe that it must have sufficient margin. The purpose of fragility capacity test is to obtain realistic seismic fragility capacity of horizontal shaft pump by vibration tests. Reactor Building Closed Cooling Water (RCW) Pump was tested as a typical horizontal shaft pump, and then bearings and liner rings were tested as important parts to evaluate critical acceleration and dispersion. Regarding RCW pump test, no damage was found, though maximum input acceleration level was 6 x 9.8 m/s 2 (6 g). Some kinds of bearings and liner rings were tested on the element test. Input load was based on seismic motion which was same with the RCW pump test, and maximum load was equivalent to over 20 times of design seismic acceleration. There was not significant damage that caused emergency stop of pump but degradation of surface roughness was found on some kinds of bearings. It would cause reduction of pump life, but such damage on bearings occurred under large seismic load condition that was equivalent to over 10 to 20 g force. Test results show that realistic fragility capacity of horizontal shaft pump would be at least four times as higher as current value which has been used for our seismic PSA. (authors)

Comparison of intraerythrocyte and intraleucocyte Sodium content and erythrocyte fragility in normotensive subjects

International Nuclear Information System (INIS)

Paci, A.; Cocci, F.; Cristofani, R.; Piras, F.; Balzan, S.; Mezzasalma, L.; Ghione; Giachetti, M.

1988-01-01

The Sodium content of mononuclear leucocytes and erythrocytes and the osmotic fragility of erythrocytes were measured in 22 young male volunteers before and after three days of increased Sodium intake. Analysis of variance for repeated measurements showed no significant correlations between intraleucocyte and intraerythrocyte Sodium and between intraerythrocyte Sodium and osmotic fragility. On the other hand, a highly significant relation was present between osmotic fragility and intraleucocyte Sodium before high salt intake, which disappeared after 3 days of increased salt intake

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia.

Science.gov (United States)

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-07-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured inventory to extract common themes specific for TB control in fragile states was conducted among twelve providers of technical assistance who have worked in fragile states. The themes were applied to the TB control programs of Afghanistan, DR Congo, Haiti and Somalia during the years 2000-2006. Case notifications and treatment outcomes have increased in all four countries since 2003 (treatment success rates 81-90%). Access to care and case detection however have remained insufficient (case detection rates 39-62%); There are four lessons learned: 1. TB control programs can function in fragile states. 2. National program leadership and stewardship are essential for quality and sustained TB control. 3. Partnerships with non-governmental providers are vital for continuous service delivery; 4. TB control programs in fragile states require consistent donor support. Despite challenges in management, coordination, security, logistics and funding, TB control programs can function in fragile states, but face considerable problems in access to diagnosis and treatment and therefore case detection. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

I’m incredible—or am I? : On the socialization of fragile self-views in children

NARCIS (Netherlands)

Brummelman, E.

2015-01-01

I’m incredible—or am I? This is a recurring and daunting question for children with fragile self-views, whose feelings of self-worth crumble in the face of setbacks. What are the origins of children’s fragile self-views, and how can interventions reduce the fragility of children’s self-views? The

Molecular biological study on genetic stability of the genome

International Nuclear Information System (INIS)

Hori, Tada-aki; Takahashi, Ei-ichi; Tsuji, Hideo; Tsuji, Satsuki

1989-01-01

A population cytogenetic study has been performed in 1022 healthy subjects and 547 cancer patients to determine baseline frequencies of autosomal rate fragile sites. Out of 17 rare autosomal fragile sites defined in HBM9 (1985), the following six were detected: fra(2)(q11), fra(10)(q25), fra(11)(q13), fra(11)(q23), fra(16)(q22) and fra(17)(q12). Other three new fragile sites were also detected: fra(8)(q24.1), fra(11)(q15.1) and fra(16)(p12.1). They were all distamycin A-inducible and located at the junctions of G/R-bands. The incidence of these autosomal fragile sites was 5% in both healthy subjects and cancer patients. Distamycin A-induced fragile sites may play a role in the etiology of leukemia, myeloproliferative disorders, and gynecological tumors. The present study also examined the mechanism of fragile X expression associated with fragile X syndrome in thymidine-prototrophic and auxotrophic human-mouse somatic cell hybrids. In these hybrid cells, both low and high thymidylate stresses were found to be effective in inducing fragile X expression, even in a hybrid clone that retained a fragile X chromosome as the only human chromosome. An addition of deoxycytidine completely abolished the effect of high thymidylate stress achieved by excess amounts of thymidine. It is concluded that the expression is an intrinsic property of the fragile X mutation resulting from chromosomal change in a special class of replicons with polypurine/polypyrimidine DNA sequence. (Namekawa, K)

Thermalization as an invisibility cloak for fragile quantum superpositions

Science.gov (United States)

Hahn, Walter; Fine, Boris V.

2017-07-01

We propose a method for protecting fragile quantum superpositions in many-particle systems from dephasing by external classical noise. We call superpositions "fragile" if dephasing occurs particularly fast, because the noise couples very differently to the superposed states. The method consists of letting a quantum superposition evolve under the internal thermalization dynamics of the system, followed by a time-reversal manipulation known as Loschmidt echo. The thermalization dynamics makes the superposed states almost indistinguishable during most of the above procedure. We validate the method by applying it to a cluster of spins ½.

Skeletal stem cells and their contribution to skeletal fragility

DEFF Research Database (Denmark)

Aldahmash, A.

2016-01-01

Age-related osteoporotic fractures are major health care problem worldwide and are the result of impaired bone formation, decreased bone mass and bone fragility. Bone formation is accomplished by skeletal stem cells (SSC) that are recruited to bone surfaces from bone marrow microenvironment....... This review discusses targeting SSC to enhance bone formation and to abolish age-related bone fragility in the context of using stem cells for treatment of age-related disorders. Recent studies are presented that have demonstrated that SSC exhibit impaired functions during aging due to intrinsic senescence...

Dopamine transporter imaging study in parkinsonism occurring in fragile X premutation carriers.

Science.gov (United States)

Ceravolo, R; Antonini, A; Volterrani, D; Rossi, C; Goldwurm, S; Di Maria, E; Kiferle, L; Bonuccelli, U; Murri, L

2005-12-27

The authors studied four patients with parkinsonism carrying the fragile X premutation using SPECT with ([23)I]FP-CIT. They found evidence of preserved presynaptic nigrostriatal function, suggesting that parkinsonism in the X fragile premutation might be related to postsynaptic dopaminergic changes or different neurotransmitter alterations.

Epilepsy in fragile-X-syndrome mimicking panayiotopoulos syndrome: Description of three patients.

Science.gov (United States)

Bonanni, Paolo; Casellato, Susanna; Fabbro, Franco; Negrin, Susanna

2017-10-01

Fragile-X-syndrome is the most common cause of inherited intellectual disability. Epilepsy is reported to occur in 10-20% of individuals with Fragile-X-syndrome. A frequent seizure/electroencephalogram (EEG) pattern resembles that of benign rolandic epilepsy. We describe the clinical features, EEG findings and evolution in three patients affected by Fragile-X-syndrome and epilepsy mimicking Panayiotopoulos syndrome. Age at seizure onset was between 4 and about 7 years. Seizures pattern comprised a constellation of autonomic symptoms with unilateral deviation of the eyes and ictal syncope. Duration of the seizures could be brief or lengthy. Interictal EEGs revealed functional multifocal abnormalities. The evolution was benign in all patients with seizures remission before the age of 14. This observation expands the spectrum of benign epileptic phenotypes present in Fragile-X-syndrome and may be quite helpful in guiding anticonvulsant management and counseling families as to expectations regarding seizure remission. © 2017 Wiley Periodicals, Inc.

The effect of atom mismatch on the fragility of supercooled Lennard-Jones binary mixtures

International Nuclear Information System (INIS)

Sun Minhua; Sun Yongli; Wang Aiping; Ma Congxiao; Li Jiayun; Cheng Weidong; Liu Fang

2006-01-01

The shear viscosity of the well-known binary Lennard-Jones mixture is simulated under constant temperature and constant volume conditions (NVT) by a molecular-dynamics (MD) method. The effect of atomic size mismatch on the fragility parameter and glass-forming ability is studied. The fragility parameters calculated from shear viscosity data decrease with the increment of the atomic size mismatch. The value of the fragility changes from 168.963 to 22.976 when the mismatch changes from 0.023 to 0.25. It is shown that the fragility parameter is sensitive to the atomic size mismatch. The calculated pair distribution functions and mean square displacements indicate that the glass-forming ability increases with the atomic size mismatch

A nonsense mutation in FMR1 causing fragile X syndrome

DEFF Research Database (Denmark)

Grønskov, Karen; Brøndum-Nielsen, Karen; Dedic, Alma

2011-01-01

Fragile X syndrome is a common cause of inherited intellectual disability. It is caused by lack of the FMR1 gene product FMRP. The most frequent cause is the expansion of a CGG repeat located in the 5'UTR of FMR1. Alleles with 200 or more repeats become hypermethylated and transcriptionally silent....... Only few patients with intragenic point mutations in FMR1 have been reported and, currently, routine analysis of patients referred for fragile X syndrome includes solely analysis for repeat expansion and methylation status. We identified a substitution in exon 2 of FMR1, c.80C>A, causing a nonsense...... mutation p.Ser27X, in a patient with classical clinical symptoms of fragile X syndrome. The mother who carried the mutation in heterozygous form presented with mild intellectual impairment. We conclude that further studies including western blot and DNA sequence analysis of the FMR1 gene should...

Seismic margins review of nuclear power plants: Fragility aspects

International Nuclear Information System (INIS)

Ravindra, M.K.; Hardy, G.S.; Hashimoto, P.S.

1987-01-01

The fragility analysis is utilised in the seismic margin review in initial screening of certain components in the plant based on their generically high seismic capacities. A detailed walkdown of the plant is conducted to confirm that the initial screening is valid i.e., the generically high seismic capacity components do not possess any potential weaknesses (e.g., inadequate bracing, inadequate anchorage and potential systems interaction). For the components that are screened in, their seismic capacities are evaluated using either a probabilistic analysis of a deterministic evaluation. Based on a system analysis, the Boolean expressions for critical accident sequences are derived. These Boolean expressions are quantified using the component fragilities and nonseismic unavailabilities of components. The final product is the High Confidence Low Probability of Failure (HCLPF) capacity of the plant and the identification of potential seismic vulnerabilities in the plant. The objective of the paper is to describe the application of fragility analysis procedures in the seismic margin review of Maine Yankee and to document the insights obtained in this trial plant review. (orig./HP)

Clinical assessment tools identify functional deficits in fragility fracture patients

Directory of Open Access Journals (Sweden)

Ames TD

2016-05-01

Full Text Available Tyler D Ames,1 Corinne E Wee,1 Khoi M Le,1 Tiffany L Wang,1 Julie Y Bishop,2 Laura S Phieffer,2 Carmen E Quatman2 1The Ohio State University College of Medicine, 2Department of Orthopaedics, The Ohio State University Wexner Medical Center, Columbus, OH, USA Purpose: To identify inexpensive, noninvasive, portable, clinical assessment tools that can be used to assess functional performance measures that may put older patients at risk for falls such as balance, handgrip strength, and lumbopelvic control.Patients and methods: Twenty fragility fracture patients and 21 healthy control subjects were evaluated using clinical assessment tools (Nintendo Wii Balance Board [WBB], a handheld dynamometer, and an application for the Apple iPod Touch, the Level Belt that measure functional performance during activity of daily living tasks. The main outcome measurements were balance (WBB, handgrip strength (handheld dynamometer, and lumbopelvic control (iPod Touch Level Belt, which were compared between fragility fracture patients and healthy controls.Results: Fragility fracture patients had lower scores on the vertical component of the WBB Torso Twist task (P=0.042 and greater medial–lateral lumbopelvic sway during a 40 m walk (P=0.026 when compared to healthy controls. Unexpectedly, the fracture patients had significantly higher scores on the left leg (P=0.020 and total components (P=0.010 of the WBB Single Leg Stand task as well as less faults during the left Single Leg Stand task (P=0.003.Conclusion: The clinical assessment tools utilized in this study are relatively inexpensive and portable tools of performance measures capable of detecting differences in postural sway between fragility fracture patients and controls. Keywords: fall risk, geriatric fracture, Nintendo Wii Balance Board, Level Belt, fragility fracture

Fragility analysis methodology for degraded structures and passive components in nuclear power plantsIllustrated using a condensate storage tank

International Nuclear Information System (INIS)

Nie, Jinsuo; Braverman, Joseph; Hofmayer, Charles; Choun, Young Sun; Kim, Min Kyu; Choi, In Kil

2010-06-01

This report describes the seismic fragility capacity for a condensate storage tank with various degradation scenarios. The conservative deterministic failure margin method has been utilized for the undegraded case and has been modified to accommodate the degraded cases. A total of five seismic fragility analysis cases have been described: (1) undegraded case, (2) degraded stainless tank shell, (3) degraded anchor bolts, (4) anchorage concrete cracking, and (5) a perfect correlation of the three degradation scenarios. Insights from these fragility analyses are also presented. An overview of the methods for seismic fragility analysis and generic approaches to incorporate time-dependent degradation models into a fragility analysis is presented. Fundamental concepts of seismic fragility analysis are summarized to facilitate discussions in later sections. The seismic fragility analysis of the undegraded CST, which is assumed to have all of its components in design condition, is described. The subject CST was located in an operating Korean NPP. The baseline fragility capacity of the CST is calculated and the basic procedure of seismic fragility analysis is established. This report presents the results and insights of the seismic fragility analysis of the CST under various postulated degradation scenarios

Visual Pathway Deficit in Female Fragile X Premutation Carriers: A Potential Endophenotype

Science.gov (United States)

Keri, Szabolcs; Benedek, Gyorgy

2009-01-01

Previous studies indicated impaired magnocellular (M) and relatively spared parvocellular (P) visual pathway functioning in patients with fragile X syndrome. In this study, we assessed M and P pathways in 22 female fragile X premutation carriers with normal intelligence and in 20 healthy non-carrier controls. Testing procedure included visual…

Mechanisms of diabetes mellitus-induced bone fragility

DEFF Research Database (Denmark)

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D

2017-01-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM...... and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia......-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus....

Vibrio chromosome-specific families

DEFF Research Database (Denmark)

Lukjancenko, Oksana; Ussery, David

2014-01-01

We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...... chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown.) Of the chromosome specific core protein...... families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different "Molecular Function" GO categories were found for chromosome 1...

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice.

Science.gov (United States)

Foote, Molly; Arque, Gloria; Berman, Robert F; Santos, Mónica

2016-10-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.

Evaluation of structural fragilities for an IPEEE seismic probabilistic risk assessment study

International Nuclear Information System (INIS)

Ghiocel, D.M.; Wilson, P.R.; Stevenson, J.D.

1995-01-01

The paper presents the main issues and results of a structural fragility analysis for a Seismic Probabilistic Risk Assessment (SPRA) study of a nuclear power plant (NPP) in the Eastern US. The fragility evaluations were performed for the Reactor Building, Auxiliary Building, Intake Structure and Diesel Generator Building. The random seismic input is defined in terms of the Uniform Hazard Spectrum (UHS) earthquake on the NPP site anchored to a reference level of 0.40 g Zero Period Ground Acceleration (ZPGA). Because of the soft soil conditions new Soil-Structure Interaction (SSI) analyses were performed using the original finite element (stick) structural models and the complex frequency approach. The soil deposit randomness was described by the variations in both the low strain soil shear modules and in its dependence with the shear strain. The probabilistic SSI analyses were performed using digital simulation techniques. The critical failure modes for each structure are investigated and the fragility evaluations are discussed. Concluding remarks and recommendations for improving the quality of the structural fragility analyses are included

Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice

Science.gov (United States)

Foote, Molly; Arque, Gloria; Berman, Robert F.; Santos, Mónica

2016-01-01

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that affects some carriers of the Fragile X premutation (PM). In PM carriers there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the Fragile X Mental Retardation Protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that cause PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically we will discuss the construct, face and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms and potential treatments. PMID:27255703

Seismic Margin Assessment for Research Reactor using Fragility based Fault Tree Analysis

Energy Technology Data Exchange (ETDEWEB)

Kwag, Shinyoung; Oh, Jinho; Lee, Jong-Min; Ryu, Jeong-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2016-10-15

The research reactor has been often subjected to external hazards during the design lifetime. Especially, a seismic event can be one of significant threats to the failure of structure system of the research reactor. This failure is possibly extended to the direct core damage of the reactor. For this purpose, the fault tree for structural system failure leading to the core damage under an earthquake accident is developed. The failure probabilities of basic events are evaluated as fragility curves of log-normal distributions. Finally, the plant-level seismic margin is investigated by the fault tree analysis combining with fragility data and the critical path is identified. The plant-level probabilistic seismic margin assessment using the fragility based fault tree analysis was performed for quantifying the safety of research reactor to a seismic hazard. For this, the fault tree for structural system failure leading to the core damage of the reactor under a seismic accident was developed. The failure probabilities of basic events were evaluated as fragility curves of log-normal distributions.

Giemsa C-banding of Barley Chromosomes. IV. Chromosomal Constitution of Autotetraploid Barley

DEFF Research Database (Denmark)

Linde-Laursen, Ib

1984-01-01

The progeny of an autotetraploid barley plant (C1) consisted of 45 tetraploids and 33 aneuploids. Giemsa C-banding was used to identify each of the chromosomes in 20 euploid and 31 aneuploid C2--seedlings, and in 11 C3--offspring of aneuploid C2--plants. The euploid C2--seedlings all had four...... homologues of each of the chromosomes. The aneuploid C2--seedlings were fairly equally distributed on hypo-and hyperploids, and on the seven chromosome groups. This suggests that a particular chromosome is lost or gained at random in gametes and embryos. The 11 C3--seedlings comprised seven true euploids......, one seedling with 2n=28 having an extra chromosome 6 and missing one chromosome 3, and three seedlings with 2n=29. The chromosomal composition of aneuploid C3--seedlings did not reflect that of their aneuploid C2--parents with respect to missing or extra chromosomes. Two hypohexaploid C2--seedlings...

Fragile X Syndrome: An Aging Perspective

Science.gov (United States)

Schneider, Andrea; Ligsay, Andrew; Hagerman, Randi J.

2013-01-01

Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical…

Fragility of superheated melts and glass-forming ability in Pr-based alloys

International Nuclear Information System (INIS)

Meng, Q.G.; Zhou, J.K.; Zheng, H.X.; Li, J.G.

2006-01-01

The kinetic viscosity (η) of superheated melts, thermal properties (T x , T m , T L ) and X-ray diffraction analysis on the Pr-based bulk metallic glasses (BMG) are reported and discussed. A new refined concept, the superheated fragility defined as M' = E S δ x /k B , has been developed based on common solidification theory and the Arrhenius equation. The interrelationship between this kind of fragility and the glass-forming ability (GFA) is elaborated on and evaluated in Pr-based BMG and Al-based amorphous ribbon alloys. Using viscosity data of superheated melts, it is shown, theoretically and experimentally, that the fragility parameter M' may be used as a GFA indicator for metallic alloys

Banking Fragility in Colombia: An Empirical Analysis Based on Balance Sheets

OpenAIRE

Ignacio Lozano; Alexander Guarín

2014-01-01

In this paper, we study the empirical relationship between credit funding sources and the financial vulnerability of the Colombian banking system. We propose a statistical model to measure and predict banking-fragility episodes associated with credit funding sources classified into retail deposits and wholesale funds. We compute the probability of financial fragility for both the aggregated banking system and the individual banks. Our approach performs a Bayesian averaging of estimated logit ...

The prospects for ecosystem services provision in fragile states’ urban areas

OpenAIRE

Bogadi, Antonija

2018-01-01

In fragile states context of climate change vulnerability, poverty and lack of infrastructure, the ability of ecosystem services to provide for numerous human needs is indispensable. The focus of this paper is describing the prospects for ecosystem services provision in fragile states’ urban areas. This paper presents a distinct approach by analyzing actors with capacity to provide ecosystem services in urban areas: government, international partners and citizens. Using infrastructure investm...

Fragile X premutation in women: recognizing the health challenges beyond primary ovarian insufficiency.

Science.gov (United States)

Hoyos, Luis R; Thakur, Mili

2017-03-01

Fragile X premutation carriers have 55-200 CGG repeats in the 5' untranslated region of the FMR1 gene. Women with this premutation face many physical and emotional challenges in their life. Approximately 20% of these women will develop fragile X-associated primary ovarian insufficiency (FXPOI). In addition, they suffer from increased rates of menstrual dysfunction, diminished ovarian reserve, reduction in age of menopause, infertility, dizygotic twinning, and risk of having an offspring with a premutation or full mutation. Consequent chronic hypoestrogenism may result in impaired bone health and increased cardiovascular risk. Neuropsychiatric issues include risk of developing fragile X-associated tremor/ataxia syndrome, neuropathy, musculoskeletal problems, increased prevalence of anxiety, depression, and sleep disturbances independent of the stress of raising an offspring with fragile X syndrome and higher risk of postpartum depression. Some studies have reported a higher prevalence of thyroid abnormalities and hypertension in these women. Reproductive health providers play an important role in the health supervision of women with fragile X premutation. Awareness of these risks and correlation of the various manifestations could help in early diagnosis and coordination of care and services for these women and their families. This paper reviews current evidence regarding the possible conditions that may present in women with premutation-sized repeats beyond FXPOI.

Side Effects of Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures

Science.gov (United States)

Utari, Agustini; Chonchaiya, Weerasak; Rivera, Susan M.; Schneider, Andrea; Hagerman, Randi J.; Faradz, Sultana M. H.; Ethell, Iryna M.; Nguyen, Danh V.

2010-01-01

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received…

An Investigation of Narrative Ability in Boys with Autism and Fragile X Syndrome

Science.gov (United States)

Hogan-Brown, Abigail L.; Losh, Molly; Martin, Gary E.; Mueffelmann, Deborah J.

2013-01-01

Whereas pragmatic language difficulties are characteristic of both autism and Fragile X syndrome, it is unclear whether such deficits are qualitatively similar or whether certain skills are differentially affected. This study compared narrative competence in boys with autism, Fragile X syndrome, Down syndrome, and typical development. Results…

The Search for an Effective Therapy to Treat Fragile X Syndrome: Dream or Reality?

OpenAIRE

Castagnola, Sara; Bardoni, Barbara; Maurin, Thomas

2017-01-01

Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies ha...

Fragility analysis of a seismically-isolated emergency diesel generator

International Nuclear Information System (INIS)

Choun, Young Sun; Choi, In Kil; Ohtori, Yasuki

2005-01-01

The seismic capacity of an Emergency Diesel Generator (EDG) in nuclear power plants influences the seismic safety of the plants significantly. A recent study showed that the increase of the seismic capacity of the EDG could reduce the core damage frequency (CDF) remarkably. It is known that the major failure mode of the EDG is a concrete coning failure due to the pulling out of the anchor bolts. The use of base isolators instead of anchor bolts can increase the seismic capacity of the EDG without any major problems. The fragility curves for a base-isolated EDG should be different from those for a conventional type because the major failure mode of the base-isolated EDG will not be a concrete coning one any more. The governing failure mode of the base-isolated EDG must be the damage of the isolators. This study introduces a fragility evaluation method for an isolated EDG, and evaluates the fragilities for the isolated EDG and compares them with those for the conventional one. Evaluation of the ground motion index is also carried out to determine the governing parameter suitable for representing the seismic responses of the base isolator

Breastfeeding of a medically fragile foster child.

Science.gov (United States)

Gribble, Karleen D

2005-02-01

A case is presented in which a medically fragile baby was breastfed by her foster mother. As a result, the child's physical and emotional health were improved. The mechanisms whereby human milk improves health are well known. The act of breastfeeding may also have an analgesic and relaxant effect as a result of hormonal influences and skin-to-skin contact. Many foster babies may benefit from human milk or breastfeeding. However, the risk of disease transmission must be minimized. Provision of human milk to all medically fragile foster babies is desirable. Breastfeeding by the foster mother may be applicable in cases in which the child is likely to be in long-term care, the child has been previously breastfed, or the child's mother expresses a desire that the infant be breastfed. However, social barriers must be overcome before breastfeeding of foster babies can become more common.

Discrimination of chromosome by autoradiography

International Nuclear Information System (INIS)

Masubuchi, Masanori

1975-01-01

This paper describes discrimination of chromosome by autoradiography. In this method, the difference in DNA synthetic phase between each chromosome was used as a standard, and the used chromosome was in metaphase, as morphological characteristics were markedly in this phase. Cell cycle and autoradiography with 3 H-thymidine were also examined. In order to discriminate chromosome by autoradiography, it was effective to utilize the labelled pattern in late DNA synthetic phase, where asynchronous replication of chromosome appeared most obviously. DNA synthesis in chromosome was examined in each DNA synthetic phase by culturing the chromosome after the treatment with 3 H-thymidine and altering the time to prepare chromosome specimen. Discrimination of chromosome in plants and animals by autoradiography was also mentioned. It was noticed as a structural and functional discrimination of chromosome to observe amino acid uptake into chromosome protein and to utilize the difference in labelled pattern between the sites of chromosome. (K. Serizawa)

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Indian Academy of Sciences (India)

An investigation to understand the dynamics and biological significance of fragile site .... This model allows the analysis of pooled data over .... breed differences and short life span in sheep. ..... relationship between common fragile sites, chromosome break- ... the nature of folic acid sensitive fragile sites in human chromo-.

Non-fragile multivariable PID controller design via system augmentation

Science.gov (United States)

Liu, Jinrong; Lam, James; Shen, Mouquan; Shu, Zhan

2017-07-01

In this paper, the issue of designing non-fragile H∞ multivariable proportional-integral-derivative (PID) controllers with derivative filters is investigated. In order to obtain the controller gains, the original system is associated with an extended system such that the PID controller design can be formulated as a static output-feedback control problem. By taking the system augmentation approach, the conditions with slack matrices for solving the non-fragile H∞ multivariable PID controller gains are established. Based on the results, linear matrix inequality -based iterative algorithms are provided to compute the controller gains. Simulations are conducted to verify the effectiveness of the proposed approaches.

Resolution of Spatial and Temporal Visual Attention in Infants with Fragile X Syndrome

Science.gov (United States)

Farzin, Faraz; Rivera, Susan M.; Whitney, David

2011-01-01

Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal-parietal networks of the…

Fragile X checklists: A meta-analysis and development of a simplified universal clinical checklist.

Science.gov (United States)

Lubala, Toni Kasole; Lumaka, Aimé; Kanteng, Gray; Mutesa, Léon; Mukuku, Olivier; Wembonyama, Stanislas; Hagerman, Randi; Luboya, Oscar Numbi; Lukusa Tshilobo, Prosper

2018-04-06

Clinical checklists available have been developed to assess the risk of a positive Fragile X syndrome but they include relatively small sample sizes. Therefore, we carried out a meta-analysis that included statistical pooling of study results to obtain accurate figures on the prevalence of clinical predictors of Fragile X syndrome among patients with intellectual disability, thereby helping health professionals to improve their referrals for Fragile X testing. All published studies consisting of cytogenetic and/or molecular screening for fragile X syndrome among patients with intellectual disability, were eligible for the meta-analysis. All patients enrolled in clinical checklists trials of Fragile X syndrome were eligible for this review, with no exclusion based on ethnicity or age. Odds ratio values, with 95% confidence intervals as well as Cronbach coefficient alpha, was reported to assess the frequency of clinical characteristics in subjects with intellectual disability with and without the fragile X mutation to determine the most discriminating. The following features were strongly associated with Fragile X syndrome: skin soft and velvety on the palms with redundancy of skin on the dorsum of hand [OR: 16.85 (95% CI 10.4-27.3; α:0.97)], large testes [OR: 7.14 (95% CI 5.53-9.22; α: 0.80)], large and prominent ears [OR: 18.62 (95% CI 14.38-24.1; α: 0.98)], pale blue eyes [OR: 8.97 (95% CI 4.75-16.97; α: 0.83)], family history of intellectual disability [OR: 3.43 (95% CI 2.76-4.27; α: 0.81)] as well as autistic-like behavior [OR: 3.08 (95% CI 2.48-3.83; α: 0.77)], Flat feet [OR: 11.53 (95% CI 6.79-19.56; α:0.91)], plantar crease [OR: 3.74 (95% CI 2.67-5.24; α: 0.70)]. We noted a weaker positive association between transverse palmar crease [OR: 2.68 (95% CI 1.70-4.18; α: 0.51)], elongated face [OR: 3.69 (95% CI 2.84-4.81; α: 0.63)]; hyperextensible metacarpo-phalangeal joints [OR: 2.68 (95% CI 2.15-3.34; α: 0.57)] and the Fragile X syndrome. This study

The Y chromosome of the Atelidae family (Platyrrhini): study by chromosome microdissection.

Science.gov (United States)

Gifalli-Iughetti, C; Koiffmann, C P

2009-01-01

In order to study the intergeneric variability of the Y chromosome, we describe the hybridization of the Y chromosome of Brachytelesarachnoides, obtained by microdissection, to metaphases of Atelesbelzebuthmarginatus, Lagothrixlagothricha, and Alouatta male specimens. Brachytelesarachnoides (Atelinae) has 62 chromosomes and a very small Y chromosome. Our results showed that the Brachytelesarachnoides Y chromosome probe hybridized to Lagothrixlagothricha metaphases yielding one hybridization signal on only the tiny Y chromosome, and when hybridized with Atelesbelzebuthmarginatus metaphases it yielded one hybridization signal on two thirds of the small acrocentric Y chromosome. However, no hybridization signal was observed in Alouatta metaphases (subfamily Alouattinae), a closely related genus in the Atelidae family. Furthermore, our data support a close phylogenetic relationship among Brachyteles, Ateles, and Lagothrix and their placement in the Atelinae subfamily, but exclude Alouatta from this group indicating its placement as basal to this group. Copyright 2009 S. Karger AG, Basel.

THE IMPORTANCE OF THE ERYTHROCYTES OSMOTIC FRAGILITY TEST PERFORMED IN CHILDREN WITH INDIRECT HYPERBILIRUB1NEMIA

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Ivana Stojanović

2005-07-01

Full Text Available The osmotic fragility test of erythrocytes is useful in the diagnosis of different types of hereditary hemolytic anemias followed with hyperbilirubinemia. Hemolytic anemias, characterized by accelerated destruction of red blood cells, are usually the consequence of many metabolic abnormalities like cellular membrane defect, erythrocyte enzymes defect or hemoglobin abnormalities – hemoglobinopathies. The object of our study was to assess the relationship between osmotic fragility test of erythrocytes and severity of indirect hyperbilirubinemia in some inherited erythrocytes’ disorders. We did the osmotic fragility test of erythrocytes by using Dacie, s method with normal values of erythrocytes hemolysis between 0,48 to 0,34% NaCl (minimal to maximal hemolysis. In hereditary spherocytosis, fragility of erythrocytes was increased (min. at 0,50 % NaCl to max. 0,44 % NaCl . In the child with β- thalassemia and cycle cell anemia erythrocytes fragility was decreased (min . at 0,42 to max. 0,32 % NaCl, that is 0,40% min. of hemolysis and 0,34% max. hemolysis in the second case. In newborn infants with high levels of indirect bilirubin in serum as a cause of physiological jaundice, the osmotic fragility test was within a normal range. Our findings point out the diagnostic value of osmotic fragility test in assessing patients with the indirect hyperbilirubinemia. This simple and important diagnostic test can be performed in small laboratories.

State fragility and its regional implications for peace and stability

DEFF Research Database (Denmark)

Mandrup, Thomas

of the Cold war left a security void, and the fragility, and in some instances collapse, of the state structures resulted in new state formations and new conflicts, both intra- and inter-state in nature. However, conflicts and security challenges in East Africa are due to amongst other things porous borders......, fragile states and bad governance regional in nature, and cannot be solved by the individual states alone. Regional institutions have been in a weak position dealing with these challenges, and attempts have been to strengthen the capacity of these regional institutions. This paper investigates...

Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions

International Nuclear Information System (INIS)

Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.

2003-01-01

Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive

Fragility fractures at Auckland City Hospital: we can do better.

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Braatvedt, Geoffrey; Wilkinson, Susan; Scott, Marilyn; Mitchell, Paul; Harris, Roger

2017-12-01

This study describes in detail the burden of caring for patients aged ≥ 50 years seen in one year with a fragility fracture in a large urban environment and shows that these fractures result in a long length of stay and significant mortality. Intervention to prevent further fracture was poorly done. To examine the epidemiology of fragility fracture in patients over age 50 years and record the number who received appropriate secondary prevention treatment. All patients aged ≥ 50 years presenting with a fracture during the 12 months following July 1 st 2011, to Auckland City Hospital or residing in central Auckland at the time of their fracture, were identified from hospital and Accident Compensation Corporation records. A random sample of 55% of these patient's records were reviewed to establish the type of fracture, prior fracture and falls history, and use of bisphosphonates in the 12 months before presentation. Their length of stay (LOS) by type of fracture was recorded. The use of bisphosphonate drugs in the following 12 months was obtained from centralised national records of prescriptions. 2729 patients aged ≥ 50 years presented with a fragility fracture in the central Auckland region in one year. Fifty-six percent of these patients were seen at Auckland Hospital and of these, 82% patients required admission with a mean LOS of 20 days (SD ± 24 days).The remaining 44% of patients were looked after in the private outpatient sector. Approximately 30% of the admissions were for hip fracture. Sixty-four percent of patients with a fragility fracture did not receive a potent bisphosphonate, 12% were considered not appropriate for treatment, and 24% received a potent bisphosphonate during their admission or in the next 12 months. Approximately 1 in 18 people aged ≥ 50 years presented in one year with a fragility fracture.Secondary prevention strategies were poorly implemented. Additional resources for identifying and initiating secondary fracture prevention

Cerebral protein synthesis in a knockin mouse model of the fragile X premutation

NARCIS (Netherlands)

M. Qin (Mei); T. Huang (Tianjian); Z. Liu (Zhonghua); M. Kader (Michael); T. Burlin (Thomas); Z. Xia (Zengyan); Z. Zeidler (Zachary); R.K. Hukema (Renate); C.B. Smith (Carolyn B.)

2014-01-01

textabstractThe (CGG)n-repeat in the 5’-untransiated region of the fragile X mental retardation gene (FMRi) gene is polymorphic and may become unstable on transmission to the next generation. In fragile X syndrome, CGG repeat lengths exceed 200, resulting in silencing of FMRi and absence of its

Micromechanics of human mitotic chromosomes

International Nuclear Information System (INIS)

Sun, Mingxuan; Kawamura, Ryo; Marko, John F

2011-01-01

Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed

Seismic fragility curves of bridge piers accounting for ground motions in Korea

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Nguyen, Duy-Duan; Lee, Tae-Hyung

2018-04-01

Korea is located in a slight-to-moderate seismic zone. Nevertheless, several studies pointed that the peak earthquake magnitude in the region can be reached to approximately 6.5. Accordingly, a seismic vulnerability evaluation of the existing structures accounting for ground motions in Korea is momentous. The purpose of this paper is to develop seismic fragility curves for bridge piers of a steel box girder bridge equipped with and without base isolators based on a set of ground motions recorded in Korea. A finite element simulation platform, OpenSees, is utilized to perform nonlinear time history analyses of the bridges. A series of damage states is defined based on a damage index which is expressed in terms of the column displacement ductility ratio. The fragility curves based on Korean motions were thereafter compared with the fragility curves generated using worldwide earthquakes to assess the effect of the two ground motion groups on the seismic fragility curves of the bridge piers. The results reveal that both non- and base-isolated bridge piers are less vulnerable during the Korean ground motions than that under worldwide earthquakes.

Fragile areas in the Alpine region: a reading between innovation and marginality

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Federica Corrado

2010-05-01

Full Text Available The paper proposes a reading and description of fragile Alpine areas that overturns the conventional standpoint, according to which marginality is often synonymous with handicap. The paper starts form a different point of view, able to recognize specific local potentialities that can still be activated with a specific creative effort. The reading regards fragile Alpine areas in the Provinces of Turin and Cuneo and is based on an empirical analysis of the actions underlying current micro-territorial innovative development trends.Cet article propose une lecture et une description des territoires alpins fragiles, en jetant un autre regard, où le concept de fragilité est associé à celui de handicap, c’est-à-dire un autre regard sur l’identification des potentiels locaux spécifiques qui peuvent être encore activés à travers une force créatrice propre aux Alpes. La lecture est effectuée en fonction des territoires alpins fragiles qui font partie des provinces de Turin et Coni et se base sur une analyse empirique des initiatives qui enclenchent en quelque façon des dynamiques micro-territoriales de développement innovant.

Organizational changes help Benin NGO better protect fragile ...

International Development Research Centre (IDRC) Digital Library (Canada)

2016-04-28

Apr 28, 2016 ... ... climate change adaptation, and sustainable management of fragile ecosystems. ... build community-level capacity for sustainable development through ... solution is to build new houses in more secure areas and to relocate ...

Fragile X mental retardation protein controls ion channel expression and activity.

Science.gov (United States)

Ferron, Laurent

2016-10-15

Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K v 3.1 and K v 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca v 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Early White-Matter Abnormalities of the Ventral Frontostriatal Pathway in Fragile X Syndrome

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Haas, Brian W.; Barnea-Goraly, Naama; Lightbody, Amy A.; Patnaik, Swetapadma S.; Hoeft, Fumiko; Hazlett, Heather; Piven, Joseph; Reiss, Allan L.

2009-01-01

Aim: Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development. Method: In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white-matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n = 17;…

Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

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Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

2016-02-01

Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

Interphase Chromosome Profiling: A Method for Conventional Banded Chromosome Analysis Using Interphase Nuclei.

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Babu, Ramesh; Van Dyke, Daniel L; Dev, Vaithilingam G; Koduru, Prasad; Rao, Nagesh; Mitter, Navnit S; Liu, Mingya; Fuentes, Ernesto; Fuentes, Sarah; Papa, Stephen

2018-02-01

- Chromosome analysis on bone marrow or peripheral blood samples fails in a small proportion of attempts. A method that is more reliable, with similar or better resolution, would be a welcome addition to the armamentarium of the cytogenetics laboratory. - To develop a method similar to banded metaphase chromosome analysis that relies only on interphase nuclei. - To label multiple targets in an equidistant fashion along the entire length of each chromosome, including landmark subtelomere and centromere regions. Each label so generated by using cloned bacterial artificial chromosome probes is molecularly distinct with unique spectral characteristics, so the number and position of the labels can be tracked to identify chromosome abnormalities. - Interphase chromosome profiling (ICP) demonstrated results similar to conventional chromosome analysis and fluorescence in situ hybridization in 55 previously studied cases and obtained useful ICP chromosome analysis results on another 29 cases in which conventional methods failed. - ICP is a new and powerful method to karyotype peripheral blood and bone marrow aspirate preparations without reliance on metaphase chromosome preparations. It will be of particular value for cases with a failed conventional analysis or when a fast turnaround time is required.

Program outline of seismic fragility capacity tests on nuclear power plant equipment

International Nuclear Information System (INIS)

Lijima, T.; Abe, H.; Fujita, T.

2004-01-01

A seismic probabilistic safety assessment (PSA) is an available method to evaluate residual risk of nuclear plant that is designed with definitive seismic design condition. Seismic fragility capacity data are necessary for seismic PSA, but we don't have sufficient data of active components of nuclear plants in Japan. This paper describes a plan of seismic fragility capacity tests on nuclear power plant equipment. The purpose of those tests is to obtain seismic fragility capacity of important equipment from a safety design point of view. And the equipment for the fragility capacity tests were selected considering effect on core damage frequency (CDF) that was evaluated by our preliminary seismic PSA. Consequently horizontal shaft pump, electric cabinets, Control Rod Drive system (CRD system) of BWR and PWR plant and vertical shaft pump were selected. The seismic fragility capacity tests are conducted from phase-1 to phase-3, and horizontal shaft pump and electric cabinets are tested on phase-1. The fragility capacity test consists of two types of tests. One is actual equipment test and another is element test. On actual equipment test, a real size model is tested with high-level seismic motion, and critical acceleration and failure mode are investigated. Regarding fragility test phase-1, we selected typical type horizontal shaft pump and electric cabinets for the actual equipment test. Those were Reactor Building Closed Cooling Water (RCW) Pump and eight kinds of electric cabinets such as relay cabinet, motor control center. On the test phase-1, maximum input acceleration for the actual equipment test is intended to be 6-G-force. Since the shaking table of TADOTSU facility did not have capability for high acceleration, we made vibration amplifying system. In this system, amplifying device is mounted on original shaking table and it moves in synchronization with original table. The element test is conducted with many samples and critical acceleration, median and

Race and the fragility of the legal distinction between juveniles and adults.

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Aneeta Rattan

Full Text Available Legal precedent establishes juvenile offenders as inherently less culpable than adult offenders and thus protects juveniles from the most severe of punishments. But how fragile might these protections be? In the present study, simply bringing to mind a Black (vs. White juvenile offender led participants to view juveniles in general as significantly more similar to adults in their inherent culpability and to express more support for severe sentencing. Indeed, these differences in participants' perceptions of this foundational legal precedent distinguishing between juveniles and adults accounted for their greater support for severe punishment. These results highlight the fragility of protections for juveniles when race is in play. Furthermore, we suggest that this fragility may have broad implications for how juveniles are seen and treated in the criminal justice system.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

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Hansen eWang

2015-02-01

Full Text Available Autism spectrum disorders (ASDs are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases.

The Pathophysiology of Fragile X (and What It Teaches Us about Synapses)

Science.gov (United States)

Bhakar, Asha L.; Dölen, Gül; Bear, Mark F.

2014-01-01

Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated by metabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way. PMID:22483044

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

Science.gov (United States)

Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

2015-01-01

Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

Recent advances in assays for the fragile X-related disorders.

Science.gov (United States)

Hayward, Bruce E; Kumari, Daman; Usdin, Karen

2017-10-01

The fragile X-related disorders are a group of three clinical conditions resulting from the instability of a CGG-repeat tract at the 5' end of the FMR1 transcript. Fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI) are disorders seen in carriers of FMR1 alleles with 55-200 repeats. Female carriers of these premutation (PM) alleles are also at risk of having a child who has an FMR1 allele with >200 repeats. Most of these full mutation (FM) alleles are epigenetically silenced resulting in a deficit of the FMR1 gene product, FMRP. This results in fragile X Syndrome (FXS), the most common heritable cause of intellectual disability and autism. The diagnosis and study of these disorders is challenging, in part because the detection of alleles with large repeat numbers has, until recently, been either time-consuming or unreliable. This problem is compounded by the mosaicism for repeat length and/or DNA methylation that is frequently seen in PM and FM carriers. Furthermore, since AGG interruptions in the repeat tract affect the risk that a FM allele will be maternally transmitted, the ability to accurately detect these interruptions in female PM carriers is an additional challenge that must be met. This review will discuss some of the pros and cons of some recently described assays for these disorders, including those that detect FMRP levels directly, as well as emerging technologies that promise to improve the diagnosis of these conditions and to be useful in both basic and translational research settings.

Behavioral Assessment of Social Anxiety in Females with Turner or Fragile X Syndrome.

Science.gov (United States)

Lesniak-Karpiak, Katarzyna; Mazzocco, Michele M. M.; Ross, Judith L.

2003-01-01

This study compared 29 females with Turner syndrome and 21 females with fragile X syndrome (ages 6-22) on a videotaped role-play interaction with 34 females in a comparison group. Three of eight behavioral measures of social skills differentiated the participant groups. Fragile-X subjects required more time to initiate interactions and Turner…

Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes

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Sebastian Pita

2013-05-01

Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.

Financial Liberalization and Financial Fragility

OpenAIRE

Enrica Detragiache; Asli Demirgüç-Kunt

1998-01-01

The authors study the empirical relationship between banking crises and financial liberalization using a panel of data for 53 countries for 1980-95. They find that banking crises are more likely to occur in liberalized financial systems. But financial liberalization's impact on a fragile banking sector is weaker where the institutional environment is strong--especially where there is respect for the rule of law, a low level of corruption, and good contract enforcement. They examine evidence o...

Paradoxical effect of baclofen on social behavior in the fragile X syndrome mouse model

NARCIS (Netherlands)

S. Zeidler (Shimriet); A.S. Pop (Andreea); I.A. Jaafar; H. De Boer (Helen); R.A.M. Buijsen (Ronald); C. de Esch (Celine); I.M. Nieuwenhuizen-Bakker; R.K. Hukema (Renate); R. Willemsen (Rob)

2018-01-01

textabstractIntroduction: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator

Emotion Potentiated Startle in Fragile X Syndrome

Science.gov (United States)

Ballinger, Elizabeth C.; Cordeiro, Lisa; Chavez, Alyssa D.; Hagerman, Randi J.; Hessl, David

2014-01-01

Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We…

Telomere dysfunction and chromosome instability

Energy Technology Data Exchange (ETDEWEB)

Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

2012-02-01

The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

Persistence of Breakage in Specific Chromosome Bands 6 Years after Acute Exposure to Oil.

Directory of Open Access Journals (Sweden)

Alexandra Francés

Full Text Available The identification of breakpoints involved in chromosomal damage could help to detect genes involved in genetic disorders, most notably cancer. Until now, only one published study, carried out by our group, has identified chromosome bands affected by exposure to oil from an oil spill. In that study, which was performed two years after the initial oil exposure in individuals who had participated in clean-up tasks following the wreck of the Prestige, three chromosomal bands (2q21, 3q27, 5q31 were found to be especially prone to breakage. A recent follow-up study, performed on the same individuals, revealed that the genotoxic damage had persisted six years after oil exposure.To determine whether there exist chromosome bands which are especially prone to breakages and to know if there is some correlation with those detected in the previous study. In addition, to investigate if the DNA repair problems detected previously persist in the present study.Follow-up study performed six years after the Prestige oil spill.Fishermen cooperatives in coastal villages.Fishermen highly exposed to oil spill who participated in previous genotoxic study six years after the oil.Chromosome damage in peripheral lymphocytes. For accurate identification of the breakpoints involved in chromosome damage of circulating lymphocytes, a sequential stain/G-banding technique was employed. To determine the most break-prone chromosome bands, two statistical methods, the Fragile Site Multinomial and the chi-square tests (where the bands were corrected by their length were used. To compare the chromosome lesions, structural chromosome alterations and gaps/breaks between two groups of individuals we used the GEE test which takes into account a possible within-individual correlation. Dysfunctions in DNA repair mechanisms, expressed as chromosome damage, were assessed in cultures with aphidicolin by the GEE test.Cytogenetic analyses were performed in 47 exposed individuals. A total of

Fetal chromosome analysis

DEFF Research Database (Denmark)

Philip, J; Tabor, A; Bang, J

1983-01-01

The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...

Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium

Science.gov (United States)

The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...

Microdissection and chromosome painting of the alien chromosome in an addition line of wheat--Thinopyrum intermedium.

Science.gov (United States)

Deng, Chuanliang; Bai, Lili; Fu, Shulan; Yin, Weibo; Zhang, Yingxin; Chen, Yuhong; Wang, Richard R-C; Zhang, Xiangqi; Han, Fangpu; Hu, Zanmin

2013-01-01

In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat--Thinopyrum intermedium addition line, and the chromosomes of the three different genomes of Th. Intermedium. The smallest alien chromosome of TAi-27 was microdissected and its DNA amplified by DOP-PCR was used as a probe to hybridize with metaphase chromosomes of TAi-27 and Th. intermedium. Results showed that hybridization signals were observed in all regions of a pair of the smallest alien chromosomes and the pericentromeric area of another pair of alien chromosomes in TAi-27, indicating that the probe from microdissected chromosome is species specific. In Th. intermedium, 14 chromosomes had wide and strong hybridization signals distributed mainly on the pericentromere area and 9 chromosomes with narrow and weak signals on the pericentromere area. The remaining chromosomes displayed a very weak or no signal. Sequential FISH/GISH on Th. intermedium chromosomes using the DNAs of microdissected chromosome, Pseudoroegneria spicata (St genome) and pDbH12 (a J(s) genome specific probe) as the probes indicated that the microdissected chromosome belonged to the St genome, three genomes (J(s) , J and St) in Th. intermedium could be distinguished, in which there is no hybridization signal on J genome that is similar to the genome of Th. bessarabicum. Our results showed that the smallest alien chromosomes may represent a truncated chromosome and the repetitive sequence distribution might be similar in different chromosomes within the St genome. However, the repetitive sequence distributions are different within the J(s) genome, within a single chromosome, and among different genomes in Th. intermedium. Our results suggested that chromosome painting could be feasible in some plants and useful in detecting chromosome variation and repetitive sequence distribution in different genomes of polyploidy plants, which is helpful for understanding the evolution of different

Microdissection and Chromosome Painting of the Alien Chromosome in an Addition Line of Wheat - Thinopyrum intermedium

Science.gov (United States)

Yin, Weibo; Zhang, Yingxin; Chen, Yuhong; Wang, Richard R.-C.; Zhang, Xiangqi; Han, Fangpu; Hu, Zanmin

2013-01-01

In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat - Thinopyrum intermedium addition line, and the chromosomes of the three different genomes of Th. Intermedium. The smallest alien chromosome of TAi-27 was microdissected and its DNA amplified by DOP-PCR was used as a probe to hybridize with metaphase chromosomes of TAi-27 and Th . intermedium . Results showed that hybridization signals were observed in all regions of a pair of the smallest alien chromosomes and the pericentromeric area of another pair of alien chromosomes in TAi-27, indicating that the probe from microdissected chromosome is species specific. In Th . intermedium , 14 chromosomes had wide and strong hybridization signals distributed mainly on the pericentromere area and 9 chromosomes with narrow and weak signals on the pericentromere area. The remaining chromosomes displayed a very weak or no signal. Sequential FISH/GISH on Th . intermedium chromosomes using the DNAs of microdissected chromosome, Pseudoroegneria spicata (St genome) and pDbH12 (a Js genome specific probe) as the probes indicated that the microdissected chromosome belonged to the St genome, three genomes (Js, J and St) in Th . intermedium could be distinguished, in which there is no hybridization signal on J genome that is similar to the genome of Th . bessarabicum . Our results showed that the smallest alien chromosomes may represent a truncated chromosome and the repetitive sequence distribution might be similar in different chromosomes within the St genome. However, the repetitive sequence distributions are different within the Js genome, within a single chromosome, and among different genomes in Th . intermedium . Our results suggested that chromosome painting could be feasible in some plants and useful in detecting chromosome variation and repetitive sequence distribution in different genomes of polyploidy plants, which is helpful for understanding the evolution of different

Designing of plant artificial chromosome (PAC) by using the Chlorella smallest chromosome as a model system.

Science.gov (United States)

Noutoshi, Y; Arai, R; Fujie, M; Yamada, T

1997-01-01

As a model for plant-type chromosomes, we have been characterizing molecular organization of the Chlorella vulgaris C-169 chromosome I. To identify chromosome structural elements including the centromeric region and replication origins, we constructed a chromosome I specific cosmid library and aligned each cosmid clones to generate contigs. So far, more than 80% of the entire chromosome I has been covered. A complete clonal physical reconstitution of chromosome I provides information on the structure and genomic organization of plant genome. We propose our strategy to construct an artificial chromosome by assembling the functional chromosome structural elements identified on Chrorella chromosome I.

Local variation of fragility and glass transition temperature of ultra-thin supported polymer films.

Science.gov (United States)

Hanakata, Paul Z; Douglas, Jack F; Starr, Francis W

2012-12-28

Despite extensive efforts, a definitive picture of the glass transition of ultra-thin polymer films has yet to emerge. The effect of film thickness h on the glass transition temperature T(g) has been widely examined, but this characterization does not account for the fragility of glass-formation, which quantifies how rapidly relaxation times vary with temperature T. Accordingly, we simulate supported polymer films of a bead-spring model and determine both T(g) and fragility, both as a function of h and film depth. We contrast changes in the relaxation dynamics with density ρ and demonstrate the limitations of the commonly invoked free-volume layer model. As opposed to bulk polymer materials, we find that the fragility and T(g) do not generally vary proportionately. Consequently, the determination of the fragility profile--both locally and for the film as a whole--is essential for the characterization of changes in film dynamics with confinement.

Sex-chromosome anaphase movements in crane-fly spermatocytes are coordinated: ultraviolet microbeam irradiation of one kinetochore of one sex chromosome blocks the movements of both sex chromosomes

International Nuclear Information System (INIS)

Swedak, J.A.M.; Forer, A.

1987-01-01

Sex chromosomes in crane-fly spermatocytes move polewards at anaphase after the autosomes have reached the poles. We irradiated one kinetochore of one sex chromosome using an ultraviolet microbeam. When both sex chromosomes were normally oriented, irradiation of a single kinetochore permanently blocked movement of both sex chromosomes. Irradiation of non-kinetochore chromosomal regions or of spindle fibres did not block movement, or blocked movement only temporarily. We argue that ultraviolet irradiation of one kinetochore blocks movement of both sex chromosomes because of effects on a 'signal' system. Irradiation of one kinetochore of a maloriented sex chromosome did not block motion of either sex chromosome. However, irradiation of one kinetochore of a normally oriented sex chromosome permanently blocked motion of both that sex chromosome and the maloriented sex chromosome. Thus for the signal system to allow the sex chromosomes to move to the pole each sex chromosome must have one spindle fibre to each pole. (author)

Modeling Chromosomes

Science.gov (United States)

Robertson, Carol

2016-01-01

Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

Chromosomal Conditions

Science.gov (United States)

... and more. Stony Point, NY 10980 Close X Home > Complications & Loss > Birth defects & other health conditions > Chromosomal conditions Chromosomal conditions ... Disorders See also: Genetic counseling , Your family health history Last reviewed: February, 2013 ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & ...

Electochemical detection of chromosome translocation

DEFF Research Database (Denmark)

Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

2014-01-01

Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

On the fragility of fractional-order PID controllers for FOPDT processes.

Science.gov (United States)

Padula, Fabrizio; Visioli, Antonio

2016-01-01

This paper analyzes the fragility issue of fractional-order proportional-integral-derivative controllers applied to integer first-order plus-dead-time processes. In particular, the effects of the variations of the controller parameters on the achieved control system robustness and performance are investigated. Results show that this kind of controllers is more fragile with respect to the standard proportional-integral-derivative controllers and therefore a significant attention should be paid by the user in their tuning. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Growth, history, or institutions? What explains state fragility in sub-Saharan Africa

OpenAIRE

Bertocchi, Graziella; Guerzoni, Andrea

2010-01-01

We explore the determinants of state fragility in sub-Saharan Africa. Controlling for a wide range of economic, demographic, geographic and institutional regressors, we find that institutions, and in particular the civil liberties index and the number of revolutions, are the main determinants of fragility, even taking into account their potential endogeneity. Economic factors such as income growth and investment display a non robust impact after controlling for omitted variables and reverse c...

Microdissection and chromosome painting of the alien chromosome in an addition line of wheat--Thinopyrum intermedium.

Directory of Open Access Journals (Sweden)

Chuanliang Deng

Full Text Available In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat--Thinopyrum intermedium addition line, and the chromosomes of the three different genomes of Th. Intermedium. The smallest alien chromosome of TAi-27 was microdissected and its DNA amplified by DOP-PCR was used as a probe to hybridize with metaphase chromosomes of TAi-27 and Th. intermedium. Results showed that hybridization signals were observed in all regions of a pair of the smallest alien chromosomes and the pericentromeric area of another pair of alien chromosomes in TAi-27, indicating that the probe from microdissected chromosome is species specific. In Th. intermedium, 14 chromosomes had wide and strong hybridization signals distributed mainly on the pericentromere area and 9 chromosomes with narrow and weak signals on the pericentromere area. The remaining chromosomes displayed a very weak or no signal. Sequential FISH/GISH on Th. intermedium chromosomes using the DNAs of microdissected chromosome, Pseudoroegneria spicata (St genome and pDbH12 (a J(s genome specific probe as the probes indicated that the microdissected chromosome belonged to the St genome, three genomes (J(s , J and St in Th. intermedium could be distinguished, in which there is no hybridization signal on J genome that is similar to the genome of Th. bessarabicum. Our results showed that the smallest alien chromosomes may represent a truncated chromosome and the repetitive sequence distribution might be similar in different chromosomes within the St genome. However, the repetitive sequence distributions are different within the J(s genome, within a single chromosome, and among different genomes in Th. intermedium. Our results suggested that chromosome painting could be feasible in some plants and useful in detecting chromosome variation and repetitive sequence distribution in different genomes of polyploidy plants, which is helpful for understanding the evolution of

The impact of autism spectrum disorder symptoms on gesture use in fragile X syndrome and Down syndrome

Directory of Open Access Journals (Sweden)

Emily Lorang

2017-12-01

Full Text Available Background & aims This study compared gesture rate and purpose in participants with Down syndrome and fragile X syndrome, and the impact of autism spectrum disorder symptoms on each syndrome. Methods Twenty individuals with fragile X syndrome and 20 individuals with Down syndrome between nine and 22 years of age participated in this study. We coded gesture rate and purpose from an autism spectrum disorder evaluation, the Autism Diagnostic Observation Schedule – Second Edition. Results We did not find between-group differences (Down syndrome compared to fragile X syndrome in gesture rate or purpose. Notably, as autism spectrum disorder symptoms increased, the group with Down syndrome produced a lower rate of gestures, but used gestures for the same purpose. Gesture rate did not change based on autism spectrum disorder symptoms in the participants with fragile X syndrome, but as autism spectrum disorder symptoms increased, the participants with fragile X syndrome produced a larger proportion of gestures to regulate behavior and a smaller proportion for joint attention/social interaction. Conclusions Overall, the amount or purpose of gestures did not differentiate individuals with Down syndrome and fragile X syndrome. However, the presence of autism spectrum disorder symptoms had a significant and unique impact on these genetic disorders. In individuals with Down syndrome, the presence of more autism spectrum disorder symptoms resulted in a reduction in the rate of gesturing, but did not change the purpose. However, in fragile X syndrome, the rate of gestures remained the same, but the purpose of those gestures changed based on autism spectrum disorder symptoms. Implications Autism spectrum disorder symptoms differentially impact gestures in Down syndrome and fragile X syndrome. Individuals with Down syndrome and more autism spectrum disorder symptoms are using gestures less frequently. Therefore, clinicians may need to consider children with

Multipartnered Fertility and Depression among Fragile Families

Science.gov (United States)

Turney, Kristin; Carlson, Marcia J.

2011-01-01

We used data from the Fragile Families and Child Wellbeing Study to examine the association between multipartnered fertility (MPF)--when parents have children with more than one partner--and depression. Random-effects models suggested that MPF is associated with a greater likelihood of depression, net of family structure and other covariates.…

Comparative Erythrocytes Osmotic Fragility Test and some ...

African Journals Online (AJOL)

Erythrocytes osmotic fragility and haematological parameters of subjects with HbAS (sickle cell trait) and HbSS (sickle cell anaemia) were determined and compared with subjects with HbAA (normal adult haemoglobin), which acted as control. They were divided into three groups of 40 subjects for HbAA, 35 subjects for ...

Pure chromosome-specific PCR libraries from single sorted chromosomes

NARCIS (Netherlands)

VanDevanter, D. R.; Choongkittaworn, N. M.; Dyer, K. A.; Aten, J. A.; Otto, P.; Behler, C.; Bryant, E. M.; Rabinovitch, P. S.

1994-01-01

Chromosome-specific DNA libraries can be very useful in molecular and cytogenetic genome mapping studies. We have developed a rapid and simple method for the generation of chromosome-specific DNA sequences that relies on polymerase chain reaction (PCR) amplification of a single flow-sorted

Young Adult Female Fragile X Premutation Carriers Show Age- and Genetically-Modulated Cognitive Impairments

Science.gov (United States)

Goodrich-Hunsaker, Naomi J.; Wong, Ling M.; McLennan, Yingratana; Srivastava, Siddharth; Tassone, Flora; Harvey, Danielle; Rivera, Susan M.; Simon, Tony J.

2011-01-01

The high frequency of the fragile X premutation in the general population and its emerging neurocognitive implications highlight the need to investigate the effects of the premutation on lifespan cognitive development. Until recently, cognitive function in fragile X premutation carriers (fXPCs) was presumed to be unaffected by the mutation. Here…

Determination of a modal interaction correction for narrowband fragility data

International Nuclear Information System (INIS)

Kana, D.D.; Pomerening, D.J.

1987-01-01

Laboratory tests for safety equipment operation under seismic environments in nuclear power plants have typically included various motion simulations based on either successively-applied multiple narrowband waveforms or simultaneous multifrequency broadband random waveforms. However, only broadband excitations are directly applicable when equipment performance is affected by interaction between simultaneously responding modes. Therefore, a modal interaction correction factor is developed so that a narrowed response spectrum can be transformed to an approximately equivalent broadband spectrum which accounts for modal interaction effects. The approach includes study of the fragility response of a simple two-degree-of-freedom oscillator for representative narrowband and broadband excitations, and relating the two resulting fragility response spectra. It is found that multiplication of the narrowband response spectrum by an 0.7 factor produces a conservative equivalent broadband response spectrum. The results are interpreted in terms of a secondary device responding on a primary support structure, or a primary structure having two resonances. The approach is useful for updating existing test results based on narrowband spectra, developing composite spectra for similar equipment, or providing more flexibility in designing new tests, and is applicable to qualification proof test data as well as fragility data. 10 refs., 8 figs

Seismic Fragility Curves of Industrial Buildings by Using Nonlinear Analysis

Directory of Open Access Journals (Sweden)

Mohamed Nazri Fadzli

2017-01-01

Full Text Available This study presents the steel fragility curves and performance curves of industrial buildings of different geometries. The fragility curves were obtained for different building geometries, and the performance curves were developed based on lateral load, which is affected by the geometry of the building. Three records of far-field ground motion were used for incremental dynamic analysis (IDA, and the design lateral loads for pushover analysis (POA. All designs were based on British Standard (BS 5950; however, Eurocode 8 was preferred for seismic consideration in the analysis because BS 5950 does not specify any seismic provision. The five levels of performance stated by FEMA-273, namely, operational phase, immediate occupancy, damage control, life safety, and collapse prevention (CP were used as main guidelines for evaluating structural performance. For POA, Model 2 had highest base shear, followed by Model 1 and Model 3, even though Model 2 has a smaller structure compared with Model 3. Meanwhile, the fragility curves showed that the probability of reaching or exceeding the CP level of Model 2 is the highest, followed by that of Models 1 and 3.

Chromosomal homologies among vampire bats revealed by chromosome painting (phyllostomidae, chiroptera).

Science.gov (United States)

Sotero-Caio, C G; Pieczarka, J C; Nagamachi, C Y; Gomes, A J B; Lira, T C; O'Brien, P C M; Ferguson-Smith, M A; Souza, M J; Santos, N

2011-01-01

Substantial effort has been made to elucidate karyotypic evolution of phyllostomid bats, mostly through comparisons of G-banding patterns. However, due to the limited number of G-bands in respective karyotypes and to the similarity of non-homologous bands, an accurate evolutionary history of chromosome segments remains questionable. This is the case for vampire bats (Desmodontinae). Despite several proposed homologies, banding data have not yet provided a detailed understanding of the chromosomal changes within vampire genera. We examined karyotype differentiation of the 3 species within this subfamily using whole chromosomal probes from Phyllostomus hastatus (Phyllostominae) and Carollia brevicauda (Carolliinae). Painting probes of P. hastatus respectively detected 22, 21 and 23 conserved segments in Diphylla ecaudata, Diaemus youngi, and Desmodus rotundus karyotypes, whereas 27, 27 and 28 were respectively detectedwith C. brevicauda paints. Based on the evolutionary relationships proposed by morphological and molecular data, we present probable chromosomal synapomorphies for vampire bats and propose chromosomes that were present in the common ancestor of the 5 genera analyzed. Karyotype comparisons allowed us to relate a number of conserved chromosomal segments among the 5 species, providing a broader database for understanding karyotype evolution in the family. 2010 S. Karger AG, Basel.

Structure and management of tuberculosis control programs in fragile states--Afghanistan, DR Congo, Haiti, Somalia

NARCIS (Netherlands)

Mauch, Verena; Weil, Diana; Munim, Aayid; Boillot, Francois; Coninx, Rudi; Huseynova, Sevil; Powell, Clydette; Seita, Akihiro; Wembanyama, Henriette; van den Hof, Susan

2010-01-01

Health care delivery is particularly problematic in fragile states often connected with increased incidence of communicable diseases, among them tuberculosis. This article draws upon experiences in tuberculosis control in four fragile states from which four lessons learned were derived. A structured

The osmotic fragility of human erythrocytes is inhibited by laser irradiation

International Nuclear Information System (INIS)

Habodaszova, D.; Sikurova, L.; Waczulikova, I.

2004-01-01

In this study we investigated the influence of green laser irradiation (532 nm, 30 mW, 31,7 J/cm 2 ) on the membrane integrity of human erythrocytes and compared the results with the effect of infrared laser irradiation (810 nm, 50 mW, 31,3 J/cm 2 ). To evaluate the membrane integrity of erythrocytes, one clinical parameter, the osmotic fragility, was investigated. We observed a decrease in osmotic fragility of the erythrocytes after irradiation by the green laser light as well as by the infrared laser compared to non-irradiated controls (Authors)

Measurements of the Poisson ratio and fragility of glass-forming liquids

DEFF Research Database (Denmark)

Christensen, Tage Emil; Olsen, Niels Boye

Recently much attention has been given to models and phenomenology of glass-forming liquids that correlates fast and slow degrees of freedom . In particular the Poisson ratio has been correlated with fragility. We present data on shear - and bulk modulus obtained by the techniques...... of the piezoelectric transducers PBG and PSG on a number of glass-forming liquids. Hereby the Poisson ratio can be found. Furthermore the PSG also gives the temperature dependence of shear viscosity and thereby the fragility. The validity of the conjectured relation is discussed...

Development of fragility descriptions of equipment for seismic risk assessment of nuclear power plants

International Nuclear Information System (INIS)

Hardy, G.S.; Campbell, R.D.

1983-01-01

Probabilistic risk assessment (PRA) of a nuclear power plant for postulated hazard requires the development of fragility relationships for the plants' safety related equipment. The objective of this paper is to present some general results and conclusions concerning the development of these seismic fragility levels. Participation in fragility-related research and experience gained from the completion of several PRA studies of a variety of nuclear power plants have provided much insight as to the most vulnerable equipment and the most efficient use of resources for development of fragilities. Plants studied had seismic design bases ranging from very simple equivalent static analysis for some of the earlier plants to state-of-the-art complex multimode dyanamic analyses for plants currently under construction. Increased sophistication and rigor in seismic qualification of equipment has resulted for the most part in increased seismic resistance. The majority of equipment has been found, however, to possess more than adequate resistance to seismic loading regardless of the degree of sophistication utilized in design as long as seismic loading was included in the design process. This paper presents conclusions of the authors as to which items of equipment typically require an individual ''plant-specific'' fragility analysis and which can be treated in a generic fashion. In addition, general conclusions on the relative seismic capacity levels and most frequent failure modes are summarized for generic equipment groups

The X chromosome in space.

Science.gov (United States)

Jégu, Teddy; Aeby, Eric; Lee, Jeannie T

2017-06-01

Extensive 3D folding is required to package a genome into the tiny nuclear space, and this packaging must be compatible with proper gene expression. Thus, in the well-hierarchized nucleus, chromosomes occupy discrete territories and adopt specific 3D organizational structures that facilitate interactions between regulatory elements for gene expression. The mammalian X chromosome exemplifies this structure-function relationship. Recent studies have shown that, upon X-chromosome inactivation, active and inactive X chromosomes localize to different subnuclear positions and adopt distinct chromosomal architectures that reflect their activity states. Here, we review the roles of long non-coding RNAs, chromosomal organizational structures and the subnuclear localization of chromosomes as they relate to X-linked gene expression.

Modeling Family Adaptation to Fragile X Syndrome

Science.gov (United States)

Raspa, Melissa; Bailey, Donald, Jr.; Bann, Carla; Bishop, Ellen

2014-01-01

Using data from a survey of 1,099 families who have a child with Fragile X syndrome, we examined adaptation across 7 dimensions of family life: parenting knowledge, social support, social life, financial impact, well-being, quality of life, and overall impact. Results illustrate that although families report a high quality of life, they struggle…

Fragility: The Next Wave in Critical Infrastructure Protection

Directory of Open Access Journals (Sweden)

Allan McDougall

2009-01-01

Full Text Available In North America today, we are about to embark on a significant effort to repair, or even upgrade, many aspects of our infrastructure. Many of these efforts are linked to economic recovery packages. Others are based on sheer need. The challenge for decision makers and planners involves ensuring that scarce economic resources are put to their best use. Understanding the concept of fragility plays a pivotal part in reaching that understanding.Fragility, like many other systems—particularly Information Technology (IT systems—works on the concept of subjects and objects. Subjects are those entities that seek to exploit the services (or capacity offered by the object. Objects, on the other hand, are those entities that deliver some good or service to the overall system. Of course, something may act as the object in one pairing and the subject in another pairing—they are not exclusive in nature.

Fragile-to-strong transition in liquid silica

Science.gov (United States)

Geske, Julian; Drossel, Barbara; Vogel, Michael

2016-03-01

We investigate anomalies in liquid silica with molecular dynamics simulations and present evidence for a fragile-to-strong transition at around 3100 K-3300 K. To this purpose, we studied the structure and dynamical properties of silica over a wide temperature range, finding four indicators of a fragile-to-strong transition. First, there is a density minimum at around 3000 K and a density maximum at 4700 K. The turning point is at 3400 K. Second, the local structure characterized by the tetrahedral order parameter changes dramatically around 3000 K from a higher-ordered, lower-density phase to a less ordered, higher-density phase. Third, the correlation time τ changes from an Arrhenius behavior below 3300 K to a Vogel-Fulcher-Tammann behavior at higher temperatures. Fourth, the Stokes-Einstein relation holds for temperatures below 3000 K, but is replaced by a fractional relation above this temperature. Furthermore, our data indicate that dynamics become again simple above 5000 K, with Arrhenius behavior and a classical Stokes-Einstein relation.

Fragile-to-strong transition in liquid silica

Directory of Open Access Journals (Sweden)

Julian Geske

2016-03-01

Full Text Available We investigate anomalies in liquid silica with molecular dynamics simulations and present evidence for a fragile-to-strong transition at around 3100 K-3300 K. To this purpose, we studied the structure and dynamical properties of silica over a wide temperature range, finding four indicators of a fragile-to-strong transition. First, there is a density minimum at around 3000 K and a density maximum at 4700 K. The turning point is at 3400 K. Second, the local structure characterized by the tetrahedral order parameter changes dramatically around 3000 K from a higher-ordered, lower-density phase to a less ordered, higher-density phase. Third, the correlation time τ changes from an Arrhenius behavior below 3300 K to a Vogel-Fulcher-Tammann behavior at higher temperatures. Fourth, the Stokes-Einstein relation holds for temperatures below 3000 K, but is replaced by a fractional relation above this temperature. Furthermore, our data indicate that dynamics become again simple above 5000 K, with Arrhenius behavior and a classical Stokes-Einstein relation.

Mechanisms of diabetes mellitus-induced bone fragility.

Science.gov (United States)

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

2017-04-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

New Y chromosomes and early stages of sex chromosome ...

Indian Academy of Sciences (India)

2010-09-06

Sep 6, 2010 ... chromosomes are evolutionary consequences of that func- tion. Given sufficient ... (for a review, see Charlesworth et al. 2005). ... In the present paper, I review sex deter- mination .... part had apparently been exchanged against the homologous ... age group III-Y chromosomes were successful while in well-.

Premature ovarian failure (POF in Brazilian fragile X carriers

Directory of Open Access Journals (Sweden)

Angela M. Vianna-Morgante

1999-12-01

Full Text Available The gynecological and reproductive histories of 193 women from fragile X families were surveyed. Among the 101 carriers of the premutation, 14 experienced premature menopause, contrarily to their 37 fully mutated and 55 noncarrier female relatives. Although premature menopause showed a tendency to cluster in certain fragile X families, as a group, the premutated women experienced menopause earlier than noncarriers. This suggests that premature menopause may be the extreme effect of a spectrum of ovarian anomalies associated with the fragile X premutation.Entrevistamos 193 mulheres de famílias com afetados pela síndrome do cromossomo X frágil, quanto a sua história ginecológica e reprodutiva. Entre as 101 portadoras da pré-mutação, 14 tiveram menopausa precoce, mas nenhuma das 37 portadoras da mutação completa ou das 55 não portadoras apresentaram esta anomalia. Observamos uma tendência para a concentração da menopausa precoce em certas famílias, o que poderia significar uma peculiariedade de certas pré-mutações. Entretanto, o fato de as mulheres pré-mutadas tenderem a entrar em menopausa mais cedo do que as não portadoras sugere que a menopausa precoce seja o extremo do espectro de efeitos ovarianos da pré-mutação.

Using 3-color chromosome painting to decide between chromosome aberration models

International Nuclear Information System (INIS)

Lucas, J.N.; Sachs, R.K.

1993-01-01

Ionizing radiation produces chromosome aberrations when DNA double strand breaks (DSB) interact pairwise. For more than 30 years there have been two main, competing theories of such binary DSB interactions. The classical theory asserts that an unrepaired DSB makes two ends which separate, with each end subsequently able to join any similar (non-telomeric) end. The exchange theory asserts that the two DSB ends remain associated until repair or a reciprocal chromosome exchange involving a second DSB occurs. The authors conducted an experiment to test these models, using 3-color chromosome painting. After in vitro irradiation of resting human lymphocytes, they observed cells with three-color triplets at first metaphase: three derivative chromosomes having permuted colors, as if three broken chromosomes had played musical chairs. On the exchange model in its standard form such 3-color triplets cannot occur. On the classical model the expected frequency can be calculated. They report data and computer calculations which exclude the exchange model and favor the classical model

Epidemiology of diabetes mellitus in the fragility fracture population of a region of Southern Italy.

Science.gov (United States)

Notarnicola, A; Maccagnano, G; Tafuri, S; Moretti, L; Laviola, L; Moretti, B

2016-01-01

Increased risk of osteoporosis and its clinical significance in patients with diabetes is controversial. This study aims to increase the data which are available regarding the prevalence of diabetes mellitus in patients affected by fragility fracture in Italy. We retrospectively studied Hospital Discharge Data (HDD) in the Apulian database for the period 2006–2010 to identify a fragility fracture diagnosis in males over 65 years of age and in females over 50. The database was then checked for drug prescriptions to identify those persons who had taken at least one osteoporosis drug. Within this latter group, thanks to hospital admission and prescription records, the subjects affected with diabetes mellitus were identified. Between 2006 and 2010 in Apulia 177,639 patients were hospitalized and diagnosed as having fragility fracture. The greatest number of those fragility fractures were found to be in the 70 to 79 age range (64,917 total; females 56,994, males 7,923). The prevalence of diabetes subjects in Apulia in this period was estimated at 6.5%. In the same region and period 21.1% of subjects affected by diabetes experienced a fragility fracture; in particular, this number was 27% for males and for 20.5% females. This is the first study providing data on the prevalence of fragility fractures and diabetes in the Apulian population. The data confirm that diabetes is a risk factor which influences bone density and risk of fractures and therefore the need of osteoporosis screening and treatment in diabetic patients.

Development of fragility functions to estimate homelessness after an earthquake

Science.gov (United States)

Brink, Susan A.; Daniell, James; Khazai, Bijan; Wenzel, Friedemann

2014-05-01

Immediately after an earthquake, many stakeholders need to make decisions about their response. These decisions often need to be made in a data poor environment as accurate information on the impact can take months or even years to be collected and publicized. Social fragility functions have been developed and applied to provide an estimate of the impact in terms of building damage, deaths and injuries in near real time. These rough estimates can help governments and response agencies determine what aid may be required which can improve their emergency response and facilitate planning for longer term response. Due to building damage, lifeline outages, fear of aftershocks, or other causes, people may become displaced or homeless after an earthquake. Especially in cold and dangerous locations, the rapid provision of safe emergency shelter can be a lifesaving necessity. However, immediately after an event there is little information available about the number of homeless, their locations and whether they require public shelter to aid the response agencies in decision making. In this research, we analyze homelessness after historic earthquakes using the CATDAT Damaging Earthquakes Database. CATDAT includes information on the hazard as well as the physical and social impact of over 7200 damaging earthquakes from 1900-2013 (Daniell et al. 2011). We explore the relationship of both earthquake characteristics and area characteristics with homelessness after the earthquake. We consider modelled variables such as population density, HDI, year, measures of ground motion intensity developed in Daniell (2014) over the time period from 1900-2013 as well as temperature. Using a base methodology based on that used for PAGER fatality fragility curves developed by Jaiswal and Wald (2010), but using regression through time using the socioeconomic parameters developed in Daniell et al. (2012) for "socioeconomic fragility functions", we develop a set of fragility curves that can be

Primary Retrograde Tibiotalocalcaneal Nailing For Fragility Ankle Fractures.

Science.gov (United States)

Taylor, Benjamin C; Hansen, Dane C; Harrison, Ryan; Lucas, Douglas E; Degenova, Daniel

2016-01-01

Ankle fragility fractures are difficult to treat due to poor bone quality and soft tissues as well as the near ubiquitous presence of comorbidities including diabetes mellitus and peripheral neuropathy. Conventional open reduction and internal fixation in this population has been shown to lead to a significant rate of complications. Given the high rate of complications with contemporary fixation methods, the present study aims to critically evaluate the use of acute hindfoot nailing as a percutaneous fixation technique for high-risk ankle fragility fractures. In this study, we retrospectively evaluated 31 patients treated with primary retrograde tibiotalocalcaneal nail without joint preparation for a mean of 13.6 months postoperatively from an urban Level I trauma center during the years 2006-2012. Overall, there were two superficial infections (6.5%) and three deep infections (9.7%) in the series. There were 28 (90.3%) patients that went on to radiographic union at a mean of 22.2 weeks with maintenance of foot and ankle alignment. There were three cases of asymptomatic screw breakage observed at a mean of 18.3 months postoperatively, which were all treated conservatively.. This study shows that retrograde hindfoot nailing is an acceptable treatment option for treatment of ankle fragility fractures. Hindfoot nailing allows early weightbearing, limited soft tissue injury, and a relatively low rate of complications, all of which are advantages to conventional open reduction internal fixation techniques. Given these findings, larger prospective randomized trials comparing this treatment with conventional open reduction internal fixation techniques are warranted.

Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia.

Science.gov (United States)

Zaccaria, Alfonso; Valenti, Anna Maria; Donti, Emilio; Gozzetti, Alessandro; Ronconi, Sonia; Spedicato, Francesco

2007-04-01

Five Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients with additional chromosome abnormalities at diagnosis have been followed during Imatinib therapy. In all, the Ph chromosome disappeared, while the 5 cases, additional abnormalities [dup(1); del(5), +8 (2 patients) and +14] persisted in the subsequent studies, performed over a period of 11 to 49 months, either alone or together with a karyotypically normal cell population. This finding is consistent with a secondary origin of the Ph chromosome in these patients. It is still to early to evaluate the possible prognostic value of these additional abnormalities.

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

International Nuclear Information System (INIS)

Cho, Sung Gook; Joe, Yang Hee

2005-01-01

By nature, the seismic fragility analysis results will be considerably affected by the statistical data of design information and site-dependent ground motions. The engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are analyzed in this paper. An improved method of seismic fragility analysis is evaluated by comparative analyses to verify its efficiency for practical application to nuclear power plant structures. The effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures are also evaluated from the comparative studies. Observing the obtained results, the proposed method is more efficient for the multi-modes structures. The case study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

Energy Technology Data Exchange (ETDEWEB)

Cho, Sung Gook [Department of Civil and Environmental System Engineering, University of Incheon, 177 Dohwa-dong, Nam-gu, Incheon 402-749 (Korea, Republic of)]. E-mail: sgcho@incheon.ac.kr; Joe, Yang Hee [Department of Civil and Environmental System Engineering, University of Incheon, 177 Dohwa-dong, Nam-gu, Incheon 402-749 (Korea, Republic of)

2005-08-01

By nature, the seismic fragility analysis results will be considerably affected by the statistical data of design information and site-dependent ground motions. The engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are analyzed in this paper. An improved method of seismic fragility analysis is evaluated by comparative analyses to verify its efficiency for practical application to nuclear power plant structures. The effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures are also evaluated from the comparative studies. Observing the obtained results, the proposed method is more efficient for the multi-modes structures. The case study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities.

High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells.

Science.gov (United States)

Kumari, Daman; Swaroop, Manju; Southall, Noel; Huang, Wenwei; Zheng, Wei; Usdin, Karen

2015-07-01

: Fragile X syndrome (FXS), the most common form of inherited cognitive disability, is caused by a deficiency of the fragile X mental retardation protein (FMRP). In most patients, the absence of FMRP is due to an aberrant transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. FXS has no cure, and the available treatments only provide symptomatic relief. Given that FMR1 gene silencing in FXS patient cells can be partially reversed by treatment with compounds that target repressive epigenetic marks, restoring FMRP expression could be one approach for the treatment of FXS. We describe a homogeneous and highly sensitive time-resolved fluorescence resonance energy transfer assay for FMRP detection in a 1,536-well plate format. Using neural stem cells differentiated from an FXS patient-derived induced pluripotent stem cell (iPSC) line that does not express any FMRP, we screened a collection of approximately 5,000 known tool compounds and approved drugs using this FMRP assay and identified 6 compounds that modestly increase FMR1 gene expression in FXS patient cells. Although none of these compounds resulted in clinically relevant levels of FMR1 mRNA, our data provide proof of principle that this assay combined with FXS patient-derived neural stem cells can be used in a high-throughput format to identify better lead compounds for FXS drug development. In this study, a specific and sensitive fluorescence resonance energy transfer-based assay for fragile X mental retardation protein detection was developed and optimized for high-throughput screening (HTS) of compound libraries using fragile X syndrome (FXS) patient-derived neural stem cells. The data suggest that this HTS format will be useful for the identification of better lead compounds for developing new therapeutics for FXS. This assay can also be adapted for FMRP detection in clinical and research settings. ©AlphaMed Press.

SEISMIC FRAGILITY ANALYSIS OF IMPROVED RC FRAMES USING DIFFERENT TYPES OF BRACING

Directory of Open Access Journals (Sweden)

HAMED HAMIDI JAMNANI

2017-04-01

Full Text Available Application of bracings to increase the lateral stiffness of building structures is a technique of seismic improvement that engineers frequently have recourse to. Accordingly, investigating the role of bracings in concrete structures along with the development of seismic fragility curves are of overriding concern to civil engineers. In this research, an ordinary RC building, designed according to the 1st edition of Iranian seismic code, was selected for examination. According to FEMA 356 code, this building is considered to be vulnerable. To improve the seismic performance of this building, 3 different types of bracings, which are Concentrically Braced Frames, Eccentrically Braced Frames and Buckling Restrained Frames were employed, and each bracing element was distributed in 3 different locations in the building. The researchers developed fragility curves and utilized 30 earthquake records on the Peak Ground Acceleration seismic intensity scale to carry out a time history analysis. Tow damage scale, including Inter-Story Drifts and Plastic Axial Deformation were also used. The numerical results obtained from this investigation confirm that Plastic Axial Deformation is more reliable than conventional approaches in developing fragility curves for retrofitted frames. In lieu of what is proposed, the researchers selected the suitable damage scale and developed and compared log-normal distribution of fragility curves first for the original and then for the retrofitted building.

Currency crisis and external fragility: a Minskyan interpretation applied to the Brazilian economy between 1999 and 2013

Directory of Open Access Journals (Sweden)

Victor Hugo Rocha Sarto

2016-12-01

Full Text Available This work has two goals. The first one is to develop an interpretation for open economies founded on Minsky’s financial fragility hypothesis about the process of a currency crisis and its determinants. The deterioration of an economy’s external financial structure is identified as the reason for the increase of its crisis susceptibility. With this approach, we create external fragility indexes intending to measure an economy’s crisis susceptibility. Our second objective is to evaluate the Brazilian external fragility between 1999 and 2013 using the index and the interpretation previously developed. The results suggest that Brazilian’s external fragility suffered a gradual and significant decrease and tends to follow stable trend in the coming years.

Chromosomal instability and double minute chromosomes in a breast cancer patient

International Nuclear Information System (INIS)

Lalic, H.; Radosevic-Stasic, B.

2004-01-01

Cytogenetic analysis was performed in peripheral blood lymphocytes (PBL) of a woman with ductal breast carcinoma, who as a hospital employee was exposed professionally for 15 years to low doses of ionizing radiation. The most important finding after the chemotherapy in combination with radiotherapy was the presence of double minutes (DM) chromosomes, in combination with other chromosomal abnormalities (on 200 scored metaphases were found 2 chromatid breaks, 10 dicentrics, 11 acentric fragments, 2 gaps, and 3 double min chromosomes). In a repeated analysis (after 6 months), DM chromosomes were still present. To rule out the possibility that the patient was overexposed to ionizing radiation at work, her blood test was compared with a group of coworkers as well as with a group of professionally unexposed people. The data rejected this possibility, but the retroactive analysis showed that the patient even at the time of employment had a moderately increased number of chromosomal aberrations (3.5%) consisting of 3 isochromatids and 4 gaps, suggesting that her initial genomic instability enhanced the later development. The finding of a continuous presence of rare DM chromosomes in her PBL (4 and 10 months after radio-chemotherapy) was considered as an indicator of additional risk, which might have some prognostic significance. (author)

Brief Report: Acamprosate in Fragile X Syndrome

Science.gov (United States)

Erickson, Craig A.; Mullett, Jennifer E.; McDougle, Christopher J.

2010-01-01

Glutamatergic dysfunction is implicated in the pathophysiology of fragile X syndrome (FXS). We report on the first trial of acamprosate, a drug with putative mGluR5 antagonism, in three adults with FXS and autism. Medical records describing open-label treatment with acamprosate in 3 patients with FXS and a comorbid diagnosis of autistic disorder…

Chromosome painting in plants.

NARCIS (Netherlands)

Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

2001-01-01

The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in

Noninvolvement of the X chromosome in radiation-induced chromosome translocations in the human lymphoblastoid cell line TK6

International Nuclear Information System (INIS)

Jordan, R.; Schwartz, J.L.

1994-01-01

Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by 60 Co γ rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized autosome chromosome 7. When corrected for DNA content, acentric fragments were induced with equal frequency in the X and 7 chromosomes. Dose-dependent increases in chromosomal interchanges involving chromosome 7 were noted, and the frequencies of balanced translocations and dicentrics produced were approximately equal. Chromosome interchanges involving the X chromosome were rare and showed no apparent dose dependence. Thus, while chromosomes 7 and X are equally sensitive to the induction of chromosome breaks, the X chromosome is much less likely to interact with autosomes than chromosome 7. The noninvolvement of the X chromosome in translocations with autosomes may reflect a more peripheral and separate location for the X chromosome in the mammalian nucleus. 20 refs., 2 figs., 1 tab

Soil erosion fragility assessment using an impact model and geographic information system

OpenAIRE

Jorge,Luiz Alberto Blanco

2009-01-01

A study was taken in a 1566 ha watershed situated in the Capivara River basin, municipality of Botucatu, São Paulo State, Brazil. This environment is fragile and can be subjected to different forms of negative impacts, among them soil erosion by water. The main objective of the research was to develop a methodology for the assessment of soil erosion fragility at the various different watershed positions, using the geographic information system ILWIS version 3.3 for Windows. An impact model wa...

Autism genetic database (AGD: a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

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Talebizadeh Zohreh

2009-09-01

Full Text Available Abstract Background Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors. Description AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided. Conclusion AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research

Chromosome painting in biological dosimetry: Semi-automatic system to score stable chromosome aberrations

International Nuclear Information System (INIS)

Garcia-Sagredo, J.M.; Vallcorba, I.; Sanchez-Hombre, M.C.; Ferro, M.T.; San Roman Cos-Gayon, C.; Santos, A.; Malpica, N.; Ortiz, C.

1997-01-01

From the beginning of the description of the procedure of chromosome painting by fluorescence in situ hybridization (FISH), it was thought its possible application to score induced chromosomal aberrations in radiation exposition. With chromosome painting it is possible to detect changes between chromosomes that has been validated in radiation exposition. Translocation scoring by FISH, contrarily to the unstable dicentrics, mainly detect stable chromosome aberrations that do not disappear, it allows the capability of quantify delayed acute expositions or chronic cumulative expositions. The large number of cells that have to be analyzed for high accuracy, specially when dealing with low radiation doses, makes it almost imperative to use an automatic analysis system. After validate translocation scoring by FISH in our, we have evaluated the ability and sensitivity to detect chromosomal aberrations by chromosome using different paint probes used, showing that any combination of paint probes can be used to score induced chromosomal aberrations. Our group has developed a FISH analysis that is currently being adapted for translocation scoring analysis. It includes systematic error correction and internal control probes. The performance tests carried out show that 9,000 cells can be analyzed in 10 hr. using a Sparc 4/370. Although with a faster computer, a higher throughput is expected, for large population screening or very low radiation doses, this performance still has to be improved. (author)

On the importance of uncertain factors in seismic fragility assessment

International Nuclear Information System (INIS)

Borgonovo, E.; Zentner, I.; Pellegri, A.; Tarantola, S.; Rocquigny, E. de

2013-01-01

This paper addresses the definition of importance measures for helping the modeller to detect the factors on which to focus modelling activity and data collection in seismic fragility analysis. We study sensitivity measures consistent with the decision-support criteria of interest, namely, the (mean) fragility curve and the “High Confidence of Low Probability of Failure” (HCLPF) value. The importance measures are obtained analytically for the EPRI safety factor method, which is nowadays used worldwide for seismic risk assessment of nuclear plants. We illustrate and discuss the use of both variance-based and CDF-based importance measures in the application to two case studies, the first analytical and based on the EPRI method, the second numerical.

Scaling in soft spheres: fragility invariance on the repulsive potential softness

International Nuclear Information System (INIS)

Michele, Cristiano De; Sciortino, Francesco; Coniglio, Antonio

2004-01-01

We address the question of the dependence of the fragility of glass forming supercooled liquids on the 'softness' of an interacting potential by performing numerical simulation of a binary mixture of soft spheres with different power n of the interparticle repulsive potential. We show that the temperature dependence of the diffusion coefficients for various n collapses onto a universal curve, supporting the unexpected view that fragility is not related to the hard core repulsion. We also find that the configurational entropy correlates with the slowing down of the dynamics for all studied n. (letter to the editor)

Fragile X and autism: Intertwined at the molecular level leading to targeted treatments

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Hagerman Randi

2010-09-01

Full Text Available Abstract Fragile X syndrome (FXS is caused by an expanded CGG repeat (> 200 repeats in the 5' untranslated portion of the fragile mental retardation 1 gene (FMR1, leading to deficiency or absence of the FMR1 protein (FMRP. FMRP is an RNA carrier protein that controls the translation of several other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS cases, and pervasive developmental disorder, not otherwise specified (PDD-NOS occurs in an additional 30% of cases. Premutation repeat expansions (55 to 200 CGG repeats may also give rise to autism spectrum disorders (ASD, including both autism and PDD-NOS, through a different molecular mechanism that involves a direct toxic effect of the expanded CGG repeat FMR1 mRNA. RNA toxicity can also lead to aging effects including tremor, ataxia and cognitive decline, termed fragile X-associated tremor ataxia syndrome (FXTAS, in premutation carriers in late life. In studies of mice bearing premutation expansions, there is evidence of early postnatal neuronal cell toxicity, presenting as reduced cell longevity, decreased dendritic arborization and altered synaptic morphology. There is also evidence of mitochondrial dysfunction in premutation carriers. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in autism without fragile X mutations. Research regarding dysregulation of neurotransmitter systems in FXS, including the metabotropic glutamate receptor (mGluR1/5 pathway and γ aminobutyric acid (GABAA pathways, have led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism.

Drug-induced premature chromosome condensation (PCC) protocols: cytogenetic approaches in mitotic chromosome and interphase chromatin.

Science.gov (United States)

Gotoh, Eisuke

2015-01-01

Chromosome analysis is a fundamental technique which is used in wide areas of cytogenetic study including karyotyping species, hereditary diseases diagnosis, or chromosome biology study. Chromosomes are usually prepared from mitotic cells arrested by colcemid block protocol. However, obtaining mitotic chromosomes is often hampered under several circumstances. As a result, cytogenetic analysis will be sometimes difficult or even impossible in such cases. Premature chromosome condensation (PCC) (see Note 1) is an alternative method that has proved to be a unique and useful way in chromosome analysis. Former, PCC has been achieved following cell fusion method (cell-fusion PCC) mediated either by fusogenic viruses (e.g., Sendai virus) or cell fusion chemicals (e.g., polyethylene glycol), but the cell fusion PCC has several drawbacks. The novel drug-induced PCC using protein phosphatase inhibitors was introduced about 20 years ago. This method is much simpler and easier even than the conventional mitotic chromosome preparation protocol use with colcemid block and furthermore obtained PCC index (equivalent to mitotic index for metaphase chromosome) is usually much higher than colcemid block method. Moreover, this method allows the interphase chromatin to be condensed to visualize like mitotic chromosomes. Therefore drug-induced PCC has opened the way for chromosome analysis not only in metaphase chromosomes but also in interphase chromatin. The drug-induced PCC has thus proven the usefulness in cytogenetics and other cell biology fields. For this second edition version, updated modifications/changes are supplemented in Subheadings 2, 3, and 4, and a new section describing the application of PCC in chromosome science fields is added with citation of updated references.

Non-fragile guaranteed cost control for uncertain neutral dynamic systems with time-varying delays in state and control input

International Nuclear Information System (INIS)

Lien, C.-H.

2007-01-01

This article considers non-fragile guaranteed cost control problem for a class of uncertain neutral system with time-varying delays in both state and control input. Delay-dependent criteria are proposed to guarantee the robust stabilization of systems. Linear matrix inequality (LMI) optimization approach is used to solve the non-fragile guaranteed cost control problem. Non-fragile guaranteed cost control for unperturbed neutral system is considered in the first step. Robust non-fragile guaranteed cost control for uncertain neutral system is designed directly from the unperturbed condition. An efficient approach is proposed to design the non-fragile guaranteed cost control for uncertain neutral systems. LMI toolbox of Matlab is used to implement the proposed results. Finally, a numerical example is illustrated to show the usefulness of the proposed results

Mitotic chromosome condensation in vertebrates

International Nuclear Information System (INIS)

Vagnarelli, Paola

2012-01-01

Work from several laboratories over the past 10–15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292–301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories—a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307–316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119–1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579–589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different

Mitotic chromosome condensation in vertebrates

Energy Technology Data Exchange (ETDEWEB)

Vagnarelli, Paola, E-mail: P.Vagnarelli@ed.ac.uk

2012-07-15

Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes

Resolution of spatial and temporal visual attention in infants with fragile X syndrome

OpenAIRE

Farzin, Faraz; Rivera, Susan M.; Whitney, David

2011-01-01

Fragile X syndrome is the most common cause of inherited intellectual impairment and the most common single-gene cause of autism. Individuals with fragile X syndrome present with a neurobehavioural phenotype that includes selective deficits in spatiotemporal visual perception associated with neural processing in frontal–parietal networks of the brain. The goal of the current study was to examine whether reduced resolution of spatial and/or temporal visual attention may underlie perceptual def...

The Social Consequences of Raising Medically Fragile and ...

African Journals Online (AJOL)

2011-10-02

Oct 2, 2011 ... who are medically fragile and/or developmentally challenged. It is an ... The overarching theme was the families' search for safety ... children. It is important for policy makers to understand the situation of such parents so ... their family members, children and families without disabilities and, service providers.

Intergenerational Relationships and Union Stability in Fragile Families

Science.gov (United States)

Hognas, Robin S.; Carlson, Marcia J.

2010-01-01

Using data from the Fragile Families and Child Wellbeing Study (N = 2,656), we examined the association between intergenerational relationships and parents' union stability 5 years after a baby's birth. Results showed that more amiable relationships between parents and each partner's parents, and children's spending more time with paternal…

Adaptive Skills, Behavior Problems, and Parenting Stress in Mothers of Boys with Fragile X Syndrome

Science.gov (United States)

Sarimski, Klaus

2010-01-01

The relationship of temperament, atypical behaviors, and adaptive behavior of young boys with Fragile X syndrome on mothers' parenting stress was analyzed. Twenty-six boys with Fragile X syndrome (30-88 months of age) participated. The overall development of the participants was significantly delayed with a specific profile of adaptive behaviors…

Localisation of aphidicolin-induced break points in Holstein-Friesian cattle (Bos taurus using RBG-banding

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Mernies Beatriz

2002-11-01

Full Text Available Abstract Fragile sites (FS seem to play a role in genome instability and may be involved in karyotype evolution and chromosome aberrations. The majority of common fragile sites are induced by aphidicolin. Aphidicolin was used at two different concentrations (0.15 and 0.30 μM to study the occurrence of FS in the cattle karyotype. In this paper, a map of aphidicolin induced break points and fragile sites in cattle chromosomes was constructed. The statistical analysis indicated that any band with three or more breaks was significantly damaged (P r = 0.54. On the contrary, 21 FS were identified on negative R bands while 9 FS were located on positive R bands.

Prefrontal Cortex Dysfunction in Fragile X Mice Depends on the Continued Absence of Fragile X Mental Retardation Protein in the Adult Brain.

Science.gov (United States)

Siegel, Jennifer J; Chitwood, Raymond A; Ding, James M; Payne, Clayton; Taylor, William; Gray, Richard; Zemelman, Boris V; Johnston, Daniel

2017-08-02

Fragile X Syndrome (FX) is generally considered a developmental disorder, arising from a mutation that disrupts the transcription of Fragile X Mental Retardation Protein (FMRP). However, FMRP regulates the transcription of other proteins and participates in an unknown number of protein-protein interactions throughout life. In addition to known developmental issues, it is thus likely that some dysfunction is also due to the ongoing absence of FMRP. Dissociating dysfunction due to developmental dysregulation from dysfunction due to the continued absence of FMRP is necessary to understand the different roles of FMRP and to treat patients effectively throughout life. We show here that FX model mice display substantial deficits in a PFC-dependent task. We then use conditional knock-out mice to eliminate FMRP only in the PFC alone of adult mice. We observe an increase in the proportion of nonlearners and a delay in the onset of learning in both FX and conditional knock-out mice. The results suggest that these deficits (1) are due to the absence of FMRP in the PFC alone and (2) are not the result of developmental dysregulation. Furthermore, PFC-associated deficits are rescued by initiating production of FMRP in adult conditional restoration mice, suggesting that PFC dysfunction may persist as long as FMRP is absent and therefore can be rescued after development. The data suggest that it is possible to dissociate the roles of FMRP in neural function from developmental dysregulation, and that PFC function can be restored in the adult FX brain. SIGNIFICANCE STATEMENT The absence of Fragile X Mental Retardation Protein (FMRP) from birth results in developmental disabilities and lifelong impairments. We show here that in mouse models PFC dysfunction in Fragile X Syndrome (FX) can be attributed to the continued absence of FMRP from the PFC, independent of FMRP status during development. Furthermore, initiation of FMRP production in the PFC of adult FX animals rescues PFC

Chromosomal rearrangement interferes with meiotic X chromosome inactivation

Czech Academy of Sciences Publication Activity Database

Homolka, David; Ivánek, Robert; Čapková, Jana; Jansa, Petr; Forejt, Jiří

2007-01-01

Roč. 17, č. 10 (2007), s. 1431-1437 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA301/06/1334; GA ČR GA301/07/1383 Grant - others:Howard Hughes Medical Institute(US) HHMI 55000306 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromosomal translocations * meiotic X chromosome inactivation * spermatogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

Paternal isodisomy of chromosome 6 in association with a maternal supernumerary marker chromosome (6)

Energy Technology Data Exchange (ETDEWEB)

James, R.S.; Crolla, J.A.; Sitch, F.L. [Salisbury District Hospital, Wiltshire (United Kingdom)] [and others

1994-09-01

Uniparental disomy may arise by a number of different mechanisms of aneuploidy correction. A population that has been identified as being at increased risk of aneuploidy are those individuals bearing supernumerary marker chromosomes (SMCs). There have been a number of cases reported of trisomy 21 in association with bi-satellited marker chromosomes have described two individuals with small inv dup (15) markers. One had paternal isodisomy of chromosome 15 and Angelman syndrome. The other had maternal heterodisomy (15) and Prader-Willi syndrome. At the Wessex Regional Genetics Laboratory we have conducted a search for uniparental disomy of the normal homologues of the chromosomes from which SMCs originated. Our study population consists of 39 probands with SMCs originating from a number of different autosomes, including 17 with SMCs of chromosome 15 origin. Using PCR amplification of microsatellite repeat sequences located distal to the regions included in the SMCs we have determined the parental origin of the two normal homologues in each case. We have identified paternal isodisomy of chromosome 6 in a female child with a supernumerary marker ring chromosome 6 in approximately 70% of peripheral blood lymphocytes. The marker was found to be of maternal origin. This is the second case of paternal isodisomy of chromosome 6 to be reported, and the first in association with a SMC resulting in a partial trisomy for a portion of the short arm of chromosome 6. In spite of this, the patient appears to be functioning appropriately for her age.

Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

Science.gov (United States)

Usdin, Karen; Kumari, Daman

2015-01-01

The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

Gonadal sex chromosome complement in individuals with sex chromosomal and/or gonadal disorders

Energy Technology Data Exchange (ETDEWEB)

Bridge, J.A.; Sanger, W.G.; Seemayer, T. [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

1994-09-01

Gonadal abnormalities are characteristically seen in patients with sex chromosomal aneuploidy. Morphologically these abnormalities can be variable and are hypothesized to be dependent on the sex chromosomal consititution of the gonad (independent of the chromosomal complement of other tissues, such as peripheral blood lymphocytes). In this study, the gonadal sex chromosome complement was evaluated for potential mosaicism and correlated with the histopathology from 5 patients with known sex chromosomal and/or gonadal disorders. FISH techniques using X and Y chromosome specific probes were performed on nuclei extracted from paraffin embedded tissue. Gonadal tissue obtained from case 1 (a true hemaphroditic newborn) consisted of ovotestes and epididymis (left side) and ovary with fallopian tube (right side). Cytogenetic and FISH studies performed on blood, ovotestes and ovary revealed an XX complement. Cytogenetic analysis of blood from case 2, a 4-year-old with suspected Turner syndrome revealed 45,X/46,X,del(Y)(q11.21). FISH analysis of the resected gonads (histologically = immature testes) confirmed an X/XY mosaic complement. Histologically, the gonadal tissue was testicular. Severe autolysis prohibited successful analysis in the 2 remaining cases. In summary, molecular cytogenetic evaluation of gonadal tissue from individuals with sex chromosomal and/or gonadal disorders did not reveal tissue-specific anomalies which could account for differences observed pathologically.

The distribution of chromosome aberrations among chromosomes of karyotype in exposed human lymphocyte

International Nuclear Information System (INIS)

Que Tran; Tien Hoang Hung

1997-01-01

Induced chromosome aberrations (ch. ab.) in exposed Human peripheral blood lymphocyte have been used to assay radio.bio.doses, because of their characters such as: the maintaining Go phase in cell cycle in body, the distribution of cell in blood system and the distribution of ch. ab. in exposed cells of body and among chromosomes of karyotype. The frequency of ch. ab. reflected the quantity of radiation dose, dose rate and radiation energy. The dependence between radiation dose and frequency of ch. ab. was illustrated by the mathematic equations. The distribution of induced ch. ab. among the cells exposed to uniform radiation fields was Poisson's, but the distribution of ch. ab. among chromosomes in karyotype depended on radiation field and mononucleotid sequence of DNA molecular of each chromosome. The minimum influence of mononucleotid sequence of DNA molecular in inform ch. ab. will be advantageous state for dose-assessments. The location of induced ch. ab. in exposed Human lymphocyte had been determined by karyotype analyses. The data of statistic analyse had improved that the number of ch. ab. depended on the size of chromosomes in karyotype. The equal distribution of ch. ab.among chromosomes in karyotype provided the objectiveness and the accuracy of using the chromosomal aberrant analysis technique on bio-dosimetry. (author)

Multifarious Functions of the Fragile X Mental Retardation Protein.

Science.gov (United States)

Davis, Jenna K; Broadie, Kendal

2017-10-01

Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dependent critical period development, and the excitation-inhibition (E/I) neural circuitry balance. In this review, we contextualize 3 years of FXS model research. Future directions extrapolated from recent advances focus on discovering links between FMRP roles to determine whether FMRP has a multitude of unrelated functions or whether combinatorial mechanisms can explain its multifaceted existence. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of the Ceratitis capitata y chromosome using in situ hybridization to mitotic chromosomes

International Nuclear Information System (INIS)

Willhoeft, U.; Franz, G.

1998-01-01

In Ceratitis capitata the Y chromosome is responsible for sex-determination. We used fluorescence in situ hybridization (FISH) for cytogenetic analysis of mitotic chromosomes. FISH with the wild-type strain EgyptII and two repetitive DNA probes enabled us to differentiate between the short and the long arm of the Y chromosome and gives a much better resolution than C-banding of mitotic chromosomes. We identified the Y-chromosomal breakpoints in Y-autosome translocations using FISH. Even more complex rearrangements i.e. deletions and insertions in some translocation strains were detected by this method. A strategy for mapping the primary sex determination factor in Ceratitis capitata by FISH is presented. (author)

Systems Fragility: The Sociology of Chaos

Science.gov (United States)

2015-03-01

shuttle explosion was found to be “a failure in the joint between the two lower segments of the right Solid Rocket Motor.” The report goes on to state...2013, http://www.bloomberg.com/news/2013-09-24/flooded-estes-park-greets- tourists -as- locals-can-t-flush html 137 Koehler, Kress, and Miller, What... market research questions about animals.166 For the purposes of this research, purposive event sampling is used to study community fragility in

Numerically abnormal chromosome constitutions in humans

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-12-31

Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

Inactivation of the maternal fragile X gene results in sensitization of GABAB receptor function in the offspring

OpenAIRE

Zupan, Bojana; Toth, Miklos

2008-01-01

Fragile X syndrome is an X linked disorder caused by the inactivation of the FMR-1 gene with symptoms ranging from impaired cognitive functions to seizures, anxiety, sensory abnormalities and hyperactivity. Although Fragile X syndrome is considered a typical Mendelian disorder, we have recently reported that the environment, specifically the fmr-1+/− or fmr-1−/− (H or KO) maternal environment, elicits on its own a partial fragile X-like phenotype and can contribute to the overall phenotype of...

The Trajectory of Mathematics Skills and Working Memory Thresholds in Girls with Fragile X Syndrome

Science.gov (United States)

Murphy, Melissa M.; Mazzocco, Michele M. M.

2009-01-01

Fragile X syndrome is a common genetic disorder associated with executive function deficits and poor mathematics achievement. In the present study, we examined changes in math performance during the elementary and middle school years in girls with fragile X syndrome, changes in the working memory loads under which children could complete a…

Chromosomal Abnormalities in ADHD

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2002-07-01

Full Text Available The prevalence of fragile X syndrome, velocardiofacial syndrome (VCFS, and other cytogenetic abnormalities among 100 children (64 boys with combined type ADHD and normal intelligence was assessed at the NIMH and Georgetown University Medical Center.

Imitation in Fragile X Syndrome: Implications for Autism

Science.gov (United States)

Macedoni-Luksic, Marta; Greiss-Hess, Laura; Rogers, Sally J.; Gosar, David; Lemons-Chitwood, Kerrie; Hagerman, Randi

2009-01-01

To address the specific impairment of imitation in autism, the imitation abilities of 22 children with fragile X syndrome (FXS) with and without autism were compared. Based on previous research, we predicted that children with FXS and autism would have significantly more difficulty with non-meaningful imitation tasks. After controlling for…

Normal RNAi response in human fragile x fibroblasts

DEFF Research Database (Denmark)

Madsen, Charlotte; Grønskov, Karen; Brøndum-Nielsen, Karen

2009-01-01

BACKGROUND: Fragile x syndrome is caused by loss of expression of the FMRP protein involved in the control of a large number of mRNA targets. The Drosophila ortholog dFXR interacts with a protein complex that includes Argonaute2, an essential component of the RNA-induced silencing complex (RISC...

Ricci curvature: An economic indicator for market fragility and systemic risk.

Science.gov (United States)

Sandhu, Romeil S; Georgiou, Tryphon T; Tannenbaum, Allen R

2016-05-01

Quantifying the systemic risk and fragility of financial systems is of vital importance in analyzing market efficiency, deciding on portfolio allocation, and containing financial contagions. At a high level, financial systems may be represented as weighted graphs that characterize the complex web of interacting agents and information flow (for example, debt, stock returns, and shareholder ownership). Such a representation often turns out to provide keen insights. We show that fragility is a system-level characteristic of "business-as-usual" market behavior and that financial crashes are invariably preceded by system-level changes in robustness. This was done by leveraging previous work, which suggests that Ricci curvature, a key geometric feature of a given network, is negatively correlated to increases in network fragility. To illustrate this insight, we examine daily returns from a set of stocks comprising the Standard and Poor's 500 (S&P 500) over a 15-year span to highlight the fact that corresponding changes in Ricci curvature constitute a financial "crash hallmark." This work lays the foundation of understanding how to design (banking) systems and policy regulations in a manner that can combat financial instabilities exposed during the 2007-2008 crisis.

Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X.

Science.gov (United States)

Hagerman, R J; Leehey, M; Heinrichs, W; Tassone, F; Wilson, R; Hills, J; Grigsby, J; Gage, B; Hagerman, P J

2001-07-10

The authors report five elderly men with the fragile X premutation who had a progressive action tremor associated with executive function deficits and generalized brain atrophy. These individuals had elevated fragile X mental retardation 1 gene (FMR1) messenger RNA and normal or borderline levels of FMR1 protein. The authors propose that elevations of FMR1 messenger RNA may be causative for a neurodegenerative syndrome in a subgroup of elderly men with the FMR1 premutation.

Seismic fragility analyses of nuclear power plant structures based on the recorded earthquake data in Korea

International Nuclear Information System (INIS)

Joe, Yang Hee; Cho, Sung Gook

2003-01-01

This paper briefly introduces an improved method for evaluating seismic fragilities of components of nuclear power plants in Korea. Engineering characteristics of small magnitude earthquake spectra recorded in the Korean peninsula during the last several years are also discussed in this paper. For the purpose of evaluating the effects of the recorded earthquake on the seismic fragilities of Korean nuclear power plant structures, several cases of comparative studies have been performed. The study results show that seismic fragility analysis based on the Newmark's spectra in Korea might over-estimate the seismic capacities of Korean facilities. (author)

Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus.

Science.gov (United States)

Sourial, Mary; Doering, Laurie C

2017-07-01

The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST + CD15 + CD133 + ) and an increased proportion of neuroblasts (PSA-NCAM + CD15 + ) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G 2 /M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Origin of amphibian and avian chromosomes by fission, fusion, and retention of ancestral chromosomes

Science.gov (United States)

Voss, Stephen R.; Kump, D. Kevin; Putta, Srikrishna; Pauly, Nathan; Reynolds, Anna; Henry, Rema J.; Basa, Saritha; Walker, John A.; Smith, Jeramiah J.

2011-01-01

Amphibian genomes differ greatly in DNA content and chromosome size, morphology, and number. Investigations of this diversity are needed to identify mechanisms that have shaped the evolution of vertebrate genomes. We used comparative mapping to investigate the organization of genes in the Mexican axolotl (Ambystoma mexicanum), a species that presents relatively few chromosomes (n = 14) and a gigantic genome (>20 pg/N). We show extensive conservation of synteny between Ambystoma, chicken, and human, and a positive correlation between the length of conserved segments and genome size. Ambystoma segments are estimated to be four to 51 times longer than homologous human and chicken segments. Strikingly, genes demarking the structures of 28 chicken chromosomes are ordered among linkage groups defining the Ambystoma genome, and we show that these same chromosomal segments are also conserved in a distantly related anuran amphibian (Xenopus tropicalis). Using linkage relationships from the amphibian maps, we predict that three chicken chromosomes originated by fusion, nine to 14 originated by fission, and 12–17 evolved directly from ancestral tetrapod chromosomes. We further show that some ancestral segments were fused prior to the divergence of salamanders and anurans, while others fused independently and randomly as chromosome numbers were reduced in lineages leading to Ambystoma and Xenopus. The maintenance of gene order relationships between chromosomal segments that have greatly expanded and contracted in salamander and chicken genomes, respectively, suggests selection to maintain synteny relationships and/or extremely low rates of chromosomal rearrangement. Overall, the results demonstrate the value of data from diverse, amphibian genomes in studies of vertebrate genome evolution. PMID:21482624

Comparison of main-shock and aftershock fragility curves developed for New Zealand and US buildings

Science.gov (United States)

Uma, S.R.; Ryu, H.; Luco, N.; Liel, A.B.; Raghunandan, M.

2011-01-01

Seismic risk assessment involves the development of fragility functions to express the relationship between ground motion intensity and damage potential. In evaluating the risk associated with the building inventory in a region, it is essential to capture 'actual' characteristics of the buildings and group them so that 'generic building types' can be generated for further analysis of their damage potential. Variations in building characteristics across regions/countries largely influence the resulting fragility functions, such that building models are unsuitable to be adopted for risk assessment in any other region where a different set of building is present. In this paper, for a given building type (represented in terms of height and structural system), typical New Zealand and US building models are considered to illustrate the differences in structural model parameters and their effects on resulting fragility functions for a set of main-shocks and aftershocks. From this study, the general conclusion is that the methodology and assumptions used to derive basic capacity curve parameters have a considerable influence on fragility curves.

Molecular fundamentals of chromosomal mutagenesis

International Nuclear Information System (INIS)

Ganassi, E.Eh.; Zaichkina, S.I.; Malakhova, L.V.

1987-01-01

Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages

[The fragility of the self].

Science.gov (United States)

Rubia Vila, Francisco José

2002-01-01

This presentation raises the hypothesis that the "self" is a construction of the brain and extremely fragile. In order to support this statement, Prof. Rubia provides three different reasonings: firstly, we are not borne with the "self", but rather it is the result of development during childhood; secondly, the self is subject to cultural influences, so that the perception of this "self" or of the own personality varies according to different cultures. And thirdly, the self is not indivisible, as shown by epileptic patients with a "split-brain" operation, or the psychiatric cases of double personality or the multiple personality disorder.

Exchange of core chromosomes and horizontal transfer of lineage-specific chromosomes in Fusarium oxysporum

NARCIS (Netherlands)

Vlaardingerbroek, I.; Beerens, B.; Rose, L.; Fokkens, L.; Cornelissen, B.J.C.; Rep, M.

2016-01-01

Horizontal transfer of supernumerary or lineage-specific (LS) chromosomes has been described in a number of plant pathogenic filamentous fungi. So far it was not known whether transfer is restricted to chromosomes of certain size or properties, or whether 'core' chromosomes can also undergo

Chromosomal geometry in the interface from the frequency of the radiation induced chromosome aberrations

International Nuclear Information System (INIS)

Nasazzi, N.; Otero, D.; Di Giorgio, M.

1996-01-01

Ionizing radiation induces DNA double-strand breaks (DSBs) and their interaction and illegitimate recombination produces chromosomal aberrations. Stable chromosomal aberrations comprise inter-chromosomal events (translocations) and intra-chromosomal events (inversions). When DSBs induction and interaction is done at random, and the proximity effects are neglected, the expected relation between translocations and inversions is F=86, based on chromosome arm length. The number of translocations and inversions is analyzed by using G-banding in 16 lymphocytes cultures from blood samples acutely irradiated with γ-rays (dose range: 0,5 Gy - 3 Gy). The result obtained was: F=13,5, significantly smaller than F=86. Literature data show similar small F values, but strongly spread. The excess of inversions could be explained by a 'proximity effect', it means that more proximate DSBs have more interaction probability. Therefore, it is possible to postulate a special chromosome arrangement during irradiation and the subsequent interval. We propose a model where individual chromosomes show spherical confinement with some degree of overlapping and DSBs induction proportional to cross section. A DSBs interaction probability function with cut-off length= 1μ is assumed. According to our results, the confinement volume is ≅ 6.4% of the nuclear volume. Nevertheless, we presume that large spread in F data could be due to temporal variation in overlapping and spatial chromosomal confinement. (authors). 14 refs

Effect of laser light on the fragility and permeability of the red blood cell membrane

International Nuclear Information System (INIS)

El-Yassin, H. D.

2005-01-01

The resistance of red blood cells to hypotonic hemolysis is often characterized in terms of their osmotic fragility. The percentage of cells that hemolize when plotted as a function of different concentrations of NaCl forms fragility curve, which has a sigmoidal shape. In this study we show that the exposure of red blood cells to laser light converts the sigmoidal shape of the fragility curve to a hyperbolic one, which means that the old population of the red blood cells are the ones more affected by the light which cause their destruction. At the same time it seems that transport across the cell membrane is affected also. The biochemical and physiological implications of this finding are discussed. (author)

General rules prospected for the liquid fragility in various material groups and different thermodynamic conditions

Energy Technology Data Exchange (ETDEWEB)

Paluch, M.; Masiewicz, E.; Grzybowski, A.; Pawlus, S.; Wojnarowska, Z. [Institute of Physics, University of Silesia, Uniwersytecka 4, 40-007 Katowice (Poland); Silesian Center for Education and Interdisciplinary Research, 75 Pulku Piechoty 1A, 41-500 Chorzow (Poland); Pionteck, J. [Leibniz Institute of Polymer Research Dresden, Hohe Str. 6, D-01069 Dresden (Germany)

2014-10-07

The fragility parameter has been acknowledged as one of the most important characteristics of glass-forming liquids. We show that the mystery of the dramatic change in molecular dynamics of systems approaching the glass transition can be better understood by the high pressure study of fragility parameters defined in different thermodynamic conditions. We formulate and experimentally confirm a few rules obeyed by the fragility parameters, which are also rationalized by the density scaling law and its modification suggested for associated liquids. In this way, we successfully explore and gain a new insight into the pressure effect on molecular dynamics of van der Waals liquids, polymer melts, ionic liquids, and hydrogen-bonded systems near the glass transition.

Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.

Science.gov (United States)

Johansson, Anna-Mia; Stenberg, Per; Bernhardsson, Carolina; Larsson, Jan

2007-05-02

Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

Chromosome Territories

OpenAIRE

Cremer, Thomas; Cremer, Marion

2010-01-01

Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions wit...

Fragile Thermodynamic Order

International Nuclear Information System (INIS)

Bernhoeft, N.; Lander, G.H.; Colineau, E.

2003-01-01

An asymmetric shift in the position of the magnetic Bragg peak with respect to the fiducial lattice has been observed by resonant X-ray scattering in a diverse series of antiferromagnetic compounds. This apparent violation of Bragg's law is interpreted in terms of a dynamically phased order parameter. We demonstrate the use of this effect as a novel probe of fragile or dynamic thermodynamic order in strongly correlated electronic systems. In particular, fresh light is shed on the paradoxical situation encountered in URu 2 Si 2 where the measured entropy gain on passing through T Neel is incompatible with the ground state moment estimated by neutron diffraction. The intrinsic space-time averaging of the probe used to characterise the thermodynamic macroscopic state may play a crucial and previously neglected role. In turn, this suggests the further use of resonant X-ray scattering in investigations of systems dominated by quantum fluctuations. (author)

Chromosomal Evolution in Chiroptera.

Science.gov (United States)

Sotero-Caio, Cibele G; Baker, Robert J; Volleth, Marianne

2017-10-13

Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62). As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae), focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems.

Chromosomal Evolution in Chiroptera

Directory of Open Access Journals (Sweden)

Cibele G. Sotero-Caio

2017-10-01

Full Text Available Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62. As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae, focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems.

Mathematics Learning Disabilities in Girls with Fragile X or Turner Syndrome during Late Elementary School

Science.gov (United States)

Murphy, Melissa M.; Mazzocco, Michele M. M.

2008-01-01

The present study focuses on math and related skills among 32 girls with fragile X (n = 14) or Turner (n = 18) syndrome during late elementary school. Performance in each syndrome group was assessed relative to Full Scale IQ-matched comparison groups of girls from the general population (n = 32 and n = 89 for fragile X syndrome and Turner…

GSK-3 inhibitors induce chromosome instability

Directory of Open Access Journals (Sweden)

Staples Oliver D

2007-08-01

Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

Dielectrophoretic manipulation of human chromosomes in microfluidic channels: extracting chromosome dielectric properties

DEFF Research Database (Denmark)

Clausen, Casper Hyttel; Dimaki, Maria; Buckley, Sonia

2011-01-01

An investigation of the dielectric properties of polyamine buffer prepared human chromosomes is presented in this paper. Chromosomes prepared in this buffer are only a few micrometers in size and shaped roughly like spherical discs. Dielectrophoresis was therefore chosen as the method...... of manipulation combined with a custom designed microfluidic system containing the required electrodes for dielectrophoresis experiments. Our results show that although this system is presently not able to distinguish between the different chromosomes, it can provide average data for the dielectric properties...... of human chromosomes in polyamine buffer. These can then be used to optimize system designs for further characterization and even sorting. The experimental data from the dielectrophoretic manipulation were combined with theoretical calculations to extract a range of values for the permittivity...

Social Approach and Emotion Recognition in Fragile X Syndrome

Science.gov (United States)

Williams, Tracey A.; Porter, Melanie A.; Langdon, Robyn

2014-01-01

Evidence is emerging that individuals with Fragile X syndrome (FXS) display emotion recognition deficits, which may contribute to their significant social difficulties. The current study investigated the emotion recognition abilities, and social approachability judgments, of FXS individuals when processing emotional stimuli. Relative to…

Therapeutic Targets and Translational Endpoints in Fragile X Syndrome

NARCIS (Netherlands)

C.E.F. de Esch (Celine)

2014-01-01

markdownabstract__Abstract__ Fragile X syndrome is the most common inherited cause of intellectual disability. It is more common in boys (1 in 4000) than girls (1 in 6000). In addition to the intellectual disability patients often exhibit behavioral abnormalities including hyperactivity and

Major Chromosomal Breakpoint Intervals in Breast Cancer Co-Localize with Differentially Methylated Regions

Energy Technology Data Exchange (ETDEWEB)

Eric Tang, Man-Hung [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Varadan, Vinay; Kamalakaran, Sitharthan [Philips Research North America, Briarcliff Manor, NY (United States); Zhang, Michael Q. [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States); The University of Texas at Dallas, Richardson, TX (United States); Tsinghua University, Beijing (China); Dimitrova, Nevenka, E-mail: nevenka.dimitrova@philips.com [Philips Research North America, Briarcliff Manor, NY (United States); Hicks, James, E-mail: hicks@cshl.edu [Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (United States)

2012-12-27

Solid tumors exhibit chromosomal rearrangements resulting in gain or loss of multiple chromosomal loci (copy number variation, or CNV), and translocations that occasionally result in the creation of novel chimeric genes. In the case of breast cancer, although most individual tumors each have unique CNV landscape, the breakpoints, as measured over large datasets, appear to be non-randomly distributed in the genome. Breakpoints show a significant regional concentration at genomic loci spanning perhaps several megabases. The proximal cause of these breakpoint concentrations is a subject of speculation, but is, as yet, largely unknown. To shed light on this issue, we have performed a bio-statistical analysis on our previously published data for a set of 119 breast tumors and normal controls (Wiedswang et al., 2003), where each sample has both high-resolution CNV and methylation data. The method examined the distribution of closeness of breakpoint regions with differentially methylated regions (DMR), coupled with additional genomic parameters, such as repeat elements and designated “fragile sites” in the reference genome. Through this analysis, we have identified a set of 93 regional loci called breakpoint enriched DMR (BEDMRs) characterized by altered DNA methylation in cancer compared to normal cells that are associated with frequent breakpoint concentrations within a distance of 1 Mb. BEDMR loci are further associated with local hypomethylation (66%), concentrations of the Alu SINE repeats within 3 Mb (35% of the cases), and tend to occur near a number of cancer related genes such as the protocadherins, AKT1, DUB3, GAB2. Furthermore, BEDMRs seem to deregulate members of the histone gene family and chromatin remodeling factors, e.g., JMJD1B, which might affect the chromatin structure and disrupt coordinate signaling and repair. From this analysis we propose that preference for chromosomal breakpoints is related to genome structure coupled with alterations in DNA

Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21

DEFF Research Database (Denmark)

McGinniss, M J; Kazazian, H H; Stetten, G

1992-01-01

We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage......), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another......). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy....

Fragile States, Infectious Disease and Health Security: The Case for Timor-Leste

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John M. Quinn

2014-01-01

Full Text Available Timor-Leste is a very young and developing nation state. Endemic infectious disease and weakened health security coupled with its growing and inclusive public institutions keep Timor-Leste fragile and in transition on the spectrum of state stability. The objective here is to systematically review Timor-Leste's state and public health successes, showing how a fragile state can consistently improve its status on the continuum of stability and improve health security for the population. The case study follows a state case study approach, together with a disease burden review and a basic description of the health portrait in relation to Timor-Leste's fragile state status. Disease burden and health security are directly proportional to state stability and indirectly proportional to state failure. Timor-Leste is a clear example of how public health can feed into increased state stability. Our discussion attempts to describe how the weak and fragile island nation of Timor-Leste can continue on its current path of transition to state stability by increasing health security for its citizens. We surmise that this can be realized when public policy focuses on primary healthcare access, inclusive state institutions, basic hygiene and preventative vaccination programs. Based on our review, the core findings indicate that by increasing health security, a positive feedback loop of state stability follows. The use of Timor-Leste as a case study better describes the connection between public health and health security; and state stability, development and inclusive state institutions that promote health security.

Dementia in Fragile X-associated Tremor/Ataxia Syndrome

Directory of Open Access Journals (Sweden)

Ricardo Nitrini

Full Text Available Abstract Fragile X-associated tremor/ataxia syndrome (FXTAS is a cause of movement disorders and cognitive decline which has probably been underdiagnosed, especially if its prevalence proves similar to those of progressive supranuclear palsy and amyotrophic lateral sclerosis. We report a case of a 74-year-old man who presented with action tremor, gait ataxia and forgetfulness. There was a family history of tremor and dementia, and one of the patient's grandsons was mentally deficient. Neuropsychological evaluation disclosed a frontal network syndrome. MRI showed hyperintensity of both middle cerebellar peduncles, a major diagnostic hallmark of FXTAS. Genetic testing revealed premutation of the FMR1 gene with an expanded (CGG90 repeat. The diagnosis of FXTAS is important for genetic counseling because the daughters of the affected individuals are at high risk of having offspring with fragile X syndrome. Tremors and cognitive decline should raise the diagnostic hypothesis of FXTAS, which MRI may subsequently reinforce, while the detection of the FMR1 premutation can confirm the condition.

A Guide to Improving the Care of Patients with Fragility Fractures, Edition 2

Science.gov (United States)

Mears, Simon C.

2015-01-01

Over the past 4 decades, much has been learned about the pathophysiology and treatment of osteoporosis, the prevention of fragility fractures, and the perioperative management of patients who have these debilitating injuries. However, the volume of published literature on this topic is staggering and far too voluminous for any clinician to review and synthesize by him or herself. This manuscript thoroughly summarizes the latest research on fragility fractures and provides the reader with valuable strategies to optimize the prevention and management of these devastating injuries. The information contained in this article will prove invaluable to any health care provider or health system administrator who is involved in the prevention and management of fragility hip fractures. As providers begin to gain a better understanding of the principles espoused in this article, it is our hope that they will be able to use this information to optimize the care they provide for elderly patients who are at risk of or who have osteoporotic fractures. PMID:26246957

Validation of fragility fractures in primary care electronic medical records: A population-based study.

Science.gov (United States)

Martinez-Laguna, Daniel; Soria-Castro, Alberto; Carbonell-Abella, Cristina; Orozco-López, Pilar; Estrada-Laza, Pilar; Nogues, Xavier; Díez-Perez, Adolfo; Prieto-Alhambra, Daniel

2017-11-28

Electronic medical records databases use pre-specified lists of diagnostic codes to identify fractures. These codes, however, are not specific enough to disentangle traumatic from fragility-related fractures. We report on the proportion of fragility fractures identified in a random sample of coded fractures in SIDIAP. Patients≥50 years old with any fracture recorded in 2012 (as per pre-specified ICD-10 codes) and alive at the time of recruitment were eligible for this retrospective observational study in 6 primary care centres contributing to the SIDIAP database (www.sidiap.org). Those with previous fracture/s, non-responders, and those with dementia or a serious psychiatric disease were excluded. Data on fracture type (traumatic vs fragility), skeletal site, and basic patient characteristics were collected. Of 491/616 (79.7%) patients with a registered fracture in 2012 who were contacted, 331 (349 fractures) were included. The most common fractures were forearm (82), ribs (38), and humerus (32), and 225/349 (64.5%) were fragility fractures, with higher proportions for classic osteoporotic sites: hip, 91.7%; spine, 87.7%; and major fractures, 80.5%. This proportion was higher in women, the elderly, and patients with a previously coded diagnosis of osteoporosis. More than 4 in 5 major fractures recorded in SIDIAP are due to fragility (non-traumatic), with higher proportions for hip (92%) and vertebral (88%) fracture, and a lower proportion for fractures other than major ones. Our data support the validity of SIDIAP for the study of the epidemiology of osteoporotic fractures. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Surgical treatment for medically refractory focal epilepsy in a patient with fragile X syndrome.

Science.gov (United States)

Kenmuir, Cynthia; Richardson, Mark; Ghearing, Gena

2015-10-01

Medication resistant temporal lobe epilepsy occurs in a small population of patients with fragile X syndrome. We present the case of a 24-year-old man with medically refractory temporal lobe epilepsy and fragile X syndrome who underwent left anterior temporal lobectomy resulting in cessation of seizures. Our patient was diagnosed with fragile X syndrome with a fully mutated, fully methylated FMR1 gene resulting in 572 CGG repeats. He developed seizures initially controlled with Depakote monotherapy, but progressed to become medically refractive to combination treatment with Depakote, lamotrigine and zonisamide. Prolonged video EEG monitoring revealed interictal left temporal sharp waves and slowing as well as subclinical and clinical seizures, each with left temporal onset. 3T MRI was consistent with left mesial temporal sclerosis. After discussing the case in our multidisciplinary surgical epilepsy conference, he was referred for presurgical evaluation including neuropsychological testing and Wada testing. He underwent an asleep left anterior temporal lobectomy, sparing the superior temporal gyrus. Pathology showed neuronal loss and gliosis in the hippocampus and amygdala. Twelve months after surgery, the patient has not experienced a seizure. He is described by his parents as less perseverative and less restless. We have presented the case of a 24 year-old-man with fragile X syndrome who underwent successful left anterior temporal lobectomy for the treatment of medically refractory epilepsy who is now seizure free without further functional impairment. This case report demonstrates the feasibility of surgical treatment for a patient with comorbid fragile X syndrome and mesial temporal sclerosis. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Emerging Powers and Effective Governance in Fragile States | IDRC ...

International Development Research Centre (IDRC) Digital Library (Canada)

New and emerging development organizations are providing assistance to countries experiencing tensions and challenges after periods of conflict. This research will test whether their development assistance approaches are more effective at addressing the political and social realities of fragile states than those used by ...

Linking structure to fragility in bulk metallic glass-forming liquids

International Nuclear Information System (INIS)

Wei, Shuai; Stolpe, Moritz; Gross, Oliver; Gallino, Isabella; Hembree, William; Busch, Ralf; Evenson, Zach; Bednarcik, Jozef; Kruzic, Jamie J.

2015-01-01

Using in-situ synchrotron X-ray scattering, we show that the structural evolution of various bulk metallic glass-forming liquids can be quantitatively connected to their viscosity behavior in the supercooled liquid near T g . The structural signature of fragility is identified as the temperature dependence of local dilatation on distinct key atomic length scales. A more fragile behavior results from a more pronounced thermally induced dilatation of the structure on a length scale of about 3 to 4 atomic diameters, coupled with shallower temperature dependence of structural changes in the nearest neighbor environment. These findings shed light on the structural origin of viscous slowdown during undercooling of bulk metallic glass-forming liquids and demonstrate the promise of predicting the properties of bulk metallic glasses from the atomic scale structure

Linking structure to fragility in bulk metallic glass-forming liquids

Energy Technology Data Exchange (ETDEWEB)

Wei, Shuai, E-mail: shuai.wei@asu.edu, E-mail: m.stolpe@mx.uni-saarland.de [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287 (United States); Stolpe, Moritz, E-mail: shuai.wei@asu.edu, E-mail: m.stolpe@mx.uni-saarland.de; Gross, Oliver; Gallino, Isabella; Hembree, William; Busch, Ralf [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Evenson, Zach [Department of Materials Science and Engineering, Saarland University, Campus C63, 66123 Saarbrücken (Germany); Institut für Materialphysik im Weltraum, Deutsches Zentrum für Luft- und Raumfahrt (DLR), 51170 Köln (Germany); Bednarcik, Jozef [Deutsches Elektronen-Synchrotron DESY, Notkestrasse 85, D-22603 Hamburg (Germany); Kruzic, Jamie J. [Material Science, School of Mechanical, Industrial, and Manufacturing Engineering, Oregon State University, Corvallis, Oregon 97331 (United States)

2015-05-04

Using in-situ synchrotron X-ray scattering, we show that the structural evolution of various bulk metallic glass-forming liquids can be quantitatively connected to their viscosity behavior in the supercooled liquid near T{sub g}. The structural signature of fragility is identified as the temperature dependence of local dilatation on distinct key atomic length scales. A more fragile behavior results from a more pronounced thermally induced dilatation of the structure on a length scale of about 3 to 4 atomic diameters, coupled with shallower temperature dependence of structural changes in the nearest neighbor environment. These findings shed light on the structural origin of viscous slowdown during undercooling of bulk metallic glass-forming liquids and demonstrate the promise of predicting the properties of bulk metallic glasses from the atomic scale structure.

Post-surgical rehabilitative approach to fragility fractures.

Science.gov (United States)

Gimigliano, F; Iolascon, G; Riccio, I; Frizzi, L; Gimigliano, R

2013-10-01

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. The most frequent sites of fragility fractures are the hip, the distal radius, the spine, the proximal humerus, and the ankle. In most cases, a surgical approach with subsequent rehabilitative treatment is required. The general aims of rehabilitation are to increase functioning and improve patients' activities, participation level, and quality of life.

Mean-coordination number dependence of the fragility in Ge-Se-In glass-forming liquids

International Nuclear Information System (INIS)

Saffarini, G.; Saiter, A.; Garda, M.R.; Saiter, J.M.

2007-01-01

Differential scanning calorimetry measurements have been performed on elemental Se as well as on Ge x Se 94- x In 6 (x=4, 8, and 11 at%) and on Ge y Se 88- y In 12 (y=5, 7, and 9 at%) chalcogenide glasses. From the cooling rate dependence of the fictive temperature, the apparent activation energies, Δh*, and the fragility indices, m, as defined in the strong-fragile glass-forming liquid concept, are determined. It is found that, in Ge-Se-In system, there is an evolution from strong (m=67) to fragile (m=116) glass-forming liquids. The dependence of 'm' on the mean-coordination number, Z, is also obtained. This dependence is rationalized by assuming that, in this glassy alloy system, there is a tendency for the formation of In 2 Se 3 clusters

Chromosome analysis of arsenic affected cattle

Directory of Open Access Journals (Sweden)

S. Shekhar

2014-10-01

Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.

The tsunami probabilistic risk assessment of nuclear power plant (3). Outline of tsunami fragility analysis

International Nuclear Information System (INIS)

Mihara, Yoshinori

2012-01-01

Tsunami Probabilistic Risk Assessment (PRA) standard was issued in February 2012 by Standard Committee of Atomic Energy Society of Japan (AESJ). This article detailed tsunami fragility analysis, which calculated building and structure damage probability contributing core damage and consisted of five evaluation steps: (1) selection of evaluated element and damage mode, (2) selection of evaluation procedure, (3) evaluation of actual stiffness, (4) evaluation of actual response and (5) evaluation of fragility (damage probability and others). As an application example of the standard, calculation results of tsunami fragility analysis investigation by tsunami PRA subcommittee of AESJ were shown reflecting latest knowledge of damage state caused by wave force and others acted by tsunami from the 'off the Pacific Coast of Tohoku Earthquake'. (T. Tanaka)

Consideration of time-evolving capacity distributions and improved degradation models for seismic fragility assessment of aging highway bridges

International Nuclear Information System (INIS)

Ghosh, Jayadipta; Sood, Piyush

2016-01-01

This paper presents a methodology to develop seismic fragility curves for deteriorating highway bridges by uniquely accounting for realistic pitting corrosion deterioration and time-dependent capacity distributions for reinforced concrete columns under chloride attacks. The proposed framework offers distinct improvements over state-of-the-art procedures for fragility assessment of degrading bridges which typically assume simplified uniform corrosion deterioration model and pristine limit state capacities. Depending on the time in service life and deterioration mechanism, this study finds that capacity limit states for deteriorating bridge columns follow either lognormal distribution or generalized extreme value distributions (particularly for pitting corrosion). Impact of column degradation mechanism on seismic response and fragility of bridge components and system is assessed using nonlinear time history analysis of three-dimensional finite element bridge models reflecting the uncertainties across structural modeling parameters, deterioration parameters and ground motion. Comparisons are drawn between the proposed methodology and traditional approaches to develop aging bridge fragility curves. Results indicate considerable underestimations of system level fragility across different damage states using the traditional approach compared to the proposed realistic pitting model for chloride induced corrosion. Time-dependent predictive functions are provided to interpolate logistic regression coefficients for continuous seismic reliability evaluation along the service life with reasonable accuracy. - Highlights: • Realistic modeling of chloride induced corrosion deterioration in the form of pitting. • Time-evolving capacity distribution for aging bridge columns under chloride attacks. • Time-dependent seismic fragility estimation of highway bridges at component and system level. • Mathematical functions for continuous tracking of seismic fragility along service

Ricci curvature: An economic indicator for market fragility and systemic risk

Science.gov (United States)

Sandhu, Romeil S.; Georgiou, Tryphon T.; Tannenbaum, Allen R.

2016-01-01

Quantifying the systemic risk and fragility of financial systems is of vital importance in analyzing market efficiency, deciding on portfolio allocation, and containing financial contagions. At a high level, financial systems may be represented as weighted graphs that characterize the complex web of interacting agents and information flow (for example, debt, stock returns, and shareholder ownership). Such a representation often turns out to provide keen insights. We show that fragility is a system-level characteristic of “business-as-usual” market behavior and that financial crashes are invariably preceded by system-level changes in robustness. This was done by leveraging previous work, which suggests that Ricci curvature, a key geometric feature of a given network, is negatively correlated to increases in network fragility. To illustrate this insight, we examine daily returns from a set of stocks comprising the Standard and Poor’s 500 (S&P 500) over a 15-year span to highlight the fact that corresponding changes in Ricci curvature constitute a financial “crash hallmark.” This work lays the foundation of understanding how to design (banking) systems and policy regulations in a manner that can combat financial instabilities exposed during the 2007–2008 crisis. PMID:27386522

Estimating structural collapse fragility of generic building typologies using expert judgment

Science.gov (United States)

Jaiswal, Kishor S.; Wald, D.J.; Perkins, D.; Aspinall, W.P.; Kiremidjian, Anne S.; Deodatis, George; Ellingwood, Bruce R.; Frangopol, Dan M.

2014-01-01

The structured expert elicitation process proposed by Cooke (1991), hereafter referred to as Cooke’s approach, is applied for the first time in the realm of structural collapse-fragility assessment for selected generic construction types. Cooke’s approach works on the principle of objective calibration scoring of judgments coupled with hypothesis testing used in classical statistics. The performance-based scoring system reflects the combined measure of an expert’s informativeness about variables in the problem area under consideration, and their ability to enumerate, in a statistically accurate way through expressing their true beliefs, the quantitative uncertainties associated with their assessments. We summarize the findings of an expert elicitation workshop in which a dozen earthquake-engineering professionals from around the world were engaged to estimate seismic collapse fragility for generic construction types. Development of seismic collapse fragility functions was accomplished by combining their judgments using weights derived from Cooke’s method. Although substantial effort was needed to elicit the inputs of these experts successfully, we anticipate that the elicitation strategy described here will gain momentum in a wide variety of earthquake seismology and engineering hazard and risk analyses where physical model and data limitations are inherent and objective professional judgment can fill gaps.

Chromosome heteromorphisms in the Japanese, 3

International Nuclear Information System (INIS)

Sofuni, Toshio; Awa, A.A.

1982-12-01

The type and frequency of chromosome variants detected by the C-staining method were ascertained in 1,857 individuals residing in Hiroshima. The most frequent heteromorphic variant was the total inversion of the C-band in chromosome 9 found in 27 individuals (1.45%). The total inversion of the C-band in chromosome 1 was not seen in this sample, but the partial inversion of the C-band in chromosome 1 was found in 18 persons (0.97%). Partial inversion was also detected in the C-band in chromosome 9 in 22 individuals (1.18%). In chromosome 16, neither total nor partial inversion of the C-band was observed in the present study. The frequencies of chromosomes 1, 9, and 16 with a very large C-band were 0.70%, 0.22%, and 0.54%, respectively. Aside from these (1, 9, and 16) a very large C-band was found occasionally in chromosomes 4, 5, 6, 11, 12, 14, and 15, and an unusual insertion of the Y chromosome was observed. A total of 128 C-band variants (6.89%) was found in the 1,857 Hiroshima residents. (author)

Seismic fragility of nuclear power plant components: Phase 2, Motor control center, switchboard, panelboard and power supply

International Nuclear Information System (INIS)

Bandyopadhyay, K.K.; Hofmayer, C.H.; Kassir, M.K.; Pepper, S.E.

1987-12-01

In Phase I of the Component Fragility Program, Brookhaven National Laboratory (BNL) has developed a procedure to establish the seismic fragility of nuclear power plant equipment by use of existing test data and demonstrated its application by considering two equipment pieces. In Phase II of the program, BNL has collected additional test data, and has further advanced and is applying the methodology to determine the fragility levels of selected essential equipment categories. The data evaluation of four equipment families, namely, motor control center, switchboard, panelboard and power supply has been completed. Fragility levels have been determined for various failure modes of each equipment class and the deterministic results are presented in terms of test response spectra. In addition, the test data have been analyzed for determination of the respective probabilistic fragility levels. To this end, a single g-value has been selected to approximately represent the test vibration level and a statistical analysis has been performed with the g-values corresponding to a particular failure mode. The zero period acceleration and the average spectral acceleration over a frequency range of interest are separately used as the single g-value. The resulting parameters are presented in terms of a median value, an uncertainty coefficient and a randomness coefficient. Ultimately, each fragility level is expressed in terms of a single descriptor called an HCLPF value corresponding to a high (95%) confidence of a low (5%) probability of failure. The important observations made in the process of data analysis are included in this report

Social Cognition in Adolescent Girls with Fragile X Syndrome

Science.gov (United States)

Turkstra, Lyn S.; Abbeduto, Leonard; Meulenbroek, Peter

2014-01-01

This study aimed to characterize social cognition, executive functions (EFs), and everyday social functioning in adolescent girls with fragile X syndrome, and identify relationships among these variables. Participants were 20 girls with FXS and 20 age-matched typically developing peers. Results showed significant between-groups differences in…

Semi-automatic laser beam microdissection of the Y chromosome and analysis of Y chromosome DNA in a dioecious plant, Silene latifolia

International Nuclear Information System (INIS)

Matsunaga, S.; Kawano, S.; Michimoto, T.; Higashiyama, T.; Nakao, S.; Sakai, A.; Kuroiwa, T.

1999-01-01

Silene latifolia has heteromorphic sex chromosomes, the X and Y chromosomes. The Y chromosome, which is thought to carry the male determining gene, was isolated by UV laser microdissection and amplified by degenerate oligonucleotide-primed PCR. In situ chromosome suppression of the amplified Y chromosome DNA in the presence of female genomic DNA as a competitor showed that the microdissected Y chromosome DNA did not specifically hybridize to the Y chromosome, but-hybridized to all chromosomes. This result suggests that the Y chromosome does not contain Y chromosome-enriched repetitive sequences. A repetitive sequence in the microdissected Y chromosome, RMY1, was isolated while screening repetitive sequences in the amplified Y chromosome. Part of the nucleotide sequence shared a similarity to that of X-43.1, which was isolated from microdissected X chromosomes. Since fluorescence in situ hybridization analysis with RMY1 demonstrated that RMY1 was localized at the ends of the chromosome, RMY1 may be a subtelomeric repetitive sequence. Regarding the sex chromosomes, RMY1 was detected at both ends of the X chromosome and at one end near the pseudoautosomal region of the Y chromosome. The different localization of RMY1 on the sex chromosomes provides a clue to the problem of how the sex chromosomes arose from autosomes

The kinetic fragility of natural silicate melts

International Nuclear Information System (INIS)

Giordano, Daniele; Dingwell, Donald B

2003-01-01

Newtonian viscosities of 19 multicomponent natural and synthetic silicate liquids, with variable contents of SiO 2 (41-79 wt%), Al 2 O 3 (10-19 wt%), TiO 2 (0-3 wt%), FeO tot (0-11 wt%); alkali oxides (5-17 wt%), alkaline-earth oxides (0-35 wt%), and minor oxides, obtained at ambient pressure using the high-temperature concentric cylinder, the low-temperature micropenetration, and the parallel plates techniques, have been analysed. For each silicate liquid, regression of the experimentally determined viscosities using the well known Vogel-Fulcher-Tammann (VFT) equation allowed the viscosity of all these silicates to be accurately described. The results of these fits, which provide the basis for the subsequent analysis here, permit qualitative and quantitative correlations to be made between the VFT adjustable parameters (A VFT , B VFT , and T 0 ). The values of B VFT and T 0 , calibrated via the VFT equation, are highly correlated. Kinetic fragility appears to be correlated with the number of non-bridging oxygens per tetrahedrally coordinated cation (NBO/T). This is taken to infer that melt polymerization controls melt fragility in liquid silicates. Thus NBO/T might form an useful ingredient of a structure-based model of non-Arrhenian viscosity in multicomponent silicate melts

Of Men and Mice: Modeling the Fragile X Syndrome

Science.gov (United States)

Dahlhaus, Regina

2018-01-01

The Fragile X Syndrome (FXS) is one of the most common forms of inherited intellectual disability in all human societies. Caused by the transcriptional silencing of a single gene, the fragile x mental retardation gene FMR1, FXS is characterized by a variety of symptoms, which range from mental disabilities to autism and epilepsy. More than 20 years ago, a first animal model was described, the Fmr1 knock-out mouse. Several other models have been developed since then, including conditional knock-out mice, knock-out rats, a zebrafish and a drosophila model. Using these model systems, various targets for potential pharmaceutical treatments have been identified and many treatments have been shown to be efficient in preclinical studies. However, all attempts to turn these findings into a therapy for patients have failed thus far. In this review, I will discuss underlying difficulties and address potential alternatives for our future research. PMID:29599705

Chromosomal instability induced by ionizing radiation

International Nuclear Information System (INIS)

Morgan, W.F.; Marder, B.A.; Day, J.P.

1995-01-01

There is accumulating evidence indicating genomic instability can manifest multiple generations after cellular exposure to DNA damaging agents. For instance, some cells surviving exposure to ionizing radiations show delayed reproductive cell death, delayed mutation and / or delayed chromosomal instability. Such instability, especially chromosome destabilization has been implicated in mutation, gene amplification, cellular transformation, and cell killing. To investigate chromosomal instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells. The relationship between delayed chromosomal destabilization and other endpoints of genomic instability, namely; delayed mutation and gene amplification will be discussed, as will the potential cytogenetic and molecular mechanisms contributing to delayed chromosomal instability

Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles

Directory of Open Access Journals (Sweden)

Boussaha Mekki

2006-05-01

Full Text Available Abstract Background The Fragile Histidine Triad gene (FHIT is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus. Results The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs. Conclusion A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis

Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles.

Science.gov (United States)

Uboldi, Cristina; Guidi, Elena; Roperto, Sante; Russo, Valeria; Roperto, Franco; Di Meo, Giulia Pia; Iannuzzi, Leopoldo; Floriot, Sandrine; Boussaha, Mekki; Eggen, André; Ferretti, Luca

2006-05-23

The Fragile Histidine Triad gene (FHIT) is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus. The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs. A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis, especially of vesical papillomavirus-associated cancers of

Unique mosaicism of structural chromosomal rearrangement: is chromosome 18 preferentially involved?

NARCIS (Netherlands)

Pater, J.M. de; Smeets, D.F.C.M.; Scheres, J.M.J.C.

2003-01-01

The mentally normal mother of a 4-year-old boy with del(18)(q21.3) syndrome was tested cytogenetically to study the possibility of an inherited structural rearrangement of chromosome 18. She was found to carry an unusual mosaicism involving chromosomes 18 and 21. Two unbalanced cell lines were seen

B chromosomes are associated with redistribution of genetic recombination towards lower recombination chromosomal regions in perennial ryegrass.

Science.gov (United States)

Harper, John; Phillips, Dylan; Thomas, Ann; Gasior, Dagmara; Evans, Caron; Powell, Wayne; King, Julie; King, Ian; Jenkins, Glyn; Armstead, Ian

2018-04-09

Supernumerary 'B' chromosomes are non-essential components of the genome present in a range of plant and animal species-including many grasses. Within diploid and polyploid ryegrass and fescue species, including the forage grass perennial ryegrass (Lolium perenne L.), the presence of B chromosomes has been reported as influencing both chromosome pairing and chiasma frequencies. In this study, the effects of the presence/absence of B chromosomes on genetic recombination has been investigated through generating DArT (Diversity Arrays Technology) marker genetic maps for six perennial ryegrass diploid populations, the pollen parents of which contained either two B or zero B chromosomes. Through genetic and cytological analyses of these progeny and their parents, we have identified that, while overall cytological estimates of chiasma frequencies were significantly lower in pollen mother cells with two B chromosomes as compared with zero B chromosomes, the recombination frequencies within some marker intervals were actually increased, particularly for marker intervals in lower recombination regions of chromosomes, namely pericentromeric regions. Thus, in perennial ryegrass, the presence of two B chromosomes redistributed patterns of meiotic recombination in pollen mother cells in ways which could increase the range of allelic variation available to plant breeders.

HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis.

Science.gov (United States)

Phillips, Carolyn M; Wong, Chihunt; Bhalla, Needhi; Carlton, Peter M; Weiser, Pinky; Meneely, Philip M; Dernburg, Abby F

2005-12-16

The him-8 gene is essential for proper meiotic segregation of the X chromosomes in C. elegans. Here we show that loss of him-8 function causes profound X chromosome-specific defects in homolog pairing and synapsis. him-8 encodes a C2H2 zinc-finger protein that is expressed during meiosis and concentrates at a site on the X chromosome known as the meiotic pairing center (PC). A role for HIM-8 in PC function is supported by genetic interactions between PC lesions and him-8 mutations. HIM-8 bound chromosome sites associate with the nuclear envelope (NE) throughout meiotic prophase. Surprisingly, a point mutation in him-8 that retains both chromosome binding and NE localization fails to stabilize pairing or promote synapsis. These observations indicate that stabilization of homolog pairing is an active process in which the tethering of chromosome sites to the NE may be necessary but is not sufficient.

HIM-8 binds to the X chromosome pairing center and mediates chromosome-specific meiotic synapsis

International Nuclear Information System (INIS)

Phillips, Carolyn M.; Wong, Chihunt; Bhalla, Needhi; Carlton, Peter M.; Weiser, Pinky; Meneely, Philip M.; Dernburg, Abby F.

2005-01-01

The him-8 gene is essential for proper meiotic segregation of the X chromosomes in C. elegans. Here we show that loss of him-8 function causes profound X-chromosome-specific defects in homolog pairing and synapsis.him-8 encodes a C2H2 zinc finger protein that is expressed during meiosis and concentrates at a site on the X chromosome known as themeiotic Pairing Center (PC). A role for HIM-8 in PC function is supported by genetic interactions between PC lesions and him-8 mutations. HIM-8-bound chromosome sites associate with the nuclear envelope (NE)throughout meiotic prophase. Surprisingly, a point mutation in him-8 that retains both chromosome binding and NE localization fails to stabilize pairing or promote synapsis. These observations indicate that stabilization of homolog pairing is an active process in which the tethering of chromosome sites to the NE may be necessary but is not sufficient

Dissociation of social and nonsocial anxiety in a mouse model of fragile X syndrome

OpenAIRE

Liu, Zhong-Hua; Smith, Carolyn Beebe

2009-01-01

Anxiety is a common symptom in fragile X patients. However, an anxiety-prone phenotype in mouse models of fragile X syndrome is not clear. In most studies of fmr1 knockout mice, decreased anxiety-like responses in exploratory-based models are found, but mice also exhibit abnormal social interactions. We hypothesize the coexistence of elevated social anxiety and reduced nonsocial anxiety in fmr1 knockout mice. In the present study, we applied an automated three-chambered social approach method...

Statistics for X-chromosome associations.

Science.gov (United States)

Özbek, Umut; Lin, Hui-Min; Lin, Yan; Weeks, Daniel E; Chen, Wei; Shaffer, John R; Purcell, Shaun M; Feingold, Eleanor

2018-06-13

In a genome-wide association study (GWAS), association between genotype and phenotype at autosomal loci is generally tested by regression models. However, X-chromosome data are often excluded from published analyses of autosomes because of the difference between males and females in number of X chromosomes. Failure to analyze X-chromosome data at all is obviously less than ideal, and can lead to missed discoveries. Even when X-chromosome data are included, they are often analyzed with suboptimal statistics. Several mathematically sensible statistics for X-chromosome association have been proposed. The optimality of these statistics, however, is based on very specific simple genetic models. In addition, while previous simulation studies of these statistics have been informative, they have focused on single-marker tests and have not considered the types of error that occur even under the null hypothesis when the entire X chromosome is scanned. In this study, we comprehensively tested several X-chromosome association statistics using simulation studies that include the entire chromosome. We also considered a wide range of trait models for sex differences and phenotypic effects of X inactivation. We found that models that do not incorporate a sex effect can have large type I error in some cases. We also found that many of the best statistics perform well even when there are modest deviations, such as trait variance differences between the sexes or small sex differences in allele frequencies, from assumptions. © 2018 WILEY PERIODICALS, INC.

FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome.

Science.gov (United States)

Sherman, Stephanie L; Kidd, Sharon A; Riley, Catharine; Berry-Kravis, Elizabeth; Andrews, Howard F; Miller, Robert M; Lincoln, Sharyn; Swanson, Mark; Kaufmann, Walter E; Brown, W Ted

2017-06-01

Advances in the care of patients with fragile X syndrome (FXS) have been hampered by lack of data. This deficiency has produced fragmentary knowledge regarding the natural history of this condition, healthcare needs, and the effects of the disease on caregivers. To remedy this deficiency, the Fragile X Clinic and Research Consortium was established to facilitate research. Through a collective effort, the Fragile X Clinic and Research Consortium developed the Fragile X Online Registry With Accessible Research Database (FORWARD) to facilitate multisite data collection. This report describes FORWARD and the way it can be used to improve health and quality of life of FXS patients and their relatives and caregivers. FORWARD collects demographic information on individuals with FXS and their family members (affected and unaffected) through a 1-time registry form. The longitudinal database collects clinician- and parent-reported data on individuals diagnosed with FXS, focused on those who are 0 to 24 years of age, although individuals of any age can participate. The registry includes >2300 registrants (data collected September 7, 2009 to August 31, 2014). The longitudinal database includes data on 713 individuals diagnosed with FXS (data collected September 7, 2012 to August 31, 2014). Longitudinal data continue to be collected on enrolled patients along with baseline data on new patients. FORWARD represents the largest resource of clinical and demographic data for the FXS population in the United States. These data can be used to advance our understanding of FXS: the impact of cooccurring conditions, the impact on the day-to-day lives of individuals living with FXS and their families, and short-term and long-term outcomes. Copyright © 2017 by the American Academy of Pediatrics.

[Fragile X syndrome and white matter abnormalities: Case study of two brothers].

Science.gov (United States)

Wallach, E; Bieth, E; Sevely, A; Cances, C

2017-03-01

Fragile X syndrome is the most usual cause of hereditary intellectual deficiency. Typical symptoms combine intellectual deficiency, social anxiety, intense emotional vigilance, and a characteristic facial dysmorphy. This is subsequent to a complete mutation of the FMR1 gene, considering a semidominant transmission linked to the unstable X. The expansion of the CGG triplet greater than 200 units combined with a high methylation pattern lead to a transcriptional silence of the FMR1 gene, and the protein product, the FMRP, is not synthesized. This protein is involved in synaptic plasticity. Brain MRI can show an increased volume of the caudate nucleus and hippocampus, combined with hypoplasia of the cerebellar vermis. Fragile X Associated Tremor Ataxia Syndrome (FXTAS) syndrome is a neurodegenerative disorder occurring in carriers of the premutation in FMR1. Brain MRI shows an increased T2 signal in the middle cerebellar peduncles. This syndrome is linked to a premutation in the FMR1 gene. We report here the case of two brothers presenting a typical fragile X symptomatology. Brain MRI showed hyperintensities of the middle cerebellar peduncles. Such MRI findings support the assumption of a genetic mosaicism. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Delineating the Profile of Autism Spectrum Disorder Characteristics in Cornelia de Lange and Fragile X Syndromes

Science.gov (United States)

Moss, Joanna; Oliver, Chris; Nelson, Lisa; Richards, Caroline; Hall, Scott

2013-01-01

An atypical presentation of autism spectrum disorder is noted in Cornelia de Lange and Fragile X syndromes, but there are few detailed empirical descriptions. Participants in this study were individuals with Cornelia de Lange syndrome (n = 130, M age = 17.19), Fragile X syndrome (n = 182, M age = 16.94), and autism spectrum disorder (n = 142, M…

Centromere Destiny in Dicentric Chromosomes: New Insights from the Evolution of Human Chromosome 2 Ancestral Centromeric Region.

Science.gov (United States)

Chiatante, Giorgia; Giannuzzi, Giuliana; Calabrese, Francesco Maria; Eichler, Evan E; Ventura, Mario

2017-07-01

Dicentric chromosomes are products of genomic rearrangements that place two centromeres on the same chromosome. Due to the presence of two primary constrictions, they are inherently unstable and overcome their instability by epigenetically inactivating and/or deleting one of the two centromeres, thus resulting in functionally monocentric chromosomes that segregate normally during cell division. Our understanding to date of dicentric chromosome formation, behavior and fate has been largely inferred from observational studies in plants and humans as well as artificially produced de novo dicentrics in yeast and in human cells. We investigate the most recent product of a chromosome fusion event fixed in the human lineage, human chromosome 2, whose stability was acquired by the suppression of one centromere, resulting in a unique difference in chromosome number between humans (46 chromosomes) and our most closely related ape relatives (48 chromosomes). Using molecular cytogenetics, sequencing, and comparative sequence data, we deeply characterize the relicts of the chromosome 2q ancestral centromere and its flanking regions, gaining insight into the ancestral organization that can be easily broadened to all acrocentric chromosome centromeres. Moreover, our analyses offered the opportunity to trace the evolutionary history of rDNA and satellite III sequences among great apes, thus suggesting a new hypothesis for the preferential inactivation of some human centromeres, including IIq. Our results suggest two possible centromere inactivation models to explain the evolutionarily stabilization of human chromosome 2 over the last 5-6 million years. Our results strongly favor centromere excision through a one-step process. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chromosome Connections: Compelling Clues to Common Ancestry

Science.gov (United States)

Flammer, Larry

2013-01-01

Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

Insulin signaling misregulation underlies circadian and cognitive deficits in a Drosophila fragile X model.

Science.gov (United States)

Monyak, R E; Emerson, D; Schoenfeld, B P; Zheng, X; Chambers, D B; Rosenfelt, C; Langer, S; Hinchey, P; Choi, C H; McDonald, T V; Bolduc, F V; Sehgal, A; McBride, S M J; Jongens, T A

2017-08-01

Fragile X syndrome (FXS) is an undertreated neurodevelopmental disorder characterized by low intelligence quotent and a wide range of other symptoms including disordered sleep and autism. Although FXS is the most prevalent inherited cause of intellectual disability, its mechanistic underpinnings are not well understood. Using Drosophila as a model of FXS, we showed that select expression of dfmr1 in the insulin-producing cells (IPCs) of the brain was sufficient to restore normal circadian behavior and to rescue the memory deficits in the fragile X mutant fly. Examination of the insulin signaling (IS) pathway revealed elevated levels of Drosophila insulin-like peptide 2 (Dilp2) in the IPCs and elevated IS in the dfmr1 mutant brain. Consistent with a causal role for elevated IS in dfmr1 mutant phenotypes, the expression of dfmr1 specifically in the IPCs reduced IS, and genetic reduction of the insulin pathway also led to amelioration of circadian and memory defects. Furthermore, we showed that treatment with the FDA-approved drug metformin also rescued memory. Finally, we showed that reduction of IS is required at different time points to rescue circadian behavior and memory. Our results indicate that insulin misregulation underlies the circadian and cognitive phenotypes displayed by the Drosophila fragile X model, and thus reveal a metabolic pathway that can be targeted by new and already approved drugs to treat fragile X patients.

Linkage group-chromosome correlations in Sordaria macrospora: Chromosome identification by three dimensional reconstruction of their synaptonemal complex.

Science.gov (United States)

Zickler, D; Leblon, G; Haedens, V; Collard, A; Thuriaux, P

1984-01-01

Reconstruction of serially sectioned zygotene and pachytene nuclei has allowed, by measuring the lengths of synaptonemal complexes, an assignment of the 7 linkage (LG) groups to the 7 chromosomes in the fungus Sordaria macrospora. The 7 LG have been established using 19 mutants showing low second division segregation frequencies. Eight chromosomal rearrangements mapped on the 7 LG were used to identify the chromosomes involved. The following one to one assignment of the 7 LG to specific chromosomes was obtained: LG a: chromosome (chr) 1, LG b: chr5, LG c: chr6, LG d: chr7, LG e: chr4, LG f: chr3 and LG g: chr2 (the chromosome carrying the nucleolus organizer region).

Characterization of a chromosome-specific chimpanzee alpha satellite subset: Evolutionary relationship to subsets on human chromosomes

Energy Technology Data Exchange (ETDEWEB)

Warburton, P.E.; Gosden, J.; Lawson, D. [Western General Hospital, Edinburgh (United Kingdom)] [and others

1996-04-15

Alpha satellite DNA is a tandemly repeated DNA family found at the centromeres of all primate chromosomes examined. The fundamental repeat units of alpha satellite DNA are diverged 169- to 172-bp monomers, often found to be organized in chromosome-specific higher-order repeat units. The chromosomes of human (Homo sapiens (HSA)), chimpanzee (Pan troglodytes (PTR) and Pan paniscus), and gorilla (Gorilla gorilla) share a remarkable similarity and synteny. It is of interest to ask if alpha satellite arrays at centromeres of homologous chromosomes between these species are closely related (evolving in an orthologous manner) or if the evolutionary processes that homogenize and spread these arrays within and between chromosomes result in nonorthologous evolution of arrays. By using PCR primers specific for human chromosome 17-specific alpha satellite DNA, we have amplified, cloned, and characterized a chromosome-specific subset from the PTR chimpanzee genome. Hybridization both on Southern blots and in situ as well as sequence analysis show that this subset is most closely related, as expected, to sequences on HSA 17. However, in situ hybridization reveals that this subset is not found on the homologous chromosome in chimpanzee (PTR 19), but instead on PTR 12, which is homologous to HSA 2p. 40 refs., 3 figs.

Are We Ready for Fragile X Newborn Screening Testing?—Lessons Learnt from a Feasibility Study

Directory of Open Access Journals (Sweden)

Tiffany Wotton

2018-02-01

Full Text Available Fragile X syndrome (FXS is the most prevalent heritable cause of cognitive impairment but is not yet included in a newborn screening (NBS program within Australia. This paper aims to assess the feasibility and reliability of population screening for FXS using a pilot study in one hospital. A total of 1971 mothers consented for 2000 newborns to be tested using routine NBS dried blood spot samples. DNA was extracted and a modified PCR assay with a chimeric CGG primer was used to detect fragile X alleles in both males and females in the normal, premutation, and full mutation ranges. A routine PCR-based fragile X assay was run in parallel to validate the chimeric primer assay. Babies with CGG repeat number ≥59 were referred for family studies. One thousand nine hundred and ninety NBS samples had a CGG repeat number less than 55 (1986 < 50; 10 had premutation alleles >54 CGG repeats (1/123 females and 1/507 males. There was complete concordance between the two PCR-based assays. A recent review revealed no clinically identified cases in the cohort up to 5 years later. The cost per test was $AUD19. Fragile X status can be determined on routine NBS samples using the chimeric primer assay. However, whilst this assay may not be considered cost-effective for population screening, it could be considered as a second-tier assay to a developed immunoassay for fragile X mental retardation protein (FMRP.

Comparative physical mapping between wheat chromosome arm 2BL and rice chromosome 4.

Science.gov (United States)

Lee, Tong Geon; Lee, Yong Jin; Kim, Dae Yeon; Seo, Yong Weon

2010-12-01

Physical maps of chromosomes provide a framework for organizing and integrating diverse genetic information. DNA microarrays are a valuable technique for physical mapping and can also be used to facilitate the discovery of single feature polymorphisms (SFPs). Wheat chromosome arm 2BL was physically mapped using a Wheat Genome Array onto near-isogenic lines (NILs) with the aid of wheat-rice synteny and mapped wheat EST information. Using high variance probe set (HVP) analysis, 314 HVPs constituting genes present on 2BL were identified. The 314 HVPs were grouped into 3 categories: HVPs that match only rice chromosome 4 (298 HVPs), those that match only wheat ESTs mapped on 2BL (1), and those that match both rice chromosome 4 and wheat ESTs mapped on 2BL (15). All HVPs were converted into gene sets, which represented either unique rice gene models or mapped wheat ESTs that matched identified HVPs. Comparative physical maps were constructed for 16 wheat gene sets and 271 rice gene sets. Of the 271 rice gene sets, 257 were mapped to the 18-35 Mb regions on rice chromosome 4. Based on HVP analysis and sequence similarity between the gene models in the rice chromosomes and mapped wheat ESTs, the outermost rice gene model that limits the translocation breakpoint to orthologous regions was identified.

A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

Science.gov (United States)

Asia, Saba; Vaziri Nasab, Hamed; Sabbaghian, Marjan; Kalantari, Hamid; Zari Moradi, Shabnam; Gourabi, Hamid; Mohseni Meybodi, Anahita

2014-01-01

Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

Chromosome Banding in Amphibia. XXXVI. Multimorphic Sex Chromosomes and an Enigmatic Sex Determination in Eleutherodactylus johnstonei (Anura, Eleutherodactylidae).

Science.gov (United States)

Schmid, Michael; Steinlein, Claus

2018-01-01

A detailed cytogenetic study on the leaf litter frog Eleutherodactylus johnstonei from 14 different Caribbean islands and the mainlands of Venezuela and Guyana revealed the existence of multimorphic XY♂/XX♀ sex chromosomes 14. Their male sex determination and development depends either on the presence of 2 telocentric chromosomes 14 (XtYt), or on 1 submetacentric chromosome 14 (Xsm) plus 1 telocentric chromosome 14 (Yt), or on the presence of 2 submetacentric chromosomes 14 (XsmYsm). The female sex determination and development requires either the presence of 2 telocentric chromosomes 14 (XtXt) or 2 submetacentric chromosomes 14 (XsmXsm). In all individuals analyzed, the sex chromosomes 14 carry a prominent nucleolus organizer region in their long arms. An explanation is given for the origin of the (XtYt)♂, (XsmYt)♂, (XsmYsm)♂, (XtXt)♀, and (XsmXsm)♀ in the different populations of E. johnstonei. Furthermore, the present study gives detailed data on the chromosome banding patterns, in situ hybridization experiments, and the genome size of E. johnstonei. © 2018 S. Karger AG, Basel.

Erythrocyte Osmotic Fragility and Excitability Score in Rabbit fed ...

African Journals Online (AJOL)

olayemitoyin

protect cells against oxidative stress in rats (Wang et al., 2000) and ... method, total red blood cell (RBC) count, total leukocyte (WBC) count .... maturative stages of the erythroblast (pluripotent stem cells) involved in cell formation (Kaur and. Kapoor, 2005). ... effect of zinc on chlorpyrifos- induced erythrocyte fragility in wistar ...

Modeling Family Dynamics in Children with Fragile X Syndrome

Science.gov (United States)

Hall, Scott S.; Burns, David D.; Reiss, Allan L.

2007-01-01

Few studies have examined the impact of children with genetic disorders and their unaffected siblings on family functioning. In this study, the reciprocal causal links between problem behaviors and maternal distress were investigated in 150 families containing a child with fragile X syndrome (FXS) and an unaffected sibling. Both children's…

Implicit Procedural Learning in Fragile X and Down Syndrome

Science.gov (United States)

Bussy, G.; Charrin, E.; Brun, A.; Curie, A.; des Portes, V.

2011-01-01

Background: Procedural learning refers to rule-based motor skill learning and storage. It involves the cerebellum, striatum and motor areas of the frontal lobe network. Fragile X syndrome, which has been linked with anatomical abnormalities within the striatum, may result in implicit procedural learning deficit. Methods: To address this issue, a…

Long term government debt, financial fragility, and sovereign default risk

NARCIS (Netherlands)

van der Kwaak, C.; van Wijnbergen, S.

2013-01-01

We analyze the interaction between bank rescues, financial fragility and sovereign debt discounts. To that end we set up a model that contains balance sheet constrained financial intermediaries financing both capital expenditure of intermediate goods producers and government deficits. The financial

Language and Learning in Boys with Fragile X Syndrome: Syntactic Processing and the Role of Phonological Memory

Science.gov (United States)

Kover, Sara T.

2012-01-01

Fragile X syndrome is the leading inherited cause of intellectual disability. Most boys with fragile X syndrome have impaired cognition and language deficits, with significant within-syndrome variability. Syntax may be especially delayed relative to nonverbal cognition; however, little is known about the specificity of delay, the sources of that…

Frequencies of chromosome aberration on radiation workers

International Nuclear Information System (INIS)

Yanti Lusiyanti; Zubaidah Alatas

2016-01-01

Radiation exposure of the body can cause damage to the genetic material in cells (cytogenetic) in the form of changes in the structure or chromosomal aberrations in peripheral blood lymphocytes. Chromosomal aberrations can be unstable as dicentric and ring chromosomes, and is stable as translocation. Dicentric chromosome is the gold standard biomarker due to radiation exposure, and chromosome translocation is a biomarker for retrospective biodosimetry. The aim of this studi is to conduct examination of chromosomal aberrations in the radiation worker to determine the potential damage of cell that may arise due to occupational radiation exposure. The examination have been carried out on blood samples from 55 radiation workers in the range of 5-30 year of service. Chromosome aberration frequency measurement starts with blood sampling, culturing, harvesting, slide preparations, and lymphocyte chromosome staining with Giemsa and painting with Fluorescence In Situ Hybridization (FISH) technique. The results showed that chromosomal translocations are not found in blood samples radiation workers and dicentric chromosomes found only on 2 blood samples of radiation workers with a frequency of 0.001/cell. The frequency of chromosomal aberrations in the blood cells such workers within normal limits and this means that the workers have been implemented a radiation safety aspects very well. (author)

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies

Energy Technology Data Exchange (ETDEWEB)

Pampalona, J.; Soler, D.; Genesca, A. [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain); Tusell, L., E-mail: laura.tusell@uab.es [Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra E-08193 (Spain)

2010-01-05

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16{sup INK4a} protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies

International Nuclear Information System (INIS)

Pampalona, J.; Soler, D.; Genesca, A.; Tusell, L.

2010-01-01

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16 INK4a protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and nuclear

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies.

Science.gov (United States)

Pampalona, J; Soler, D; Genescà, A; Tusell, L

2010-01-05

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16(INK4a) protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and nuclear

Label Free Chromosome Translocation Detection with Silicon nanowires

DEFF Research Database (Denmark)

Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer

HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method is a Fluore......HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method...

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Science.gov (United States)

Machiela, Mitchell J.; Zhou, Weiyin; Karlins, Eric; Sampson, Joshua N.; Freedman, Neal D.; Yang, Qi; Hicks, Belynda; Dagnall, Casey; Hautman, Christopher; Jacobs, Kevin B.; Abnet, Christian C.; Aldrich, Melinda C.; Amos, Christopher; Amundadottir, Laufey T.; Arslan, Alan A.; Beane-Freeman, Laura E.; Berndt, Sonja I.; Black, Amanda; Blot, William J.; Bock, Cathryn H.; Bracci, Paige M.; Brinton, Louise A.; Bueno-de-Mesquita, H Bas; Burdett, Laurie; Buring, Julie E.; Butler, Mary A.; Canzian, Federico; Carreón, Tania; Chaffee, Kari G.; Chang, I-Shou; Chatterjee, Nilanjan; Chen, Chu; Chen, Constance; Chen, Kexin; Chung, Charles C.; Cook, Linda S.; Crous Bou, Marta; Cullen, Michael; Davis, Faith G.; De Vivo, Immaculata; Ding, Ti; Doherty, Jennifer; Duell, Eric J.; Epstein, Caroline G.; Fan, Jin-Hu; Figueroa, Jonine D.; Fraumeni, Joseph F.; Friedenreich, Christine M.; Fuchs, Charles S.; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gaziano, J. Michael; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goldin, Lynn; Goldstein, Alisa M.; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Henriksson, Roger; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hsiung, Chao A.; Hu, Nan; Hu, Wei; Hunter, David J.; Hutchinson, Amy; Jenab, Mazda; Johansen, Christoffer; Khaw, Kay-Tee; Kim, Hee Nam; Kim, Yeul Hong; Kim, Young Tae; Klein, Alison P.; Klein, Robert; Koh, Woon-Puay; Kolonel, Laurence N.; Kooperberg, Charles; Kraft, Peter; Krogh, Vittorio; Kurtz, Robert C.; LaCroix, Andrea; Lan, Qing; Landi, Maria Teresa; Marchand, Loic Le; Li, Donghui; Liang, Xiaolin; Liao, Linda M.; Lin, Dongxin; Liu, Jianjun; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Malats, Nuria; Matsuo, Keitaro; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Mirabello, Lisa; Moore, Lee; Olson, Sara H.; Orlow, Irene; Park, Jae Yong; Patiño-Garcia, Ana; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Pooler, Loreall; Prescott, Jennifer; Prokunina-Olsson, Ludmila; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Real, Francisco X.; Riboli, Elio; Risch, Harvey A.; Rodriguez-Santiago, Benjamin; Ruder, Avima M.; Savage, Sharon A.; Schumacher, Fredrick; Schwartz, Ann G.; Schwartz, Kendra L.; Seow, Adeline; Wendy Setiawan, Veronica; Severi, Gianluca; Shen, Hongbing; Sheng, Xin; Shin, Min-Ho; Shu, Xiao-Ou; Silverman, Debra T.; Spitz, Margaret R.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael; Stram, Daniel; Tang, Ze-Zhong; Taylor, Philip R.; Teras, Lauren R.; Tobias, Geoffrey S.; Van Den Berg, David; Visvanathan, Kala; Wacholder, Sholom; Wang, Jiu-Cun; Wang, Zhaoming; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolpin, Brian M.; Wong, Maria Pik; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xia, Lucy; Yang, Hannah P.; Yang, Pan-Chyr; Yu, Kai; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Ziegler, Regina G.; Perez-Jurado, Luis A.; Caporaso, Neil E.; Rothman, Nathaniel; Tucker, Margaret; Dean, Michael C.; Yeager, Meredith; Chanock, Stephen J.

2016-01-01

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. PMID:27291797

Stabilization of chromosomes by DNA intercalators for flow karyotyping and identification by banding of isolated chromosomes

NARCIS (Netherlands)

Aten, J. A.; Buys, C. H.; van der Veen, A. Y.; Mesa, J. R.; Yu, L. C.; Gray, J. W.; Osinga, J.; Stap, J.

1987-01-01

A number of structurally unrelated DNA intercalators have been studied as stabilizers of mitotic chromosomes during isolation from rodent and human metaphase cells. Seven out of the nine intercalators tested were found to be useful as chromosome stabilizing agents. Chromosome suspensions prepared in

Bile salt-induced increases in duodenal brush-border membrane proton permeability, fluidity, and fragility

International Nuclear Information System (INIS)

Zhao, D.L.; Hirst, B.H.

1990-01-01

Rabbit duodenal brush-border membrane vesicles were treated in vitro with deoxycholate, glycodeoxycholate, or taurodeoxycholate. Intravesicular [14C]glucose space at equilibrium, 0.54 microliters/mg protein, was reduced by exposure to the three bile salts in a concentration (0.1-5.0 mM)-dependent manner, equatable with increased membrane fragility. Net proton permeability (Pnet), determined by acridine orange fluorescence quenching, was increased from 6.3 x 10(-4) cm/sec in untreated vesicles, by approximately 120, 150, and 170%, by treatment with bile salts at 0.1, 0.5 and 1.0 mM, respectively. The three bile salts were equipotent. The increases in membrane fragility and Pnet were not accompanied by significant increases in membrane fluidity, as assessed from steady-state and time-resolved diphenylhexatriene fluorescence anisotropy. The data demonstrate direct effects of bile salts on duodenal apical membrane fragility and proton permeability that are likely to be early events in bile salt-induced mucosal damage

Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males

Energy Technology Data Exchange (ETDEWEB)

Cohen, I.L.; Sudhalter, V.; Nolin, S.L. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)

1996-08-09

Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome. 21 refs., 3 figs.

The numerical computation of seismic fragility of base-isolated Nuclear Power Plants buildings

International Nuclear Information System (INIS)

Perotti, Federico; Domaneschi, Marco; De Grandis, Silvia

2013-01-01

Highlights: • Seismic fragility of structural components in base isolated NPP is computed. • Dynamic integration, Response Surface, FORM and Monte Carlo Simulation are adopted. • Refined approach for modeling the non-linearities behavior of isolators is proposed. • Beyond-design conditions are addressed. • The preliminary design of the isolated IRIS is the application of the procedure. -- Abstract: The research work here described is devoted to the development of a numerical procedure for the computation of seismic fragilities for equipment and structural components in Nuclear Power Plants; in particular, reference is made, in the present paper, to the case of isolated buildings. The proposed procedure for fragility computation makes use of the Response Surface Methodology to model the influence of the random variables on the dynamic response. To account for stochastic loading, the latter is computed by means of a simulation procedure. Given the Response Surface, the Monte Carlo method is used to compute the failure probability. The procedure is here applied to the preliminary design of the Nuclear Power Plant reactor building within the International Reactor Innovative and Secure international project; the building is equipped with a base isolation system based on the introduction of High Damping Rubber Bearing elements showing a markedly non linear mechanical behavior. The fragility analysis is performed assuming that the isolation devices become the critical elements in terms of seismic risk and that, once base-isolation is introduced, the dynamic behavior of the building can be captured by low-dimensional numerical models

Neocentromeres Provide Chromosome Segregation Accuracy and Centromere Clustering to Multiple Loci along a Candida albicans Chromosome.

Directory of Open Access Journals (Sweden)

Laura S Burrack

2016-09-01

Full Text Available Assembly of kinetochore complexes, involving greater than one hundred proteins, is essential for chromosome segregation and genome stability. Neocentromeres, or new centromeres, occur when kinetochores assemble de novo, at DNA loci not previously associated with kinetochore proteins, and they restore chromosome segregation to chromosomes lacking a functional centromere. Neocentromeres have been observed in a number of diseases and may play an evolutionary role in adaptation or speciation. However, the consequences of neocentromere formation on chromosome missegregation rates, gene expression, and three-dimensional (3D nuclear structure are not well understood. Here, we used Candida albicans, an organism with small, epigenetically-inherited centromeres, as a model system to study the functions of twenty different neocentromere loci along a single chromosome, chromosome 5. Comparison of neocentromere properties relative to native centromere functions revealed that all twenty neocentromeres mediated chromosome segregation, albeit to different degrees. Some neocentromeres also caused reduced levels of transcription from genes found within the neocentromere region. Furthermore, like native centromeres, neocentromeres clustered in 3D with active/functional centromeres, indicating that formation of a new centromere mediates the reorganization of 3D nuclear architecture. This demonstrates that centromere clustering depends on epigenetically defined function and not on the primary DNA sequence, and that neocentromere function is independent of its distance from the native centromere position. Together, the results show that a neocentromere can form at many loci along a chromosome and can support the assembly of a functional kinetochore that exhibits native centromere functions including chromosome segregation accuracy and centromere clustering within the nucleus.

Developmental Trajectories of Young Girls with Fragile X Syndrome

Science.gov (United States)

Hatton, Deborah D.; Wheeler, Anne; Sideris, John; Sullivan, Kelly; Reichardt, Alison; Roberts, Jane; Clark, Renee; Bailey, Donald B., Jr.

2009-01-01

To describe the early phenotype of girls with full mutation fragile X, we used 54 observations of 15 girls between the ages of 6 months and 9 years to examine developmental trajectories as measured by the Battelle Development Inventory. In this sample, autistic behavior was associated with poorer developmental outcomes, primarily due to…

Fiscal deficits, financial fragility, and the effectiveness of government policies

NARCIS (Netherlands)

Kirchner, M.; van Wijnbergen, S.

2012-01-01

Recent macro developments in the euro area have highlighted the interactions between fiscal policy, sovereign debt, and financial fragility. We take a structural macroeconomic model with frictions in the financial intermediation process, in line with recent research, but introduce asset choice and

Effects of Sampling Context on Spontaneous Expressive Language in Males with Fragile X Syndrome or Down Syndrome

Science.gov (United States)

Kover, Sara T.; McDuffie, Andrea; Abbeduto, Leonard; Brown, W. Ted

2012-01-01

Purpose: In this study, the authors examined the impact of sampling context on multiple aspects of expressive language in male participants with fragile X syndrome in comparison to male participants with Down syndrome or typical development. Method: Participants with fragile X syndrome (n = 27), ages 10-17 years, were matched groupwise on…

Seismic Fragility Analysis of a Condensate Storage Tank with Age-Related Degradations

Energy Technology Data Exchange (ETDEWEB)

Nie, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Braverman, J. [Brookhaven National Lab. (BNL), Upton, NY (United States); Hofmayer, C [Brookhaven National Lab. (BNL), Upton, NY (United States); Choun, Y-S [Brookhaven National Lab. (BNL), Upton, NY (United States); Kim, MK [Brookhaven National Lab. (BNL), Upton, NY (United States); Choi, I-K [Brookhaven National Lab. (BNL), Upton, NY (United States)

2011-04-01

The Korea Atomic Energy Research Institute (KAERI) is conducting a five-year research project to develop a realistic seismic risk evaluation system which includes the consideration of aging of structures and components in nuclear power plants (NPPs). The KAERI research project includes three specific areas that are essential to seismic probabilistic risk assessment (PRA): (1) probabilistic seismic hazard analysis, (2) seismic fragility analysis including the effects of aging, and (3) a plant seismic risk analysis. Since 2007, Brookhaven National Laboratory (BNL) has entered into a collaboration agreement with KAERI to support its development of seismic capability evaluation technology for degraded structures and components. The collaborative research effort is intended to continue over a five year period. The goal of this collaboration endeavor is to assist KAERI to develop seismic fragility analysis methods that consider the potential effects of age-related degradation of structures, systems, and components (SSCs). The research results of this multi-year collaboration will be utilized as input to seismic PRAs. This report describes the research effort performed by BNL for the Year 4 scope of work. This report was developed as an update to the Year 3 report by incorporating a major supplement to the Year 3 fragility analysis. In the Year 4 research scope, an additional study was carried out to consider an additional degradation scenario, in which the three basic degradation scenarios, i.e., degraded tank shell, degraded anchor bolts, and cracked anchorage concrete, are combined in a non-perfect correlation manner. A representative operational water level is used for this effort. Building on the same CDFM procedure implemented for the Year 3 Tasks, a simulation method was applied using optimum Latin Hypercube samples to characterize the deterioration behavior of the fragility capacity as a function of age-related degradations. The results are summarized in Section 5

Microdissection and molecular manipulation of single chromosomes in woody fruit trees with small chromosomes using pomelo (Citrus grandis) as a model. I. Construction of single chromosomal DNA libraries.

Science.gov (United States)

Huang, D; Wu, W; Zhou, Y; Hu, Z; Lu, L

2004-05-01

Construction of single chromosomal DNA libraries by means of chromosome microdissection and microcloning will be useful for genomic research, especially for those species that have not been extensively studied genetically. Application of the technology of microdissection and microcloning to woody fruit plants has not been reported hitherto, largely due to the generally small sizes of metaphase chromosomes and the difficulty of chromosome preparation. The present study was performed to establish a method for single chromosome microdissection and microcloning in woody fruit species using pomelo as a model. The standard karyotype of a pomelo cultivar ( Citrus grandis cv. Guanxi) was established based on 20 prometaphase photomicrographs. According to the standard karyotype, chromosome 1 was identified and isolated with fine glass microneedles controlled by a micromanipulator. DNA fragments ranging from 0.3 kb to 2 kb were acquired from the isolated single chromosome 1 via two rounds of PCR mediated by Sau3A linker adaptors and then cloned into T-easy vectors to generate a DNA library of chromosome 1. Approximately 30,000 recombinant clones were obtained. Evaluation based on 108 randomly selected clones showed that the sizes of the cloned inserts varied from 0.5 kb to 1.5 kb with an average of 860 bp. Our research suggests that microdissection and microcloning of single small chromosomes in woody plants is feasible.

Synaptic vesicle dynamic changes in a model of fragile X.

Science.gov (United States)

Broek, Jantine A C; Lin, Zhanmin; de Gruiter, H Martijn; van 't Spijker, Heleen; Haasdijk, Elize D; Cox, David; Ozcan, Sureyya; van Cappellen, Gert W A; Houtsmuller, Adriaan B; Willemsen, Rob; de Zeeuw, Chris I; Bahn, Sabine

2016-01-01

Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS.

Delimiting the origin of a B chromosome by FISH mapping, chromosome painting and DNA sequence analysis in Astyanax paranae (Teleostei, Characiformes.

Directory of Open Access Journals (Sweden)

Duílio M Z de A Silva

Full Text Available Supernumerary (B chromosomes have been shown to contain a wide variety of repetitive sequences. For this reason, fluorescent in situ hybridisation (FISH is a useful tool for ascertaining the origin of these genomic elements, especially when combined with painting from microdissected B chromosomes. In order to investigate the origin of B chromosomes in the fish species Astyanax paranae, these two approaches were used along with PCR amplification of specific DNA sequences obtained from the B chromosomes and its comparison with those residing in the A chromosomes. Remarkably, chromosome painting with the one-arm metacentric B chromosome probe showed hybridization signals on entire B chromosome, while FISH mapping revealed the presence of H1 histone and 18S rDNA genes symmetrically placed in both arms of the B chromosome. These results support the hypothesis that the B chromosome of A. paranae is an isochromosome. Additionally, the chromosome pairs Nos. 2 or 23 are considered the possible B chromosome ancestors since both contain syntenic H1 and 18S rRNA sequences. The analysis of DNA sequence fragments of the histone and rRNA genes obtained from the microdissected B chromosomes showed high similarity with those obtained from 0B individuals, which supports the intraspecific origin of B chromosomes in A. paranae. Finally, the population hereby analysed showed a female-biased B chromosome presence suggesting that B chromosomes in this species could influence sex determinism.

Acute nursing care of the older adult with fragility hip fracture

DEFF Research Database (Denmark)

Maher, A.B.; Meehan, A.J.; Hertz, K.

2013-01-01

. Pressure Ulcers. Fluid Balance/Nutrition. Constipation/Catheter Associated Urinary Tract Infection. Vigilant nursing assessment and prompt intervention may prevent the development of the complications we discuss. If they do occur and are identified early on, they may resolve with appropriate and timely......The second part of this paper provides those who care for orthopaedic patients with evidence-supported international perspectives about acute nursing care of the older adult with fragility hip fracture. Developed by an international group of nurse experts and guided by a range of information from...... research and clinical practice, it focuses on nurse sensitive quality indicators during the acute hospitalisation for fragility hip fracture. Optimal care for the patient who has experienced such a fracture is the focus. This includes (in the first, earlier, part):. Pain. Delirium. and in this part...

An Efficient Semi-fragile Watermarking Scheme for Tamper Localization and Recovery

Science.gov (United States)

Hou, Xiang; Yang, Hui; Min, Lianquan

2018-03-01

To solve the problem that remote sensing images are vulnerable to be tampered, a semi-fragile watermarking scheme was proposed. Binary random matrix was used as the authentication watermark, which was embedded by quantizing the maximum absolute value of directional sub-bands coefficients. The average gray level of every non-overlapping 4×4 block was adopted as the recovery watermark, which was embedded in the least significant bit. Watermarking detection could be done directly without resorting to the original images. Experimental results showed our method was robust against rational distortions to a certain extent. At the same time, it was fragile to malicious manipulation, and realized accurate localization and approximate recovery of the tampered regions. Therefore, this scheme can protect the security of remote sensing image effectively.

Retrospective dosimetry using chromosome painting

International Nuclear Information System (INIS)

Nasazzi, N.B.; Giorgio, M.D.; Taja, M.R.

2000-01-01

Chromosome aberration frequency measured in peripheral lymphocytes of persons exposed to ionizing radiation has been used since 1960s for dose assessment. Suspected overexposure is usually evaluated by the frequency of dicentrics and centric rings using an appropriate in vitro calibration curve. However, these chromosome aberrations are unstable with time after exposure and dose reconstruction may encounter uncertainties when the time between the exposure and the analysis is considerable or even unknown. It appears that translocations persist with time after exposure and may be used as an indication of acute past overexposures. Moreover, they appear to accumulate the cytogenetical information, which correlates with the dose received under fractionated, chronic or even occupational exposure conditions. Translocations may be detected using G-banding, which allows to score the total amount of radiation induced translocations but it is a time consuming method, or by Chromosome Painting, a method base on the Fluorescence in situ Hybridization (FISH) technique, painting only some chromosome pairs with specific whole chromosome probes and then extrapolating the observed translocation frequencies to the full genome. The latter method allows a faster aberration scoring than G-banding and appears to be the most promissory tool for biodosimetry, particularly when it is necessary to assess low doses and consequently to score a large number of metaphases, e.g. radiation workers exposed within dose limits. As with the unstable chromosome aberration, it is necessary an in vitro calibration curve based on the frequency of stable chromosome aberrations to assess doses. Our laboratory performed calibration curves for Co 60 γ-rays based on the frequencies of unstable (dicentrics and centric rings detected by conventional Giemsa staining) and stable chromosome aberrations (translocations and inversions, detected by G-banding). In order to minimize the interlaboratory variability, we

Preliminary Seismic Response and Fragility Analysis for DACS Cabinet

Energy Technology Data Exchange (ETDEWEB)

Oh, Jinho; Kwag, Shinyoung; Lee, Jongmin; Kim, Youngki [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-05-15

A DACS cabinet is installed in the main control room. The objective of this paper is to perform seismic analyses and evaluate the preliminary structural integrity and seismic capacity of the DACS cabinet. For this purpose, a 3-D finite element model of the DACS cabinet was developed and its modal analyses are carried out to analyze the dynamic characteristics. The response spectrum analyses and the related safety evaluation are then performed for the DACS cabinet subject to seismic loads. Finally, the seismic margin and seismic fragility of the DACS cabinet are investigated. A seismic analysis and preliminary structural integrity of the DACS cabinet under self weight and SSE load have been evaluated. For this purpose, 3-D finite element models of the DACS cabinet were developed. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. Therefore, it is concluded that the DACS cabinet was safely designed in that no damage to the preliminary structural integrity and sufficient seismic margin is expected.

Preliminary Seismic Response and Fragility Analysis for DACS Cabinet

International Nuclear Information System (INIS)

Oh, Jinho; Kwag, Shinyoung; Lee, Jongmin; Kim, Youngki

2013-01-01

A DACS cabinet is installed in the main control room. The objective of this paper is to perform seismic analyses and evaluate the preliminary structural integrity and seismic capacity of the DACS cabinet. For this purpose, a 3-D finite element model of the DACS cabinet was developed and its modal analyses are carried out to analyze the dynamic characteristics. The response spectrum analyses and the related safety evaluation are then performed for the DACS cabinet subject to seismic loads. Finally, the seismic margin and seismic fragility of the DACS cabinet are investigated. A seismic analysis and preliminary structural integrity of the DACS cabinet under self weight and SSE load have been evaluated. For this purpose, 3-D finite element models of the DACS cabinet were developed. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. A modal analysis, response spectrum analysis, and seismic fragility analysis were then performed. From the structural analysis results, the DACS cabinet is below the structural design limit of under SSE 0.3g, and can structurally withstand until less than SSE 3g based on an evaluation of the maximum effective stresses. The HCLPF capacity for the DGRS of the SSE 0.3g is 0.55g. Therefore, it is concluded that the DACS cabinet was safely designed in that no damage to the preliminary structural integrity and sufficient seismic margin is expected

Infant Development in Fragile X Syndrome: Cross-Syndrome Comparisons

Science.gov (United States)

Roberts, Jane E.; McCary, Lindsay M.; Shinkareva, Svetlana V.; Bailey, Donald B., Jr.

2016-01-01

This study examined the developmental profile of male infants with fragile X syndrome (FXS) and its divergence from typical development and development of infants at high risk for autism associated with familial recurrence (ASIBs). Participants included 174 boys ranging in age from 5 to 28 months. Cross-sectional profiles on the Mullen Scales of…

Parenting Young Children with and without Fragile X Syndrome

Science.gov (United States)

Sterling, Audra; Barnum, Leah; Skinner, Debra; Warren, Steven F.; Fleming, Kandace

2012-01-01

The purpose of this study was to examine maternal parenting styles across age-matched siblings using a within-family design, in which one child has Fragile X syndrome. Thirteen families participated; children were aged 16 to 71 months. Mothers completed several videotaped activities with each child separately as well as an interview. Mothers used…

Soil-Structure Interaction Effect on Fragility Curve of 3D Models of Concrete Moment-Resisting Buildings

Directory of Open Access Journals (Sweden)

Ali Anvarsamarin

2018-01-01

Full Text Available This paper presents the probabilistic generation of collapse fragility curves for evaluating the performance of 3D, reinforced concrete (RC moment-resisting building models, considering soil-structure interaction (SSI by concentration on seismic uncertainties. It considers collapse as the loss of lateral load-resisting capacity of the building structures due to severe ground shaking and consequent large interstory drifts intensified by P-Δ effects as well as the strength and stiffness deterioration of their lateral load carrying systems. The estimation of the collapse performance of structures requires the relation between the intensity measure (IM and the probability of collapse that is determined using the generated collapse fragility curves. Considering a number of 6-, 12-, and 18-story, 3D, RC moment-resisting buildings, two scalar IMs are employed to estimate their collapse fragility curve. On the other hand, the effect of the site soil type on the collapse fragility curves was taken into account by considering the soil-structure interaction. According to the obtained results, adopting the average of spectral acceleration (Saavg intensity measure is more efficient in capturing the effect of the inherent uncertainties of the strong ground motions on the structural response parameters. In addition, considering the SSI for soil type D with shear-wave velocity of 180 m/s to 360 m/s reduces the median of intensity measure (IM = Sa(T1 of fragility curve in 6-, 12-, and 18-story buildings by 4.92%, 22.26%, and 23.03%, respectively.

Atomic and electronic structures of an extremely fragile liquid.

Science.gov (United States)

Kohara, Shinji; Akola, Jaakko; Patrikeev, Leonid; Ropo, Matti; Ohara, Koji; Itou, Masayoshi; Fujiwara, Akihiko; Yahiro, Jumpei; Okada, Junpei T; Ishikawa, Takehiko; Mizuno, Akitoshi; Masuno, Atsunobu; Watanabe, Yasuhiro; Usuki, Takeshi

2014-12-18

The structure of high-temperature liquids is an important topic for understanding the fragility of liquids. Here we report the structure of a high-temperature non-glass-forming oxide liquid, ZrO2, at an atomistic and electronic level. The Bhatia-Thornton number-number structure factor of ZrO2 does not show a first sharp diffraction peak. The atomic structure comprises ZrO5, ZrO6 and ZrO7 polyhedra with a significant contribution of edge sharing of oxygen in addition to corner sharing. The variety of large oxygen coordination and polyhedral connections with short Zr-O bond lifetimes, induced by the relatively large ionic radius of zirconium, disturbs the evolution of intermediate-range ordering, which leads to a reduced electronic band gap and increased delocalization in the ionic Zr-O bonding. The details of the chemical bonding explain the extremely low viscosity of the liquid and the absence of a first sharp diffraction peak, and indicate that liquid ZrO2 is an extremely fragile liquid.

Seismic fragility evaluation of unreinforced masonry walls

International Nuclear Information System (INIS)

Park, Y.J.; Hofmayer, C.H.; Reich, M.; Lee, S.K.

1991-01-01

A practical analysis scheme to evaluate the seismic fragility of unreinforced masonry walls which are used at various places in older reactor facilities is presented. Among the several failure modes for such walls, the out-of-plane bending failure is considered to be a major risk contributor in seismic PRA studies. In order to evaluate this failure mode, the use of an equivalent linear approximation method is examined based on comparisons with available test data and nonlinear time history analyses. (author)

GENERAL OVERGROWTH IN THE FRAGILE-X SYNDROME - VARIABILITY IN THE PHENOTYPIC-EXPRESSION OF THE FMR1 GENE MUTATION