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

Chromosome fragility at FRAXA in human cleavage stage embryos at risk for fragile X syndrome.

Science.gov (United States)

Verdyck, Pieter; Berckmoes, Veerle; De Vos, Anick; Verpoest, Willem; Liebaers, Inge; Bonduelle, Maryse; De Rycke, Martine

2015-10-01

Fragile X syndrome (FXS), the most common inherited intellectual disability syndrome, is caused by expansion and hypermethylation of the CGG repeat in the 5' UTR of the FMR1 gene. This expanded repeat, also known as the rare fragile site FRAXA, causes X chromosome fragility in cultured cells from patients but only when induced by perturbing pyrimidine synthesis. We performed preimplantation genetic diagnosis (PGD) on 595 blastomeres biopsied from 442 cleavage stage embryos at risk for FXS using short tandem repeat (STR) markers. In six blastomeres, from five embryos an incomplete haplotype was observed with loss of all alleles telomeric to the CGG repeat. In all five embryos, the incomplete haplotype corresponded to the haplotype carrying the CGG repeat expansion. Subsequent analysis of additional blastomeres from three embryos by array comparative genomic hybridization (aCGH) confirmed the presence of a terminal deletion with a breakpoint close to the CGG repeat in two blastomeres from one embryo. A blastomere from another embryo showed the complementary duplication. We conclude that a CGG repeat expansion at FRAXA causes X chromosome fragility in early human IVF embryos at risk for FXS. © 2015 Wiley Periodicals, Inc.

The fragile X syndrome: Isolation of the FMR-1 gene and characterization of the fragile X mutation

NARCIS (Netherlands)

B.A. Oostra (Ben); A. Verkerk

1992-01-01

markdownabstractConclusion Rapid progress has been made in the analysis of the fragile X syndrome during 1991. Different groups have discovered that fragile X chromosomes are preferentially methylated. In these X chromosomes an insertion has been found in the methylated region. The FMR-1 gene,

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 ...

The Detection and Analysis of Chromosome Fragile Sites

DEFF Research Database (Denmark)

Bjerregaard, Victoria A; Özer, Özgün; Hickson, Ian D

2018-01-01

A fragile site is a chromosomal locus that is prone to form a gap or constriction visible within a condensed metaphase chromosome, particularly following exposure of cells to DNA replication stress. Based on their frequency, fragile sites are classified as either common (CFSs; present in all...... for detection and analysis of chromosome fragile sites....

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.

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.

Frequency of fragile-x in x‑linked mental retardation

African Journals Online (AJOL)

... with isolated mental retardation or autism of unknown etiology with considerable fragile X dysmorphic features or established family history of fragile X syndrome, chromosomal study that identifies the fragile site at Xq27.3 in addition to other cytogenetic abnormalities could be useful or early diagnosis and intervention by ...

Chapitre 8 – Production et qualification de l’espace urbain : entre informel et corruption

OpenAIRE

David, Jean-Claude

2014-01-01

Les habitants/créateurs de quartiers informels à l’est de la ville, sous-produits de l’urbanisme, la jeunesse dorée des quartiers aisés de l’ouest qui fréquente les fast foods et renforce le profond clivage social entre l’est et l’ouest, les réfugiés palestiniens et leurs descendants habitants de deux « camps » à Alep, qui entretiennent leur propre marginalité, les imams originaires de la région rurale d’Alep qui « entrent » dans la ville et l’investissent par la confrérie Nabhaniyya, n’ont p...

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...

Physico-chemical characteristics of uraniferous supergene minerals (1960); Caracteristiques physico-chimiques des mineraux uraniferes supergenes (1960)

Energy Technology Data Exchange (ETDEWEB)

Semat, M A [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

1960-07-01

Transport and deposit conditions of uraniferous minerals are briefly described. The synthesis of crystallographic, physical, optical and thermal properties allows to define the main characteristics of this mineralogical group. Tables have been arranged in order to make easy the identification of the supergene U minerals: - investigation by anion and cation; - system, cleavages, cell parameters, interplanar spacings, refractive indices, optical bearings; - classification by decreasing values of the most intense line of the powder diagram; - by anion, diagram for the 3 higher interplanar spacings; - by anion, diagram of the refractive indices. (author) [French] Les conditions de transport et de depot des mineraux uraniferes sont brievement exposees. La synthese des proprietes cristallographiques, physiques, optiques et thermiques permet de definir les caracteristiques essentielles de ce groupe mineralogique. Les tableaux suivants ont ete etablis pour faciliter l'identification des mineraux uraniferes supergenes: - recherche par anion et cation; - systeme, clivages, parametres, distances reticulaires, indices et refraction, orientation optique; - classement par valeurs decroissantes de la raie la plus intense du diagramme de poudre; - diagramme, etabli par anion, selon les 3 distances reticulaires les plus elevees; - diagramme, etabli par anion, d'indices de refraction. (auteur)

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

Molecular characterization of X chromosome fragility in idiopathic ...

African Journals Online (AJOL)

Heba Alla Hosny Omar

2015-11-23

Nov 23, 2015 ... Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients ... hence the wide clinical spectrum of disorders caused by this ... fragile X syndrome, autism and other less well-characterized.

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.

Temps professionnel et temps personnel des travailleuses du care : perméabilité ou clivage ? Care Workers’ professional time and personal time: permeability or disconnection? The hazard of the “right distance”

Directory of Open Access Journals (Sweden)

Pascale Molinier

2009-09-01

Full Text Available Les recherches en ergonomie ont montré de longue date l’existence d’une perméabilité psychologique entre les temps professionnels et personnels. Toutefois la situation des travailleuses du care a peu été étudiée sous cet angle. Les femmes qui ont à faire avec les mêmes sortes d’activités, au travail et à domicile, seraient-elles plus vulnérables que d’autres et plus susceptibles de connaître un surmenage ? L’article traite de cette question à partir d’enquêtes de psychodynamique du travail réalisées auprès d’infirmières. Pour les infirmières ayant elles-mêmes des enfants, la confrontation professionnelle avec la maladie et la mort d’enfants est particulièrement anxiogène. Différentes conduites défensives sont décrites et analysées : les stratégies de distanciation affective, de cloisonnement temporel, l’activisme et l’intolérance à la plainte de ses propres enfants. Ces stratégies protectrices visent à instaurer un clivage entre vies professionnelle et privée. Ce clivage est en partie inévitable, mais il augmente en importance, au prix d’une perte du sens du travail, quand les conditions qui autorisent le libre jeu du collectif comme instance d’élaboration de la souffrance dans le travail sont dégradées.Ergonomic research has long shown that professional and personal times are permeable. Yet, the situation of care workers has seldom been studied from that point of view. Are women who have to cope with the same activities both at work and at home more vulnerable than others? more likely to experience burnout? The author tackles the question, beginning with psychodynamic investigations on nurses. For nurses who are mothers themselves, coping with the illness and death of children is particularly anxiety-ridden. Various defensive behaviours are described and analyzed: remaining emotionally aloof, separating time periods, being militant, finding one’s own children’s complaints

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

Molecular characterization of X chromosome fragility in idiopathic ...

African Journals Online (AJOL)

Background: Fragile X syndrome (FXS) is the most common form of inherited mental retardation. Frequency of fragile X syndrome among male siblings and relatives of mentally retarded patients is relatively high. Cytogenetic diagnosis of FXS is unreliable since it is ineffective for the diagnosis of premutated males or ...

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

Directed and persistent movement arises from mechanochemistry of the ParA/ParB system.

Science.gov (United States)

Hu, Longhua; Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Neuman, Keir C; Liu, Jian

2015-12-22

The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos-an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

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)

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...

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

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

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%

FooPar

DEFF Research Database (Denmark)

Hargreaves, F. P.; Merkle, D.

2013-01-01

We present FooPar, an extension for highly efficient Parallel Computing in the multi-paradigm programming language Scala. Scala offers concise and clean syntax and integrates functional programming features. Our framework FooPar combines these features with parallel computing techniques. Foo......, results based on a empirical analysis on two supercomputers are given. We achieve close-to-optimal performance wrt. theoretical peak performance. Based on this result we conclude that FooPar allows programmers to fully access Scalas design features without suffering from performance drops when compared...

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, ...

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

Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

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Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

2015-01-01

Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

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Grégory Baronian

Full Text Available Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

Fragility and hysteretic creep in frictional granular jamming.

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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

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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

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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

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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

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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...

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

Science.gov (United States)

Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

2016-01-01

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

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

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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.

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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.

Par Pond water balance

International Nuclear Information System (INIS)

Hiergesell, R.A.; Dixon, K.L.

1996-06-01

A water budget for the Par Pond hydrologic system was established in order to estimate the rate of groundwater influx to Par Pond. This estimate will be used in modeling exercises to predict Par Pond reservoir elevation and spillway discharge in the scenario where Savannah River water is no longer pumped and discharged into Par Pond. The principal of conservation of mass was used to develop the water budget, where water inflow was set equal to water outflow. Components of the water budget were identified, and the flux associated with each was determined. The water budget was considered balanced when inflow and outflow summed to zero. The results of this study suggest that Par Pond gains water from the groundwater system in the upper reaches of the reservoir, but looses water to the groundwater system near the dam. The rate of flux of groundwater from the water table aquifer into Par Pond was determined to be 13 cfs. The rate of flux from Par Pond to the water table aquifer near the dam was determined to be 7 cfs

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

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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)

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, ...

suPAR

DEFF Research Database (Denmark)

Hodges, Gethin W; Bang, Casper N; Wachtell, Kristian

2015-01-01

The fundamental role of inflammation in cardiovascular disease (CVD) has prompted interest in numerous biomarkers that detect subclinical levels of inflammation. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker that correlates significantly with cardiovascular events ...... comprehensive review of suPAR in CVD and explore its function and usefulness in predicting cardiovascular events....

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

Directory of Open Access Journals (Sweden)

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.

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

C9.A/14 steelwork joints de poutres par plaque frontale : assemblages par gousset

CERN Document Server

2015-01-01

Les Tables de résistances ultimes des assemblages boulonnés par plaque frontale et par gousset, complétées par une description des modèles de calcul et des exemples d’application, ont pour but de faciliter la tâche de l'ingénieur et du constructeur. Cette première partie C9.A/14 contient les chapitres suivants: - Joints de poutres par plaque frontale en acier S235 et S355 - Assemblages par gousset en acier S235 et S355 Les Tables contiennent des données relatives à la géométrie ainsi que les valeurs de calcul correspondantes des résistances ultimes des assemblages ; elles remplacent le chapitre « Assemblages par plaques frontales et boulons HR » des anciennes Tables C9.1 de 1983 / 2002. Le calcul de ces assemblages par plaque frontale est basé sur les hypothèses du modèle de la méthode des composants décrite dans la norme SN EN 1993-1-8. Les vérifications sont effectuées selon la norme SIA 263:2013. Les assemblages par gousset remplacent les assemblages par double cornière, (telle...

Fluorescent in-situ hybridization of cattle and sheep chromosomes with cloned human fragile-X DNA

DEFF Research Database (Denmark)

Ali, Ahmd; Thomsen, Preben Dybdahl; Babar, M.E.

2009-01-01

An extensive study on spontaneous and 5-Fluorodeoxyuridine induced fragile sites identified Xq31 in cattle (Bos taurus) and (Xq24, Xq26) in sheep (Ovis aries) in addition to several autosomal fragile sites (under publication). A ZOO-FISH study using three cloned human fragile-X probes with CCG....../CGG(n) trinucleotide repeat sequence was carried out to determine homology between human and bovine fragile-X. The hybridisation results showed only a weak signal on a human chromosome that was not an X with all three fragile site probes. No signals were detected in sheep chromosomes. The signal of all three human...... fragile-X probes on cattle chromosomes was however, medium-prominent sub-centromeric signal on two homologues. BrdU administration in 12 h before harvesting identified these homologues to be chromosome number 5. In addition retrospective slides of cattle and sheep chromosomes used for fragile site studies...

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.

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...

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…

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.

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

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.

Parálisis cerebral :

OpenAIRE

Cabrero Izquierdo, María del Carmen

2012-01-01

Se aborda el tema de la parálisis cerebral definiendo qué es, clasificando los tipos de parálisis dependiendo de la afectación y las características principales. Se explican algunos de sus tratamientos, se dan sistemas alternativos y/o aumentativos de comunicación para un alumno con PC (parálisis cerebral).

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.

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.

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

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....

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…

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.

Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

Science.gov (United States)

Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

2012-05-11

Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

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

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

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

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

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…

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…

Par Pond vegetation status 1996

International Nuclear Information System (INIS)

Mackey, H.E. Jr.; Riley, R.S.

1996-12-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned

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....

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.

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.

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.

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

Directory of Open Access Journals (Sweden)

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...

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

Science.gov (United States)

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

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

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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

Science.gov (United States)

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;…

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)

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

Science.gov (United States)

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.

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

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.

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

Directory of Open Access Journals (Sweden)

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

Directory of Open Access Journals (Sweden)

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

Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis

NARCIS (Netherlands)

Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C. Arnold

2015-01-01

Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced

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…

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…

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.

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.

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)

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...

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

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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

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

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 ...

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

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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.

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

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.

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

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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.

Premature ovarian failure (POF in Brazilian fragile X carriers

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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.

Par Pond vegetation status Summer 1995 -- Summary

International Nuclear Information System (INIS)

Mackey, H.E. Jr.; Riley, R.S.

1996-01-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

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.

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

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

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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.

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…

ParABS system in chromosome partitioning in the bacterium Myxococcus xanthus.

Directory of Open Access Journals (Sweden)

Antonio A Iniesta

Full Text Available Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster.

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...

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 founder chromosomes in Italy: A few initial events and possible explanation for their heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Chiurazzi, P.; Genuardi, M.; Kozak, L.; Neri, G. [Universita Cattolica and Centro Ricerche per la Disabilita Mentale e Motoria, Roma (Italy)] [and others

1996-07-12

A total of 137 fragile X and 235 control chromosomes from various regions of Italy were haplotyped by analyzing two neighbouring marker microsatellites, FRAXAC1 and DXS548. The number of CGG repeats at the 5{prime} end of the FMR1 gene was also assessed in 141 control chromosomes and correlated with their haplotypes. Significant linkage disequilibrium between some {open_quotes}major{close_quotes} haplotypes and fragile X was observed, while other {open_quotes}minor{close_quotes} haplotypes may have originated by subsequent mutation at the marker microsatellite loci and/or recombination between them. Recent evidence suggests that the initial mechanism leading to CGG instability might consist of rare (10{sup -6/-7}) CGG repeat slippage events and/or loss of a stabilizing AGG via A-to-C transversion. Also, the apparently high variety of fragile X chromosomes may be partly due to the relatively high mutation rate (10{sup -4/-5}) of the microsatellite markers used in haplotyping. Our fragile X sample also showed a higher than expected heterozygosity when compared to the control sample and we suggest that this might be explained by the chance occurrence of the few founding events on different chromosomes, irrespective of their actual frequency in the population. Alternatively, a local mechanism could enhance the microsatellite mutation rate only on fragile X chromosomes, or fragile X mutations might occur more frequently on certain background haplotypes. 59 refs., 4 figs.

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

Directory of Open Access Journals (Sweden)

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.

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

Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

Science.gov (United States)

Pillet, Flavien; Passot, Fanny Marie; Pasta, Franck; Anton Leberre, Véronique; Bouet, Jean-Yves

2017-01-01

Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

La pelade par plaques

Science.gov (United States)

Spano, Frank; Donovan, Jeff C.

2015-01-01

Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

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…

Keratometric alterations following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy.

Science.gov (United States)

Citirik, Mehmet; Batman, Cosar; Bicer, Tolga; Zilelioglu, Orhan

2009-09-01

To assess the alterations in keratometric astigmatism following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy. Sixteen consecutive patients were enrolled into the study. Conventional vitrectomy was applied to eight of the cases and 25-gauge transconjunctival sutureless vitrectomy was performed in eight patients. Keratometry was performed before and after the surgery. In the 25-gauge transconjunctival sutureless pars plana vitrectomy group, statistically significant changes were not observed in the corneal curvature in any post-operative follow-up measurement (p > 0.05); whereas in the conventional pars plana vitrectomy group, statistically significant changes were observed in the first postoperative day (p = 0.01) and first postoperative month (p = 0.03). We noted that these changes returned to baseline in three months (p = 0.26). Both 25-gauge transconjunctival sutureless and conventional pars plana vitrectomy are effective surgical modalities for selected diseases of the posterior segment. Surgical procedures are critical for the visual rehabilitation of the patients. The post-operative corneal astigmatism of the vitrectomised eyes can be accurately determined at least two months post-operatively.

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

Centromere pairing by a plasmid-encoded type I ParB protein

DEFF Research Database (Denmark)

Ringgaard, Simon; Löwe, Jan; Gerdes, Kenn

2007-01-01

The par2 locus of Escherichia coli plasmid pB171 encodes two trans-acting proteins, ParA and ParB, and two cis-acting sites, parC1 and parC2, to which ParB binds cooperatively. ParA is related to MinD and oscillates in helical structures and thereby positions ParB/parC-carrying plasmids regularly......, hence identifying the N terminus of ParB as a requirement for ParB-mediated centromere pairing. These observations suggest that centromere pairing is an important intermediate step in plasmid partitioning mediated by the common type I loci....

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.

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 ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

Directory of Open Access Journals (Sweden)

Flavien Pillet

Full Text Available Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

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

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…

CFD analysis of PAR performance as function of inlet design

International Nuclear Information System (INIS)

Park, Kweonha; Khor, Chong Lee

2016-01-01

Highlights: • The new concept of PAR (passive autocatalytic recombiner) was proposed and analyzed. • Guidance wall was added at the bottom of PAR to enhance the flow rate through the catalyst. • The new concept of PAR was proved to have a better hydrogen removal performance. - Abstract: Passive autocatalytic recombiner (PAR) is very useful hydrogen mitigation measurement. It is widely implemented in the current and advanced light water reactors (ALWRs). The design of the PARs should be optimized for the specific use under severe accident scenarios. Several techniques and innovations have been fused into the PAR, as an effort to increase its efficiency of hydrogen mitigation. This study proposes different concepts of PAR, which applied some changes to the honeycomb catalyst PAR made by the Korea Nuclear Technology (KNT) Inc. Two slices of plate are added to the bottom of PAR model, which intended to act as a reflection wall and promote the gas flow into PAR. Hydrogen volume fraction was given 4 vol. % which tested by KNT to investigate the performance of PAR in different direction gas flow conditions to see maximum hydrogen recombination rate. The new concept of PAR was proved to have a better hydrogen removal performance compared to the original honeycomb catalyst PAR.

CFD analysis of PAR performance as function of inlet design

Energy Technology Data Exchange (ETDEWEB)

Park, Kweonha, E-mail: khpark@kmou.ac.kr [Division of Mechanical and Energy systems Engineering, Korea Maritime University, Dongsam-dong, Yeongdo-gu, Busan 606-791 (Korea, Republic of); Khor, Chong Lee, E-mail: itachi_829@hotmail.com [Department of Mechanical Engineering, Korea Maritime University (Korea, Republic of)

2016-01-15

Highlights: • The new concept of PAR (passive autocatalytic recombiner) was proposed and analyzed. • Guidance wall was added at the bottom of PAR to enhance the flow rate through the catalyst. • The new concept of PAR was proved to have a better hydrogen removal performance. - Abstract: Passive autocatalytic recombiner (PAR) is very useful hydrogen mitigation measurement. It is widely implemented in the current and advanced light water reactors (ALWRs). The design of the PARs should be optimized for the specific use under severe accident scenarios. Several techniques and innovations have been fused into the PAR, as an effort to increase its efficiency of hydrogen mitigation. This study proposes different concepts of PAR, which applied some changes to the honeycomb catalyst PAR made by the Korea Nuclear Technology (KNT) Inc. Two slices of plate are added to the bottom of PAR model, which intended to act as a reflection wall and promote the gas flow into PAR. Hydrogen volume fraction was given 4 vol. % which tested by KNT to investigate the performance of PAR in different direction gas flow conditions to see maximum hydrogen recombination rate. The new concept of PAR was proved to have a better hydrogen removal performance compared to the original honeycomb catalyst PAR.

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…

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…

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.

Par Pond Fish, Water, and Sediment Chemistry

International Nuclear Information System (INIS)

Paller, M.H.; Wike, L.D.

1996-06-01

The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond

Par Pond Fish, Water, and Sediment Chemistry

Energy Technology Data Exchange (ETDEWEB)

Paller, M.H. [Westinghouse Savannah River Company, AIKEN, SC (United States); Wike, L.D.

1996-06-01

The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

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.

Concerning the dynamic instability of actin homolog ParM

International Nuclear Information System (INIS)

Popp, David; Yamamoto, Akihiro; Iwasa, Mitsusada; Narita, Akihiro; Maeda, Kayo; Maeda, Yuichiro

2007-01-01

Using in vitro TIRF- and electron-microscopy, we reinvestigated the dynamics of native ParM, a prokaryotic DNA segregation protein and actin homolog. In contrast to a previous study, which used a cysteine ParM mutant, we find that the polymerization process of wild type ATP-ParM filaments consists of a polymerization phase and a subsequent steady state phase, which is dynamically unstable, like that of microtubules. We find that the apparent bidirectional polymerization of ParM, is not due to the intrinsic nature of this filament, but results from ParM forming randomly oriented bundles in the presence of crowding agents. Our results imply, that in the bacterium, ParM filaments spontaneously form bipolar bundles. Due to their intrinsic dynamic instability, ParM bundles can efficiently 'search' the cytoplasmic lumen for DNA, bind it equally well at the bipolar ends and segregate it approximately symmetrically, by the insertion of ParM subunits at either end

First-in-human uPAR PET

DEFF Research Database (Denmark)

Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene

2015-01-01

A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive...... for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment...... of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu...

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.

uPAR as anti-cancer target

DEFF Research Database (Denmark)

Lund, Ida K; Illemann, Martin; Thurison, Tine

2011-01-01

, and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...... using mouse monoclonal antibodies (mAbs) against mouse uPA or uPAR. These reagents will target uPA and uPAR in both stromal cells and cancer cells, and their therapeutic potential can now be assessed in syngenic mouse cancer models....

[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.

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.

Protease-activated receptor (PAR2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

Directory of Open Access Journals (Sweden)

Lisa G van den Hengel

Full Text Available AIMS: In collateral development (i.e. arteriogenesis, mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. METHODS AND RESULTS: PAR1-deficient (PAR1-/-, PAR2-deficient (PAR2-/- and wild-type (WT mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low monocytes and the number of repair-associated (CD206-positive macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. CONCLUSION: PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD patients.

Apoplejía pituitaria con parálisis del III par craneal: Reporte de caso

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Miguel Pinto Valdivia

2011-10-01

Full Text Available Se describe el caso de un varón de 65 años de edad, sin antecedentes patológicos de importancia, que acudió a emergencia del Hospital Nacional Cayetano Heredia por presentar cefalea intensa y ptosis palpebral izquierda. El examen físico mostró parálisis aislada del III par craneal izquierdo. Los análisis de laboratorio mostraron hiponatremia e hipopituitarismo y la resonancia magnética nuclear un adenoma pituitario con áreas de hemorragia e invasión de los senos cavernosos. El tratamiento incluyó glucocorticoides y descompresión quirúrgica transesfenoidal. La anatomía patológica confirmó el diagnóstico de infarto hemorrágico de un adenoma pituitario. El paciente fue dado de alta con terapia sustitutiva de levotiroxina y prednisona. La ptosis palpebral izquierda se recuperó en forma parcial. La apoplejía pituitaria es un síndrome clínico producido por un proceso expansivo dentro de la silla turca, secundario a hemorragia o infarto de un adenoma pituitario, que se caracteriza por cefalea, déficit visual, oftalmoplejía y alteración del nivel de conciencia. Este proceso expansivo puede comprimir los pares craneales en los senos cavernosos, produciendo diferentes grados de parálisis de los músculos oculomotores. La parálisis aislada del III par craneal es rara.(Rev Med Hered 2011;22:186-189.

Copenhagen uPAR prostate cancer (CuPCa) database

DEFF Research Database (Denmark)

Lippert, Solvej; Berg, Kasper D; Høyer-Hansen, Gunilla

2016-01-01

AIM: Urokinase plasminogen activator receptor (uPAR) plays a central role during cancer invasion by facilitating pericellular proteolysis. We initiated the prospective 'Copenhagen uPAR Prostate Cancer' study to investigate the significance of uPAR levels in prostate cancer (PCa) patients. METHODS...

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)

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…

Recombination in the human Pseudoautosomal region PAR1.

Directory of Open Access Journals (Sweden)

Anjali G Hinch

2014-07-01

Full Text Available The pseudoautosomal region (PAR is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

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

Plasma suPAR is lowered by smoking cessation

DEFF Research Database (Denmark)

Eugen-Olsen, Jesper; Ladelund, Steen; Sørensen, Lars Tue

2016-01-01

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a stable inflammatory biomarker. In patients, suPAR is a marker of disease presence, severity and prognosis. In the general population, suPAR is predictive of disease development, such as diabetes and cardiovascular disease a...

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

Directory of Open Access Journals (Sweden)

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

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

Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites

Directory of Open Access Journals (Sweden)

Pierce Levi CT

2009-01-01

Full Text Available Abstract Background Gene rearrangements such as chromosomal translocations have been shown to contribute to cancer development. Human chromosomal fragile sites are regions of the genome especially prone to breakage, and have been implicated in various chromosome abnormalities found in cancer. However, there has been no comprehensive and quantitative examination of the location of fragile sites in relation to all chromosomal aberrations. Results Using up-to-date databases containing all cancer-specific recurrent translocations, we have examined 444 unique pairs of genes involved in these translocations to determine the correlation of translocation breakpoints and fragile sites in the gene pairs. We found that over half (52% of translocation breakpoints in at least one gene of these gene pairs are mapped to fragile sites. Among these, we examined the DNA sequences within and flanking three randomly selected pairs of translocation-prone genes, and found that they exhibit characteristic features of fragile DNA, with frequent AT-rich flexibility islands and the potential of forming highly stable secondary structures. Conclusion Our study is the first to examine gene pairs involved in all recurrent chromosomal translocations observed in tumor cells, and to correlate the location of more than half of breakpoints to positions of known fragile sites. These results provide strong evidence to support a causative role for fragile sites in the generation of cancer-specific chromosomal rearrangements.

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.

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…

The inflammatory marker suPAR after cardiac arrest

DEFF Research Database (Denmark)

Rundgren, Malin; Lyngbaek, Stig; Fisker, Helle

2015-01-01

. This pilot study aimed at investigating suPAR levels in relation to outcome after CA and mild induced hypothermia. METHODS: suPAR levels were measured at 6, 36, and 72 hours in patients treated with hypothermia after CA. suPAR levels were analyzed in relation to survival after 6 months. Receiver operating...

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

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...

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.

It's quicker "Par Avignon"!

CERN Multimedia

2005-01-01

For a few years, the CERN Library has been receiving books from the University of Hanover sent via Avignon, at least that's what it says on the envelope. Such a detour would mean that parcels were travelling 720 km more than the distance separating Geneva and Hanover, which would be a very strange state of affairs. The explanation lies in a spelling mistake. The sender has been stamping parcels with a stamp that says "Par Avignon prioritaire" (first-class via Avignon) instead of "Par Avion prioritaire" (First Class Air Mail), a source of much amusement to the librarians!

[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.

Serum suPAR in patients with FSGS: trash or treasure?

Science.gov (United States)

Maas, Rutger J H; Deegens, Jeroen K J; Wetzels, Jack F M

2013-07-01

The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both overexpression of uPAR on podocytes and the administration of suPAR cause proteinuria in mice. The common pathogenic mechanism involves the activation of podocyte β3-integrin. Increased activation of β3-integrin is also observed in patients with focal and segmental glomerulosclerosis (FSGS). These observations form the basis for the hypothesis that suPAR may be the circulating factor causing FSGS. A recent study fosters this idea by demonstrating increased suPAR levels in the serum of patients with FSGS and reporting an association with recurrence after transplantation and response to plasmapheresis. However, this study was heavily biased, and subsequent studies have given conflicting results. Although the experimental work is very suggestive, at present there is no proof that any known human suPAR fragment causes FSGS in humans. We therefore suggest that the measurement of suPAR using currently available assays has absolutely no value at the present time in decision-making in routine clinical practice.

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…

Proteinase-Activated Receptor 1 (PAR1 regulates leukemic stem cell functions.

Directory of Open Access Journals (Sweden)

Nicole Bäumer

Full Text Available External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

Science.gov (United States)

Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

2014-01-01

External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

Serum suPAR in patients with FSGS: trash or treasure?

NARCIS (Netherlands)

Maas, R.J.H.; Deegens, J.K.J.; Wetzels, J.F.M.

2013-01-01

The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both

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.

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.

Accouchement par forceps: indications et pronostic materno-foetal ...

African Journals Online (AJOL)

L'accouchement par voie basse, peut être parfois compromis par des facteurs maternels, foetaux ou materno-foetaux nécessitant des moyens thérapeutiques comme le forceps pour achever l'accouchement par voie naturelle. Le forceps, une méthode qui n'est pas sans risque pour la mère et le nouveau-né. Nous avons ...

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…

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

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

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.

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.

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

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

Science.gov (United States)

Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

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

NARCIS (Netherlands)

DEVRIES, BBA; ROBINSON, H; STOLTEDIJKSTRA, [No Value; GI, CVTP; DIJKSTRA, PF; VANDOOM, J; HALLEY, DJJ; OOSTRA, BA; TURNER, G; NIERMEIJER, MF

1995-01-01

The fragile X syndrome, which often presents in childhood with overgrowth, may in some cases show some diagnostic overlap with classical Sotos syndrome. We describe four fragile X patients with general overgrowth, all of whom are from families with other affected relatives who show the classic

Immune mediated disorders in women with a fragile X expansion and FXTAS.

Science.gov (United States)

Jalnapurkar, Isha; Rafika, Nuva; Tassone, Flora; Hagerman, Randi

2015-01-01

Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations. © 2014 Wiley Periodicals, Inc.

A tool for the calculation of rockfall fragility curves for masonry buildings

Science.gov (United States)

Mavrouli, Olga

2017-04-01

Masonries are common structures in mountainous and coastal areas and they exhibit substantial vulnerability to rockfalls. For big rockfall events or precarious structures the damage is very high and the repair is not cost-effective. Nonetheless, for small or moderate rockfalls, the damage may vary in function of the characteristics of the impacting rock blocks and of the buildings. The evaluation of the expected damage for masonry buildings, and for different small and moderate rockfall scenarios, is useful for assessing the expected direct loss at constructed areas, and its implications for life safety. A tool for the calculation of fragility curves for masonry buildings which are impacted by rock blocks is presented. The fragility curves provide the probability of exceeding a given damage state (low, moderate and high) for increasing impact energies of the rock blocks on the walls. The damage states are defined according to a damage index equal to the percentage of the damaged area of a wall, as being proportional to the repair cost. Aleatoric and epistemic uncertainties are incorporated with respect to the (i) rock block velocity, (ii) rock block size, (iii) masonry width, and (iv) masonry resistance. The calculation of the fragility curves is applied using a Monte Carlo simulation. Given user-defined data for the average value of these four parameters and their variability, random scenarios are developed, the respective damage index is assessed for each scenario, and the probability of exceedance of each damage state is calculated. For the assessment of the damage index, a database developed by the results of 576 analytical simulations is used. The variables range is: wall width 0.4 - 1.0 m, wall tensile strength 0.1 - 0.6 MPa, rock velocity 1-20 m/s, rock size 1-20 m3. Nonetheless this tool permits the use of alternative databases, on the condition that they contain data that correlate the damage with the four aforementioned variables. The fragility curves can

Fragile X syndrome: Current insight | Dean | Egyptian Journal of ...

African Journals Online (AJOL)

Fragile X syndrome (FXS) is a multigenerational disorder having massive adverse effect not only on the individuals but also on their families. It is the most common type of intellectual disability after Down's syndrome. Over two decades have passed since the discovery of FMR1, the causal gene for FXS, but still little is known ...

Seizures in Fragile X Syndrome: Characteristics and Comorbid Diagnoses

Science.gov (United States)

Berry-Kravis, Elizabeth; Raspa, Melissa; Loggin-Hester, Lisa; Bishop, Ellen; Holiday, David; Bailey, Donald B., Jr.

2010-01-01

A national survey of caregivers of individuals with fragile X syndrome addressed characteristics of epilepsy and co-occurring conditions. Of the 1,394 individuals (1,090 males and 304 females) with the full mutation, 14% of males and 6% of females reported seizures. Seizures were more often partial, began between ages 4 and 10 years, and were…

PAR1 activation affects the neurotrophic properties of Schwann cells.

Science.gov (United States)

Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

2017-03-01

Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

Protease-Activated Receptor 4 (PAR4: A Promising Target for Antiplatelet Therapy

Directory of Open Access Journals (Sweden)

Gamariel Rwibasira Rudinga

2018-02-01

Full Text Available Cardiovascular diseases (CVDs are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs, including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR. Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Incarceration in fragile families.

Science.gov (United States)

Wildeman, Christopher; Western, Bruce

2010-01-01

Since the mid-1970s the U.S. imprisonment rate has increased roughly fivefold. As Christopher Wildeman and Bruce Western explain, the effects of this sea change in the imprisonment rate--commonly called mass imprisonment or the prison boom--have been concentrated among those most likely to form fragile families: poor and minority men with little schooling. Imprisonment diminishes the earnings of adult men, compromises their health, reduces familial resources, and contributes to family breakup. It also adds to the deficits of poor children, thus ensuring that the effects of imprisonment on inequality are transferred intergenerationally. Perversely, incarceration has its most corrosive effects on families whose fathers were involved in neither domestic violence nor violent crime before being imprisoned. Because having a parent go to prison is now so common for poor, minority children and so negatively affects them, the authors argue that mass imprisonment may increase future racial and class inequality--and may even lead to more crime in the long-term, thereby undoing any benefits of the prison boom. U.S. crime policy has thus, in the name of public safety, produced more vulnerable families and reduced the life chances of their children. Wildeman and Western advocate several policy reforms, such as limiting prison time for drug offenders and for parolees who violate the technical conditions of their parole, reconsidering sentence enhancements for repeat offenders, and expanding supports for prisoners and ex-prisoners. But Wildeman and Western argue that criminal justice reform alone will not solve the problems of school failure, joblessness, untreated addiction, and mental illness that pave the way to prison. In fact, focusing solely on criminal justice reforms would repeat the mistakes the nation made during the prison boom: trying to solve deep social problems with criminal justice policies. Addressing those broad problems, they say, requires a greater social

Hybrid glasses from strong and fragile metal-organic framework liquids.

Science.gov (United States)

Bennett, Thomas D; Tan, Jin-Chong; Yue, Yuanzheng; Baxter, Emma; Ducati, Caterina; Terrill, Nick J; Yeung, Hamish H-M; Zhou, Zhongfu; Chen, Wenlin; Henke, Sebastian; Cheetham, Anthony K; Greaves, G Neville

2015-08-28

Hybrid glasses connect the emerging field of metal-organic frameworks (MOFs) with the glass formation, amorphization and melting processes of these chemically versatile systems. Though inorganic zeolites collapse around the glass transition and melt at higher temperatures, the relationship between amorphization and melting has so far not been investigated. Here we show how heating MOFs of zeolitic topology first results in a low density 'perfect' glass, similar to those formed in ice, silicon and disaccharides. This order-order transition leads to a super-strong liquid of low fragility that dynamically controls collapse, before a subsequent order-disorder transition, which creates a more fragile high-density liquid. After crystallization to a dense phase, which can be remelted, subsequent quenching results in a bulk glass, virtually identical to the high-density phase. We provide evidence that the wide-ranging melting temperatures of zeolitic MOFs are related to their network topologies and opens up the possibility of 'melt-casting' MOF glasses.

Seismic-fragility tests of new and accelerated-aged Class 1E battery cells

International Nuclear Information System (INIS)

Bonzon, L.L.; Janis, W.J.; Black, D.A.; Paulsen, G.A.

1987-01-01

The seismic-fragility response of naturally-aged nuclear station safety-related batteries is of interest for two reasons: (1) to determine actual failure modes and thresholds and (2) to determine the validity of using the electrical capacity of individual cells as an indicator of the potential survivability of a battery given a seismic event. Prior reports in this series discussed the seismic-fragility tests and results for three specific naturally-aged cell types: 12-year old NCX-2250, 10-year old LCU-13, and 10-year old FHC-19. This report focuses on the complementary approach, namely, the seismic-fragility response of accelerated-aged batteries. Of particular interest is the degree to which such approaches accurately reproduce the actual failure modes and thresholds. In these tests the significant aging effects observed, in terms of seismic survivability, were: embrittlement of cell cases, positive bus material and positive plate grids; and excessive sulphation of positive plate active material causing hardening and expansion of positive plates. The IEEE Standard 535 accelerated aging method successfully reproduced seismically significant aging effects in new cells but accelerated grid embrittlement an estimated five years beyond the conditional age of other components

Vote par sondage uniforme incorruptible

OpenAIRE

Blanchard , Nicolas

2016-01-01

International audience; Introduit en 2012 par David Chaum, le vote par sondage uniforme (random-sample voting) est un protocole de vote basé sur un choix d'une sous-population représentative , permettant de limiter les coûts tout en ayant de nombreux avantages, principalement lorsqu'il est couplé a d'autres techniques comme ThreeBallot. Nous analysons un problème de corruptibilité potentielle où les votants peuvent vendre leur vote au plus offrant et proposons une variation du protocole reméd...

Osteoporosis associated with pulmonary silicosis in an equine bone fragility syndrome.

Science.gov (United States)

Arens, A M; Barr, B; Puchalski, S M; Poppenga, R; Kulin, R M; Anderson, J; Stover, S M

2011-05-01

California horses incur a bone fragility syndrome manifested by pathologic fractures. This study investigated gross, radiographic, and histologic features of the disorder as well as relationships with silicosis and levels of heavy metals and trace minerals through a postmortem study of 9 affected and 3 unaffected horses. Bones and soft tissues were evaluated grossly and histologically. Bones, lymph nodes, and lung tissue were evaluated radiographically. Tissues were evaluated for silicon levels, intracytoplasmic crystals, heavy metals, and trace minerals. All 9 affected horses had osteoporosis and clinical or subclinical pulmonary disease due to silicosis (8/9) or pneumoconiosis (1/9). All affected horses had radiographic findings consistent with osteopenia and histologic evidence of osteoporosis characterized by osteopenia, numerous resorption cavities, cement lines, and a mosaic lamellar pattern indicative of multiple remodeling events. Silicosis was characterized by widespread pulmonary granuloma formation with fibrosis; variable tracheobronchiolar and mediastinal granulomatous lymphadenitis; intracellular crystals within lung and lymph node macrophages; and pronounced lymph node fibrosis, focal necrosis, and dystrophic calcification. Crystals in lung (6/9) and lymph node (8/9) tissues were identified as cytotoxic silica dioxide polymorphs. Lung and liver tissue from affected horses had elevated levels of elemental silicon. Osteoporosis was highly correlated (r = 0.8, P horses with bone fragility disorder have systemic osteoporosis associated with fibrosing pulmonary silicosis. The etiopathogenesis of the bone fragility syndrome is unknown; however, this study provides circumstantial evidence for a silicate associated osteoporosis.

Ectodermal dysplasia-skin fragility syndrome

Directory of Open Access Journals (Sweden)

Vijay S Adhe

2011-01-01

Full Text Available Ectodermal dysplasia-skin fragility (EDSF syndrome is a rare and first described inherited disorder of desmosomes. It occurs due to loss-of-function mutations in PKP1 gene resulting in poorly formed desmosomes and loss of desmosomal and epidermal integrity. We report a case of a 2-year-old Indian male child who presented with palmoplantar hyperkeratosis with fissuring, short, sparse, and easily pluckable scalp hair, nail dystrophy, and multiple erosions over the skin. Skin biopsy showed epidermal hyperplasia with widening of intercellular spaces. His developmental milestones were delayed but intelligence was normal. Echocardiography, X-ray chest, and electrocardiogram were normal. Very few cases of this syndrome have been reported in the literature. We consider this as the first case report from India.

Genome Organization Drives Chromosome Fragility.

Science.gov (United States)

Canela, Andres; Maman, Yaakov; Jung, Seolkyoung; Wong, Nancy; Callen, Elsa; Day, Amanda; Kieffer-Kwon, Kyong-Rim; Pekowska, Aleksandra; Zhang, Hongliang; Rao, Suhas S P; Huang, Su-Chen; Mckinnon, Peter J; Aplan, Peter D; Pommier, Yves; Aiden, Erez Lieberman; Casellas, Rafael; Nussenzweig, André

2017-07-27

In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT. Published by Elsevier Inc.

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 to 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. 6 refs., 4 figs., 3 tabs

The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA

DEFF Research Database (Denmark)

Ebersbach, G; Gerdes, K; Charbon, Gitte Ebersbach

2001-01-01

Prokaryotic plasmids and chromosomes encode partitioning (par) loci that segregate DNA to daughter cells before cell division. Recent database analyses showed that almost all known par loci encode an ATPase and a DNA-binding protein, and one or more cis-acting regions where the proteins act. All...

The role of pars flaccida in human middle ear sound transmission.

Science.gov (United States)

Aritomo, H; Goode, R L; Gonzalez, J

1988-04-01

The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.

Fragility, anharmonicity and anelasticity of silver borate glasses

International Nuclear Information System (INIS)

Carini, Giovanni; Carini, Giuseppe; D'Angelo, Giovanna; Tripodo, Gaspare; Bartolotta, Antonio; Marco, Gaetano Di

2006-01-01

The fragility and the anharmonicity of (Ag 2 O) x (B 2 O 3 ) 1-x borate glasses have been quantified by measuring the change in the specific heat capacity at the glass transition temperature T g and the room-temperature thermodynamic Grueneisen parameter. Increasing the silver oxide content above X = 0.10 leads to an increase of both the parameters, showing that a growing fragility of a glass-forming liquid is predictive of an increasing overall anharmonicity of its glassy state. The attenuation and velocity of ultrasonic waves of frequencies in the range of 10-70 MHz have also been measured in silver borate glasses as a function of temperature between 1.5 and 300 K. The experimental data reveal anelastic behaviours which are governed by (i) quantum-mechanical tunnelling below 20 K (ii) thermally activated relaxations between 20 and 200 K and (iii) vibrational anharmonicity at even higher temperatures. Evaluation of tunnelling (C) and relaxation (C * ) strengths shows that C is independent of the structural changes affecting the borate network with increasing metal oxide content and is at least one order of magnitude smaller than C * . The latter observation implies that only a small fraction of the locally mobile defects are subjected to tunnelling motions

What occurs in the fragile-to-strong liquid transition regime?

DEFF Research Database (Denmark)

Yue, Yuanzheng; Hu, L.N.

The slow dynamics of glass-forming liquids is a complex subject of the condensed matter science. But the fragile-to-strong transition, which was observed not long ago [Ito, et al, Nature 1999], makes this subject even more complex since it is extremely challenging to directly probe the structural...

Phonological Awareness and Reading in Boys with Fragile X Syndrome

Science.gov (United States)

Adlof, Suzanne M.; Klusek, Jessica; Shinkareva, Svetlana V.; Robinson, Marissa L.; Roberts, Jane E.

2015-01-01

Background: Reading delays are well documented in children with fragile X syndrome (FXS), but few studies have examined linguistic precursors of reading in this population. This study examined the longitudinal development of phonological awareness and its relationship with basic reading in boys with FXS. Individual differences in genetic,…

Ebselen exhibits glycation-inhibiting properties and protects against osmotic fragility of human erythrocytes in vitro.

Science.gov (United States)

Soares, Julio C M; Folmer, Vanderlei; Da Rocha, João B T; Nogueira, Cristina W

2014-05-01

Diabetic status is associated with an increase on oxidative stress markers in humans and animal models. We have investigated the in vitro effects of high concentrations of glucose on the profile of oxidative stress and osmotic fragility of blood from control and diabetic patients; we considered whether its antioxidant properties could afford some protection against glucose-induced osmotic fragility, and whether ebselen could act as an inhibitor of hemoglobin glycation. Raising blood glucose to 5-100 mmol/L resulted in a concentration-dependent increase of glycated hemoglobin (HbA1c; P Ebselen significantly reduced the glucose-induced increase in osmotic fragility and inhibited HbA1c formation (P < 0.0001). These results indicate that blood from patients with uncontrolled diabetes are more sensitive to osmotic shock than from patients with controlled diabetes and control subjects in relation to increased production of free radicals in vivo. © 2014 International Federation for Cell Biology.

Analysis of unstable DNA sequence in FRM1 gene in Polish families with fragile X syndrome

International Nuclear Information System (INIS)

Milewski, Michal; Bal, Jerzy; Obersztyn, Ewa; Bocian, Ewa; Mazurczak, Tadeusz; Zygulska, Marta; Horst, Juergen; Deelen, Wout H.; Halley, Dicky J.J.

1996-01-01

The unstable DNA sequence in the FMR1 gene was analyzed in 85 individuals from Polish families with fragile X syndrome in order to characterize mutations responsible for the disease in Poland. In all affected individuals classified on the basis of clinical features and expression of the fragile site at X(q27.3) a large expansion of the unstable sequence (full mutation) was detected. About 5% (2 of 43) of individuals with full mutation did not express the fragile site. Among normal alleles, ranging in size from 20 to 41 CGC repeats, allele with 29 repeats was the most frequent (37%). Transmission of premutated and fully mutated alleles to the offspring was always associated with size increase. No change in repeat number was found when normal alleles were transmitted. (author). 19 refs., 4 figs, 1 tab

Movement and equipositioning of plasmids by ParA filament disassembly

DEFF Research Database (Denmark)

Ringgaard, Simon; van Zon, Jeroen; Howard, Martin

2009-01-01

, plasmids consistently migrate behind disassembling ParA cytoskeletal structures, suggesting that ParA filaments pull plasmids by depolymerization. The perpetual cycles of ParA assembly and disassembly result in continuous relocation of plasmids, which, on time averaging, results in equidistribution...

Molecular Testing for Fragile X: Analysis of 5062 Tests from 1105 Fragile X Families—Performed in 12 Clinical Laboratories in Spain

Directory of Open Access Journals (Sweden)

María-Isabel Tejada

2014-01-01

Full Text Available Fragile X syndrome is the most common inherited form of intellectual disability. Here we report on a study based on a collaborative registry, involving 12 Spanish centres, of molecular diagnostic tests in 1105 fragile X families comprising 5062 individuals, of whom, 1655 carried a full mutation or were mosaic, three cases had deletions, 1840 had a premutation, and 102 had intermediate alleles. Two patients with the full mutation also had Klinefelter syndrome. We have used this registry to assess the risk of expansion from parents to children. From mothers with premutation, the overall rate of allele expansion to full mutation is 52.5%, and we found that this rate is higher for male than female offspring (63.6% versus 45.6%; P<0.001. Furthermore, in mothers with intermediate alleles (45–54 repeats, there were 10 cases of expansion to a premutation allele, and for the smallest premutation alleles (55–59 repeats, there was a 6.4% risk of expansion to a full mutation, with 56 repeats being the smallest allele that expanded to a full mutation allele in a single meiosis. Hence, in our series the risk for alleles of <59 repeats is somewhat higher than in other published series. These findings are important for genetic counselling.

PAR-1 contributes to the innate immune response during viral infection

Science.gov (United States)

Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

2013-01-01

Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

Wild-Type Male Offspring of fmr-1+/− Mothers Exhibit Characteristics of the Fragile X Phenotype

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. Males are more severely affected than heterozygote (H) females, who, as carriers, have a 50% chance of transmitting the mutated allele in each pregnancy. fmr-1 knockout (KO) mice reproduce fragile X symptoms, including hyperactivity, seizures, and abnormal sensory processing. In contrast ...

Flow cytometric osmotic fragility test and eosin-5'-maleimide dye-binding tests are better than conventional osmotic fragility tests for the diagnosis of hereditary spherocytosis.

Science.gov (United States)

Arora, R D; Dass, J; Maydeo, S; Arya, V; Radhakrishnan, N; Sachdeva, A; Kotwal, J; Bhargava, M

2018-03-24

Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia with heterogeneous clinico-laboratory manifestations. We evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT) for the diagnosis of hereditary spherocytosis (HS). One hundred two suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA) were included, and performance of the above 4 tests was evaluated. For EMA and FOFT, 5 normal controls were assessed together with the patients and cutoffs were calculated using receiver-operator-characteristics curve (ROC) analysis. The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%, respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow cytometric tests performed better. Sensitivity and specificity of EMA was 86.2% and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of 100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the severity of the disease while %EMA decrease and %RRC did not correlate with severity of the disease. Flow-cytometric osmotic fragility test is the best possible single test followed by EMA for diagnosis of HS. A combination of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to replace conventional OFTs in future. © 2018 John Wiley & Sons Ltd.

Emotion Recognition and Visual-Scan Paths in Fragile X Syndrome

Science.gov (United States)

Shaw, Tracey A.; Porter, Melanie A.

2013-01-01

This study investigated emotion recognition abilities and visual scanning of emotional faces in 16 Fragile X syndrome (FXS) individuals compared to 16 chronological-age and 16 mental-age matched controls. The relationships between emotion recognition, visual scan-paths and symptoms of social anxiety, schizotypy and autism were also explored.…

Determination of Fragility in Organic Small Molecular Glass Forming Liquids: Comparison of Calorimetric and Spectroscopic Data and Commentary on Pharmaceutical Importance.

Science.gov (United States)

Chakravarty, Paroma; Pandya, Keyur; Nagapudi, Karthik

2018-03-05

The fragility index ( m) and conversely the strength parameter ( D) are widely used to categorize glass forming liquids and are used to characterize temperature dependency of viscosity and relaxation time as the supercooled liquid approaches glass transition. The currently used calorimetric methods in pharmaceutical literature lead to wide variability in measured values of m. In this work, a modulated differential scanning calorimetry (DSC) method is introduced that can directly determine m with minimal variability. Although calorimetric fragility is easy to measure due to availability and ease of use of DSC, there is no correlation between calorimetric and dielectric fragility (calculated spectroscopically from relaxation times). In addition, there is also no correlation between calorimetric fragility and the so-called "thermodynamic fragility" that can be calculated using only thermodynamic parameters. No relationship can be found between the crystallization propensity in the supercooled liquid state and D. However, the crystallization propensity shows a reasonable correlation with the Kohlrausch distribution parameter β k , which defines the breadth of the relaxation time distribution.

A mouse model of the human Fragile X syndrome I304N mutation.

Directory of Open Access Journals (Sweden)

Julie B Zang

2009-12-01

Full Text Available The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA-binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5'UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1 in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N in the second FMRP KH-type RNA-binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1-null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder.

Shocks in fragile matter

Science.gov (United States)

Vitelli, Vincenzo

2012-02-01

Non-linear sound is an extreme phenomenon typically observed in solids after violent explosions. But granular media are different. Right when they unjam, these fragile and disordered solids exhibit vanishing elastic moduli and sound speed, so that even tiny mechanical perturbations form supersonic shocks. Here, we perform simulations in which two-dimensional jammed granular packings are continuously compressed, and demonstrate that the resulting excitations are strongly nonlinear shocks, rather than linear waves. We capture the full dependence of the shock speed on pressure and compression speed by a surprisingly simple analytical model. We also treat shear shocks within a simplified viscoelastic model of nearly-isostatic random networks comprised of harmonic springs. In this case, anharmonicity does not originate locally from nonlinear interactions between particles, as in granular media; instead, it emerges from the global architecture of the network. As a result, the diverging width of the shear shocks bears a nonlinear signature of the diverging isostatic length associated with the loss of rigidity in these floppy networks.

Peptide-Based Optical uPAR Imaging for Surgery

DEFF Research Database (Denmark)

Juhl, Karina; Christensen, Anders; Persson, Morten

2016-01-01

Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical...... tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered...... an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft...

Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders

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Xiao-Nan Zhao

2016-09-01

Full Text Available The Fragile X-related disorders (FXDs are a group of clinical conditions resulting from the expansion of a CGG/CCG-repeat tract in exon 1 of the Fragile X mental retardation 1 (FMR1 gene. While expansions of the repeat tract predominate, contractions are also seen with the net result being that individuals can show extensive repeat length heterogeneity in different tissues. The mechanisms responsible for expansion and contraction are still not well understood. This review will discuss what is known about these processes and current evidence that supports a model in which expansion arises from the interaction of components of the base excision repair, mismatch repair and transcription coupled repair pathways.

Density-temperature scaling of the fragility in a model glass-former

DEFF Research Database (Denmark)

Schrøder, Thomas; Sengupta, Shiladitya; Sastry, Srikanth

2013-01-01

. Such a scaling, referred to as density-temperature (DT) scaling, is exact for liquids with inverse power law (IPL) interactions but has also been found to be approximately valid in many non-IPL liquids. We have analyzed the consequences of DT scaling on the density dependence of the fragility in a model glass......Dynamical quantities e.g. diffusivity and relaxation time for some glass-formers may depend on density and temperature through a specific combination, rather than independently, allowing the representation of data over ranges of density and temperature as a function of a single scaling variable......-former. We find the density dependence of kinetic fragility to be weak, and show that it can be understood in terms of DT scaling and deviations of DT scaling at low densities. We also show that the Adam-Gibbs relation exhibits DT scaling and the scaling exponent computed from the density dependence...

Skin fragility syndrome in a cat with cholangiohepatitis and hepatic lipidosis.

Science.gov (United States)

Daniel, Alexandre G T; Lucas, Sílvia R R; Júnior, Archivaldo R; Monteiro, Paula R G; Ramos, Daniela; Pires, Carolina G; Sinhorini, Idércio L

2010-02-01

A case of acquired skin fragility syndrome associated with hepatic disease in a 9-year-old, spayed female, domestic shorthair cat is described. The cat was admitted to the veterinary hospital of the University of São Paulo (Brazil) with a 6-week history of vomiting, inappetence and weight loss. Remarkable signs were weakness, lethargy and profound jaundice that had been present for 10 days according to the owner. On completion of the physical examination, when the cat was gently manipulated for blood collection the thoracic limb and interscapular skin tore. Liver enzymes and bilirubin levels were all above the normal range. On histological examination of skin and liver, Masson's trichrome stain showed collagen fibre alteration and major hepatocyte abnormalities. Findings were consistent with feline skin fragility syndrome associated with cholangiohepatitis and hepatic lipidosis. Copyright 2009 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Arousal Modulation in Females with Fragile X or Turner Syndrome

Science.gov (United States)

Roberts, Jane; Mazzocco, Michele M. M.; Murphy, Melissa M.; Hoehn-Saric, Rudolf

2008-01-01

The present study was carried out to examine physiological arousal modulation (heart activity and skin conductance), across baseline and cognitive tasks, in females with fragile X or Turner syndrome and a comparison group of females with neither syndrome. Relative to the comparison group, for whom a greater increase in skin conductance was…

Noncomprehension Signaling in Males and Females with Fragile X Syndrome

Science.gov (United States)

Thurman, Angela John; Kover, Sara T.; Brown, W. Ted; Harvey, Danielle J.; Abbeduto, Leonard

2017-01-01

Purpose: This study used a prospective longitudinal design to evaluate the trajectory and predictors of noncomprehension signaling in male and female youth with fragile X syndrome (FXS). Method: A direction-following task in which some of the directions were inadequate was administered. Participants were 52 youth (36 boys, 16 girls) with FXS. Upon…

Effect of road transport stress on Erthrocyte Osmotic Fragility (EOF ...

African Journals Online (AJOL)

After an overnight fast, venous blood was collected from each subject for the determination of serum cortisol, glucose concentration and erythrocyte osmotic fragility. The subjects were then transported at a speed of 65 – 75Km/h covering a distance of 180km. Thereafter venous blood was again collected (within 10 minutes) ...

Fabrication of free-standing replicas of fragile, laminar, chitinous biotemplates

Energy Technology Data Exchange (ETDEWEB)

Lakhtakia, Akhlesh; Motyka, Michael A [Materials Research Institute and Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802 (United States); MartIn-Palma, Raul J; Pantano, Carlo G [Materials Research Institute and Department of Materials Science and Engineering, Pennsylvania State University, University Park, PA 16802 (United States)], E-mail: akhlesh@psu.edu

2009-09-01

The conformal-evaporated-film-by-rotation technique, followed by the dissolution of chitin in an aqueous solution of orthophosphoric acid, can be used to fabricate free-standing replicas of fragile, laminar, chitinous biotemplates. This novel approach was demonstrated using butterfly wings as biotemplates and GeSeSb chalcogenide glass for replicas. (communication)

Fabrication of free-standing replicas of fragile, laminar, chitinous biotemplates

International Nuclear Information System (INIS)

Lakhtakia, Akhlesh; Motyka, Michael A; MartIn-Palma, Raul J; Pantano, Carlo G

2009-01-01

The conformal-evaporated-film-by-rotation technique, followed by the dissolution of chitin in an aqueous solution of orthophosphoric acid, can be used to fabricate free-standing replicas of fragile, laminar, chitinous biotemplates. This novel approach was demonstrated using butterfly wings as biotemplates and GeSeSb chalcogenide glass for replicas. (communication)

Soudage des aciers pour application mécanique

CERN Document Server

Deveaux, Dominique

2016-01-01

Ce guide détermine les bonnes pratiques pour comprendre les risques d’une forme d’assemblage multimatériaux : celui par soudage de nuances à forte teneur en carbone avec des éléments en acier de construction. Dans un premier temps, le rapport passe en revue l’examen des avaries sur des assemblages soudés pour l’application mécanique mettant en cause les aciers. Fissuration par fatigue, rupture fragile, rupture ductile, fissuration à chaud ou à froid sont autant de causes qui seront analysées. Dans un deuxième temps, il se concentre sur la conception des joints soudés. Du choix des nuances à la tenue vis-à-vis de la rupture fragile en passant par l’analyse en fatigue des assemblages soudés, c’est l’ensemble de la problématique qui est pris en compte.

Fragile X syndrome: Current insight

Directory of Open Access Journals (Sweden)

Deepika Delsa Dean

2016-10-01

Full Text Available Fragile X syndrome (FXS is a multigenerational disorder having massive adverse effect not only on the individuals but also on their families. It is the most common type of intellectual disability after Down’s syndrome. Over two decades have passed since the discovery of FMR1, the causal gene for FXS, but still little is known about the pathophysiology of this disease. This lack of knowledge presents the major barrier encountered by the scientific community for early diagnosis and effective treatment. Since early diagnosis has important implication in determining the disease status among members of the family tree so the genetic counseling and supportive therapy get hampered in larger perspective. The present review emphasizes on the recent findings in FXS pathophysiology, therapeutics and technical challenges in molecular diagnosis.

International strategies in fragile states : expanding the toolbox?

OpenAIRE

Klotzle, Kurt

2006-01-01

"In recent years, international actors have taken significant strides in attempting to develop strategies and instruments that effectively address the problem of weak and failing states. On the one hand, the intensified focus on state failure has to do with general, fundamental shifts in the international security environment since the end of the Cold War. On the other hand, however, the sharpened concern with fragile states arises from the specific challenges, experiences, and interests of k...

Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein.

Directory of Open Access Journals (Sweden)

Anthony J Brzoska

Full Text Available Actin-like proteins (Alps are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments.

Seismic Fragility of the LANL Fire Water Distribution System

Energy Technology Data Exchange (ETDEWEB)

Greg Mertz

2007-03-30

The purpose of this report is to present the results of a site-wide system fragility assessment. This assessment focuses solely on the performance of the water distribution systems that supply Chemical and Metallurgy Research (CMR), Weapons Engineering and Tritium Facility (WETF), Radioactive Liquid Waste Treatment Facility (RLWTF), Waste Characterization, Reduction, Repackaging Facility (WCRRF), and Transuranic Waste Inspectable Storage Project (TWISP). The analysis methodology is based on the American Lifelines Alliance seismic fragility formulations for water systems. System fragilities are convolved with the 1995 LANL seismic hazards to develop failure frequencies. Acceptance is determined by comparing the failure frequencies to the DOE-1020 Performance Goals. This study concludes that: (1) If a significant number of existing isolation valves in the water distribution system are closed to dedicate the entire water system to fighting fires in specific nuclear facilities; (2) Then, the water distribution systems for WETF, RLWTF, WCRRF, and TWISP meet the PC-2 performance goal and the water distribution system for CMR is capable of surviving a 0.06g earthquake. A parametric study of the WETF water distribution system demonstrates that: (1) If a significant number of valves in the water distribution system are NOT closed to dedicate the entire water system to fighting fires in WETF; (2) Then, the water distribution system for WETF has an annual probability of failure on the order of 4 x 10{sup -3} that does not meet the PC-2 performance goal. Similar conclusions are expected for CMR, RLWTF, WCRRF, and TWISP. It is important to note that some of the assumptions made in deriving the results should be verified by personnel in the safety-basis office and may need to be incorporated in technical surveillance requirements in the existing authorization basis documentation if credit for availability of fire protection water is taken at the PC-2 level earthquake levels

Seismic Fragility of the LANL Fire Water Distribution System

International Nuclear Information System (INIS)

Greg Mertz Jason Cardon Mike Salmon

2007-01-01

The purpose of this report is to present the results of a site-wide system fragility assessment. This assessment focuses solely on the performance of the water distribution systems that supply Chemical and Metallurgy Research (CMR), Weapons Engineering and Tritium Facility (WETF), Radioactive Liquid Waste Treatment Facility (RLWTF), Waste Characterization, Reduction, Repackaging Facility (WCRRF), and Transuranic Waste Inspectable Storage Project (TWISP). The analysis methodology is based on the American Lifelines Alliance seismic fragility formulations for water systems. System fragilities are convolved with the 1995 LANL seismic hazards to develop failure frequencies. Acceptance is determined by comparing the failure frequencies to the DOE-1020 Performance Goals. This study concludes that: (1) If a significant number of existing isolation valves in the water distribution system are closed to dedicate the entire water system to fighting fires in specific nuclear facilities; (2) Then, the water distribution systems for WETF, RLWTF, WCRRF, and TWISP meet the PC-2 performance goal and the water distribution system for CMR is capable of surviving a 0.06g earthquake. A parametric study of the WETF water distribution system demonstrates that: (1) If a significant number of valves in the water distribution system are NOT closed to dedicate the entire water system to fighting fires in WETF; (2) Then, the water distribution system for WETF has an annual probability of failure on the order of 4 x 10 -3 that does not meet the PC-2 performance goal. Similar conclusions are expected for CMR, RLWTF, WCRRF, and TWISP. It is important to note that some of the assumptions made in deriving the results should be verified by personnel in the safety-basis office and may need to be incorporated in technical surveillance requirements in the existing authorization basis documentation if credit for availability of fire protection water is taken at the PC-2 level earthquake levels

Plastic deformation tests on fragile materials using a thermal expansion machine

International Nuclear Information System (INIS)

Orozco, E.; Morales, A.; Mendoza, A.

1991-01-01

Applying an electrical current on an iron bar, a thermal expansion can be induced. We have taken advantage of this to deform fragile materials, in order to study their mechanical properties. In this paper we show some gels and high T c oxide superconductors (Author)

Safe and Inclusive Cities: A key entry point to addressing fragility ...

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

2016-05-18

May 18, 2016 ... Job seekers are converging on cities to find work, and in many ... “I think in any fragile situation there's a breakdown, and so this is a moment ... Community Work Programme has positive and negative effects on social bonds in ...

Language Development in School-Age Girls with Fragile X Syndrome

Science.gov (United States)

Sterling, A.; Abbeduto, L.

2012-01-01

Background: Girls with fragile X syndrome (FXS) have a wide range of cognitive and language abilities. The range of language outcomes experienced by girls with FXS, however, has been relatively unexplored. The purpose of this exploratory study was to examine receptive and expressive language, with a focus on vocabulary and syntax, in a group of…

Drift-free MPEG-4 AVC semi-fragile watermarking

Science.gov (United States)

Hasnaoui, M.; Mitrea, M.

2014-02-01

While intra frame drifting is a concern for all types of MPEG-4 AVC compressed-domain video processing applications, it has a particular negative impact in watermarking. In order to avoid the drift drawbacks, two classes of solutions are currently considered in the literature. They try either to compensate the drift distortions at the expense of complex decoding/estimation algorithms or to restrict the insertion to the blocks which are not involved in the prediction, thus reducing the data payload. The present study follows a different approach. First, it algebraically models the drift distortion spread problem by considering the analytic expressions of the MPEG-4 AVC encoding operations. Secondly, it solves the underlying algebraic system under drift-free constraints. Finally, the advanced solution is adapted to take into account the watermarking peculiarities. The experiments consider an m-QIM semi-fragile watermarking method and a video surveillance corpus of 80 minutes. For prescribed data payload (100 bit/s), robustness (BER < 0.1 against transcoding at 50% in stream size), fragility (frame modification detection with accuracies of 1/81 from the frame size and 3s) and complexity constraints, the modified insertion results in gains in transparency of 2 dB in PSNR, of 0.4 in AAD, of 0.002 in IF, of 0.03 in SC, of 0.017 NCC and 22 in DVQ.

First (18)F-labeled ligand for PET imaging of uPAR

DEFF Research Database (Denmark)

Persson, Morten; Liu, Hongguang; Madsen, Jacob

2013-01-01

Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA......-conjugated version (NOTA-AE105) for development of the first (18)F-labeled uPAR positron-emission-tomography PET ligand using the Al(18)F radiolabeling method. In this study, the potential of (18)F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated....

Ethiopia : tous les projets | Page 2 | CRDI - Centre de recherches ...

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

À ce jour, plus de 40 pays ont signé le New Deal pour l'engagement dans les États fragiles, lequel fait de la consolidation de la paix et de l'édification de l'État deux objectifs essentiels au développement dans les États fragiles et touchés par un conflit. Région: Ethiopia, Ivory Coast, Kenya, Rwanda, Sierra Leone.

Fragile X--a challenge to models of the mind and to best clinical practice.

Science.gov (United States)

Hay, David A

2008-06-01

Cornish et al. (2008, this issue) provide an excellent review of Fragile X a common but very complex cause of intellectual disability. They report on a cohort of such males of normal intelligence quotient (IQ) and socioeconomic status (SES), but who have deficits in selective attention and growing impairment in response inhibition. This paper has theoretical views for our models of the mind and clinical implications for families where Fragile X may never have been considered as a possible cause of some of the problems in male and female family members and possibly as well for other disorders such as attention deficit hyperactivity disorder (ADHD) and autism.

Fragile X mental retardation protein: A paradigm for translational control by RNA-binding proteins.

Science.gov (United States)

Chen, Eileen; Joseph, Simpson

2015-07-01

Translational control is a common mechanism used to regulate gene expression and occur in bacteria to mammals. Typically in translational control, an RNA-binding protein binds to a unique sequence in the mRNA to regulate protein synthesis by the ribosomes. Alternatively, a protein may bind to or modify a translation factor to globally regulate protein synthesis by the cell. Here, we review translational control by the fragile X mental retardation protein (FMRP), the absence of which causes the neurological disease, fragile X syndrome (FXS). Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

Narrative Identities and the Plebiscite in Pará: An Analysis of the Front Pages for O Liberal and Diário do Pará

Directory of Open Access Journals (Sweden)

Alda Cristina Silva da Costa

2017-05-01

Full Text Available On December 11, 2011, a plebiscite was held in Pará proposing to create two separatist states, Carajás and Tapajós, out of the state of Pará. The public voted against both projects. This article analyzes the narrative identities found on the front pages of O Liberal and Diário do Pará newspapers about the plebiscite in Pará. Depth Hermeneutics (DH, as proposed by Thompson (2011, was used as the methodological reference. DH emphasizes the object of analysis as a meaningful symbolic construction requiring interpretation. Narrative analysis, as proposed by Motta (2007, was the main research technique used to highlight the movement of construction of journalistic (discursive characters. The narrative identities built by the two newspapers showed that both were against the creation of the new states, but for very different reasons. The flag of Pará was the main object used to induce the idea of unity. Em 11 de dezembro de 2011, o plebiscito no Pará propôs a criação dos estados de Carajás e de Tapajós a partir da divisão do estado do Pará. O resultado da consulta pública foi negativo aos dois projetos. O artigo analisa as identidades narrativas constituídas pelas primeiras páginas dos jornais O Liberal e Diário do Pará sobre o plebiscito no Pará. Utilizou-se como referencial metodológico a Hermenêutica em Profundidade (HP, proposta por Thompson (2011. A HP evidencia o fato de que o objeto de análise é uma construção simbólica significativa, que exige uma interpretação. Como principal técnica de pesquisa, a análise narrativa, proposta por Motta (2007, com ênfase no movimento de construção de personagens jornalísticas (discursivas. As identidades narrativas construídas pelos dois jornais indicaram que ambos eram contrários à criação dos novos estados, porém por motivos divergentes. A bandeira do Pará foi o principal elemento utilizado para evocar a ideia de unidade. En 11 de diciembre de 2011, el plebiscito en

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

Directory of Open Access Journals (Sweden)

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.

Correlation Between Superheated Liquid Fragility And Onset Temperature Of Crystallization For Al-Based Amorphous Alloys

Directory of Open Access Journals (Sweden)

Guo J.

2015-06-01

Full Text Available Amorphous alloys or metallic glasses have attracted significant interest in the materials science and engineering communities due to their unique physical, mechanical, and chemical properties. The viscous flow of amorphous alloys exhibiting high strain rate sensitivity and homogeneous deformation is considered to be an important characteristic in thermoplastic forming processes performed within the supercooled liquid region because it allows superplastic-like deformation behavior. Here, the correlation between the superheated liquid fragility, and the onset temperature of crystallization for Al-based alloys, is investigated. The activation energy for viscous flow of the liquid is also investigated. There is a negative correlation between the parameter of superheated liquid fragility and the onset temperature of crystallization in the same Al-based alloy system. The activation energy decreases as the onset temperature of crystallization increases. This indicates that the stability of a superheated liquid can affect the thermal stability of the amorphous alloy. It also means that a liquid with a large superheated liquid fragility, when rapidly solidified, forms an amorphous alloy with a low thermal stability.

Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

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Yuping Luo

2010-04-01

Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

Limnological database for Par Pond: 1959 to 1980

International Nuclear Information System (INIS)

Tilly, L.J.

1981-03-01

A limnological database for Par Pond, a cooling reservoir for hot reactor effluent water at the Savannah River Plant, is described. The data are derived from a combination of research and monitoring efforts on Par Pond since 1959. The approximately 24,000-byte database provides water quality, primary productivity, and flow data from a number of different stations, depths, and times during the 22-year history of the Par Pond impoundment. The data have been organized to permit an interpretation of the effects of twenty years of cooling system operations on the structure and function of an aquatic ecosystem

The iso-structural viscosity, configurational entropy and fragility of oxide liquids

DEFF Research Database (Denmark)

Yue, Yuanzheng

2009-01-01

the variation of the configurational entropy (Sc) with temperature (T) are obtained from the Avramov-Milchev (AM) and the Vogel-Fulcher- Tammann (VFT) viscosity equations, respectively. The two Sc(T) functions exhibit different relations to the liquid fragility. The AM Sc(T) function is a power function...

Soluble urokinase plasminogen activator receptor (suPAR) in acute care

DEFF Research Database (Denmark)

Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck

2016-01-01

for age, sex, Charlson score and C reactive protein. Area under the curve for receiver operating characteristics curve analysis of suPAR for 30-day mortality was 0.84 (95% CI 0.81 to 0.86). Furthermore, in the entire cohort, women had slightly higher suPAR compared with men, and suPAR was associated...

The State of Synapses in Fragile X Syndrome

OpenAIRE

Pfeiffer, Brad E.; Huber, Kimberly M.

2009-01-01

Fragile X Syndrome is the most common inherited form of mental retardation and a leading genetic cause of autism. There is increasing evidence in both FXS and other forms of autism that alterations in synapse number, structure and function are associated and contribute to these prevalent diseases. FXS is caused by loss of function of the Fmr1 gene which encodes the RNA binding protein, FMRP. Therefore, FXS is a tractable model to understand synaptic dysfunction in cognitive disorders. FMRP is...

Theory of Mind Deficits in Children with Fragile X Syndrome

Science.gov (United States)

Cornish, K.; Burack, J. A.; Rahman, A.; Munir, F.; Russo, N.; Grant, C.

2005-01-01

Given the consistent findings of theory of mind deficits in children with autism, it would be extremely beneficial to examine the profile of theory of mind abilities in other clinical groups such as fragile X syndrome (FXS) and Down syndrome (DS). The aim of the present study was to assess whether boys with FXS are impaired in simple social…

The Fragile X Mental Retardation Protein, FMRP, Recognizes G-Quartets

Science.gov (United States)

Darnell, Jennifer C.; Warren, Stephen T.; Darnell, Robert B.

2004-01-01

Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling some aspects of memory and behavior. Recent evidence suggests that one of the predominant RNA motifs recognized by the FMRP…

Reading and Phonological Skills in Boys with Fragile X Syndrome

Science.gov (United States)

Klusek, Jessica; Hunt, Anna W.; Mirrett, Penny L.; Hatton, Deborah D.; Hooper, Stephen R.; Roberts, Jane E.; Bailey, Donald B.

2015-01-01

Although reading skills are critical for the success of individuals with intellectual disabilities, literacy has received little attention in fragile X syndrome (FXS). This study examined the literacy profile of FXS. Boys with FXS (n = 51; mean age 10.2 years) and mental age-matched boys with typical development (n = 35) participated in…

Brief Report: Autism Symptoms in Infants with Fragile X Syndrome

Science.gov (United States)

Roberts, Jane E.; Tonnsen, Bridgette L.; McCary, Lindsay M.; Caravella, Kelly E.; Shinkareva, Svetlana V.

2016-01-01

Fragile X syndrome (FXS) is the most common known genetic cause of autism spectrum disorder (ASD). Although 50-75% of children with FXS meet ASD criteria, no studies have compared ASD symptoms in infants with FXS versus other high risk groups, such as siblings of children with ASD (ASIBs). Using the Autism Observation Scale for Infants, our…

Fragile DNA Motifs Trigger Mutagenesis at Distant Chromosomal Loci in Saccharomyces cerevisiae

Science.gov (United States)

Saini, Natalie; Zhang, Yu; Nishida, Yuri; Sheng, Ziwei; Choudhury, Shilpa; Mieczkowski, Piotr; Lobachev, Kirill S.

2013-01-01

DNA sequences capable of adopting non-canonical secondary structures have been associated with gross-chromosomal rearrangements in humans and model organisms. Previously, we have shown that long inverted repeats that form hairpin and cruciform structures and triplex-forming GAA/TTC repeats induce the formation of double-strand breaks which trigger genome instability in yeast. In this study, we demonstrate that breakage at both inverted repeats and GAA/TTC repeats is augmented by defects in DNA replication. Increased fragility is associated with increased mutation levels in the reporter genes located as far as 8 kb from both sides of the repeats. The increase in mutations was dependent on the presence of inverted or GAA/TTC repeats and activity of the translesion polymerase Polζ. Mutagenesis induced by inverted repeats also required Sae2 which opens hairpin-capped breaks and initiates end resection. The amount of breakage at the repeats is an important determinant of mutations as a perfect palindromic sequence with inherently increased fragility was also found to elevate mutation rates even in replication-proficient strains. We hypothesize that the underlying mechanism for mutagenesis induced by fragile motifs involves the formation of long single-stranded regions in the broken chromosome, invasion of the undamaged sister chromatid for repair, and faulty DNA synthesis employing Polζ. These data demonstrate that repeat-mediated breaks pose a dual threat to eukaryotic genome integrity by inducing chromosomal aberrations as well as mutations in flanking genes. PMID:23785298

Validation of two conceptualizations of fragile self-esteem: Contingent high self-esteem and incongruent high self-esteem

OpenAIRE

Bodroža Bojana

2014-01-01

The aim of this research was to validate two aspects of fragile high self-esteem: a combination of contingent and high (explicit) self-esteem and a combination of high explicit and low implicit self-esteem (i.e. incongruent high self-esteem), as well as to examine the relationship between these aspects of fragile self-esteem and narcissism. No convergence was found between contingent high and incongruent high self-esteem. The result was consistent regardles...

ANALYSIS OF ENVIRONMENTAL FRAGILITY USING MULTI-CRITERIA ANALYSIS (MCE FOR INTEGRATED LANDSCAPE ASSESSMENT

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Abimael Cereda Junior

2014-01-01

Full Text Available The Geographic Information Systems brought greater possibilitie s to the representation and interpretation of the landscap e as well as the integrated a nalysis. However, this approach does not dispense technical and methodological substan tiation for achieving the computational universe. This work is grounded in ecodynamic s and empirical analysis of natural and anthr opogenic environmental Fragility a nd aims to propose and present an integrated paradigm of Multi-criteria Analysis and F uzzy Logic Model of Environmental Fragility, taking as a case study of the Basin of Monjolinho Stream in São Carlos-SP. The use of this methodology allowed for a reduct ion in the subjectivism influences of decision criteria, which factors might have its cartographic expression, respecting the complex integrated landscape.

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

Energy Technology Data Exchange (ETDEWEB)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment.

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

International Nuclear Information System (INIS)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil

2013-01-01

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment

Chromosome fragility in Freemartin cattle

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V. Barbieri

2010-04-01

Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.

Acute nursing care of the older adult with fragility hip fracture: An international perspective (Part 2)

LENUS (Irish Health Repository)

Maher, Ann Butler

2012-10-23

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):\\r\

Empirical Fragility Analysis of Buildings and Boats Damaged By the 2011 Great East Japan Tsunami and Their Practical Application

Science.gov (United States)

Suppasri, A.; Charvet, I.; Leelawat, N.; Fukutani, Y.; Muhari, A.; Futami, T.; Imamura, F.

2014-12-01

This study focused in turn on detailed data of buildings and boats damage caused by the 2011 tsunami in order to understand its main causes and provide damage probability estimates. Tsunami-induced building damage data was collected from field surveys, and includes inundation depth, building material, number of stories and occupancy type for more than 80,000 buildings. Numerical simulations with high resolution bathymetry and topography data were conducted to obtain characteristic tsunami measures such as flow velocity. These data were analyzed using advanced statistical methods, ordinal regression analysis to create not only empirical 2D tsunami fragility curves, but also 3D tsunami fragility surfaces for the first time. The effect of floating debris was also considered, by using a binary indicator of debris impact based on the proximity of a structure from a debris source (i.e. washed away building). Both the 2D and 3D fragility analyses provided results for each different building damage level, and different topography. While 2D fragility curves provide easily interpretable results relating tsunami flow depth to damage probability for different damage levels, 3D fragility surfaces allow for several influential tsunami parameters to be taken into account thus reduce uncertainty in the probability estimations. More than 20,000 damaged boats were used in the analysis similar to the one carried out on the buildings. Detailed data for each boat comprises information on the damage ratio (paid value over insured value), tonnage, engine type, material type and damage classification. The 2D and 3D fragility analyses were developed using representative tsunami heights for each port obtained from field surveys and flow velocities obtained from the aforementioned simulations. The results are currently being adapted for practical disaster mitigation. They are being integrated with the probabilistic tsunami hazard analysis, in order to create offshore and onshore

Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer

DEFF Research Database (Denmark)

Rasch, M.G.; Lund, I.K.; Hoyer-Hansen, G.

2008-01-01

identified in tissue and body fluids. It is well-established, that the total amount of all uPAR forms is a strong prognostic marker in different types of cancer. Using immunoassays, measuring the individual uPAR forms, has revealed that the cleaved uPAR forms are even stronger prognostic markers and have...... diagnostic utility. This review will focus on the mechanism of uPAR cleavage and the functional consequences, as well as the clinical applicability of cleaved uPAR forms Udgivelsesdato: 2008...

Trabecular bone score as a skeletal fragility index in acromegaly patients.

Science.gov (United States)

Hong, A R; Kim, J H; Kim, S W; Kim, S Y; Shin, C S

2016-03-01

Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients. Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients. We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis. Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041). Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.

Fragile X Premutation Carrier Epidemiology and Symptomatology in Israel-Results from a Tertiary Child Developmental Center.

Science.gov (United States)

Gabis, Lidia V; Gruber, Noah; Berkenstadt, Michal; Shefer, Shahar; Attia, Odelia Leon; Mula, Dana; Cohen, Yoram; Elizur, Shai E

2016-10-01

Fragile X syndrome (FXS) is the most prevalent known genetically inherited cause for autism and intellectual disability. Premutation state can cause several clinical disorders as well. We aimed to perform a nesting approach to acquire data with regard to first degree relatives of index fragile X cases at the largest child development center in Israel in order to map characteristics of Israeli FXS permutation women carriers. Seventy-nine women were referred due to a related fragile X syndrome patient, mainly an offspring or sibling. General information regarding demographics, ethnicity, and associated medical conditions were collected using interviews and structured questionnaires. Thirteen (17 %) of the women who were referred as "carrier" were proven to be actually full mutation. The mean years of education were 14 (±1.51, range 12-17). Twenty-one women (27 %) originated from Tunisia (mainly from the island of Djerba). Ten women (13 %) reported delivery of their affected offspring beyond 41 gestational weeks. Twenty-two percent of women with premutation reported symptoms consistent with learning difficulties, mainly dyscalculia, and 14 % reported ADHD symptoms. Awareness about clinical disorders of the carriers was existent only in 25 % of the patients. Increased awareness and knowledge dissemination concerning premutation symptomatology and associated medical conditions are warranted. We suggest a national registry to be installed in different countries in order to identify fragile X premutation carriers at increased risk for various medical complications.

It's Not about "You," It's about "Us": A Black Woman Administrator's Efforts to Disrupt White Fragility in an Urban School

Science.gov (United States)

Patton, Lori D.; Jordan, Jodi L.

2017-01-01

This case centers on a Black woman school administrator and efforts to disrupt Whiteness among an urban elementary school teaching staff. The case details the resistance she encounters while encouraging teachers to confront "White fragility" and consider how their fragile perspectives on race and racism shape how they educate Black…

A Bipolar Spindle of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation

DEFF Research Database (Denmark)

Gayathri, P; Fujii, T; Møller-Jensen, Jakob

2012-01-01

the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture...... of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles....

Visual Attention and Autistic Behavior in Infants with Fragile X Syndrome

Science.gov (United States)

Roberts, Jane E.; Hatton, Deborah D.; Long, Anna C. J.; Anello, Vittoria; Colombo, John

2012-01-01

Aberrant attention is a core feature of fragile X syndrome (FXS), however, little is known regarding the developmental trajectory and underlying physiological processes of attention deficits in FXS. Atypical visual attention is an early emerging and robust indicator of autism in idiopathic (non-FXS) autism. Using a biobehavioral approach with gaze…

Non-fragile consensus algorithms for a network of diffusion PDEs with boundary local interaction

Science.gov (United States)

Xiong, Jun; Li, Junmin

2017-07-01

In this study, non-fragile consensus algorithm is proposed to solve the average consensus problem of a network of diffusion PDEs, modelled by boundary controlled heat equations. The problem deals with the case where the Neumann-type boundary controllers are corrupted by additive persistent disturbances. To achieve consensus between agents, a linear local interaction rule addressing this requirement is given. The proposed local interaction rules are analysed by applying a Lyapunov-based approach. The multiplicative and additive non-fragile feedback control algorithms are designed and sufficient conditions for the consensus of the multi-agent systems are presented in terms of linear matrix inequalities, respectively. Simulation results are presented to support the effectiveness of the proposed algorithms.

PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity

Directory of Open Access Journals (Sweden)

Henrique FUKUSHIMA

Full Text Available Abstract Recent studies investigating protease-activated receptor type 2 (PAR-2 suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF of patients with moderate chronic periodontitis (MP. The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19 at baseline, and from MP patients (n = 19 and severe chronic periodontitis (SP (n = 19 patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR. PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05 PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

Science.gov (United States)

Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

2015-07-02

Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

Financial structure, financial development and banking fragility: International evidence

OpenAIRE

Ruiz-Porras, Antonio

2008-01-01

We study the effects of financial structure and financial development on banking fragility. We develop our study by using fixed-effects panel-data regressions and by controlling the effects of certain banking indicators. We use individual and principal-components indicators of the activity, size and efficiency of intermediaries and markets. The indicators include data for 211 countries between 1990 and 2003. Our main findings suggest that banking stability is enhanced in market-based financia...

Paternal Incarceration and Father–Child Contact in Fragile Families

OpenAIRE

Geller, Amanda

2013-01-01

High rates of incarceration in the United States have motivated a broad examination of the effects of parental incarceration on child well-being. Although a growing literature documents challenges facing the children of incarcerated men, most incarcerated fathers lived apart from their children before their arrest, raising questions of whether they were sufficiently involved with their families for their incarceration to affect their children. The author used the Fragile Families and Child We...

Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

Science.gov (United States)

Mazzocco, Michele M. M.

2001-01-01

This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

Initiative Villes sûres et inclusive : Un point de départ essentiel pour ...

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

18 mai 2016 ... Ces villes fragiles, dirigées par des pouvoirs municipaux qui ne sont pas en mesure d'offrir services élémentaires et logement à leurs citoyens – sont de plus ... Je crois qu'on observe une dégradation des conditions dans toute situation fragile; qu'il s'agit d'une période de transition — et que c'est l'occasion ...

Emerging pharmacologic treatment options for fragile X syndrome

Science.gov (United States)

Schaefer, Tori L; Davenport, Matthew H; Erickson, Craig A

2015-01-01

Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and autism spectrum disorder. Caused by a silenced fragile X mental retardation 1 gene and the subsequent deficiency in fragile X mental retardation protein, patients with FXS experience a range of physical, behavioral, and intellectual debilitations. The FXS field, as a whole, has recently met with some challenges, as several targeted clinical trials with high expectations of success have failed to elucidate significant improvements in a variety of symptom domains. As new clinical trials in FXS are planned, there has been much discussion about the use of the commonly used clinical outcome measures, as well as study design considerations, patient stratification, and optimal age range for treatment. The evidence that modification of these drug targets and use of these failed compounds would prove to be efficacious in human clinical study were rooted in years of basic and translational research. There are questions arising as to the use of the mouse models for studying FXS treatment development. This issue is twofold: many of the symptom domains and molecular and biochemical changes assessed and indicative of efficacy in mouse model study are not easily amenable to clinical trials in people with FXS because of the intolerability of the testing paradigm or a lack of noninvasive techniques (prepulse inhibition, sensory hypersensitivity, startle reactivity, or electrophysiologic, biochemical, or structural changes in the brain); and capturing subtle yet meaningful changes in symptom domains such as sociability, anxiety, and hyperactivity in human FXS clinical trials is challenging with the currently used measures (typically parent/caregiver rating scales). Clinicians, researchers, and the pharmaceutical industry have all had to take a step back and critically evaluate the way we think about how to best optimize future investigations into pharmacologic FXS treatments. As new clinical

Earthquake Magnitude and Shaking Intensity Dependent Fragility Functions for Rapid Risk Assessment of Buildings

Directory of Open Access Journals (Sweden)

Marie-José Nollet

2018-01-01

Full Text Available An integrated web application, referred to as ER2 for rapid risk evaluator, is under development for a user-friendly seismic risk assessment by the non-expert public safety community. The assessment of likely negative consequences is based on pre-populated databases of seismic, building inventory and vulnerability parameters. To further accelerate the computation for near real-time analyses, implicit building fragility curves were developed as functions of the magnitude and the intensity of the seismic shaking defined with a single intensity measure, input spectral acceleration at 1.0 s implicitly considering the epicentral distance and local soil conditions. Damage probabilities were compared with those obtained with the standard fragility functions explicitly considering epicentral distances and local site classes in addition to the earthquake magnitudes and respective intensity of the seismic shaking. Different seismic scenarios were considered first for 53 building classes common in Eastern Canada, and then a reduced number of 24 combined building classes was proposed. Comparison of results indicate that the damage predictions with implicit fragility functions for short (M ≤ 5.5 and medium strong motion duration (5.5 < M ≤ 7.5 show low variation with distance and soil class, with average error of less than 3.6%.

Par and IR reflectance, transmittance, and absorptance of four crop canopies

International Nuclear Information System (INIS)

Wanjura, D.F.; Hatfield, J.L.

1986-01-01

Reflectance, transmittance and absorptance of electromagnetic radiation by cotton, soybeans, grain sorghum, and sunflower was measured at three growth stages in two wavebands (PAR: 0.4 to 0.7 pun and IR: 0.7 to 1.1 yim). As leaf area increased in each crop there were increases in IR reflectance and PAR absorptance and decreases in PAR reflectance and both PAR and IR transmittance. IR radiation was concentrated at the soil surface between rows by reflectance from the sides of canopies when crop cover was less than 80%. Across all crops one parameter, leaf overlap index, explained 81 and 71% of the PAR reflectance and another, crop cover, explained 86 and 94% of IR reflectance from rows and interrows, respectively. Attenuation of PAR radiation through the canopies of cotton and sunflower was similar (K = 0.62 and 0.67) but different from that of soybeans and grain sorghum (K = 0.46 and 0.43) which were the same

Épidémiologie de l'intoxication par envenimation chez les enfants ...

African Journals Online (AJOL)

Introduction: L'intoxication par envenimation est l'ensemble des manifestations locales et générales induites par la pénétration dans l'organisme d'une substance toxique produite par un animal venimeux. Le but de notre travail était d'étudier les signes cliniques des intoxications par envenimation chez les enfants de 0 à 15 ...

PARs for combustible gas control in advanced light water reactors

International Nuclear Information System (INIS)

Hosler, J.; Sliter, G.

1997-01-01

This paper discusses the progress being made in the United States to introduce passive autocatalytic recombiner (PAR) technology as a cost-effective alternative to electric recombiners for controlling combustible gas produced in postulated accidents in both future Advanced Light Water Reactors (ALWRs) and certain U. S. operating nuclear plants. PARs catalytically recombine hydrogen and oxygen, gradually producing heat and water vapor. They have no moving parts and are self-starting and self-feeding, even under relatively cold and wet containment conditions. Buoyancy of the hot gases they create sets up natural convective flow that promotes mixing of combustible gases in a containment. In a non-inerted ALWR containment, two approaches each employing a combination of PARs and igniters are being considered to control hydrogen in design basis and severe accidents. In pre-inerted ALWRs, PARs alone control radiolytic oxygen produced in either accident type. The paper also discusses regulatory feedback regarding these combustible gas control approaches and describes a test program being conducted by the Electric Power Research Institute (EPRI) and Electricite de France (EdF) to supplement the existing PAR test database with performance data under conditions of interest to U.S. plants. Preliminary findings from the EPRI/EdF PAR model test program are included. Successful completion of this test program and confirmatory tests being sponsored by the U. S. NRC are expected to pave the way for use of PARs in ALWRs and operating plants. (author)

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.

Discriminating Down Syndrome and Fragile X Syndrome Based on Language Ability

Science.gov (United States)

Finestack, Lizbeth H.; Sterling, Audra M.; Abbeduto, Leonard

2013-01-01

This study compared the receptive and expressive language profiles of verbally expressive children and adolescents with Down Syndrome (DS) and those with Fragile X syndrome (FXS) and examined the extent to which these profiles reliably differentiate the diagnostic groups. A total of twenty-four verbal participants with DS (mean age: 12 years),…

Safe and Inclusive Cities: A key entry point to addressing fragility ...

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

3 juil. 2015 ... Job seekers are converging on cities to find work, and in many countries urban slums are sprawling. Fragile cities — where municipal powers fail to provide citizens with basic services and shelter — are increasingly at risk of extreme violence. In an interview with the Independent Commission on ...

Astrocytic Contributions to Synaptic and Learning Abnormalities in a Mouse Model of Fragile X Syndrome.

Science.gov (United States)

Hodges, Jennifer L; Yu, Xinzhu; Gilmore, Anthony; Bennett, Hannah; Tjia, Michelle; Perna, James F; Chen, Chia-Chien; Li, Xiang; Lu, Ju; Zuo, Yi

2017-07-15

Fragile X syndrome (FXS) is the most common type of mental retardation attributable to a single-gene mutation. It is caused by FMR1 gene silencing and the consequent loss of its protein product, fragile X mental retardation protein. Fmr1 global knockout (KO) mice recapitulate many behavioral and synaptic phenotypes associated with FXS. Abundant evidence suggests that astrocytes are important contributors to neurological diseases. This study investigates astrocytic contributions to the progression of synaptic abnormalities and learning impairments associated with FXS. Taking advantage of the Cre-lox system, we generated and characterized mice in which fragile X mental retardation protein is selectively deleted or exclusively expressed in astrocytes. We performed in vivo two-photon imaging to track spine dynamics/morphology along dendrites of neurons in the motor cortex and examined associated behavioral defects. We found that adult astrocyte-specific Fmr1 KO mice displayed increased spine density in the motor cortex and impaired motor-skill learning. The learning defect coincided with a lack of enhanced spine dynamics in the motor cortex that normally occurs in response to motor skill acquisition. Although spine density was normal at 1 month of age in astrocyte-specific Fmr1 KO mice, new spines formed at an elevated rate. Furthermore, fragile X mental retardation protein expression in only astrocytes was insufficient to rescue most spine or behavioral defects. Our work suggests a joint astrocytic-neuronal contribution to FXS pathogenesis and reveals that heightened spine formation during adolescence precedes the overabundance of spines and behavioral defects found in adult Fmr1 KO mice. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas

Science.gov (United States)

Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.

2010-01-01

Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident. PMID:21991216

Fragile X Mental Retardation Protein (FMRP) controls diacylglycerol kinase activity in neurons.

Science.gov (United States)

Tabet, Ricardos; Moutin, Enora; Becker, Jérôme A J; Heintz, Dimitri; Fouillen, Laetitia; Flatter, Eric; Krężel, Wojciech; Alunni, Violaine; Koebel, Pascale; Dembélé, Doulaye; Tassone, Flora; Bardoni, Barbara; Mandel, Jean-Louis; Vitale, Nicolas; Muller, Dominique; Le Merrer, Julie; Moine, Hervé

2016-06-28

Fragile X syndrome (FXS) is caused by the absence of the Fragile X Mental Retardation Protein (FMRP) in neurons. In the mouse, the lack of FMRP is associated with an excessive translation of hundreds of neuronal proteins, notably including postsynaptic proteins. This local protein synthesis deregulation is proposed to underlie the observed defects of glutamatergic synapse maturation and function and to affect preferentially the hundreds of mRNA species that were reported to bind to FMRP. How FMRP impacts synaptic protein translation and which mRNAs are most important for the pathology remain unclear. Here we show by cross-linking immunoprecipitation in cortical neurons that FMRP is mostly associated with one unique mRNA: diacylglycerol kinase kappa (Dgkκ), a master regulator that controls the switch between diacylglycerol and phosphatidic acid signaling pathways. The absence of FMRP in neurons abolishes group 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkκ expression. The reduction of Dgkκ in neurons is sufficient to cause dendritic spine abnormalities, synaptic plasticity alterations, and behavior disorders similar to those observed in the FXS mouse model. Overexpression of Dgkκ in neurons is able to rescue the dendritic spine defects of the Fragile X Mental Retardation 1 gene KO neurons. Together, these data suggest that Dgkκ deregulation contributes to FXS pathology and support a model where FMRP, by controlling the translation of Dgkκ, indirectly controls synaptic proteins translation and membrane properties by impacting lipid signaling in dendritic spine.

Les territoires fragiles dans la région alpine : une proposition de lecture entre innovation et marginalité

Directory of Open Access Journals (Sweden)

Federica Corrado

2010-05-01

Full Text Available 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.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.

Detect Image Tamper by Semi-Fragile Digital Watermarking

Institute of Scientific and Technical Information of China (English)

LIUFeilong; WANGYangsheng

2004-01-01

To authenticate the integrity of image while resisting some valid image processing such as JPEG compression, a semi-fragile image watermarking is described. Image name, one of the image features, has been used as the key of pseudo-random function to generate the special watermarks for the different image. Watermarks are embedded by changing the relationship between the blocks' DCT DC coefficients, and the image tamper are detected with the relationship of these DCT DC coefficients.Experimental results show that the proposed technique can resist JPEG compression, and detect image tamper in the meantime.

Elusloom lennukiga puhkusele / Inge Parring

Index Scriptorium Estoniae

Parring, Inge

2003-01-01

Ilmunud ka: Delovõje Vedomosti 1. okt. lk. 13. Air Cargo Estonia/ACE Logisticsi müügijuht Inge Parring tutvustab elusloomade transpordivõimalusi. Vt. samas: Loomade transportimiseks vajalikud dokumendid

suPAR

DEFF Research Database (Denmark)

Eugen-Olsen, Jesper; Giamarellos-Bourboulis, Evangelos J

2015-01-01

Investigation of biomarkers that can promptly predict unfavourable outcome of critically illness is an emerging necessity taking into consideration the need for early intervention, the shortage of available beds in intensive care units and the considerable cost of hospitalisation. The most...... promising biomarker is soluble urokinase-type plasminogen activator receptor (suPAR). Three studies in large populations of critically ill patients and patients admitted to the emergency department have shown that concentrations >12ng/mL can safely predict unfavourable outcome. This review presents...

Urine suPAR levels compared with plasma suPAR levels as predictors of post-consultation mortality risk among individuals assumed to be TB-negative: a prospective cohort study

DEFF Research Database (Denmark)

Rabna, Paulo; Andersen, Andreas; Wejse, Christian

2010-01-01

-suPAR was measured using a commercial ELISA (suPARnostic®). We found that U-suPAR carried significant prognostic information on mortality for HIV-infected subjects with an area under the ROC curve of 0.75. For HIV-negative individuals, little or no prognostic effect was observed. However, in both HIV positives...... and negatives, the predictive effect of U-suPAR was found to be inferior to that of P-suPAR....

Brésil : La contamination par le mercure en Amazonie | CRDI ...

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

11 janv. 2011 ... En tentant de déceler la source de la contamination de l'Amazone par le ... par Jean-Rémy Davy Guimaraes de l'Université fédérale de Rio de Janeiro ... ces mattes est circonscrite par la conservation et la restauration en rive.

The Fragility of Employability: A Dynamic Perspective and Examples from the Netherlands

NARCIS (Netherlands)

Sanders, J.; Dorenbosch, L.; Blonk, R.

2015-01-01

This contribution aims to provide a framework for viewing the fragility of employability and potentially fruitful routes for making employability more sustainable. A second goal, is to inspire readers with examples from the Netherlands, to create and test promising interventions, so that a broad set

Externalizing shame responses in children: The role of fragile positive self-esteem

NARCIS (Netherlands)

Thomaes, Sander

2007-01-01

When faced with shame, children can either respond in submissive ways to withdraw from their environment or in externalizing ways to oppose their environment. This study tested the hypothesis that fragile-positive views of self predispose children to respond in externalizing ways to shame

Externalizing shame responses in children: The role of fragile-positive self-esteem

NARCIS (Netherlands)

Thomaes, S.; Stegge, G.T.M.; Olthof, T.

2007-01-01

When faced with shame, children can either respond in submissive ways to withdraw from their environment or in externalizing ways to oppose their environment. This study tested the hypothesis that fragile-positive views of self predispose children to respond in externalizing ways to shame

The FMR1 gene and fragile X-associated tremor/ataxia syndrome

NARCIS (Netherlands)

J. Brouwer (Jaap); R.A. Willemsen (Ralph); B.A. Oostra (Ben)

2009-01-01

textabstractThe CGG-repeat present in the 5′UTR of the FMR1 gene is unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In fragile X patients, a repeat length exceeding 200 CGGs (full mutation: FM) generally leads to methylation of the repeat

New mechanisms and targets in the treatment of bone fragility.

Science.gov (United States)

Martin, T John; Seeman, Ego

2007-01-01

Bone modelling and remodelling are cell-mediated processes responsible for the construction and reconstruction of the skeleton throughout life. These processes are chiefly mediated by locally generated cytokines and growth factors that regulate the differentiation, activation, work and life span of osteoblasts and osteoclasts, the cells that co-ordinate the volumes of bone resorbed and formed. In this way, the material composition and structural design of bone is regulated in accordance with its loading requirements. Abnormalities in this regulatory system compromise the material and structural determinants of bone strength producing bone fragility. Understanding the intercellular control processes that regulate bone modelling and remodelling is essential in planning therapeutic approaches to prevention and treatment of bone fragility. A great deal has been learnt in the last decade. Clinical trials carried out exclusively with drugs that inhibit bone resorption have identified the importance of reducing the rate of bone remodelling and so the progression of bone fragility to achieved fracture reductions of approx. 50%. These trials have also identified limitations that should be placed upon interpretation of bone mineral density changes in relation to treatment. New resorption inhibitors are being developed, based on mechanisms of action that are different from existing drugs. Some of these might offer resorption inhibition without reducing bone formation. More recent research has provided the first effective anabolic therapy for bone reconstruction. Daily injections of PTH (parathyroid hormone)-(1-34) have been shown in preclinical studies and in a large clinical trial to increase bone tissue mass and reduce the risk of fractures. The action of PTH differs from that of the resorption inhibitors, but whether it is more effective in fracture reduction is not known. Understanding the cellular and molecular mechanisms of PTH action, particularly its interactions with

Fragile X-Associated Tremor Ataxia Syndrome: The Expanding Clinical Picture, Pathophysiology, Epidemiology, and Update on Treatment

Directory of Open Access Journals (Sweden)

Deborah A. Hall

2012-05-01

Full Text Available Fragile X-associated tremor/ataxia syndrome (FXTAS is a progressive degenerative movement disorder characterized by kinetic tremor, cerebellar gait ataxia, parkinsonism, and cognitive decline. This disorder occurs in both males and females, frequently in families with children who have fragile X syndrome. The clinical features of this disorder, both classic and newly described, are summarized in this paper. In screening studies, fragile X mental retardation 1 (FMR1 gene premutation (55–200 CGG expansions are most frequently seen in men with ataxia who have tested negative for spinocerebellar ataxias. Since the original description, the classic FXTAS phenotype has now been reported in females and in carriers of smaller (45–54 CGG and larger (>200 CGG expansions in FMR1. Premutation carriers may present with a Parkinson disease phenotype or hypotension, rather than with tremor and/or ataxia. Parkinsonism and gait ataxia may also be seen in individuals with gray zone (41–54 CGG expansions. Studies regarding medication to treat the symptoms in FXTAS are few in number and suggest that medications targeted to specific symptoms, such as kinetic tremor or gait ataxia, may be most beneficial. Great progress has been made in regards to FXTAS research, likely given the readily available gene test and the screening of multiple family members, including parents and grandparents, of fragile X syndrome children. Expansion of genotypes and phenotypes in the disorder may suggest that a broader disease definition might be necessary in the future.

Electron microscope study of vacancy clusters produced by quenching in magnesium; Etude par microscopie electronique des amas de lacunes crees par trempe dans le magnesium

Energy Technology Data Exchange (ETDEWEB)

Levy, V; Espinasse, J; Mairy, C; Hillairet, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1969-07-01

Vacancy clustering in quenched magnesium has been studied by transmission electron microscopy. The nature of the vacancy loops observed, seems to depend essentially on the impurity content of the metal; this effect can be attributed to a variation of the stacking fault energy of magnesium due to impurities. (authors) [French] On a etudie par microscopie electronique en transmission les defauts crees par trempe dans le magnesium. Un effet considerable des impuretes du metal sur la nature des boucles obtenues par condensation de lacunes a ete mis en evidence; cet effet semble s'expliquer de facon satisfaisante par un abaissement de l'energie de faute d'empilement du magnesium du aux impuretes. (auteur)

The fragile X mental retardation protein has nucleic acid chaperone properties.

Science.gov (United States)

Gabus, Caroline; Mazroui, Rachid; Tremblay, Sandra; Khandjian, Edouard W; Darlix, Jean-Luc

2004-01-01

The fragile X syndrome is the most common cause of inherited mental retardation resulting from the absence of the fragile X mental retardation protein (FMRP). FMRP contains two K-homology (KH) domains and one RGG box that are landmarks characteristic of RNA-binding proteins. In agreement with this, FMRP associates with messenger ribonucleoparticles (mRNPs) within actively translating ribosomes, and is thought to regulate translation of target mRNAs, including its own transcript. To investigate whether FMRP might chaperone nucleic acid folding and hybridization, we analysed the annealing and strand exchange activities of DNA oligonucleotides and the enhancement of ribozyme-directed RNA substrate cleavage by FMRP and deleted variants relative to canonical nucleic acid chaperones, such as the cellular YB-1/p50 protein and the retroviral nucleocapsid protein HIV-1 NCp7. FMRP was found to possess all the properties of a potent nucleic acid chaperone, requiring the KH motifs and RGG box for optimal activity. These findings suggest that FMRP may regulate translation by acting on RNA-RNA interactions and thus on the structural status of mRNAs.

Non-fragile switched H∞ control for morphing aircraft with asynchronous switching

Directory of Open Access Journals (Sweden)

Haoyu CHENG

2017-06-01

Full Text Available This paper deals with the problem of non-fragile linear parameter-varying (LPV H∞ control for morphing aircraft with asynchronous switching. The switched LPV model of morphing aircraft is established by Jacobian linearization approach according to the nonlinear model. The data missing is taken into account in the link from sensors to controllers and the link from controllers to actuators, which satisfies Bernoulli distribution. The non-fragile switched LPV controllers are constructed with consideration of the uncertainties of controllers and asynchronous switching phenomenon. The parameter-dependent Lyapunov functional method and mode-dependent average dwell time (MDADT method are combined to guarantee the stability and prescribed performance of the system. The sufficient conditions on the solvability of the problem are derived in the form of linear matrix inequalities (LMI. In order to achieve higher efficiency of the designing process, an algorithm is applied to divide the whole set into subsets automatically. Simulation results are provided to verify the effectiveness and superiority of the method in the paper.

ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

Science.gov (United States)

Dubarry, Nelly; Pasta, Franck; Lane, David

2006-01-01

Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

MODIS-derived daily PAR simulation from cloud-free images and its validation

Energy Technology Data Exchange (ETDEWEB)

Chen, Liangfu; Gu, Xingfa; Tian, Guoliang [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); The Center for National Spaceborne Demonstration, Beijing 100101 (China); Gao, Yanhua [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101 (China); Yang, Lei [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); Jilin University, Changchun 130026 (China); Liu, Qinhuo [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China)

2008-06-15

In this paper, a MODIS-derived daily PAR (photosynthetically active radiation) simulation model from cloud-free image over land surface has been developed based on Bird and Riordan's model. In this model, the total downwelling spectral surface irradiance is divided into two parts: one is beam irradiance, and another is diffuse irradiance. The attenuation of solar beam irradiance comprises scattering by the gas mixture, absorption by ozone, the gas mixture and water vapor, and scattering and absorption by aerosols. The diffuse irradiance is scattered out of the direct beam and towards the surface. The multiple ground-air interactions have been taken into account in the diffuse irradiance model. The parameters needed in this model are atmospheric water vapor content, aerosol optical thickness and spectral albedo ranging from 400 nm to 700 nm. They are all retrieved from MODIS data. Then, the instantaneous photosynthetically available radiation (IPAR) is integrated by using a weighted sum at each of the visible MODIS wavebands. Finally, a daily PAR is derived by integration of IPAR. In order to validate the MODIS-derived PAR model, we compared the field PAR measurements in 2003 and 2004 against the simulated PAR. The measurements were made at the Qianyanzhou ecological experimental station, Chinese Ecosystem Research Network. A total of 54 days of cloud-free MODIS L1B level images were used for the PAR simulation. Our results show that the simulated PAR is consistent with field measurements, where the correlation coefficient of linear regression between calculated PAR and measured PAR is 0.93396. However, there were some uncertainties in the comparison of 1 km pixel PAR with the tower flux stand measurement. (author)

Contrasting dynamics of fragile and non-fragile polyalcohols through the glass, and dynamical, transitions: A comparison of neutron scattering and dielectric relaxation data for sorbitol and glycerol.

Science.gov (United States)

Migliardo, F; Angell, C A; Magazù, S

2017-01-01

Glycerol and sorbitol are glass-forming hydrogen-bonded systems characterized by intriguing properties which make these systems very interesting also from the applications point of view. The goal of this work is to relate the hydrogen-bonded features, relaxation dynamics, glass transition properties and fragility of these systems, in particular to seek insight into their very different liquid fragilities. The comparison between glycerol and sorbitol is carried out by collecting the elastic incoherent neutron scattering (EINS) intensity as a function of temperature and of the instrumental energy resolution. Intensity data vs temperature and resolution are analyzed in terms of thermal restraint and Resolution Elastic Neutron Scattering (RENS) approaches. The number of OH groups, which are related to the connecting sites, is a significant parameter both in the glass transition and in the dynamical transition. On the other hand, the disordered nature of sorbitol is confirmed by the existence of different relaxation processes. From the applications point of view, glycerol and sorbitol have remarkable bioprotectant properties which make these systems useful in different technological and industrial fields. Furthermore, polyols are rich in glassforming liquid phenomenology and highly deserving of study in their own right. The comparison of EINS and calorimetric data on glycerol and sorbitol helps provide a connection between structural relaxation, dynamical transition, glass transition, and fragility. The evaluation of the inflection point in the elastic intensity behavior as a function of temperature and instrumental energy resolution provides a confirmation of the validity of the RENS approach. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazù and Dr. Federica Migliardo. Copyright © 2016. Published by Elsevier B.V.

Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.

Science.gov (United States)

Hunter, Jessica Ezzell; Epstein, Michael P; Tinker, Stuart W; Charen, Krista H; Sherman, Stephanie L

2008-09-01

The fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5' untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of approximately 55-199, termed premutation alleles, are associated with an increased risk for fragile-X-associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random-effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55-0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P-values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency. (c) 2008 Wiley-Liss, Inc.

PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

Science.gov (United States)

Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

2017-01-26

Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

Financial fragility, sovereign default risk and the limits to commercial bank bail-outs

NARCIS (Netherlands)

van Wijnbergen, S.; van der Kwaak, C.

2013-01-01

We analyse the poisonous interaction between bank rescues, financial fragility and sovereign debt discounts. In our model balance sheet constrained financial intermediaries finance both capital expenditure of intermediate goods producers and government deficits. The financial intermediaries face the

Fragile X mental retardation protein stimulates ribonucleoprotein assembly of influenza A virus

Science.gov (United States)

Zhou, Zhuo; Cao, Mengmeng; Guo, Yang; Zhao, Lili; Wang, Jingfeng; Jia, Xue; Li, Jianguo; Wang, Conghui; Gabriel, Gülsah; Xue, Qinghua; Yi, Yonghong; Cui, Sheng; Jin, Qi; Wang, Jianwei; Deng, Tao

2014-02-01

The ribonucleoprotein (RNP) of the influenza A virus is responsible for the transcription and replication of viral RNA in the nucleus. These processes require interplay between host factors and RNP components. Here, we report that the Fragile X mental retardation protein (FMRP) targets influenza virus RNA synthesis machinery and facilitates virus replication both in cell culture and in mice. We demonstrate that FMRP transiently associates with viral RNP and stimulates viral RNP assembly through RNA-mediated interaction with the nucleoprotein. Furthermore, the KH2 domain of FMRP mediates its association with the nucleoprotein. A point mutation (I304N) in the KH2 domain, identified from a Fragile X syndrome patient, disrupts the FMRP-nucleoprotein association and abolishes the ability of FMRP to participate in viral RNP assembly. We conclude that FMRP is a critical host factor used by influenza viruses to facilitate viral RNP assembly. Our observation reveals a mechanism of influenza virus RNA synthesis and provides insights into FMRP functions.

An investigation on vulnerability assessment of steel structures with thin steel shear wall through development of fragility curves

OpenAIRE

Mohsen Gerami; Saeed Ghaffari; Amir Mahdi Heidari Tafreshi

2017-01-01

Fragility curves play an important role in damage assessment of buildings. Probability of damage induction to the structure against seismic events can be investigated upon generation of afore mentioned curves. In current research 360 time history analyses have been carried out on structures of 3, 10 and 20 story height and subsequently fragility curves have been adopted. The curves are developed based on two indices of inter story drifts and equivalent strip axial strains of the shear wall. T...

Molecular mechanism of bundle formation by the bacterial actin ParM

Energy Technology Data Exchange (ETDEWEB)

Popp, David, E-mail: dpopp@imcb.a-star.edu.sg [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673 Singapore (Singapore); Narita, Akihiro [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Nagoya University Graduate School of Science, Structural Biology Research Center and Division of Biological Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Iwasa, Mitsusada [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Maeda, Yuichiro [ERATO ' Actin Filament Dynamics' Project, Japan Science and Technology Corporation, c/o RIKEN Harima Institute at Spring 8, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Nagoya University Graduate School of Science, Structural Biology Research Center and Division of Biological Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Robinson, Robert C. [Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673 Singapore (Singapore)

2010-01-22

The actin homolog ParM plays a microtubule-like role in segregating DNA prior to bacterial cell division. Fluorescence and cryo-electron microscopy have shown that ParM forms filament bundles between separating DNA plasmids in vivo. Given the lack of ParM bundling proteins it remains unknown how ParM bundles form at the molecular level. Here we show using time-lapse TIRF microscopy, under in vitro molecular crowding conditions, that ParM-bundle formation consists of two distinct phases. At the onset of polymerization bundle thickness and shape are determined in the form of nuclei of short helically disordered filaments arranged in a liquid-like lattice. These nuclei then undergo an elongation phase whereby they rapidly increase in length. At steady state, ParM bundles fuse into one single large aggregate. This behavior had been predicted by theory but has not been observed for any other cytomotive biopolymer, including F-actin. We employed electron micrographs of ParM rafts, which are 2-D analogs of 3-D bundles, to identify the main molecular interfilament contacts within these suprastructures. The interface between filaments is similar for both parallel and anti-parallel orientations and the distribution of filament polarity is random within a bundle. We suggest that the interfilament interactions are not due to the interactions of specific residues but rather to long-range, counter ion mediated, electrostatic attractive forces. A randomly oriented bundle ensures that the assembly is rigid and that DNA may be captured with equal efficiency at both ends of the bundle via the ParR binding protein.

Longitudinal Changes in Intellectual Development in Children with Fragile X Syndrome

Science.gov (United States)

Hall, Scott S.; Burns, David D.; Lightbody, Amy A.; Reiss, Allan L.

2008-01-01

Structural equation modeling (SEM) was used to examine the development of intellectual functioning in 145 school-age pairs of siblings. Each pair included one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of children were evaluated on the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) at time 1 and 80…

Deficient Sleep in Mouse Models of Fragile X Syndrome

Directory of Open Access Journals (Sweden)

R. Michelle Saré

2017-09-01

Full Text Available In patients with fragile X syndrome (FXS, sleep problems are commonly observed but are not well characterized. In animal models of FXS (dfmr1 and Fmr1 knockout (KO/Fxr2 heterozygote circadian rhythmicity is affected, but sleep per se has not been examined. We used a home-cage monitoring system to assess total sleep time in both light and dark phases in Fmr1 KO mice at different developmental stages. Fmr1 KOs at P21 do not differ from controls, but genotype × phase interactions in both adult (P70 and P180 groups are statistically significant indicating that sleep in Fmr1 KOs is reduced selectively in the light phase compared to controls. Our results show the emergence of abnormal sleep in Fmr1 KOs during the later stages of brain maturation. Treatment of adult Fmr1 KO mice with a GABAB agonist, R-baclofen, did not restore sleep duration in the light phase. In adult (P70 Fmr1 KO/Fxr2 heterozygote animals, total sleep time was further reduced, once again in the light phase. Our data highlight the importance of the fragile X genes (Fmr1 and Fxr2 in sleep physiology and confirm the utility of these mouse models in enhancing our understanding of sleep disorders in FXS.

Neurological and endocrine phenotypes of fragile X carrier women.

Science.gov (United States)

Hall, D; Todorova-Koteva, K; Pandya, S; Bernard, B; Ouyang, B; Walsh, M; Pounardjian, T; Deburghraeve, C; Zhou, L; Losh, M; Leehey, M; Berry-Kravis, E

2016-01-01

Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. Premutation carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 ± 24.9 in the FMR1 PMC women. Seventy percent of the PMC women had an abnormal neurological examination. PMC women had significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Par Pond vegetation status Summer 1995 -- October survey descriptive summary

International Nuclear Information System (INIS)

Mackey, H.E. Jr.; Riley, R.S.

1995-11-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

Par Pond vegetation status Summer 1995 -- September survey descriptive summary

International Nuclear Information System (INIS)

Mackey, H.E. Jr.; Riley, R.S.

1995-09-01

The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies.

Directory of Open Access Journals (Sweden)

Deyan Luan

2007-07-01

Full Text Available The role that mechanistic mathematical modeling and systems biology will play in molecular medicine and clinical development remains uncertain. In this study, mathematical modeling and sensitivity analysis were used to explore the working hypothesis that mechanistic models of human cascades, despite model uncertainty, can be computationally screened for points of fragility, and that these sensitive mechanisms could serve as therapeutic targets. We tested our working hypothesis by screening a model of the well-studied coagulation cascade, developed and validated from literature. The predicted sensitive mechanisms were then compared with the treatment literature. The model, composed of 92 proteins and 148 protein-protein interactions, was validated using 21 published datasets generated from two different quiescent in vitro coagulation models. Simulated platelet activation and thrombin generation profiles in the presence and absence of natural anticoagulants were consistent with measured values, with a mean correlation of 0.87 across all trials. Overall state sensitivity coefficients, which measure the robustness or fragility of a given mechanism, were calculated using a Monte Carlo strategy. In the absence of anticoagulants, fluid and surface phase factor X/activated factor X (fX/FXa activity and thrombin-mediated platelet activation were found to be fragile, while fIX/FIXa and fVIII/FVIIIa activation and activity were robust. Both anti-fX/FXa and direct thrombin inhibitors are important classes of anticoagulants; for example, anti-fX/FXa inhibitors have FDA approval for the prevention of venous thromboembolism following surgical intervention and as an initial treatment for deep venous thrombosis and pulmonary embolism. Both in vitro and in vivo experimental evidence is reviewed supporting the prediction that fIX/FIXa activity is robust. When taken together, these results support our working hypothesis that computationally derived points of

Improved Satellite-based Photosysnthetically Active Radiation (PAR) for Air Quality Studies

Science.gov (United States)

Pour Biazar, A.; McNider, R. T.; Cohan, D. S.; White, A.; Zhang, R.; Dornblaser, B.; Doty, K.; Wu, Y.; Estes, M. J.

2015-12-01

One of the challenges in understanding the air quality over forested regions has been the uncertainties in estimating the biogenic hydrocarbon emissions. Biogenic volatile organic compounds, BVOCs, play a critical role in atmospheric chemistry, particularly in ozone and particulate matter (PM) formation. In southeastern United States, BVOCs (mostly as isoprene) are the dominant summertime source of reactive hydrocarbon. Despite significant efforts in improving BVOC estimates, the errors in emission inventories remain a concern. Since BVOC emissions are particularly sensitive to the available photosynthetically active radiation (PAR), model errors in PAR result in large errors in emission estimates. Thus, utilization of satellite observations to estimate PAR can help in reducing emission uncertainties. Satellite-based PAR estimates rely on the technique used to derive insolation from satellite visible brightness measurements. In this study we evaluate several insolation products against surface pyranometer observations and offer a bias correction to generate a more accurate PAR product. The improved PAR product is then used in biogenic emission estimates. The improved biogenic emission estimates are compared to the emission inventories over Texas and used in air quality simulation over the period of August-September 2013 (NASA's Discover-AQ field campaign). A series of sensitivity simulations will be performed and evaluated against Discover-AQ observations to test the impact of satellite-derived PAR on air quality simulations.

Biobehavioral Indicators of Social Fear in Young Children with Fragile X Syndrome

Science.gov (United States)

Tonnsen, Bridgette L.; Shinkareva, Svetlana V.; Deal, Sara C.; Hatton, Deborah D.; Roberts, Jane E.

2013-01-01

Anxiety is among the most impairing conditions associated with Fragile X syndrome (FXS) and is putatively linked to atypical physiological arousal. However, few studies have examined this association in young children with FXS. The authors examined whether patterns of arousal and behavior during an experimental stranger approach paradigm differ…

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…

Influences on Maternal Responsivity in Mothers of Children with Fragile X Syndrome

Science.gov (United States)

Sterling, Audra M.; Warren, Steven F.; Brady, Nancy; Fleming, Kandace

2013-01-01

This study investigated the influence of maternal and child variables on the maternal responsivity of 55 mothers with young children with fragile X syndrome. Data included video observations of mother-child interactions in four different contexts, standardized assessments with the children, and standardized questionnaires for the mothers. The…

The Emergence of Effortful Control in Young Boys with Fragile X Syndrome

Science.gov (United States)

Robinson, Marissa; Klusek, Jessica; Poe, Michele D.; Hatton, Deborah D.; Roberts, Jane E.

2018-01-01

Effortful control, or the ability to suppress a dominant response to perform a subdominant response, is an early-emerging temperament trait that is linked with positive social-emotional development. Fragile X syndrome (FXS) is a single-gene disorder characterized by hallmark regulatory impairments, suggesting diminished effortful control. This…

Seismic Fragility Assessment of an Isolated Multipylon Cable-Stayed Bridge Using Shaking Table Tests

Directory of Open Access Journals (Sweden)

Yutao Pang

2017-01-01

Full Text Available In recent decades, cable-stayed bridges have been widely built around the world due to the appealing aesthetics and efficient and fast mode of construction. Numerous studies have concluded that the cable-stayed bridges are sensitive to earthquakes because they possess low damping characteristics and high flexibility. Moreover, cable-stayed bridges need to warrant operability especially in the moderate-to-severe earthquakes. The provisions implemented in the seismic codes allow obtaining adequate seismic performance for the cable-stayed bridge components; nevertheless, they do not provide definite yet reliable rules to protect the bridge. To date, very few experimental tests have been carried out on the seismic fragility analysis of cable-stayed bridges which is the basis of performance-based analyses. The present paper is aimed at proposing a method to derive the seismic fragility curves of multipylon cable-stayed bridge through shake table tests. Toward this aim, a 1/20 scale three-dimensional model of a 22.5 m cable-stayed bridge in China is constructed and tested dynamically by using the shaking table facility of Tongji University. The cable-stayed bridge contains three pylons and one side pier. The outcomes of the comprehensive shaking table tests carried out on cable-stayed bridge have been utilized to derive fragility curves based on a systemic approach.

Divergent effects of obesity on fragility fractures

Directory of Open Access Journals (Sweden)

Caffarelli C

2014-09-01

Full Text Available Carla Caffarelli, Chiara Alessi, Ranuccio Nuti, Stefano Gonnelli Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy Abstract: Obesity was commonly thought to be advantageous for maintaining healthy bones due to the higher bone mineral density observed in overweight individuals. However, several recent studies have challenged the widespread belief that obesity is protective against fracture and have suggested that obesity is a risk factor for certain fractures. The effect of obesity on fracture risk is site-dependent, the risk being increased for some fractures (humerus, ankle, upper arm and decreased for others (hip, pelvis, wrist. Moreover, the relationship between obesity and fracture may also vary by sex, age, and ethnicity. Risk factors for fracture in obese individuals appear to be similar to those in nonobese populations, although patterns of falling are particularly important in the obese. Research is needed to determine if and how visceral fat and metabolic complications of obesity (type 2 diabetes mellitus, insulin resistance, chronic inflammation, etc are causally associated with bone status and fragility fracture risk. Vitamin D deficiency and hypogonadism may also influence fracture risk in obese individuals. Fracture algorithms such as FRAX® might be expected to underestimate fracture probability. Studies specifically designed to evaluate the antifracture efficacy of different drugs in obese patients are not available; however, literature data may suggest that in obese patients higher doses of the bisphosphonates might be required in order to maintain efficacy against nonvertebral fractures. Therefore, the search for better methods for the identification of fragility fracture risk in the growing population of adult and elderly subjects with obesity might be considered a clinical priority which could improve the prevention of fracture in obese individuals. Keywords: bone mineral density, BMI

SAFARI 2000 PAR Measurements, Kalahari Transect, Botswana, Wet Season 2000

Data.gov (United States)

National Aeronautics and Space Administration — Ceptometer data from a Decagon AccuPAR (Model PAR-80) were collected at four sites in Botswana during the SAFARI 2000 Kalahari Transect Wet Season Campaign (March,...

FMR1 Knockout mice: A model to study fragile X mental retardation

Energy Technology Data Exchange (ETDEWEB)

Oostra, B.A.; Bakker, C.E.; Reyniers, E. [Erasmus Univ., Rotterdam (Netherlands)] [and others

1994-09-01

The fragile X syndrome is the most frequent form of inherited mental retardation in humans with an incidence of 1 in 1250 males and 1 in 2500 females. The clinical syndrome includes moderate to severe mental retardation, autistic behavior, macroorchidism, and facial features, such as long face with mandibular prognathism and large, everted ears. The molecular basis for this disease is a large expansion of a triplet repeat (CGG){sub n} in the 5{prime} untranslated region of the FMR1 gene. Due to this large expansion of the CGG repeat, the promoter region becomes methylated and the FMR1 gene is subsequently silenced. Hardly anything is known about the physiologic function of FMR1 and the pathologic mechanisms leading to these symptoms. Since the FMR1 gene is highly conserved in the mouse, we used the mouse to design a knockout model for the fragile X syndrome. These knockout mice lacking Fmrp have normal litter size suggesting that FMR1 is not essential in human gametogenesis and embryonic development. The knockout mice show the abnormalities also seen in the affected organs of human patients. Mutant mice show a gradual development through time of macroorchidism. In the knockout mice we observed cognitive defects in the form of deficits in learning (as shown by the hidden platform Morris water maze task) and behavioral abnormalities such as increased exploratory behavior and hyperactivity. Therefore this knockout mouse may serve as a valuable tool in studying the role of FMR1 in the fragile X syndrome and may serve as a model to elucidate the mechanisms involved in macroorchidism, abnormal behavior, and mental retardation.

Assessing the Fragile X Syndrome Newborn Screening Landscape.

Science.gov (United States)

Riley, Catharine; Wheeler, Anne

2017-06-01

Fragile X syndrome (FXS) is the most common known inherited form of intellectual disability. Early identification is an important step in linking FXS individuals with appropriate and timely medical and social services. Newborn screening (NBS) is 1 approach that has been used for other conditions to facilitate early identification. A literature review was conducted to identify issues, barriers, challenges, and approaches to addressing challenges related to NBS for FXS. Search terms included: fragile X syndrome, FMR1, newborn screening, screening, and genetic testing. To supplement the literature review, 9 key informant interviews were conducted. Information gathered through these interviews supplemented what was identified in the literature. Information from both the literature review and supplemental interviews was reviewed by 3 researchers who discussed and came to consensus on thematic areas and categorization of issues. The barriers and challenges related to NBS for FXS identified in the literature and by experts and stakeholders are categorized into 5 thematic areas: public health burden, treatment, timing, screening/testing methodologies, and translating results. Summaries of these issues and barriers are provided, along with potential approaches to addressing them. The issues and barriers described in this article highlight limited areas of knowledge that need be addressed to improve our understanding of FXS and the potential benefit of NBS. The landscape of NBS for FXS could be influenced by a series of research findings over time or a larger breakthrough that demonstrates an effective targeted treatment that has to be implemented early in life. Copyright © 2017 by the American Academy of Pediatrics.

Lumbar lordosis and pars interarticularis fractures: a case-control study

International Nuclear Information System (INIS)

Bugg, William G.; Lewis, Mark; Juette, Arne; Cahir, John G.; Toms, Andoni P.

2012-01-01

The aim of this study is to examine the relationship between lumbar lordosis and pars interarticularis fractures. In this retrospective case-control study we compare the angle of lumbar lordosis and the angle of the S1 vertebral endplate (as a measure of pelvic tilt) in patients with bilateral L5 pars interarticularis fractures with age- and sex-matched control cases with normal MRI examinations of the lumbar spine. Twenty-nine cases of bilateral L5 pars interarticularis fractures with matched control-cases were identified on MRI (16 male, 13 female, age 9-63 years). The angle of lordosis was measured between the inferior L4 and superior S1 vertebral endplates on a standing lateral lumbar spine radiograph for both groups. The mean angle of lordosis about the L5 vertebra was 36.9 (SD = 6.5 ) in the pars interarticularis fracture group, and 30.1 (SD = 6.4 ) in the control group. The difference between the two groups was significant (mean difference 6.8 , Student's t test: P < 0.001). The mean angle of sacral tilt measured was 122.2 (SD = 10.16 ) for controls and 136.4 (SD = 10.86 ) for patients with pars defects. The difference in the means of 14.2 was statistically significantly different (P < 0.0001). Sacral tilt represented by a steeply angled superior endplate of S1 is associated with a significantly increased angle of lordosis, between L4 and S1, and pars fractures at L5. Steep angulation of the first sacral vertebral segment maybe the predisposing biomechanical factor that leads to pincer-like impingement of the pars interarticularis and then spondylolysis. (orig.)

Lumbar lordosis and pars interarticularis fractures: a case-control study

Energy Technology Data Exchange (ETDEWEB)

Bugg, William G; Lewis, Mark; Juette, Arne; Cahir, John G; Toms, Andoni P [Cotman Centre, Norwich Radiology Academy, Norwich, Norfolk (United Kingdom)

2012-07-15

The aim of this study is to examine the relationship between lumbar lordosis and pars interarticularis fractures. In this retrospective case-control study we compare the angle of lumbar lordosis and the angle of the S1 vertebral endplate (as a measure of pelvic tilt) in patients with bilateral L5 pars interarticularis fractures with age- and sex-matched control cases with normal MRI examinations of the lumbar spine. Twenty-nine cases of bilateral L5 pars interarticularis fractures with matched control-cases were identified on MRI (16 male, 13 female, age 9-63 years). The angle of lordosis was measured between the inferior L4 and superior S1 vertebral endplates on a standing lateral lumbar spine radiograph for both groups. The mean angle of lordosis about the L5 vertebra was 36.9 (SD = 6.5 ) in the pars interarticularis fracture group, and 30.1 (SD = 6.4 ) in the control group. The difference between the two groups was significant (mean difference 6.8 , Student's t test: P < 0.001). The mean angle of sacral tilt measured was 122.2 (SD = 10.16 ) for controls and 136.4 (SD = 10.86 ) for patients with pars defects. The difference in the means of 14.2 was statistically significantly different (P < 0.0001). Sacral tilt represented by a steeply angled superior endplate of S1 is associated with a significantly increased angle of lordosis, between L4 and S1, and pars fractures at L5. Steep angulation of the first sacral vertebral segment maybe the predisposing biomechanical factor that leads to pincer-like impingement of the pars interarticularis and then spondylolysis. (orig.)

Lumbar lordosis and pars interarticularis fractures: a case-control study

Energy Technology Data Exchange (ETDEWEB)

Bugg, William G.; Lewis, Mark; Juette, Arne; Cahir, John G.; Toms, Andoni P. [Cotman Centre, Norwich Radiology Academy, Norwich, Norfolk (United Kingdom)

2012-07-15

The aim of this study is to examine the relationship between lumbar lordosis and pars interarticularis fractures. In this retrospective case-control study we compare the angle of lumbar lordosis and the angle of the S1 vertebral endplate (as a measure of pelvic tilt) in patients with bilateral L5 pars interarticularis fractures with age- and sex-matched control cases with normal MRI examinations of the lumbar spine. Twenty-nine cases of bilateral L5 pars interarticularis fractures with matched control-cases were identified on MRI (16 male, 13 female, age 9-63 years). The angle of lordosis was measured between the inferior L4 and superior S1 vertebral endplates on a standing lateral lumbar spine radiograph for both groups. The mean angle of lordosis about the L5 vertebra was 36.9 (SD = 6.5 ) in the pars interarticularis fracture group, and 30.1 (SD = 6.4 ) in the control group. The difference between the two groups was significant (mean difference 6.8 , Student's t test: P < 0.001). The mean angle of sacral tilt measured was 122.2 (SD = 10.16 ) for controls and 136.4 (SD = 10.86 ) for patients with pars defects. The difference in the means of 14.2 was statistically significantly different (P < 0.0001). Sacral tilt represented by a steeply angled superior endplate of S1 is associated with a significantly increased angle of lordosis, between L4 and S1, and pars fractures at L5. Steep angulation of the first sacral vertebral segment maybe the predisposing biomechanical factor that leads to pincer-like impingement of the pars interarticularis and then spondylolysis. (orig.)

Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

Science.gov (United States)

Belanger, Simon

La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

Study on the fragility of structure with several elements in its story. Part 2: structure with ductile elements

International Nuclear Information System (INIS)

Kai, Y.; Fukushima, S.

1995-01-01

The relationship among the fragility of element, that of story and that of system, is examined using the Monte Carlo simulation. In this study, 2-story models whose stories consist of 2 ductile elements are employed. A method is proposed which includes a nonlinear effect into the evaluation of elements capacities. This method does not require the nonlinear MCS, therefore saving computational efforts. Also, a method to estimate the stories and the system fragilities is proposed. (author). 2 refs., 7 figs., 3 tabs

ParTIES: a toolbox for Paramecium interspersed DNA elimination studies.

Science.gov (United States)

Denby Wilkes, Cyril; Arnaiz, Olivier; Sperling, Linda

2016-02-15

Developmental DNA elimination occurs in a wide variety of multicellular organisms, but ciliates are the only single-celled eukaryotes in which this phenomenon has been reported. Despite considerable interest in ciliates as models for DNA elimination, no standard methods for identification and characterization of the eliminated sequences are currently available. We present the Paramecium Toolbox for Interspersed DNA Elimination Studies (ParTIES), designed for Paramecium species, that (i) identifies eliminated sequences, (ii) measures their presence in a sequencing sample and (iii) detects rare elimination polymorphisms. ParTIES is multi-threaded Perl software available at https://github.com/oarnaiz/ParTIES. ParTIES is distributed under the GNU General Public Licence v3. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Deconstructing Civil Society Actors and Functions: On the Limitations of International Frameworks for Fragile States

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Simone Datzberger

2018-02-01

Full Text Available Over the past three decades, there has been a steady increase of funds by the international community to support civil society organizations (CSOs in fragile states. Surprisingly, this growing attention has not strengthened local civil society landscapes in a way that it would lead to processes of social transformation. On the contrary, civic freedom and space is shrinking around the globe. In analyzing prominent international aid-effectiveness frameworks and donor strategies towards civil society, this paper will put forward one central argument. The way in which civil society actors and functions are currently appropriated threatens deep-rooted social transformation thereby impeding processes of structural and political change—necessary for the transition from conflict to sustainable peace. In delineating, how actors and functional approaches informed peacebuilding and development policy and practice, their strengths and limitations will be examined. Doing so, we draw on different case studies and examples from the literature. We find that existing frameworks for fragile states operate on a presumed model of a public sphere and civil society that may or may not exist. Such an approach disregards an organic formation of a civil society landscape thereby impeding processes of structural, social, and political change in times of fragility.

Tissue differences in fragile X mosaics: Mosaicism in blood cells may differ greatly from skin

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Dobkin, C.S.; Nolin, S.L.; Cohen, I. [NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States)] [and others

1996-08-09

The fragile X mutation is diagnosed from the structure of the FMR1 gene in blood cell DNA. An estimated 12 to 41% of affected males are mosaics who carry both a {open_quotes}full mutation{close_quotes} allele from which there is no gene expression and a {open_quotes}premutation{close_quotes} allele which has normal gene expression. We compared the DNA in blood cells and skin fibroblasts from four mosaic fragile X males to see if there was a difference in the relative amounts of premutation and full mutation alleles within the tissues of these individuals. Two of these males showed striking differences in the ratio of premutation to full mutation in different tissues while the other two showed only slight differences. These observations conform with the widely accepted hypothesis that the fragile X CGG repeat is unstable in somatic tissue during early embryogenesis. Accordingly, the mosaicism in brain and skin, which are both ectodermal in origin, may be similar to each other but different from blood which is not ectodermal in origin. Thus, the ratio of full mutation to premutation allele in skin fibroblasts might be a better indicator of psychological impairment than the ratio in blood cells. 24 refs., 4 figs., 1 tab.

Why Stay Engaged with a State Deemed Fragile?

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Andersson, Magnus; Bae, Jinsun

Based on the constructivist international relations (IR) approach, the authors study Sweden’s engagement with the DPRK as a unique case to understand motivations for engaging in a so-called fragile state. Besides having its embassy in Pyongyang and serving as a protecting power for the U.S., Sweden...... has provided capacity building programs for North Korean government officials and scholars. It has also made a consistent commitment to aid and human rights advocacy. In a nutshell, Sweden has been a facilitator between the DPRK and the outside world. Its motivations are mixed and multiple, including...