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Sample records for hutchinson gilford progeria

  1. Hutchinson-Gilford Progeria Syndrome

    Directory of Open Access Journals (Sweden)

    Gopal G

    2014-08-01

    Full Text Available Hutchinson-Gilford Progeria syndrome (HGPS is a rare pediatric genetic syndrome associated with a characteristic aged appearance very early in life, generally leading to death in the second decade of life. Apart from premature aging, the other notable characteristics of children with HGPS include extreme short stature, prominent superficial veins, poor weight gain, alopecia, as well as various skeletal and cardiovascular pathologies associated with advanced age. The pattern of inheritance of HGPS is uncertain, though both autosomal dominant and autosomal recessive modes have been described. Recent genetic studies have demonstrated mutations in the LMNA gene in children with HGPS. In this article, we report a 16 years old girl who had the phenotypic features of HGPS and was later confirmed to have LMNA mutation by genetic analysis.

  2. Genetics Home Reference: Hutchinson-Gilford progeria syndrome

    Science.gov (United States)

    ... mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome. Proc Natl Acad ... Health & Human Services National Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical ...

  3. Hutchinson-Gilford progeria syndrome: review of the phenotype

    NARCIS (Netherlands)

    Hennekam, Raoul C. M.

    2006-01-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity characterized by extreme short stature, low body weight, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial features that resemble aged persons. Cardiovascular compromise leads

  4. Ocular manifestations in the Hutchinson-Gilford progeria syndrome

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    Shivcharan L Chandravanshi

    2011-01-01

    Full Text Available The Hutchinson-Gilford progeria (HGP syndrome is an extremely rare genetic condition characterized by an appearance of accelerated aging in children. The word progeria is derived from the Greek word progeros meaning ′prematurely old′. It is caused by de novo dominant mutation in the LMNA gene (gene map locus 1q21.2 and characterized by growth retardation and accelerated degenerative changes of the skin, musculoskeletal and cardiovascular systems. The most common ocular manifestations are prominent eyes, loss of eyebrows and eyelashes, and lagophthalmos. In the present case some additional ocular features such as horizontal narrowing of palpebral fissure, superior sulcus deformity, upper lid retraction, upper lid lag in down gaze, poor pupillary dilatation, were noted. In this case report, a 15-year-old Indian boy with some additional ocular manifestations of the HGP syndrome is described.

  5. Radiological Diagnosis of a Rare Premature Aging Genetic Disorder: Progeria (Hutchinson-Gilford Syndrome

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    Haji Mohammed Nazir

    2017-01-01

    Full Text Available Hutchinson-Gilford Progeria Syndrome (HGPS is a rare disease with a combination of short stature, bone abnormalities, premature ageing, and skin changes. Though the physical appearance of these patients is characteristic, there is little emphasis on the characteristic radiological features. In this paper, we report a 16-year-old boy with clinical and radiological features of this rare genetic disorder. He had a characteristic facial appearance with a large head, large eyes, thin nose with beaked tip, small chin, protruding ears, prominent scalp veins, and absence of hair.

  6. Hypoparathyroidism in an Egyptian child with Hutchinson-Gilford progeria syndrome: a case report

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    Kalil Kotb

    2012-01-01

    Full Text Available Abstract Introduction Hutchinson-Gilford progeria syndrome is a rare genetic disorder. It is reported to be present in one in eight million and is characterized by severe growth failure, early loss of hair, lipodystrophy, scleroderma, decreased joint mobility, osteolysis, early atherosclerosis and facial features that resemble those of an aged person. Apart from diabetes mellitus, there are no reported abnormalities of thyroid, parathyroid, pituitary or adrenal function. Here, we report the case of a 10-year-old Egyptian child with Hutchinson-Gilford progeria syndrome and hypoparathyroidism. Case presentation A 10-year-old Egyptian boy was referred to our institution for an evaluation of recurrent attacks of muscle cramps, paresthesia of his fingertips and perioral numbness of two months duration. On examination, we found dilated veins present over his scalp with alopecia and frontal bossing, a beaked nose, thin lips, protruding ears, a high pitched voice with sparse hair over his eyebrows and eyelashes and micrognathia but normal dentition. His eyes appeared prominent and our patient appeared to have poor sexual development. A provisional diagnosis of progeria was made, which was confirmed by molecular genetics study. Chvostek's and Trousseau's signs were positive. He had low total calcium (5.4 mg/dL, low ionized calcium (2.3 mg/dL, raised serum phosphate (7.2 mg/dL, raised alkaline phosphatase (118 U/L and low intact parathyroid hormone (1.2 pg/mL levels. He was started on oral calcium salt and vitamin D; his symptoms improved with the treatment and his serum calcium, urinary calcium and alkaline phosphates level were monitored every three months to ensure adequacy of therapy and to avoid hypercalcemia. Conclusion Routine checking of serum calcium, phosphorus and parathyroid hormone will help in the early detection of hypoparathyrodism among children with progeria.

  7. Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome

    Czech Academy of Sciences Publication Activity Database

    Raška, Ivan

    2010-01-01

    Roč. 3, č. 3 (2010), s. 89-93 ISSN 1337-6853 Grant - others:GA MŠk(CZ) LC535 Program:LC Institutional research plan: CEZ:AV0Z50110509 Keywords : laminopathies * Hutchinson-Gilford progeria syndrome * progerin Subject RIV: EA - Cell Biology

  8. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  9. Chemical screening identifies ROCK as a target for recovering mitochondrial function in Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Kang, Hyun Tae; Park, Joon Tae; Choi, Kobong; Choi, Hyo Jei Claudia; Jung, Chul Won; Kim, Gyu Ree; Lee, Young-Sam; Park, Sang Chul

    2017-06-01

    Hutchinson-Gilford progeria syndrome (HGPS) constitutes a genetic disease wherein an aging phenotype manifests in childhood. Recent studies indicate that reactive oxygen species (ROS) play important roles in HGPS phenotype progression. Thus, pharmacological reduction in ROS levels has been proposed as a potentially effective treatment for patient with this disorder. In this study, we performed high-throughput screening to find compounds that could reduce ROS levels in HGPS fibroblasts and identified rho-associated protein kinase (ROCK) inhibitor (Y-27632) as an effective agent. To elucidate the underlying mechanism of ROCK in regulating ROS levels, we performed a yeast two-hybrid screen and discovered that ROCK1 interacts with Rac1b. ROCK activation phosphorylated Rac1b at Ser71 and increased ROS levels by facilitating the interaction between Rac1b and cytochrome c. Conversely, ROCK inactivation with Y-27632 abolished their interaction, concomitant with ROS reduction. Additionally, ROCK activation resulted in mitochondrial dysfunction, whereas ROCK inactivation with Y-27632 induced the recovery of mitochondrial function. Furthermore, a reduction in the frequency of abnormal nuclear morphology and DNA double-strand breaks was observed along with decreased ROS levels. Thus, our study reveals a novel mechanism through which alleviation of the HGPS phenotype is mediated by the recovery of mitochondrial function upon ROCK inactivation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  10. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Cleveland, Robert H. [Harvard Medical School, Pediatric Radiology, Children' s Hospital Boston, Boston, MA (United States); Gordon, Leslie B. [Harvard Medical School, Department of Anesthesia, Children' s Hospital Boston, Boston, MA (United States); Warren Alpert Medical School of Brown University, Department of Pediatrics, Hasbro Children' s Hospital, Providence, RI (United States); Kleinman, Monica E. [Harvard Medical School, Department of Anesthesia, Children' s Hospital Boston, Boston, MA (United States); Miller, David T. [Harvard Medical School, Division of Genetics, Children' s Hospital Boston, Boston, MA (United States); Gordon, Catherine M. [Harvard Medical School, Division of Endocrinology and Adolescent Medicine, Children' s Hospital Boston, Boston, MA (United States); Snyder, Brian D. [Harvard Medical School, Department of Orthopedic Surgery, Children' s Hospital Boston, Boston, MA (United States); Nazarian, Ara [Harvard Medical School, Boston, MA (United States); Giobbie-Hurder, Anita [Dana-Farber Cancer Institute, Department of Biostatistics and Computational Biology, Boston, MA (United States); Neuberg, Donna [Dana-Farber Cancer Institute, Department of Biostatistics and Computational Biology, Boston, MA (United States); Harvard School of Public Health, Department of Biostatistics, Boston, MA (United States); Kieran, Mark W. [Dana-Farber Cancer Institute and Children' s Hospital Boston, Division of Pediatric Oncology, Boston, MA (United States)

    2012-09-15

    Progeria is a rare segmental premature aging disease with significant skeletal abnormalities. Defining the full scope of radiologic abnormalities requires examination of a large proportion of the world's progeria population (estimated at 1 in 4 million). There has been no comprehensive prospective study describing the skeletal abnormalities associated with progeria. To define characteristic radiographic features of this syndrome. Thirty-nine children with classic progeria, ages 2-17 years, from 29 countries were studied at a single site. Comprehensive radiographic imaging studies were performed. Sample included 23 girls and 16 boys - the largest number of patients with progeria evaluated prospectively to date. Eight new and two little known progeria-associated radiologic findings were identified (frequencies of 3-36%). Additionally, 23 commonly reported findings were evaluated. Of these, 2 were not encountered and 21 were present and ranked according to their frequency. Nine abnormalities were associated with increasing patient age (P = 0.02-0.0001). This study considerably expands the radiographic morphological spectrum of progeria. A better understanding of the radiologic abnormalities associated with progeria and improved understanding of the biology of progerin (the molecule responsible for this disease), will improve our ability to treat the spectrum of bony abnormalities. (orig.)

  11. A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome

    International Nuclear Information System (INIS)

    Cleveland, Robert H.; Gordon, Leslie B.; Kleinman, Monica E.; Miller, David T.; Gordon, Catherine M.; Snyder, Brian D.; Nazarian, Ara; Giobbie-Hurder, Anita; Neuberg, Donna; Kieran, Mark W.

    2012-01-01

    Progeria is a rare segmental premature aging disease with significant skeletal abnormalities. Defining the full scope of radiologic abnormalities requires examination of a large proportion of the world's progeria population (estimated at 1 in 4 million). There has been no comprehensive prospective study describing the skeletal abnormalities associated with progeria. To define characteristic radiographic features of this syndrome. Thirty-nine children with classic progeria, ages 2-17 years, from 29 countries were studied at a single site. Comprehensive radiographic imaging studies were performed. Sample included 23 girls and 16 boys - the largest number of patients with progeria evaluated prospectively to date. Eight new and two little known progeria-associated radiologic findings were identified (frequencies of 3-36%). Additionally, 23 commonly reported findings were evaluated. Of these, 2 were not encountered and 21 were present and ranked according to their frequency. Nine abnormalities were associated with increasing patient age (P = 0.02-0.0001). This study considerably expands the radiographic morphological spectrum of progeria. A better understanding of the radiologic abnormalities associated with progeria and improved understanding of the biology of progerin (the molecule responsible for this disease), will improve our ability to treat the spectrum of bony abnormalities. (orig.)

  12. Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells.

    Science.gov (United States)

    Aliper, Alexander M; Csoka, Antonei Benjamin; Buzdin, Anton; Jetka, Tomasz; Roumiantsev, Sergey; Moskalev, Alexy; Zhavoronkov, Alex

    2015-01-01

    For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging.

  13. Unique Preservation of Neural Cells in Hutchinson- Gilford Progeria Syndrome Is Due to the Expression of the Neural-Specific miR-9 MicroRNA

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    Xavier Nissan

    2012-07-01

    Full Text Available One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS, who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

  14. Discordant gene expression signatures and related phenotypic differences in lamin A- and A/C-related Hutchinson-Gilford progeria syndrome (HGPS.

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    Martina Plasilova

    Full Text Available Hutchinson-Gilford progeria syndrome (HGPS is a genetic disorder displaying features reminiscent of premature senescence caused by germline mutations in the LMNA gene encoding lamin A and C, essential components of the nuclear lamina. By studying a family with homozygous LMNA mutation (K542N, we showed that HGPS can also be caused by mutations affecting both isoforms, lamin A and C. Here, we aimed to elucidate the molecular mechanisms underlying the pathogenesis in both, lamin A- (sporadic and lamin A and C-related (hereditary HGPS. For this, we performed detailed molecular studies on primary fibroblasts of hetero- and homozygous LMNA K542N mutation carriers, accompanied with clinical examinations related to the molecular findings. By assessing global gene expression we found substantial overlap in altered transcription profiles (13.7%; 90/657 in sporadic and hereditary HGPS, with 83.3% (75/90 concordant and 16.7% (15/90 discordant transcriptional changes. Among the concordant ones we observed down-regulation of TWIST2, whose inactivation in mice and humans leads to loss of subcutaneous fat and dermal appendages, and loss of expression in dermal fibroblasts and periadnexial cells from a LMNA(K542N/K542N patient further confirming its pivotal role in skin development. Among the discordant transcriptional profiles we identified two key mediators of vascular calcification and bone metabolism, ENPP1 and OPG, which offer a molecular explanation for the major phenotypic differences in vascular and bone disease in sporadic and hereditary HGPS. Finally, this study correlates reduced TWIST2 and OPG expression with increased osteocalcin levels, thereby linking altered bone remodeling to energy homeostasis in hereditary HGPS.

  15. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

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    Worman Howard J

    2005-06-01

    Full Text Available Abstract Background Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670 is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT, within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. Results We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary DNA sequencing of RNA showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. Conclusion Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic

  16. Abnormal nuclear morphology is independent of longevity in a zmpste24-deficient fish model of Hutchinson-Gilford progeria syndrome (HGPS).

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    Tonoyama, Yasuhiro; Shinya, Minori; Toyoda, Atsushi; Kitano, Takeshi; Oga, Atsunori; Nishimaki, Toshiyuki; Katsumura, Takafumi; Oota, Hiroki; Wan, Miles T; Yip, Bill W P; Helen, Mok O L; Chisada, Shinichi; Deguchi, Tomonori; Au, Doris W T; Naruse, Kiyoshi; Kamei, Yasuhiro; Taniguchi, Yoshihito

    2018-07-01

    Lamin is an intermediate protein underlying the nuclear envelope and it plays a key role in maintaining the integrity of the nucleus. A defect in the processing of its precursor by a metalloprotease, ZMPSTE24, results in the accumulation of farnesylated prelamin in the nucleus and causes various diseases, including Hutchinson-Gilford progeria syndrome (HGPS). However, the role of lamin processing is unclear in fish species. Here, we generated zmpste24-deficient medaka and evaluated their phenotype. Unlike humans and mice, homozygous mutants did not show growth defects or lifespan shortening, despite lamin precursor accumulation. Gonadosomatic indices, blood glucose levels, and regenerative capacity of fins were similar in 1-year-old mutants and their wild-type (WT) siblings. Histological examination showed that the muscles, subcutaneous fat tissues, and gonads were normal in the mutants at the age of 1 year. However, the mutants showed hypersensitivity to X-ray irradiation, although p53target genes, p21 and mdm2, were induced 6 h after irradiation. Immunostaining of primary cultured cells from caudal fins and visualization of nuclei using H2B-GFP fusion proteins revealed an abnormal nuclear shape in the mutants both in vitro and in vivo. The telomere lengths were significantly shorter in the mutants compared to WT. Taken together, these results suggest that zmpste24-deficient medaka phenocopied HGPS only partially and that abnormal nuclear morphology and lifespan shortening are two independent events in vertebrates. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Physical Therapy and Occupational Therapy in Progeria

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    Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation ... Inc. All rights reserved. Page 2 of 5 Physical and Occupational Therapy in Progeria Hutchinson-Gilford Progeria ...

  18. Progeria in siblings: A rare case report

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    R Sowmiya

    2011-01-01

    Full Text Available Progeria, also known as Hutchinson-Gilford syndrome, is an extremely rare, severe genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. It is an autosomal dominant disorder. It is not seen in siblings of affected children although there are very few case reports of progeria affecting more than one child in a family. Here we are presenting two siblings, a 14-year-old male and a 13-year-old female with features of progeria, suggesting a possible autosomal recessive inheritance.

  19. Progeria (Hutchison - Gilford syndrome in siblings: In an autosomal recessive pattern of inheritance

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    Raghu Tanjore

    2001-09-01

    Full Text Available Progeria is an autosomal dominant, premature aging syndrome. Six and three year old female siblings had sclcrodermatous changes over the extremities, alopecia, beaked nose, prominent veins and bird-like facies. Radiological features were consistent with features of progeria. The present case highlights rarity of progeria in siblings with a possible autosomal recessive pattern.

  20. Transgene silencing of the Hutchinson-Gilford progeria syndrome mutation results in a reversible bone phenotype, whereas resveratrol treatment does not show overall beneficial effects

    DEFF Research Database (Denmark)

    Strandgren, Charlotte; Nasser, Hasina Abdul; McKenna, Tomás

    2015-01-01

    model to study the possibility of recovering from HGPS bone disease upon silencing of the HGPS mutation, and the potential benefits from treatment with resveratrol. We show that complete silencing of the transgenic expression of progerin normalized bone morphology and mineralization already after 7...... weeks. The improvements included lower frequencies of rib fractures and callus formation, an increased number of osteocytes in remodeled bone, and normalized dentinogenesis. The beneficial effects from resveratrol treatment were less significant and to a large extent similar to mice treated with sucrose...... alone. However, the reversal of the dental phenotype of overgrown and laterally displaced lower incisors in HGPS mice could be attributed to resveratrol. Our results indicate that the HGPS bone defects were reversible upon suppressed transgenic expression and suggest that treatments targeting aberrant...

  1. Progeria 101/FAQ

    Science.gov (United States)

    ... Progeria, but also may shed light on the phenomenon of aging and cardiovascular disease.” v “Recurrent de ... Statistics Is Progeria passed down from parent to child? HGPS is not usually passed down in families. ...

  2. Labor Market Progeria.

    Science.gov (United States)

    Rodeheaver, Dean

    1990-01-01

    Social ambivalence toward women's roles, sexuality, appearance, and aging combine with social standards of attractiveness to create both age and sex discrimination in the workplace. The life expectancy of presentability is shorter among women than men, thus creating an accelerated aging process termed labor market progeria. (SK)

  3. Progeria syndrome: A case report

    Directory of Open Access Journals (Sweden)

    Rastogi Rajul

    2008-01-01

    Full Text Available Progeria is a rare and peculiar combination of dwarfism and premature aging. The incidence is one in several million births. It occurs sporadically and is probably an autosomal recessive syndrome. Though the clinical presentation is usually typical, conventional radiological and biochemical investigations help in confirming the diagnosis. We present a rare case of progeria with most of the radiological features as a pictorial essay.

  4. Immortalization of Werner syndrome and progeria fibroblasts

    International Nuclear Information System (INIS)

    Saito, H.; Moses, R.E.

    1991-01-01

    Human fibroblast cells from two different progeroid syndromes, Werner syndrome (WS) and progeria, were established as immortalized cell lines by transfection with plasmid DNA containing the SV40 early region. The lineage of each immortalized cell line was confirmed by VNTR analysis. Each of the immortalized cell lines maintained its original phenotype of slow growth. DNA repair ability of these cells was also studied by measuring sensitivity to killing by uv or the DNA-damaging drugs methyl methansulfonate, bleomycin, and cis-dichlorodiamine platinum. The results showed that both WS and progeria cells have normal sensitivity to these agents

  5. Prostate Cancer Diagnostics and Prognostics Based on Interphase Spatial Genome Positioning

    Science.gov (United States)

    2016-03-01

    in lamin A/C and include Emery-Dreifuss muscular dystrophy (EDMD) and the premature aging disease Hutchison-Gilford progeria syndrome (HGPS) (Burke...P a g e Zhang Y, McCord RP, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, Becker MS, Alt FW, Dekker J (2012) Spatial organization of the mouse...diseases characterized by mutations in lamin A/C, and includes Emery-Dreifuss 483 muscular dystrophy and the premature aging disease Hutchinson-Gilford

  6. Protective mechanism against cancer found in progeria patient cells

    Science.gov (United States)

    NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

  7. National Uranium Resource Evaluation: Hutchinson Quadrangle, Kansas

    International Nuclear Information System (INIS)

    Fair, C.L.; Smit, D.E.; Gundersen, J.N.

    1982-08-01

    Surface reconnaissance and detailed subsurface studies were done within the Hutchinson Quadrangle, Kansas, to evaluate uranium favorability in accordance with National Uranium Resource Evaluation criteria. These studies were designed in part to follow up prior airborne radiometric, hydrogeochemical, and stream-sediment surveys. Over 4305 well records were examined in the subsurface phase of this study. The results of these investigations indicate environments favorable for channel-controlled peneconcordant sandstone deposits in rocks of Cretaceous age and for Wyoming and Texas roll-type deposits in sandstones of Pennsylvanian age. The Cretaceous sandstone environments exhibit favorable characteristics such as a bottom unconformity; high bedload; braided, fluvial channels; large-scale cross-bedding; and an anomalous outcrop. The Pennsylvanian sandstone environments exhibit favorable characteristics such as arkosic cross-bedded sandstones, included pyrite and organic debris, interbedded shales, and gamma-ray log anomalies. Environments considered unfavorable for uranium deposits are limestone and dolomite environments, marine black shale environments, evaporative precipitate environments, and some fluvial sandstone environments. Environments considered unevaluated due to insufficient data include Precambrian plutonic, metamorphic, and sedimentary rocks, even though a large number of thin sections were available for study

  8. Envelhecimento fora de tempo

    OpenAIRE

    Campos, Joana; Faria, Cristina; Domingues, António

    2014-01-01

    A síndrome de Hutchinson-Gilford ou progeria é uma patologia extremamente rara de envelJiecimento prematuro, caracterizada por atraso de crescimento e alterações degenerativas precoces a nível cutâneo, músculo-esquelético e sistema cardiovascular.Descreve-se um caso de progeria ou síndrome de Hutchinson-Gilford numa menina de três anos e seis meses que iniciou a apresentação clínica por má evolução estaturoponderal e alterações cutâneas e que posteriormente foi desenvolvendo, com carácter pro...

  9. Mandibulo-acral dysplasia

    Energy Technology Data Exchange (ETDEWEB)

    Hoeffel, J.C.; Mainard, L. [Dept. of Radiology, Children' s Hospital, Vandoeuvre (France); Chastagner, P. [Dept. of Medicine, Children' s Hospital, Vandoeuvre (France); Hoeffel, C.C. [UFR Faculte de Medecine Cochin, Paris (France)

    2000-11-01

    We report on a 7 year-old-girl with mandibulo-acral dysplasia. When she was 3 years of age it mimicked scleroderma because of skin atrophy and later on a Hutchinson-Gilford progeria syndrome (HGP). Acro-mandibular dysplasia was diagnosed because of facial hypoplasia and mandibular hypoplasia. The bilateral proximal mid-humeral notch seen in this case is unusual. (orig.)

  10. Biomechanical Strain Exacerbates Inflammation on a Progeria-on-a-Chip Model

    NARCIS (Netherlands)

    Ribas, J.; Zhang, Y.S.; Pitrez, P.R.; Leijten, Jeroen Christianus Hermanus; Miscuglio, M.; Rouwkema, Jeroen; Dokmeci, M.R.; Nissan, X.; Ferreira, L.; Khademhosseini, A.

    2017-01-01

    A progeria-on-a-chip model is engineered to recapitulate the biomechanical dynamics of vascular disease and aging. The model shows an exacerbated injury response to strain and is rescued by pharmacological treatments. The progeria-on-a-chip is expected to drive the discovery of new drugs and to

  11. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    NARCIS (Netherlands)

    van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B.; von Lindern, Marieke; Jong, Willeke M. C.; de Zeeuw, Chris I.; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J.; van der Horst, Gijsbertus T. J.; Mitchell, James R.

    2006-01-01

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a

  12. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    NARCIS (Netherlands)

    H.W.M. van de Ven (Marieke); J.-O. Andressoo (Jaan-Olle); V.B. Holcomb (Valerie); M.M. von Lindern (Marieke); W.M.C. Jong (Willeke); C.I. de Zeeuw (Chris); Y. Suh (Yousin); P. Hasty (Paul); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James)

    2006-01-01

    textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular

  13. John Hutchinson, 1811-1861: the first respiratory disease epidemiologist.

    Science.gov (United States)

    Speizer, Frank E

    2011-05-01

    In 1844, before a large medical audience in London, John Hutchinson demonstrated the use of measurements of pulmonary function to predict disease. In contrast to standard practice at that time, he conducted an epidemiological investigation that would have been acceptable by today's standards, in which he examined over 2000 people and contrasted healthy and diseased cases. His data clearly indicated how, what he called, "vital capacity" predicted disease. Exploring the history of this young Victorian-era physician is both humbling and instructive for the modern epidemiologist, who has the advantages of the successes of ever more rapid, computer-based, technical approaches to evaluate existing data sources, and fewer opportunities to actually collect primary data from large number of patients using physiologic tools.

  14. Leg ulcer in Werner syndrome (adult progeria): a case report.

    Science.gov (United States)

    Fumo, Giuseppe; Pau, Monica; Patta, Federico; Aste, Nicola; Atzori, Laura

    2013-03-15

    Werner syndrome (WS; MIM#277700) or adult progeria, is a rare disease, associated with mutations of a single gene (RECQL2 or WRN), located on chromosome 8 (8p12). It codes a DNA-helicase, whose defects cause genomic instability. The highest incidences are reported in Japan and Sardinia (Italy). On this major island of the Mediterranean Basin, the WS cases have been observed in the northern areas. The authors describe the apparently first case reported in southern Sardinia, a 51-year-old woman, who was born in and resides in the province of Cagliari. She presented with a 9-year history of an intractable leg ulcer and other characteristic symptoms, including "bird-like" face, high-pitched voice, premature greying, short stature, abdominal obesity in contrast with thin body type, scleroderma-like legs, decreased muscle mass, diabetes, atherosclerosis, and premature menopause. A specialized genetic Institute of Research (IRCCS-IDI, Rome) confirmed the clinical diagnosis. There is no cure or specific treatment and patients must be periodically screened for an increased risk of cardiovascular and cerebrovascular disease and malignancies. Among the many findings, leg ulcers significantly affect the patient's quality of life. This problem may send the patient to the dermatologist, who finally suspects the diagnosis. Poor response to medical treatment may require aggressive repeated surgery, with poor or temporary results.

  15. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice

    OpenAIRE

    Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie; Lindern, Marieke; Jong, Willeke; Zeeuw, Chris; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan; Horst, Gijsbertus; Mitchell, James

    2006-01-01

    textabstractHow congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cul...

  16. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

    Science.gov (United States)

    Kubben, Nard; Misteli, Tom

    2017-10-01

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

  17. Zmpste24-/- mouse model for senescent wound healing research.

    Science.gov (United States)

    Butala, Parag; Szpalski, Caroline; Soares, Marc; Davidson, Edward H; Knobel, Denis; Warren, Stephen M

    2012-12-01

    The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing. Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. Zmpste24(-/-) mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24(-/-) wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24(-/-) progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

  18. La presa di parola di Anne Hutchinson. Insubordinazione e conflitto nella giovane America puritana

    Directory of Open Access Journals (Sweden)

    Itala Vivan

    2016-04-01

    Full Text Available Anne Hutchinson lasciò l’Inghilterra nel 1634 per emigrare nel Massachusetts puritano, dove nel 1637 e 1638 fu processata, condannata, scomunicata ed espulsa come donna insubordinata, deviante e pericolosa. Il suo ruolo intellettuale e politico nell’alba incandescente della prima America viene qui analizzato e discusso ascoltando da presso il racconto che promana dalla voce della stessa Anne Hutchinson attraverso i verbali dei due processi, trascritti dai contemporanei con la fedeltà letterale che era tipica del puritanesimo americano. La drammatica controversia che ebbe al centro la presa di parola di questa donna segnò la prima grande crisi della neonata società coloniale – la cosiddetta crisi antinomiana -- e ne determinò gli sviluppi futuri, indirizzandoli verso un sistema di potere politico su basi teocratiche.

  19. Advanced postbuckling and imperfection sensitivity of the elastic-plastic Shanley-Hutchinson model column

    DEFF Research Database (Denmark)

    Christensen, Claus Dencker; Byskov, Esben

    2008-01-01

    The postbuckling behavior and imperfection sensitivity of the Shanley-Hutchinson plastic model column introduced by Hutchinson in 1973 are examined. The study covers the initial, buckled state and the advanced postbuckling regime of the geometrically perfect realization as well as its sensitivity...... to geometric imperfections. In Section 1, which is concerned with the perfect structure, a new, simple explicit upper bound for all solutions to the problem is found when the tangent modulus at bifurcation vanishes compared to the linear elastic (unloading) modulus. The difference between the upper bound...... and the solution to an actual problem is determined by an asymptotic expansion involving hyperbolic trial functions (instead of polynomials) which fulfill general boundary conditions at bifurcation and infinity. The method provides an accurate estimate of the maximum load even if it occurs in an advanced...

  20. Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria.

    Science.gov (United States)

    Qian, Minxian; Liu, Zuojun; Peng, Linyuan; Tang, Xiaolong; Meng, Fanbiao; Ao, Ying; Zhou, Mingyan; Wang, Ming; Cao, Xinyue; Qin, Baoming; Wang, Zimei; Zhou, Zhongjun; Wang, Guangming; Gao, Zhengliang; Xu, Jun; Liu, Baohua

    2018-05-02

    DNA damage accumulates with age (Lombard et al., 2005). However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that ATM-centered DNA damage response (DDR) progressively declines with senescence and age, while low dose of chloroquine (CQ) activates ATM, promotes DNA damage clearance, rescues age-related metabolic shift, and prolongs replicative lifespan. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 extend lifespan in Atm-/- mice, with restored metabolic homeostasis. Moreover, the treatment with CQ remarkably extends lifespan of Caenorhabditis elegans , but not the ATM-1 mutants. In a progeria mouse model with low DNA repair capacity, long-term administration of CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases. © 2018, Qian et al.

  1. Bird surveys at McKinley Bay and Hutchinson Bay, Northwest Territories, in 1990

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, B J; Dickson, D L; Dickson, H L

    1991-03-01

    Monitoring surveys of bird abundance and distribution were conducted in 1990 at McKinley Bay in the Northwest Territories, the site of a winter harbour for drillships and the proposed location for a major year-round support base for oil and gas exploration. Primary objectives of the survey were to determine whether diving duck numbers had changed since the initial phase of the study from 1981-1985, and to provide additional baseline data on natural annual fluctuations in diving duck numbers. Three aerial surveys at each bay were carried out using techniques identical to those in previous years. On 5 August 1990, when survey conditions were considered best of the three surveys, more than twice as many diving ducks were found in McKinley Bay and Hutchinson Bay than on average during the five years of 1981-1985. Old squaw and scooters comprised ca 90% of the diving ducks observed, and both species showed significant increases in numbers. The increase in abundance of diving ducks was likely unrelated to industrial activity in the area since a similar increase occurred in the control area, Hutchinson Bay. Many factors, including both environmental factors such as those affecting nesting success and timing of the moult, and factors related to the survey methods, could be involved in causing the large fluctuations observed. 9 refs., 8 figs., 10 tabs.

  2. Bird surveys at McKinley Bay and Hutchinson Bay, Northwest Territories, in 1990

    International Nuclear Information System (INIS)

    Cornish, B.J.; Dickson, D.L.; Dickson, H.L.

    1991-01-01

    Monitoring surveys of bird abundance and distribution were conducted in 1990 at McKinley Bay in the Northwest Territories, the site of a winter harbour for drillships and the proposed location for a major year-round support base for oil and gas exploration. Primary objectives of the survey were to determine whether diving duck numbers had changed since the initial phase of the study from 1981-1985, and to provide additional baseline data on natural annual fluctuations in diving duck numbers. Three aerial surveys at each bay were carried out using techniques identical to those in previous years. On 5 August 1990, when survey conditions were considered best of the three surveys, more than twice as many diving ducks were found in McKinley Bay and Hutchinson Bay than on average during the five years of 1981-1985. Old squaw and scooters comprised ca 90% of the diving ducks observed, and both species showed significant increases in numbers. The increase in abundance of diving ducks was likely unrelated to industrial activity in the area since a similar increase occurred in the control area, Hutchinson Bay. Many factors, including both environmental factors such as those affecting nesting success and timing of the moult, and factors related to the survey methods, could be involved in causing the large fluctuations observed. 9 refs., 8 figs., 10 tabs

  3. Sporadic Premature Aging in a Japanese Monkey: A Primate Model for Progeria

    Science.gov (United States)

    Oishi, Takao; Imai, Hiroo; Go, Yasuhiro; Imamura, Masanori; Hirai, Hirohisa; Takada, Masahiko

    2014-01-01

    In our institute, we have recently found a child Japanese monkey who is characterized by deep wrinkles of the skin and cataract of bilateral eyes. Numbers of analyses were performed to identify symptoms representing different aspects of aging. In this monkey, the cell cycle of fibroblasts at early passage was significantly extended as compared to a normal control. Moreover, both the appearance of senescent cells and the deficiency in DNA repair were observed. Also, pathological examination showed that this monkey has poikiloderma with superficial telangiectasia, and biochemical assay confirmed that levels of HbA1c and urinary hyaluronan were higher than those of other (child, adult, and aged) monkey groups. Of particular interest was that our MRI analysis revealed expansion of the cerebral sulci and lateral ventricles probably due to shrinkage of the cerebral cortex and the hippocampus. In addition, the conduction velocity of a peripheral sensory but not motor nerve was lower than in adult and child monkeys, and as low as in aged monkeys. However, we could not detect any individual-unique mutations of known genes responsible for major progeroid syndromes. The present results indicate that the monkey suffers from a kind of progeria that is not necessarily typical to human progeroid syndromes. PMID:25365557

  4. Adaptive Stress Response in Segmental Progeria Resembles Long-Lived Dwarfism and Calorie Restriction in Mice

    Science.gov (United States)

    Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M. C; Zeeuw, Chris I. De; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

    2006-01-01

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPDG602D/R722W/XPA−/−) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80 −/− mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage. PMID:17173483

  5. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Science.gov (United States)

    van de Ven, Marieke; Andressoo, Jaan-Olle; Holcomb, Valerie B; von Lindern, Marieke; Jong, Willeke M C; De Zeeuw, Chris I; Suh, Yousin; Hasty, Paul; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J; Mitchell, James R

    2006-12-15

    How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age), including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W)/XPA(-/-)) that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/-) mouse. Specific (but not all) types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  6. Adaptive stress response in segmental progeria resembles long-lived dwarfism and calorie restriction in mice.

    Directory of Open Access Journals (Sweden)

    Marieke van de Ven

    2006-12-01

    Full Text Available How congenital defects causing genome instability can result in the pleiotropic symptoms reminiscent of aging but in a segmental and accelerated fashion remains largely unknown. Most segmental progerias are associated with accelerated fibroblast senescence, suggesting that cellular senescence is a likely contributing mechanism. Contrary to expectations, neither accelerated senescence nor acute oxidative stress hypersensitivity was detected in primary fibroblast or erythroblast cultures from multiple progeroid mouse models for defects in the nucleotide excision DNA repair pathway, which share premature aging features including postnatal growth retardation, cerebellar ataxia, and death before weaning. Instead, we report a prominent phenotypic overlap with long-lived dwarfism and calorie restriction during postnatal development (2 wk of age, including reduced size, reduced body temperature, hypoglycemia, and perturbation of the growth hormone/insulin-like growth factor 1 neuroendocrine axis. These symptoms were also present at 2 wk of age in a novel progeroid nucleotide excision repair-deficient mouse model (XPD(G602D/R722W/XPA(-/- that survived weaning with high penetrance. However, despite persistent cachectic dwarfism, blood glucose and serum insulin-like growth factor 1 levels returned to normal by 10 wk, with hypoglycemia reappearing near premature death at 5 mo of age. These data strongly suggest changes in energy metabolism as part of an adaptive response during the stressful period of postnatal growth. Interestingly, a similar perturbation of the postnatal growth axis was not detected in another progeroid mouse model, the double-strand DNA break repair deficient Ku80(-/- mouse. Specific (but not all types of genome instability may thus engage a conserved response to stress that evolved to cope with environmental pressures such as food shortage.

  7. Transformation Resistance in a Premature Aging Disorder Identifies a Tumor-Protective Function of BRD4

    Directory of Open Access Journals (Sweden)

    Patricia Fernandez

    2014-10-01

    Full Text Available Summary: Advanced age and DNA damage accumulation are prominent risk factors for cancer. The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique opportunity for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Here, we have used HGPS patient cells to identify a protective mechanism to oncogenesis. We find that HGPS cells are resistant to neoplastic transformation. Resistance is mediated by the bromodomain protein BRD4, which exhibits altered genome-wide binding patterns in transformation-resistant cells, leading to inhibition of oncogenic dedifferentiation. BRD4 also inhibits, albeit to a lower extent, the tumorigenic potential of transformed cells from healthy individuals. BRD4-mediated tumor protection is clinically relevant given that a BRD4 gene signature predicts positive clinical outcome in breast and lung cancer. Our results demonstrate a protective function for BRD4 and suggest tissue-specific roles for BRD4 in tumorigenesis. : The premature aging disorder Hutchinson-Gilford progeria syndrome (HGPS provides a unique tool for studying the interplay between DNA damage and aging-associated tumor mechanisms, given that HGPS patients do not develop tumors despite elevated levels of DNA damage. Using a genome-wide RNAi screen, Fernandez et al. now identify the bromodomain protein BRD4 as a mediator of the oncogenic resistance of HGPS cells. This tumor-protective function of BRD4 involves inhibition of oncogenic dedifferentiation and is also active in non-HGPS cells in a tissue-specific manner.

  8. Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria.

    Science.gov (United States)

    Brace, Lear E; Vose, Sarah C; Vargas, Dorathy F; Zhao, Shuangyun; Wang, Xiu-Ping; Mitchell, James R

    2013-12-01

    Cockayne syndrome (CS) is a rare autosomal recessive segmental progeria characterized by growth failure, lipodystrophy, neurological abnormalities, and photosensitivity, but without skin cancer predisposition. Cockayne syndrome life expectancy ranges from 5 to 16 years for the two most severe forms (types II and I, respectively). Mouse models of CS have thus far been of limited value due to either very mild phenotypes, or premature death during postnatal development prior to weaning. The cause of death in severe CS models is unknown, but has been attributed to extremely rapid aging. Here, we found that providing mutant pups with soft food from as late as postnatal day 14 allowed survival past weaning with high penetrance independent of dietary macronutrient balance in a novel CS model (Csa(-/-) | Xpa(-/-)). Survival past weaning revealed a number of CS-like symptoms including small size, progressive loss of adiposity, and neurological symptoms, with a maximum lifespan of 19 weeks. Our results caution against interpretation of death before weaning as premature aging, and at the same time provide a valuable new tool for understanding mechanisms of progressive CS-related progeroid symptoms including lipodystrophy and neurodysfunction. © 2013 the Anatomical Society and John Wiley & Sons Ltd.

  9. NF-κB activation impairs somatic cell reprogramming in ageing.

    Science.gov (United States)

    Soria-Valles, Clara; Osorio, Fernando G; Gutiérrez-Fernández, Ana; De Los Angeles, Alejandro; Bueno, Clara; Menéndez, Pablo; Martín-Subero, José I; Daley, George Q; Freije, José M P; López-Otín, Carlos

    2015-08-01

    Ageing constitutes a critical impediment to somatic cell reprogramming. We have explored the regulatory mechanisms that constitute age-associated barriers, through derivation of induced pluripotent stem cells (iPSCs) from individuals with premature or physiological ageing. We demonstrate that NF-κB activation blocks the generation of iPSCs in ageing. We also show that NF-κB repression occurs during cell reprogramming towards a pluripotent state. Conversely, ageing-associated NF-κB hyperactivation impairs the generation of iPSCs by eliciting the reprogramming repressor DOT1L, which reinforces senescence signals and downregulates pluripotency genes. Genetic and pharmacological NF-κB inhibitory strategies significantly increase the reprogramming efficiency of fibroblasts from Néstor-Guillermo progeria syndrome and Hutchinson-Gilford progeria syndrome patients, as well as from normal aged donors. Finally, we demonstrate that DOT1L inhibition in vivo extends lifespan and ameliorates the accelerated ageing phenotype of progeroid mice, supporting the interest of studying age-associated molecular impairments to identify targets of rejuvenation strategies.

  10. Learning about Progeria

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  11. Progeria Research Foundation, Inc.

    Science.gov (United States)

    ... Million Views – Celebrate with Us! Sam’s talk, "My Philosophy for a Happy Life", has inspired over 25 ... July 11th, 2016 | 0 Comments PRF Continues Aggressive Research Agenda Events November 25, 2017 in Verona, NJ: ...

  12. Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations.

    Science.gov (United States)

    Core, Jason Q; Mehrabi, Mehrsa; Robinson, Zachery R; Ochs, Alexander R; McCarthy, Linda A; Zaragoza, Michael V; Grosberg, Anna

    2017-01-01

    Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. As a test case, cultured skin-fibroblast nuclei of individuals possessing LMNA splice-site mutation (c.357-2A>G), LMNA nonsense mutation (c.736 C>T, pQ246X) in exon 4, LMNA missense mutation (c.1003C>T, pR335W) in exon 6, Hutchinson-Gilford Progeria Syndrome, and no LMNA mutations were analyzed. For each cell type, the percentage of dysmorphic nuclei, and other morphological features such as average nuclear area and average eccentricity were obtained. Compared to blind observers, our procedure implemented in Matlab codes possessed similar accuracy to manual counting of dysmorphic nuclei while being significantly more consistent. The automatic quantification of nuclear defects revealed a correlation between in vitro results and age of patients for initial symptom onset. Our results demonstrate the method's utility in experimental studies of diseases affecting nuclear shape through automated, unbiased, and accurate identification of dysmorphic nuclei.

  13. Human diseases associated with defective DNA repair

    International Nuclear Information System (INIS)

    Friedberg, E.C.; Ehmann, U.K.; Williams, J.I.

    1979-01-01

    The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

  14. Survey of radiosensitivity in a variety of human cell strains

    Energy Technology Data Exchange (ETDEWEB)

    Arlett, C.F.; Harcourt, S.A.

    1980-03-01

    Gamma-ray sensitivity for cell killing was assayed in 54 human cell strains, including some derived from individuals suffering from certain hereditary diseases. The overall range of Do values in this study was 38 to 180 rads, indicating a considerable range of variability in humans. The normal sensitivity was described by a range of Do values of 97 to 180 rads. All ten ataxia telangiectasia cell strains tested proved radiosensitive and gave a mean Do value of 57 +- 15 (S.E.) rads, and these represent the most radiosensitive human skin fibroblasts currently available. Representative cell strains from familial retinoblastoma, Fanconi's anemia, and Hutchinson-Gilford progeria occupied positions of intermediate sensitivity, as did one of two ataxia telangiectasia heterozygotes. Six xeroderma pigmentosum cell strains together with two Cockayne's syndrome cell strains (all known to be sensitive to ultraviolet light) fell into the normal range, indicating an absence of cross-sensitivity between ultraviolet light and gamma-irradiation.

  15. Nuclear protein import is reduced in cells expressing nuclear envelopathy-causing lamin A mutants

    International Nuclear Information System (INIS)

    Busch, Albert; Kiel, Tilman; Heupel, Wolfgang-M.; Wehnert, Manfred; Huebner, Stefan

    2009-01-01

    Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import.

  16. Epigenomic maintenance through dietary intervention can facilitate DNA repair process to slow down the progress of premature aging.

    Science.gov (United States)

    Ghosh, Shampa; Sinha, Jitendra Kumar; Raghunath, Manchala

    2016-09-01

    DNA damage caused by various sources remains one of the most researched topics in the area of aging and neurodegeneration. Increased DNA damage causes premature aging. Aging is plastic and is characterised by the decline in the ability of a cell/organism to maintain genomic stability. Lifespan can be modulated by various interventions like calorie restriction, a balanced diet of macro and micronutrients or supplementation with nutrients/nutrient formulations such as Amalaki rasayana, docosahexaenoic acid, resveratrol, curcumin, etc. Increased levels of DNA damage in the form of double stranded and single stranded breaks are associated with decreased longevity in animal models like WNIN/Ob obese rats. Erroneous DNA repair can result in accumulation of DNA damage products, which in turn result in premature aging disorders such as Hutchinson-Gilford progeria syndrome. Epigenomic studies of the aging process have opened a completely new arena for research and development of drugs and therapeutic agents. We propose here that agents or interventions that can maintain epigenomic stability and facilitate the DNA repair process can slow down the progress of premature aging, if not completely prevent it. © 2016 IUBMB Life, 68(9):717-721, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

  17. Directed Differentiation of Human-Induced Pluripotent Stem Cells to Mesenchymal Stem Cells.

    Science.gov (United States)

    Lian, Qizhou; Zhang, Yuelin; Liang, Xiaoting; Gao, Fei; Tse, Hung-Fat

    2016-01-01

    Multipotent stromal cells, also known as mesenchymal stem cells (MSCs), possess great potential to generate a wide range of cell types including endothelial cells, smooth muscle cells, bone, cartilage, and lipid cells. This protocol describes in detail how to perform highly efficient, lineage-specific differentiation of human-induced pluripotent stem cells (iPSCs) with an MSCs fate. The approach uses a clinically compliant protocol with chemically defined media, feeder-free conditions, and a CD105 positive and CD24 negative selection to achieve a single cell-based MSCs derivation from differentiating human pluripotent cells in approximately 20 days. Cells generated with this protocol express typical MSCs surface markers and undergo adipogenesis, osteogenesis, and chondrogenesis similar to adult bone marrow-derived MSCs (BM-MSCs). Nonetheless, compared with adult BM-MSCs, iPSC-MSCs display a higher proliferative capacity, up to 120 passages, without obvious loss of self-renewal potential and constitutively express MSCs surface antigens. MSCs generated with this protocol have numerous applications, including expansion to large scale cell numbers for tissue engineering and the development of cellular therapeutics. This approach has been used to rescue limb ischemia, allergic disorders, and cigarette smoke-induced lung damage and to model mesenchymal and vascular disorders of Hutchinson-Gilford progeria syndrome (HGPS).

  18. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.

    Science.gov (United States)

    Hilton, Benjamin A; Liu, Ji; Cartwright, Brian M; Liu, Yiyong; Breitman, Maya; Wang, Youjie; Jones, Rowdy; Tang, Hui; Rusinol, Antonio; Musich, Phillip R; Zou, Yue

    2017-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene, resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA sequestration likely exposed ds-ssDNA junctions at replication forks for XPA binding. Depletion of XPA or progerin each significantly restored PCNA at replication forks. Our results suggest that although PCNA is much more competitive than XPA in binding replication forks, PCNA sequestration by progerin may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that progerin-induced apoptosis could be rescued by XPA, suggesting that XPA-replication fork binding may prevent apoptosis in HGPS cells. Our results propose a mechanism for progerin-induced genome instability and accelerated replicative senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman, M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes. © FASEB.

  19. A crucial role of ROCK for alleviation of senescence-associated phenotype.

    Science.gov (United States)

    Park, Joon Tae; Kang, Hyun Tae; Park, Chi Hyun; Lee, Young-Sam; Cho, Kyung A; Park, Sang Chul

    2018-06-01

    In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells. Moreover, microarray analysis revealed that the up-regulated pathway upon ROCK inhibition is enriched for chromatin remodeling genes, which may play an important role in the alleviation of senescence-associated cell cycle arrest. Indeed, ROCK inhibition induced cellular proliferation, concomitant with the amelioration of senescent phenotype. Furthermore, the restorative effect by ROCK inhibition was observed in vivo as evidenced by the facilitated cutaneous wound healing. Taken together, our data indicate that ROCK inhibition might be utilized to ameliorate normal aging process and to treat age-related disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Aged induced pluripotent stem cell (iPSCs) as a new cellular model for studying premature aging.

    Science.gov (United States)

    Petrini, Stefania; Borghi, Rossella; D'Oria, Valentina; Restaldi, Fabrizia; Moreno, Sandra; Novelli, Antonio; Bertini, Enrico; Compagnucci, Claudia

    2017-05-31

    Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents. Confocal and four-dimensional imaging combined with molecular analyses, showed that aged iPSCs are characterized by nuclear dysmorphisms, nucleoskeletal components (lamin A/C-prelamin isoforms, lamin B1, emerin, and nesprin-2) imbalance, leading to impaired nucleo-cytoplasmic MKL1 shuttling, actin polymerization defects, mitochondrial dysfunctions, SIRT7 downregulation and NF-kBp65 hyperactivation. The observed age-related NE features of iPSCs closely resemble those reported for premature aging syndromes (e.g., Hutchinson-Gilford progeria syndrome) and for somatic cell senescence. These findings validate the use of aged iPSCs as a suitable cellular model to study senescence and for investigating therapeutic strategies aimed to treat premature aging.

  1. Mitotic defects lead to pervasive aneuploidy and accompany loss of RB1 activity in mouse LmnaDhe dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    C Herbert Pratt

    2011-03-01

    Full Text Available Lamin A (LMNA is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350 and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670. Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1 activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood.We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (Lmna(Dhe. We found that dermal fibroblasts from heterozygous Lmna(Dhe (Lmna(Dhe/+ mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, Lmna(Dhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3, a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1 also was perturbed in Lmna(Dhe/+ cells. Lmna(Dhe/+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects.These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control.

  2. Mitotic Defects Lead to Pervasive Aneuploidy and Accompany Loss of RB1 Activity in Mouse LmnaDhe Dermal Fibroblasts

    Science.gov (United States)

    Pratt, C. Herbert; Curtain, Michelle; Donahue, Leah Rae; Shopland, Lindsay S.

    2011-01-01

    Background Lamin A (LMNA) is a component of the nuclear lamina and is mutated in several human diseases, including Emery-Dreifuss muscular dystrophy (EDMD; OMIM ID# 181350) and the premature aging syndrome Hutchinson-Gilford progeria syndrome (HGPS; OMIM ID# 176670). Cells from progeria patients exhibit cell cycle defects in both interphase and mitosis. Mouse models with loss of LMNA function have reduced Retinoblastoma protein (RB1) activity, leading to aberrant cell cycle control in interphase, but how mitosis is affected by LMNA is not well understood. Results We examined the cell cycle and structural phenotypes of cells from mice with the Lmna allele, Disheveled hair and ears (LmnaDhe). We found that dermal fibroblasts from heterozygous LmnaDhe (LmnaDhe/+) mice exhibit many phenotypes of human laminopathy cells. These include severe perturbations to the nuclear shape and lamina, increased DNA damage, and slow growth rates due to mitotic delay. Interestingly, LmnaDhe/+ fibroblasts also had reduced levels of hypophosphorylated RB1 and the non-SMC condensin II-subunit D3 (NCAP-D3), a mitosis specific centromere condensin subunit that depends on RB1 activity. Mitotic check point control by mitotic arrest deficient-like 1 (MAD2L1) also was perturbed in LmnaDhe /+ cells. LmnaDhe /+ fibroblasts were consistently aneuploid and had higher levels of micronuclei and anaphase bridges than normal fibroblasts, consistent with chromosome segregation defects. Conclusions These data indicate that RB1 may be a key regulator of cellular phenotype in laminopathy-related cells, and suggest that the effects of LMNA on RB1 include both interphase and mitotic cell cycle control. PMID:21464947

  3. Aerial gamma ray and magnetic survey: Fremont Quadrangle, Nebraska, Iowa; Lincoln Quadrangle, Nebraska; Manhattan Quadrangle, Kansas; Hutchinson Quadrangle, Kansas. Final report. Volume I

    International Nuclear Information System (INIS)

    1977-11-01

    A high sensitivity airborne radiometric and magnetic survey of the East Salina Basin Area (Kansas and Nebraska) was conducted. The project area, the Hutchinson and Manhattan, Kansas sheets, consists of approximately 30,800 square miles. A total of 11,287 line miles of high sensitivity radiometric and magnetic data were collected. All data were collected utilizing a fixed wing aircraft, and over 3,500 cubic inches of NaI crystal detector. Magnetometer data were collected utilizing a high sensitivity 0.25 gamma, proton magnetometer. All field data were returned to GeoMetrics, Sunnyvale, California computer facilities for processing, statistical analysis and interpretation. As an integral part of this final report, other data are presented which include corrected profiles of all radiometric variables (total count, K, U, Th, U/Th, U/K, and Th/K, ratios), magnetic data, radar altimeter data, barometric altimeter data, air temperature and airborne Bi contributions. Radiometric data presented are corrected for Compton Scatter, altitude dependence and atmospheric Bismuth. These data are presented in the form of strip charts as averaged one second samples using a 5 second moving average window, microfiche and digital magnetic tapes containing raw spectral data, single record data, averaged record data, and statistical analysis results. In addition, computer generated anomaly maps and interpretation maps are presented relating known geology or soil distribution to the corrected radiometric data

  4. Human longevity and common variations in the LMNA gene: a meta-analysis

    Science.gov (United States)

    Conneely, Karen N.; Capell, Brian C.; Erdos, Michael R.; Sebastiani, Paola; Solovieff, Nadia; Swift, Amy J.; Baldwin, Clinton T.; Budagov, Temuri; Barzilai, Nir; Atzmon, Gil; Puca, Annibale A.; Perls, Thomas T.; Geesaman, Bard J.; Boehnke, Michael; Collins, Francis S.

    2012-01-01

    Summary A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (US Caucasians with age ≥95 years, N=873) and genetically matched younger controls (N=443). We tested all common non-redundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on 4 SNPs, remained significant after adjustment for multiple testing (OR = 1.56, P=2.5×10−5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3448 subjects from four independent samples of long-lived individuals and control subjects from 1) the New England Centenarian Study (NECS) (N=738), 2) the Southern Italian Centenarian Study (SICS) (N=905), 3) France (N=1103), and 4) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR = 1.60, P=0.0023), but not in the other three samples (P>.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR = 1.18, P=7.5×10−4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. PMID:22340368

  5. Differential temporal and spatial progerin expression during closure of the ductus arteriosus in neonates.

    Directory of Open Access Journals (Sweden)

    Regina Bökenkamp

    Full Text Available Closure of the ductus arteriosus (DA at birth is essential for the transition from fetal to postnatal life. Before birth the DA bypasses the uninflated lungs by shunting blood from the pulmonary trunk into the systemic circulation. The molecular mechanism underlying DA closure and degeneration has not been fully elucidated, but is associated with apoptosis and cytolytic necrosis in the inner media and intima. We detected features of histology during DA degeneration that are comparable to Hutchinson Gilford Progeria syndrome and ageing. Immunohistochemistry on human fetal and neonatal DA, and aorta showed that lamin A/C was expressed in all layers of the vessel wall. As a novel finding we report that progerin, a splicing variant of lamin A/C was expressed almost selectively in the normal closing neonatal DA, from which we hypothesized that progerin is involved in DA closure. Progerin was detected in 16.2%±7.2 cells of the DA. Progerin-expressing cells were predominantly located in intima and inner media where cytolytic necrosis accompanied by apoptosis will develop. Concomitantly we found loss of α-smooth muscle actin as well as reduced lamin A/C expression compared to the fetal and non-closing DA. In cells of the adjacent aorta, that remains patent, progerin expression was only sporadically detected in 2.5%±1.5 of the cells. Data were substantiated by the detection of mRNA of progerin in the neonatal DA but not in the aorta, by PCR and sequencing analysis. The fetal DA and the non-closing persistent DA did not present with progerin expressing cells. Our analysis revealed that the spatiotemporal expression of lamin A/C and progerin in the neonatal DA was mutually exclusive. We suggest that activation of LMNA alternative splicing is involved in vascular remodeling in the circulatory system during normal neonatal DA closure.

  6. Progeria Research Foundation Diagnostic Testing Program

    Science.gov (United States)

    ... Share the DVD Meet the Kids in the Movie Bring LATS to the classroom! Close News/Events ... this could severely affect their research results and interpretation. Through the PRF Diagnostics Program, each cell line ...

  7. 核纤层蛋白病--一个基因,多种疾病%Laminopathies -one gene, multiple diseases

    Institute of Scientific and Technical Information of China (English)

    宋书娟; 章远志; Nanbert ZHONG

    2005-01-01

    @@ 核纤层蛋白病(laminopathies)是指由LMNA基因及其编码蛋白lamin A/C异常引起的一组人类遗传病[1].根据临床特征不同,至今被认识的核纤层蛋白病已有10种,除一种由影响成熟lamin A形成的FACE-1基因突变引起外[2],其余9种均由LMNA基因突变引起,其中包括2种既可以常染色体显性又可以常染色体隐性遗传的遗传病:Emery-Dreifuss 肌营养不良(Emery-Dreifuss muscular dystrophy, EDMD,常显EDMD2,常隐EDMD3)[3,4] 和腓骨肌萎缩症2型(Charcot-Marie-Tooth2,常显AD-CMT2,常隐AR-CMT2)[5,6];6种常染色体显性遗传病:肢带型肌营养不良1B(limb girdle muscular dystrophy1B,LGMD1B)[7],扩张性心肌病伴心脏传导阻滞1A(dilated cardiomyopathy and cardiac conduction defects1A, CMD1A)[8],家族部分性脂肪营养不良(familial partial lipodystrophy, FPLD)[9],脂肪营养不良、胰岛素抵抗型糖尿病、弥漫性白黑皮病样丘疹、肝脂肪变性和心肌病综合征(lipoatrophy & insulin-resistant diabetes & disseminated leukomelanodermic papules & liver steatosis and cardiomyopathy,LDHPC)[10],Werner综合征(Werner syndrome, WRN)[11]和早老症(Hutchinson-Gilford progeria syndrome,HGPS)[12];1种常染色体隐性遗传病: Mandibuloacral dysplasia(MAD)[13].

  8. MicroRNA transcriptome analysis identifies miR-365 as a novel negative regulator of cell proliferation in Zmpste24-deficient mouse embryonic fibroblasts

    International Nuclear Information System (INIS)

    Xiong, Xing-dong; Jung, Hwa Jin; Gombar, Saurabh; Park, Jung Yoon; Zhang, Chun-long; Zheng, Huiling; Ruan, Jie; Li, Jiang-bin; Kaeberlein, Matt

    2015-01-01

    Highlights: • A comprehensive miRNA transcriptome of MEFs from Zmpste24 −/− and control mice. • Identification of miR-365 as a down-regulated miRNA in Zmpste24 −/− MEFs. • Characterization of miR-365 as a modulator of cellular growth in part by targeting Rasd1. - Abstract: Zmpste24 is a metalloproteinase responsible for the posttranslational processing and cleavage of prelamin A into mature laminA. Zmpste24 −/− mice display a range of progeroid phenotypes overlapping with mice expressing progerin, an altered version of lamin A associated with Hutchinson-Gilford progeria syndrome (HGPS). Increasing evidence has demonstrated that miRNAs contribute to the regulation of normal aging process, but their roles in progeroid disorders remain poorly understood. Here we report the miRNA transcriptomes of mouse embryonic fibroblasts (MEFs) established from wild type (WT) and Zmpste24 −/− progeroid mice using a massively parallel sequencing technology. With data from 19.5 × 10 6 reads from WT MEFs and 16.5 × 10 6 reads from Zmpste24 −/− MEFs, we discovered a total of 306 known miRNAs expressed in MEFs with a wide dynamic range of read counts ranging from 10 to over 1 million. A total of 8 miRNAs were found to be significantly down-regulated, with only 2 miRNAs upregulated, in Zmpste24 −/− MEFs as compared to WT MEFs. Functional studies revealed that miR-365, a significantly down-regulated miRNA in Zmpste24 −/− MEFs, modulates cellular growth phenotypes in MEFs. Overexpression of miR-365 in Zmpste24 −/− MEFs increased cellular proliferation and decreased the percentage of SA-β-gal-positive cells, while inhibition of miR-365 function led to an increase of SA-β-gal-positive cells in WT MEFs. Furthermore, we identified Rasd1, a member of the Ras superfamily of small GTPases, as a functional target of miR-365. While expression of miR-365 suppressed Rasd1 3′ UTR luciferase-reporter activity, this effect was lost with mutations in the

  9. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    International Nuclear Information System (INIS)

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-01-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  10. Tumor-Protective Mechanism Identified from Premature Aging Disease | Center for Cancer Research

    Science.gov (United States)

    Hutchinson-Gilford Progeria Syndrome (HGPS) is an extraordinarily rare genetic disorder caused by a mutation in the LMNA gene, which encodes architectural proteins of the human cell nucleus. The mutation causes the production of a mutant protein called progerin. Patients with HGPS display signs of premature aging, such as hair loss, slowed growth, weakening of bone and joint integrity, and cardiovascular disease. Most die in their mid-teens of heart disease or stroke. Intriguingly, these patients do not develop another aging-related disease, cancer, despite having dramatically elevated levels of DNA damage. Tom Misteli, Ph.D., of CCR’s Laboratory of Receptor Biology and Gene Expression, and his colleagues hypothesized that, rather than patients not living long enough to develop cancer, a resistance mechanism was operating in HGPS cells to prevent cancer formation. To begin testing this idea, the researchers transformed fibroblasts from HGPS patients or age-matched, healthy controls with telomerase, constitutively-activated HRAS, and SV40 large and small T antigens. Transformed HGPS cells displayed morphological changes and increased proliferation similar to transformed controls but formed fewer colonies in soft agar and fewer tumors when injected into mice. When the investigators examined global gene expression in the two populations of cells, they found that transformed HGPS cells failed to activate many of the genes that are induced in response to transformation in controls, including oncogenic and proliferation pathways. In addition the transformed HGPS cells were unable to undergo oncogenic de-differentiation. Importantly, the tumor resistance in HGPS cells was due to the presence of the progerin protein, which was both necessary and sufficient to protect cells from oncogenic transformation. Together these results suggested that HGPS cells resist cancer-inducing stimuli by not undergoing the genetic reprogramming necessary for tumor initiation. The scientists

  11. Exome sequencing reveals a de novo POLD1 mutation causing phenotypic variability in mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL).

    Science.gov (United States)

    Elouej, Sahar; Beleza-Meireles, Ana; Caswell, Richard; Colclough, Kevin; Ellard, Sian; Desvignes, Jean Pierre; Béroud, Christophe; Lévy, Nicolas; Mohammed, Shehla; De Sandre-Giovannoli, Annachiara

    2017-06-01

    Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance and metabolic abnormalities. This syndrome is caused by heterozygous de novo mutations in the POLD1 gene. To date, 19 patients with MDPL have been reported in the literature and among them 14 patients have been characterized at the molecular level. Twelve unrelated patients carried a recurrent in-frame deletion of a single codon (p.Ser605del) and two other patients carried a novel heterozygous mutation in exon 13 (p.Arg507Cys). Additionally and interestingly, germline mutations of the same gene have been involved in familial polyposis and colorectal cancer (CRC) predisposition. We describe a male and a female patient with MDPL respectively affected with mild and severe phenotypes. Both of them showed mandibular hypoplasia, a beaked nose with bird-like facies, prominent eyes, a small mouth, growth retardation, muscle and skin atrophy, but the female patient showed such a severe and early phenotype that a first working diagnosis of Hutchinson-Gilford Progeria was made. The exploration was performed by direct sequencing of POLD1 gene exon 15 in the male patient with a classical MDPL phenotype and by whole exome sequencing in the female patient and her unaffected parents. Exome sequencing identified in the latter patient a de novo heterozygous undescribed mutation in the POLD1 gene (NM_002691.3: c.3209T>A), predicted to cause the missense change p.Ile1070Asn in the ZnF2 (Zinc Finger 2) domain of the protein. This mutation was not reported in the 1000 Genome Project, dbSNP and Exome sequencing databases. Furthermore, the Isoleucine1070 residue of POLD1 is highly conserved among various species, suggesting that this substitution may cause a major impairment of POLD1 activity. For the second patient, affected with a typical MDPL phenotype, direct sequencing

  12. Brabazon House Nursing Home, 2 Gilford Road, Sandymount, Dublin 4.

    LENUS (Irish Health Repository)

    Xiao, Liang

    2011-02-01

    In this paper, we give an overview of methadone treatment in Ireland and outline the rationale for designing an electronic health record (EHR) with extensibility, interoperability and decision support functionality. Incorporating several international standards, a conceptual model applying a problem orientated approach in a hierarchical structure has been proposed for building the EHR.

  13. Plasma myelin basic protein assay using Gilford enzyme immunoassay cuvettes.

    Science.gov (United States)

    Groome, N P

    1981-10-01

    The assay of myelin basic protein in body fluids has potential clinical importance as a routine indicator of demyelination. Preliminary details of a competitive enzyme immunoassay for this protein have previously been published by the author (Groome, N. P. (1980) J. Neurochem. 35, 1409-1417). The present paper now describes the adaptation of this assay for use on human plasma and various aspects of routine data processing. A commercially available cuvette system was found to have advantages over microtitre plates but required a permuted arrangement of sample replicates for consistent results. For dose interpolation, the standard curve could be fitted to a three parameter non-linear equation by regression analysis or linearised by the logit/log transformation.

  14. Asteraceae - an evaluation of hutchinsons beetle-daisy hypothesis

    CSIR Research Space (South Africa)

    Midgley, JJ

    1993-05-01

    Full Text Available repel the beetles. However in this review of plant mimicry worldwide, it is considered an exceptionally intriguing example of Batesian mimicry. Despite the fact there still appears to be a dearth of information on the interaction between beetle...

  15. 33 CFR 117.793 - Hutchinson River (Eastchester Creek).

    Science.gov (United States)

    2010-07-01

    ... high tide. For the purposes of this section, predicted high tide occurs four hours after predicted high water for New York (Battery), as given in the tide tables published by private entities using data provided by the National Ocean Service. (1) At all other times, the bridge shall open on signal if at least...

  16. Hutchinson's sign as a marker of ocular involvement in HIVpositive ...

    African Journals Online (AJOL)

    Background. A positive Hutchinsonfs sign indicates an increased risk of ocular involvement in herpes zoster ophthalmicus (HZO). We examined the sensitivity of Hutchinsonfs sign as an indicator of ocular involvement in a consecutive series of patients presenting with HZO. Methods. We conducted a descriptive ...

  17. MicroRNA transcriptome analysis identifies miR-365 as a novel negative regulator of cell proliferation in Zmpste24-deficient mouse embryonic fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Xiong, Xing-dong [Institute of Aging Research, Guangdong Medical College, Xin Cheng Avenue 1#, Songshan Lake, Dongguan, Guangdong 523808 (China); Institute of Biochemistry & Molecular Biology, Guangdong Medical College, Zhanjiang 524023 (China); Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan 523808 (China); Institute of Laboratory Medicine, Guangdong Medical College, Dongguan, Guangdong 523808 (China); Jung, Hwa Jin [Departments of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Gombar, Saurabh [Departments of Systems Biology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Park, Jung Yoon [Departments of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Zhang, Chun-long; Zheng, Huiling [Institute of Aging Research, Guangdong Medical College, Xin Cheng Avenue 1#, Songshan Lake, Dongguan, Guangdong 523808 (China); Institute of Biochemistry & Molecular Biology, Guangdong Medical College, Zhanjiang 524023 (China); Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan 523808 (China); Ruan, Jie; Li, Jiang-bin [Institute of Aging Research, Guangdong Medical College, Xin Cheng Avenue 1#, Songshan Lake, Dongguan, Guangdong 523808 (China); Institute of Biochemistry & Molecular Biology, Guangdong Medical College, Zhanjiang 524023 (China); Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Dongguan 523808 (China); Institute of Laboratory Medicine, Guangdong Medical College, Dongguan, Guangdong 523808 (China); Kaeberlein, Matt [Institute of Aging Research, Guangdong Medical College, Xin Cheng Avenue 1#, Songshan Lake, Dongguan, Guangdong 523808 (China); Department of Pathology, University of Washington, Seattle, WA 98195 (United States); and others

    2015-07-15

    Highlights: • A comprehensive miRNA transcriptome of MEFs from Zmpste24{sup −/−} and control mice. • Identification of miR-365 as a down-regulated miRNA in Zmpste24{sup −/−} MEFs. • Characterization of miR-365 as a modulator of cellular growth in part by targeting Rasd1. - Abstract: Zmpste24 is a metalloproteinase responsible for the posttranslational processing and cleavage of prelamin A into mature laminA. Zmpste24{sup −/−} mice display a range of progeroid phenotypes overlapping with mice expressing progerin, an altered version of lamin A associated with Hutchinson-Gilford progeria syndrome (HGPS). Increasing evidence has demonstrated that miRNAs contribute to the regulation of normal aging process, but their roles in progeroid disorders remain poorly understood. Here we report the miRNA transcriptomes of mouse embryonic fibroblasts (MEFs) established from wild type (WT) and Zmpste24{sup −/−} progeroid mice using a massively parallel sequencing technology. With data from 19.5 × 10{sup 6} reads from WT MEFs and 16.5 × 10{sup 6} reads from Zmpste24{sup −/−} MEFs, we discovered a total of 306 known miRNAs expressed in MEFs with a wide dynamic range of read counts ranging from 10 to over 1 million. A total of 8 miRNAs were found to be significantly down-regulated, with only 2 miRNAs upregulated, in Zmpste24{sup −/−} MEFs as compared to WT MEFs. Functional studies revealed that miR-365, a significantly down-regulated miRNA in Zmpste24{sup −/−} MEFs, modulates cellular growth phenotypes in MEFs. Overexpression of miR-365 in Zmpste24{sup −/−} MEFs increased cellular proliferation and decreased the percentage of SA-β-gal-positive cells, while inhibition of miR-365 function led to an increase of SA-β-gal-positive cells in WT MEFs. Furthermore, we identified Rasd1, a member of the Ras superfamily of small GTPases, as a functional target of miR-365. While expression of miR-365 suppressed Rasd1 3′ UTR luciferase-reporter activity

  18. Archaeological Investigation of the Marine Railway Site, Hutchinson’s Island, Savannah, Georgia

    Science.gov (United States)

    1985-03-14

    Fields of praise: The official history of the Welsh Rugby Union , by David Smith and Gareth Williams IN Choice May 1981 Fighting knives: An illustrated...This is indicative of different support demands because the main load would be born by the metal plates on which the carriage supporting the vessel’s...coupled with necessary harbor widening, led to allowing its removal. • While the sUe was first identified by its physical remains, most of the 57

  19. 77 FR 6012 - Drawbridge Operation Regulations; Hutchinson River (Eastchester Creek), Bronx, NY

    Science.gov (United States)

    2012-02-07

    ... INFORMATION CONTACT: If you have questions on this rule, call or email Ms. Judy Leung-Yee, Project Officer, First Coast Guard District, [email protected] , or telephone (212) 668-7165. If you have...

  20. OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.

    Science.gov (United States)

    Simon, Dan N; Wriston, Amanda; Fan, Qiong; Shabanowitz, Jeffrey; Florwick, Alyssa; Dharmaraj, Tejas; Peterson, Sherket B; Gruenbaum, Yosef; Carlson, Cathrine R; Grønning-Wang, Line M; Hunt, Donald F; Wilson, Katherine L

    2018-05-17

    The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails. Using mass spectrometry, we identified 11 O -GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O -GlcNAc-modified at seven sites. By contrast, O -GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. Interestingly, deletion Δ35, which does not remove the majority of identified O -GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1. These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function. The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.

  1. Structure of the lamin A/C R482W mutant responsible for dominant familial partial lipodystrophy (FPLD)

    Energy Technology Data Exchange (ETDEWEB)

    Magracheva, Eugenia; Kozlov, Serguei; Stewart, Colin L.; Wlodawer, Alexander; Zdanov, Alexander; (NCI)

    2009-08-07

    Proteins of the A-type lamin family, which consists of two members, lamin A and lamin C, are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A-type lamins have recently become the focus of extensive functional studies as a consequence of the linking of at least eight congenital diseases to mutations in the lamin A/C gene (LMNA). This spectrum of pathologies, which mostly manifest themselves as dominant traits, includes muscle dystrophies, dilated cardiomyopathies, the premature aging syndrome Hutchinson-Guilford progeria and familial partial lipodystrophy (FPLD). The crystal structure of the lamin A/C mutant R482W, a variant that causes FPLD, has been determined at 1.5 {angstrom} resolution. A completely novel aggregation state of the C-terminal globular domain and the position of the mutated amino-acid residue suggest means by which the mutation may affect lamin A/C-protein and protein-DNA interactions.

  2. Federal Grant "Seed Money"--Sprouted, Growing and Blooming in the Kansas Sandhills: Interdisciplinary Studies--Their "Place in the Sun."

    Science.gov (United States)

    Bogner, Donna

    The Outdoor Research Project of Hutchinson Senior High School in Hutchinson, Kansas, was funded in 1977 to conduct a scientific baseline study of an outdoor education center and a state park. Gifted students used initial limnology tests, fish population studies, and groundcover analyses to produce management recommendations and a computer…

  3. 76 FR 8917 - Pears Grown in Oregon and Washington; Continuance Referendum

    Science.gov (United States)

    2011-02-16

    ...: Teresa Hutchinson, Marketing Specialist, or Gary D. Olson, Regional Manager, Northwest Marketing Field...) 326-2724, Fax: (503) 326-7440, or E-mail: [email protected] or GaryD.Olson@ams.usda.gov.... Teresa Hutchinson and Gary D. Olson of the Northwest Marketing Field Office, Fruit and Vegetable Programs...

  4. 75 FR 4844 - Chesapeake and Ohio Canal National Historical Park Advisory Commission; Notice of Public Meeting

    Science.gov (United States)

    2010-01-29

    .... Mr. Charles J. Weir. Mr. Barry A. Passett. Mr. James G. McCleaf, II. Mr. John A. Ziegler. Mrs. Mary E.... Gilford. Brother James Kirkpatrick. Dr. George E. Lewis, Jr. Mr. Charles D. McElrath. Ms. Patricia Schooley. Mr. Jack Reeder. Ms. Merrily Pierce. Topics that will be presented during the meeting include: 1...

  5. 75 FR 41520 - Chesapeake and Ohio Canal National Historical Park Advisory Commission; Notice of Public Meeting

    Science.gov (United States)

    2010-07-16

    ... Rabb Weidenfeld, Chairperson Mr. Charles J. Weir Mr. Barry A. Passett Mr. James G. McCleaf II Mr. John... Reynolds Dr. James H. Gilford Brother James Kirkpatrick Dr. George E. Lewis, Jr. Mr. Charles D. McElrath Ms. Patricia Schooley Mr. Jack Reeder Ms. Merrily Pierce Topics that will be presented during the meeting...

  6. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    Science.gov (United States)

    ... Testing (1 link) Genetic Testing Registry: Acute myeloid leukemia Other Diagnosis and Management Resources (3 links) Fred Hutchinson Cancer Research Center National Cancer Institute: Acute Myeloid Leukemia Treatment St. Jude Children's Research Hospital General Information ...

  7. A new approach to superfractals

    International Nuclear Information System (INIS)

    Singh, S.L.; Jain, Sarika; Mishra, S.N.

    2009-01-01

    V-variable fractals and superfractals have recently been introduced by Barnsley [Barnsley Michael, Hutchinson John, Stenflo Orjan. A fractal valued random iteration algorithm and fractal hierarchy. Fractals 2005;13(2):111-46 [MR2151094 (2006b:28014)

  8. A new approach to superfractals

    Energy Technology Data Exchange (ETDEWEB)

    Singh, S.L. [Vedic MRI, 21, Govind Nagar, Rishikesh 249201 (India)], E-mail: vedicmri@gmail.com; Jain, Sarika [Department of Computer Science and Engineering, Amity School of Engineering and Technology, Amity University, Noida, UP (India); Mishra, S.N. [Department of Mathematics and Applied Mathematics, Walter Sisulu University, Nelson Mandela Drive, Mthatha 5117 (South Africa)

    2009-12-15

    V-variable fractals and superfractals have recently been introduced by Barnsley [Barnsley Michael, Hutchinson John, Stenflo Orjan. A fractal valued random iteration algorithm and fractal hierarchy. Fractals 2005;13(2):111-46 [MR2151094 (2006b:28014)

  9. Diet and Cancer Prevention: Chewing on the Human Complexities | Division of Cancer Prevention

    Science.gov (United States)

    Speaker Johanna W. Lampe, PhD, RD Research Professor University of Washington Full Member and Associate Division Director Cancer Prevention Program Public Health Sciences Division Fred Hutchinson Cancer Research Center Seattle, WA |

  10. New Partnership Seeks to Increase Availability of Lifesaving Transplants | FNLCR

    Science.gov (United States)

    The Frederick National Laboratory for Cancer Research has entered into a new partnership with Fred Hutchinson Cancer Research Center that if successful, could improve current methods of donor selection and thereby make lifesaving transplant procedure

  11. 77 FR 35958 - Northern Natural Gas Company; Notice of Application

    Science.gov (United States)

    2012-06-15

    ..., Hutchinson, and Carson Counties in Texas, Beaver County in Oklahoma, and Kiowa and Clark Counties in Kansas...'s issuance of the final environmental impact statement (FEIS) or EA for this proposal. The filing of...

  12. Reaching Rural Mammographers for Quality Improvement

    National Research Council Canada - National Science Library

    Urban, Nicole

    1997-01-01

    The Fred Hutchinson Cancer Research Center, the University of Washington, and the Washington State Department of Health are collaborating to develop and implement a mammography quality improvement program (MQIP...

  13. Reaching Rural Mammographers for Quality Improvement

    National Research Council Canada - National Science Library

    Urban, Nicole

    1998-01-01

    The Fred Hutchinson Cancer Research Center, the University of Washington, and the Washington State Department of Health are collaborating to develop and implement a mammography quality improvement. program (MQIP...

  14. Reaching Rural Mammographers for Quality Improvement

    National Research Council Canada - National Science Library

    Urban, Nicole

    1999-01-01

    The Fred Hutchinson Cancer Research Center, the University of Washington, and the Washington State Department of Health are collaborating to develop and implement a mammography quality improvement program (MQIP...

  15. Osborne's trilogy : a critique of the management philosophy of David Osborne / Jan-Erik Lane

    Index Scriptorium Estoniae

    Lane, Jan-Erik

    2006-01-01

    Kriitiline lühiülevaade David Osborne'i raamatutes Reinventing government (kaasautor T. Gaebler, 1992), Banishing bureaucracy (kaasautor P. Plastrik, 1997) ja The price of government (kaasautor P. Hutchinson, 2004) avaldatud teooriatest

  16. Historical Imagery

    Data.gov (United States)

    Kansas Data Access and Support Center — Black and white aerial photographs of Coffeyville, Emporia, Galena, Hays, Hutchinson, Iola, McPherson, Pittsburgh, Salina, and Wichita from various dates between the...

  17. From the Bench to the Clinic Part 1: Martin McIntosh, Ph.D., Introduces His Lab's Immunotherapy Research | Office of Cancer Genomics

    Science.gov (United States)

    The field of immunotherapy is rapidly advancing and genomics techniques are being incorporated to add a “precision” approach. OCG spoke with two CTD2 investigators from the Fred Hutchinson Cancer Research Center (FHCRC) about new advances in immunotherapy. For the first article of this two-part series, we interviewed Martin McIntosh, Ph.D., member of the Fred Hutchinson Translational Research program and previously Program Head in Computational Biology at FHCRC/University of Washington Comprehensive Cancer Center.

  18. Dynamic Multiaxial Response of a Hot-Pressed Aluminum Nitride

    Science.gov (United States)

    2012-01-05

    Hutchinson, Adv. Appl . Mech. 29 (1992). [34] H. Ming-Yuan, J.W. Hutchinson, Int. J. Solids Struct. 25 (1989) 1053. [35] J. Salem , L. Ghosn, Int. J...Dynamic Multiaxial Response of a Hot- Pressed Aluminum Nitride by Guangli Hu, C. Q. Chen, K. T. Ramesh, and J. W. McCauley ARL-RP-0487...Laboratory Aberdeen Proving Ground, MD 21005-5066 ARL-RP-0487 June 2014 Dynamic Multiaxial Response of a Hot- Pressed Aluminum Nitride

  19. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    NARCIS (Netherlands)

    I. van der Pluijm (Ingrid); G.A. Garinis (George); R.M.C. Brandt (Renata); T.G.M.F. Gorgels (Theo); S.W.P. Wijnhoven (Susan); K.E.M. Diderich (Karin); J. de Wit (Jan); J.R. Mitchell (James); C.T.M. van Oostrom (Conny); R.B. Beems (Rudolf); L.J. Niedernhofer (Laura); S. Velasco (Susana); E.C. Friedberg (Errol); K. Tanaka (Kiyoji); H. van Steeg (Harry); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus)

    2006-01-01

    textabstractCockayne syndrome (CS) is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER). Here, complete inactivation of NER in Csb(m/m)/Xpa(-/-) mutants causes a phenotype that

  20. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza

    2015-01-01

    , the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  1. Microencapsulation of Self-healing Concrete Properties

    Science.gov (United States)

    2012-08-01

    design and development. Other factors that can affect concrete and its lifespan include shrinkage , design flaws or poor quality of construction...possible shrinkage , design flaws or poor quality of construction materials, reinforced concrete will eventually develop cracks. Inevitable damage to...SELF-HEALING CONCRETE PROPERTIES N00244-l 0-G-0004 Sb. GRANT NUMBER Sc. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Sd. PROJECT NUMBER James Gilford III

  2. Asymmetry reversal of ion collection by mach probes in flowing unmagnetized plasmas

    International Nuclear Information System (INIS)

    Ko, E; Hershkowitz, N

    2006-01-01

    Measurements of ion current in flowing unmagnetized plasmas were performed with planar and spherical Mach probes in two different devices, one a dc multi-dipole plasma device for subsonic flow within a presheath region and the other a double plasma device for supersonic flow. Asymmetry reversal, which is higher ion current to the downstream side of the probe compared with the upstream side current, was observed for high probe bias compared with the electron temperature, relatively low ion drift velocity and Debye length comparable to probe radius. These data are in qualitative agreement with a recent numerical calculation by Hutchinson. As suggested by Hutchinson, it was found that the current ratio depended on the plasma parameters, especially for finite Debye length and high probe bias. Asymmetry reversal emphasizes the lack of validity of using the current ratio except for narrow parameter ranges. This study is the first experiment to demonstrate the non-intuitive phenomenon predicted by Hutchinson's numerical calculation

  3. Collisionless ion drag force on a spherical grain

    International Nuclear Information System (INIS)

    Hutchinson, I H

    2006-01-01

    The ion drag force on a spherical grain situated in a flowing collisionless plasma is obtained from the specialized coordinate electrostatic particle and thermals in cell simulation code (SCEPTIC) (Hutchinson 2002 Plasma Phys. Control. Fusion 44 1953, Hutchinson 2003 Plasma Phys. Control. Fusion 45 1477, Hutchinson 2005 Plasma Phys. Control. Fusion 47 71) and compared with recent analytic approximate treatments in the interesting and relevant case when the Debye length is only moderately larger than the sphere radius. There is a substantial complex structure in the results for transonic flows, which is explained in terms of the details of ion orbits. Naturally the prior analytic approximations miss this structure, and as a result they seriously underestimate the drag for speeds near the sound speed. An easy-to-evaluate expression for force is provided that fits the comprehensive results of the code. This expression, with minor modification, also fits the results even for Debye length much smaller than the sphere radius

  4. Targeting the Prostate Cancer Microenvironment to Improve Therapeutic Outcomes

    Science.gov (United States)

    2013-06-01

    Hutchinson Cancer Research Center, respectively. B. Torok-Strorb, Fred Hutchinson Cancer Research Center, provided HS5 and HS27A HPV E6 / E7 immortalized...BCR-ABLþ, Arf-null lymphoblastic leukemia. Genes Dev 2007;21:2283–7. 13. Yamamoto-SugitaniM, Kuroda J, Ashihara E,Nagoshi H, Kobayashi T, Matsumoto Y ...xenografts compring PCa cells (PC3/VCaP) with PSC27 fibroblasts and examine tumor responses to single agent or combination therapy. ( y 1/m 1-6) 1

  5. Sister chromatid exchanges in X-ray irradiated blood lymphocytes from patients with hereditary diseases with radioresistant DNA synthesis

    International Nuclear Information System (INIS)

    Pleskach, N.M.; Andriadze, M.I.; Mikhel'son, V.M.; Zhestyanikov, V.D.

    1988-01-01

    X-ray irradiation induced sister chromatid exchanges (SCE) in blood lymphocytes from patient with Down's syndrome and adult progeria (in both the cases radioresistant DNA synthesis takes place). In normal lymphocytes (in which ionizing radiation inhibits the replicative synthesis of DNA) the rate of SCE rises with the rise of radiation dose. Thus, the rate of SCE in X-ray irradiated lymphocytes is in reverse dependence with radioresistance of replicative synthesis of DNA. The data obtained are explained in accordance with the replicative hypothesis of the SCE nature (Painter, 1980a): in cells of patients with Down's syndrome, xeroderma pigmentosum from 2 and progeria of adults the time of existence of partly replicated clusters of replicons is decreased due to radioresistant replicative synthesis of DNA, but the presence of partly replicated clusters of replicons in necessary for SCE formation. Therefore the rate of SCF in X-irradiated cells of these patients decreases

  6. Implant Supported Prosthesıs in a Patıent wıth Progerıa: Case Report

    Directory of Open Access Journals (Sweden)

    Gözlem Ceylan

    2009-08-01

    Full Text Available Prosthodontic rehabilitation can be accomplished with fixed, overdenture, complete, or implant-retained prostheses. Dental treatment overcomes the patient’s functional, psychological, esthetic and phonation problems. Remaining healthy teeth may allow the dentist to fabrícate a removable partial overdenture, fixed partial prosthesis or implant - supported prosthesis. The retention of a number of abutments helps maintain a positive ridge form with greater height and volume of the alveolar bone, improving masticatory performance, as well as providing a more stable prostheses. Dental patients who have medical problems need many treatment procedures. Multidisciplinary treatment planning is invaluable for patient’s dental health. Progeria is a rare genetic condition where symptoms resembling aspects of aging are manifested at an early age. characteristic clinical findings of Progeria disease include abnormalities of the skin and hair in conjunction with char-acteristic facial features and skeletal abnormalities. The characteristic facies show protruding ears, beaked nose, thin lips with centrofacial cyanosis, prominent eyes, frontal and parietal bossing with pseudohydrocephaly, midface hypoplasia with micrognathia and large anterior fontanel. The other reported anomalies are dystrophic nails, hypertrophic scars and hypoplastic nipples. The findings that are nearly interested in dentistry are delayed dentition, anodontia, hypodontia, or crowding of teeth. This article presents the multidisciplinary dental treatment planning includes surgical, endodontic and prosthetic treatment of a patient with a history of progeria. In this case complete-arch fixed prostheses in both maxilla and mandible, supported by a combination of im-plants and teeth are reported.

  7. Coefficients for Use in the U. S. Army Corps of Engineers Reservoir Model, CE-QUAL-R1.

    Science.gov (United States)

    1983-10-01

    temiper- atares . 53 . Tem,:n ratur: acclimation . The temperature cf1- cicnts for aiaIpoutonare ucoecndesnt upon the acclima- t ion te rt i nd th...Health Bulletin No. 171. 101 4 4- " / Hutchinson, G. E. 1957. A Treatise on Limnology. I. Geog- raphy, Physics and Chemistry . John Wiley and Sons, NY

  8. A Paradigm for EST Materials Preparation.

    Science.gov (United States)

    Carreon, Edwina S.; Balarbar, Corazon V.

    In many countries, suitable English for special purposes (ESP) textbooks and materials are difficult to find. ESP teachers and program coordinators often must develop their own materials, but preparing such materials requires training. One model that has served as a guide to numerous ESP materials projects is the Hutchinson and Waters' model. This…

  9. Annals of African Surgery January 2012 16.12.2012.indd

    African Journals Online (AJOL)

    andrew

    2012-01-16

    Jan 16, 2012 ... be a great motivation for many hospital managers (14). A weakness of the study is the fact that outcome data ... N Engl J Med. 2009;360 (5):491-9. 3. AlBuhairan B, Hind D, Hutchinson A. Antibiotic prophy- laxis for wound infections in total joint arthroplasty: a sys- tematic review. J Bone Joint Surg Br. 2008 ...

  10. Personal news

    NARCIS (Netherlands)

    NN,

    1950-01-01

    Dr J. Hutchinson retired after 44 years of service in the Royal Botanic Gardens at Kew (May 31, 1948), as Keeper of the Museum. He will devote his time mainly to the writing of some general handbooks especially his Genera Plantarum. He was succeeded by F.N. Howes, D. Sc. Mr H.K. Airy Shaw was

  11. Strain gradient plasticity effects in whisker-reinforced metals

    DEFF Research Database (Denmark)

    Niordson, Christian Frithiof

    2003-01-01

    A metal reinforced by fibers in the micron range is studied using the strain gradient plasticity theory of Fleck and Hutchinson (J. Mech. Phys. Solids 49 (2001) 2245). Cell-model analyses are used to study the influence of the material length parameters numerically, for both a single parameter...

  12. R-ES-ONANCE--INo-ve-mber

    Indian Academy of Sciences (India)

    Physiology or Medicine: has been jointly awarded to. Leland H Hartwell, Fred Hutchinson Cancer Research Center, University of Seattle, USA. R Timothy (Tim) Hunt, Clare Hall Laboratories, Cell Cycle Control Laboratory, UK. Paul M Nurse, Lincoln's Inn Fields Laboratories, Cell Cycle Laboratory, UK for their discoveries of ...

  13. Common variant of 5,10-methylenetetrahydrofolate reductase may ...

    African Journals Online (AJOL)

    Marzieh Attar

    2017-12-07

    Dec 7, 2017 ... Aim: The aim of this study was to determine the association of 5 ... as age, smoking, high blood pressure, family history, diabetes, lack ..... Homocysteine and coronary heart disease: meta-analysis of MTHFR case- ... 2016. [15] Shahbazi M, Fryer AA, Pravica V, Brogan IJ, Ramsay HM, Hutchinson IV, et al.

  14. 77 FR 20782 - Foreign-Trade Zone 161-Sedgwick County, KS; Application for Temporary/Interim Manufacturing...

    Science.gov (United States)

    2012-04-06

    ... Turbine Nacelles and Hubs); Hutchinson, KS An application has been submitted to the Executive Secretary of... County), Kansas. Under T/IM procedures, Siemens has requested authority to produce wind turbine nacelles... (4008.11), hydraulic hoses (4009.21, 4009.42), rubber gaskets and o-rings (4016.93), vibration dampeners...

  15. European Scientific Notes. Volume 37, Number 6.

    Science.gov (United States)

    1983-06-30

    Univ. voir membrane systems or with specially of Mainz, West Germany). shaped devices, essentially linear Dr. F.G. Hutchinson (ICI Pharma - release can...languages, such as Course- of the printing press. writer, TUTOR , and PILOT, are themselves software systems that help educators write courseware. According

  16. 75 FR 29199 - Changes in Flood Elevation Determinations

    Science.gov (United States)

    2010-05-25

    ..., February 25, 2010; The Honorable Jim February 18, 2010 085074 (10-08-0001P). March 5, 2010; The Woodward.... Commissioners, P.O. Box 850, Eagle, CO 81631. Larimer City of Fort Collins, February 8, 2010; The Honorable Doug February 24, 2010 080102 (09-08-0465P). February 15, 2010; Hutchinson, Mayor, City Fort Collins of Fort...

  17. response of cowpea lines to inoculation with four seed transmitted ...

    African Journals Online (AJOL)

    Admin

    nitrogen fixation and in the control of erosion and weeds. (Hutchinson and McGiffen, 2000). ... (BCMV – BlC) was reported in Brazil, India, Kenya,. Nigeria, and other parts of the ... J. d'A. Hughes, Plant Health Management Division, International Institute of Tropical Agriculture, Ibadan, Nigeria. 18. M. A. ITTAH, I. FAWOLE, ...

  18. Nutritional food content of seed and effects of five different growing ...

    African Journals Online (AJOL)

    NABDA

    2015-01-13

    Jan 13, 2015 ... confirmed at the herbarium of the Department of Plant Science and. Biotechnology, University of Nigeria, Nsukka, following the procedure described by Hutchinson and Dalziel (1964). Two thousand and five seeds (Figure 1) obtained from the trees were split into two parts of 1000 seeds each. The first batch ...

  19. Karyotype analysis in Machaerium lunatum (Linn. f.) Ducke ...

    African Journals Online (AJOL)

    ADOWIE PERE

    2017-12-11

    Dec 11, 2017 ... Ducke (syn. Drepanocarpus lunatus (Linn. f.) G.F.W. Mey) belongs to the family Fabaceae-Papilionaceae. (Hutchinson and Dalziel 1954). It has about 130 species distributed from Mexico to Argentina which are difficult to delimit taxonomically (Rudd 1987) and 150 species distributed from Mexico to South.

  20. Formulated Delivery of Enzyme/Prodrug and Cytokine Gene Therapy to Promote Immune Reduction of Treated and Remote Tumors in Mouse Models of Prostate Cancer

    Science.gov (United States)

    2007-01-01

    by identical adenovirus vectors. Clin. Cancer Res. (1997) 3(11):2075-2080. 48. WU L, MATHERLY J, SMALLWOOD A et al.: Chimeric PSA enhancers exhibit...Dr. Norman Greenberg, Fred Hutchinson Cancer Research Centre, Seattle, WA) were cultured in the presence of 10-8 M Dihydrotestosterone (DHT) as

  1. 76 FR 46898 - Quarterly Publication of Individuals, Who Have Chosen To Expatriate, as Required by Section 6039G

    Science.gov (United States)

    2011-08-03

    ... SOCORRO-VALLEJO ANGELA MARIE DELEEDE ANTHONY G DESAI ANAND R DESPERT ALAIN FERNAND DIEMER INGRID H DINGER... VELLOSO FREIRE HENTSCH FLAVIA VELLOSO FREIRE HERRERA GUSTAVO A HERZ STEPHEN OLIVER HEURTEMATTE ELIZABETH... HOYES STEPHEN HSU CHIN CHI HSU MING YU HSU TSUI CHING HUANG KUO-WEI HUI KAM KWEI HUTCHINSON MARY JEANNE...

  2. NCBI nr-aa BLAST: CBRC-AGAM-07-0042 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-AGAM-07-0042 ref|YP_679651.1| potassium efflux system protein [Cytophaga hutchinson...ii ATCC 33406] gb|ABG60309.1| potassium efflux system protein [Cytophaga hutchinsonii ATCC 33406] YP_679651.1 6e-79 46% ...

  3. NCBI nr-aa BLAST: CBRC-BTAU-01-2676 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-BTAU-01-2676 ref|YP_678738.1| hypothetical protein CHU_2133 [Cytophaga hutchinson...ii ATCC 33406] gb|ABG59396.1| conserved hypothetical protein [Cytophaga hutchinsonii ATCC 33406] YP_678738.1 0.11 23% ...

  4. NCBI nr-aa BLAST: CBRC-ACAR-01-0087 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ACAR-01-0087 ref|YP_677558.1| CHU large protein; uncharacterized [Cytophaga hutchinson...ii ATCC 33406] gb|ABG58218.1| CHU large protein; uncharacterized [Cytophaga hutchinsonii ATCC 33406] YP_677558.1 3.8 22% ...

  5. NCBI nr-aa BLAST: CBRC-PMAR-01-0373 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PMAR-01-0373 ref|YP_676710.1| hypothetical protein CHU_0076 [Cytophaga hutchinson...ii ATCC 33406] gb|ABG57370.1| conserved hypothetical protein [Cytophaga hutchinsonii ATCC 33406] YP_676710.1 8.8 25% ...

  6. NCBI nr-aa BLAST: CBRC-PTRO-14-0004 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PTRO-14-0004 ref|YP_676711.1| hypothetical protein CHU_0077 [Cytophaga hutchinson...ii ATCC 33406] gb|ABG57371.1| hypothetical protein CHU_0077 [Cytophaga hutchinsonii ATCC 33406] YP_676711.1 0.28 23% ...

  7. NCBI nr-aa BLAST: CBRC-DNOV-01-1085 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DNOV-01-1085 ref|YP_678347.1| hypothetical protein CHU_1738 [Cytophaga hutchinson...ii ATCC 33406] gb|ABG59005.1| conserved hypothetical protein [Cytophaga hutchinsonii ATCC 33406] YP_678347.1 0.90 23% ...

  8. NCBI nr-aa BLAST: CBRC-XTRO-01-2145 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-XTRO-01-2145 ref|YP_676712.1| hypothetical protein CHU_0078 [Cytophaga hutchinson...ii ATCC 33406] gb|ABG57372.1| conserved hypothetical protein [Cytophaga hutchinsonii ATCC 33406] YP_676712.1 0.16 24% ...

  9. Miscellaneous information

    NARCIS (Netherlands)

    NN,

    1955-01-01

    Flora of West tropical Africa. A new edition of Hutchinson and Dalziel’s useful work is being prepared by Mr R.W.J. Keay (assisted by Mr F.N. Hepper). Part 1, containing the introductory matter, Gymnosperms and families Annonaceae to Guttiferae appeared August 1954; obtainable from the Crown Agents

  10. 7 CFR 1210.501 - Realignment of districts.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Realignment of districts. 1210.501 Section 1210.501 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING..., Hutchinson, Roberts, Hemphill, Oldham, Potter, Carson, Gray, Wheeler, Deaf Smith, Randall, Armstrong, Donley...

  11. 76 FR 46651 - Sweet Cherries Grown in Designated Counties in Washington; Continuance Referendum

    Science.gov (United States)

    2011-08-03

    ... Specialist, or Gary D. Olson, Regional Manager, Northwest Marketing Field Office, Marketing Order..., or E-mail: [email protected] or GaryD.Olson@ams.usda.gov , respectively. SUPPLEMENTARY... the vote tabulation. Teresa L. Hutchinson and Gary D. Olson of the Northwest Marketing Field Office...

  12. Teaching Social Studies with Video Games

    Science.gov (United States)

    Maguth, Brad M.; List, Jonathan S.; Wunderle, Matthew

    2015-01-01

    Today's youth have grown up immersed in technology and are increasingly relying on video games to solve problems, engage socially, and find entertainment. Yet research and vignettes of teachers actually using video games to advance student learning in social studies is scarce (Hutchinson 2007). This article showcases how social studies…

  13. Morphological mutants of Neurospora crassa: possible evidence of abnormal morphology due to changes in DNA composition

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhuri, R K; Dutta, S.K. Ojha, M.

    1973-01-01

    DNA from seven experimentally induced morphological mutants and the wild type strain 74A of Neurospora crassa showed typical bimodal denaturation profiles in a Gilford 2400 spectrophotometer. The ''slime'' and ''ropy'' mutants showed a comparatively high proportion of A + T rich DNA sequences. Studies on thermal denaturation, percent hybridization, and thermal stability indicate the DNA sequences of the slime mutant were distinctly different from the normal genomes of parental DNA as well as other wild type DNAs. No such difference was noticed in any other mutant and natural isolate of the species N. crassa tested. These studies indicate possible correlation between a change in DNA nucleotide sequences and abnormal morphogenesis.

  14. Aproximaciones proteómicas para el estudio del envejecimiento

    OpenAIRE

    Fanjul Hevia, Víctor

    2014-01-01

    La población mundial está envejeciendo progresivamente y la edad es el factor principal de riesgo de enfermedad cardiovascular (ECV), que a su vez es el principal problema de salud en países desarrollados. Aún no se conocen en profundidad los mecanismos moleculares que provocan el envejecimiento ni aquéllos que originan la ECV, y su estudio podría conducir hacia el desarrollo de estrategias preventivas o de terapias que alarguen significativamente la vida y mejoren su calidad. La progeria ...

  15. Advancing Our Understanding of the Etiologies and Mutational Landscapes of Basal-Like, Luminal A, and Luminal B Breast Cancers

    Science.gov (United States)

    2017-10-01

    adaptive focused acoustics shearing. Status: Ongoing, we have optimized conditions to process FFPE specimens. All quality control measures are in...in progress. Page 5 BODY: Task 1. Develop Interview Instrument , Other Study Materials, and Tracking System, Months 1-3, completed under Dr. Li’s...supervision at Fred Hutchinson Cancer Research Center (FHCRC): a. Refinement of interview instrument , Months 1-2: The telephone interview that will

  16. Can the Short-Term Toxicity of Water-Soluble Jet Fuel Hydrocarbons Produce Long-Lasting Effects in Lake Plankton Communities?

    Science.gov (United States)

    1983-09-01

    Hutchinson. 1975. The effects of water soluble petroleum components on the growth ot Chlorella vulgaris Beijerinck. Environ. Pollut. 9:157-1/4. Karydis, M. and...Richard Starr Algal collection or Ankistrodesmus sp. or Chlorella sp. from the Carolina Biological collection. The cultures were unialgal but not... Chlorella were grown in BBM medium. After five days ot growth, half ot the flasks (3) for each species were spiked with 0.1 ml of toluene. The , .. flasks

  17. Characterization of Gasolines, Diesel Fuels and Their Water Soluble Fractions

    Science.gov (United States)

    1983-09-01

    Hutchinson, et al.,1979 ) with the marine algae, Chlorella vulgaris and Chlamydomonas angulosa, suggests that the toxicity of hydrocarbons is a...water-soluble petroleum components on the growth of Chlorella vulgaris Beijernck. Environ. Poll. 9: 157. Morrow, J.E., et al. 1975. Effects of some...P.B., and T.C. Hutchison. 1975. The effects of water-soluble petroleum components on the growth of Chlorella vulqaris Beijerinck. Environ. Poll. 9

  18. Attribution of Spear Phishing Attacks: A Literature Survey

    Science.gov (United States)

    2013-08-01

    However, the efficacy of methods using syntactic features as features rely on the availability and accuracy of a natural language processing ( NLP ) tool...92] implemented TAT — an author profiling tool with application to Arabic emails demographic traits (age, gender and education), and psychometric...pp. 1–9. 93. Estival, D., Gaustad, T., Pham, S. B., Radford, W. and Hutchinson, B. 2007. TAT: an author profiling tool with application to Arabic

  19. High Power Broadband Multispectral Source on a Hybrid Silicon Chip

    Science.gov (United States)

    2017-03-14

    optical bandwidth of the erbium-doped- fiber -amplifier with densely-spaced frequency channels. To extend the spectral capacity of the Si-on-insulator...associated with non-uniform undercut at the taper tip across the chip after wet etching the active region. Figure 14. Normalized optical emission...Hutchinson, J., Shin, J.-H., Fish, G., and Fang, A., “Integrated silicon photonic laser sources for telecom and datacom,” in [National Fiber Optic

  20. Notas sobre Matisia longiflora Gleas. (Bombacaceae Notas sobre Matisia longiflora Gleas. (Bombacaceae

    Directory of Open Access Journals (Sweden)

    Fernández Alonso José Luis

    1992-09-01

    Full Text Available Dentro del grupo de géneros de bombacáceas de hojas simples que componen la tribu Quararibeae (= Matisieae Hutchinson, es Matisia Humb. & Bonpl. el que cuenta con mayor número de especies en Colombia. Al respecto se presentaron recientemente algunas consideraciones preliminares sobre la diversidad de especies en este grupo en Colombia (Fernández Alonso, 1991.

  1. Sexuality as an Independent Variable: The Contribution to (or Protection against) Chronic Disease,

    Science.gov (United States)

    1978-01-05

    a few. A parallel objective would be to test the idea that patterns of sexual activity increase vulnerability to disease in general and to premature...study envisioned here. p. 13 References Armenian, H. K., Lilienfeld , A. M., & Diamond, E. L. Epidemiologic characteristics of patients with prostatic...Hutchinson & Ross, 1974. Ellis, H. Studies in the psychology of sex. (2 volumes). New York: Random House, 1936. Ellis, H. My life. Boston: Houghton Mifflin

  2. Evaluation of Lands for Recreational Snowmobile Use (Guidelines for Natural Resources Management and Land Use Compatibility).

    Science.gov (United States)

    1981-05-01

    Percy , E. C., "The Snowmobile: Friend or Foe?" Journal of Trauma, Vol 12, No. 5 (May 1972), pp 444-446. Price, V. J., "Snowmobiles, The Winter Revolution...Fort Dix, NJ Hasset, John J., Agronomy Department, University of Illinois, Champaign, IL Huber, Phil, Environmental Offices, Fort Benning, GA Jackson ...Outdoor Recreation Director, Fort McCoy, WI Houser, James, Forester, Fort McCoy, WI Hutchinson, Julian, Land Manager, Fort McCoy, WI Jackson , Gary

  3. Salt dissolution in oil and gas test holes in central Kansas. Part I. Salt beds in the subsurface in Russell, Lincoln, Ellsworth, Barton, and Rice Counties, central Kansas

    International Nuclear Information System (INIS)

    Walters, R.F.

    1975-06-01

    The Hutchinson Salt Member of the Permian Wellington Formation is described in a five-county study area of 4,000 square miles. Most of the 22,200 oil and gas test holes in the study area were drilled with fresh water, causing dissolution of the salt during drilling, commonly resulting in borehole enlargement to three times the diameter of the drill bit (some older rotary drilled holes have borehole enlargement up to 10 ft). After drilling ceases, no salt dissolution occurs in oil and gas test holes which have properly cemented surface casing protecting all aquifers above the salt. The conclusion is reached that extensive dissolution of the Hutchinson Salt in oil and gas test holes in central Kansas is a rare and unusual event in the 50-year history since the discovery of oil in Russell County in 1923. In only seven known instances (six of which are within the study area) did such dissolution lead to collapse and surface subsidence. With an estimated 72,000 holes drilled through the Hutchinson Salt Member within the State of Kansas, this is a ratio of approximately one occurrence for every 10,000 oil and gas test holes

  4. Hallmarks of progeroid syndromes: lessons from mice and reprogrammed cells

    Directory of Open Access Journals (Sweden)

    Dido Carrero

    2016-07-01

    Full Text Available Ageing is a process that inevitably affects most living organisms and involves the accumulation of macromolecular damage, genomic instability and loss of heterochromatin. Together, these alterations lead to a decline in stem cell function and to a reduced capability to regenerate tissue. In recent years, several genetic pathways and biochemical mechanisms that contribute to physiological ageing have been described, but further research is needed to better characterize this complex biological process. Because premature ageing (progeroid syndromes, including progeria, mimic many of the characteristics of human ageing, research into these conditions has proven to be very useful not only to identify the underlying causal mechanisms and identify treatments for these pathologies, but also for the study of physiological ageing. In this Review, we summarize the main cellular and animal models used in progeria research, with an emphasis on patient-derived induced pluripotent stem cell models, and define a series of molecular and cellular hallmarks that characterize progeroid syndromes and parallel physiological ageing. Finally, we describe the therapeutic strategies being investigated for the treatment of progeroid syndromes, and their main limitations.

  5. Recent Developments in the Formability of Aluminum Alloys

    Science.gov (United States)

    Banabic, Dorel; Cazacu, Oana; Paraianu, Liana; Jurco, Paul

    2005-08-01

    The paper presents a few recent contributions brought by the authors in the field of the formability of aluminum alloys. A new concept for calculating Forming Limit Diagrams (FLD) using the finite element method is presented. The article presents a new strategy for calculating both branches of an FLD, using a Hutchinson - Neale model implemented in a finite element code. The simulations have been performed with Abaqus/Standard. The constitutive model has been implemented using a UMAT subroutine. The plastic anisotropy of the sheet metal is described by the Cazacu-Barlat and the BBC2003 yield criteria. The theoretical predictions have been compared with the results given by the classical Hutchinson - Neale method and also with experimental data for different aluminum alloys. The comparison proves the capability of the finite element method to predict the strain localization. A computer program used for interactive calculation and graphical representation of different Yield Loci and Forming Limit Diagrams has also been developed. The program is based on a Hutchinson-Neale model. Different yield criteria (Hill 1948, Barlat-Lian and BBC 2003) are implemented in this model. The program consists in three modules: a graphical interface for input, a module for the identification and visualization of the yield surfaces, and a module for calculating and visualizing the forming limit curves. A useful facility offered by the program is the possibility to perform the sensitivity analysis both for the yield surface and the forming limit curves. The numerical results can be compared with experimental data, using the import/export facilities included in the program.

  6. Recent Developments in the Formability of Aluminum Alloys

    International Nuclear Information System (INIS)

    Banabic, Dorel; Paraianu, Liana; Jurco, Paul; Cazacu, Oana

    2005-01-01

    The paper presents a few recent contributions brought by the authors in the field of the formability of aluminum alloys. A new concept for calculating Forming Limit Diagrams (FLD) using the finite element method is presented. The article presents a new strategy for calculating both branches of an FLD, using a Hutchinson - Neale model implemented in a finite element code. The simulations have been performed with Abaqus/Standard. The constitutive model has been implemented using a UMAT subroutine. The plastic anisotropy of the sheet metal is described by the Cazacu-Barlat and the BBC2003 yield criteria. The theoretical predictions have been compared with the results given by the classical Hutchinson - Neale method and also with experimental data for different aluminum alloys. The comparison proves the capability of the finite element method to predict the strain localization. A computer program used for interactive calculation and graphical representation of different Yield Loci and Forming Limit Diagrams has also been developed. The program is based on a Hutchinson-Neale model. Different yield criteria (Hill 1948, Barlat-Lian and BBC 2003) are implemented in this model. The program consists in three modules: a graphical interface for input, a module for the identification and visualization of the yield surfaces, and a module for calculating and visualizing the forming limit curves. A useful facility offered by the program is the possibility to perform the sensitivity analysis both for the yield surface and the forming limit curves. The numerical results can be compared with experimental data, using the import/export facilities included in the program

  7. CO₂-st on saanud oluline strateegiliste äriotsuste mõjutaja / interv. Axel Threfall

    Index Scriptorium Estoniae

    2008-01-01

    Ilmunud ka: Finansovõi Menedzhment : infovõpusk juuli nr. 26 lk. 10-13. Euroopa Liidu saastekaubanduse, saastekvootide hinna ja prognoosimise võimalikkuse üle arutlevad konsultatsioonifirma BeCitizen direktor Philippe Freund, Inteli Euroopa ja Lähis Ida treasury-operatsioonide asedirektor Tamiko Hutchinson ja Ahlstrom Corporationi treasury-operatsioonide direktor Annika Westerholm. Vt samas Lõviosa vabatahtlikest kvoodiostudest teevad erafirmad; Millest sõltub saastekvootide hind?; Lühike heitmekaubanduse sõnastik. Tabel: Eestile 2008-2012 eraldatud saastekvootide jagunemine

  8. Strain gradient crystal plasticity effects on flow localization

    DEFF Research Database (Denmark)

    Borg, Ulrik

    2007-01-01

    for metals described by the reformulated Fleck-Hutchinson strain gradient plasticity theory. The theory is implemented numerically within a finite element framework using slip rate increments and displacement increments as state variables. The formulation reduces to the classical crystal plasticity theory...... in the absence of strain gradients. The model is used to study the effect of an internal material length scale on the localization of plastic flow in shear bands in a single crystal under plane strain tension. It is shown that the mesh sensitivity is removed when using the nonlocal material model considered...

  9. Lactate uptake against a concentration gradient

    DEFF Research Database (Denmark)

    Nordström, Carl-Henrik; Nielsen, Troels Halfeld; Nielsen, Hans Boye

    2014-01-01

    The recently published article by Jalloh et al (Jalloh I, Helmy A, Shannon RJ, Gallagher CN, Menon D, Carpenter K, Hutchinson P. Lactate uptake by the injured human brain - evidence from an arterio-venous gradient and cerebral microdialysis study. J Neurotrauma. 2013 Aug 22. [Epub ahead of print......]) concludes that lactate may be transported across the blood brain barrier into the brain against a concentration gradient. Unfortunately the authors have misinterpreted the concept of analytical imprecision and their conclusion is based on analytical artifact. As the topic of lactate transport into the brain...

  10. Strain gradient plasticity effects in whisker-reinforced metals

    DEFF Research Database (Denmark)

    Niordson, Christian Frithiof

    2002-01-01

    A metal reinforced by fibers in the micron range is studied using the strain gradient plasticity theory of Fleck and Hutchinson (2001). Cell-model analyzes are used to study the influence of the material length parameters numerically. Different higher order boundary conditions are considered...... at the fiber-matrix interface. The results are presented as overall stress-strain curves for the whisker-reinforced metal, and also contour plots of effective plastic strain are shown. The strain gradient plasticity theory predicts a significant stiffening effect when compared to conventional models...

  11. Evaluation of instructional material while in use: Welcome to Brazil, Level 1

    Directory of Open Access Journals (Sweden)

    Maria Angela Masin

    2014-04-01

    Full Text Available The aim of this paper is to evaluate the use of the instructional material Welcome to Brazil - Level 1 (Fenton and McLarty, 2011 in a technological course in Tourism Management in the city of São Paulo. The textbook content was evaluated according to Ramos (2009 and a questionnaire was used to collect the students’ impressions.  It was concluded that the textbook needs to be complemented for an effective result with the students. The theoretical foundation is based on Cunningsworth (1984, Hutchinson and Waters (1987, Dudley-Evans and St. John (1998, Tomlinson (1998, 2001, Ramos (2009.

  12. Derivation and computation of discrete-delay and continuous-delay SDEs in mathematical biology.

    Science.gov (United States)

    Allen, Edward J

    2014-06-01

    Stochastic versions of several discrete-delay and continuous-delay differential equations, useful in mathematical biology, are derived from basic principles carefully taking into account the demographic, environmental, or physiological randomness in the dynamic processes. In particular, stochastic delay differential equation (SDDE) models are derived and studied for Nicholson's blowflies equation, Hutchinson's equation, an SIS epidemic model with delay, bacteria/phage dynamics, and glucose/insulin levels. Computational methods for approximating the SDDE models are described. Comparisons between computational solutions of the SDDEs and independently formulated Monte Carlo calculations support the accuracy of the derivations and of the computational methods.

  13. Isobaric PVT Behavior of Poly(Carbonate) (PC)

    Science.gov (United States)

    Grassia, Luigi; D'Amore, Alberto

    2010-06-01

    The scaling law for relaxation times, τ(V,T) = ℑ(TVγ), recently proposed by Casalini and Roland, is utilized in the framework of KAHR (Kovacs Aklonis Hutchinson and Ramos) phenomenological theory. With this approach it is shown that the Pressure, Volume, Temperature (PVT) data obtained on Poly(carbonate)(PC) can be reliably predicted, in the region of the alpha relaxation, by using only two fitting parameters, namely: the relaxation time in the reference condition, τg, and the fractional exponent, β that describes the dispersion of the alpha relaxation.

  14. Final Environmental Impact Report/Environmental Impact Statement. Cullinan Ranch Specific Plan. Chapter 13. Comments and Responses.

    Science.gov (United States)

    1984-05-01

    said area resident now, or some type of private finmc- taxes are from the River Park Terence Savory . One piece of his land ing may have to be...Mrs Mary Hutchinson Syto McLo Chuck Forter Robert Kirkwood Founder Arthur J. POuUl Allan B. Jacobs’ "£xecufte Com"Who Gerrie Kretimer Dorothy Erskin t...KLIEWER, Dixon ALLAN WITT. Vice President- Fairfield MILTON WALLACE. Rio Vista GUIDO!E. COLLA. Secretary - Suisun DON MUSANTE. Benicia ..., RAYMOND

  15. In short supply

    Energy Technology Data Exchange (ETDEWEB)

    Lotocki, C.; Marshall, M. [Hutchinson Tyres (Australia)

    2006-02-15

    The paper proposes a means by which to alleviate current tyre shortages. Hutchinson Industries manufactures a rubber linear insert that is re-usable (referred to as an RL) which is able to save tyres on industrial and mining equipment from premature death. The RL carries the load; the tyre holds the RL within the casing. RL inserts were successfully fitted to a Joy S10SC32 at BHP Dendrobium coal mine. The tyre in use was a Michelin 14.00 R 24 XKA and a tyre on this shuttle car had suffered a large sidewall injury. 4 figs.

  16. Needs Analysis and English Teaching in Professional Contexts

    Directory of Open Access Journals (Sweden)

    Orlando Vian Jr.

    2011-07-01

    Full Text Available Based on the concept of needs analysis as proposed by Hutchinson and Waters (1987, this article discusses some aspects of English teaching in professional contexts in Brazil. We start with a brief historical view of needs analysis in order to discuss its application to teaching English for specific business purposes in professional contexts and its role for the instructor teaching in-company classes. We also aim to discuss the importance of needs analysis and its relation to the business area, as well as other features related to teaching in these contexts and its relevance to the professionals involved with business English teaching.

  17. Gain-scheduling control of a monocular vision-based human-following robot

    CSIR Research Space (South Africa)

    Burke, Michael G

    2011-08-01

    Full Text Available , R. and Zisserman, A. (2004). Multiple View Geometry in Computer Vision. Cambridge University Press, 2nd edition. Hutchinson, S., Hager, G., and Corke, P. (1996). A tutorial on visual servo control. IEEE Trans. on Robotics and Automation, 12... environment, in a passive manner, at relatively high speeds and low cost. The control of mobile robots using vision in the feed- back loop falls into the well-studied field of visual servo control. Two primary approaches are used: image-based visual...

  18. Room Temperature Spin Mediated Coupling in Hybrid Magnetic, Organic, and Oxide Structures and Devices

    Science.gov (United States)

    2015-12-07

    ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 spintronics, magnetic memory , multiferroics, organic...nano-oscillators for memory and computation, Nanotechnology, (03 2011): 0. doi: 10.1088/0957-4484/22/9/095301 F. Wang, J. Rybicki, K. Hutchinson...A dI/dV characteristics ( colour coded) as a function of four-terminal voltage V23 and side gate voltage Vsg in the open wire. c, dI/dV

  19. Room-Temperature Spin-Mediated Coupling in Hybrid Magnetic, Organic, and Oxide Structures and Devices

    Science.gov (United States)

    2015-12-07

    ADDRESS (ES) U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 spintronics, magnetic memory , multiferroics, organic...nano-oscillators for memory and computation, Nanotechnology, (03 2011): 0. doi: 10.1088/0957-4484/22/9/095301 F. Wang, J. Rybicki, K. Hutchinson...A dI/dV characteristics ( colour coded) as a function of four-terminal voltage V23 and side gate voltage Vsg in the open wire. c, dI/dV

  20. The emerging role of alternative splicing in senescence and aging.

    Science.gov (United States)

    Deschênes, Mathieu; Chabot, Benoit

    2017-10-01

    Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age-related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF-1, SIRT1, and ING-1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that changes in the activity of splicing factors and in the production of key splice variants can impact cellular senescence and the aging phenotype. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  1. Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Khandogina, E K; Mutovin, G R; Filyushkin, I V; Akif' ev, A P

    1980-02-01

    The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during ..gamma..-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source /sup 60/Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed.

  2. Radiation injuries to chromosomes in lymphocytes of patients with hereditary diseases

    International Nuclear Information System (INIS)

    Khandogina, E.K.; Mutovin, G.R.; Filyushkin, I.V.; Akif'ev, A.P.

    1980-01-01

    The authors studied dose dependences of the output of choromosomal aberrations in peripheral blood lymphocytes during γ-irradiation in vitro in patients with Parkinson's syndrome, in a patient with progeria, in a child with translocational Down's syndrome and his mother, phenotypically normal woman, with translocation, and also in control donors. Irradiation was conducted up to the stimulation with PHA (stage Go) from the source 60 Co in the dose range of 0.25-3.0 Gy. It was established that the output of metabolic aberrations is depicted by the linear-quadratic function of the dose better than by the grade one. The lymphocytes of one of the female patients with Parkinson's syndrome suffering from papilloma of the larynx showed an increase in the spontaneous level of chromosomal abberrations and also a tendency to an increase in the fragment output in comparison with the control. The lymphocytes of the patient with progeria showed an insignificantly increased spontaneous level of chromosomal aberrations and a considerable increase in the output of radiation-induced exchanges. In the child with translocational Down's syndrome the output of radiation-induced exchanges was increased in comparison with control, mainly with doses less than 1 Gy and in the lymphocytes of the woman with translocation the output of fragments was increased. In both cases the increase in the spontaneous level of aberrations was observed. A relationship between increased radiosensitivity and the inclusion of patients into a high risk group with reference to a relative increase in the incidence of malignant neoplasms and reduced life span is discussed

  3. Spherical conducting probes in finite Debye length plasmas and E x B fields

    International Nuclear Information System (INIS)

    Patacchini, Leonardo; Hutchinson, Ian H

    2011-01-01

    The particle-in-cell code SCEPTIC3D (Patacchini and Hutchinson 2010 Plasma Phys. Control. Fusion 52 035005) is used to calculate the interaction of a transversely flowing magnetized plasma with a negatively charged spherical conductor, in the entire range of magnetization and Debye length. The results allow the first fully self-consistent analysis of probe operation where neither the ion Larmor radius nor the Debye length are approximated by zero or infinity. An important transition in plasma structure occurs when the Debye length exceeds the average ion Larmor radius, as the sphere starts to shield the convective electric field driving the flow. A remarkable result is that in those conditions, the ion current can significantly exceed the unmagnetized orbital motion limit. When both the Debye length and the Larmor radius are small compared with the probe dimensions, however, their ratio does not affect the collection pattern significantly, and Mach-probe calibration methods derived in the context of quasineutral strongly magnetized plasmas (Patacchini and Hutchinson 2009 Phys. Rev. E 80 036403) hold for Debye lengths and ion Larmor radii smaller than about 10% of the probe radius.

  4. Crack deflection in brittle media with heterogeneous interfaces and its application in shale fracking

    Science.gov (United States)

    Zeng, Xiaguang; Wei, Yujie

    Driven by the rapid progress in exploiting unconventional energy resources such as shale gas, there is growing interest in hydraulic fracture of brittle yet heterogeneous shales. In particular, how hydraulic cracks interact with natural weak zones in sedimentary rocks to form permeable cracking networks is of significance in engineering practice. Such a process is typically influenced by crack deflection, material anisotropy, crack-surface friction, crustal stresses, and so on. In this work, we extend the He-Hutchinson theory (He and Hutchinson, 1989) to give the closed-form formulae of the strain energy release rate of a hydraulic crack with arbitrary angles with respect to the crustal stress. The critical conditions in which the hydraulic crack deflects into weak interfaces and exhibits a dependence on crack-surface friction and crustal stress anisotropy are given in explicit formulae. We reveal analytically that, with increasing pressure, hydraulic fracture in shales may sequentially undergo friction locking, mode II fracture, and mixed mode fracture. Mode II fracture dominates the hydraulic fracturing process and the impinging angle between the hydraulic crack and the weak interface is the determining factor that accounts for crack deflection; the lower friction coefficient between cracked planes and the greater crustal stress difference favor hydraulic fracturing. In addition to shale fracking, the analytical solution of crack deflection could be used in failure analysis of other brittle media.

  5. Uchronian Scenarios in the Context of Irish Literature: The case of C. B. Gilford’s The Crooked Shamrock

    Directory of Open Access Journals (Sweden)

    Juan F. Elices

    2014-03-01

    Full Text Available The outburst of the science fiction phenomenon, very much sustained on the notoriety and popular acclaim received by some television series and films, has made it very complex to withdraw the literary artefact proper from the influence exerted by these audio-visual productions. Even though the presence of the fantastic has been quite recurrent in the context of Irish literature, it would be difficult to argue that the tradition of science fiction and alternate history and writing, which builds up “what-if” speculations on the basis of what would have happened had certain historical episodes been different, has hardly constituted a significant trend, perhaps due to the prevalence of other more realistic genres and also due to the very limited critical and commercial impact these works have had. Among these works, C. B. Gilford’s The Crooked Shamrock stands as a most suitable example of how accepted and unquestioned historical assumptions can be re-invented and re-inscribed within an alternate historical scenario in which the author very suggestively constructs a series of counterfactuals that challenge the foundations of the Anglo-Irish relations. Therefore, the purpose of this paper will revolve around the way Gilford manages to build up “what-if” speculations that basically purport to unveil and undermine some long unquestioned historical assumptions.

  6. Probe colorimeter for quantitating enzyme-linked immunosorbent assays and other colorimetric assays performed with microplates.

    Science.gov (United States)

    Ackerman, S B; Kelley, E A

    1983-03-01

    The performance of a fiberoptic probe colorimeter (model PC800; Brinkmann Instruments, Inc., Westbury, N.Y.) for quantitating enzymatic or colorimetric assays in 96-well microtiter plates was compared with the performances of a spectrophotometer (model 240; Gilford Instrument Laboratories, Inc., Oberlin, Ohio) and a commercially available enzyme immunoassay reader (model MR590; Dynatech Laboratories, Inc., Alexandria, Va.). Alkaline phosphatase-p-nitrophenyl phosphate in 3 M NaOH was used as the chromophore source. Six types of plates were evaluated for use with the probe colorimeter; they generated reproducibility values (100% coefficient of variation) ranging from 91 to 98% when one individual made 24 independent measurements on the same dilution of chromophore on each plate. Eleven individuals each performed 24 measurements with the colorimeter on either a visually light (absorbance of 0.10 at 420 nm) or a dark (absorbance of 0.80 at 420 nm) dilution of chromophore; reproducibilities averaged 87% for the light dilution and 97% for the dark dilution. When one individual measured the same chromophore sample at least 20 times in the colorimeter, in the spectrophotometer or in the enzyme immunoassay reader, reproducibility for each instrument was greater than 99%. Measurements of a dilution series of chromophore in a fixed volume indicated that the optical responses of each instrument were linear in a range of 0.05 to 1.10 absorbance units.

  7. Experimental Investigation of the Plasma-Wall Transition

    International Nuclear Information System (INIS)

    Lunt, Tilmann; Fussmann, Gerd; Waldmann, Ole

    2008-01-01

    We report on measurements of the ion velocity distribution as a function of distance to a target immersed in a magnetized argon plasma. Two situations are investigated: (a) practically the whole plasma streams onto a large target, and (b) the size of the target is significantly smaller than the plasma diameter. The Mach number M=u/c s decreases from M=1 at the target surface to values around 0.5 at a typical scale of λ a =30 mm and λ b =5 mm, respectively. In order to explain these small decay lengths, the measurements of case (a) are compared with a source-diffusion model and those of (b) to Hutchinson's model. In (a) good agreement between modeling and experiment is obtained assuming a low neutral gas temperature. The data in (b) also agree excellently with modeled profiles, although the large fitting parameter D=20 m 2 /s indicates that other processes than diffusion contribute significantly to the transport

  8. Reconsiderando el nicho hutchinsoniano

    OpenAIRE

    Vázquez, Diego P

    2005-01-01

    El nicho es un concepto central en ecología. Sin embargo, ha sido difícil contar con una definición clara y general. Una definición históricamente importante e influyente hasta nuestros días es la propuesta por G. E. Hutchinson. A pesar de su importancia, esta definición también presenta varias limitaciones, particularmente en su conexión con la idea de la competencia interespecífica. Esta conexión entre nicho y competencia ha permanecido hasta nuestros días, dificultando la evolución de un c...

  9. Virginia Apgar y la música de cuerdas

    Directory of Open Access Journals (Sweden)

    Leonardo Palacios Sánchez

    2011-04-01

    Full Text Available Virginia Apgar (1909-1974 is one of the most recognized American doctors, worldwide known by his contribution as the developer of the “Apgar test” a method used for the evaluation of newborns all over the world. She had many interests. She was anesthesiologist, a brilliant teacher and researcher, but she also loved lecture, basketball, fishing, golf, philately, and music. She played violin and cello and she interpreted that instruments in various chamber groups. Being motivated by one of her patients, Carleen Hutchinson, a science and music teacher, she made fourinstruments, viola, violin, cello, and mezzo violin. Nearly twenty years of her death, on October24 1994, on the occasion of the annual meeting of the American Academy of Pediatrics and the issue by American Postal Service of a stamp honoring her, some of the preferred Dr. Apgar musicpieces where performed with the instruments she made. Her life mixed different activities and let invaluable contributions for humanity.

  10. Patents and innovation in cancer therapeutics: lessons from CellPro.

    Science.gov (United States)

    Bar-Shalom, Avital; Cook-Deegan, Robert

    2002-01-01

    This article discusses the interaction between intellectual property and cancer treatment. CellPro developed a stem cell separation technology based on research at the Fred Hutchinson Cancer Center. A patent with broad claims to bone marrow stem cell antibodies had been awarded to Johns Hopkins University and licensed to Baxter Healthcare under the 1980 Bayh-Dole Act to promote commercial use of inventions from federally funded research. CellPro got FDA approval more than two years before Baxter but lost patent infringement litigation. NIH elected not to compel Hopkins to license its patents to CellPro. CellPro went out of business, selling its technology to its competitor. Decisions at both firms and university licensing offices, and policies at the Patent and Trademark Office, NIH, and the courts influenced the outcome.

  11. Ultraviolet photometry of the Cepheid beta Doradus from the ANS satellite

    CERN Document Server

    Lub, J; Pel, J W; Wesselius, P R

    1979-01-01

    Extensive satellite (ANS) and ground-based (VBLUW-system) photometry is presented for the Cepheid. These data cover the wavelength range 5500-1800 AA. The ANS photometry does not confirm the evidence for shock waves as found by Hutchinson et al. from OAO-2 ultraviolet photometry of beta Doradus. A comparison of the theoretical fluxes of Kurucz with the observed energy distributions of beta Doradus gives very good agreement in the wavelength range 5500-3300 AA. In the ultraviolet the agreement is still satisfactory around maximum light, but towards lower temperatures there appear discrepancies, particularly shortly after light minimum. The difference in these discrepancies on the rising and on the falling branches of the lightcurve indicates that the observed excess ultraviolet flux is probably partly due to that the observed excess ultraviolet flux is probably partly due to dynamical effects in the moving atmosphere of the Cepheid. (25 refs).

  12. Teaching and Learning of Aural and Oral Skills in Foreign Languages for Specific Purposes: The Preparation of Bilingual Hosts for the CONFINTEA VI

    Directory of Open Access Journals (Sweden)

    Edwiges Conceição de Souza Fernandes

    2013-12-01

    Full Text Available This paper focuses on a FLSP1 course where principles on the aural and oral development skills were addressed with the aim of preparing competent conference hosts to work for the CONFINTEA VI. The course takers were selected from two Public Brazilian Universities: The State University of Pará and The Federal University of Pará, by a process which involved previous needs assessment, course design, material selection and continuous collaborative teaching. Contextualized communicative strategies were used in order to facilitate interaction in the foreign languages with distinct groups of foreigners invited for the international event. The theoretical foundation of this paper lies principally on the works of Almeida Filho (1998, Dudley-Evans and St. John (1998, Hutchinson and Waters (1987, Munby (1978 and Nunan (1988. This teaching experience is reported through a qualitative perspective and its positive results were accredited to the effective learning environment created for the development of multicultural linguistic knowledge.

  13. Historia del Lupus

    Directory of Open Access Journals (Sweden)

    Alvaro Rodríguez Gama

    2004-09-01

    Se encontrarán los lectores con una gran cantidad y calidad de biografías sobre investigaciones, médicos y científicos que han enfrentado el reto de tratar de entender y tratar el lupus, desde los médicos clásicos como Hipócrates, Galeno y Celso, los protodermatólogos Daniel Turner, Jean Astruc, Antoine Lorry y Josef von Plenk; el primer dematológo Robert Willam y médicos de los siglos XVIII y XIX como Thomas Bateman, Jean Lous Alibert, Theódore Biett, Olive Rayer, Pierre Cazenave, Antoine Bazin, Ferdinand von Hebra, Moriz Kaposi, Ernest Besnier, Alfred Fournier, Louis Brocq, Jean Darier, el clasificador Jonathan Hutchinson, Paul Unna, William Osler, Emanuel Libman, George Baehr y así decenas de colosos de la ciencia médica, cuyas historias son descritas minuciosamente por el Dr. Iglesias...

  14. Catastrophic sinkhole formation in Kansas: A case study

    Science.gov (United States)

    Lambrecht, J.L.; Miller, R.D.

    2006-01-01

    Sinkholes represent a hazard to property and human safety in a wide variety of geologic settings across the globe. In most cases, the subsidence rate of a sinkhole represents the most significant potential impact and risk to public safety. Since 1979, the Kansas Geological Survey has studied numerous sinkholes using high-resolution seismic reflection in an attempt to better understand the mechanisms that control their formation. Most sinkholes in central Kansas form as a result of dissolution of the Permian Hutchinson salt (Figure 1). The fluid source and associated pathway responsible for leaching these bedded evaporites have been natural, anthropogenic, and a combination of both. Sinkholes have been a part of the landscape in the North American midcontinent long before modern oil, gas, and mineral exploration, but clearly the activities of man have played a significant role in both increasing the number of sinkholes and affecting their subsidence rates.

  15. A phytogeographic survey of Southern Benin

    Directory of Open Access Journals (Sweden)

    G. Paradis

    1983-11-01

    Full Text Available Southern Benin has a dry subequatoriai climate with a rainfall gradient from 850 mm in the west to 1 500 mm in the east, the geomorphology is varied and the vegetation has been subjected to strong human influence. There are numerous plant formations, namely: 1, forest islands which are probably relics of the primitive vegetation and include (a dense semi-deciduous forests of several types, (b swamp forests of two types, (c periodically flooded forest of two types, (d Lophira lanceolata  (Hutchinson & Dalziel, 1954-72 woodlands and (e mangrove swamps; 2, formations which are probably derived and include (a thickets of several types, (b tree savannas and shrub savannas, (c grassy savannas and prairies varying according to soil characteristics and (d halophytic grasslands; and 3, floating vegetation on fresh-water lakes.

  16. Insights into cytokine release syndrome and neurotoxicity after CD19-specific CAR-T cell therapy.

    Science.gov (United States)

    Gauthier, Jordan; Turtle, Cameron J

    2018-04-03

    T-cells engineered to express CD19-specific chimeric antigen receptors (CD19 CAR-T cells) can achieve high response rates in patients with refractory/relapsed (R/R) CD19+ hematologic malignancies. Nonetheless, the efficacy of CD19-specific CAR-T cell therapy can be offset by significant toxicities, such as cytokine release syndrome (CRS) and neurotoxicity. In this report of our presentation at the 2018 Second French International Symposium on CAR-T cells (CAR-T day), we describe the clinical presentations of CRS and neurotoxicity in a cohort of 133 adults treated with CD19 CAR-T cells at the Fred Hutchinson Cancer Research Center, and provide insights into the mechanisms contributing to these toxicities. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. A self-consistent model for polycrystal deformation. Description and implementation

    International Nuclear Information System (INIS)

    Clausen, B.; Lorentzen, T.

    1997-04-01

    This report is a manual for the ANSI C implementation of an incremental elastic-plastic rate-insensitive self-consistent polycrystal deformation model based on (Hutchinson 1970). The model is furthermore described in the Ph.D. thesis by Clausen (Clausen 1997). The structure of the main program, sc m odel.c, and its subroutines are described with flow-charts. Likewise the pre-processor, sc i ni.c, is described with a flowchart. Default values of all the input parameters are given in the pre-processor, but the user is able to select from other pre-defined values or enter new values. A sample calculation is made and the results are presented as plots and examples of the output files are shown. (au) 4 tabs., 28 ills., 17 refs

  18. Stability of Microturbulent Drift Modes during Internal Transport Barrier Formation in the Alcator C-Mod Radio Frequency Heated H-mode

    International Nuclear Information System (INIS)

    Redi, M.H.; Fiore, C.L.; Dorland, W.; Mikkelsen, D.R.; Rewoldt, G.; Bonoli, P.T.; Ernst, D.R.; Rice, J.E.; Wukitch, S.J.

    2003-01-01

    Recent H-mode experiments on Alcator C-Mod [I.H. Hutchinson, et al., Phys. Plasmas 1 (1994) 1511] which exhibit an internal transport barrier (ITB), have been examined with flux tube geometry gyrokinetic simulations, using the massively parallel code GS2 [M. Kotschenreuther, G. Rewoldt, and W.M. Tang, Comput. Phys. Commun. 88 (1995) 128]. The simulations support the picture of ion/electron temperature gradient (ITG/ETG) microturbulence driving high xi/ xe and that suppressed ITG causes reduced particle transport and improved ci on C-Mod. Nonlinear calculations for C-Mod confirm initial linear simulations, which predicted ITG stability in the barrier region just before ITB formation, without invoking E x B shear suppression of turbulence. Nonlinear fluxes are compared to experiment, which both show low heat transport in the ITB and higher transport within and outside of the barrier region

  19. A theoretical model of semi-elliptic surface crack growth

    Directory of Open Access Journals (Sweden)

    Shi Kaikai

    2014-06-01

    Full Text Available A theoretical model of semi-elliptic surface crack growth based on the low cycle strain damage accumulation near the crack tip along the cracking direction and the Newman–Raju formula is developed. The crack is regarded as a sharp notch with a small curvature radius and the process zone is assumed to be the size of cyclic plastic zone. The modified Hutchinson, Rice and Rosengren (HRR formulations are used in the presented study. Assuming that the shape of surface crack front is controlled by two critical points: the deepest point and the surface point. The theoretical model is applied to semi-elliptic surface cracked Al 7075-T6 alloy plate under cyclic loading, and five different initial crack shapes are discussed in present study. Good agreement between experimental and theoretical results is obtained.

  20. A viscoplastic strain gradient analysis of materials with voids or inclusions

    DEFF Research Database (Denmark)

    Borg, Ulrik; Niordson, Christian Frithiof; Fleck, N. A.

    2006-01-01

    -2454] of the strain gradient plasticity theory proposed by Fleck and Hutchinson (2001) [Journal of the Mechanics and Physics of Solids 49, 2245-2271]. The formulation is based on a viscoplastic potential that enables the formulation of the model so that it reduces to the strain gradient plasticity theory...... in the absence of viscous effects. The numerical implementation uses increments of the effective plastic strain rate as degrees of freedom in addition to increments of displacement. To illustrate predictions of the model, results are presented for materials containing either voids or rigid inclusions......A finite strain viscoplastic nonlocal plasticity model is formulated and implemented numerically within a finite element framework. The model is a viscoplastic generalisation of the finite strain generalisation by Niordson and Redanz (2004) [Journal of the Mechanics and Physics of Solids 52, 2431...

  1. A self-consistent model for polycrystal deformation. Description and implementation

    Energy Technology Data Exchange (ETDEWEB)

    Clausen, B.; Lorentzen, T.

    1997-04-01

    This report is a manual for the ANSI C implementation of an incremental elastic-plastic rate-insensitive self-consistent polycrystal deformation model based on (Hutchinson 1970). The model is furthermore described in the Ph.D. thesis by Clausen (Clausen 1997). The structure of the main program, sc{sub m}odel.c, and its subroutines are described with flow-charts. Likewise the pre-processor, sc{sub i}ni.c, is described with a flowchart. Default values of all the input parameters are given in the pre-processor, but the user is able to select from other pre-defined values or enter new values. A sample calculation is made and the results are presented as plots and examples of the output files are shown. (au) 4 tabs., 28 ills., 17 refs.

  2. The changing features of the body-mind problem.

    Science.gov (United States)

    Agassi, Joseph

    2007-01-01

    The body-mind problem invites scientific study, since mental events are repeated and repeatable and invite testable explanations. They seemed troublesome because of the classical theory of substance that failed to solve its own central problems. These are soluble with the aid of the theory of the laws of nature, particularly in its emergentist version [Bunge, M., 1980. The Body-mind Problem, Pergamon, Oxford] that invites refutable explanations [Popper, K.R., 1959. The Logic of Scientific Discovery, Hutchinson, London]. The view of mental properties as emergent is a modification of the two chief classical views, materialism and dualism. As this view invites testable explanations of events of the inner world, it is better than the quasi-behaviorist view of self-awareness as computer-style self-monitoring [Minsky, M., Laske, O., 1992. A conversation with Marvin Minsky. AI Magazine 13 (3), 31-45].

  3. Mode I and mixed mode crack-tip fields in strain gradient plasticity

    DEFF Research Database (Denmark)

    Goutianos, Stergios

    2011-01-01

    Strain gradients develop near the crack-tip of Mode I or mixed mode cracks. A finite strain version of the phenomenological strain gradient plasticity theory of Fleck–Hutchinson (2001) is used here to quantify the effect of the material length scales on the crack-tip stress field for a sharp...... stationary crack under Mode I and mixed mode loading. It is found that for material length scales much smaller than the scale of the deformation gradients, the predictions converge to conventional elastic–plastic solutions. For length scales sufficiently large, the predictions converge to elastic solutions....... Thus, the range of length scales over which a strain gradient plasticity model is necessary is identified. The role of each of the three material length scales, incorporated in the multiple length scale theory, in altering the near-tip stress field is systematically studied in order to quantify...

  4. NPP physical protection and information security as necessary conditions for reducing nuclear and radiation accident risks

    International Nuclear Information System (INIS)

    Pogosov, O.Yu.; Derevyanko, O.V.

    2017-01-01

    The paper focuses on the fact that nuclear failures and incidents can lead to radioactive contamination of NPP premises. Nuclear and radiation hazard may be caused by malefactors in technological processes when applying computers or inadequate control in case of insufficient level of information security.The researchers performed analysis of factors for reducing risks of nuclear and radiation accidents at NPPs considering specific conditions related to information security of NPP physical protection systems. The paper considers connection of heterogeneous factors that may increase the risk of NPP accidents, possibilities and ways to improve adequate modelling of security of information with limited access directly related to the functioning of automated set of engineering and technical means for NPP physical protection. Within the overall Hutchinson formalization, it is proposed to include additional functional dependencies on indicators specific for NPPs into analysis algorithms.

  5. Alcator C-Mod predictive modeling

    International Nuclear Information System (INIS)

    Pankin, Alexei; Bateman, Glenn; Kritz, Arnold; Greenwald, Martin; Snipes, Joseph; Fredian, Thomas

    2001-01-01

    Predictive simulations for the Alcator C-mod tokamak [I. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] are carried out using the BALDUR integrated modeling code [C. E. Singer et al., Comput. Phys. Commun. 49, 275 (1988)]. The results are obtained for temperature and density profiles using the Multi-Mode transport model [G. Bateman et al., Phys. Plasmas 5, 1793 (1998)] as well as the mixed-Bohm/gyro-Bohm transport model [M. Erba et al., Plasma Phys. Controlled Fusion 39, 261 (1997)]. The simulated discharges are characterized by very high plasma density in both low and high modes of confinement. The predicted profiles for each of the transport models match the experimental data about equally well in spite of the fact that the two models have different dimensionless scalings. Average relative rms deviations are less than 8% for the electron density profiles and 16% for the electron and ion temperature profiles

  6. Plasticity dependent damage evolution in composites with strain-gradient effects

    DEFF Research Database (Denmark)

    Legarth, Brian Nyvang

    2015-01-01

    . (2013). In this study the reinforcement is assumed perfectly stiff and consequently only one new cohesive material parameter is introduced. Results are shown for both conventional isotropy as well as plastic anisotropy with higher-order material behavior. Due to fiber-matrix decohesion a sudden stress......A unit cell approach is adopted to numerically analyze the effect of reinforcement size on fracture evolution in metal matrix composites. The matrix material shows plastic size-effects and is modeled by an anisotropic version of the single parameter strain-gradient (higher-order) plasticity model...... by Fleck and Hutchinson (2001). The fracture process along the fiber-matrix interface is modeled using a recently proposed cohesive law extension, where plasticity affects the fracture process as both the average as well as the jump in plastic strain across the interface are accounted for Tvergaard et al...

  7. Geotechnical evaluation of rocks and soils in Catoca kimberlitic mining complex (Angola

    Directory of Open Access Journals (Sweden)

    Domingos M. Dos Santos Neves-Margarida

    2012-10-01

    Full Text Available Landslides and rock sliding occur very frequently in the mining area of Catoca, located in Angola. Therefore, a physical/mechanical and geotechnical characterization of the massif and the rock matrix was carried out adopting the landslide classifications as proposed by Hutchinson and Varnes. The safety factor was applied based on the structural weakness coefficient (λ; resulting in 0.70 in surface rocks, sandstones and intraformational sands; 0.58 in oversaturated eluvial gneiss; 0.50 in cracked gneiss and 0.47 in the ore compound of weathered, moist kimberlitic porphyric and weathered porphyric kimberlite. These results indicate the low strength of the massif and the need to reformulate the activities in the mine and the construction of more stable slopes. It could also be observed that deformation of rocks in the slopes and the cuts in the Catoca mine is conditioned by the movement of underground water within the rock massif itself.

  8. [A Case of Small Intestinal Metastasis with Intussusception Due to Barium].

    Science.gov (United States)

    Tsujio, Gen; Nagahara, Hisashi; Nakao, Shigetomi; Fukuoka, Tatsunari; Shibutani, Masatsune; Maeda, Kiyoshi; Matsutani, Shinji; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Yashiro, Masakazu; Hirakawa, Kosei; Ohira, Masaichi

    2017-11-01

    A 48-year-old man noticed nausea and took health examination. After chest X-ray and gastrointestinal barium study was underwent, he was referred to our hospital because of abnormal shadow in the chest X-ray. CT scan revealed about 4 cm tumor in the hilum of left lung and target sign in the small intestine. He was diagnosed with intussusception and emergency operation was performed. During the laparotomy, we found 2 intussusceptions in the small intestine and we performed manual reduction using Hutchinson's maneuver. We confirmed the mass in oral side of the intussusception site but we did not confirmed any tumor in anal of the intussusception. This suggests the intussusception was caused by barium. Finally 3 small intestine tumor was observed and we resected and reconstructed each of the tumor. Histopathological examination showed small intestinal metastasis from pleomorphic carcinoma of the lung.

  9. Investigation of interactions in a biological membrane using structure factor/pair correlation function approach: a first communication on nerve myelin

    International Nuclear Information System (INIS)

    Gbordzoe, M.K.

    1984-09-01

    Interactions in biological and artificial membranes have been studied by applying mostly the methods of biochemical analysis and determination of thermodynamic parameters related to phase transition phenomena. Structure factor, obtained by measuring scattered intensity from small-angle X-ray or neutron scattering experiments, has been used mainly for determining electron density distribution. Drawing upon the experience of the theory of liquids, where Johnson and March (1963) and Johnson, Hutchinson and March (1964) first established the possibility of deriving interparticle potential from experimental measurement of structure factor, it is suggested that structure factor/distance correlation function approach, can be a useful method for studying interactions between various membrane components. Preliminary experimental data presented for nerve myelin are to demonstrate the possibility of studying interactions from the distance correlation function of a membrane pair. (author)

  10. Congenital syphilis in the skeleton of a child from Poland (Radom, 18th–19th century AD

    Directory of Open Access Journals (Sweden)

    Tomczyk Jacek

    2015-03-01

    Full Text Available An incomplete skeleton of a 3-year-old child with suspected congenital syphilis was found in the Radom area of Poland. Squama frontalis and zygomatic bones are characterized by significant bone loss. Radiographic pictures show a geographic destructive lesion of a serpiginous shape surrounded by a zone of reactive osteosclerosis in the squama frontalis. The radiographic findings included a slight widening and contour irregularities of the distal humeral metaphyses. The appearance of teeth did not suggest Hutchinson teeth, but the examination of the permanent molars showed signs of mulberry molars. Two teeth were tested for the presence of mercury. Chemical analysis did not indicate mercury accumulation (enamel: 0.07 μg/g, dentine: 0.14 μg/g, bone: 0.11 μg/g. Mercury values obtained for the examined samples were similar to those that are typical of healthy teeth in today’s individuals.

  11. MATERIAL DIDÁTICO DE LÍNGUA INGLESA: UMA POSSÍVEL FERRAMENTA NA PROMOÇÃO DA INCLUSÃO DE ALUNOS EM SITUAÇÃO DE RISCO

    Directory of Open Access Journals (Sweden)

    Rubens Fernando Souza Lopes

    2016-12-01

    Full Text Available Este artigo visa discutir a inclusão-exclusão de crianças e adolescentes em situação de risco para, em seguida, propor um procedimento de elaboração de material específico de língua inglesa que procura viabilizar a participação desses sujeitos em seu processo de ensino-aprendizagem. Esta proposta fundamenta-se em uma pesquisa-ação, e se amplia por meio de autores que abordam a questão de inclusão-exclusão, como Gentili & Alencar (2007, Maciel (2005, e a elaboração de material didático, tais como Hutchinson e Waters (1987, e Dolz, Noverraz & Schneuwly (2004. Os resultados demonstram que o material desenvolvido e utilizado procurou considerar a análise de necessidades e expectativas.

  12. Microindentation deformation of lithium dihydrogen phosphate single crystals: Microhardness measurement and indentation size effect

    Energy Technology Data Exchange (ETDEWEB)

    Iurchenko, Anton [Institute for Single Crystals, National Academy of Sciences of Ukraine, Lenin Avenue 60, 61001 Kharkiv (Ukraine); Borc, Jarosław, E-mail: j.borc@pollub.pl [Department of Applied Physics, Lublin University of Technology, ul. Nadbystrzycka 38, 20-618 Lublin (Poland); Sangwal, Keshra [Department of Applied Physics, Lublin University of Technology, ul. Nadbystrzycka 38, 20-618 Lublin (Poland); Voronov, Alexei [Institute for Single Crystals, National Academy of Sciences of Ukraine, Lenin Avenue 60, 61001 Kharkiv (Ukraine)

    2016-02-15

    The Vickers microhardness H{sub V} of the (110) and (111) as-grown faces of lithium dihydrogen phosphate (LDP) crystals was investigated as a function of applied load P. The microhardness H{sub V} of the two faces increases with load P i.e. reverse indentation size effect (reverse ISE) and the hardness of the (110) face is somewhat lower than that of the (111) face but this difference is not easily recognized for these planes due to large scatter in the data. The origin of observed ISE was analyzed using different approaches. It was found that: (1) Hays–Kendall's and Begley–Hutchinson's relations do not explain the origin of reverse ISE but Meyer's law describes the reverse ISE satisfactorily and its constants provide a link between ISE and formation of radial cracks with applied indentation load P, (2) reverse ISE is associated with tensile surface stresses, (3) despite its failure to explain reverse ISE, Begley–Hutchinson's relation is reliable to obtain load-independent hardness H{sub 0}, is 2337 MPa for LDP, and (4) the value of fracture toughness K{sub C} of LDP crystals lies between 4.7 and 12 MPa m{sup 1/2}. The load-independent hardness H{sub 0} of LDP is higher by a factor of 1.5 than that reported for undoped KDP and ADP crystals whereas its fracture toughness K{sub C} is higher by factor of about 20 than that of undoped KDP crystals. - Highlights: • Vickers indentations on the (110) and (111) faces of LDP crystals were made. • The microhardness H{sub V} was investigated as a function of applied load P. • Reverse indentation size effect was observed. • Fracture toughness K{sub C} from the radial cracks was calculated.

  13. Monitoring of bird abundance and distribution at McKinley Bay and Hutchison Bay, Northwest Territories, 1981 to 1993

    Energy Technology Data Exchange (ETDEWEB)

    Cornish, B J; Dickson, D L

    1994-04-01

    McKinley Bay has been identified as a preferred site for a harbor to support oil and gas production in the Beaufort Sea. As the bay is a molting area for several species of diving duck, a study was initiated to monitor the effect of harbor development on birds using the bay. Baseline information on the natural annual fluctuations in the number of birds were collected for nine years at McKinley Bay and eight years at neighboring Hutchinson Bay, an area chosen as the control. The final report of the predevelopment phase of the monitoring study is presented, including results of the 1993 surveys and a summary of results of all years of surveys. There were significantly more diving ducks in McKinley Bay in early August 1990 to 1993, on average, than from 1981 to 1985. No statistically significant change in total diving ducks was noted at Hutchinson Bay. Numbers of species of divers varied substantially between years at the two bays but not to the same degree. Significantly more Pacific loons, red-throated loons, and northern pintails were recorded in the 1990-1993 surveys at McKinley Bay than in earlier surveys. Potential explanations for the large between-year fluctuations in diving duck numbers are discussed. The variations may be due to bird responses to changes in the physical environment or related to the limitations of the aerial survey techniques used. Because of the large natural fluctuations in numbers of molting diving ducks using these bays in early August, it will be difficult to detect future impacts of industrial disturbance, even when sources of survey bias are minimized. It is concluded that aerial surveys of molting diving ducks in the two bays are unsuitable for monitoring the effects of industrial development. 41 refs., 7 figs., 23 tabs.

  14. Potential for Sulfate Reduction in Mangrove Forest Soils: Comparison between Two Dominant Species of the Americas

    KAUST Repository

    Balk, Melike

    2016-11-18

    Avicennia and Rhizophora are globally occurring mangrove genera with different traits that place them in different parts of the intertidal zone. It is generally accepted that the oxidizing capacity of Avicennia roots is larger than that of Rhizophora roots, which initiates more reduced conditions in the soil below the latter genus. We hypothesize that the more reduced conditions beneath Rhizophora stands lead to more active sulfate-reducing microbial communities compared to Avicennia stands. To test this hypothesis, we measured sulfate reduction traits in soil samples collected from neighboring Avicennia germinans and Rhizophora mangle stands at three different locations in southern Florida. The traits measured were sulfate reduction rates (SRR) in flow-through reactors containing undisturbed soil layers in the absence and presence of easily degradable carbon compounds, copy numbers of the dsrB gene, which is specific for sulfate-reducing microorganisms, and numbers of sulfate-reducing cells that are able to grow in liquid medium on a mixture of acetate, propionate and lactate as electron donors. At the tidal locations Port of the Islands and South Hutchinson Islands, steady state SRR, dsrB gene copy numbers and numbers of culturable cells were higher at the A. germinans than at the R. mangle stands, although not significantly for the numbers at Port of the Islands. At the non-tidal location North Hutchinson Island, results are mixed with respect to these sulfate reduction traits. At all locations, the fraction of culturable cells were significantly higher at the R. mangle than at the A. germinans stands. The dynamics of the initial SRR implied a more in situ active sulfate-reducing community at the intertidal R. mangle stands. It was concluded that in agreement with our hypothesis R. mangle stands accommodate a more active sulfate-reducing community than A. germinans stands, but only at the tidal locations. The differences between R. mangle and A. germinans stands

  15. Microindentation deformation of lithium dihydrogen phosphate single crystals: Microhardness measurement and indentation size effect

    International Nuclear Information System (INIS)

    Iurchenko, Anton; Borc, Jarosław; Sangwal, Keshra; Voronov, Alexei

    2016-01-01

    The Vickers microhardness H_V of the (110) and (111) as-grown faces of lithium dihydrogen phosphate (LDP) crystals was investigated as a function of applied load P. The microhardness H_V of the two faces increases with load P i.e. reverse indentation size effect (reverse ISE) and the hardness of the (110) face is somewhat lower than that of the (111) face but this difference is not easily recognized for these planes due to large scatter in the data. The origin of observed ISE was analyzed using different approaches. It was found that: (1) Hays–Kendall's and Begley–Hutchinson's relations do not explain the origin of reverse ISE but Meyer's law describes the reverse ISE satisfactorily and its constants provide a link between ISE and formation of radial cracks with applied indentation load P, (2) reverse ISE is associated with tensile surface stresses, (3) despite its failure to explain reverse ISE, Begley–Hutchinson's relation is reliable to obtain load-independent hardness H_0, is 2337 MPa for LDP, and (4) the value of fracture toughness K_C of LDP crystals lies between 4.7 and 12 MPa m"1"/"2. The load-independent hardness H_0 of LDP is higher by a factor of 1.5 than that reported for undoped KDP and ADP crystals whereas its fracture toughness K_C is higher by factor of about 20 than that of undoped KDP crystals. - Highlights: • Vickers indentations on the (110) and (111) faces of LDP crystals were made. • The microhardness H_V was investigated as a function of applied load P. • Reverse indentation size effect was observed. • Fracture toughness K_C from the radial cracks was calculated.

  16. Effects from placental exposure

    Energy Technology Data Exchange (ETDEWEB)

    Kawamoto, S [Radiation Effect Research Foundation, Hiroshima (Japan)

    1975-12-01

    Investigations of the effects on the people who had received placental exposure at either Hiroshima or Nagasaki were discussed. All of the subjects were children who had been born at either Hiroshima or Nagasaki between noon of 31, May, 1946 and the atomic-bomb detornation. Deaths of embryos and neonates were determined by the radiation dosage and the growth phase of embryos. Bifid uvula and a slight decrease of number of lumbar vertebra were observed in 14 males and 3 females at Nagasaki. Mental deficiency occurred in 25% of the children whose mothers had received radiation at Nagasaki, and in 8% at Hiroshima. The occurrence of microcephaly was high at both places in the children who had received placental exposure of more than 150 rad. A significant retardation of growth was observed in those who had had a high radiation dosage. Congenitally abnormal persistence of pupillary membrane was very frequently observed in the group which had received a high dosage of radiation. Concerning progeria, mortality of infants under one year of age was increased in the group which had received a high dosage of radiation, but mortality statistics should continue to be observed.

  17. Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus.

    Science.gov (United States)

    Stephens, Andrew D; Banigan, Edward J; Adam, Stephen A; Goldman, Robert D; Marko, John F

    2017-07-07

    The cell nucleus must continually resist and respond to intercellular and intracellular mechanical forces to transduce mechanical signals and maintain proper genome organization and expression. Altered nuclear mechanics is associated with many human diseases, including heart disease, progeria, and cancer. Chromatin and nuclear envelope A-type lamin proteins are known to be key nuclear mechanical components perturbed in these diseases, but their distinct mechanical contributions are not known. Here we directly establish the separate roles of chromatin and lamin A/C and show that they determine two distinct mechanical regimes via micromanipulation of single isolated nuclei. Chromatin governs response to small extensions (<3 μm), and euchromatin/heterochromatin levels modulate the stiffness. In contrast, lamin A/C levels control nuclear strain stiffening at large extensions. These results can be understood through simulations of a polymeric shell and cross-linked polymer interior. Our results provide a framework for understanding the differential effects of chromatin and lamin A/C in cell nuclear mechanics and their alterations in disease. © 2017 Stephens et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  18. Volume regulation and shape bifurcation in the cell nucleus.

    Science.gov (United States)

    Kim, Dong-Hwee; Li, Bo; Si, Fangwei; Phillip, Jude M; Wirtz, Denis; Sun, Sean X

    2015-09-15

    Alterations in nuclear morphology are closely associated with essential cell functions, such as cell motility and polarization, and correlate with a wide range of human diseases, including cancer, muscular dystrophy, dilated cardiomyopathy and progeria. However, the mechanics and forces that shape the nucleus are not well understood. Here, we demonstrate that when an adherent cell is detached from its substratum, the nucleus undergoes a large volumetric reduction accompanied by a morphological transition from an almost smooth to a heavily folded surface. We develop a mathematical model that systematically analyzes the evolution of nuclear shape and volume. The analysis suggests that the pressure difference across the nuclear envelope, which is influenced by changes in cell volume and regulated by microtubules and actin filaments, is a major factor determining nuclear morphology. Our results show that physical and chemical properties of the extracellular microenvironment directly influence nuclear morphology and suggest that there is a direct link between the environment and gene regulation. © 2015. Published by The Company of Biologists Ltd.

  19. miR-9: a versatile regulator of neurogenesis

    Directory of Open Access Journals (Sweden)

    Marion Coolen

    2013-11-01

    Full Text Available Soon after its discovery, microRNA-9 (miR-9 attracted the attention of neurobiologists, since it is one of the most highly expressed microRNAs in the developing and adult vertebrate brain. Functional analyses in different vertebrate species have revealed a prominent role of this microRNA in balancing proliferation in embryonic neural progenitor populations. Key transcriptional regulators such as FoxG1, Hes1 or Tlx, were identified as direct targets of miR-9, placing it at the core of the gene network controlling the progenitor state. Recent data also suggest that this function could extend to adult neural stem cells. Other studies point to a role of miR-9 in differentiated neurons. Moreover miR-9 has been implicated in human brain pathologies, either displaying a protective role, such as in Progeria, or participating in disease progression in brain cancers. Altogether functional studies highlight a prominent feature of this highly conserved microRNA, its functional versatility, both along its evolutionary history and across cellular contexts.

  20. Modeling Late-Onset Sporadic Alzheimer’s Disease through BMI1 Deficiency

    Directory of Open Access Journals (Sweden)

    Anthony Flamier

    2018-05-01

    Full Text Available Late-onset sporadic Alzheimer’s disease (AD is the most prevalent form of dementia, but its origin remains poorly understood. The Bmi1/Ring1 protein complex maintains transcriptional repression of developmental genes through histone H2A mono-ubiquitination, and Bmi1 deficiency in mice results in growth retardation, progeria, and neurodegeneration. Here, we demonstrate that BMI1 is silenced in AD brains, but not in those with early-onset familial AD, frontotemporal dementia, or Lewy body dementia. BMI1 expression was also reduced in cortical neurons from AD patient-derived induced pluripotent stem cells but not in neurons overexpressing mutant APP and PSEN1. BMI1 knockout in human post-mitotic neurons resulted in amyloid beta peptide secretion and deposition, p-Tau accumulation, and neurodegeneration. Mechanistically, BMI1 was required to repress microtubule associated protein tau (MAPT transcription and prevent GSK3beta and p53 stabilization, which otherwise resulted in neurodegeneration. Restoration of BMI1 activity through genetic or pharmaceutical approaches could represent a therapeutic strategy against AD.

  1. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  2. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (uv) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either x-ray-like (i.e., they cause damage that XP cells can repair) or uv-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed. (U.S.)

  3. Human diseases with genetically altered DNA repair processes

    International Nuclear Information System (INIS)

    Cleaver, J.E.; Bootsma, D.; Friedberg, E.

    1975-01-01

    DNA repair of single-strand breaks (produced by ionizing radiation) and of base damage (produced by ultraviolet (UV) light) are two repair mechanisms that most mammalian cells possess. Genetic defects in these repair mechanisms are exemplified by cells from the human premature-aging disease, progeria, which fail to rejoin single-strand breaks, and the skin disease, xeroderma pigmentosum (XP), which exhibits high actinic carcinogenesis and involves failure to repair base damage. In terms of the response of XP cells, many chemical carcinogens can be classified as either X-ray-like (i.e., they cause damage that XP cells can repair) or UV-like (i.e., they cause damage that XP cells cannot repair). The first group contains some of the more strongly carcinogenic chemicals (e.g., alkylating agents). XP occurs in at least two clinical forms, and somatic cell hybridization indicates at least three complementation groups. In order to identify cell lines from various different laboratories unambiguously, a modified nomenclature of XP lines is proposed

  4. Human lipodystrophies: genetic and acquired diseases of adipose tissue

    Science.gov (United States)

    Capeau, Jacqueline; Magré, Jocelyne; Caron-Debarle, Martine; Lagathu, Claire; Antoine, Bénédicte; Béréziat, Véronique; Lascols, Olivier; Bastard, Jean-Philippe; Vigouroux, Corinne

    2010-01-01

    Human lipodystrophies represent a heterogeneous group of diseases characterized by generalized or partial fat loss, with fat hypertrophy in other depots when partial. Insulin resistance, dyslipidemia and diabetes are generally associated, leading to early complications. Genetic forms are uncommon: recessive generalized congenital lipodystrophies result in most cases from mutations in the genes encoding seipin or the 1-acyl-glycerol-3-phosphate-acyltransferase 2 (AGPAT2). Dominant partial familial lipodystrophies result from mutations in genes encoding the nuclear protein lamin A/C or the adipose transcription factor PPARγ. Importantly, lamin A/C mutations are also responsible for metabolic laminopathies, resembling the metabolic syndrome and progeria, a syndrome of premature aging. A number of lipodystrophic patients remain undiagnosed at the genetic level. Acquired lipodystrophy can be generalized, resembling congenital forms, or partial, as the Barraquer-Simons syndrome, with loss of fat in the upper part of the body contrasting with accumulation in the lower part. Although their aetiology is generally unknown, they could be associated with signs of auto-immunity. The most common forms of lipodystrophies are iatrogenic. In human immunodeficiency virus-infected patients, some first generation antiretroviral drugs were strongly related with peripheral lipoatrophy and metabolic alterations. Partial lipodystrophy also characterize patients with endogenous or exogenous long-term corticoid excess. Treatment of fat redistribution can sometimes benefit from plastic surgery. Lipid and glucose alterations are difficult to control leading to early occurrence of diabetic, cardio-vascular and hepatic complications. PMID:20551664

  5. Adult Stem Cells and Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Lisa B. Boyette

    2014-01-01

    Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

  6. Accelerated ageing and renal dysfunction links lower socioeconomic status and dietary phosphate intake.

    Science.gov (United States)

    McClelland, Ruth; Christensen, Kelly; Mohammed, Suhaib; McGuinness, Dagmara; Cooney, Josephine; Bakshi, Andisheh; Demou, Evangelia; MacDonald, Ewan; Caslake, Muriel; Stenvinkel, Peter; Shiels, Paul G

    2016-05-01

    We have sought to explore the impact of dietary Pi intake on human age related health in the pSoBid cohort (n=666) to explain the disparity between health and deprivation status in this cohort. As hyperphosphataemia is a driver of accelerated ageing in rodent models of progeria we tested whether variation in Pi levels in man associate with measures of biological ageing and health. We observed significant relationships between serum Pi levels and markers of biological age (telomere length (p=0.040) and DNA methylation content (p=0.028), gender and chronological age (p=0.032). When analyses were adjusted for socio-economic status and nutritional factors, associations were observed between accelerated biological ageing (telomere length, genomic methylation content) and dietary derived Pi levels among the most deprived males, directly related to the frequency of red meat consumption. Accelerated ageing is associated with high serum Pi levels and frequency of red meat consumption. Our data provide evidence for a mechanistic link between high intake of Pi and age-related morbidities tied to socio-economic status.

  7. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  8. Hallermann-Streiff syndrome associated with small cerebellum, endocrinopathy and increased chromosomal breakage.

    Science.gov (United States)

    Hou, J W

    2003-07-01

    Hallermann-Streiff syndrome (HSS) is a rare clinic entity of unknown aetiology. Further clinical and metabolic-genetic evaluations are indicated. A 2-mo-old female baby presented with ocular abnormalities and severe failure to thrive since birth. The clinical features were compatible with the diagnosis of HSS. Further imaging, metabolic and cytogenetic examinations were performed. Features characteristic of HSS were dyscephaly with mandibular and nasal cartilage hypoplasia, microphthalmia, bilateral cataracts with congenital glaucoma, natal teeth and proportionate dwarfism. Rare anomalies such as choanal atresia and small cerebellum, very low insulin-like growth factor I level, hypothyroidism, generalized organic aciduria were also noticed. An increased chromosomal breakage rate is suggestive of the existence of some DNA repair defects in HSS patients. The associated anomalies in this patient may broaden the clinical spectrum of HSS. Underlying conditions of organic aciduria, growth factor deficiency and impaired DNA repair are likely to contribute to the progeria-like facies, congenital cataracts and growth failure.

  9. Nutriepigenetic regulation by folate-homocysteine-methionine axis: a review.

    Science.gov (United States)

    Bhargava, Seema; Tyagi, S C

    2014-02-01

    Although normally folic acid is given during pregnancy, presumably to prevent neural tube defects, the mechanisms of this protection are unknown. More importantly it is unclear whether folic acid has other function during development. It is known that folic acid re-methylates homocysteine (Hcy) to methionine by methylene tetrahydrofolate reductase-dependent pathways. Folic acid also generates high-energy phosphates, behaves as an antioxidant and improves nitric oxide (NO) production by endothelial NO synthase. Interestingly, during epigenetic modification, methylation of DNA/RNA generate homocysteine unequivocally. The enhanced overexpression of methyl transferase lead to increased yield of Hcy. The accumulation of Hcy causes vascular dysfunction, reduces perfusion in the muscles thereby causing musculopathy. Another interesting fact is that children with severe hyperhomocysteinaemia (HHcy) have skeletal deformities, and do not live past teenage. HHcy is also associated with the progeria syndrome. Epilepsy is primarily caused by inhibition of gamma-amino-butyric-acid (GABA) receptor, an inhibitory neurotransmitter in the neuronal synapse. Folate deficiency leads to HHcy which then competes with GABA for binding on the GABA receptors. With so many genetic and clinical manifestations associated with folate deficiency, we propose that folate deficiency induces epigenetic alterations in the genes and thereby results in disease.

  10. Caged Protein Prenyltransferase Substrates: Tools for Understanding Protein Prenylation

    Energy Technology Data Exchange (ETDEWEB)

    DeGraw, Amanda J.; Hast, Michael A.; Xu, Juhua; Mullen, Daniel; Beese, Lorena S.; Barany, George; Distefano, Mark D. (Duke); (UMM)

    2010-11-15

    Originally designed to block the prenylation of oncogenic Ras, inhibitors of protein farnesyltransferase currently in preclinical and clinical trials are showing efficacy in cancers with normal Ras. Blocking protein prenylation has also shown promise in the treatment of malaria, Chagas disease and progeria syndrome. A better understanding of the mechanism, targets and in vivo consequences of protein prenylation are needed to elucidate the mode of action of current PFTase (Protein Farnesyltransferase) inhibitors and to create more potent and selective compounds. Caged enzyme substrates are useful tools for understanding enzyme mechanism and biological function. Reported here is the synthesis and characterization of caged substrates of PFTase. The caged isoprenoid diphosphates are poor substrates prior to photolysis. The caged CAAX peptide is a true catalytically caged substrate of PFTase in that it is to not a substrate, yet is able to bind to the enzyme as established by inhibition studies and X-ray crystallography. Irradiation of the caged molecules with 350 nm light readily releases their cognate substrate and their photolysis products are benign. These properties highlight the utility of those analogs towards a variety of in vitro and in vivo applications.

  11. The effects from placental exposure

    International Nuclear Information System (INIS)

    Kawamoto, Sadahisa

    1975-01-01

    Investigations of the effects on the people who had received placental exposure at either Hiroshima or Nagasaki were discussed. All of the subjects were children who had been born at either Hiroshima or Nagasaki between noon of 31, May, 1946 and the atomic-bomb detornation. Deaths of embryos and neonates were determined by the radiation dosage and the growth phase of embryos. Bifid uvula and a slight decrease of number of lumbar vertebra were observed in 14 males and 3 females at Nagasaki. Mental deficiency occurred in 25% of the children whose mothers had received radiation at Nagasaki, and in 8% at Hiroshima. The occurrence of microcephaly was high at both places in the children who had received placental exposure of more than 150 rad. A significant retardation of growth was observed in those who had had a high radiation dosage. Congenitally abnormal persistence of pupillary membrane was very frequently observed in the group which had received a high dosage of radiation. Concerning progeria, mortality of infants under one year of age was increased in the group which had received a high dosage of radiation, but mortality statistics should continue to be observed. (Kanao, N.)

  12. EL PROGRAMA CITI: UNA ALTERNATIVA PARA LA CAPACITACIÓN EN ÉTICA DE LA INVESTIGACIÓN EN AMÉRICA LATINA O PROGRAMA CITI: UMA ALTERNATIVA PARA A CAPACITAÇÃO NA ÉTICA DA PESQUISA NA AMÉRICA LATINA THE CITI PROGRAM: AN ALTERNATIVE TO TRAIN LATIN AMERICA IN INVESTIGATION'S ETHICS

    Directory of Open Access Journals (Sweden)

    Sergio Litewka

    2008-01-01

    Full Text Available El Programa CITI (Collaborative Institutional Training Initiative es un curso basado en Internet y desarrollado por voluntarios, que brinda material educacional sobre protección de sujetos humanos en investigaciones biomédicas y de conducta, buenas prácticas clínicas, conducta responsable de la investigación y trato humanitario a animales de laboratorio. Es un esfuerzo conjunto del Fred Hutchinson Cancer Research Center y la Universidad de Miami. Con la colaboración de expertos locales, gran parte del contenido se ha adaptado para América Latina, se ha traducido al español y portugués y se han establecido acuerdos de colaboración con instituciones especializadas en bioética en Chile, Brasil, Costa Rica y Perú. Los autores presentan una metodología accesible para la capacitación en ética de la investigación y una justificación de su uso y difusión en América Latina.O programa CITI (Iniciativa de treinamento institucional colaborativo é um curso baseado na internet e desenvolvido por voluntários, que fornece material educacional sobre a proteção de sujeitos humanos nas pesquisas biomédicas e de conduta, boas práticas clínicas, conduta responsável da pesquisa e trato humanitário para animais em laboratório. É um esforço conjunto do Fred Hutchinson Câncer Research Center e a Universidade de Miami. Com a colaboração de peritos locais, grande parte do conteúdo foi adaptado para a América Latina e traduzido para o espanhol e português e se estabeleceram acordos de colaboração com instituições especializadas em bioética no Chile, Brasil,Costa Rica e, Peru. Os autores apresentam uma metodologia acessível para a capacitação em ética da pesquisa e uma justificação de seu uso e difusão na América Latina.The CITI Program (Collaborative Institutional Training Initiative is a course based on Internet with no profit intention; it has been developed by volunteers who offer educational subjects on human beings

  13. Effects of cigarette smoking on human aggressive behavior.

    Science.gov (United States)

    Cherek, D R

    1984-01-01

    Nicotine administered by smoking experimental cigarettes produced decreases in two types of aggressive responses elicited by low and high frequency subtractions of money which were attributed to another "person". The suppressing effects of smoking different doses of nicotine on aggressive responses was dose-dependent, in that smoking the high dose of nicotine produced more suppression than smoking the low dose. The ostensible subtraction of money from another "person", the more aggressive response option available to research subjects, was generally more sensitive to the suppressing effects of nicotine than aggressive noise delivery responses. Although this effect could be attributed to another constituent of tobacco, the dose-dependent effect observed with these cigarettes which contained the same amount of tar suggest the effects are due to nicotine. The relatively selective suppression of aggressive behavior observed in humans in the present study is highly consistent with the effects of nicotine observed in a number of infrahuman species. Nicotine has been found to suppress aggressive behavior in ants (Kostowski 1968), rats (Silverman 1971), and cats (Berntson et. al. 1976). In addition, nicotine has been observed to suppress shock elicited fighting in rats (Driscoll, Baettig 1981; Rodgers 1979; Waldbillig 1980) as well as shock elicited biting in monkeys (Hutchinson, Emley 1973). The importance of determining specificity of drug action on aggressive behavior has been repeatedly emphasized in the field of behavioral pharmacology (Sidman 1959; Cook, Kelleher 1963; Thompson, Boren 1977; Miczek, Krsiak 1979). One method employed to evaluate drug specificity and identify a general non-specific excitatory or depressant drug effect is to determine the drug effect on more than one response option which is available to the subject (Sidman 1959). In this study, the same doses of nicotine which suppressed aggressive responding increased nonaggressive monetary

  14. Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies

    Science.gov (United States)

    Head, Elizabeth; Schmitt, Frederick A.; Davis, Paulina R.; Neltner, Janna H.; Jicha, Gregory A.; Abner, Erin L.; Smith, Charles D.; Van Eldik, Linda J.; Kryscio, Richard J.; Scheff, Stephen W.

    2011-01-01

    Human studies are reviewed concerning whether “aging”-related mechanisms contribute to Alzheimer’s disease (AD) pathogenesis. AD is defined by specific neuropathology: neuritic amyloid plaques and neocortical neurofibrillary tangles. AD pathology is driven by genetic factors related not to aging per se, but instead to the amyloid precursor protein (APP). In contrast to genes involved in APP-related mechanisms, there is no firm connection between genes implicated in human “accelerated aging” diseases (progerias) and AD. The epidemiology of AD in advanced age is highly relevant but deceptively challenging to address given the low autopsy rates in most countries. In extreme old age, brain diseases other than AD approximate AD prevalence while the impact of AD pathology appears to peak by age 95 and decline thereafter. Many distinct brain diseases other than AD afflict older human brains and contribute to cognitive impairment. Additional prevalent pathologies include cerebrovascular disease and hippocampal sclerosis, both high-morbidity brain diseases that appear to peak in incidence later than AD chronologically. Because of these common brain diseases of extreme old age, the epidemiology differs between clinical “dementia” and the subset of dementia cases with AD pathology. Additional aging-associated mechanisms for cognitive decline such as diabetes and synapse loss have been linked to AD and these hypotheses are discussed. Criteria are proposed to define an “aging-linked” disease, and AD fails all of these criteria. In conclusion, it may be most fruitful to focus attention on specific pathways involved in AD rather than attributing it to an inevitable consequence of aging. PMID:21516511

  15. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    Science.gov (United States)

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  16. Werner complex deficiency in cells disrupts the Nuclear Pore Complex and the distribution of lamin B1.

    Science.gov (United States)

    Li, Zhi; Zhu, Yizhou; Zhai, Yujia; R Castroagudin, Michelle; Bao, Yifei; White, Tommy E; Glavy, Joseph S

    2013-12-01

    From the surrounding shell to the inner machinery, nuclear proteins provide the functional plasticity of the nucleus. This study highlights the nuclear association of Pore membrane (POM) protein NDC1 and Werner protein (WRN), a RecQ helicase responsible for the DNA instability progeria disorder, Werner Syndrome. In our previous publication, we connected the DNA damage sensor Werner's Helicase Interacting Protein (WHIP), a binding partner of WRN, to the NPC. Here, we confirm the association of the WRN/WHIP complex and NDC1. In established WRN/WHIP knockout cell lines, we further demonstrate the interdependence of WRN/WHIP and Nucleoporins (Nups). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE) but do affect the distribution of FG Nups and the RAN gradient, which are necessary for nuclear transport. Evidence from WRN/WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B1. The appearance of "RAN holes" void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B1. From WRN/WHIP knockout cell line extracts, we found three forms of lamin B1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein. Upon treatment with topoisomerase inhibitors lamin B1 cleavage occurs only in WRN/WHIP knockout cells. Our data suggest the link of the NDC1 and WRN as one facet of the network between the nuclear periphery and genome stability. Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus. © 2013. Published by Elsevier B.V. All rights reserved.

  17. Biogenesis of the Saccharomyces cerevisiae Pheromone a-Factor, from Yeast Mating to Human Disease

    Science.gov (United States)

    Barrowman, Jemima

    2012-01-01

    Summary: The mating pheromone a-factor secreted by Saccharomyces cerevisiae is a farnesylated and carboxylmethylated peptide and is unusually hydrophobic compared to other extracellular signaling molecules. Mature a-factor is derived from a precursor with a C-terminal CAAX motif that directs a series of posttranslational reactions, including prenylation, endoproteolysis, and carboxylmethylation. Historically, a-factor has served as a valuable model for the discovery and functional analysis of CAAX-processing enzymes. In this review, we discuss the three modules comprising the a-factor biogenesis pathway: (i) the C-terminal CAAX-processing steps carried out by Ram1/Ram2, Ste24 or Rce1, and Ste14; (ii) two sequential N-terminal cleavage steps, mediated by Ste24 and Axl1; and (iii) export by a nonclassical mechanism, mediated by the ATP binding cassette (ABC) transporter Ste6. The small size and hydrophobicity of a-factor present both challenges and advantages for biochemical analysis, as discussed here. The enzymes involved in a-factor biogenesis are conserved from yeasts to mammals. Notably, studies of the zinc metalloprotease Ste24 in S. cerevisiae led to the discovery of its mammalian homolog ZMPSTE24, which cleaves the prenylated C-terminal tail of the nuclear scaffold protein lamin A. Mutations that alter ZMPSTE24 processing of lamin A in humans cause the premature-aging disease progeria and related progeroid disorders. Intriguingly, recent evidence suggests that the entire a-factor pathway, including all three biogenesis modules, may be used to produce a prenylated, secreted signaling molecule involved in germ cell migration in Drosophila. Thus, additional prenylated signaling molecules resembling a-factor, with as-yet-unknown roles in metazoan biology, may await discovery. PMID:22933563

  18. Comparison of Water Turbidity Removal Efficiencies of Moringa oleifera Seed Extract and Poly-aluminum Chloride

    Directory of Open Access Journals (Sweden)

    Bijan Bina

    2007-03-01

    Full Text Available Coagulation and flocculation are essential processes in water treatment plants. Metal salts such as aluminum sulphate and ferric chloride are commonly used in the coagulation process in Iran. Poly-aluminum chloride (PAC has been used recently in Baba-Sheykhali Water Treatment Plant in Isfahan. Synthetic coagulants have health problems associated with them and are additionally uneconomical for use in developing countries. In this study, PAC and Moringa oleifera seed extract were compared for their efficiency as coagulants. Moringa oleifera, locally called “oil gaz” in Iran, grows in southern parts of Iran. One variety of this tree, Moringa progeria, is indigenous to Iran. For the purposes of this study, lab experiments were performed using distilled water containing synthetic caoline. Four turbidity levels of 10, 50, 500, and1000 (NTU and four pH levels of 5, 6, 7, and 8 were used for the jar test. It was found that oleifera seed extract was capable of removing 98, 97, 89, and 55% of the turbidity in the four experiments at optimum concentration levels of 10-30 (mg/l for all four pH levels of 6 to 8, respectively. PAC, in contrast, removed 99, 98, 95, and 89% of the turbidity at optimum concentrations of 20-30 (mg/l for a pH level of 8. The results indicate that Moringa oleifera seed extract has little effect on pH level and enjoys higher removal efficiency for higher turbidity levels. Reducing pH level decreased PAC turbidity removal efficiency.

  19. On the theory of drainage area for regular and non-regular points

    Science.gov (United States)

    Bonetti, S.; Bragg, A. D.; Porporato, A.

    2018-03-01

    The drainage area is an important, non-local property of a landscape, which controls surface and subsurface hydrological fluxes. Its role in numerous ecohydrological and geomorphological applications has given rise to several numerical methods for its computation. However, its theoretical analysis has lagged behind. Only recently, an analytical definition for the specific catchment area was proposed (Gallant & Hutchinson. 2011 Water Resour. Res. 47, W05535. (doi:10.1029/2009WR008540)), with the derivation of a differential equation whose validity is limited to regular points of the watershed. Here, we show that such a differential equation can be derived from a continuity equation (Chen et al. 2014 Geomorphology 219, 68-86. (doi:10.1016/j.geomorph.2014.04.037)) and extend the theory to critical and singular points both by applying Gauss's theorem and by means of a dynamical systems approach to define basins of attraction of local surface minima. Simple analytical examples as well as applications to more complex topographic surfaces are examined. The theoretical description of topographic features and properties, such as the drainage area, channel lines and watershed divides, can be broadly adopted to develop and test the numerical algorithms currently used in digital terrain analysis for the computation of the drainage area, as well as for the theoretical analysis of landscape evolution and stability.

  20. Delay-induced wave instabilities in single-species reaction-diffusion systems

    Science.gov (United States)

    Otto, Andereas; Wang, Jian; Radons, Günter

    2017-11-01

    The Turing (wave) instability is only possible in reaction-diffusion systems with more than one (two) components. Motivated by the fact that a time delay increases the dimension of a system, we investigate the presence of diffusion-driven instabilities in single-species reaction-diffusion systems with delay. The stability of arbitrary one-component systems with a single discrete delay, with distributed delay, or with a variable delay is systematically analyzed. We show that a wave instability can appear from an equilibrium of single-species reaction-diffusion systems with fluctuating or distributed delay, which is not possible in similar systems with constant discrete delay or without delay. More precisely, we show by basic analytic arguments and by numerical simulations that fast asymmetric delay fluctuations or asymmetrically distributed delays can lead to wave instabilities in these systems. Examples, for the resulting traveling waves are shown for a Fisher-KPP equation with distributed delay in the reaction term. In addition, we have studied diffusion-induced instabilities from homogeneous periodic orbits in the same systems with variable delay, where the homogeneous periodic orbits are attracting resonant periodic solutions of the system without diffusion, i.e., periodic orbits of the Hutchinson equation with time-varying delay. If diffusion is introduced, standing waves can emerge whose temporal period is equal to the period of the variable delay.

  1. Organizing for a Peaceful Crowd: An Example of a Football Match

    Directory of Open Access Journals (Sweden)

    Ingrid Hylander

    2010-03-01

    Full Text Available Crowd violence has interested researchers in social psychology for many years and is an important issue for sports psychology (STOTT, ADANG, LIVINGSTONE & SCHREIBER, 2007; STOTT, HUTCHINSON & DRURY, 2001; RUSSELL, 2004; MUSTONEN, ARMS & RUSSELL, 1996. Riots in crowds have been explained from different theoretical perspectives (HYLANDER, 2008, such as individual differences, de-individuation (PRENTICE-DUNN & ROGERS, 1989, group interaction (DRURY & REICHER, 2000, history (GUTTMAN, 1986, 1998 and cultural perspectives (CRABBE, 2003. In this study, a social psychology model focusing on group interaction, the Aggravation and Mitigation (AM model (GUVÅ & HYLANDER, 2008; GRANSTRÖM, 2008; GRANSTRÖM & ROSANDER, 2008, is used as a means of analysis. This article applies the AM model to a sporting event to identify if and how peacemaking processes can be detected. Furthermore, the intention is to discern and illuminate organizational strategies that maybe linked to peacemaking processes. The main results indicate that when arrangements are based on (a "festival-making," (b arrangements for basic needs and recognizable order and (c the creation of a superordinate identity, then the outcome of mass events may turn out peaceful, which is also in line with the AM model. URN: urn:nbn:de:0114-fqs100283

  2. Clinical verification of genetic results returned to research participants: findings from a Colon Cancer Family Registry.

    Science.gov (United States)

    Laurino, Mercy Y; Truitt, Anjali R; Tenney, Lederle; Fisher, Douglass; Lindor, Noralane M; Veenstra, David; Jarvik, Gail P; Newcomb, Polly A; Fullerton, Stephanie M

    2017-11-01

    The extent to which participants act to clinically verify research results is largely unknown. This study examined whether participants who received Lynch syndrome (LS)-related findings pursued researchers' recommendation to clinically verify results with testing performed by a CLIA-certified laboratory. The Fred Hutchinson Cancer Research Center site of the multinational Colon Cancer Family Registry offered non-CLIA individual genetic research results to select registry participants (cases and their enrolled relatives) from 2011 to 2013. Participants who elected to receive results were counseled on the importance of verifying results at a CLIA-certified laboratory. Twenty-six (76.5%) of the 34 participants who received genetic results completed 2- and 12-month postdisclosure surveys; 42.3% of these (11/26) participated in a semistructured follow-up interview. Within 12 months of result disclosure, only 4 (15.4%) of 26 participants reported having verified their results in a CLIA-certified laboratory; of these four cases, all research and clinical results were concordant. Reasons for pursuing clinical verification included acting on the recommendation of the research team and informing future clinical care. Those who did not verify results cited lack of insurance coverage and limited perceived personal benefit of clinical verification as reasons for inaction. These findings suggest researchers will need to address barriers to seeking clinical verification in order to ensure that the intended benefits of returning genetic research results are realized. © 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  3. Potential use of custirsen to treat prostate cancer

    Directory of Open Access Journals (Sweden)

    Higano CS

    2013-06-01

    Full Text Available Celestia S Higano Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Over the last few years, five agents have demonstrated a survival benefit over a comparator treatment or placebo in the treatment of metastatic castration-resistant prostate cancer and have been approved by the US Food and Drug Administration: sipuleucel-T (a dendritic cell immunotherapy; cabazitaxel; abiraterone acetate and enzalutamide (both hormonal agents; and radium 223 (an alpha emitter. The development of these agents pivoted on whether patients had been treated with docetaxel, which remains the first-line chemotherapy of choice. To date, no combination of docetaxel and another active agent has demonstrated superiority to docetaxel alone despite numerous Phase III trials. Clusterin is a cytoprotective chaperone protein that is upregulated in response to various anticancer therapies. When overexpressed, clusterin interferes with apoptotic signaling, thereby promoting cell survival and conferring broad-spectrum resistance in cancer cell lines. Custirsen (OGX-011 is a second-generation 2´-methoxyethyl modified phosphorothioate antisense oligonucleotide that inhibits expression of clusterin. This review presents the preclinical and clinical data that provided the rationale for the combination of custirsen with chemotherapy in ongoing Phase III trials. Keywords: castration-resistant prostate cancer, clusterin, custirsen, OGX-011, antisense, OGX-427, apoptosis

  4. Targeting gastrointestinal stromal tumors: the role of regorafenib

    Directory of Open Access Journals (Sweden)

    Schroeder B

    2016-05-01

    Full Text Available Brett Schroeder,1 Zula Li,2,3 Lee D Cranmer,2,3 Robin L Jones,4 Seth M Pollack2,3 1College of Human Medicine, Michigan State University, Grand Rapids, MI, 2Division of Medical Oncology, University of Washington, 3Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 4Royal Marsden Hospital, Institute of Cancer Research, London, UK Abstract: Gastrointestinal stromal tumor (GIST is a devastating disease in the metastatic setting, but its natural history has been dramatically altered by the development of small molecule tyrosine kinase inhibitors, most notably imatinib. Although patients with advanced GIST live much longer today than they did in the past, imatinib-refractory disease remains a tremendous problem. For disease that is refractory to imatinib and sunitinib, regorafenib is an excellent option. In this review, we discuss the biology and clinical work establishing regorafenib as the standard of care for advanced GIST refractory to both imatinib and sunitinib. Keywords: regorafenib, GIST, refractory, imatinib

  5. Ductile fracture prediction of an axially cracked pressure vessel under pressurized thermal shock

    International Nuclear Information System (INIS)

    Takahashi, Jun; Okamura, Hiroyuki

    1991-01-01

    In this paper, the J-value of an axially cracked cylinder under several PTS conditions are evaluated using a simple estimation scheme which we proposed. Results obtained are summerized as follow: (1) Under any PTS conditions, the effect of internal pressure is so predominant upon the J-value and dJ/da that it is very important to grasp the transient of internal pressure under any imaginable accident from the viewpoint of structural integrity. (2) Under any IP, TS, and PTS conditions, J - a/W relation shows that the J-value reaches its maximum at a certain crack depth, then drops to zero at a/W ≅ 0.9. Though the effect of inertia is not taken into account, this fact may explain the phenomena of crack arrest qualitatively. (3) The compliance of a cylindrical shell plays an important role in the fracture prediction of a pressure vessel. (4) Under typical PTS conditions, the region at the crack tip dominated by the Hutchinson-Rice-Rosengren singularity is substantially large enough to apply the J-based criterion to predict unstable ductile fracture. (author)

  6. Plasma Vitellogenin in Free-Ranging Loggerhead Sea Turtles (Caretta caretta of the Northwest Atlantic Ocean

    Directory of Open Access Journals (Sweden)

    Kimberly Smelker

    2014-01-01

    Full Text Available Vitellogenin is the egg yolk precursor protein produced by oviparous vertebrates. As endogenous estrogen increases during early reproductive activity, hepatic production of vitellogenin is induced and is assumed to be complete in female sea turtles before the first nesting event. Until the present study, innate production of vitellogenin has not been described in free-ranging sea turtles. Our study describes circulating concentrations of vitellogenin in loggerhead sea turtles (Caretta caretta from the Northwest Atlantic Ocean. We collected blood samples from juveniles and adults via in-water captures off the coast of the Southeast USA from May to August, and from nesting females in June and July at Hutchinson Island, Florida. All samples were analyzed using an in-house ELISA developed specifically to measure Caretta caretta vitellogenin concentration. As expected, plasma vitellogenin declined in nesting turtles as the nesting season progressed, although it still remained relatively elevated at the end of the season. In addition, mean vitellogenin concentration in nesting turtles was 1,000 times greater than that measured in samples from in-water captures. Our results suggest that vitellogenesis may continue throughout the nesting season, albeit at a decreasing rate. Further, vitellogenin detected in turtles captured in-water may have resulted from exposure to endocrine disrupting chemicals.

  7. Radiative and three-body recombination in the Alcator C-Mod divertor

    International Nuclear Information System (INIS)

    Lumma, D.; Terry, J.L.; Lipschultz, B.

    1997-01-01

    Significant recombination of the majority ion species has been observed in the divertor region of Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] under detached conditions. This determination is made by analysis of the visible spectrum from the divertor, in particular the Balmer series line emission and the observed recombination continuum, including an apparent recombination edge at ∼375 nm. The analysis shows that the electron temperature in the recombining plasma is 0.8 endash 1.5 eV. The measured volume recombination rate is comparable to the rate of ion collection at the divertor plates. The dominant recombination mechanism is three-body recombination into excited states (e+e+D + Right-arrow D 0 +e), although radiative recombination (e+D + Right-arrow D 0 +hν) contributes ∼5% to the total rate. Analysis of the Balmer series line intensities (from n upper =3 through 10) shows that the upper levels of these transitions are populated primarily by recombination. Thus the brightnesses of the Balmer series (and Lyman series) are directly related to the recombination rate. copyright 1997 American Institute of Physics

  8. Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

    1992-09-01

    This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides.

  9. Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway. Hanford Environmental Dose Reconstruction Project

    Energy Technology Data Exchange (ETDEWEB)

    Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

    1992-09-01

    This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides.

  10. Responses to the Holocaust in Modern Irish Poetry

    Directory of Open Access Journals (Sweden)

    Benjamin Keatinge

    2011-03-01

    Full Text Available This essay examines twentieth and twenty-first century responses by Irish poets to the Holocaust. It argues that, despite the illiberal tendencies of the Irish state towards Jewish immigration during and after the 1939-1945 war, recent commemorative activities in Ireland have included the Holocaust and are part of a wider commemorative ‘opening up’ in Ireland towards twentieth-century historical events. Important contemporary Irish poets have written Holocaust poems of notable merit including: Seamus Heaney, Harry Clifton, Derek Mahon, Pearse Hutchinson, Paul Durcan, Paul Muldoon, Thomas Kinsella and Tom Paulin, all of whom are discussed here. These poets are noted as second-generation Holocaust poets, more at home in the lyric form and less troubled by communicative dilemmas than their precursors such as Paul Celan and Samuel Beckett whose resemblance is briefly discussed. The essay concludes by arguing that Giorgio Agamben’s arguments about testimony after Auschwitz are strikingly pertinent to some of the poems under discussion. It also suggests that the historical essays of Hubert Butler may have acted as an unseen influence on some of these writers.

  11. Introducing People – Genre Analysis and Oral Comprehension and Oral Production Tasks

    Directory of Open Access Journals (Sweden)

    Keila Rocha Reis de Carvalho

    2012-02-01

    Full Text Available This paper aims at presenting an analysis of the genre introducing people and at suggesting listening comprehension and oral production tasks. This work was developed according to the characterization of the rhetorical organization of situations taken from seventeen films that contain the genre under analysis. Although several studies in the ESP area carried out recently (Andrade, 2003; Cardoso, 2003; Shergue, 2003; Belmonte, 2003; Serafini, 2003 have identified listening comprehension and oral production as the abilities that should be prioritized in an English course, much needs to be done, especially concerning the oral genres that take into account the language the learners of English as a second language need in their target situation. This work is based on Hutchinson & Waters (1987 theoretical background on ESP, Swales’ (1990 genre analysis, Ramos’ (2004 pedagogical proposal, and also on Ellis´ (2003 tasks concept. The familiarization of learners of English as a second language with this genre will provide them with the opportunity to better understand and use the English language in their academic and professional life.

  12. Parameters used in the environmental pathways (DESCARTES) and radiological dose (CIDER) modules of the Hanford Environmental Dose Reconstruction Integrated Codes (HEDRIC) for the air pathway

    International Nuclear Information System (INIS)

    Snyder, S.F.; Farris, W.T.; Napier, B.A.; Ikenberry, T.A.; Gilbert, R.O.

    1992-09-01

    This letter report is a description of work performed for the Hanford Environmental Dose Reconstruction (HEDR) Project. The HEDR Project was established to estimate the radiation doses to individuals resulting from releases of radionuclides from the Hanford Site since 1944. This work is being done by staff at Battelle, Pacific Northwest Laboratories (Battelle) under a contract with the Centers for Disease Control (CDC) with technical direction provided by an independent Technical Steering Panel (TSP). The objective of this report is to-document the environmental accumulation and dose-assessment parameters that will be used to estimate the impacts of past Hanford Site airborne releases. During 1993, dose estimates made by staff at Battelle will be used by the Fred Hutchinson Cancer Research Center as part of the Hanford Thyroid Disease Study (HTDS). This document contains information on parameters that are specific to the airborne release of the radionuclide iodine-131. Future versions of this document will include parameter information pertinent to other pathways and radionuclides

  13. Science.gov (United States)

    Litewka, Sergio; Goodman, Kenneth; Braunschweiger, Y Paul

    2008-01-01

    El Programa CITI (Collaborative Institutional Training Initiative) es un curso basado en Internet y desarrollado por voluntarios, que brinda material educacional sobre protección de sujetos humanos en investigaciones biomédicas y de conducta, buenas prácticas clínicas, conducta responsable de la investigación y trato humanitario a animales de laboratorio. Es un esfuerzo conjunto del Fred Hutchinson Cancer Research Center y la Universidad de Miami.Con la colaboración de expertos locales, gran parte del contenido se ha adaptado para América Latina, se ha traducido al español y portugués y se han establecido acuerdos de colaboración con instituciones especializadas en bioética en Chile, Brasil, Costa Rica y Perú. Los autores presentan una metodología accesible para la capacitación en ética de la investigación y una justificación de su uso y difusión en América Latina.

  14. Impurity toroidal rotation and transport in Alcator C-Mod ohmic high confinement mode plasmas

    International Nuclear Information System (INIS)

    Rice, J. E.; Goetz, J. A.; Granetz, R. S.; Greenwald, M. J.; Hubbard, A. E.; Hutchinson, I. H.; Marmar, E. S.; Mossessian, D.; Pedersen, T. Sunn; Snipes, J. A.

    2000-01-01

    Central toroidal rotation and impurity transport coefficients have been determined in Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] Ohmic high confinement mode (H-mode) plasmas from observations of x-ray emission following impurity injection. Rotation velocities up to 3x10 4 m/sec in the co-current direction have been observed in the center of the best Ohmic H-mode plasmas. Purely ohmic H-mode plasmas display many characteristics similar to ion cyclotron range of frequencies (ICRF) heated H-mode plasmas, including the scaling of the rotation velocity with plasma parameters and the formation of edge pedestals in the electron density and temperature profiles. Very long impurity confinement times (∼1 sec) are seen in edge localized mode-free (ELM-free) Ohmic H-modes and the inward impurity convection velocity profile has been determined to be close to the calculated neoclassical profile. (c) 2000 American Institute of Physics

  15. Genetic structure of Florida green turtle rookeries as indicated by mitochondrial DNA control region sequences

    Science.gov (United States)

    Shamblin, Brian M.; Bagley, Dean A.; Ehrhart, Llewellyn M.; Desjardin, Nicole A.; Martin, R. Erik; Hart, Kristen M.; Naro-Maciel, Eugenia; Rusenko, Kirt; Stiner, John C.; Sobel, Debra; Johnson, Chris; Wilmers, Thomas; Wright, Laura J.; Nairn, Campbell J.

    2014-01-01

    Green turtle (Chelonia mydas) nesting has increased dramatically in Florida over the past two decades, ranking the Florida nesting aggregation among the largest in the Greater Caribbean region. Individual beaches that comprise several hundred kilometers of Florida’s east coast and Keys support tens to thousands of nests annually. These beaches encompass natural to highly developed habitats, and the degree of demographic partitioning among rookeries was previously unresolved. We characterized the genetic structure of ten Florida rookeries from Cape Canaveral to the Dry Tortugas through analysis of 817 base pair mitochondrial DNA (mtDNA) control region sequences from 485 nesting turtles. Two common haplotypes, CM-A1.1 and CM-A3.1, accounted for 87 % of samples, and the haplotype frequencies were strongly partitioned by latitude along Florida’s Atlantic coast. Most genetic structure occurred between rookeries on either side of an apparent genetic break in the vicinity of the St. Lucie Inlet that separates Hutchinson Island and Jupiter Island, representing the finest scale at which mtDNA structure has been documented in marine turtle rookeries. Florida and Caribbean scale analyses of population structure support recognition of at least two management units: central eastern Florida and southern Florida. More thorough sampling and deeper sequencing are necessary to better characterize connectivity among Florida green turtle rookeries as well as between the Florida nesting aggregation and others in the Greater Caribbean region.

  16. EL PROGRAMA CITI: UNA ALTERNATIVA PARA LA CAPACITACIÓN EN ÉTICA DE LA INVESTIGACIÓN EN AMÉRICA LATINA

    Science.gov (United States)

    Litewka, Sergio; Goodman, Kenneth; Braunschweiger, y Paul

    2011-01-01

    El Programa CITI (Collaborative Institutional Training Initiative) es un curso basado en Internet y desarrollado por voluntarios, que brinda material educacional sobre protección de sujetos humanos en investigaciones biomédicas y de conducta, buenas prácticas clínicas, conducta responsable de la investigación y trato humanitario a animales de laboratorio. Es un esfuerzo conjunto del Fred Hutchinson Cancer Research Center y la Universidad de Miami. Con la colaboración de expertos locales, gran parte del contenido se ha adaptado para América Latina, se ha traducido al español y portugués y se han establecido acuerdos de colaboración con instituciones especializadas en bioética en Chile, Brasil, Costa Rica y Perú. Los autores presentan una metodología accesible para la capacitación en ética de la investigación y una justificación de su uso y difusión en América Latina PMID:21687817

  17. Body Image in Primary Schools: A pilot evaluation of a primary school intervention program designed by teachers to improve children's body satisfaction.

    Science.gov (United States)

    Halliwell, Emma; Yager, Zali; Paraskeva, Nicole; Diedrichs, Phillippa C; Smith, Hilary; White, Paul

    2016-12-01

    Body Image in the Primary School (Hutchinson & Calland, 2011) is a body image curriculum that is widely available but has not yet been evaluated. This study evaluates a set of 6 of the 49 available lessons from this curriculum. Seventy-four girls and 70 boys aged 9-10 were recruited from four primary schools in the UK. Schools were randomly allocated into the intervention condition, where students received 6hours of body image lessons, or to lessons as normal. Body esteem was significantly higher among girls in the intervention group, compared to the control group, immediately post intervention, and at 3-month follow-up. Moreover, girls with lowest levels of body esteem at baseline reported the largest gains. Internalization was significantly lower among boys in the control group compared to the intervention group at 3-month follow-up. The pattern of results among the control group raises interesting issues for intervention evaluation. Copyright © 2016. Published by Elsevier Ltd.

  18. Internal transport barriers on Alcator C-Mod

    International Nuclear Information System (INIS)

    Fiore, C.L.; Rice, J.E.; Bonoli, P.T.; Boivin, R.L.; Goetz, J.A.; Hubbard, A.E.; Hutchinson, I.H.; Granetz, R.S.; Greenwald, M.J.; Marmar, E.S.; Mossessian, D.; Porkolab, M.; Taylor, G.; Snipes, J.; Wolfe, S.M.; Wukitch, S.J.

    2001-01-01

    The formation of internal transport barriers (ITBs) has been observed in the core region of Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] under a variety of conditions. The improvement in core confinement following pellet injection (pellet enhanced performance or PEP mode) has been well documented on Alcator C-Mod in the past. Recently three new ITB phenomena have been observed which require no externally applied particle or momentum input. Short lived ITBs form spontaneously following the high confinement to low confinement mode transition and are characterized by a large increase in the global neutron production (enhanced neutron or EN modes). Experiments with ion cyclotron range of frequencies power injection to the plasma off-axis on the high field side results in the central density rising abruptly and becoming peaked. The ITB formed at this time lasts for ten energy confinement times. The central toroidal rotation velocity decreases and changes sign as the density rises. Similar spontaneous ITBs have been observed in ohmically heated H-mode plasmas. All of these ITB events have strongly peaked density profiles with a minimum in the density scale length occurring near r/a=0.5 and have improved confinement parameters in the core region of the plasma

  19. Harvesting in delayed food web model with omnivory

    Science.gov (United States)

    Collera, Juancho A.

    2016-02-01

    We consider a tri-trophic community module called intraguild predation (IGP) that includes a prey and its predator which share a common basal resource for their sustenance. The growth of the basal resource in the absence of predation follows the Hutchinson's equation where the delay parameter arises, while functional responses in our model are of Lotka-Volterra type. Moreover, the basal resource is harvested for its economic value with a constant harvesting rate. This work generalizes the previous works on the same model with no harvesting and no time delay. We show that the harvesting rate has to be small enough in order for the equilibria to exist. Moreover, we show that by increasing the delay parameter the stability of the equilibrium solutions may change, and periodic solutions may emerge through Hopf bifurcations. In the case of the positive equilibrium solution, multiple stability switches are obtained, and numerical continuation shows that a stable branch of periodic solutions emerges once the positive equilibrium loses its stability at the first Hopf bifurcation point. This result is important because it gives an alternative for the coexistence of all three species, avoiding extinction of one or more species when the positive equilibrium becomes unstable.

  20. The determination of the local conditions for void initiation in front of a crack tip for materials with second-phase particles

    Energy Technology Data Exchange (ETDEWEB)

    Sabirov, I. [Erich Schmid Institute of Materials Science, Austrian Academy of Sciences, Jahnstrasse 12, A-8700 Leoben (Austria)]. E-mail: sabirov@unileoben.ac.at; Duschlbauer, D. [Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Gusshausstrasse 27-29, A-1040 Vienna (Austria); Pettermann, H.E. [Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Gusshausstrasse 27-29, A-1040 Vienna (Austria); Kolednik, O. [Erich Schmid Institute of Materials Science, Austrian Academy of Sciences, Jahnstrasse 12, A-8700 Leoben (Austria)

    2005-02-25

    A procedure is proposed to determine, for second-phase particles near a crack tip, the maximum particle stresses at the moment of void initiation by either particle fracture or particle/matrix interface separation. A digital image analysis system is applied to perform a quantitative analysis of corresponding fracture surface regions from stereo image pairs taken in the scanning electron microscope. The fracture surface analysis is used to measure, for individual particles, the crack tip opening displacement at the moment of void initiation and the particle location with respect to the crack tip. From these data, the stress tensor at the moment of void initiation is calculated from the Hutchinson-Rice-Rosengren (HRR) field theory. The corresponding average local stresses within the particle are evaluated by a non-linear Mori-Tanaka-type approach. These stresses are compared to estimates according to the models by Argon et al. [A.S. Argon, J. Im, R. Safoglu, Metall. Trans. 6 (1975) 825] and Beremin [F.M. Beremin, Metall. Trans. 12 (1981) 723]. The procedure is demonstrated on an Al6061-10% Al{sub 2}O{sub 3} metal matrix composite.

  1. Effects of the Crack Tip Constraint on the Fracture Assessment of an Al 5083-O Weldment for Low Temperature Applications

    Directory of Open Access Journals (Sweden)

    Dong Hyun Moon

    2017-07-01

    Full Text Available The constraint effect is the key issue in structural integrity assessments based on two parameter fracture mechanics (TPFM to make a precise prediction of the load-bearing capacity of cracked structural components. In this study, a constraint-based failure assessment diagram (FAD was used to assess the fracture behavior of an Al 5083-O weldment with various flaws at cryogenic temperature. The results were compared with those of BS 7910 Option 1 FAD, in terms of the maximum allowable stress. A series of fracture toughness tests were conducted with compact tension (CT specimens at room and cryogenic temperatures. The Q parameter for the Al 5083-O weldment was evaluated to quantify the constraint level, which is the difference between the actual stress, and the Hutchinson-Rice-Rosengren (HRR stress field near the crack tip. Nonlinear 3D finite element analysis was carried out to calculate the Q parameter at cryogenic temperature. Based on the experimental and numerical results, the influence of the constraint level correction on the allowable applied stress was investigated using a FAD methodology. The results showed that the constraint-based FAD procedure is essential to avoid an overly conservative allowable stress prediction in an Al 5083-O weldment with flaws.

  2. Thermal residual stresses in amorphous thermoplastic polymers

    Science.gov (United States)

    Grassia, Luigi; D'Amore, Alberto

    2010-06-01

    An attempt to calculate the internal stresses in a cylindrically shaped polycarbonate (LEXAN-GE) component, subjected to an arbitrary cooling rate, will be described. The differential volume relaxation arising as a result of the different thermal history suffered by each body point was considered as the primary source of stresses build up [1-3]. A numerical routine was developed accounting for the simultaneous stress and structural relaxation processes and implemented within an Ansys® environment. The volume relaxation kinetics was modeled by coupling the KAHR (Kovacs, Aklonis, Hutchinson, Ramos) phenomenological theory [4] with the linear viscoelastic theory [5-7]. The numerical algorithm translates the specific volume theoretical predictions at each body point as applied non-mechanical loads acting on the component. The viscoelastic functions were obtained from two simple experimental data, namely the linear viscoelastic response in shear and the PVT (pressure volume temperature) behavior. The dimensionless bulk compliance was extracted from PVT data since it coincides with the memory function appearing in the KAHR phenomenological theory [7]. It is showed that the residual stress scales linearly with the logarithm of the Biot's number.

  3. Determination of the Nonlinearity Parameter in the TNM Model of Structural Recovery

    Science.gov (United States)

    Bari, Rozana; Simon, Sindee

    Structural recovery of non-equilibrium glassy materials takes place by evolution of volume and enthalpy as the glass attempts to reach to equilibrium. Structural recovery is nonlinear, nonexponential, and depends on thermal history and the process can be described by phenomenological models of structural recovery, such as the Tool-Narayanaswamy-Moynihan (TNM) and the Kovacs-Aklonis-Hutchinson-Ramos (KAHR) models. The goal of the present work is to analyze methods to determine the nonlinearity parameter x and activation energy Δh/R. The methods to determine x includes the inflectional analysis, time-temperature superposition, and two-step temperature jump methods. The activation energy Δh/R can also be obtained by the first two methods. The TNM model is used to simulate structural recovery data, which are then used to test the accuracy of the methods to determine x and Δh/R, with a particular interest in data obtained after cooling at high rates as can be obtained in the Flash DSC. The nonlinearity parameter x by the inflectional analysis and two-step temperature methods are accurate for exponential recovery. However, for real systems with nonexponential relaxation, methods to determine x are not reliable. The activation energy is well estimated by both the time-temperature superposition and inflectional analysis methods, with the former being slightly better.

  4. Enthalpy recovery in glassy materials: Heterogeneous versus homogenous models

    Science.gov (United States)

    Mazinani, Shobeir K. S.; Richert, Ranko

    2012-05-01

    Models of enthalpy relaxations of glasses are the basis for understanding physical aging, scanning calorimetry, and other phenomena that involve non-equilibrium and non-linear dynamics. We compare models in terms of the nature of the relaxation dynamics, heterogeneous versus homogeneous, with focus on the Kovacs-Aklonis-Hutchinson-Ramos (KAHR) and the Tool-Narayanaswamy-Moynihan (TNM) approaches. Of particular interest is identifying the situations for which experimental data are capable of discriminating the heterogeneous from the homogeneous scenario. The ad hoc assumption of a single fictive temperature, Tf, is common to many models, including KAHR and TNM. It is shown that only for such single-Tf models, enthalpy relaxation of a glass is a two-point correlation function in reduced time, implying that experimental results are not decisive regarding the underlying nature of the dynamics of enthalpy relaxation. We also find that the restriction of the common TNM model to a Kohlrausch-Williams-Watts type relaxation pattern limits the applicability of this approach, as the particular choice regarding the distribution of relaxation times is a more critical factor compared with isothermal relaxation experiments. As a result, significant improvements in fitting calorimetry data can be achieved with subtle adjustments in the underlying relaxation time distribution.

  5. Close friends', parents', and older siblings' smoking: reevaluating their influence on children's smoking.

    Science.gov (United States)

    Bricker, Jonathan B; Peterson, Arthur V; Robyn Andersen, M; Leroux, Brian G; Bharat Rajan, K; Sarason, Irwin G

    2006-04-01

    A number of longitudinal studies have explored the role of friends', parents', and older siblings' smoking in children's smoking acquisition. A reasonable implication of this previous research is that intervention efforts could be beneficially directed toward countering the potential influence of friends' and possibly older siblings' smoking but not parents' smoking. However, methodological limitations of this previous research motivated our reevaluation of the role of friends', parents', and older siblings' smoking in children's smoking. Close friends' smoking status was assessed when children were in 5th grade, whereas parents' and older siblings' smoking status was assessed when children were in 3rd grade. The outcome, children's daily smoking status, was assessed in 12th grade. The setting was 40 Washington state school districts that participated in the long-term Hutchinson Smoking Prevention Project. Participants were the 4,576 families for whom close friends', parents', and older siblings' smoking status as well as children's smoking status were available. The probability that each close friend's smoking influenced the child to smoke daily was 9% (95% CI = 6%-12%), the probability that each parent's smoking influenced the child to smoke daily was 11% (95% CI = 9%-14%), and the probability that each older sibling's smoking influenced the child to smoke daily was 7% (95% CI = 1%-13%). These results suggest that close friends', parents', and siblings' smoking were similarly important influences on children's smoking. Family-focused interventions could be a valuable future direction of prevention research.

  6. Edge turbulence imaging in the Alcator C-Mod tokamak

    International Nuclear Information System (INIS)

    Zweben, S.J.; Stotler, D.P.; Terry, J.L.; La Bombard, B.; Greenwald, M.; Muterspaugh, M.; Pitcher, C.S.; Hallatschek, K.; Maqueda, R.J.; Rogers, B.; Lowrance, J.L.; Mastrocola, V.J.; Renda, G.F.

    2002-01-01

    The two-dimensional (2D) radial vs poloidal structure of edge turbulence in the Alcator C-Mod tokamak [I. H. Hutchinson, R. Boivin, P. T. Bonoli et al., Nucl. Fusion 41, 1391 (2001)] was measured using fast cameras and compared with three-dimensional numerical simulations of edge plasma turbulence. The main diagnostic is gas puff imaging, in which the visible D α emission from a localized D 2 gas puff is viewed along a local magnetic field line. The observed D α fluctuations have a typical radial and poloidal scale of ≅1 cm, and often have strong local maxima ('blobs') in the scrape-off layer. The motion of this 2D structure motion has also been measured using an ultrafast framing camera with 12 frames taken at 250 000 frames/s. Numerical simulations produce turbulent structures with roughly similar spatial and temporal scales and transport levels as that observed in the experiment; however, some differences are also noted, perhaps requiring diagnostic improvement and/or additional physics in the numerical model

  7. Life in the salinity gradient: Discovering mechanisms behind a new biodiversity pattern

    Science.gov (United States)

    Telesh, Irena; Schubert, Hendrik; Skarlato, Sergei

    2013-12-01

    A recently discovered paradoxical maximum of planktonic protistan species in the salinity gradient of the Baltic Sea revealed an inverse trend of species number/salinity relation in comparison to the previously accepted species-minimum model for macrozoobenthos. Here, we review long-term data on organisms of different size classes and ecological groups to show that eukaryotic and prokaryotic microbes in plankton demonstrate a maximum species richness in the challenging zone of the critical salinity 5-8, where the large-bodied bottom dwellers (macrozoobenthos, macroalgae and aquatic higher plants) experience large-scale salinity stress which leads to an impoverished diversity. We propose a new conceptual model to explain why the diversity of small, fast-developing, rapidly evolving unicellular plankton organisms benefits from relative vacancy of brackish-water ecological niches and impaired competitiveness therein. The ecotone theory, Hutchinson's Ecological Niche Concept, species-area relationships and the Intermediate Disturbance Hypothesis are considered as a theoretical framework for understanding extinctions, speciation and variations in the evolution rates of different aquatic species in ecosystems with the pronounced salinity gradient.

  8. Lack of association between drought and mental health in a cohort of 45-61 year old rural Australian women.

    Science.gov (United States)

    Powers, Jennifer R; Dobson, Annette J; Berry, Helen L; Graves, Anna M; Hanigan, Ivan C; Loxton, Deborah

    2015-12-01

    To evaluate the impact of drought on the mental health of rural Australian women and those in vulnerable sub-populations: women who were more isolated, poorer and less educated; and women who had histories of chronic disease or poor mental health. Surveys were mailed in 1996, 1998, 2001, 2004 and 2008 to 6,664 women born between 1946 and1951 who were participating in the Australian Longitudinal Study on Women's Health. The surveys included the Mental Health Index of the Medical Outcomes Study Short-Form 36 (MHI). Drought was assessed by linking the latitude and longitude of women's place of residence at each survey to the Hutchinson Drought Index. Associations between MHI and drought were assessed using linear mixed-models. While 31% of the women experienced drought in 1998 and 50% experienced drought in 2007; experience of droughts was less common in the other years. Although drought varied from survey year to survey year, mental health did not vary with drought conditions for rural women or vulnerable sub-populations. These findings are contrary to the long-held assumption that droughts increase mental health problems in Australia. While similar results may not be true for men, empirical evidence (rather than assumptions) is required on associations between drought and mental health. © 2015 Public Health Association of Australia.

  9. Mood food: chocolate and depressive symptoms in a cross-sectional analysis.

    Science.gov (United States)

    Rose, Natalie; Koperski, Sabrina; Golomb, Beatrice A

    2010-04-26

    Much lore but few studies describe a relation of chocolate to mood. We examined the cross-sectional relationship of chocolate consumption with depressed mood in adult men and women. A sample of 1018 adults (694 men and 324 women) from San Diego, California, without diabetes or known coronary artery disease was studied in a cross-sectional analysis. The 931 subjects who were not using antidepressant medications and provided chocolate consumption information were the focus of the analysis. Mood was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Cut points signaling a positive depression screen result (CES-D score, >or=16) and probable major depression (CES-D score, >or=22) were used. Chocolate servings per week were provided by 1009 subjects. Chocolate consumption frequency and rate data from the Fred Hutchinson Food Frequency Questionnaire were also available for 839 subjects. Chocolate consumption was compared for those with lower vs higher CES-D scores. In addition, a test of trend was performed. Those screening positive for possible depression (CES-D score >or=16) had higher chocolate consumption (8.4 servings per month) than those not screening positive (5.4 servings per month) (P = .004); those with still higher CES-D scores (>or=22) had still higher chocolate consumption (11.8 servings per month) (P value for trend, chocolate consumption. Whether there is a causal connection, and if so in which direction, is a matter for future prospective study.

  10. Mood Food

    Science.gov (United States)

    Rose, Natalie; Koperski, Sabrina; Golomb, Beatrice A.

    2013-01-01

    Background Much lore but few studies describe a relation of chocolate to mood. We examined the cross-sectional relationship of chocolate consumption with depressed mood in adult men and women. Methods A sample of 1018 adults (694 men and 324 women) from San Diego, California, without diabetes or known coronary artery disease was studied in a cross-sectional analysis. The 931 subjects who were not using antidepressant medications and provided chocolate consumption information were the focus of the analysis. Mood was assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Cut points signaling a positive depression screen result (CES-D score, ≥16) and probable major depression (CES-D score, ≥22) were used. Chocolate servings per week were provided by 1009 subjects. Chocolate consumption frequency and rate data from the Fred Hutchinson Food Frequency Questionnaire were also available for 839 subjects. Chocolate consumption was compared for those with lower vs higher CES-D scores. In addition, a test of trend was performed. Results Those screening positive for possible depression (CES-D score ≥16) had higher chocolate consumption (8.4 servings per month) than those not screening positive (5.4 servings per month) (P = .004); those with still higher CES-D scores (≥22) had still higher chocolate consumption (11.8 servings per month) (P value for trend, chocolate consumption. Whether there is a causal connection, and if so in which direction, is a matter for future prospective study. PMID:20421555

  11. The 2011-2016 Transdisciplinary Research on Energetics and Cancer (TREC) initiative: rationale and design.

    Science.gov (United States)

    Patterson, Ruth E; Colditz, Graham A; Hu, Frank B; Schmitz, Kathryn H; Ahima, Rexford S; Brownson, Ross C; Carson, Kenneth R; Chavarro, Jorge E; Chodosh, Lewis A; Gehlert, Sarah; Gill, Jeff; Glanz, Karen; Haire-Joshu, Debra; Herbst, Karen Louise; Hoehner, Christine M; Hovmand, Peter S; Irwin, Melinda L; Jacobs, Linda A; James, Aimee S; Jones, Lee W; Kerr, Jacqueline; Kibel, Adam S; King, Irena B; Ligibel, Jennifer A; Meyerhardt, Jeffrey A; Natarajan, Loki; Neuhouser, Marian L; Olefsky, Jerrold M; Proctor, Enola K; Redline, Susan; Rock, Cheryl L; Rosner, Bernard; Sarwer, David B; Schwartz, J Sanford; Sears, Dorothy D; Sesso, Howard D; Stampfer, Meir J; Subramanian, S V; Taveras, Elsie M; Tchou, Julia; Thompson, Beti; Troxel, Andrea B; Wessling-Resnick, Marianne; Wolin, Kathleen Y; Thornquist, Mark D

    2013-04-01

    Recognition of the complex, multidimensional relationship between excess adiposity and cancer control outcomes has motivated the scientific community to seek new research models and paradigms. The National Cancer Institute developed an innovative concept to establish a center grant mechanism in nutrition, energetics, and physical activity, referred to as the Transdisciplinary Research on Energetics and Cancer (TREC) Initiative. This paper gives an overview of the 2011-2016 TREC Collaborative Network and the 15 research projects being conducted at the centers. Four academic institutions were awarded TREC center grants in 2011: Harvard University, University of California San Diego, University of Pennsylvania, and Washington University in St. Louis. The Fred Hutchinson Cancer Research Center is the Coordination Center. The TREC research portfolio includes three animal studies, three cohort studies, four randomized clinical trials, one cross-sectional study, and two modeling studies. Disciplines represented by TREC investigators include basic science, endocrinology, epidemiology, biostatistics, behavior, medicine, nutrition, physical activity, genetics, engineering, health economics, and computer science. Approximately 41,000 participants will be involved in these studies, including children, healthy adults, and breast and prostate cancer survivors. Outcomes include biomarkers of cancer risk, changes in weight and physical activity, persistent adverse treatment effects (e.g., lymphedema, urinary and sexual function), and breast and prostate cancer mortality. The NIH Science of Team Science group will evaluate the value added by this collaborative science. However, the most important outcome will be whether this transdisciplinary initiative improves the health of Americans at risk of cancer as well as cancer survivors.

  12. Effect of magnetic and density fluctuations on the propagation of lower hybrid waves in tokamaks

    Science.gov (United States)

    Vahala, George; Vahala, Linda; Bonoli, Paul T.

    1992-12-01

    Lower hybrid waves have been used extensively for plasma heating, current drive, and ramp-up as well as sawteeth stabilization. The wave kinetic equation for lower hybrid wave propagation is extended to include the effects of both magnetic and density fluctuations. This integral equation is then solved by Monte Carlo procedures for a toroidal plasma. It is shown that even for magnetic/density fluctuation levels on the order of 10-4, there are significant magnetic fluctuation effects on the wave power deposition into the plasma. This effect is quite pronounced if the magnetic fluctuation spectrum is peaked within the plasma. For Alcator-C-Mod [I. H. Hutchinson and the Alcator Group, Proceedings of the IEEE 13th Symposium on Fusion Engineering (IEEE, New York, 1990), Cat. No. 89CH 2820-9, p. 13] parameters, it seems possible to be able to infer information on internal magnetic fluctuations from hard x-ray data—especially since the effects of fluctuations on electron power density can explain the hard x-ray data from the JT-60 tokamak [H. Kishimoto and JT-60 Team, in Plasma Physics and Controlled Fusion (International Atomic Energy Agency, Vienna, 1989), Vol. I, p. 67].

  13. High-confinement-mode edge stability of Alcator C-mod plasmas

    International Nuclear Information System (INIS)

    Mossessian, D.A.; Snyder, P.; Hubbard, A.; Hughes, J.W.; Greenwald, M.; La Bombard, B.; Snipes, J.A.; Wolfe, S.; Wilson, H.

    2003-01-01

    For steady state high-confinement-mode (H-mode) operation, a relaxation mechanism is required to limit build-up of the edge gradient and impurity content. Alcator C-Mod [Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] sees two such mechanisms--EDA (enhanced D-alpha H mode) and grassy ELMs (edge localized modes), but not large type I ELMs. In EDA the edge relaxation is provided by an edge localized quasicoherent (QC) electromagnetic mode that exists at moderate pedestal temperature T 95 >3.5, and does not limit the buildup of the edge pressure gradient. The q boundary of the operational space of the mode depends on plasma shape, with the q 95 limit moving down with increasing plasma triangularity. At high edge pressure gradients and temperatures the mode is replaced by broadband fluctuations ( f<50 kHz) and small irregular ELMs are observed. Ideal MHD (magnetohydrodynamic) stability analysis that includes both pressure and current driven edge modes shows that the discharges where the QC mode is observed are stable. The ELMs are identified as medium n (10< n<50) coupled peeling/ballooning modes. The predicted stability boundary of the modes as a function of pedestal current and pressure gradient is reproduced in experimental observations. The measured dependence of the ELMs' threshold and amplitude on plasma triangularity is consistent with the results of ideal MHD analysis performed with the linear stability code ELITE [Wilson et al., Phys. Plasmas 9, 1277 (2002)

  14. H-mode pedestal and threshold studies over an expanded operating space on Alcator C-Moda)

    Science.gov (United States)

    Hubbard, A. E.; Hughes, J. W.; Bespamyatnov, I. O.; Biewer, T.; Cziegler, I.; LaBombard, B.; Lin, Y.; McDermott, R.; Rice, J. E.; Rowan, W. L.; Snipes, J. A.; Terry, J. L.; Wolfe, S. M.; Wukitch, S.

    2007-05-01

    This paper reports on studies of the edge transport barrier and transition threshold of the high confinement (H) mode of operation on the Alcator C-Mod tokamak [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)], over a wide range of toroidal field (2.6-7.86T) and plasma current (0.4-1.7MA). The H-mode power threshold and edge temperature at the transition increase with field. Barrier widths, pressure limits, and confinement are nearly independent of field at constant current, but the operational space at high B shifts toward higher temperature and lower density and collisionality. Experiments with reversed field and current show that scrape-off-layer flows in the high-field side depend primarily on configuration. In configurations with the B ×∇B drift away from the active X-point, these flows lead to more countercurrent core rotation, which apparently contributes to higher H-mode thresholds. In the unfavorable case, edge temperature thresholds are higher, and slow evolution of profiles indicates a reduction in thermal transport prior to the transition in particle confinement. Pedestal temperatures in this case are also higher than in the favorable configuration. Both high-field and reversed-field results suggest that parameters at the L-H transition are influencing the evolution and parameters of the H-mode pedestal.

  15. Experimental studies of edge turbulence and confinement in Alcator C-Moda)

    Science.gov (United States)

    Cziegler, I.; Terry, J. L.; Hughes, J. W.; LaBombard, B.

    2010-05-01

    The steep gradient edge region and scrape-off-layer (SOL) on the low-field-side of Alcator C-Mod [I. H. Hutchinson, R. Boivin, F. Bombarda et al., Phys. Plasmas 1, 1511 (1994)] tokamak plasmas are studied using gas-puff-imaging diagnostics. In L-mode plasmas, the region extending ˜2 cm inside the magnetic separatrix has fluctuations showing a broad, turbulent spectrum, propagating in the electron diamagnetic drift direction, whereas features in the open field line region propagate in the ion diamagnetic drift direction. This structure is robust against toroidal field strength, poloidal null-point geometry, plasma current, and plasma density. Global parameter dependence of spectral and spatial structure of the turbulence inside the separatrix is explored and characterized, and both the intensity and spectral distributions are found to depend strongly on the plasma density normalized to the tokamak density limit. In H-mode discharges the fluctuations at and inside the magnetic separatrix show fundamentally different trends compared to L-mode, with the electron diamagnetic direction propagating turbulence greatly reduced in ELM-free [F. Wagner et al., Proceedings of the Thirteenth Conference on Plasma Physics and Controlled Nuclear Fusion Research (IAEA, Vienna, 1982), Vol. I, p. 277], and completely dominated by the modelike structure of the quasicoherent mode in enhanced D-alpha regimes [A. E. Hubbard, R. L. Boivin, R. S. Granetz et al., Phys. Plasmas 8, 2033 (2001)], while the normalized SOL turbulence is largely unaffected.

  16. The cell biology of aging.

    Science.gov (United States)

    Hayflick, L

    1985-02-01

    It is only within the past ten years that biogerontology has become attractive to a sufficient number of biologists so that the field can be regarded as a seriously studied discipline. Cytogerontology, or the study of aging at the cellular level, had its genesis about 20 years ago when the dogma that maintained that cultured normal cells could replicate forever was overturned. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Only abnormal somatic cells are capable of immortality. In recent years it has been found that the number of population doublings of which cultured normal cells are capable is inversely proportional to donor age. There is also good evidence that the number of population doublings of cultured normal fibroblasts is directly proportional to the maximum lifespan of ten species that have been studied. Cultures prepared from patients with accelerated aging syndromes (progeria and Werner's syndrome) undergo far fewer doublings than do those of age-matched controls. The normal human fibroblast cell strain WI-38 was established in 1962 from fetal lung, and several hundred ampules of these cells were frozen in liquid nitrogen at that time. These ampules have been reconstituted periodically and shown to be capable of replication. This represents the longest period of time that a normal human cell has ever been frozen. Normal human fetal cell strains such as WI-38 have the capacity to double only about 50 times. If cultures are frozen at various population doublings, the number of doublings remaining after reconstitution is equal to 50 minus the number of doublings that occurred prior to freezing. The memory of the cells has been found to be accurate after 23 years of preservation in liquid nitrogen. Normal human cells incur many physiologic decrements that herald the approach of their

  17. Mislocalization of XPF-ERCC1 nuclease contributes to reduced DNA repair in XP-F patients.

    Directory of Open Access Journals (Sweden)

    Anwaar Ahmad

    2010-03-01

    Full Text Available Xeroderma pigmentosum (XP is caused by defects in the nucleotide excision repair (NER pathway. NER removes helix-distorting DNA lesions, such as UV-induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. The severity of XP varies tremendously depending upon which NER gene is mutated and how severely the mutation affects DNA repair capacity. XPF-ERCC1 is a structure-specific endonuclease essential for incising the damaged strand of DNA in NER. Missense mutations in XPF can result not only in XP, but also XPF-ERCC1 (XFE progeroid syndrome, a disease of accelerated aging. In an attempt to determine how mutations in XPF can lead to such diverse symptoms, the effects of a progeria-causing mutation (XPF(R153P were compared to an XP-causing mutation (XPF(R799W in vitro and in vivo. Recombinant XPF harboring either mutation was purified in a complex with ERCC1 and tested for its ability to incise a stem-loop structure in vitro. Both mutant complexes nicked the substrate indicating that neither mutation obviates catalytic activity of the nuclease. Surprisingly, differential immunostaining and fractionation of cells from an XFE progeroid patient revealed that XPF-ERCC1 is abundant in the cytoplasm. This was confirmed by fluorescent detection of XPF(R153P-YFP expressed in Xpf mutant cells. In addition, microinjection of XPF(R153P-ERCC1 into the nucleus of XPF-deficient human cells restored nucleotide excision repair of UV-induced DNA damage. Intriguingly, in all XPF mutant cell lines examined, XPF-ERCC1 was detected in the cytoplasm of a fraction of cells. This demonstrates that at least part of the DNA repair defect and symptoms associated with mutations in XPF are due to mislocalization of XPF-ERCC1 into the cytoplasm of cells, likely due to protein misfolding. Analysis of these patient cells therefore reveals a novel mechanism to potentially

  18. The lucid interval associated with epidural bleeding: evolving understanding.

    Science.gov (United States)

    Ganz, Jeremy C

    2013-04-01

    The aim of this paper was to elucidate the evolution of our understanding of the term "lucid interval." A number of texts were reviewed to assess their suitability for analysis. The primary requirement was that the text contain detailed descriptions of a series of patients. Details of the clinical course, the findings and timing of surgery, and, when relevant, the time of death and postmortem findings were required. Books written by Henri-François Le Dran, Percival Pott, and James Hill fulfilled these criteria. Surgical findings included the presence and type of fractures, changes in the bone, separation of periosteum, malodorous or purulent material, tense brain, and hematoma. Postmortem findings supplemented and/or complemented the surgical findings. The courses of the patients were then tabulated, and the correlation between different clinical and operative findings was thereby determined. Our understanding of a lucid interval began in the early 18th century with the work of Henri-François Le Dran and Percival Pott in London. They did not, however, demonstrate an interval without symptoms between trauma and deterioration in patients with epidural hematomas (EDHs). The interval they described was longer than usually expected with EDHs and occurred exclusively in patients who had a posttraumatic infection. In 1751, James Hill, from Dumfries, Scotland, described the first hematoma-related lucid interval in a patient with a subdural hematoma. The first case of a lucid interval associated with an EDH was described by John Abernethy. In the 19th century, Jonathan Hutchinson and Walter Jacobson described the interval as it is known today, in cases of EDH. The most recent work on the topic came from studies in Cincinnati and Oslo, where it was demonstrated that bleeding can separate dura mater and that hemorrhage into the epidural space can be shunted out via the veins. This shunting could delay the accumulation of a hematoma and thus the rise in intracranial pressure

  19. Application of the Unity Rockfall Model to Variable Surface Material Conditions

    Science.gov (United States)

    Sala, Zac; Hutchinson, D. Jean; Ondercin, Matthew

    2017-04-01

    affect the dominant processes controlling rockfall movement downslope. In comparison to rock on rock collisions, impacts with soil and talus exhibit lower restitution values, with more energy loss occurring, but less overall fragmentation expected. The current modelling efforts present example workflows for each case, showing the steps taken to run realistic simulations using the Unity rockfall model. A comparison of the setup, model inputs and methods implemented in the model for each case study demonstrates the adaptability of the tool to different rockfall environments. References: [1] Ondercin, M.: An Exploration of Rockfall Modelling Through Game Engines, M.A.Sc Thesis, Queen's University, Kingston, 2016 [2] Kromer, R., Hutchinson, D.J., Lato, M., Gauthier, D., and Edwards, T. 2015. Identifying rock slope failure precursors using LiDAR for transportation corridor hazard management. Engineering Geology, 195, 93-103. doi:10.1016/j.enggeo.2015.05.012 [3] van Veen, M., Hutchinson, D.J., Kromer, R., Lato, M., and Edwards, T. (Submitted September 2016) Effects of Sampling Interval on the Frequency-Magnitude Relationship of Rockfalls Detected from Terrestrial Laser Scanning using Semi-Automated Methods. Landslides, MS number: LASL-D-16-00258. [4] Vick, L.M.: Evaluation of Field Data and 3D Modelling for Rockfall Hazard Assessment, Ph.D Thesis, University of Canterbury, Christchurch, 2015

  20. Catálogo florístico y claves de identificación de las ciperáceas de los Estados de Paraíba y Pernambuco (nordeste de Brasil

    Directory of Open Access Journals (Sweden)

    Luceño, Modesto

    1997-06-01

    Full Text Available The present work presents the results of our studies of the family Cyperaceae in the northeastern Brazilian States of Pernambuco and Paraiba. The introduction includes a historical synopsis of previous work and summarizes the main types of vegetation found in the región. Keys for identification of the 22 genera and 127 species which comprise the catalogue are included. The species are enumerated for each genus, along with synonyms which have been employed in the región, material examined, frequency, habitat, general geographic distribution, and taxonomic observations where appropriate. More than half of the species are new records for Pernambuco and Paraiba. Two species are reported as new to science. Fuirena lainzii Luceño & M. Alves (1996 and Scleria pernambucana Luceño & M. Alves (1997. Two species are first reports from the American continent, Pycreus pumilus (L. Nees and P. pelophilus (Ridley C.B. Clarke, and two are first repoits for Brazil, Kyllinga nemoralis (J.R. Forster & G. Forster Dandy ex Hutchinson & Daziel and Scleria mexicana (Liebm. Boeck. Six genera and 10 species are new citations for the northeastem región of Brazil. A lectotype for Cyperus grossianus T.M. Ped. is chosen. Additionally, new localities are given for regional endemisms considered for be rare; other findings represent disjunctions of considerable biogeographical importance.En el presente trabajo se exponen los resultados de las investigaciones que hemos llevado a cabo, sobre la familia de las Ciperáceas, en los Estados brasileños de Pemambuco y Paraíba. En la introducción se presenta una sinopsis histórica de los trabajos anteriores y se resumen las principales formaciones vegetales. Se ofrecen claves para la identificación de los 22 géneros y las 136 especies que componen el catálogo. Tras las claves de cada género se enumeran las diversas especies del mismo, junto con los sinónimos que han sido empleados en la región, materiales examinados

  1. Borehole strain observations of very low frequency earthquakes

    Science.gov (United States)

    Hawthorne, J. C.; Ghosh, A.; Hutchinson, A. A.

    2016-12-01

    We examine the signals of very low frequency earthquakes (VLFEs) in PBO borehole strain data in central Cascadia. These MW 3.3 - 4.1 earthquakes are best observed in seismograms at periods of 20 to 50 seconds. We look for the strain they produce on timescales from about 1 to 30 minutes. First, we stack the strain produced by 13 VLFEs identified by a grid search moment tensor inversion algorithm by Ghosh et. al. (2015) and Hutchinson and Ghosh (2016), as well as several thousand VLFEs detected through template matching these events. The VLFEs are located beneath southernmost Vancouver Island and the eastern Olympic Peninsula, and are best recorded at co-located stations B005 and B007. However, even at these stations, the signal to noise in the stack is often low, and the records are difficult to interpret. Therefore we also combine data from multiple stations and VLFE locations, and simply look for increases in the strain rate at the VLFE times, as increases in strain rate would suggest an increase in the moment rate. We compare the background strain rate in the 12 hours centered on the VLFEs with the strain rate in the 10 minutes centered on the VLFEs. The 10-minute duration is chosen as a compromise that averages out some instrumental noise without introducing too much longer-period random walk noise. Our results suggest a factor of 2 increase in strain rate--and thus moment rate--during the 10-minute VLFE intervals. The increase gives an average VLFE magnitude around M 3.5, within the range of magnitudes obtained with seismology. Further analyses are currently being carried out to better understand the evolution of moment release before, during, and after the VLFEs.

  2. Modeling of the mechanical behavior of austenitic stainless steels under pure fatigue and fatigue relaxation loadings

    International Nuclear Information System (INIS)

    Hajjaji-Rachdi, Fatima

    2015-01-01

    Austenitic stainless steels are potential candidates for structural components of sodium-cooled fast neutron reactors. Many of these components will be subjected to cyclic loadings including long hold times (1 month) under creep or relaxation at high temperature. These hold times are unattainable experimentally. The aim of the present study is to propose mechanical models which take into account the involved mechanisms and their interactions during such complex loadings. First, an experimental study of the pure fatigue and fatigue-relaxation behavior of 316L(N) at 500 C has been carried out with very long hold times (10 h and 50 h) compared with the ones studied in literature. Tensile tests at 600 C with different applied strain rates have been undertaken in order to study the dynamic strain ageing phenomenon. Before focusing on more complex loadings, the mean field homogenization approach has been used to predict the mechanical behavior of different FCC metals and alloys under low cycle fatigue at room temperature. Both Hill-Hutchinson and Kroener models have been used. Next, a physically-based model based on dislocation densities has been developed and its parameters measured. The model allows predictions in a qualitative agreement with experimental data for tensile loadings. Finally, this model has been enriched to take into account visco-plasticity, dislocation climb and interaction between dislocations and solute atoms, which are influent during creep-fatigue or fatigue relaxation at high temperature. The proposed model uses three adjustable parameters only and allows rather accurate prediction of the behavior of 316L(N) steel under tensile loading and relaxation. (author) [fr

  3. Fluctuating zonal flows in the I-mode regime in Alcator C-Mod

    Energy Technology Data Exchange (ETDEWEB)

    Cziegler, I.; Diamond, P. H.; Fedorczak, N.; Manz, P.; Tynan, G. R.; Xu, M. [Center for Momentum Transport and Flow Organization, University of California, San Diego, La Jolla, California 92093 (United States); Churchill, R. M.; Hubbard, A. E.; Lipschultz, B.; Sierchio, J. M.; Terry, J. L.; Theiler, C. [Plasma Science and Fusion Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02138 (United States)

    2013-05-15

    Velocity fields and density fluctuations of edge turbulence are studied in I-mode [F. Ryter et al., Plasma Phys. Controlled Fusion 40, 725 (1998)] plasmas of the Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] tokamak, which are characterized by a strong thermal transport barrier in the edge while providing little or no barrier to the transport of both bulk and impurity particles. Although previous work showed no clear geodesic-acoustic modes (GAM) on C-Mod, using a newly implemented, gas-puff-imaging based time-delay-estimate velocity inference algorithm, GAM are now shown to be ubiquitous in all I-mode discharges examined to date, with the time histories of the GAM and the I-mode specific [D. Whyte et al., Nucl. Fusion 50, 105005 (2010)] Weakly Coherent Mode (WCM, f = 100–300 kHz, Δf/f≈0.5, and k{sub θ}≈1.3 cm{sup −1}) closely following each other through the entire duration of the regime. Thus, the I-mode presents an example of a plasma state in which zero frequency zonal flows and GAM continuously coexist. Using two-field (density-velocity and radial-poloidal velocity) bispectral methods, the GAM are shown to be coupled to the WCM and to be responsible for its broad frequency structure. The effective nonlinear growth rate of the GAM is estimated, and its comparison to the collisional damping rate seems to suggest a new view on I-mode threshold physics.

  4. Effects of temperature, temperature gradients, stress, and irradiation on migration of brine inclusions in a salt repository

    International Nuclear Information System (INIS)

    Jenks, G.H.

    1979-07-01

    Available experimental and theoretical information on brine migration in bedded salt are reviewed and analyzed. The effects of temperature, thermal gradients, stress, irradiation, and pressure in a salt repository are among the factors considered. The theoretical and experimental (with KCl) results of Anthony and Cline were used to correlate and explain the available data for rates of brine migration at temperatures up to 250 0 C in naturally occurring crystals of bedded salt from Lyons and Hutchinson, Kansas. Considerations of the effects of stressing crystals of bedded salt on the migratin properties of brine inclusions within the crystals led to the conclusion that the most probable effects are a small fractional increase in the solubility of the salt within the liquid and a concomitant and equal fractional increase in the rate of the thermal gradient-induced migration of the brine. The greatest uncertainty relative to the prediction of rates of migration of brine into a waste emplacement cavity in bedded salt is associated with questions concerning the effects of the grain boundaries (within the aggregates of single crystals which comprise a bedded salt deposit) on brine migration through the deposit. The results of some of the estimates of rates and total amounts of brine inflow to HLW and SURF waste packages emplaced in bedded salt were included to illustrate the inflow volumes which might occur in a repository. The results of the brine inflow estimates for 10-year-old HLW emplaced at 150 kW/acre indicated inflow rates starting at 0.7 liter/year and totaling 12 liters at 30 years after emplacement. The results of the estimates for 10-year-old PWR SURF emplaced at 60 kW/acre indicated a constant inflow of 0.035 liter/year for the first 35 years after emplacement

  5. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients

    Science.gov (United States)

    Keel, Siobán B.; Scott, Angela; Sanchez-Bonilla, Marilyn; Ho, Phoenix A.; Gulsuner, Suleyman; Pritchard, Colin C.; Abkowitz, Janis L.; King, Mary-Claire; Walsh, Tom; Shimamura, Akiko

    2016-01-01

    The clinical and histopathological distinctions between inherited versus acquired bone marrow failure and myelodysplastic syndromes are challenging. The identification of inherited bone marrow failure/myelodysplastic syndromes is critical to inform appropriate clinical management. To investigate whether a subset of pediatric and young adults undergoing transplant for aplastic anemia or myelodysplastic syndrome have germline mutations in bone marrow failure/myelodysplastic syndrome genes, we performed a targeted genetic screen of samples obtained between 1990–2012 from children and young adults with aplastic anemia or myelodysplastic syndrome transplanted at the Fred Hutchinson Cancer Research Center. Mutations in inherited bone marrow failure/myelodysplastic syndrome genes were found in 5.1% (5/98) of aplastic anemia patients and 13.6% (15/110) of myelodysplastic syndrome patients. While the majority of mutations were constitutional, a RUNX1 mutation present in the peripheral blood at a 51% variant allele fraction was confirmed to be somatically acquired in one myelodysplastic syndrome patient. This highlights the importance of distinguishing germline versus somatic mutations by sequencing DNA from a second tissue or from parents. Pathological mutations were present in DKC1, MPL, and TP53 among the aplastic anemia cohort, and in FANCA, GATA2, MPL, RTEL1, RUNX1, SBDS, TERT, TINF2, and TP53 among the myelodysplastic syndrome cohort. Family history or physical examination failed to reliably predict the presence of germline mutations. This study shows that while any single specific bone marrow failure/myelodysplastic syndrome genetic disorder is rare, screening for these disorders in aggregate identifies a significant subset of patients with inherited bone marrow failure/myelodysplastic syndrome. PMID:27418648

  6. Mineral sources of water and their influence on the safe disposal of radioactive wastes in bedded salt deposits

    Energy Technology Data Exchange (ETDEWEB)

    Fallis, S.M.

    1973-12-01

    With the increased use of nuclear energy, there will be subsequent increases in high-level radioactive wastes such as Sr/sup 90/, Cs/sup 137/, and Pu/sup 239/. Several agencies have considered the safest possible means to store or dispose of wastes in geologic environments such as underground storage in salt deposits, shale beds, abandoned dry mines, and in clay and shale pits. Salt deposits have received the most favorable attention because they exist in dry environments and because of other desirable properties of halite (its plasticity, gamma-ray shielding, heat dissipation ability, low mining cost, and worldwide abundance). Much work has been done on bedded salt deposits, particularly the Hutchinson Salt Member of the Wellington Formation at Lyons, Kansas. Salt beds heated by the decay of the radioactive wastes may release water by dehydration of hydrous minerals commonly present in evaporite sequences or water present in other forms such as fluid inclusions. More than 80 hydrous minerals are known to occur in evaporite deposits. The occurrences, total water contents (up to 63%) and dehydration temperatures (often less that 150/sup 0/C) of these minerals are given. Since it is desirable to dispose of radioactive wastes in a dry environment, care must be taken that large quantities of water are not released through the heating of hydrous minerals. Seventy-four samples from four cores taken at Lyons, Kansas, were analyzed by x-ray diffraction. The minerals detected were halite, anhydrite, gypsum, polyhalite, dolomite, magnesite, quartz, feldspar, and the clay minerals illite, chlorite, kaolinite, vermiculite, smectite, mixed-layer clay, and corrensite (interstratified chlorite-vermiculite). Of these, gypsum, polyhalite and the clay minerals are all capable of releasing water when heated.

  7. Characterisation of polycrystal deformation by numerical modelling and neutron diffraction measurements

    International Nuclear Information System (INIS)

    Clausen, B.

    1997-09-01

    The deformation of polycrystals are modelled using three micron mechanic models; the Taylor model, the Sachs model and Hutchinson's self-consistent (SC) model. The predictions of the rigid plastic Taylor and Sachs models are compared with the predictions of the SC model. As expected, the results of the SC model is about half-way between the upper- and lower-bound models. The influence of the elastic anisotropy is investigated by comparing the SC predictions for aluminium, copper and a hypothetical material (Hybrid) with the elastic anisotropy of copper and the Young's modulus and hardening behaviour of aluminium. It is concluded that the effect of the elastic anisotropy is limited to the very early stages of plasticity, as the deformation pattern is almost identical for the three materials at higher strains. The predictions of the three models are evaluated by neutron diffraction measurements of elastic lattice strains in grain sub-sets within the polycrystal. The two rigid plastic models do not include any material parameters and therefore the predictions of the SC model is more accurate and more detailed than the predictions of the Taylor and Sachs models. The SC model is used to determine the most suitable reflection for technological applications of neutron diffraction, where focus is on the volume average stress state in engineering components. To be able to successfully to convert the measured elastic lattice strains for a specific reflection into overall volume average stresses, there must be a linear relation between the lattice strain of the reflection and the overall stress. According to the model predictions the 311-reflection is the most suitable reflection as it shows the smallest deviations from linearity and thereby also the smallest build-up of residual strains. The model predictions have pin pointed that the selection of the reflection is crucial for the validity of stresses calculated from the measured elastic lattice strains. (au) 14 tabs., 41

  8. FRAGMENTATION STUDIES OF D6,7-ANHIDROERITROMISIN-A BY LIQUID CHROMATOGRAPHY-MASS SPECTROSCOPY (LC-MS

    Directory of Open Access Journals (Sweden)

    Khairan Khairan

    2010-06-01

    Full Text Available Semisynthesis of D6,7-Anhydroerythromycin-A was done by biomodification technique by addition of 0.2% INH into a culture fermentation of Saccharopolyspora erythraea ATCC 11635 in medium Hutchinson. The aim of this research is to studies of fragmentation pattern from new matabolite of D6,7-Anhydroerythromycin-A by Liquid Chromatography-Mass Spectroscopy (LC-MS and the ionization of mass spectroscopy is use by ESI (Electrospray Ionization pattern. The FT-IR spectrometric analyzes showed a stretching vibration of C=C conjugated group at wave number 1602.7 cm-1. This C=C conjugated vibration indicated the existence of double bond between C6 and C7 (D6,7, this confirmed that isolate contained D6,7-Anhydroerythromycin-A (the possibility of D6,7 was positive. For complementation, a LC-MS (Liquid Chromatography-Mass Spectroscopy analyzes using ESI-MS (Electrospray Ionization-Mass Spectroscopy ionization pattern was conducted to the isolate which resulted Quassimolecular ions [M+H]+ of D7,8- and D6,7-Anhydroerythromycin-A. LC-MS spectrogram of the isolate, which gave two peaks of m/z 732.2460 and m/z 716.2522, confirmed that the m/z 732.2460 possibly was D7,8-Anhydroerythromycin-A, while the m/z 716.2502 and m/z 715.2522 possibly were D6,7-Anhydroerythromycin-A.   Keywords: isoniazid, enoyl reduction, D6,7-Anhidroeritromisin-A, fragmentation, LC-MS.

  9. Implementation of comparative effectiveness research in personalized medicine applications in oncology: current and future perspectives

    Directory of Open Access Journals (Sweden)

    IJzerman MJ

    2015-11-01

    Full Text Available Maarten J IJzerman,1,3 Andrea Manca,2,3 Julia Keizer,1 Scott D Ramsey4 1Department of Health Technology and Services Research, University of Twente, Enschede, the Netherlands; 2Centre for Health Economics, University of York, York, UK; 3Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg, 4Fred Hutchinson Cancer Research Center, Seattle, WA, USAAbstract: Personalized medicine (PM or precision medicine has been defined as an innovative approach that takes into account individual differences in people's genes, environments, and lifestyles in prevention and treatment of disease. In PM, genomic information may contribute to the molecular understanding of disease, to optimize preventive health care strategies, and to fit the best drug therapies to the patient's individual characteristics. Evidence development in the era of genomic medicine is extremely challenging due to a number of factors. These include the rapid technological innovation in molecular diagnostics and targeted drug discoveries, and hence the large number of mutations and multiple ways these may influence treatment decisions. Although the evidence base for PM is evolving rapidly, the main question to be explored in this article is whether existing evidence is also fit for comparative effectiveness research (CER. As a starting point, this paper therefore reflects on the evidence required for CER and the evidence gaps preventing decisions on market access and coverage. The paper then discusses challenges and potential barriers for applying a CER paradigm to PM, identifies common methodologies for designing clinical trials in PM, discusses various approaches for analyzing clinical trials to infer from population to individual level, and presents an example of a clinical trial in PM (The RxPONDER TRIAL demonstrating good practice. The paper concludes with a future perspective, including modeling approaches for evidence synthesis.Keywords: personalized

  10. Bacteria dialog with Santa Rosalia: Are aggregations of cosmopolitan bacteria mainly explained by habitat filtering or by ecological interactions?

    Science.gov (United States)

    Pascual-García, Alberto; Tamames, Javier; Bastolla, Ugo

    2014-12-04

    Since the landmark Santa Rosalia paper by Hutchinson, niche theory addresses the determinants of biodiversity in terms of both environmental and biological aspects. Disentangling the role of habitat filtering and interactions with other species is critical for understanding microbial ecology. Macroscopic biogeography explores hypothetical ecological interactions through the analysis of species associations. These methods have started to be incorporated into microbial ecology relatively recently, due to the inherent experimental difficulties and the coarse grained nature of the data. Here we investigate the influence of environmental preferences and ecological interactions in the tendency of bacterial taxa to either aggregate or segregate, using a comprehensive dataset of bacterial taxa observed in a wide variety of environments. We assess significance of taxa associations through a null model that takes into account habitat preferences and the global distribution of taxa across samples. The analysis of these associations reveals a surprisingly large number of significant aggregations between taxa, with a marked community structure and a strong propensity to aggregate for cosmopolitan taxa. Due to the coarse grained nature of our data we cannot conclusively reject the hypothesis that many of these aggregations are due to environmental preferences that the null model fails to reproduce. Nevertheless, some observations are better explained by ecological interactions than by habitat filtering. In particular, most pairs of aggregating taxa co-occur in very different environments, which makes it unlikely that these associations are due to habitat preferences, and many are formed by cosmopolitan taxa without well defined habitat preferences. Moreover, known cooperative interactions are retrieved as aggregating pairs of taxa. As observed in similar studies, we also found that phylogenetically related taxa are much more prone to aggregate than to segregate, an observation

  11. Does probability of occurrence relate to population dynamics?

    Science.gov (United States)

    Thuiller, Wilfried; Münkemüller, Tamara; Schiffers, Katja H; Georges, Damien; Dullinger, Stefan; Eckhart, Vincent M; Edwards, Thomas C; Gravel, Dominique; Kunstler, Georges; Merow, Cory; Moore, Kara; Piedallu, Christian; Vissault, Steve; Zimmermann, Niklaus E; Zurell, Damaris; Schurr, Frank M

    2014-12-01

    Hutchinson defined species' realized niche as the set of environmental conditions in which populations can persist in the presence of competitors. In terms of demography, the realized niche corresponds to the environments where the intrinsic growth rate ( r ) of populations is positive. Observed species occurrences should reflect the realized niche when additional processes like dispersal and local extinction lags do not have overwhelming effects. Despite the foundational nature of these ideas, quantitative assessments of the relationship between range-wide demographic performance and occurrence probability have not been made. This assessment is needed both to improve our conceptual understanding of species' niches and ranges and to develop reliable mechanistic models of species geographic distributions that incorporate demography and species interactions. The objective of this study is to analyse how demographic parameters (intrinsic growth rate r and carrying capacity K ) and population density ( N ) relate to occurrence probability ( P occ ). We hypothesized that these relationships vary with species' competitive ability. Demographic parameters, density, and occurrence probability were estimated for 108 tree species from four temperate forest inventory surveys (Québec, Western US, France and Switzerland). We used published information of shade tolerance as indicators of light competition strategy, assuming that high tolerance denotes high competitive capacity in stable forest environments. Interestingly, relationships between demographic parameters and occurrence probability did not vary substantially across degrees of shade tolerance and regions. Although they were influenced by the uncertainty in the estimation of the demographic parameters, we found that r was generally negatively correlated with P occ , while N, and for most regions K, was generally positively correlated with P occ . Thus, in temperate forest trees the regions of highest occurrence

  12. Implementing a Death with Dignity program at a comprehensive cancer center.

    Science.gov (United States)

    Loggers, Elizabeth Trice; Starks, Helene; Shannon-Dudley, Moreen; Back, Anthony L; Appelbaum, Frederick R; Stewart, F Marc

    2013-04-11

    The majority of Death with Dignity participants in Washington State and Oregon have received a diagnosis of terminal cancer. As more states consider legislation regarding physician-assisted death, the experience of a comprehensive cancer center may be informative. We describe the implementation of a Death with Dignity program at Seattle Cancer Care Alliance, the site of care for the Fred Hutchinson-University of Washington Cancer Consortium, a comprehensive cancer center in Seattle that serves the Pacific Northwest. Institution-level data were compared with publicly available statewide data from Oregon and Washington. A total of 114 patients inquired about our Death with Dignity program between March 5, 2009, and December 31, 2011. Of these, 44 (38.6%) did not pursue the program, and 30 (26.3%) initiated the process but either elected not to continue or died before completion. Of the 40 participants who, after counseling and upon request, received a prescription for a lethal dose of secobarbital (35.1% of the 114 patients who inquired about the program), all died, 24 after medication ingestion (60% of those obtaining prescriptions). The participants at our center accounted for 15.7% of all participants in the Death with Dignity program in Washington (255 persons) and were typically white, male, and well educated. The most common reasons for participation were loss of autonomy (97.2%), inability to engage in enjoyable activities (88.9%), and loss of dignity (75.0%). Eleven participants lived for more than 6 months after prescription receipt. Qualitatively, patients and families were grateful to receive the lethal prescription, whether it was used or not. Overall, our Death with Dignity program has been well accepted by patients and clinicians.

  13. A unifying concept of coccolithophore sensitivity to changing carbonate chemistry embedded in an ecological framework

    Science.gov (United States)

    Bach, Lennart Thomas; Riebesell, Ulf; Gutowska, Magdalena A.; Federwisch, Luisa; Schulz, Kai Georg

    2015-06-01

    Coccolithophores are a group of unicellular phytoplankton species whose ability to calcify has a profound influence on biogeochemical element cycling. Calcification rates are controlled by a large variety of biotic and abiotic factors. Among these factors, carbonate chemistry has gained considerable attention during the last years as coccolithophores have been identified to be particularly sensitive to ocean acidification. Despite intense research in this area, a general concept harmonizing the numerous and sometimes (seemingly) contradictory responses of coccolithophores to changing carbonate chemistry is still lacking to date. Here, we present the "substrate-inhibitor concept" which describes the dependence of calcification rates on carbonate chemistry speciation. It is based on observations that calcification rate scales positively with bicarbonate (HCO3-), the primary substrate for calcification, and carbon dioxide (CO2), which can limit cell growth, whereas it is inhibited by protons (H+). This concept was implemented in a model equation, tested against experimental data, and then applied to understand and reconcile the diverging responses of coccolithophorid calcification rates to ocean acidification obtained in culture experiments. Furthermore, we (i) discuss how other important calcification-influencing factors (e.g. temperature and light) could be implemented in our concept and (ii) embed it in Hutchinson's niche theory, thereby providing a framework for how carbonate chemistry-induced changes in calcification rates could be linked with changing coccolithophore abundance in the oceans. Our results suggest that the projected increase of H+ in the near future (next couple of thousand years), paralleled by only a minor increase of inorganic carbon substrate, could impede calcification rates if coccolithophores are unable to fully adapt. However, if calcium carbonate (CaCO3) sediment dissolution and terrestrial weathering begin to increase the oceans' HCO3

  14. O fantasma de Evans-Pritchard: diálogos da antropologia com a sua história The ghost of Evans-Pritchard: anthropology’s dialogues with its own history

    Directory of Open Access Journals (Sweden)

    Frederico Delgado Rosa

    2011-06-01

    Full Text Available Tomando como estudo de caso a monografia de Sharon Hutchinson sobre os nuer, o presente artigo explora os quiproquós do diálogo entre a antropologia contemporânea e os clássicos, procurando detetar certas genealogias invisíveis que remontam aos funcionalistas britânicos, e nomeadamente a Evans-Pritchard. Procede a um esbatimento de certas oposições explícitas entre o presente e o passado da antropologia, revelando que as noções clássicas perpassam de forma subterrânea o discurso daqueles que dizem rejeitá-las e que muitas das preocupações atuais já tinham expressão nas etnografias modernas. É demonstrado que as abordagens estáticas - como a de Evans-Pritchard - tinham uma componente histórica e que a antropologia social britânica teve as suas respostas teóricas e metodológicas para as transformações dos contextos africanos sob domínio colonial.Through the reading of Sharon Hutchinson’s monograph on the Nuer, this article explores the misunderstandings between contemporary anthropology and the modern classics. It tries to identify invisible genealogies that go back to the British functionalists, particularly to Evans-Pritchard, and minimizes the explicit oppositions between the present and the past of anthropology. It reveals that some classical notions are detectable in non-explicit ways among those who claim to reject them and, at the same time, that contemporary concerns have their roots in modern ethnographies. The author shows that static approaches - as the one by Evans-Pritchard on the Nuer - had a historical meaning and recalls that British social anthropology had its own theoretical and methodological answers to the transformations of African contexts under colonial rule.

  15. Prospective prediction of children's smoking transitions: role of parents' and older siblings' smoking.

    Science.gov (United States)

    Bricker, Jonathan B; Peterson, Arthur V; Leroux, Brian G; Andersen, M Robyn; Rajan, K Bharat; Sarason, Irwin G

    2006-01-01

    To use a novel social epidemic probability model to investigate longitudinally the extent to which parents' and older siblings' smoking predict children's smoking transitions. Parents' and older siblings' smoking status was assessed when children were in 3rd grade (baseline). Three smoking transitions were assessed over the period of child/adolescent smoking acquisition (up to 12th grade): (1) transition from never smoking to trying smoking, (2) transition from trying to monthly smoking and (3) transition from monthly to daily smoking. Forty Washington State school districts participating in the long term Hutchinson Smoking Prevention Project (HSPP). Participants were the 5520 families for whom data on both parents' and older siblings' baseline smoking status, as well as on children's smoking transitions, were available. The probability that a smoking parent influenced their child to make the first transition to trying smoking was 32% (95% CI: 27%, 36%); to make the second transition from trying to monthly smoking, 15% (95% CI: 10%, 19%); and to make the third transition from monthly to daily smoking, 28% (95% CI: 21%, 34%). The probability that an older sibling influenced a child to make the first transition to trying smoking was 29% (95% CI: 17%, 39%); to make the second transition from trying to monthly smoking, 0% (95% CI: 0%, 8%); and to make the third transition from monthly to daily smoking, 20% (95% CI: 4%, 33%). In contrast to previous research, the results provide new evidence suggesting that family smoking influences both initiation and escalation of children's smoking. Results also quantify, in terms of probabilities, the importance of parents' and older siblings' smoking on children's three major smoking transitions. Parents' smoking, as well as older siblings' smoking, are important behaviors to target in preventing adolescents from making smoking transitions.

  16. Dental signs attributed to congenital syphilis and its treatments in the Hamann-Todd Skeletal Collection

    Directory of Open Access Journals (Sweden)

    Ioannou Stella

    2017-12-01

    Full Text Available Syphilis in the United States during the 1800s and 1900s had a high prevalence rate causing great concern to health officials. Various measures were taken to control its spread. Mercuric treatments were used up until the introduction of penicillin. The aim of this paper is to determine whether dental abnormalities related to congenital syphilis in individuals who died of syphilis or syphilis-related causes, in the Hamman Todd Osteological Collection, occur and whether mercurial treatment was effective. Hutchinson, Moon and Fournier’s works were analyzed to determine dental abnormalities associated with congenital syphilis and its treatments and used as criteria. Hillson et al. (AJPA,107:25-40 standardized method of description of dental changes was used. In the Hamman Todd Osteological Collection in Cleveland, Ohio, 102 individuals had cause of death recorded in the catalogue as syphilis or lues, and 69 had causes of death relating to syphilis which included paresis (53, aortic insufficiency (15 and pericarditis (1. Thus altogether 171 individuals were studied. Dentition was examined to determine if dental abnormalities associated with congenital syphilis and its treatments were present in individuals not recorded as having congenital syphilis. Crania were examined for any osteological changes. One individual (2266 demonstrated dental malformations possibly related to the congenital disease itself, while three demonstrated dental abnormalities associated with mercuric treatments in childhood (2118, 2263 and 3097. No remarkable bone pathologies were evident on any skull. The use of pre-penicillin treatment of congenital syphilis may have been effective to maintain health into adulthood but not always in eradicating the infection. Effects of mercury on enamel formation and bone changes, need to be considered when making a differential diagnosis of syphilis/congenital syphilis.

  17. Mineral sources of water and their influence on the safe disposal of radioactive wastes in bedded salt deposits

    International Nuclear Information System (INIS)

    Fallis, S.M.

    1973-12-01

    With the increased use of nuclear energy, there will be subsequent increases in high-level radioactive wastes such as Sr 90 , Cs 137 , and Pu 239 . Several agencies have considered the safest possible means to store or dispose of wastes in geologic environments such as underground storage in salt deposits, shale beds, abandoned dry mines, and in clay and shale pits. Salt deposits have received the most favorable attention because they exist in dry environments and because of other desirable properties of halite (its plasticity, gamma-ray shielding, heat dissipation ability, low mining cost, and worldwide abundance). Much work has been done on bedded salt deposits, particularly the Hutchinson Salt Member of the Wellington Formation at Lyons, Kansas. Salt beds heated by the decay of the radioactive wastes may release water by dehydration of hydrous minerals commonly present in evaporite sequences or water present in other forms such as fluid inclusions. More than 80 hydrous minerals are known to occur in evaporite deposits. The occurrences, total water contents (up to 63%) and dehydration temperatures (often less that 150 0 C) of these minerals are given. Since it is desirable to dispose of radioactive wastes in a dry environment, care must be taken that large quantities of water are not released through the heating of hydrous minerals. Seventy-four samples from four cores taken at Lyons, Kansas, were analyzed by x-ray diffraction. The minerals detected were halite, anhydrite, gypsum, polyhalite, dolomite, magnesite, quartz, feldspar, and the clay minerals illite, chlorite, kaolinite, vermiculite, smectite, mixed-layer clay, and corrensite (interstratified chlorite-vermiculite). Of these, gypsum, polyhalite and the clay minerals are all capable of releasing water when heated

  18. Nonaxisymmetric field effects on Alcator C-Mod

    International Nuclear Information System (INIS)

    Wolfe, S.M.; Hutchinson, I.H.; Granetz, R.S.; Rice, J.; Hubbard, A.; Lynn, A.; Phillips, P.; Hender, T.C.; Howell, D.F.; La Haye, R.J.; Scoville, J.T.

    2005-01-01

    A set of external coils (A-coils) capable of producing nonaxisymmetric, predominantly n=1, fields with different toroidal phase and a range of poloidal mode m spectra has been used to determine the threshold amplitude for mode locking over a range of plasma parameters in Alcator C-Mod [I. H. Hutchinson, R. Boivin, F. Bombarda, P. Bonoli, S. Fairfax, C. Fiore, J. Goetz, S. Golovato, R. Granetz, M. Greenwald et al., Phys. Plasmas 1, 1511 (1994)]. The threshold perturbations and parametric scalings, expressed in terms of (B 21 /B T ), are similar to those observed on larger, lower field devices. The threshold is roughly linear in density, with typical magnitudes of order 10 -4 . This result implies that locked modes should not be significantly more problematic for the International Thermonuclear Experimental Reactor [I. P. B. Editors, Nucl. Fusion 39, 2286 (1999)] than for existing devices. Coordinated nondimensional identity experiments on the Joint European Torus [Fusion Technol. 11, 13 (1987)], DIII-D [Fusion Technol. 8, 441 (1985)], and C-Mod, with matching applied mode spectra, have been carried out to determine more definitively the field and size scalings. Locked modes on C-Mod are observed to result in braking of core toroidal rotation, modification of sawtooth activity, and significant reduction in energy and particle confinement, frequently leading to disruptions. Intrinsic error fields inferred from the threshold studies are found to be consistent in amplitude and phase with a comprehensive model of the sources of field errors based on 'as-built' coil and bus-work details and coil imperfections inferred from measurements using in situ magnetic diagnostics on dedicated test pulses. Use of the A-coils to largely cancel the 2/1 component of the intrinsic nonaxisymmetric field has led to expansion of the accessible operating space in C-Mod, including operation up to 2 MA plasma current at 8 T

  19. Polyvalent Vaccines Targeting Oncogenic Driver Pathways

    Science.gov (United States)

    Mary L. (Nora) Disis, MD, is the Athena Distinguished Professor of Breast Cancer Research and Associate Dean for Translational Health Sciences in the University of Washington (UW) School of Medicine. She is a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics and Gynecology at UW, and a Member of the Fred Hutchinson Cancer Research Center (FHCRC). She is also an American Cancer Society Clinical Professor and a Komen Scholar. In addition to directing work in the Tumor Vaccine Group, Dr. Disis is the Director of the Institute of Translational Health Sciences and the Director for the Center for Translational Medicine in Women’s Health at the UW. Dr. Disis is an expert in breast and ovarian cancer immunology and translational research. She is one of the pioneering investigators who discovered that HER-2/neu is a tumor antigen. Her work has led to several clinical trials which evaluate boosting immunity to HER-2/neu with cancer vaccines. Her research interest is in the discovery of new molecular immunologic targets in solid tumors for the development of vaccine and cellular therapy for the treatment and prevention of common malignancies. Dr. Disis is a member of Alpha Omega Alpha and the American Society of Clinical Investigation. She is also the Editor-in-Chief for JAMA Oncology, and is a member of several committees and task forces for both the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Dr. Disis received her MD from the University of Nebraska Medical School and completed a residency and chief residency in Internal Medicine at the University of Illinois in Chicago and her fellowship in oncology at UW/FHCRC.

  20. Horizontal well drilled to intersect existing vertical well

    International Nuclear Information System (INIS)

    Price, C.; Reynolds, J.

    1991-01-01

    Morse oilfield, in eastern Gray County of the Texas Panhandle, was originally developed between 1928 and 1937. It is but a very small part of the huge Texas Pandhandle field, which covers over 200,000 productive acres, containing 12,500 active wells with a cumulative production of one billion barrels of oil. The field produces from Permian age dolomites and the Pennsylvanian Granite Wash. This paper reports on multiple production techniques that have been used over the years with varying levels of success. Acidizing techniques in the late 1930s increased development, but the advent of hydraulic fracturing resulted in extensive development. The primary drive mechanism was solution-gas drive. Approximately one-fourth of Panhandle field has been subjected to gas injection, resulting in an estimated 50 million barrels of additional oil production. In 1955, waterflooding appeared to offer the most economical possibility of increasing ultimate recovery from the Brown Dolomite reservoir. The Morse Brown Dolomite pilot flood in Gray County and another Brown Dolomite pilot flood in Hutchinson County were the first two successful pilot floods in Panhandle field. The Morse flood has a total of 40 oil and 27 water injection wells on 500 flood acres. Morse field has a cumulative production of 15.7 million barrels of oil. The operating company, Future Petroleum Corp., a Dallas-based independent, believes that a third alternative using horizontal drilling has the potential to increase production. And it appears that the Brown Dolomite formation of Morse field offers the right combination of factors to attempt this type of venture

  1. A modified Gurson-type plasticity model at finite strains: formulation, numerical analysis and phase-field coupling

    Science.gov (United States)

    Aldakheel, Fadi; Wriggers, Peter; Miehe, Christian

    2017-12-01

    The modeling of failure in ductile materials must account for complex phenomena at the micro-scale, such as nucleation, growth and coalescence of micro-voids, as well as the final rupture at the macro-scale, as rooted in the work of Gurson (J Eng Mater Technol 99:2-15, 1977). Within a top-down viewpoint, this can be achieved by the combination of a micro-structure-informed elastic-plastic model for a porous medium with a concept for the modeling of macroscopic crack discontinuities. The modeling of macroscopic cracks can be achieved in a convenient way by recently developed continuum phase field approaches to fracture, which are based on the regularization of sharp crack discontinuities, see Miehe et al. (Comput Methods Appl Mech Eng 294:486-522, 2015). This avoids the use of complex discretization methods for crack discontinuities, and can account for complex crack patterns. In this work, we develop a new theoretical and computational framework for the phase field modeling of ductile fracture in conventional elastic-plastic solids under finite strain deformation. It combines modified structures of Gurson-Tvergaard-Needelman GTN-type plasticity model outlined in Tvergaard and Needleman (Acta Metall 32:157-169, 1984) and Nahshon and Hutchinson (Eur J Mech A Solids 27:1-17, 2008) with a new evolution equation for the crack phase field. An important aspect of this work is the development of a robust Explicit-Implicit numerical integration scheme for the highly nonlinear rate equations of the enhanced GTN model, resulting with a low computational cost strategy. The performance of the formulation is underlined by means of some representative examples, including the development of the experimentally observed cup-cone failure mechanism.

  2. Does probability of occurrence relate to population dynamics?

    Science.gov (United States)

    Thuiller, Wilfried; Münkemüller, Tamara; Schiffers, Katja H.; Georges, Damien; Dullinger, Stefan; Eckhart, Vincent M.; Edwards, Thomas C.; Gravel, Dominique; Kunstler, Georges; Merow, Cory; Moore, Kara; Piedallu, Christian; Vissault, Steve; Zimmermann, Niklaus E.; Zurell, Damaris; Schurr, Frank M.

    2014-01-01

    Hutchinson defined species' realized niche as the set of environmental conditions in which populations can persist in the presence of competitors. In terms of demography, the realized niche corresponds to the environments where the intrinsic growth rate (r) of populations is positive. Observed species occurrences should reflect the realized niche when additional processes like dispersal and local extinction lags do not have overwhelming effects. Despite the foundational nature of these ideas, quantitative assessments of the relationship between range-wide demographic performance and occurrence probability have not been made. This assessment is needed both to improve our conceptual understanding of species' niches and ranges and to develop reliable mechanistic models of species geographic distributions that incorporate demography and species interactions.The objective of this study is to analyse how demographic parameters (intrinsic growth rate r and carrying capacity K ) and population density (N ) relate to occurrence probability (Pocc ). We hypothesized that these relationships vary with species' competitive ability. Demographic parameters, density, and occurrence probability were estimated for 108 tree species from four temperate forest inventory surveys (Québec, western USA, France and Switzerland). We used published information of shade tolerance as indicators of light competition strategy, assuming that high tolerance denotes high competitive capacity in stable forest environments.Interestingly, relationships between demographic parameters and occurrence probability did not vary substantially across degrees of shade tolerance and regions. Although they were influenced by the uncertainty in the estimation of the demographic parameters, we found that r was generally negatively correlated with Pocc, while N, and for most regions K, was generally positively correlated with Pocc. Thus, in temperate forest trees the regions of highest occurrence

  3. Physically-based modeling of the cyclic macroscopic behaviour of metals

    International Nuclear Information System (INIS)

    Sauzay, M.; Evrard, P.; Steckmeyer, A.; Ferrie, E.

    2010-01-01

    Grain size seems to have only a minor influence on the cyclic strain strain curves (CSSCs) of metallic polycrystals of medium to high stacking fault energy (SFE). That is why many authors tried to deduce the macroscopic CSSCs curves from the single crystals ones. Either crystals oriented for single slip or crystals oriented for multiple slip could be considered. In addition, a scale transition law should be used (from the grain scale to the macroscopic scale). Authors generally used either the Sachs rule (homogeneous single slip) or the Taylor one (homogeneous plastic strain, multiple slip). But the predicted macroscopic CSSCs do not generally agree with the experimental data for metals and alloys, presenting various SFE values. In order to avoid the choice of a particular scale transition rule, many finite element (FE) computations have been carried out using meshes of polycrystals including more than one hundred grains without texture. This allows the study of the influence of the crystalline constitutive laws on the macroscopic CSSCs. Activation of a secondary slip system in grains oriented for single slip is either allowed or hindered (slip planarity), which affects strongly the macroscopic CSSCs. The more planar the slip, the higher the predicted macroscopic stress amplitudes. If grains oriented for single slip obey slip planarity and two crystalline CSSCs are used (one for single slip grains and one for multiple slip grains), then the predicted macroscopic CSSCs agree well with experimental data provided the SFE is not too low (316L, copper, nickel, aluminium). Finally, the incremental self-consistent Hill-Hutchinson homogenization model is used for predicting CSS curves and partially validated with respect to the curves computed by the FE method. (authors)

  4. Employee Stock Options plans, Growth Opportunities and Development: data from BM&FBovespa

    Directory of Open Access Journals (Sweden)

    Renata Tamirez Ramalho

    2017-12-01

    Full Text Available This paper aims to analyze how Growth Opportunities can influence the relationship between Employee Stock Options Plans (ESOP and company development. The theoretical line of this study comes from the search to mitigate agency conflicts, thus mechanisms are necessary for the alignment of interests between organization managers (agents and stockholders (principal, in order to guarantee company valuation. This article replies to and extends studies by Perobelli, Lopes and Silveira (2012 and Hutchinson and Gul (2006. Given this paper’s aim, the work method analyzes companies which had their stocks negotiated on at least 90% of the days when there was trading on the stock market exchange. The sample comprises 115 companies, between 2012 and 2014. The data were extracted from the Reference Forms (FR, available in CVM, and from the database Com Dinheiro. To estimate the models, panel data analysis method was used. Research hypothesis 1, in which companies use ESOP with a view to maximizing their development, was refuted. The tests showed that whether or not ESOP is used alone wealth is not generated for the stockholder, but quality in plan structuring, that is, when there is a distance between the exercise price and the stock price on the grant date (out-of-money stocks. Research hypothesis 2, which affirms that the effect of the presence of ESOP is influenced by Growth Opportunities, was accepted. Consistent data were found that performance calculated according to stock returns are positively influenced by Growth Opportunities. Further, the presence of ESOP, its Quality (QESOP and Corporate Management (GC expand amplify this effect.

  5. Fluctuating zonal flows in the I-mode regime in Alcator C-Moda)

    Science.gov (United States)

    Cziegler, I.; Diamond, P. H.; Fedorczak, N.; Manz, P.; Tynan, G. R.; Xu, M.; Churchill, R. M.; Hubbard, A. E.; Lipschultz, B.; Sierchio, J. M.; Terry, J. L.; Theiler, C.

    2013-05-01

    Velocity fields and density fluctuations of edge turbulence are studied in I-mode [F. Ryter et al., Plasma Phys. Controlled Fusion 40, 725 (1998)] plasmas of the Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] tokamak, which are characterized by a strong thermal transport barrier in the edge while providing little or no barrier to the transport of both bulk and impurity particles. Although previous work showed no clear geodesic-acoustic modes (GAM) on C-Mod, using a newly implemented, gas-puff-imaging based time-delay-estimate velocity inference algorithm, GAM are now shown to be ubiquitous in all I-mode discharges examined to date, with the time histories of the GAM and the I-mode specific [D. Whyte et al., Nucl. Fusion 50, 105005 (2010)] Weakly Coherent Mode (WCM, f = 100-300 kHz, Δf/f≈0.5, and kθ≈1.3 cm-1) closely following each other through the entire duration of the regime. Thus, the I-mode presents an example of a plasma state in which zero frequency zonal flows and GAM continuously coexist. Using two-field (density-velocity and radial-poloidal velocity) bispectral methods, the GAM are shown to be coupled to the WCM and to be responsible for its broad frequency structure. The effective nonlinear growth rate of the GAM is estimated, and its comparison to the collisional damping rate seems to suggest a new view on I-mode threshold physics.

  6. Nonaxisymmetric field effects on Alcator C-Moda)

    Science.gov (United States)

    Wolfe, S. M.; Hutchinson, I. H.; Granetz, R. S.; Rice, J.; Hubbard, A.; Lynn, A.; Phillips, P.; Hender, T. C.; Howell, D. F.; La Haye, R. J.; Scoville, J. T.

    2005-05-01

    A set of external coils (A-coils) capable of producing nonaxisymmetric, predominantly n =1, fields with different toroidal phase and a range of poloidal mode m spectra has been used to determine the threshold amplitude for mode locking over a range of plasma parameters in Alcator C-Mod [I. H. Hutchinson, R. Boivin, F. Bombarda, P. Bonoli, S. Fairfax, C. Fiore, J. Goetz, S. Golovato, R. Granetz, M. Greenwald et al., Phys. Plasmas 1, 1511 (1994)]. The threshold perturbations and parametric scalings, expressed in terms of (B21/BT), are similar to those observed on larger, lower field devices. The threshold is roughly linear in density, with typical magnitudes of order 10-4. This result implies that locked modes should not be significantly more problematic for the International Thermonuclear Experimental Reactor [I. P. B. Editors, Nucl. Fusion 39, 2286 (1999)] than for existing devices. Coordinated nondimensional identity experiments on the Joint European Torus [Fusion Technol. 11, 13 (1987)], DIII-D [Fusion Technol. 8, 441 (1985)], and C-Mod, with matching applied mode spectra, have been carried out to determine more definitively the field and size scalings. Locked modes on C-Mod are observed to result in braking of core toroidal rotation, modification of sawtooth activity, and significant reduction in energy and particle confinement, frequently leading to disruptions. Intrinsic error fields inferred from the threshold studies are found to be consistent in amplitude and phase with a comprehensive model of the sources of field errors based on "as-built" coil and bus-work details and coil imperfections inferred from measurements using in situ magnetic diagnostics on dedicated test pulses. Use of the A-coils to largely cancel the 2/1 component of the intrinsic nonaxisymmetric field has led to expansion of the accessible operating space in C-Mod, including operation up to 2 MA plasma current at 8 T.

  7. Disposal of Radioactive Wastes in Natural Salt; Elimination des Dechets Radioactifs dans le Sel Naturel; 0423 0414 ; Evacuacion de Desechos Radiactivos en Formaciones Salinas Naturales

    Energy Technology Data Exchange (ETDEWEB)

    Parker, F. L.; Boegly, W. J.; Bradshaw, R. L.; Empson, F. M.; Hemphill, L.; Struxness, E. G.; Tamura, T. [Health Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1960-07-01

    The proposed use of cavities in salt formations as a disposal site for radioactive wastes is based upon : 1. Existence of salt for geologic time periods, 2. The impermeability of salt to the passage of water; 3. The widespread geographical distribution of salt; 4. The extremely large quantities of salt available; 5. The structural strength of salt; 6. The relatively high thermal conductivity of salt in comparison with other general geologic formations; 7. The possible recovery of valuable fission products in the wastes injected into the salt; 8. The relative ease of forming cavities in salt by mining, and the even greater ease and low cost of developing solution cavities in salt; and 9. The low seismicity in the areas of major salt deposits. Radioactive liquid wastes can be stored in cavities in natural salt formations if the structural properties of the salt are not adversely affected by chemical interaction, pressure, temperature, and radiation. Analytical studies show that it is possible to-store 2-year-old 10,000 MWD/T, 800 gal/ton waste in a sphere of 10 ft diameter without exceeding a temperature of 200 Degree-Sign F. Laboratory tests show that the structural properties and thermal conductivity of rock salt are not greatly altered by high radiation doses, although high temperatures increase the creep rate for both irradiated and unirradiated samples. Chemical interaction of liquid wastes with salt produces chlorine and other chlorine compound gases, but the volumes are not excessive. The migration of nuclides through the salt and deformation of the cavity and chamber can only be studied in undisturbed salt in situ. One-fifth-scale models have been run in a bedded salt deposit in Hutchinson, Kansas, and full-scale field tests are in progress. (author) [French] L'emploi envisage des cavites des gisements de sel comme lieu d'evacuation des dechets radioactifs se-fonde sur les considerations suivantes: 1. L'existence du sel dans des formations correspondant a

  8. Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study.

    Science.gov (United States)

    Akpek, Gorgun; Lee, Stephanie J; Flowers, Mary E; Pavletic, Steven Z; Arora, Mukta; Lee, Shing; Piantadosi, Steven; Guthrie, Katherine A; Lynch, James C; Takatu, Alessandra; Horowitz, Mary M; Antin, Joseph H; Weisdorf, Daniel J; Martin, Paul J; Vogelsang, Georgia B

    2003-08-01

    We recently reported 3 risk factors (RFs) at diagnosis of chronic graft-versus-host disease (cGVHD) that were significantly associated with increased nonrelapse mortality. These included extensive skin involvement (ESI), thrombocytopenia (TP), and progressive type of onset (PTO). The hazard ratio (HR) for mortality of the patients with prognostic score (PS) between 0 and 2 (intermediate-risk; 1 RF) compared to those with PS 0 (favorable-risk; 0 RF) was 3.7 (95% CI, 1.4, 9.3); the HR for patients with PS equal to or more than 2 (high-risk; > 1 RF) compared with intermediate-risk group was 6.9 (3.8, 12.4). A rare presentation of TP and PTO without ESI yielded a PS of 1.8 (intermediate-risk). This paper reports the performance of the prognostic model and the individual RFs using data from an additional 1105 patients from University of Nebraska (n = 60), International Bone Marrow Transplantation Registry (n = 708), Fred Hutchinson Cancer Research Center (n = 188), and University of Minnesota (n = 149). The extent of skin involvement was quantified in 3 cohorts using the available data collected in different formats before the analysis. Although the HR for mortality of the patients in the intermediate-risk group versus those in the favorable-risk group ranged from 2.3 to 8.9 across the centers, it was between 1.6 to 6.9 for patients in the high-risk group versus those in the intermediate-risk group. Although TP itself was uniformly associated with increased risk of mortality across all test samples, ESI and PTO showed statistically significant associations with mortality in 1 and 2 cohorts, respectively. In conclusion, the model was predictive of cGVHD-specific survival, but the mortality hazard associated with ESI was lower in each of these test samples compared with the learning sample. Although the new clinical grading based on the model is promising because of its utility across multiple independent data sets, prospective validation is needed.

  9. Acute Complications After High-Dose Chemotherapy and Stem-Cell Rescue in Pediatric Patients With High-Risk Neuroblastoma Treated in Countries With Different Resources

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Elzembely

    2018-03-01

    Full Text Available Purpose: High-dose chemotherapy with autologous stem-cell rescue (SCR is a key component of high-risk neuroblastoma (HRNB therapy. Carboplatin, etoposide, and melphalan (CEM or busulfan and melphalan (Bu/Mel are the most evaluated, effective high-dose chemotherapy for HRNB on the basis of results from major cooperative group studies. Toxicity profiles vary between these regimens, and practice variation exists regarding the preferred high-dose therapy (HDT. We sought to evaluate the safety of HDT and autologous SCR for HRNB in a resource-limited country (Egypt compared with the resource-rich United States. Patients and Methods: We performed a retrospective comparative review of single CEM-based HDT/SCR outcomes through day 100 for HRNB at the Fred Hutchinson Cancer Research Center (FH in the United States (2005 to 2015 versus Bu/Mel-based HDT at El-Sheikh Zayed Specialized Hospital (SZ in Egypt (2009 to 2015. Results: Forty-four patients at FH and 77 patients at SZ were reviewed. Pretransplant hepatic comorbidities were significantly higher at SZ (29 of 77 v nine of 44; P = .05, with 19 of 77 patients at SZ having hepatitis infection. Engraftment was delayed after SZ-Bu/Mel therapy compared with FH-CEM therapy for neutrophils (median 12 days v 10 days, respectively; P < .001 and platelets (median 20 days v 18 days, respectively; P < .001. Sinusoidal obstruction syndrome occurred later, after SZ-Bu/Mel therapy (median 19 days v 7 days; P = .033, and four of eight cases were fatal (six of eight patients had underlying hepatitis infection, whereas three of three cases after FH-CEM therapy were moderately severe. Resource utilization associated with the number of days with fever, antibiotic use, and the number of transfusions administered was significantly higher after FH-CEM therapy than after SZ-Bu/Mel therapy. Conclusion: Use of autologous stem-cell transplantation is feasible in the context of a resource-limited country.

  10. “Quit stalling…!”: Destiny and Destination on L.A.’s Inner City Roads

    Directory of Open Access Journals (Sweden)

    Martin Zeilinger

    2009-12-01

    Full Text Available If driving has today really become a Western "metaphor for being" (Hutchinson, then common roadside signs proclaiming "Right lane must exit" or "Through traf-fic merge left", inventions such as the automatic transmission, and the agreeable straightness of freeways can all be understood as symptoms of an ongoing socio-political struggle between the driver as democratic agent, and the state as institu-tionalized regulatory force. Nowhere is this more obvious than in the context of urban traffic, where private motorized transportation represents both the supreme (if illusory expression of personal freedom, and official efforts to channel indivi-dualism by obliterating its sense of direction and ideological divergence. On the concrete proving grounds of the clogged inner-city freeway, "nomad science" and "state science" (Deleuze & Guattari thus oscillate between the pseudo-liberatory expressivity of mainstream car culture and the self-effacing dromoscopic "amne-sia of driving" (Baudrillard. Are a city's multitudes of cars resistant "projectiles" (Virilio or, rather, hegemonic "sites of containment" (Jane Jacobs? This essay approaches the complex tensions between "untamable" democratic mobility and state-regulated transit by way of two Hollywood-produced films that focus on traffic in Los Angeles: in Collateral (2004, a cab driver comes to recognize and transcend the hopelessly directionless circularity dictated by his job; in Falling Down (1993, a frustrated civil service employee abandons his car on a rush-hour freeway and decides to walk home, forced to traverse the supposedly unwalkable city without the "masking screen of the windshield" (Virilio. As they "quit stal-ling", both protagonists become dangerous variants of the defiant nomad - one a driver who remains on the road but goes "under the radar", the other a transient pedestrian whose movement becomes viral and unpredictable. My analysis of the films' metropolitan setting and of the

  11. Evolution is a cooperative process: the biodiversity-related niches differentiation theory (BNDT) can explain why.

    Science.gov (United States)

    Gatti, Roberto Cazzolla

    2011-01-01

    A. McFayden and G.E. Hutchinson defined a niche as a multidimensional space or hypervolume within the environment that allows an individual or a species to survive, we consider niches as a fundamental ecological variable that regulate species' composition and relation in ecosystems. Successively the niche concept has been associated to the genetic term "phenotype" by MacArthurstressing the importance on what a species or a genome can show outside, either in the environmental functions or in body characteristics. Several indexes have been developed to evaluate the grade of overlapping and similarities of species' niches, even utilizing the theory of information. However, which are the factors that determine the number of species that can coexist in a determinate environment and why a generalist species do not compete until the exclusion of the remaining species to maximize its fitness, is still quite unknown. Moreover, there are few studies and theories that clearly explain why the number of niches is so variable through ecosystems and how can several species live in the same basal niche, intended in a comprehensive sense as the range of basic conditions (temperature, humidity, food-guild, etc.). Here I show that the number of niches in an ecosystem depends on the number of species present in a particular moment and that the species themselves allow the enhancement of niches in terms of space and number. I found that using a three-dimensional model as hypervolume and testing the theory on a Mediterranean, temperate and tropical forest ecosystem it is possible to demonstrate that each species plays a fundamental role in facilitating the colonization by other species by simply modifying the environment and exponentially increasing the available niches' space and number. I resumed these hypothesis, after some preliminary empiric tests, in the Biodiversity-related Niches Differentiation Theory (BNDT), stressing with these definition that the process of niches

  12. Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Hutchinson D

    2018-01-01

    Full Text Available David Hutchinson,1,2 Judith Müller,3 Joseph E McCarthy,4 Yurii K Gun’ko,4,5 Navin Kumar Verma,6 Xuezhi Bi,7 Luisana Di Cristo,8 Laura Kickham,8 Dania Movia,8 Adriele Prina-Mello,5,8 Yuri Volkov5,8,9 1Royal Cornwall Hospital NHS Trust, Treliske, 2University of Exeter Medical School Cornwall, UK; 3University of Basel, Basel, Switzerland; 4School of Chemistry, 5Advanced Materials for BioEngineering Research Centre (AMBER, Trinity College Dublin, Dublin, Ireland; 6Lee Kong Chian School of Medicine, Nanyang Technological University, 7Bioprocessing Technology Institute, A*STAR Graduate Academy, Singapore; 8Department of Clinical Medicine, School of Medicine, Trinity College Dublin, Dublin, Ireland; 9International Laboratory of Magnetically Controlled Nanosystems for Theranostics of Oncological and Cardiovascular Diseases, ITMO University, St. Petersburg, Russia Objective: The objective of the study was to determine whether the cadmium-derived materials induce intracellular protein citrullination. Methods: Human A549 lung epithelial cells were exposed to cadmium in soluble and nanoparticulate forms represented by cadmium chloride (CdCl2 and cadmium oxide (CdO, respectively, and their combinations with ultrafine carbon black (ufCB produced by high temperature combustion, imitating cigarette burning. Protein citrullination in cell lysates was analyzed by Western immunoblotting and verified by immunofluorescent confocal microscopy. Target citrullinated proteins were identified by proteomic analysis. Results: CdO, ufCB and its combination with CdCl2 and CdO after high temperature combustion induced protein citrullination in cultured human lung epithelial cells, as detected by immunoblotting with anti-citrullinated protein antibody. Cytokeratins of type II (1, 2, 5, 6A, 6B and 77 and type I (9, 10 were identified as major intracellular citrullination targets. Immunofluorescent staining confirmed the localization of citrullinated proteins both in the

  13. Abiraterone in the treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Mostaghel EA

    2014-01-01

    Full Text Available Elahe A Mostaghel Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC. Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an

  14. Harmonization of Food-Frequency Questionnaires and Dietary Pattern Analysis in 4 Ethnically Diverse Birth Cohorts.

    Science.gov (United States)

    de Souza, Russell J; Zulyniak, Michael A; Desai, Dipika; Shaikh, Mateen R; Campbell, Natalie C; Lefebvre, Diana L; Gupta, Milan; Wilson, Julie; Wahi, Gita; Atkinson, Stephanie A; Teo, Koon K; Subbarao, Padmaja; Becker, Allan B; Mandhane, Piushkumar J; Turvey, Stuart E; Sears, Malcolm R; Anand, Sonia S

    2016-11-01

    Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice. We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes. The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins. CHILD used a multiethnic FFQ based on a previously validated instrument designed by the Fred Hutchinson Cancer Research Center, whereas FAMILY, START, and ABC used questionnaires specifically designed for use in white European, South Asian, and Aboriginal people, respectively. The serving sizes and consumption frequencies of individual food items within the 4 FFQs were harmonized and aggregated into 36 common food groups. Principal components analysis was used to identify dietary patterns that were internally validated against self-reported vegetarian status and externally validated against a modified Alternative Healthy Eating Index (mAHEI). Three maternal dietary patterns were identified-"plant-based," "Western," and "health-conscious"-which collectively explained 29% of the total variability in eating habits observed in the NutriGen Alliance. These patterns were strongly associated with self-reported vegetarian status (OR: 3.85; 95% CI: 3.47, 4.29; r 2 = 0.30, P < 0.001; for a plant-based diet), and average adherence to the plant-based diet was higher in participants in the fourth quartile of the mAHEI than in the first quartile (mean difference: 46.1%; r 2 = 0.81, P < 0.001). Dietary data collected by using FFQs from ethnically diverse pregnant women can be

  15. Strongly enhanced colorectal cancer risk stratification by combining family history and genetic risk score

    Directory of Open Access Journals (Sweden)

    Weigl K

    2018-01-01

    Full Text Available Korbinian Weigl,1,2 Jenny Chang-Claude,3,4 Phillip Knebel,5 Li Hsu,6 Michael Hoffmeister,1 Hermann Brenner1,2,7 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ, Heidelberg, 2German Cancer Consortium (DKTK, German Cancer Research Center (DKFZ, Heidelberg, 3Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ, Heidelberg, 4University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, 5Department for General, Visceral and Transplantation Surgery, University Heidelberg, Heidelberg, Germany; 6Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 7Division of Preventive Oncology, German Cancer Research Center (DKFZ and National Center for Tumor Diseases (NCT, Heidelberg, Germany Background and aim: Family history (FH and genetic risk scores (GRSs are increasingly used for risk stratification for colorectal cancer (CRC screening. However, they were mostly considered alternatively rather than jointly. The aim of this study was to assess the potential of individual and joint risk stratification for CRC by FH and GRS.Patients and methods: A GRS was built based on the number of risk alleles in 53 previously identified single-nucleotide polymorphisms among 2,363 patients with a first diagnosis of CRC and 2,198 controls in DACHS [colorectal cancer: chances for prevention through screening], a population-based case-control study in Germany. Associations between GRS and FH with CRC risk were quantified by multiple logistic regression.Results: A total of 316 cases (13.4% and 214 controls (9.7% had a first-degree relative (FDR with CRC (adjusted odds ratio [aOR] 1.86, 95% CI 1.52–2.29. A GRS in the highest decile was associated with a 3.0-fold increased risk of CRC (aOR 3.00, 95% CI 2.24–4.02 compared with the lowest decile. This association was tentatively more pronounced in older age groups. FH and GRS were essentially unrelated, and their

  16. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  17. Control of internal transport barriers on Alcator C-Mod

    International Nuclear Information System (INIS)

    Fiore, C.L.; Bonoli, P.T.; Ernst, D.R.; Hubbard, A.E.; Greenwald, M.J.; Lynn, A.; Marmar, E.S.; Phillips, P.; Redi, M.H.; Rice, J.E.; Wolfe, S.M.; Wukitch, S.J.; Zhurovich, K.

    2004-01-01

    Recent studies of internal transport and double transport barrier regimes in the Alcator C-Mod [I. H. Hutchinson et al., Phys. Plasmas 1, 1511 (1994)] have explored the limits for forming, maintaining, and controlling these plasmas. The C-Mod provides a unique platform for studying such discharges: the ions and electrons are tightly coupled by collisions and the plasma has no internal particle or momentum sources. The double-barrier mode comprised of an edge barrier with an internal transport barrier (ITB) can be induced at will using off-axis ion cyclotron range of frequency (ICRF) injection on either the low or high field side of the plasma with either of the available ICRF frequencies (70 or 80 MHz). When an enhanced D α high confinement mode (EDA H-mode) is accessed in Ohmic plasmas, the double barrier ITB forms spontaneously if the H-mode is sustained for ∼2 energy confinement times. The ITBs formed in both Ohmic and ICRF heated plasmas are quite similar regardless of the trigger method. They are characterized by strong central peaking of the electron density, and a reduction of the core particle and energy transport. The control of impurity influx and heating of the core plasma in the presence of the ITB have been achieved with the addition of central ICRF power in both the Ohmic H-mode and ICRF induced ITBs. The radial location of the particle transport barrier is dependent on the toroidal magnetic field but not on the location of the ICRF resonance. A narrow region of decreased electron thermal transport, as determined by sawtooth heat pulse analysis, is found in these plasmas as well. Transport analysis indicates that a reduction of the particle diffusivity in the barrier region allows the neoclassical pinch to drive the density and impurity accumulation in the plasma center. An examination of the gyrokinetic stability at the trigger time for the ITB suggests that the density and temperature profiles are inherently stable to ion temperature gradient and

  18. 20 years of research on the Alcator C-Mod tokamak

    International Nuclear Information System (INIS)

    Greenwald, M.; Baek, S.; Barnard, H.; Beck, W.; Bonoli, P.; Brunner, D.; Burke, W.; Ennever, P.; Ernst, D.; Faust, I.; Fiore, C.; Fredian, T.; Gao, C.; Golfinopoulos, T.; Granetz, R.; Hartwig, Z.; Hubbard, A.; Hughes, J.; Hutchinson, I.; Irby, J.

    2014-01-01

    The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental

  19. 20 years of research on the Alcator C-Mod tokamaka)

    Science.gov (United States)

    Greenwald, M.; Bader, A.; Baek, S.; Bakhtiari, M.; Barnard, H.; Beck, W.; Bergerson, W.; Bespamyatnov, I.; Bonoli, P.; Brower, D.; Brunner, D.; Burke, W.; Candy, J.; Churchill, M.; Cziegler, I.; Diallo, A.; Dominguez, A.; Duval, B.; Edlund, E.; Ennever, P.; Ernst, D.; Faust, I.; Fiore, C.; Fredian, T.; Garcia, O.; Gao, C.; Goetz, J.; Golfinopoulos, T.; Granetz, R.; Grulke, O.; Hartwig, Z.; Horne, S.; Howard, N.; Hubbard, A.; Hughes, J.; Hutchinson, I.; Irby, J.; Izzo, V.; Kessel, C.; LaBombard, B.; Lau, C.; Li, C.; Lin, Y.; Lipschultz, B.; Loarte, A.; Marmar, E.; Mazurenko, A.; McCracken, G.; McDermott, R.; Meneghini, O.; Mikkelsen, D.; Mossessian, D.; Mumgaard, R.; Myra, J.; Nelson-Melby, E.; Ochoukov, R.; Olynyk, G.; Parker, R.; Pitcher, S.; Podpaly, Y.; Porkolab, M.; Reinke, M.; Rice, J.; Rowan, W.; Schmidt, A.; Scott, S.; Shiraiwa, S.; Sierchio, J.; Smick, N.; Snipes, J. A.; Snyder, P.; Sorbom, B.; Stillerman, J.; Sung, C.; Takase, Y.; Tang, V.; Terry, J.; Terry, D.; Theiler, C.; Tronchin-James, A.; Tsujii, N.; Vieira, R.; Walk, J.; Wallace, G.; White, A.; Whyte, D.; Wilson, J.; Wolfe, S.; Wright, G.; Wright, J.; Wukitch, S.; Zweben, S.

    2014-11-01

    The object of this review is to summarize the achievements of research on the Alcator C-Mod tokamak [Hutchinson et al., Phys. Plasmas 1, 1511 (1994) and Marmar, Fusion Sci. Technol. 51, 261 (2007)] and to place that research in the context of the quest for practical fusion energy. C-Mod is a compact, high-field tokamak, whose unique design and operating parameters have produced a wealth of new and important results since it began operation in 1993, contributing data that extends tests of critical physical models into new parameter ranges and into new regimes. Using only high-power radio frequency (RF) waves for heating and current drive with innovative launching structures, C-Mod operates routinely at reactor level power densities and achieves plasma pressures higher than any other toroidal confinement device. C-Mod spearheaded the development of the vertical-target divertor and has always operated with high-Z metal plasma facing components—approaches subsequently adopted for ITER. C-Mod has made ground-breaking discoveries in divertor physics and plasma-material interactions at reactor-like power and particle fluxes and elucidated the critical role of cross-field transport in divertor operation, edge flows and the tokamak density limit. C-Mod developed the I-mode and the Enhanced Dα H-mode regimes, which have high performance without large edge localized modes and with pedestal transport self-regulated by short-wavelength electromagnetic waves. C-Mod has carried out pioneering studies of intrinsic rotation and demonstrated that self-generated flow shear can be strong enough in some cases to significantly modify transport. C-Mod made the first quantitative link between the pedestal temperature and the H-mode's performance, showing that the observed self-similar temperature profiles were consistent with critical-gradient-length theories and followed up with quantitative tests of nonlinear gyrokinetic models. RF research highlights include direct experimental

  20. Biosynthesis and regulation of coronatine, a non-host-specific phytotoxin produced by Pseudomonas syringae.

    Science.gov (United States)

    Bender, C L; Palmer, D A; Peñaloza-Vázquez, A; Rangaswamy, V; Ullrich, M

    1998-01-01

    Many P. syringae pathovars are known to produce low-molecular-weight, diffusible toxins in infected host plants. These phytotoxins reproduce some of the symptoms of the relevant bacterial disease and are effective at very low concentrations. Phytotoxins generally enhance the virulence of the P. syringae pathovar which produces them, but are not required for pathogenesis. Genes encoding phytotoxin production have been identified and cloned from several P. syringae pathovars. With the exception of coronatine, toxin biosynthetic gene clusters are generally chromosomally encoded. In several pathovars, the toxin biosynthetic gene cluster also contains a resistance gene which functions to protect the producing strain from the biocidal effects of the toxin. In the case of phaseolotoxin, a resistance gene (argK) has been utilized to engineer phaseolotoxin-resistant tobacco plants. Although P. syringae phytotoxins can induce very similar effects in plants (chlorosis and necrosis), their biosynthesis and mode of action can be quite different. Knowledge of the biosynthetic pathways to these toxins and the cloning of the structural genes for their biosynthesis has relevance to the development of new bioactive compounds with altered specificity. For example, polyketides constitute a huge family of structurally diverse natural products including antibiotics, chemotherapeutic compounds, and antiparasitics. Most of the research on polyketide synthesis in bacteria has focused on compounds synthesized by Streptomyces or other actinomycetes. It is also important to note that it is now possible to utilize a genetic rather than synthetic approach to biosynthesize novel polyketides with altered biological properties (Hutchinson and Fujii, 1995; Kao et al., 1994; Donadio et al., 1993; Katz and Donadio, 1993). Most of the reprogramming or engineering of novel polyketides has been done using actinomycete PKSs, but much of this technology could also be applied to polyketides synthesized by

  1. A prospective study of the substance use and mental health outcomes of young adult former and current cannabis users.

    Science.gov (United States)

    Silins, Edmund; Swift, Wendy; Slade, Tim; Toson, Barbara; Rodgers, Bryan; Hutchinson, Delyse M

    2017-09-01

    The extent to which young adult former cannabis users fare better than infrequent users is unclear. We investigated the association between cannabis use status at age 23 and substance use and mental health outcomes at age 27. Data were from the 20+ year cohort of the PATH Through Life Study. Lifetime cannabis users (n = 1410) at age 23 were classified as former/occasional/regular users. Multivariable logistic regression was used to estimate the association between cannabis use status at age 23 and six outcomes assessed at age 27. Compared with occasional cannabis users: (i) former users had odds of subsequent tobacco use [odds ratio (OR) = 0.67, 95% confidence interval (CI) 0.52-0.85], illicit drug use (cannabis, OR = 0.22, 95% CI 0.17-0.28; other illicit drugs, OR = 0.29, 95% CI 0.22-0.39) and mental health impairment (OR = 0.71, 95% CI 0.55-0.92) that were 29-78% lower; and (ii) regular users had odds of subsequent frequent alcohol use (OR = 2.34, 95% CI 0.67-1.34), tobacco use (OR = 3.67, 95% CI 2.54-5.30), cannabis use (OR = 11.73, 95% CI 6.81-20.21) and dependence symptoms (OR = 12.60, 95% CI 8.38-18.94), and other illicit drug use (OR = 2.95, 95% CI 2.07-4.21) that were 2-13 times greater. Associations attenuated after covariate adjustment, and most remained significant. Clear associations exist between cannabis use status in young adulthood and subsequent mental health and substance use. While early intervention remains important to prevent regular cannabis use and the associated harms, experimentation with cannabis use in the years leading into young adulthood may not necessarily determine an immutable pathway to mental health problems and illicit substance use. [Silins E, Swift W, Slade T, Toson B, Rodgers B, Hutchinson DM. A prospective study of the substance use and mental health outcomes of young adult former and current cannabis users. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other

  2. Does Effectiveness of Adolescent Smoking-Cessation Intervention Endure Into Young Adulthood? 7-Year Follow-Up Results from a Group-Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Arthur V Peterson

    Full Text Available The Hutchinson Study of High School Smoking was the first randomized trial to show effectiveness of a smoking cessation intervention on 6-months prolonged smoking abstinence at one year post-intervention in a large population-based sample of adolescent smokers. An important question remains: Do the positive effects from teen smoking cessation interventions seen at up to 12 months post-intervention endure into young adulthood? This study examines for the first time whether such positive early effects from teen smoking cessation intervention can endure into young adulthood in the absence of additional intervention.High school smokers (n = 2,151 were proactively recruited into the trial from fifty randomly selected Washington State high schools randomized to the experimental (Motivational Interviewing + Cognitive Behavioral Skills Training telephone counseling intervention or control (no intervention condition. These smokers were followed to 7 years post high school to ascertain rates of six-year prolonged smoking abstinence in young adulthood. All statistical tests are two-sided.No evidence of intervention impact at seven years post high school was observed for the main endpoint of six-year prolonged abstinence, neither among all smokers (14.2% in the experimental condition vs. 13.1% in the control condition, difference = +1.1%, 95% confidence interval (CI = -3.4 to 5.8, p = .61, nor among the subgroups of daily smokers and less-than-daily smokers, nor among other a priori subgroups. But, observed among males was some evidence of an intervention impact on two endpoints related to progress towards quitting: reduction in number of days smoked in the past month, and increase in the length of the longest quit attempt in the past year.There was no evidence from this trial among adolescent smokers that positive effectiveness of the proactive telephone intervention for smoking abstinence, observed previously at one year post-intervention, was sustained

  3. Does Effectiveness of Adolescent Smoking-Cessation Intervention Endure Into Young Adulthood? 7-Year Follow-Up Results from a Group-Randomized Trial.

    Science.gov (United States)

    Peterson, Arthur V; Marek, Patrick M; Kealey, Kathleen A; Bricker, Jonathan B; Ludman, Evette J; Heffner, Jaimee L

    2016-01-01

    The Hutchinson Study of High School Smoking was the first randomized trial to show effectiveness of a smoking cessation intervention on 6-months prolonged smoking abstinence at one year post-intervention in a large population-based sample of adolescent smokers. An important question remains: Do the positive effects from teen smoking cessation interventions seen at up to 12 months post-intervention endure into young adulthood? This study examines for the first time whether such positive early effects from teen smoking cessation intervention can endure into young adulthood in the absence of additional intervention. High school smokers (n = 2,151) were proactively recruited into the trial from fifty randomly selected Washington State high schools randomized to the experimental (Motivational Interviewing + Cognitive Behavioral Skills Training telephone counseling intervention) or control (no intervention) condition. These smokers were followed to 7 years post high school to ascertain rates of six-year prolonged smoking abstinence in young adulthood. All statistical tests are two-sided. No evidence of intervention impact at seven years post high school was observed for the main endpoint of six-year prolonged abstinence, neither among all smokers (14.2% in the experimental condition vs. 13.1% in the control condition, difference = +1.1%, 95% confidence interval (CI) = -3.4 to 5.8, p = .61), nor among the subgroups of daily smokers and less-than-daily smokers, nor among other a priori subgroups. But, observed among males was some evidence of an intervention impact on two endpoints related to progress towards quitting: reduction in number of days smoked in the past month, and increase in the length of the longest quit attempt in the past year. There was no evidence from this trial among adolescent smokers that positive effectiveness of the proactive telephone intervention for smoking abstinence, observed previously at one year post-intervention, was sustained for the long

  4. Aging as Evolution-Facilitating Program and a Biochemical Approach to Switch It Off

    Science.gov (United States)

    Skulachev, Vladimir P.

    decelerates the development of three types of accelerated aging (progeria) and also of normal aging, and this effect is especially demonstrative at early stages of aging. The same pattern is shown in invertebrates (Drosophila and Daphnia), and fungus (Podospora anserina). In mammals, the effect of SkQs on aging is accompanied by inhibition of development of such age-related diseases as osteoporosis, involution of thymus, cataract, retinopathy, etc. SkQ1 manifests a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision is recovered in 66 of 96 animals (dogs, cats and horses) who became blind because of retinopathy. SkQ1-containing drops instilled into eyes prevent the loss of sight in rabbits suffering from experimental uveitis and restore vision to animals that had already become blind due to this pathology. A favorable effect is also achieved in experimental glaucoma in rabbits. Moreover, the pretreatment of rats with 0.2 nM SkQ1 significantly decreases the H2O2-induced arrhythmia of the isolated heart. SkQ1 strongly reduces the damaged area in myocardial infarction or stroke and prevents the death of animals from kidney infarction. In p53-/- mice, SkQ1 decreases the ROS level in the spleen cells and inhibits appearance of lymphomas which are the main cause of death of such animals. As a result, the lifespan increases. SkQs look like promising drugs to treat aging and age-related diseases.

  5. Sex, kings and serial killers and other group-selected human traits.

    Science.gov (United States)

    Bowles, J T

    2000-06-01

    (Note: This unorthodox paper contains the first argument for heart disease being a programmed age change and promoted by the dramatic, post age-40 increases in the hormones FSH and hCG seen in some individuals.) A recent issue of Science suggests that the evolutionary purpose of sex is unknown. Surviving to adulthood implies a valuable gene combination which is destroyed by sexual recombination. This should be detrimental to offspring. PROPOSED: Sex is group-selected in prey to allow coalescence of beneficial, and disposal of detrimental, mutations in single individuals enabling rapid adaptation to novel predation. Group selection is a universal force driven by local inter-species (not intra-species) competition. Aging, metabolism, litter size, and fixed body size are directly linked. Sexual recombination and chromosomes destroy gene linkage and exist because mutations are usually detrimental, rarely positive, and occur in linked groups. In unevolving environments, sex is selected against and asexuality emerges. Periodic evolution of novel predators, like man, can explain the 'punctuated equilibria' fossil record. Genes inhibited by methylation or chromatin condensation, expressed at older ages in predation-minimized environments, allow for group selection. Stress increases mutation rates and beneficial mutation likelihood. Females select bigger, brighter, louder, or stronger males that can survive predator attention. Size approximates age and thus predator encounters; male traits represent predation-survival potential. Human male traits include, balding, acne, beard-length, wrinkling, graying, nose/ear growth. Progeria accelerates development of most male traits. Domination of groups by single males allows rapid predation-defense evolution: adolescent males are expelled, brave the wild, and expel another group's male to mate. If expelled and dominant males are culled by predation, males reaching puberty first will reproduce. Hormonal acceleration of puberty

  6. PREFACE: 31st European Physical Society Conference on Plasma Physics

    Science.gov (United States)

    Dendy, Richard

    2004-12-01

    chaired by Henry Hutchinson (RAL, Chilton), and to the Plasma Physics and Controlled Fusion journal team (Institute of Physics Publishing, Bristol), for their work on this conference. At the 2004 European Physical Society Conference on Plasma Physics, plenary invited speakers whose talks spanned the entire field were followed, each day, by multiple parallel sessions which also included invited talks. Invited speakers in both these categories were asked to contribute papers to this special issue (the contributed papers at this conference, and at all recent conferences in this series, are archived at http://epsppd.epfl.ch). The Programme Committee is very grateful to the many invited speakers who have responded positively to this request. Invited papers appear here in their order of presentation during the week beginning 28 June 2004; this ordering provides an echo of the character of the conference, as it was experienced by those who took part. Programme Committee 2004 Professor Richard Dendy UKAEA Culham Division, UK Chairman and guest editor Dr Jean-Luc Dorier Centre de Recherches en Physique des Plasmas, Lausanne, Switzerland (Co-ordinator of dusty plasmas and guest editor) Professor Jürgen Meyer-ter-Vehn Max-Planck-Institut für Quantenoptik, Garching, Germany (Co-ordinator of laser-plasma interaction and beam plasma physics and guest editor) Dr Peter Norreys Rutherford Appleton Laboratory, Chilton, UK (Scientific Secretary and guest editor) Dr Emilia R Solano CIEMAT Laboratorio Nacional de Fusión, Madrid, Spain ( Co-ordinator of magnetic confinement fusion and guest editor) Dr Shalom Eliezer Soreq Nuclear Research Centre, Israel Dr Wim Goedheer FOM-Instituut voor Plasmafysica, Rijnhuizen, Netherlands Professor Henry Hutchinson Rutherford Appleton Laboratory, Chilton, UK Professor John Kirk Max-Planck-Institut für Kernphysik, Heidelberg, Germany Dr Raymond Koch Ecole Royale Militaire/Koninklijke Militaire School, Brussels, Belgium Professor Gerrit Kroesen Technische

  7. Climate change in the Carpathian-Balkan Area. Advancing research and cooperation

    Directory of Open Access Journals (Sweden)

    Marcel MINDRESCU

    2013-06-01

    researchers and scholars can find common grounds for discussion and collaboration (Hutchinson and Mindrescu, 2012.In this regard an international meeting was organized at the Geography Department, University of Suceava, Romania, and was cosponsored by the University of Suceava, the Applied Geography Association (GEOCONCEPT, Past Global Changes (PAGES and the Mountain Research Initiative (MRI. The purpose of the workshop was to bring together an international group of scientists interested in the Carpathian-Balkan region to discuss research results and promote opportunities for interdisciplinary and international collaboration. The entire workshop was webcast. The program centered on 36 oral and 15 poster presentations as well as open discussions on the climatic and environmental dynamics during the Pleistocene and Holocene. The 70 participants were from Romania, Hungary, Germany, United Kingdom, Bulgaria, Slovenia, Ukraine, Poland, Switzerland, Czech Republic, Greece and Belgium. For many young researchers and students the workshop offered an educational opportunity to present their results to an international audience and discuss their research in a multidisciplinary community.To promote follow-up activities in the region, the “Suceava working group” was created under the lead of Marcel Mindrescu, Angelica Feurdean, Eniko Magyari and Daniel Veres. A group website is currently being set up (http://atlas.usv.ro/www/climatechange/ and grant proposals will be prepared. The group will also coordinate the organization of a second regional workshop in 2014 in Romania. Further activities, such as summer camps or meetings in the field are also considered.

  8. Can terrestrial diversity be predicted from soil morphology?

    Science.gov (United States)

    Fournier, Bertrand; Guenat, Claire; Mitchell, Edward

    2010-05-01

    Restoration ecology is a young discipline and, as a consequence, many concepts and methods are not yet mature. A good example of this is the case of floodplains which have been intensively embanked, dammed or otherwise engineered in industrialized countries, but are now increasingly being restored, often at high cost. There is however much confusion over the goals of floodplain restoration projects and the methods, criteria, and indicators to assess their success. Nature practitioners are interested in knowing how many and which variables are needed for an efficient monitoring and/or assessment. Although many restoration success assessment methods have been developed to meet this need, most indicators currently used are complicated and expensive or provide only spatially or temporally limited information on these complex systems. Perhaps as a result, no standard method has yet been defined and post-restoration monitoring is not systematically done. Optimizing indicators would help improve the credibility of restoration projects and would thus help to convince stakeholders and managers to support monitoring programs. As a result, defining the predictive power of restoration success indicators, as well as selecting the most pertinent variables among the ones currently used is of major importance for a sustainable and adaptive management of our river ecosystems. Soil characteristics determine key functions (e.g. decomposition) and ecosystem structure (e.g. vegetation) in terrestrial ecosystems. They therefore have a high potential information value that is, however, generally not considered in floodplain restoration assessment. In order to explore this potential, we recently developed a new synthetic indicator based on soil morphology for the evaluation of river restoration success. Following Hutchinson's ecological niche concept, we hypothesised that terrestrial biodiversity can be predicted based on soil characteristics, but that these characteristics do not perform

  9. EDITORIAL: Proceedings of the IUTAM Symposium on Plasticity at the Micron Scale, Technical University of Denmark, 21 25 Mark 2006

    Science.gov (United States)

    Tvergaard, Viggo

    2007-01-01

    granular media and to cellular solids were discussed. The symposium consisted of thirty-six lectures, all of which were invited based on strong expertise in the area. Some of the lectures are not represented in this special issue, mainly because of prior commitments to publish elsewhere. The international Scientific Committee responsible for the symposium comprised the following: Professor V Tvergaard (Chairman) Denmark Professor A Benallal France Professor N A Fleck UK Professor L B Freund (IUTAM Representative) USA Professor E van der Giessen The Netherlands Professor J W Hutchinson USA Professor A Needleman USA Professor B Svendsen Germany The Committee gratefully acknowledges financial support for the symposium from the International Union of Theoretical and Applied Mechanics, from Novo Nordisk A/S and from the Villum Kann Rasmussen Foundation. In the organization of all parts of the symposium the enthusiastic participation of Dr C F Niordson and Dr P Redanz was invaluable. The smooth running of the symposium also owes much to the efforts and organizational skills of Bente Andersen.

  10. The Heritage of Earth Science Applications in Policy, Business, and Management of Natural Resources

    Science.gov (United States)

    Macauley, M.

    2012-12-01

    From the first hand-held cameras on the Gemini space missions to present day satellite instruments, Earth observations have enhanced the management of natural resources including water, land, and air. Applications include the development of new methodology (for example, developing and testing algorithms or demonstrating how data can be used) and the direct use of data in decisionmaking and policy implementation. Using well-defined bibliographic search indices to systematically survey a broad social science literature, this project enables identification of a host of well-documented, practical and direct applications of Earth science data in resource management. This literature has not previously been well surveyed, aggregated, or analyzed for the heritage of lessons learned in practical application of Earth science data. In the absence of such a survey, the usefulness of Earth science data is underestimated and the factors that make people want to use -- and able to use -- the data are poorly understood. The project extends and updates previous analysis of social science applications of Landsat data to show their contemporary, direct use in new policy, business, and management activities and decisionmaking. The previous surveys (for example, Blumberg and Jacobson 1997; National Research Council 1998) find that the earliest attempts to use data are almost exclusively testing of methodology rather than direct use in resource management. Examples of methodology prototyping include Green et al. (1997) who demonstrate use of remote sensing to detect and monitor changes in land cover and use, Cowen et al. (1995) who demonstrate design and integration of GIS for environmental applications, Hutchinson (1991) who shows uses of data for famine early warning, and Brondizio et al. (1996) who show the link of thematic mapper data with botanical data. Blumberg and Jacobson (in Acevedo et al. 1996) show use of data in a study of urban development in the San Francisco Bay and the

  11. Geo-structural modelling for potential large rock slide in Machu Picchu

    Science.gov (United States)

    Spizzichino, D.; Delmonaco, G.; Margottini, C.; Mazzoli, S.

    2009-04-01

    blocks with dimensions variable from 10-1 to 102m3 that form the toe accumulation on steeper slopes. The area of the citadel has also been interpreted as affected by a deep mass movement (>100m) that, if confirmed by the present day monitoring systems, could be referred to a deep-seated gravitational slope deformation (DSGSD), probably of the type of the compound bi-planar sagging (CB) described by Hutchinson (1988). The analysis of active strain processes (e.g. tension cracks) along with the damage pattern surveyed on archaeological structures (e.g. sinking, swelling, tilting) suggest that the potential failure of a large rock slide may be located at a depth of ca. 30m. The various data sets have been integrated in order to obtain a general geo-structural and geotechnical model (strength and deformation parameters, seismic input) of the citadel at the slope scale. This represents a first step in implementing a slope stability analysis capable of reconstructing present and potential landslide evolution under static and dynamic conditions. This multi-discipline study, based on geological and structural analysis integrated with geotechnical and geomechanical interpretation, will aid defining actual landslide hazard and risk levels, indispensable for the design of low impact mitigation measures to be applied at Machu Picchu Citadel.

  12. Jurassic onychites (arm hooks) from squid-like cephalopods from the Wessex Basin, southern England

    Science.gov (United States)

    Hart, Malcolm; Hughes, Zoe; Page, Kevin; Price, Gregory; Smart, Christopher

    2017-04-01

    of hook that are often arranged in pairs. Using the abundance of material available to us from the Wessex Basin, we are attempting to identify the host animals wherever this is possible. If this can be established then it may be possible, using micropalaeontological samples, to determine the stratigraphical and palaeoecological ranges of some of the host macro-fossils, many of which are otherwise rarely preserved outside known lagerstätte. A recently described specimen (Bristol Museum and Art Gallery, BRMSG Ce12385) of only the hooks associated with 4 arms can, therefore, be attributed to the Clarkeiteuthis lineage. Coming from the Lower Pliensbachian of the Dorset Coast this occurrence falls in the stratigraphical 'gap' between the known taxa of the Sinemurian (Clarkeiteuthis montefiore) and the Toarcian (Clarkeiteuthis conocauda). This specimen does, however, show paired hooks of different types, similar to another specimen in Manchester University Museum: this is not seen in C. conocauda and places the specimen in C. montefiore or a yet undescribed species of Clarkeiteuthis. Engeser, T.S. & Clarke, M.R. 1988. Cephalopod hooks, both recent and fossil. In: Clarke, M.R. & Trueman, E.R. (eds), Palaeontology and Neontology of Cephalopods, vol. 12,; Wilbur, K.M. (Ed.), The Mollusca, Academic press Inc., London, 133-151. Hart, M.B. & Hutchinson, D. in press. A newly described 'clarkeiteuthid' from the Lias Group of Dorset. Geoscience in South-West England. Hart, M.B., De Jonghe, A., Page, K.N., Price, G.D. & Smart, C.W. 2016. Exceptional accumulations of statoliths in association with the Christian Malford lagerstätte (Callovian, Jurassic) in Wiltshire, United Kingdom. Palaios, 31, 203-220. Kulicki, C. & Szaniawski, H. 1972. Cephalopod arm hooks from the Jurassic of Poland. Acta Palaeontologica Polonica, 17, 379-419. Wilby, P.R., Hudson, J.D., Clements, R.G. & Hollingworth, N.T.J. 2004. Taphonomy and origin of an accumulate of soft-bodied cephalopods in the Oxford Clay

  13. Evolution of the 1963 Vajont landslide (Northern Italy) from low and high velocity friction experiments

    Science.gov (United States)

    Ferri, F.; di Toro, G.; Hirose, T.; Han, R.; Noda, H.; Shimamoto, T.; Pennacchioni, G.

    2009-04-01

    breakdown of the Teflon ring and by the emission of H2O from the sample assembly. SEM observations show that deformation was localized in 200 micron-thick slipping zone at the contact with the marble cylinders, and that the gouge includes concentric aggregates of sub-micrometer clay + calcite + quartz grains wrapping nuclei of calcite, quartz or clay fragments. All these features suggest that rolling lubrication was concomitant to thermal pressurization. At saturated conditions, dilatancy and H2O emission were absent, deformation was diffused in the slipping zone and no concentric structures were found: these features suggest that the H2O liquid-vapour transition was not achieved, though the actual lubricating mechanism has not been fully understood yet. Our experimental data indicate that the frictional behaviour is velocity-weakening in both dry and saturated conditions and determined by the clay fraction within the gouge and it. The presence of free water in the slipping zone reduces friction to almost zero, explaining the high velocity achieved by the slide during the final collapse. REFERENCES Boutareaud S., Calugaru D. G., Han R., Fabbri O., Mizoguchi K., Tsutsumi A. and Shimamoto T., Geophys. Res. Lett., 35, L05302, 2008. Tika T. E.and Hutchinson J. N., Géotechnique 49: 59-74, 1999. Veveakis E., Vardoulakis I. and Di Toro G., J. Geophys. Res. 112: F03026, 2007.

  14. What is the cost per millimetre? Challenging traditional GNSS equipment for precise geosciences and engineering applications

    Science.gov (United States)

    Hogg, William; Boreham, Nicholas; Benedetti, Elisa; Roberts, William

    2017-04-01

    of 1cm a day. The processing techniques that are used by the STICK monitoring service are described, including the GNSS data processing, the integration of IMU and the statistical analyses used to detect, quantify and report movement. By considering operational cost in terms of power, installation difficulty, remote communication and processing complexity and along with device price, we summarize the final cost to the user. Comparisons with other GNSS solutions shows whether cost truly scales with accuracy and precision. Benedetti E., L. Brack, W. Roberts, Performance Validation of Low-Cost GNSS Sensors for Land Monitoring and Hazard Mitigation, Paper presented at ION GNSS+ 2016 Session F4: Land-Based Applications 2, ION GNSS+ 2016 Proceedings (In Press) Roberts W., E. Benedetti, M. Hutchinson, G. Phipps and A. Keal, An Expendable GNSS Sensor for the Continuous Monitoring and Risk Profiling of Land and Infrastructure, Presentation at ION GNSS+ 2015 Session A5: Applications Using Consumer GNSS

  15. Rock Slope Monitoring from 4D Time-Lapse Structure from Motion Analysis

    Science.gov (United States)

    Kromer, Ryan; Abellan, Antonio; Chyz, Alex; Hutchinson, Jean

    2017-04-01

    more accurate 3D models using time-lapse photos taken from an array of cameras than photos taken from a single camera from multiple positions. For this survey setup, it was possible to detect mm to cm level of changes, which is of sufficient accuracy to detect the pre-failure stage of rockfalls, as well as small rockfall events. Additionally, cameras mounted in a static array can be operated remotely and automatically. Time-lapse SfM photogrammetry can be a cost effective alternative to terrestrial laser scanning for rockfall prone areas and facilitates the study of surface processes with high spatial and temporal detail. We gratefully acknowledge support from the NSERC collaborative research and development grant. References Eltner, A., Kaiser, A., Castillo, C.; Rock, G., Neugirg, F., Abellán, A. Image-based surface reconstruction in geomorphometry—Merits, limits and developments. Earth Surf. Dyn. 2016, 4, 359-389. Kromer, R. A., Abellán, A., Hutchinson, D. J., Lato, M., Edwards, T., & Jaboyedoff, M. A 4D filtering and calibration technique for small-scale point cloud change detection with a terrestrial laser scanner. Remote Sensing 2015, 7(10), 13029-13052.

  16. Quantum Field Theory in Curved Spacetime

    Science.gov (United States)

    Reynolds, Sally C.; Gallagher, Andrew

    2012-03-01

    ; 19. Assimilation and modern human origins in the African peripheries Fred H. Smith, Vance T. Hutchinson and Ivor Janković; 20. Patterns of Middle Pleistocene hominin evolution in Africa and the emergence of modern humans Emma Mbua and Günter Bräuer; 21. Integration of the genetic, anatomical, and archaeological data for the African origin of modern humans: problems and prospects Osbjorn M. Pearson; Part IV. In Search of Context: Hominin Environments, Behaviour and Lithic Cultures: 22. Animal palaeocommunity variability and habitat preference of robust australopiths in South Africa Darryl J. de Ruiter, Matt Sponheimer and Julia Lee-Thorp; 23. Impacts of environmental change and community ecology on the composition and diversity of the southern African monkey fauna from the Plio-Pleistocene to the present Sarah Elton; 24. African genesis revisited: reflections on Raymond Dart and the 'Predatory Transition from Ape(-Man) to Man' Travis R. Pickering; 25. Shared intention in early artefacts: an exploration of deep structure and implications for communication and language John A. J. Gowlett; 26. Sibudu Cave: recent archaeological work on the Middle Stone Age Lyn Wadley; 27. The oldest burials and their significance Avraham Ronen; Index.

  17. THE BAIKAL RIFT: PLIOCENE (MIOCENE – QUATERNARY EPISODE OR PRODUCT OF EXTENDED DEVELOPMENT SINCE THE LATE CRETACEOUS UNDER VARIOUS TECTONIC FACTORS. A REVIEW

    Directory of Open Access Journals (Sweden)

    V. D. Mats

    2015-01-01

    that it took only about 5 Ma to form the entire syn‐rift sequence ofLake Baikal. In [Bazarov, 1986; Rasskazov et al., 2014; Mashchuk, Akulov, 2012; Hutchinson et al., 1993; Zonenshain et al., 1995; Kaz’min et al., 1995], the BR age is determined as the Miocene (Oligocene‐Miocene according to the age of the Tankhoisuite (Miocene or Oligocene‐Miocene and the correlation between the lower seismostratigraphic complex (SSC‐1 and the Tankhoi suite [Hutchinson et al., 1993; Zonenshain et al., 1995]. The Tankhoi suite lies directly on the crystalline basement of the rift and is believed to mark the start of the Baikal syn‐rift profile. However, this concept does not take into account the main specific feature of the profile, i.e. a developing rift. As shown in Fig. 6, the most ancient elements in the syn‐rift profile are inside the deep part of the rift. At the day surface, the basement is overlaid by the younger elements of the sedimentary wedge due to the ‘expansion non‐conformity effect’ (as termed in [Khain, Mikhailov, 1985]. In our opinion, it is incorrect to correlate SSC‐1 and the Tankhoi suires – the representative seismic profile (Fig. 5 shows that SSC‐1 falls out of the profile before reaching the day surface and leans against the rising slope of the basement, while SSC‐2 correlates with the Tankhoi suite. Besides, correlating SSC‐1 with the Tankhoi suite is contradicting to the data of structural studies reported in [San’kov et al., 1997; Delvaux et al., 1997]. SSC‐1 originated before the time when the Lake Baikal region was impacted by the Indo‐Eurasian collision and formed under the influence of pure expansion when tensile stresses were oriented from NW to SE across the strike of the rift along the SE 145–150° azimuth [Zonenshain et al., 1995]. By the time of the SSC‐2 formation, the stress vector turned counterclockwise towards the NE‐SW direction at an acute angle to the rift strike. The Baikal rift

  18. School-based programmes for preventing smoking.

    Science.gov (United States)

    Thomas, R; Perera, R

    2006-07-19

    abstracted outcome data. Because of the marked heterogeneity of design and outcomes, we computed pooled estimates only for those trials that could be analyzed together and for which statistical data were available. We predominantly synthesized the data using narrative systematic review. We grouped studies by intervention method (information; social competence; social influences; combined social influences/social competence; multi-modal programmes). Within each group, we placed them into three categories (low, medium and high risk of bias) according to validity using quality criteria for reported study design. Of the 94 randomized controlled trials identified, we classified 23 as category one (most valid). There was one category one study of information-giving and two of teaching social comeptence. There were thirteen category one studies of social influences interventions. Of these, nine found some positive effect of intervention on smoking prevalence, and four failed to detect an effect on smoking prevalence. The largest and most rigorous study, the Hutchinson Smoking Prevention Project, found no long-term effect of an intensive eight-year programme on smoking behaviour. There were three category one RCTs of combined social influences and social competence interventions: one provided significant results and one only for instruction by health educators compared to self-instruction. There was a lack of high quality evidence about the effectiveness of combinations of social influences and social competence approaches. There was one category one study providing data on social influences compared with information giving. There were four category one studies of multi-modal approaches but they provided limited evidence about the effectiveness of multi-modal approaches including community initiatives. There is one rigorous test of the effects of information-giving about smoking. There are well-conducted randomized controlled trials to test the effects of social influences

  19. Meteorites, Bolides and Comets: A Tale of Inconsistency

    Science.gov (United States)

    Jakes, P.; Padevet, V.

    1992-07-01

    . [11] Hutchinson R., et al., 1977, Appendix to Catalogue of Meteorites, British Museum, London. [12] Ceplecha Z. and McCrosky R. E., 1976, J. Geophys. Res., 81, 6257.

  20. Beclometasone oral--DOR BioPharma.

    Science.gov (United States)

    2007-01-01

    approval in the US for the treatment of gastrointestinal GVHD. The US FDA accepted the NDA filing and has established a target date of 21 July 2007 for completion of review of the NDA. In November 2006, the EMEA determined that the MAA for orBec for the treatment of gastrointestinal GVHD is complete and that the review process has begun. The data provided in the MAA and NDA submissions demonstrate that orBec safely provides a lower risk of mortality compared with the current standard of care. Both filings are supported by data from two randomised, double-blinded, placebo-controlled clinical trials. The first was a 129-patient pivotal phase III clinical trial for orBec conducted at 16 bone marrow/stem cell transplant centres in the US and France. The second trial was a 60-patient phase II clinical trial conducted at the Fred Hutchinson Cancer Research Centre. In the primary endpoint of its pivotal trial, time to treatment failure through day 50, orBec failed to achieve statistical significance (p-value 0.1177). However, orBec did achieve statistical significance in the secondary endpoints of time to treatment failure through day 80, and a reduction in mortality compared with placebo. In this trial, patient survival at the prespecified endpoint of 200 days post-transplant showed a statistically significant 66% reduction in mortality among patients randomised to orBec. DOR BioPharma believes the primary endpoint was not achieved due to a higher than expected rate of treatment failures during the initial 10 days in both treatment groups. The mortality benefit in favour of orBec was confirmed in a retrospective analysis of the phase II study, in which there was a 55% reduction in mortality at 200 days post-transplant. At 1 year after randomisation, there were relatively consistent 51% and 45% reductions in the risk of mortality among patients randomised to orBec in both the phase III and phase II studies, respectively.DOR BioPharma is also conducting a phase II clinical trial

  1. PERUBAHAN KARAKTER ARSITEKTUR PERMUKIMAN KAMPUNG BETING KOTA PONTIANAK KALIMANTAN BARAT

    Directory of Open Access Journals (Sweden)

    Indah Kartika Sari

    2014-01-01

    Kebudayaan. Tulisan dalam blog pribadi http://arsip-s3arskotundip.blogspot.com/2011/05/arsitektur-dalam-perubahan-kebudayaan-2.html Ching, Francis D.K, 2000. Arsitektur Bentuk Ruang dan Tatanan. Erlangga. Jakarta Doxiadis, C. A. 1968. Ekistic, an Introduction to the Science of Human Settlements.    Hutchinson of London. London Fuad, Zubaidi. 2009. Arsitektur Kaili sebagai Proses dan Produk Vernakular. Jurnal “ruang” volume 1 Nomor 1 September 2009. Fakultas Teknik Jurusan Arsitektur Universitas  Tadulako. Palu Habraken, N.J. 1976. Variations: The Systematic Design of Supports; MIT Cambridge. Massachusetts Mangunwijaya, YB. 1988. Wastu Citra,Pengantar ke Ilmu Budaya Bentuk Arsitektur Sendi-sendi Filsafatnya Beserta Contoh-contoh Praktis.  PT. Gramedia. Jakarta Rapoport, Amos. 1969. House Form and Culture. University of Winconsin. Milwaukee Rapoport, Amos. 1977. Human Aspects of Urban Form: Towards a Man-Environment Approach to Urban Form and Design. University ofWinconsin. Milwaukee Yunus, Hadi Sabari, 2000. Struktur dan Tata Ruang Kota. Pustaka Bel. Yogyakarta Vincent. 1983. Perencanaan Tapak Untuk Perumahan (terjemahan. Erlangga. Jakarta Zeisel, John. 1981. Inquiry by Design, Tools for Environment, Behaviour Research. Cambridge University Press. California

  2. Increasing physical activity for veterans in the Mental Health Intensive Case Management Program: A community-based intervention.

    Science.gov (United States)

    Harrold, S Akeya; Libet, Julian; Pope, Charlene; Lauerer, Joy A; Johnson, Emily; Edlund, Barbara J

    2018-04-01

    Individuals with severe mental illness (SMI), experience increased mortality-20 years greater disparity for men and 15 years greater disparity for women-compared to the general population (Thornicroft G. Physical health disparities and mental illness: The scandal of premature mortality. Br J Psychiatr. 2011;199:441-442). Numerous factors contribute to premature mortality in persons with SMI, including suicide and accidental death (Richardson RC, Faulkner G, McDevitt J, Skrinar GS, Hutchinson D, Piette JD. Integrating physical activity into mental health services for persons with serious mental illness. Psychiatr Serv. 2005;56(3):324-331; Thornicroft G. Physical health disparities and mental illness: The scandal of premature mortality. Br J Psychiatr. 2011;199:441-442), but research has shown that adverse health behaviors-including smoking, low rate of physical activity, poor diet, and high alcohol consumption-also significantly contribute to premature deaths (Jones J. Life expectancy in mental illness. Psychiatry Services. 2010. Retrieved from http://psychcentral.com/news/2010/07/13/life-expectancy-in-mental-illness). This quality improvement (QI) project sought to improve health and wellness for veterans in the Mental Health Intensive Case Management Program (MHICM), which is a community-based intensive program for veterans with SMI at risk for decompensation and frequent hospitalizations. At the time of this QI project, the program had 69 veterans who were assessed and treated weekly in their homes. The project introduced a pedometer steps intervention adapted from the VA MOVE! Program-a physical activity and weight management program-with the addition of personalized assistance from trained mental health professionals in the veteran's home environment. Because a large percentage of the veterans in the MHICM program had high blood pressure and increased weight, these outcomes were the focus of this project. Through mental health case management involvement and