WorldWideScience

Sample records for novo paracentric inversion

  1. Dependence of paracentric inversion rate on tract length

    DEFF Research Database (Denmark)

    York, Thomas L; Durrett, Rick; Nielsen, Rasmus

    2007-01-01

    BACKGROUND: We develop a Bayesian method based on MCMC for estimating the relative rates of pericentric and paracentric inversions from marker data from two species. The method also allows estimation of the distribution of inversion tract lengths. RESULTS: We apply the method to data from...... Drosophila melanogaster and D. yakuba. We find that pericentric inversions occur at a much lower rate compared to paracentric inversions. The average paracentric inversion tract length is approx. 4.8 Mb with small inversions being more frequent than large inversions.If the two breakpoints defining...... a paracentric inversion tract are uniformly and independently distributed over chromosome arms there will be more short tract-length inversions than long; we find an even greater preponderance of short tract lengths than this would predict. Thus there appears to be a correlation between the positions...

  2. A 11.7-Mb Paracentric Inversion in Chromosome 1q Detected in Prenatal Diagnosis Associated with Familial Intellectual Disability.

    Science.gov (United States)

    Rigola, Maria A; Baena, Neus; Català, Vicenç; Lozano, Iris; Gabau, Elisabet; Guitart, Miriam; Fuster, Carmen

    2015-01-01

    Most apparent balanced chromosomal inversions are usually clinically asymptomatic; however, infertility, miscarriages, and mental retardation have been reported in inversion carriers. We present a small family with a paracentric inversion 1q42.13q43 detected in routine prenatal diagnosis. Molecular cytogenetic methods defined the size of the inversion as 11.7 Mb and excluded other unbalanced chromosomal alterations in the patients. Our findings suggest that intellectual disability is caused by dysfunction, disruption, or position effects of genes located at or near the breakpoints involved in this inversion. © 2015 S. Karger AG, Basel.

  3. Recombination and synaptic adjustment in oocytes of mice heterozygous for a large paracentric inversion.

    Science.gov (United States)

    Torgasheva, Anna A; Rubtsov, Nikolai B; Borodin, Pavel M

    2013-03-01

    Homologous chromosome synapsis in inversion heterozygotes results in the formation of inversion loops. These loops might be transformed into straight, non-homologously paired bivalents via synaptic adjustment. Synaptic adjustment was discovered 30 years ago; however, its relationship with recombination has remained unclear. We analysed this relationship in female mouse embryos heterozygous for large paracentric inversion In(1)1Rk using immunolocalisation of the synaptonemal complex (SYCP3) and mature recombination nodules (MLH1) proteins. The frequency of cells containing bivalents with inversion loops decreased from 69 % to 28 % during pachytene. If an MLH1 focus was present in the non-homologously paired inverted region of the straight bivalent, it was always located in the middle of the inversion. Most of the small, incompletely adjusted loops contained MLH1 foci near the points at which pairing partners were switched. This observation indicates that the degree of synaptic adjustment depended on the crossover position. Complete synaptic adjustment was only possible if a crossover (CO) was located exactly in the middle of the inversion. If a CO was located at any other site, this interrupted synaptic adjustment and resulted in inversion loops of different sizes with an MLH1 focus at or near the edge of the remaining loop.

  4. A 15 Mb large paracentric chromosome 21 inversion identified in Czech population through a pair of flanking duplications.

    Science.gov (United States)

    Drabova, Jana; Trkova, Marie; Hancarova, Miroslava; Novotna, Drahuse; Hejtmankova, Michaela; Havlovicova, Marketa; Sedlacek, Zdenek

    2014-01-01

    Inversions are balanced structural chromosome rearrangements, which can influence gene expression and the risk of unbalanced chromosome constitution in offspring. Many examples of inversion polymorphisms exist in human, affecting both heterochromatic regions and euchromatin. We describe a novel, 15 Mb long paracentric inversion, inv(21)(q21.1q22.11), affecting more than a third of human 21q. Despite of its length, the inversion cannot be detected using karyotyping due to similar band patterns on the normal and inverted chromosomes, and is therefore likely to escape attention. Its identification was aided by the repeated observation of the same pair of 150 kb long duplications present in cis on chromosome 21 in three Czech families subjected to microarray analysis. The finding prompted us to hypothesise that this co-occurrence of two remote duplications could be associated with an inversion of the intervening segment, and this speculation turned out to be right. The inversion was confirmed in a series of FISH experiments which also showed that the second copy of each of the duplications was always located at the opposite end of the inversion. The presence of the same pair of duplications in additional individuals reported in public databases indicates that the inversion may also be present in other populations. Three out of the total of about 4000 chromosomes 21 examined in our sample carried the duplications and were inverted, corresponding to carrier frequency of about 1/660. Although the breakpoints affect protein-coding genes, the occurrence of the inversion in normal parents and siblings of our patients and the occurrence of the duplications in unaffected controls in databases indicate that this rare variant is rather non-pathogenic. The inverted segment carried an identical shared haplotype in the three families studied. The haplotypes, however, diverged very rapidly in the flanking regions, possibly pointing to an ancient founder event at the origin of the

  5. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

    Science.gov (United States)

    Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

    2010-09-01

    We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

  6. Nonhomologous Synapsis and Reduced Crossing over in a Heterozygous Paracentric Inversion in Saccharomyces Cerevisiae

    Science.gov (United States)

    Dresser, M. E.; Ewing, D. J.; Harwell, S. N.; Coody, D.; Conrad, M. N.

    1994-01-01

    Homologous chromosome synapsis (``homosynapsis'') and crossing over are well-conserved aspects of meiotic chromosome behavior. The long-standing assumption that these two processes are causally related has been challenged recently by observations in Saccharomyces cerevisiae of significant levels of crossing over (1) between small sequences at nonhomologous locations and (2) in mutants where synapsis is abnormal or absent. In order to avoid problems of local sequence effects and of mutation pleiotropy, we have perturbed synapsis by making a set of isogenic strains that are heterozygous and homozygous for a large chromosomal paracentric inversion covering a well marked genetic interval and then measured recombination. We find that reciprocal recombination in the marked interval in heterozygotes is reduced variably across the interval, on average to ~55% of that in the homozygotes, and that positive interference still modulates crossing over. Cytologically, stable synapsis across the interval is apparently heterologous rather than homologous, consistent with the interpretation that stable homosynapsis is required to initiate or consummate a large fraction of the crossing over observed in wild-type strains. When crossing over does occur in heterozygotes, dicentric and acentric chromosomes are formed and can be visualized and quantitated on blots though not demonstrated in viable spores. We find that there is no loss of dicentric chromosomes during the two meiotic divisions and that the acentric chromosome is recovered at only 1/3 to 1/2 of the expected level. PMID:7851761

  7. Transit time spreads in biased paracentric hemispherical deflection analyzers

    International Nuclear Information System (INIS)

    Sise, Omer; Zouros, Theo J.M.

    2016-01-01

    The biased paracentric hemispherical deflection analyzers (HDAs) are an alternative to conventional (centric) HDAs maintaining greater dispersion, lower angular aberrations, and hence better energy resolution without the use of any additional fringing field correctors. In the present work, the transit time spread of the biased paracentric HDA is computed over a wide range of analyzer parameters. The combination of high energy resolution with good time resolution and simplicity of design makes the biased paracentric analyzers very promising for both coincidence and singles spectroscopy applications.

  8. Transit time spreads in biased paracentric hemispherical deflection analyzers

    Energy Technology Data Exchange (ETDEWEB)

    Sise, Omer, E-mail: omersise@sdu.edu.tr [Dept. of Science Education, Faculty of Education, Suleyman Demirel Univ., 32260 Isparta (Turkey); Zouros, Theo J.M. [Dept. of Physics, Univ. of Crete, P.O. Box 2208, GR 71003 Heraklion (Greece); Tandem Lab, INPP, NCSR Demokritos, P.O. Box 60228, GR 15310 Ag. Paraskevi (Greece)

    2016-02-15

    The biased paracentric hemispherical deflection analyzers (HDAs) are an alternative to conventional (centric) HDAs maintaining greater dispersion, lower angular aberrations, and hence better energy resolution without the use of any additional fringing field correctors. In the present work, the transit time spread of the biased paracentric HDA is computed over a wide range of analyzer parameters. The combination of high energy resolution with good time resolution and simplicity of design makes the biased paracentric analyzers very promising for both coincidence and singles spectroscopy applications.

  9. Transit time spreads in biased paracentric hemispherical deflection analyzers

    Science.gov (United States)

    Sise, Omer; Zouros, Theo J. M.

    2016-02-01

    The biased paracentric hemispherical deflection analyzers (HDAs) are an alternative to conventional (centric) HDAs maintaining greater dispersion, lower angular aberrations, and hence better energy resolution without the use of any additional fringing field correctors. In the present work, the transit time spread of the biased paracentric HDA is computed over a wide range of analyzer parameters. The combination of high energy resolution with good time resolution and simplicity of design makes the biased paracentric analyzers very promising for both coincidence and singles spectroscopy applications.

  10. MORPHOMETRIC ANALYSES OF THE PARACENTRAL LOBE

    Directory of Open Access Journals (Sweden)

    Moacyr Oliveira Neto

    2014-03-01

    Full Text Available ntroduction:There are no studies that evaluate measurements of the distances between the grooves that delimit the Paracentral Lobule (PCL in the literature. This study seeks to contribute to the knowledge regarding the anatomy of the PCL, conducting an analysis of morphometric measurements in this region and its correlation with the paracentral sulcus, marginal branch of the cingulate and central sulcus. Methods:42 hemispheres were evaluated, 20 were right and 22 left. Using digital caliper Dc - 6 Western ®, measurements of the size of PCL in the sagittal axis and coronal axis were made, in addition to measures of the Central Sulcus to the Paracentral Sulcus (motor area and Central Sulcus to Marginal Branch of the Cingulate Sulcus (somesthetic area, comparing the prevalence of each of these lengths between hemispheres. Results:The average length between the Paracentral Sulcus and the Central Sulcus was 24.49 cm(14.2 to 38.6 cm in the right hemisphere and 25.50 cm(11.7 to 37.0 cm in the left. As between the Central Sulcus and the Marginal Branch of the Cingulate Sulcus was in average 10.03 cm(2.6 to 22.7 cm in the right and in the left PCL 9.17cm(2.6 to 22.7 cm. In the right hemisphere, 19 samples(86,4% presented greater motor area than somesthetic and, in the left hemisphere, 19 samples(95% had greater motor area. Conclusion:The motor area showed prevalence in relation to the sensory area in the analysis of the two hemispheres, while the comparison of other measures between the two hemispheres showed no significance.

  11. Morphology and digitally aided morphometry of the human paracentral lobule.

    Science.gov (United States)

    Spasojević, Goran; Malobabic, Slobodan; Pilipović-Spasojević, Olivera; Djukić-Macut, Nataša; Maliković, Aleksandar

    2013-02-01

    The human paracentral lobule, the junction of the precentral and postcentral gyri at the medial hemispheric surface, contains several important functional regions, and its variable morphology requires exact morphological and quantitativedata. In order to obtain precise data we investigated the morphology of the paracentral lobule and quantified its visible (extrasulcal) surface. This surface corresponds to commonly used magnetic resonance imaging scout images. We studied 84 hemispheres of adult persons (42 brains; 26 males and 16 females; 20-65 years) fixed in neutral formalin for at least 4 weeks. The medial hemispheric surface was photographed at standard distance and each digital photo was calibrated. Using the intercommissural line system (commissura anterior-commissura posterior or CA-CP line), we performed standardised measurements of the paracentral lobule. Exact determination of its boundaries and morphological types was followed by digital morphometry of its extrasulcal surface using AutoCAD software. We found two distinct morphological types of the human paracentral lobule: continuous type, which was predominant (95.2%), and rare segmented type (4.8%). In hemispheres with segmented cingulate sulcus we also found the short transitional lobulo-limbic gyrus (13.1%). The mean extrasulcal surface of the left paracentral lobule was significantly larger, both in males (left 6.79 cm2 vs. right 5.76 cm2) and in females (left 6.05 cm2 vs. right 5.16 cm2). However, even larger average surfaces in males were not significantly different than the same in females. Reported morphological and quantitative data will be useful during diagnostics and treatment of pathologies affecting the human paracentral lobule, and in further studies of its cytoarchitectonic and functional parcellations.

  12. Angelman syndrome associated with an inversion of chromosome 15q11.2q24.3

    Energy Technology Data Exchange (ETDEWEB)

    Greger, V.; Knoll, J.H.M.; Wagstaff, J.; Lalande, M. [and others

    1997-03-01

    Angelman syndrome (AS) most frequently results from large ({ge}5 Mb) de novo deletions of chromosome 15q11-q13. The deletions are exclusively of maternal origin, and a few cases of paternal uniparental disomy of chromosome 15 have been reported. The latter finding indicates that AS is caused by the absence of a maternal contribution to the imprinted 15q11-q13 region. Failure to inherit a paternal 15q11-q13 contribution results in the clinically distinct disorder of Prader-Willi syndrome. Cases of AS resulting from translocations or pericentric inversions have been observed to be associated with deletions, and there have been no confirmed reports of balanced rearrangements in AS. We report the first such case involving a paracentric inversion with a breakpoint located {approximately}25 kb proximal to the reference marker D15S10. This inversion has been inherited from a phenotypically normal mother. No deletion is evident by molecular analysis in this case, by use of cloned fragments mapped to within {approximately}1 kb of the inversion breakpoint. Several hypotheses are discussed to explain the relationship between the inversion and the AS phenotype. 47 refs., 3 figs.

  13. High rates of de novo 15q11q13 inversions in human spermatozoa

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    Molina Òscar

    2012-02-01

    Full Text Available Abstract Low-Copy Repeats predispose the 15q11-q13 region to non-allelic homologous recombination. We have already demonstrated that a significant percentage of Prader-Willi syndrome (PWS fathers have an increased susceptibility to generate 15q11q13 deletions in spermatozoa, suggesting the participation of intrachromatid exchanges. This work has been focused on assessing the incidence of de novo 15q11q13 inversions in spermatozoa of control donors and PWS fathers in order to determine the basal rates of inversions and to confirm the intrachromatid mechanism as the main cause of 15q11q13 anomalies. Semen samples from 10 control donors and 16 PWS fathers were processed and analyzed by triple-color FISH. Three differentially labeled BAC-clones were used: one proximal and two distal of the 15q11-q13 region. Signal associations allowed the discrimination between normal and inverted haplotypes, which were confirmed by laser-scanning confocal microscopy. Two types of inversions were detected which correspond to the segments involved in Class I and II PWS deletions. No significant differences were observed in the mean frequencies of inversions between controls and PWS fathers (3.59% ± 0.46 and 9.51% ± 0.87 vs 3.06% ± 0.33 and 10.07% ± 0.74. Individual comparisons showed significant increases of inversions in four PWS fathers (P Results suggest that the incidence of heterozygous inversion carriers in the general population could reach significant values. This situation could have important implications, as they have been described as predisposing haplotypes for genomic disorders. As a whole, results confirm the high instability of the 15q11-q13 region, which is prone to different types of de novo reorganizations by intrachromatid NAHR.

  14. [Family paracentric inversion of the short arm of chromosome X (Xp21.2p11.23) and connection with autism spectrum disorders].

    Science.gov (United States)

    Milovančević, Milica Pejović; Vešić, Marija; Jelisavčić, Marko; Nikšić, Snežana; Pilić, Gordana Radivojević; Maravić, Vanja Mandić

    2012-01-01

    Autism spectrum disorders (ASDs) are a group of complex pervasive developmental disorders characterized by impairments in communication, social interaction and behavior. In most cases autism is caused by a combination of genetic factors and environmental risk factors. In 10% to 20% of cases it has been shown that the cause of ASD is genetic. We are describing a 2-year-old boy who was referred to genetic counseling because of speech delay and certain autism-like behavior. By cytogenetic analysis the karyotype 46, inv(X),Y was obtained. The boy was a carrier of a paracentric inversion of the short arm of the chromosome X. After cytogenetic analysis of parental blood, it was detected that mother was a carrier of identical aberration, but had no clinical signs. The method of fluorescent in situ hybridization (FISH) yielded the precise breakpoint in the region (p21.2p11.23). Mother and son were carriers of identical X chromosome. Breakpoints are located in the regions that have already been linked to autism, which indicates that the positional effect of the gene could have been a possible cause of the patient's genotype. In addition to positional effects, in order to better understand the etiology of autism other genetic and environmental factors should be always taken into consideration.

  15. Family paracentric inversion of the short arm of chromosome X (Xp21.2p11.23 and connection with autism spectrum disorders

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    Pejović-Milovančević Milica

    2012-01-01

    Full Text Available Introduction. Autism spectrum disorders (ASDs are a group of complex pervasive developmental disorders characterized by impairments in communication, social interaction and behavior. In most cases autism is caused by a combination of genetic factors and environmental risk factors. In 10% to 20% of cases it has been shown that the cause of ASD is genetic. Case Outline. We are describing a 2-year-old boy who was referred to genetic counseling because of speech delay and certain autism-like behavior. By cytogenetic analysis the karyotype 46, inv(X,Y was obtained. The boy was a carrier of a paracentric inversion of the short arm of the chromosome X. After cytogenetic analysis of parental blood, it was detected that mother was a carrier of identical aberration, but had no clinical signs. The method of fluorescent in situ hybridization (FISH yielded the precise breakpoint in the region (p21.2p11.23. Mother and son were carriers of identical X chromosome. Conclusion. Breakpoints are located in the regions that have already been linked to autism, which indicates that the positional effect of the gene could have been a possible cause of the patient’s genotype. In addition to positional effects, in order to better understand the etiology of autism other genetic and environmental factors should be always taken into consideration. [Projekat Ministarstva nauke Republike Srbije, br. ON175013

  16. Management of a Small Paracentral Corneal Perforation Using Iatrogenic Iris Incarceration and Tissue Adhesive

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    Akira Kobayashi

    2012-07-01

    Full Text Available Background: Surgical intervention for corneal perforation is indicated when the anterior chamber does not reform within a short period of time. Herein, we report the successful management of a small paracentral corneal perforation using autologous iris incarceration and tissue adhesive. Case: A 41-year-old man developed a small paracentral corneal perforation (0.5 mm in size in the right eye, while the treating physician attempted to remove the residual rust ring after removal of a piece of metallic foreign body. Observations: The eye was initially managed with a bandage soft contact lens to ameliorate the aqueous leakage; however, without success. Iatrogenic iris incarceration of the wound was first induced, followed by application of cyanoacrylate tissue adhesive to the perforated site. As a result, the anterior chamber was immediately reformed and maintained. Complete corneal epithelialization of the perforation was achieved in 2 months without visual compromises. Conclusions: Cyanoacrylate tissue adhesive with iatrogenic incarceration of the autologous iris was effective in treating this type of small corneal perforation. This technique is simple and potentially useful for small paracentral corneal perforations outside the visual axis and without good apposition.

  17. Thin minimal rim width at Bruch’s membrane opening is associated with glaucomatous paracentral visual field loss

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    Taniguchi EV

    2017-12-01

    Full Text Available Elise V Taniguchi,1–3 Eleftherios I Paschalis,1,2 Dejiao Li,1,4 Kouros Nouri-Mahdavi,5 Stacey C Brauner,1 Scott H Greenstein,1 Angela V Turalba,1 Janey L Wiggs,1 Louis R Pasquale,1,6 Lucy Q Shen1 1Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA, 2Boston Keratoprosthesis Laboratory, Massachusetts Eye and Ear – Schepens Eye Research Institute, Harvard Medical School, Boston, MA, USA; 3Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, Brazil; 4Department of Ophthalmology, Beijing China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Department of Ophthalmology, David Geffen School of Medicine and Stein Eye Institute, Los Angeles, CA, USA; 6Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Purpose: To compare optic nerve head (ONH measurements in glaucomatous eyes with paracentral visual field (VF loss to eyes with peripheral VF loss and controls.Methods: Open-angle glaucoma (OAG patients with early paracentral VF loss or isolated peripheral VF loss as well as control subjects underwent ONH imaging with swept-source optical coherence tomography (OCT and retinal nerve fiber layer (RNFL imaging with spectral-domain OCT. Minimum rim width at Bruch’s membrane opening (BMO-MRW, lamina cribrosa depth (LCD, and RNFL thickness were compared among the glaucoma and control groups with one-way analysis of variance, Kruskal–Wallis test, and multiple regression analysis.Results: Twenty-nine eyes from 29 OAG patients (15 early paracentral and 14 isolated peripheral VF loss and 20 eyes of 20 control subjects were included. The early paracentral and isolated peripheral VF loss groups had similar VF mean deviation (MD (–5.3±2.7 dB and –3.7±3.0 dB, p=0.15, respectively. Global BMO-MRW was lower in OAG eyes than in controls (193.8±40.0 vs 322.7±62.2 µm, p<0.001, but similar

  18. Radiation induced reciprocal translocations and inversions in anopheles albimanus

    International Nuclear Information System (INIS)

    Kaiser, P.E.; Seawright, J.A.; Benedict, M.Q.; Narang, S.

    1982-01-01

    Reciprocal translocations and inversions were induced in Anopheles albimanus Wiedemann by irradiation of males with X rays. A total of 1669 sperm were assayed, and 175 new aberrations were identified as follows: 102 reciprocal translocations (67 autosomal and 35 sex-linked), 45 pericentric inversions, and 28 paracentric inversions. Eleven of the translocations were nearly whole-arm interchanges, and these were selected for the construction of 'capture systems' for compound chromosomes. Two double-heterozygous translocation strains and four homozygous translocation strains were established. Anopheles albimanus females were irradiated, and a pseudolinkage scheme involving mutant markers was employed to identify reciprocal translocations. The irradiation of females was very inefficient; only one translocation was recovered from 1080 ova tested

  19. Complex chromosomal rearrangement in a girl with psychomotor-retardation and a de novo inversion: inv(2)(p15;q24.2).

    Science.gov (United States)

    Granot-Hershkovitz, Einat; Raas-Rothschild, Annick; Frumkin, Ayala; Granot, David; Silverstein, Shira; Abeliovich, Dvorah

    2011-08-01

    Cytogenetic analysis of DNA from a girl with severe psychomotor retardation revealed a de novo pericentric inversion of chromosome 2: 46,XX,inv(2)(p15q24.2). In order to elucidate the possible role of the inversion in the girl's abnormal phenotype, we analyzed the inversion breakpoints. FISH analysis revealed BAC clones spanning the breakpoints at 2p and 2q of the inversion. Southern blot hybridization with DNA probes from the BAC regions was used to refine the localization of the breakpoints, followed by inverse-PCR which enabled us to sequence the inversion breakpoints. We found a complex chromosomal rearrangement, including five breakpoints, four at 2q and one at 2p joined with minor insertions/deletions of a few bases. The breakpoint at 2p was within the NRXN1 gene that has previously been associated with autism, intellectual disabilities, and psychiatric disorders. In 2q, the breakpoints disrupted two genes, TANC1 and RBMS1; the phenotypic effect of these genes is not currently known. Copyright © 2011 Wiley-Liss, Inc.

  20. Experimental energy resolution of a paracentric hemispherical deflector analyzer for different entry positions and bias

    International Nuclear Information System (INIS)

    Dogan, M.; Ulu, M.; Gennarakis, G. G.; Zouros, T. J. M.

    2013-01-01

    A specially designed hemispherical deflector analyzer (HDA) with 5-element input lens having a movable entry position R 0 suitable for electron energy analysis in atomic collisions was constructed and tested. The energy resolution of the HDA was experimentally determined for three different entry positions R 0 = 84, 100, 112 mm as a function of the nominal entry potential V(R 0 ) under pre-retardation conditions. The resolution for the (conventional) entry at the mean radius R 0 = 100 mm was found to be a factor of 1.6-2 times worse than the resolution for the two (paracentric) positions R 0 = 84 and 112 mm at particular values of V(R 0 ). These results provide the first experimental verification and a proof of principle of the utility of such a paracentric HDA, while demonstrating its advantages over the conventional HDA: greater dispersion with reduced angular aberrations resulting in better energy resolution without the use of any additional fringing field correction electrodes. Supporting simulations of the entire lens plus HDA spectrometer are also provided and mostly found to be within 20%–30% of experimental values. The paracentric HDA is expected to provide a lower cost and/or more compact alternative to the conventional HDA particularly useful in modern applications utilizing a position sensitive detector.

  1. Experimental energy resolution of a paracentric hemispherical deflector analyzer for different entry positions and bias

    Science.gov (United States)

    Dogan, M.; Ulu, M.; Gennarakis, G. G.; Zouros, T. J. M.

    2013-04-01

    A specially designed hemispherical deflector analyzer (HDA) with 5-element input lens having a movable entry position R0 suitable for electron energy analysis in atomic collisions was constructed and tested. The energy resolution of the HDA was experimentally determined for three different entry positions R0 = 84, 100, 112 mm as a function of the nominal entry potential V(R0) under pre-retardation conditions. The resolution for the (conventional) entry at the mean radius R0 = 100 mm was found to be a factor of 1.6-2 times worse than the resolution for the two (paracentric) positions R0 = 84 and 112 mm at particular values of V(R0). These results provide the first experimental verification and a proof of principle of the utility of such a paracentric HDA, while demonstrating its advantages over the conventional HDA: greater dispersion with reduced angular aberrations resulting in better energy resolution without the use of any additional fringing field correction electrodes. Supporting simulations of the entire lens plus HDA spectrometer are also provided and mostly found to be within 20%-30% of experimental values. The paracentric HDA is expected to provide a lower cost and/or more compact alternative to the conventional HDA particularly useful in modern applications utilizing a position sensitive detector.

  2. Experimental energy resolution of a paracentric hemispherical deflector analyzer for different entry positions and bias

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, M.; Ulu, M. [eCOL Laboratory, Department of Physics, Science and Arts Faculty, Afyon Kocatepe University, 03200 Afyonkarahisar (Turkey); Gennarakis, G. G.; Zouros, T. J. M. [Atomic Collisions and Electron Spectroscopy Laboratory, Department of Physics, University of Crete, P.O. Box 2208, 71003 Heraklion, Crete (Greece)

    2013-04-15

    A specially designed hemispherical deflector analyzer (HDA) with 5-element input lens having a movable entry position R{sub 0} suitable for electron energy analysis in atomic collisions was constructed and tested. The energy resolution of the HDA was experimentally determined for three different entry positions R{sub 0}= 84, 100, 112 mm as a function of the nominal entry potential V(R{sub 0}) under pre-retardation conditions. The resolution for the (conventional) entry at the mean radius R{sub 0}= 100 mm was found to be a factor of 1.6-2 times worse than the resolution for the two (paracentric) positions R{sub 0}= 84 and 112 mm at particular values of V(R{sub 0}). These results provide the first experimental verification and a proof of principle of the utility of such a paracentric HDA, while demonstrating its advantages over the conventional HDA: greater dispersion with reduced angular aberrations resulting in better energy resolution without the use of any additional fringing field correction electrodes. Supporting simulations of the entire lens plus HDA spectrometer are also provided and mostly found to be within 20%-30% of experimental values. The paracentric HDA is expected to provide a lower cost and/or more compact alternative to the conventional HDA particularly useful in modern applications utilizing a position sensitive detector.

  3. Megabase-Scale Inversion Polymorphism in the Wild Ancestor of Maize

    Science.gov (United States)

    Fang, Zhou; Pyhäjärvi, Tanja; Weber, Allison L.; Dawe, R. Kelly; Glaubitz, Jeffrey C.; González, José de Jesus Sánchez; Ross-Ibarra, Claudia; Doebley, John; Morrell, Peter L.; Ross-Ibarra, Jeffrey

    2012-01-01

    Chromosomal inversions are thought to play a special role in local adaptation, through dramatic suppression of recombination, which favors the maintenance of locally adapted alleles. However, relatively few inversions have been characterized in population genomic data. On the basis of single-nucleotide polymorphism (SNP) genotyping across a large panel of Zea mays, we have identified an ∼50-Mb region on the short arm of chromosome 1 where patterns of polymorphism are highly consistent with a polymorphic paracentric inversion that captures >700 genes. Comparison to other taxa in Zea and Tripsacum suggests that the derived, inverted state is present only in the wild Z. mays subspecies parviglumis and mexicana and is completely absent in domesticated maize. Patterns of polymorphism suggest that the inversion is ancient and geographically widespread in parviglumis. Cytological screens find little evidence for inversion loops, suggesting that inversion heterozygotes may suffer few crossover-induced fitness consequences. The inversion polymorphism shows evidence of adaptive evolution, including a strong altitudinal cline, a statistical association with environmental variables and phenotypic traits, and a skewed haplotype frequency spectrum for inverted alleles. PMID:22542971

  4. Detection of an inversion in the Ty-2 region between S. lycopersicum and S. habrochaites by a combination of de novo genome assembly and BAC cloning.

    Science.gov (United States)

    Wolters, Anne-Marie A; Caro, Myluska; Dong, Shufang; Finkers, Richard; Gao, Jianchang; Visser, Richard G F; Wang, Xiaoxuan; Du, Yongchen; Bai, Yuling

    2015-10-01

    A chromosomal inversion associated with the tomato Ty - 2 gene for TYLCV resistance is the cause of severe suppression of recombination in a tomato Ty - 2 introgression line. Among tomato and its wild relatives inversions are often observed, which result in suppression of recombination. Such inversions hamper the transfer of important traits from a related species to the crop by introgression breeding. Suppression of recombination was reported for the TYLCV resistance gene, Ty-2, which has been introgressed in cultivated tomato (Solanum lycopersicum) from the wild relative S. habrochaites accession B6013. Ty-2 was mapped to a 300-kb region on the long arm of chromosome 11. The suppression of recombination in the Ty-2 region could be caused by chromosomal rearrangements in S. habrochaites compared with S. lycopersicum. With the aim of visualizing the genome structure of the Ty-2 region, we compared the draft de novo assembly of S. habrochaites accession LYC4 with the sequence of cultivated tomato ('Heinz'). Furthermore, using populations derived from intraspecific crosses of S. habrochaites accessions, the order of markers in the Ty-2 region was studied. Results showed the presence of an inversion of approximately 200 kb in the Ty-2 region when comparing S. lycopersicum and S. habrochaites. By sequencing a BAC clone from the Ty-2 introgression line, one inversion breakpoint was identified. Finally, the obtained results are discussed with respect to introgression breeding and the importance of a priori de novo sequencing of the species involved.

  5. Variable Entry Biased Paracentric Hemispherical Deflector: Experimental results on energy resolution for different entry positions

    Science.gov (United States)

    Dogan, Mevlut; Ulu, Melike; Gennerakis, Giannis; Zouros, Theo J. M.

    2014-04-01

    A new hemispherical deflector analyzer (HDA) which is designed for electron energy analysis in atomic collisions has been constructed and tested. Using the crossed beam technique at the electron spectrometer, test measurements were performed for electron beam (200 eV) - Helium atoms interactions. These first experimental results show that the paracentric entries give almost twice as good resolution as that for the conventional entry. Supporting simulations of the entire lens+HDA spectrometer are found in relatively good agreement with experiment.

  6. Molecular population genetics of inversion breakpoint regions in Drosophila pseudoobscura.

    Science.gov (United States)

    Wallace, Andre G; Detweiler, Don; Schaeffer, Stephen W

    2013-07-08

    Paracentric inversions in populations can have a profound effect on the pattern and organization of nucleotide variability along a chromosome. Regions near inversion breakpoints are expected to have greater levels of differentiation because of reduced genetic exchange between different gene arrangements whereas central regions in the inverted segments are predicted to have lower levels of nucleotide differentiation due to greater levels of genetic flux among different karyotypes. We used the inversion polymorphism on the third chromosome of Drosophila pseudoobscura to test these predictions with an analysis of nucleotide diversity of 18 genetic markers near and away from inversion breakpoints. We tested hypotheses about how the presence of different chromosomal arrangements affects the pattern and organization of nucleotide variation. Overall, markers in the distal segment of the chromosome had greater levels of nucleotide heterozygosity than markers within the proximal segment of the chromosome. In addition, our results rejected the hypothesis that the breakpoints of derived inversions will have lower levels of nucleotide variability than breakpoints of ancestral inversions, even when strains with gene conversion events were removed. High levels of linkage disequilibrium were observed within all 11 breakpoint regions as well as between the ends of most proximal and distal breakpoints. The central region of the chromosome had the greatest levels of linkage disequilibrium compared with the proximal and distal regions because this is the region that experiences the highest level of recombination suppression. These data do not fully support the idea that genetic exchange is the sole force that influences genetic variation on inverted chromosomes.

  7. Male infertility associated with de novo pericentric inversion of chromosome 1.

    Science.gov (United States)

    Balasar, Özgür; Zamani, Ayşe Gül; Balasar, Mehmet; Acar, Hasan

    2017-12-01

    Inversion occurs after two breaks in a chromosome have happened and the segment rotates 180° before reinserting. Inversion carriers have produced abnormal gametes if there is an odd number crossing- over between the inverted and the normal homologous chromosomes causing a duplication or deletion. Reproductive risks such as infertility, abortion, stillbirth and birth of malformed child would be expected in that case. A 54-year- old male patient was consulted to our clinic for primary infertility. The routine chromosome study were applied using peripheral blood lymphocyte cultures and analyzed by giemsa-trypsin-giemsa (GTG) banding, and centromer banding (C-banding) stains. Y chromosome microdeletions in the azoospermia factor (AZF) regions were analyzed with polymerase chain reaction. Additional test such as fluorescence in situ hybridization (FISH) was used to detect the sex-determining region of the Y chromosome (SRY). Semen analysis showed azoospermia. A large pericentric inversion of chromosome 1 46,XY, inv(1) (p22q32) was found in routine chromosome analysis. No microdeletions were seen in AZF regions. In our patient the presence of SRY region was observed by using FISH technique with SRY-specific probe. Men who have pericentric inversion of chromosome 1, appear to be at risk for infertility brought about by spermatogenic breakdown. The etiopathogenic relationship between azoospermia and pericentric inversion of chromosome 1 is discussed.

  8. UniNovo: a universal tool for de novo peptide sequencing.

    Science.gov (United States)

    Jeong, Kyowon; Kim, Sangtae; Pevzner, Pavel A

    2013-08-15

    Mass spectrometry (MS) instruments and experimental protocols are rapidly advancing, but de novo peptide sequencing algorithms to analyze tandem mass (MS/MS) spectra are lagging behind. Although existing de novo sequencing tools perform well on certain types of spectra [e.g. Collision Induced Dissociation (CID) spectra of tryptic peptides], their performance often deteriorates on other types of spectra, such as Electron Transfer Dissociation (ETD), Higher-energy Collisional Dissociation (HCD) spectra or spectra of non-tryptic digests. Thus, rather than developing a new algorithm for each type of spectra, we develop a universal de novo sequencing algorithm called UniNovo that works well for all types of spectra or even for spectral pairs (e.g. CID/ETD spectral pairs). UniNovo uses an improved scoring function that captures the dependences between different ion types, where such dependencies are learned automatically using a modified offset frequency function. The performance of UniNovo is compared with PepNovo+, PEAKS and pNovo using various types of spectra. The results show that the performance of UniNovo is superior to other tools for ETD spectra and superior or comparable with others for CID and HCD spectra. UniNovo also estimates the probability that each reported reconstruction is correct, using simple statistics that are readily obtained from a small training dataset. We demonstrate that the estimation is accurate for all tested types of spectra (including CID, HCD, ETD, CID/ETD and HCD/ETD spectra of trypsin, LysC or AspN digested peptides). UniNovo is implemented in JAVA and tested on Windows, Ubuntu and OS X machines. UniNovo is available at http://proteomics.ucsd.edu/Software/UniNovo.html along with the manual.

  9. A chromosome 10 variant with a 12 Mb inversion [inv(10)(q11.22q21.1)] identical by descent and frequent in the Swedish population.

    Science.gov (United States)

    Entesarian, Miriam; Carlsson, Birgit; Mansouri, Mahmoud Reza; Stattin, Eva-Lena; Holmberg, Eva; Golovleva, Irina; Stefansson, Hreinn; Klar, Joakim; Dahl, Niklas

    2009-03-01

    We identified a paracentric inversion of chromosome 10 [inv(10)(q11.22q21.1)] in 0.20% of Swedish individuals (15/7,439) referred for cytogenetic analysis. A retrospective analysis of 8,896 karyotypes from amniocenteses in Sweden revealed a carrier frequency of 0.079% (7/8,896) for the inversion. Cloning and detailed analysis of the inversion breakpoint regions show enrichment for interspersed repeat elements and AT-stretches. The centromeric breakpoint coincides with that of a predicted inversion from HapMap data, which suggests that this region is involved in several chromosome 10 variants. No known gene or predicted transcript are disrupted by the inversion which spans approximately 12 Mb. Carriers from four non-related Swedish families have identical inversion breakpoints and haplotype analysis confirmed that the rearrangement is identical by descent. Diagnosis was retrieved in 6 out of the 15 carriers referred for cytogenetic analysis. No consistent phenotype was found to be associated with the inversion. Our study demonstrates that the inv(10)(q11.22q21.1) is a rare and inherited chromosome variant with a broad geographical distribution in Sweden. 2009 Wiley-Liss, Inc.

  10. Simulation of Electron Energy Spectra of a Biased Paracentric Hemispherical Deflection Analyzer as a Function of Entry Bias: Effects of Misalignments

    Directory of Open Access Journals (Sweden)

    O. Sise

    2014-01-01

    Full Text Available The performance of a biased paracentric hemispherical deflection analyzer (HDA, including fringing fields and their effect on focusing and energy resolution, is investigated using numerical methods. Electron energy spectra are calculated for three entry positions R0=84 mm, 100 mm, and 112 mm and compared with the recent experimental measurements. In both experiment and calculation, the two different paracentric entry positions R0=84 mm and R0=112 mm, on either side of the mean radius of 100 mm, are found to have a base energy resolution of about two times better than the conventional centric entry position R0=100 mm. In order to explain the discrepancies (6–30% between the simulated and the experimental resolutions the focusing characteristics are further investigated for different displacements of the input lens (ΔR0 with respect to the entry position R0 and the tilted input beam axis by αshift in the dispersive direction. We have found that the blame does not in fact lie with the theory and we have shown that the input lens may have been misaligned in the experiment. Slight misalignments affect both the true energy resolution measurement and the transmission of the beam.

  11. Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly

    DEFF Research Database (Denmark)

    Li, Yingrui; Zheng, Hancheng; Luo, Ruibang

    2011-01-01

    Here we use whole-genome de novo assembly of second-generation sequencing reads to map structural variation (SV) in an Asian genome and an African genome. Our approach identifies small- and intermediate-size homozygous variants (1-50 kb) including insertions, deletions, inversions and their precise...

  12. MRUniNovo: an efficient tool for de novo peptide sequencing utilizing the hadoop distributed computing framework.

    Science.gov (United States)

    Li, Chuang; Chen, Tao; He, Qiang; Zhu, Yunping; Li, Kenli

    2017-03-15

    Tandem mass spectrometry-based de novo peptide sequencing is a complex and time-consuming process. The current algorithms for de novo peptide sequencing cannot rapidly and thoroughly process large mass spectrometry datasets. In this paper, we propose MRUniNovo, a novel tool for parallel de novo peptide sequencing. MRUniNovo parallelizes UniNovo based on the Hadoop compute platform. Our experimental results demonstrate that MRUniNovo significantly reduces the computation time of de novo peptide sequencing without sacrificing the correctness and accuracy of the results, and thus can process very large datasets that UniNovo cannot. MRUniNovo is an open source software tool implemented in java. The source code and the parameter settings are available at http://bioinfo.hupo.org.cn/MRUniNovo/index.php. s131020002@hnu.edu.cn ; taochen1019@163.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  13. The evolutionary history of Drosophila buzzatii. XXXII. Linkage disequilibrium between allozymes and chromosome inversions in two colonizing populations.

    Science.gov (United States)

    Betrán, E; Quezada-Díaz, J E; Ruiz, A; Santos, M; Fontdevila, A

    1995-02-01

    Chromosome polymorphism in Drosophila buzzatii is under selection but the genes responsible for the effect of the inversions of fitness are unknown. On the other hand, there is evidence for selection on several allozyme loci but the presence of paracentric inversions on the second chromosome, where most of the polymorphic loci are located, complicates the interpretation. Studies of the associations between allozymes and inversions are thus necessary to help understand the effect of selection at both the chromosomal and allozymic level. Until now this kind of information has only been available in D. buzzatii for two loci, Est-1 and Est-2, in Australian populations. Here we describe the genetic constitution of two Old World populations, Carboneras and Colera. Emphasis has been placed on the analysis of the linkage disequilibria between the second chromosome arrangements and three allozyme loci, Est-2, Pept-2 and Aldox, located on this chromosome. In addition, the recombination frequencies between the loci, and between the loci and the inversion breakpoints, have been estimated and a genetic map of the three loci has been produced. The two populations differ in allele and arrangement frequencies, as well as in the pattern of one-locus disequilibria. Est-2 and Aldox are associated with the second chromosome arrangements in both populations. On the other hand, Pept-2 is associated with the inversions in Colera but not in Carboneras. The gametic associations among the three loci are discussed taking into account the position of these loci on the chromosome map and the lack of recombination in the heterokaryotypes.

  14. DeNovoGUI: an open source graphical user interface for de novo sequencing of tandem mass spectra.

    Science.gov (United States)

    Muth, Thilo; Weilnböck, Lisa; Rapp, Erdmann; Huber, Christian G; Martens, Lennart; Vaudel, Marc; Barsnes, Harald

    2014-02-07

    De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics. Our platform-independent software is freely available under the permissible Apache2 open source license. Source code, binaries, and additional documentation are available at http://denovogui.googlecode.com .

  15. Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

    Science.gov (United States)

    Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

    2017-10-05

    Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

  16. Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with the Wolf-Hirschhorn syndrome phenotype.

    Science.gov (United States)

    Beaujard, M-P; Jouannic, J-M; Bessières, B; Borie, C; Martin-Luis, I; Fallet-Bianco, C; Portnoï, M-F

    2005-06-01

    To present the prenatal diagnosis of a de novo terminal inversion duplication of the short arm of chromosome 4 and a review of the literature. An amniocentesis for chromosome analysis was performed at 33 weeks' gestation because ultrasound examination showed a female fetus with multiple abnormalities consisting of severe intrauterine growth retardation, microcephaly, a cleft lip and renal hypoplasia. Cytogenetic analysis and FISH studies of the cultured amniocytes revealed a de novo terminal inversion duplication of the short arm of chromosome 4 characterized by a duplication of 4p14-p16.1 chromosome region concomitant with a terminal deletion 4p16.1-pter. The karyotype was thus: 46,XX, inv dup del (4)(:p14-->p16.1::p16.1-->qter). The parents opted to terminate the pregnancy. Fetopathological examination showed dysmorphic features and abnormalities consistent with a Wolf-Hirschhorn syndrome (WHS) diagnosis, clinical manifestations of partial 4p trisomy being mild. Although relatively rare, inverted duplications have been reported repeatedly in an increasing number of chromosomes. Only two previous cases with de novo inv dup del (4p) and one with tandem dup 4p have been reported, all of them associated with a 4pter deletion. We report the first case diagnosed prenatally. Breakpoints are variable, resulting in different abnormal phenotype. In our case, clinical manifestations resulted in a WHS phenotype.

  17. Pesquisa de novos elementos Pesquisa de novos elementos

    Directory of Open Access Journals (Sweden)

    Gil Mário de Macedo Grassi

    1978-11-01

    Full Text Available The present study deals with the discovery of new elements synthesized by man. The introduction discusses in general the theories about nuclear transmutation, which is the method employed in these syntheses. The study shows the importance of the Periodical Table since it is through this table that one can reach a prevision of new elements and its, properties. The discoveries of the transuranic elements, together wich the data of their first preparations are also tabulated The stability of these elements is also discussed, and future speculations are showedNeste trabalho estuda-se, teoricamente, a descoberta de novos elementos sintetizados pelo homem Na introdução apresentamos um apanhado geral sobre as teorias a respeito da transmutação nuclear, que é o método utilizado nestas sínteses. Em seguida, mostramos a importância da Tabela Periódica, pois é através dela que se chega à previsão dos novos elementos e de suas propriedades. As descobertas dos transurânicos, Já realizadas com êxito, juntamente com os dados de suas primeiras preparações são tabelados. A estabilidade destes novos elementos também é discutida, e apresentadas futuras especulações.

  18. De novo complex intra chromosomal rearrangement after ICSI: characterisation by BACs micro array-CGH

    Directory of Open Access Journals (Sweden)

    Quimsiyeh Mazin

    2008-12-01

    Full Text Available Abstract Background In routine Assisted Reproductive Technology (ART men with severe oligozoospermia or azoospermia should be informed about the risk of de novo congenital or chromosomal abnormalities in ICSI program. Also the benefits of preimplantation or prenatal genetic diagnosis practice need to be explained to the couple. Methods From a routine ICSI attempt, using ejaculated sperm from male with severe oligozoospermia and having normal karyotype, a 30 years old pregnant woman was referred to prenatal diagnosis in the 17th week for bichorionic biamniotic twin gestation. Amniocentesis was performed because of the detection of an increased foetal nuchal translucency for one of the fetus by the sonographic examination during the 12th week of gestation (WG. Chromosome and DNA studies of the fetus were realized on cultured amniocytes Results Conventional, molecular cytogenetic and microarray CGH experiments allowed us to conclude that the fetus had a de novo pericentromeric inversion associated with a duplication of the 9p22.1-p24 chromosomal region, 46,XY,invdup(9(p22.1p24 [arrCGH 9p22.1p24 (RP11-130C19 → RP11-87O1x3]. As containing the critical 9p22 region, our case is in coincidence with the general phenotype features of the partial trisomy 9p syndrome with major growth retardation, microcephaly and microretrognathia. Conclusion This de novo complex chromosome rearrangement illustrates the possible risk of chromosome or gene defects in ICSI program and the contribution of array-CGH for mapping rapidly de novo chromosomal imbalance.

  19. de novo'' aneurysms following endovascular procedures

    International Nuclear Information System (INIS)

    Briganti, F.; Cirillo, S.; Caranci, F.; Esposito, F.; Maiuri, F.

    2002-01-01

    Two personal cases of ''de novo'' aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of ''de novo'' aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the ''de novo'' aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous ''de novo'' aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of ''de novo'' aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a ''de novo'' aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for ''de novo'' aneurysm formation. (orig.)

  20. Characterization of a novel cation transporter ATPase gene (ATP13A4) interrupted by 3q25-q29 inversion in an individual with language delay.

    Science.gov (United States)

    Kwasnicka-Crawford, Dorota A; Carson, Andrew R; Roberts, Wendy; Summers, Anne M; Rehnström, Karola; Järvelä, Irma; Scherer, Stephen W

    2005-08-01

    Specific language impairment (SLI) is defined as failure to acquire normal language skills despite adequate intelligence and environmental stimulation. Although SLI disorders are often heritable, the genetic basis is likely to involve a number of risk factors. This study describes a 7-year-old girl carrying an inherited paracentric inversion of the long arm of chromosome 3 [46XX, inv(3)(q25.32-q29)] having clinically defined expressive and receptive language delay. Fluorescence in situ hybridization (FISH) with locus-specific bacterial artificial chromosome clones (BACs) as probes was used to characterize the inverted chromosome 3. The proximal and distal inversion breakpoint was found to reside between markers D3S3692/D3S1553 and D3S3590/D3S2305, respectively. ATP13A4, a novel gene coding for a cation-transporting P-type ATPase, was found to be disrupted by the distal breakpoint. The ATP13A4 gene was shown to comprise a 3591-bp transcript encompassing 30 exons spanning 152 kb of the genomic DNA. This study discusses the characterization of ATP13A4 and its possible involvement in speech-language disorder.

  1. De novo malignancy after pancreas transplantation in Japan.

    Science.gov (United States)

    Tomimaru, Y; Ito, T; Marubashi, S; Kawamoto, K; Tomokuni, A; Asaoka, T; Wada, H; Eguchi, H; Mori, M; Doki, Y; Nagano, H

    2015-04-01

    Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. We clarified the incidence of de novo malignancy after pancreas transplantation in Japan. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. NovoPen Echo® insulin delivery device

    Directory of Open Access Journals (Sweden)

    Hyllested-Winge J

    2016-01-01

    Full Text Available Jacob Hyllested-Winge,1 Thomas Sparre,2 Line Kynemund Pedersen2 1Novo Nordisk Pharma Ltd, Tokyo, Japan; 2Novo Nordisk A/S, Søborg, Denmark Abstract: The introduction of insulin pen devices has provided easier, well-tolerated, and more convenient treatment regimens for patients with diabetes mellitus. When compared with vial and syringe regimens, insulin pens offer a greater clinical efficacy, improved quality of life, and increased dosing accuracy, particularly at low doses. The portable and discreet nature of pen devices reduces the burden on the patient, facilitates adherence, and subsequently contributes to the improvement in glycemic control. NovoPen Echo® is one of the latest members of the NovoPen® family that has been specifically designed for the pediatric population and is the first to combine half-unit increment (=0.5 U of insulin dosing with a simple memory function. The half-unit increment dosing amendments and accurate injection of 0.5 U of insulin are particularly beneficial for children (and insulin-sensitive adults/elders, who often require small insulin doses. The memory function can be used to record the time and amount of the last dose, reducing the fear of double dosing or missing a dose. The memory function also provides parents with extra confidence and security that their child is taking insulin at the correct doses and times. NovoPen Echo is a lightweight, durable insulin delivery pen; it is available in two different colors, which may help to distinguish between different types of insulin, providing more confidence for both users and caregivers. Studies have demonstrated a high level of patient satisfaction, with 80% of users preferring NovoPen Echo to other pediatric insulin pens. Keywords: NovoPen Echo®, memory function, half-unit increment dosing, adherence, children, adolescents 

  3. De novo origin of human protein-coding genes.

    Directory of Open Access Journals (Sweden)

    Dong-Dong Wu

    2011-11-01

    Full Text Available The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA-seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes.

  4. De Novo Origin of Human Protein-Coding Genes

    Science.gov (United States)

    Wu, Dong-Dong; Irwin, David M.; Zhang, Ya-Ping

    2011-01-01

    The de novo origin of a new protein-coding gene from non-coding DNA is considered to be a very rare occurrence in genomes. Here we identify 60 new protein-coding genes that originated de novo on the human lineage since divergence from the chimpanzee. The functionality of these genes is supported by both transcriptional and proteomic evidence. RNA–seq data indicate that these genes have their highest expression levels in the cerebral cortex and testes, which might suggest that these genes contribute to phenotypic traits that are unique to humans, such as improved cognitive ability. Our results are inconsistent with the traditional view that the de novo origin of new genes is very rare, thus there should be greater appreciation of the importance of the de novo origination of genes. PMID:22102831

  5. Combined "de novo" and "ex novo" lipid fermentation in a mix-medium of corncob acid hydrolysate and soybean oil by Trichosporon dermatis.

    Science.gov (United States)

    Huang, Chao; Luo, Mu-Tan; Chen, Xue-Fang; Qi, Gao-Xiang; Xiong, Lian; Lin, Xiao-Qing; Wang, Can; Li, Hai-Long; Chen, Xin-De

    2017-01-01

    Microbial oil is one important bio-product for its important function in energy, chemical, and food industry. Finding suitable substrates is one key issue for its industrial application. Both hydrophilic and hydrophobic substrates can be utilized by oleaginous microorganisms with two different bio-pathways (" de novo " lipid fermentation and " ex novo " lipid fermentation). To date, most of the research on lipid fermentation has focused mainly on only one fermentation pathway and little work was carried out on both " de novo " and " ex novo " lipid fermentation simultaneously; thus, the advantages of both lipid fermentation cannot be fulfilled comprehensively. In this study, corncob acid hydrolysate with soybean oil was used as a mix-medium for combined " de novo " and " ex novo " lipid fermentation by oleaginous yeast Trichosporon dermatis . Both hydrophilic and hydrophobic substrates (sugars and soybean oil) in the medium can be utilized simultaneously and efficiently by T. dermatis . Different fermentation modes were compared and the batch mode was the most suitable for the combined fermentation. The influence of soybean oil concentration, inoculum size, and initial pH on the lipid fermentation was evaluated and 20 g/L soybean oil, 5% inoculum size, and initial pH 6.0 were suitable for this bioprocess. By this technology, the lipid composition of extracellular hydrophobic substrate (soybean oil) can be modified. Although adding emulsifier showed little beneficial effect on lipid production, it can modify the intracellular lipid composition of T. dermatis . The present study proves the potential and possibility of combined " de novo " and " ex novo " lipid fermentation. This technology can use hydrophilic and hydrophobic sustainable bio-resources to generate lipid feedstock for the production of biodiesel or other lipid-based chemical compounds and to treat some special wastes such as oil-containing wastewater.

  6. Recombinant chromosome 7 in a mosaic 45,X/47,XXX patient.

    Science.gov (United States)

    Tirado, Carlos A; Gotway, Garrett; Torgbe, Emmanuel; Iyer, Santha; Dallaire, Stephanie; Appleberry, Taylor; Suterwala, Mohamed; Garcia, Rolando; Valdez, Federico; Patel, Sangeeta; Koduru, Prasad

    2012-01-01

    Individuals with pericentric inversions are at risk for producing offspring with chromosomal gains and losses, while those carrying paracentric inversions usually produce unviable gametes [Madan, 1995]. In this current study, we present a newborn with dysmorphic features and malformations, whose karyotype showed an abnormal copy of chromomosome 7 described at first as add(7)(q32) as well as mos 45,X/47,XXX. Array comparative genomic hybridization (CGH) revealed an interstitial deletion in the long arm of chromosome 7 involving bands q35 to q36.3 but retaining the 7q subtelomere. The patient's deletion is believed to be due to meiotic recombination in the inversion loop in the phenotypically normal father who seems to carry two paracentric inversions in the long arm of chromosome 7, which was described as rec(7)(7pter- > q35::q36.3- > 7qter)pat. The abnormal copy of chromosome 7 in the father has been described as: der(7)(7pter- > q22.1::q36.3- > q35::q22.1- > q35::q36.3- > 7qter). This is a unique karyotype that to our knowledge has not been previously reported in the literature and predisposes to meiotic recombination that can result in deletions or duplications of 7q35-36. Copyright © 2011 Wiley Periodicals, Inc.

  7. Genes from scratch--the evolutionary fate of de novo genes.

    Science.gov (United States)

    Schlötterer, Christian

    2015-04-01

    Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

  8. Evolutionary history of the third chromosome gene arrangements of Drosophila pseudoobscura inferred from inversion breakpoints.

    Science.gov (United States)

    Wallace, Andre G; Detweiler, Don; Schaeffer, Stephen W

    2011-08-01

    The third chromosome of Drosophila pseudoobscura is polymorphic for numerous gene arrangements that form classical clines in North America. The polytene salivary chromosomes isolated from natural populations revealed changes in gene order that allowed the different gene arrangements to be linked together by paracentric inversions representing one of the first cases where genetic data were used to construct a phylogeny. Although the inversion phylogeny can be used to determine the relationships among the gene arrangements, the cytogenetic data are unable to infer the ancestral arrangement or the age of the different chromosome types. These are both important properties if one is to infer the evolutionary forces responsible for the spread and maintenance of the chromosomes. Here, we employ the nucleotide sequences of 18 regions distributed across the third chromosome in 80-100 D. pseudoobscura strains to test whether five gene arrangements are of unique or multiple origin, what the ancestral arrangement was, and what are the ages of the different arrangements. Each strain carried one of six commonly found gene arrangements and the sequences were used to infer their evolutionary relationships. Breakpoint regions in the center of the chromosome supported monophyly of the gene arrangements, whereas regions at the ends of the chromosome gave phylogenies that provided less support for monophyly of the chromosomes either because the individual markers did not have enough phylogenetically informative sites or genetic exchange scrambled information among the gene arrangements. A data set where the genetic markers were concatenated strongly supported a unique origin of the different gene arrangements. The inversion polymorphism of D. pseudoobscura is estimated to be about a million years old. We have also shown that the generated phylogeny is consistent with the cytological phylogeny of this species. In addition, the data presented here support hypothetical as the ancestral

  9. Genome-wide patterns and properties of de novo mutations in humans

    NARCIS (Netherlands)

    Francioli, Laurent C.; Polak, Paz P.; Koren, Amnon; Menelaou, Androniki; Chun, Sung; Renkens, Ivo; van Duijn, Cornelia M.; Swertz, Morris; Wijmenga, Cisca; van Ommen, Gertjan; Slagboom, P. Eline; Boomsma, Dorret I.; Ye, Kai; Guryev, Victor; Arndt, Peter F.; Kloosterman, Wigard P.; de Bakker, Paul I. W.; Sunyaev, Shamil R.

    Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect(1-10). Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring

  10. Genome-wide patterns and properties of de novo mutations in humans

    NARCIS (Netherlands)

    Francioli, L.C.; Polak, P.P.; Koren, A.; Menelaou, A.; Chun, S.; Renkens, I.; van Duijn, C.M.; Swertz, M.A.; Wijmenga, C.; van Ommen, G.J.; Slagboom, P.E.; Boomsma, D.I.; Ye, K.; Guryev, V.; Arndt, P.F.; Kloosterman, W.P.; Bakker, P.I.W.; Sunyaev, S.R.; Dijk, F.; Neerincx, P.B.T.; Pulit, S.L.; Deelen, P.; Elbers, C.C.; Palamara, P.F.; Pe'er, I.; Abdellaoui, A.; van Oven, M.; Vermaat, M.; Li, M.; Laros, J.F.J.; Stoneking, M.; de Knijff, P.; Kayser, M.; Veldink, J.H.; Van den Berg, L.H.; Byelas, H.; den Dunnen, J.T.; Dijkstra, M.; Amin, N.; van der Velde, K.J.; Hottenga, J.J.; van Setten, J.; van Leeuwen, E.M.; Kanterakis, A.; Kattenberg, V.M.; Karssen, L.C.; van Schaik, B.D.C.; Bot, J.; Nijman, I.J.; van Enckevort, D.; Mei, H.; Koval, V.; Estrada, K.; Medina-Gomez, C.; Lameijer, E.W.; Moed, M.H.; Hehir-Kwa, J.Y.; Handsaker, R.E.; McCarroll, S.A.; Vuzman, D.; Sohail, M.; Hormozdiari, F.; Marschall, T.; Schönhuth, A.; Beekman, M.; de Craen, A.J.; Suchiman, H.E.D.; Hofman, A.; Oostra, B.; Isaacs, A.; Rivadeneira, F.; Uitterlinden, A.G.; Willemsen, G.; Platteel, M.; Pitts, S.J.; Potluri, S.; Sundar, P.; Cox, D.R.; Li, Q.; Li, Y.; Du, Y.; Chen, R.; Cao, H.; Li, N.; Cao, S.; Wang, J.; Bovenberg, J.A.; Brandsma, M.

    2015-01-01

    Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of

  11. Clinicopathologic factors associated with de novo metastatic breast cancer.

    Science.gov (United States)

    Shen, Tiansheng; Siegal, Gene P; Wei, Shi

    2016-12-01

    While breast cancers with distant metastasis at presentation (de novo metastasis) harbor significantly inferior clinical outcomes, there have been limited studies analyzing the clinicopathologic characteristics in this subset of patients. In this study, we analyzed 6126 breast cancers diagnosed between 1998 and 2013 to identify factors associated with de novo metastatic breast cancer. When compared to patients without metastasis at presentation, race, histologic grade, estrogen/progesterone receptor (ER/PR) and HER2 statuses were significantly associated with de novo metastasis in the entire cohort, whereas age, histologic grade, PR and HER2 status were the significant parameters in the subset of patients with locally advanced breast cancer (Stage IIB/III). The patients with de novo metastatic breast cancer had a significant older mean age and a lower proportion of HER2-positive tumors when compared to those with metastatic recurrence. Further, the HER2-rich subtype demonstrated a drastically higher incidence of de novo metastasis when compared to the luminal and triple-negative breast cancers in the entire cohort [odds ratio (OR)=5.68 and 2.27, respectively] and in the patients with locally advanced disease (OR=4.02 and 2.12, respectively), whereas no significant difference was seen between de novo metastatic cancers and those with metastatic recurrence. Moreover, the luminal and HER2-rich subtypes showed bone-seeking (OR=1.92) and liver-homing (OR=2.99) characteristics, respectively, for the sites of de novo metastasis, while the latter was not observed in those with metastatic recurrence. Our data suggest that an algorithm incorporating clinicopathologic factors, especially histologic grade and receptor profile, remains of significant benefit during decision making in newly diagnosed breast cancer in the pursuit of precision medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Foldability of a Natural De Novo Evolved Protein.

    Science.gov (United States)

    Bungard, Dixie; Copple, Jacob S; Yan, Jing; Chhun, Jimmy J; Kumirov, Vlad K; Foy, Scott G; Masel, Joanna; Wysocki, Vicki H; Cordes, Matthew H J

    2017-11-07

    The de novo evolution of protein-coding genes from noncoding DNA is emerging as a source of molecular innovation in biology. Studies of random sequence libraries, however, suggest that young de novo proteins will not fold into compact, specific structures typical of native globular proteins. Here we show that Bsc4, a functional, natural de novo protein encoded by a gene that evolved recently from noncoding DNA in the yeast S. cerevisiae, folds to a partially specific three-dimensional structure. Bsc4 forms soluble, compact oligomers with high β sheet content and a hydrophobic core, and undergoes cooperative, reversible denaturation. Bsc4 lacks a specific quaternary state, however, existing instead as a continuous distribution of oligomer sizes, and binds dyes indicative of amyloid oligomers or molten globules. The combination of native-like and non-native-like properties suggests a rudimentary fold that could potentially act as a functional intermediate in the emergence of new folded proteins de novo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Particulated articular cartilage: CAIS and DeNovo NT.

    Science.gov (United States)

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  14. ''de novo'' aneurysms following endovascular procedures

    Energy Technology Data Exchange (ETDEWEB)

    Briganti, F.; Cirillo, S.; Caranci, F. [Department of Neurological Sciences, Services of Neuroradiology, ' ' Federico II' ' University, Naples (Italy); Esposito, F.; Maiuri, F. [Department of Neurological Sciences, Services of Neurosurgery, ' ' Federico II' ' University, Naples (Italy)

    2002-07-01

    Two personal cases of ''de novo'' aneurysms of the anterior communicating artery (ACoA) occurring 9 and 4 years, respectively, after endovascular carotid occlusion are described. A review of the 30 reported cases (including our own two) of ''de novo'' aneurysms after occlusion of the major cerebral vessels has shown some features, including a rather long time interval after the endovascular procedure of up to 20-25 years (average 9.6 years), a preferential ACoA (36.3%) and internal carotid artery-posterior communicating artery (ICA-PCoA) (33.3%) location of the ''de novo'' aneurysms, and a 10% rate of multiple aneurysms. These data are compared with those of the group of reported spontaneous ''de novo'' aneurysms after SAH or previous aneurysm clipping. We agree that the frequency of ''de novo'' aneurysms after major-vessel occlusion (two among ten procedures in our series, or 20%) is higher than commonly reported (0 to 11%). For this reason, we suggest that patients who have been submitted to endovascular major-vessel occlusion be followed up for up to 20-25 years after the procedure, using non-invasive imaging studies such as MR angiography and high-resolution CT angiography. On the other hand, periodic digital angiography has a questionable risk-benefit ratio; it may be used when a ''de novo'' aneurysm is detected or suspected on non-invasive studies. The progressive enlargement of the ACoA after carotid occlusion, as described in our case 1, must be considered a radiological finding of risk for ''de novo'' aneurysm formation. (orig.)

  15. Language and national identity in Novo Cinema Galego

    Directory of Open Access Journals (Sweden)

    Brais ROMERO SUÁREZ

    2015-12-01

    Full Text Available The talk of town since its inception in 2010, the Cinema Novo Galego has been successful in all competitions and festivals that has been present. From the FIPRESCI prize in Cannes to the Best Emerging Director at Locarno, this new wave of cinema places Galicia in the world film stage. But does Novo Cinema Galego an accurate representation of Galicia? What's the role of Galicia in this movement?

  16. Karyotype Evolution in Birds: from Conventional Staining to Chromosome Painting

    OpenAIRE

    Ferguson-Smith, Malcolm

    2018-01-01

    In this work we performed comparative chromosome painting using probes from Gallus gallus (GGA) Linnaeus, 1758 and Leucopternis albicollis (LAL) Latham, 1790 in Synallaxis frontalis Pelzeln, 1859 (Passeriformes, Furnariidae), an exclusively Neotropical species, in order to analyze whether the complex pattern of intrachromosomal rearrangements (paracentric and pericentric inversions) proposed for Oscines and Suboscines is shared with more basal species. S. frontalis has 82 chromosomes, similar...

  17. On the Origin of De Novo Genes in Arabidopsis thaliana Populations.

    Science.gov (United States)

    Li, Zi-Wen; Chen, Xi; Wu, Qiong; Hagmann, Jörg; Han, Ting-Shen; Zou, Yu-Pan; Ge, Song; Guo, Ya-Long

    2016-08-03

    De novo genes, which originate from ancestral nongenic sequences, are one of the most important sources of protein-coding genes. This origination process is crucial for the adaptation of organisms. However, how de novo genes arise and become fixed in a population or species remains largely unknown. Here, we identified 782 de novo genes from the model plant Arabidopsis thaliana and divided them into three types based on the availability of translational evidence, transcriptional evidence, and neither transcriptional nor translational evidence for their origin. Importantly, by integrating multiple types of omics data, including data from genomes, epigenomes, transcriptomes, and translatomes, we found that epigenetic modifications (DNA methylation and histone modification) play an important role in the origination process of de novo genes. Intriguingly, using the transcriptomes and methylomes from the same population of 84 accessions, we found that de novo genes that are transcribed in approximately half of the total accessions within the population are highly methylated, with lower levels of transcription than those transcribed at other frequencies within the population. We hypothesized that, during the origin of de novo gene alleles, those neutralized to low expression states via DNA methylation have relatively high probabilities of spreading and becoming fixed in a population. Our results highlight the process underlying the origin of de novo genes at the population level, as well as the importance of DNA methylation in this process. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Extreme-Scale De Novo Genome Assembly

    Energy Technology Data Exchange (ETDEWEB)

    Georganas, Evangelos [Intel Corporation, Santa Clara, CA (United States); Hofmeyr, Steven [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Egan, Rob [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Buluc, Aydin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.; Rokhsar, Daniel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Computational Research Division; Yelick, Katherine [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint Genome Inst.

    2017-09-26

    De novo whole genome assembly reconstructs genomic sequence from short, overlapping, and potentially erroneous DNA segments and is one of the most important computations in modern genomics. This work presents HipMER, a high-quality end-to-end de novo assembler designed for extreme scale analysis, via efficient parallelization of the Meraculous code. Genome assembly software has many components, each of which stresses different components of a computer system. This chapter explains the computational challenges involved in each step of the HipMer pipeline, the key distributed data structures, and communication costs in detail. We present performance results of assembling the human genome and the large hexaploid wheat genome on large supercomputers up to tens of thousands of cores.

  19. Glucagon infusion increases rate of purine synthesis de novo in rat liver

    International Nuclear Information System (INIS)

    Itakura, Mitsuo; Maeda, Noriaki; Tsuchiya, Masami; Yamashita, Kamejiro

    1987-01-01

    Based on the parallel increases of glucagon, the second peak of hepatic cAMP, and the rate of purine synthesis de novo in the prereplicative period in regenerating rate liver after a 70% hepatectomy, it was hypothesized that glucagon is responsible for the increased rate of purine synthesis de novo. To test this hypothesis, the effect of glucagon or dibutyryl cAMP infusion on the rate of purine synthesis de novo in rat liver was studied. Glucagon infusion but not insulin or glucose infusion increased the rate of purine synthesis de novo, which was assayed by [ 14 C]glycine or [ 14 C]formate incorporation, by 2.7- to 4.3-fold. Glucagon infusion increased cAMP concentrations by 4.9-fold and 5-phosphoribosyl-1-pyrophosphate concentrations by 1.5-fold in liver but did not change the specific activity of amidophosphoribosyltransferase or purine ribonucleotide concentrations. Dibutyryl cAMP infusion also increased the rate of purine synthesis de novo by 2.2- to 4.0-fold. Because glucagon infusion increased the rate of purine synthesis de novo in the presence of unchanged purine ribonucleotide concentrations, it is concluded that glucagon after infusion or in animals after a 70% hepatectomy is playing an anabolic role to increase the rate of purine synthesis de novo by increasing cAMP and 5-phosphoribosyl-1-pyrophosphate concentrations

  20. High frequencies of de novo CNVs in bipolar disorder and schizophrenia.

    LENUS (Irish Health Repository)

    Malhotra, Dheeraj

    2011-12-22

    While it is known that rare copy-number variants (CNVs) contribute to risk for some neuropsychiatric disorders, the role of CNVs in bipolar disorder is unclear. Here, we reasoned that a contribution of CNVs to mood disorders might be most evident for de novo mutations. We performed a genome-wide analysis of de novo CNVs in a cohort of 788 trios. Diagnoses of offspring included bipolar disorder (n = 185), schizophrenia (n = 177), and healthy controls (n = 426). Frequencies of de novo CNVs were significantly higher in bipolar disorder as compared with controls (OR = 4.8 [1.4,16.0], p = 0.009). De novo CNVs were particularly enriched among cases with an age at onset younger than 18 (OR = 6.3 [1.7,22.6], p = 0.006). We also confirmed a significant enrichment of de novo CNVs in schizophrenia (OR = 5.0 [1.5,16.8], p = 0.007). Our results suggest that rare spontaneous mutations are an important contributor to risk for bipolar disorder and other major neuropsychiatric diseases.

  1. De Novo Human Cardiac Myocytes for Medical Research: Promises and Challenges

    Directory of Open Access Journals (Sweden)

    Veronique Hamel

    2017-01-01

    Full Text Available The advent of cellular reprogramming technology has revolutionized biomedical research. De novo human cardiac myocytes can now be obtained from direct reprogramming of somatic cells (such as fibroblasts, from induced pluripotent stem cells (iPSCs, which are reprogrammed from somatic cells, and from human embryonic stem cells (hESCs. Such de novo human cardiac myocytes hold great promise for in vitro disease modeling and drug screening and in vivo cell therapy of heart disease. Here, we review the technique advancements for generating de novo human cardiac myocytes. We also discuss several challenges for the use of such cells in research and regenerative medicine, such as the immature phenotype and heterogeneity of de novo cardiac myocytes obtained with existing protocols. We focus on the recent advancements in addressing such challenges.

  2. Melhoramento do cafeeiro: IV - Café Mundo Novo

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1952-06-01

    Full Text Available Em um conjunto de cafeeiros existentes em Mundo Novo, hoje Urupês, na região Araraquarense do Estado de São Paulo, foram feitas seleções de vários cafeeiros baseando-se no seu aspecto vegetativo, na produção existente na época da seleção e na provável produção do ano seguinte. Estudou-se a origem da plantação inicial desse café, tanto em Urupês como em Jaú, chegando-se à conclusão de que é provavelmente originário desta última localidade. Progênies do café "Mundo Novo", anteriormente conhecido por "Sumatra" e derivado de plantas selecionadas em Urupês e Jaú, acham-se em estudo em seis localidades do Estado : Campinas, Ribeirão Prêto, Pindorama, Mococa, Jaú e Monte Alegre do Sul. No presente trabalho são apenas aproveitados dados referentes à variabilidade morfológica e característicos da produção das progênies dos primeiros cafeeiros selecionados em Urupês e estudados em Campinas, Jaú, Pindorama e Mococa. Em tôdas as localidades, observou-se variação nos caracteres morfológicos das progênies, verificando-se a ocorrência de plantas quase improdutivas. A maioria das progênies, no entanto, se caracteriza por acentuado vigor vegetativo. Foram estudadas as produções totais das progénies e das plantas, no período 1946-1951, notando-se que algumas progénies se salientaram pela elevada produção em tôdas as localidades. Os tipos de sementes "moca", "concha" e "chato" foram determinados em amostras de tôdas as plantas, por um período de três anos, notando-se que a variação ocorrida é da mesma ordem que a encontrada em outros cafeeiros em seleção. Procurou-se eliminar, pela seleção, cafeeiros com elevada produção de frutos sem sementes em uma ou duas lojas, característico êsse que parece ser hereditário. Os resultados obtidos de cruzamento entre os melhores cafeeiros "Mundo Novo" de Campinas e plantas da variedade murta, indicaram que esses cafeeiros são do tipo bourbon. Provavelmente

  3. De Novo Collapsing Glomerulopathy in a Renal Allograft Recipient

    Directory of Open Access Journals (Sweden)

    Kanodia K

    2008-01-01

    Full Text Available Collapsing glomerulopathy (CG, characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.

  4. Purine biosynthesis de novo by lymphocytes in gout

    International Nuclear Information System (INIS)

    Kamoun, P.; Chanard, J.; Brami, M.; Funck-Brentano, J.L.

    1978-01-01

    A method of measurement in vitro of purine biosynthesis de novo in human circulating blood lymphocytes is proposed. The rate of early reactions of purine biosynthesis de novo was determined by the incorporation of [ 14 C]formate into N-formyl glycinamide ribonucleotide when the subsequent reactions of the metabolic pathway were completely inhibited by the antibiotic azaserine. Synthesis of 14 C-labelled N-formyl glycinamide ribonucleotide by lymphocytes was measured in healthy control subjects and patients with primary gout or hyperuricaemia secondary to renal failure, with or without allopurinol therapy. The average synthesis was higher in gouty patients without therapy than in control subjects, but the values contained overlap the normal range. In secondary hyperuricaemia the synthesis was at same value as in control subjects. These results are in agreement with the inconstant acceleration of purine biosynthesis de novo in gouty patients as seen by others with measurement of [ 14 C]glycine incorporation into urinary uric acid. (author)

  5. De novo giant A2 aneurysm following anterior communicating artery occlusion.

    Science.gov (United States)

    Ibrahim, Tarik F; Hafez, Ahmad; Andrade-Barazarte, Hugo; Raj, Rahul; Niemela, Mika; Lehto, Hanna; Numminen, Jussi; Jarvelainen, Juha; Hernesniemi, Juha

    2015-01-01

    De novo intracranial aneurysms are reported to occur with varying incidence after intracranial aneurysm treatment. They are purported to be observed, however, with increased incidence after Hunterian ligation; particularly in cases of carotid artery occlusion for giant or complex aneurysms deemed unclippable. We report a case of right-sided de novo giant A2 aneurysm 6 years after an anterior communicating artery (ACoA) aneurysm clipping. We believe this de novo aneurysm developed in part due to patient-specific risk factors but also a significant change in cerebral hemodynamics. The ACoA became occluded after surgery that likely altered the cerebral hemodynamics and contributed to the de novo aneurysm. We believe this to be the first reported case of a giant de novo aneurysm in this location. Following parent vessel occlusion (mostly of the carotid artery), there are no reports of any de novo aneurysms in the pericallosal arteries let alone a giant one. The patient had a dominant right A1 and the sudden increase in A2 blood flow likely resulted in increased wall shear stress, particularly in the medial wall of the A2 where the aneurysm occurred 2 mm distal to the A1-2 junction. ACoA preservation is a key element of aneurysm surgery in this location. Suspected occlusion of this vessel may warrant closer radiographic follow-up in patients with other risk factors for aneurysm development.

  6. de novo computational enzyme design.

    Science.gov (United States)

    Zanghellini, Alexandre

    2014-10-01

    Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Inverse photoemission

    International Nuclear Information System (INIS)

    Namatame, Hirofumi; Taniguchi, Masaki

    1994-01-01

    Photoelectron spectroscopy is regarded as the most powerful means since it can measure almost perfectly the occupied electron state. On the other hand, inverse photoelectron spectroscopy is the technique for measuring unoccupied electron state by using the inverse process of photoelectron spectroscopy, and in principle, the similar experiment to photoelectron spectroscopy becomes feasible. The development of the experimental technology for inverse photoelectron spectroscopy has been carried out energetically by many research groups so far. At present, the heightening of resolution of inverse photoelectron spectroscopy, the development of inverse photoelectron spectroscope in which light energy is variable and so on are carried out. But the inverse photoelectron spectroscope for vacuum ultraviolet region is not on the market. In this report, the principle of inverse photoelectron spectroscopy and the present state of the spectroscope are described, and the direction of the development hereafter is groped. As the experimental equipment, electron guns, light detectors and so on are explained. As the examples of the experiment, the inverse photoelectron spectroscopy of semimagnetic semiconductors and resonance inverse photoelectron spectroscopy are reported. (K.I.)

  8. Direct Visualization of De novo Lipogenesis in Single Living Cells

    Science.gov (United States)

    Li, Junjie; Cheng, Ji-Xin

    2014-10-01

    Increased de novo lipogenesis is being increasingly recognized as a hallmark of cancer. Despite recent advances in fluorescence microscopy, autoradiography and mass spectrometry, direct observation of de novo lipogenesis in living systems remains to be challenging. Here, by coupling stimulated Raman scattering (SRS) microscopy with isotope labeled glucose, we were able to trace the dynamic metabolism of glucose in single living cells with high spatial-temporal resolution. As the first direct visualization, we observed that glucose was largely utilized for lipid synthesis in pancreatic cancer cells, which occurs at a much lower rate in immortalized normal pancreatic epithelial cells. By inhibition of glycolysis and fatty acid synthase (FAS), the key enzyme for fatty acid synthesis, we confirmed the deuterium labeled lipids in cancer cells were from de novo lipid synthesis. Interestingly, we also found that prostate cancer cells exhibit relatively lower level of de novo lipogenesis, but higher fatty acid uptake compared to pancreatic cancer cells. Together, our results demonstrate a valuable tool to study dynamic lipid metabolism in cancer and other disorders.

  9. Response monitoring in de novo patients with Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Rita Willemssen

    Full Text Available BACKGROUND: Parkinson's disease (PD is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD". METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

  10. Precise detection of de novo single nucleotide variants in human genomes.

    Science.gov (United States)

    Gómez-Romero, Laura; Palacios-Flores, Kim; Reyes, José; García, Delfino; Boege, Margareta; Dávila, Guillermo; Flores, Margarita; Schatz, Michael C; Palacios, Rafael

    2018-05-07

    The precise determination of de novo genetic variants has enormous implications across different fields of biology and medicine, particularly personalized medicine. Currently, de novo variations are identified by mapping sample reads from a parent-offspring trio to a reference genome, allowing for a certain degree of differences. While widely used, this approach often introduces false-positive (FP) results due to misaligned reads and mischaracterized sequencing errors. In a previous study, we developed an alternative approach to accurately identify single nucleotide variants (SNVs) using only perfect matches. However, this approach could be applied only to haploid regions of the genome and was computationally intensive. In this study, we present a unique approach, coverage-based single nucleotide variant identification (COBASI), which allows the exploration of the entire genome using second-generation short sequence reads without extensive computing requirements. COBASI identifies SNVs using changes in coverage of exactly matching unique substrings, and is particularly suited for pinpointing de novo SNVs. Unlike other approaches that require population frequencies across hundreds of samples to filter out any methodological biases, COBASI can be applied to detect de novo SNVs within isolated families. We demonstrate this capability through extensive simulation studies and by studying a parent-offspring trio we sequenced using short reads. Experimental validation of all 58 candidate de novo SNVs and a selection of non-de novo SNVs found in the trio confirmed zero FP calls. COBASI is available as open source at https://github.com/Laura-Gomez/COBASI for any researcher to use. Copyright © 2018 the Author(s). Published by PNAS.

  11. De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

    DEFF Research Database (Denmark)

    2014-01-01

    in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p...... = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have...... analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1...

  12. Calculation of the inverse data space via sparse inversion

    KAUST Repository

    Saragiotis, Christos

    2011-01-01

    The inverse data space provides a natural separation of primaries and surface-related multiples, as the surface multiples map onto the area around the origin while the primaries map elsewhere. However, the calculation of the inverse data is far from trivial as theory requires infinite time and offset recording. Furthermore regularization issues arise during inversion. We perform the inversion by minimizing the least-squares norm of the misfit function by constraining the $ell_1$ norm of the solution, being the inverse data space. In this way a sparse inversion approach is obtained. We show results on field data with an application to surface multiple removal.

  13. Defining the maize transcriptome de novo using deep RNA-Seq

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

    2011-06-01

    De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

  14. Defining the maize transcriptome de novo using deep RNA-Seq

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Jeffrey; Gross, Stephen; Choi, Cindy; Zhang, Tao; Lindquist, Erika; Wei, Chia-Lin; Wang, Zhong

    2011-06-02

    De novo assembly of the transcriptome is crucial for functional genomics studies in bioenergy research, since many of the organisms lack high quality reference genomes. In a previous study we successfully de novo assembled simple eukaryote transcriptomes exclusively from short Illumina RNA-Seq reads [1]. However, extensive alternative splicing, present in most of the higher eukaryotes, poses a significant challenge for current short read assembly processes. Furthermore, the size of next-generation datasets, often large for plant genomes, presents an informatics challenge. To tackle these challenges we present a combined experimental and informatics strategy for de novo assembly in higher eukaryotes. Using maize as a test case, preliminary results suggest our approach can resolve transcript variants and improve gene annotations.

  15. Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

    Science.gov (United States)

    Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

    2008-01-01

    Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

  16. Novos paradigmas literários

    Directory of Open Access Journals (Sweden)

    Denise Azevedo Duarte Guimarães

    2005-12-01

    Full Text Available O artigo estuda a emergência de novos paradigmas literários, procurando refletir acerca das textualidades contemporâneas. Focaliza os hipertextos informatizados e a poesia multimídia, com o intuito de desvendar como estão sendo criados novos procedimentos expressivos e em que medida eles podem ser identificados com reflexões teóricas anteriores acerca do texto literário impresso. Remete a questões ligadas à leitura dos diferentes tipos de signos e aos modos como eles se integram para a constituição dessas novíssimas linguagens híbridas em novos suportes.El artículo estudia la emergencia de nuevos paradigmas literarios, procurando reflejar acerca de las textualidades contemporáneas. Enfoca los hipertextos informatizados y la poesía multimedia, intentando desvendar cómo están siendo creados nuevos procedimientos expresivos y en qué medida ellos pueden ser identificados a reflexiones teóricas anteriores acerca del texto literario impreso. Remite a cuestiones ligadas a la lectura de los diferentes tipos de signos y a los modos cómo ellos se interaccionan para la constitución de los novísimos lenguajes híbridos en nuevos supuestos.This article investigates the emergence of new literary paradigms as it tries to understand new contemporary textualities. It analyses some hypertexts and multimedia poetry trying to trace how new expressive procedures are being created. How can these new languages be identified and what are their relations to previous theories which dealt with the literary printed text? This study approaches questions linked to the reading of different types of signs and the modes they function towards the fabrication of these new hybrid languages.

  17. A Public Trial De Novo

    DEFF Research Database (Denmark)

    Vedel, Jane Bjørn; Gad, Christopher

    2011-01-01

    This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial” w.......” The article ends with a discussion of some implications of the analysis, including that policy making, academic research, and public debates might benefit from more detailed accounts of interests and stakes.......This article addresses the concept of “industrial interests” and examines its role in a topical controversy about a large research grant from a private foundation, the Novo Nordisk Foundation, to the University of Copenhagen. The authors suggest that the debate took the form of a “public trial......” where the grant and close(r) intermingling between industry and public research was prosecuted and defended. First, the authors address how the grant was framed in the media. Second, they redescribe the case by introducing new “evidence” that, because of this framing, did not reach “the court...

  18. Web Access to Digitised Content of the Exhibition Novo Mesto 1848-1918 at the Dolenjska Museum, Novo Mesto

    Directory of Open Access Journals (Sweden)

    Majda Pungerčar

    2013-09-01

    Full Text Available EXTENDED ABSTRACTFor the first time, the Dolenjska museum Novo mesto provided access to digitised museum resources when they took the decision to enrich the exhibition Novo mesto 1848-1918 by adding digital content. The following goals were identified: the digital content was created at the time of exhibition planning and design, it met the needs of different age groups of visitors, and during the exhibition the content was accessible via touch screen. As such, it also served for educational purposes (content-oriented lectures or problem solving team work. In the course of exhibition digital content was accessible on the museum website http://www.novomesto1848-1918.si. The digital content was divided into the following sections: the web photo gallery, the quiz and the game. The photo gallery was designed in the same way as the exhibition and the print catalogue and extended by the photos of contemporary Novo mesto and accompanied by the music from the orchestron machine. The following themes were outlined: the Austrian Empire, the Krka and Novo mesto, the town and its symbols, images of the town and people, administration and economy, social life and Novo mesto today followed by digitised archive materials and sources from that period such as the Commemorative book of the Uniformed Town Guard, the National Reading Room Guest Book, the Kazina guest book, the album of postcards and the Diploma of Honoured Citizen Josip Gerdešič. The Web application was also a tool for a simple and on line selection of digitised material and the creation of new digital content which proved to be much more convenient for lecturing than Power Point presentations. The quiz consisted of 40 questions relating to the exhibition theme and the catalogue. Each question offered a set of three answers only one of them being correct and illustrated by photography. The application auto selected ten questions and valued the answers immediately. The quiz could be accessed

  19. Recurrence risk in de novo structural chromosomal rearrangements.

    Science.gov (United States)

    Röthlisberger, Benno; Kotzot, Dieter

    2007-08-01

    According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

  20. Generative Recurrent Networks for De Novo Drug Design.

    Science.gov (United States)

    Gupta, Anvita; Müller, Alex T; Huisman, Berend J H; Fuchs, Jens A; Schneider, Petra; Schneider, Gisbert

    2018-01-01

    Generative artificial intelligence models present a fresh approach to chemogenomics and de novo drug design, as they provide researchers with the ability to narrow down their search of the chemical space and focus on regions of interest. We present a method for molecular de novo design that utilizes generative recurrent neural networks (RNN) containing long short-term memory (LSTM) cells. This computational model captured the syntax of molecular representation in terms of SMILES strings with close to perfect accuracy. The learned pattern probabilities can be used for de novo SMILES generation. This molecular design concept eliminates the need for virtual compound library enumeration. By employing transfer learning, we fine-tuned the RNN's predictions for specific molecular targets. This approach enables virtual compound design without requiring secondary or external activity prediction, which could introduce error or unwanted bias. The results obtained advocate this generative RNN-LSTM system for high-impact use cases, such as low-data drug discovery, fragment based molecular design, and hit-to-lead optimization for diverse drug targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  1. NovoTTF™-100A System (Tumor Treating Fields) transducer array layout planning for glioblastoma: a NovoTAL™ system user study.

    Science.gov (United States)

    Chaudhry, Aafia; Benson, Laura; Varshaver, Michael; Farber, Ori; Weinberg, Uri; Kirson, Eilon; Palti, Yoram

    2015-11-11

    Optune™, previously known as the NovoTTF-100A System™, generates Tumor Treating Fields (TTFields), an effective anti-mitotic therapy for glioblastoma. The system delivers intermediate frequency, alternating electric fields to the supratentorial brain. Patient therapy is personalized by configuring transducer array layout placement on the scalp to the tumor site using MRI measurements and the NovoTAL System. Transducer array layout mapping optimizes therapy by maximizing electric field intensity to the tumor site. This study evaluated physician performance in conducting transducer array layout mapping using the NovoTAL System compared with mapping performed by the Novocure in-house clinical team. Fourteen physicians (7 neuro-oncologists, 4 medical oncologists, and 3 neurosurgeons) evaluated five blinded cases of recurrent glioblastoma and performed head size and tumor location measurements using a standard Digital Imaging and Communications in Medicine reader. Concordance with Novocure measurement and intra- and inter-rater reliability were assessed using relevant correlation coefficients. The study criterion for success was a concordance correlation coefficient (CCC) >0.80. CCC for each physician versus Novocure on 20 MRI measurements was 0.96 (standard deviation, SD ± 0.03, range 0.90-1.00), indicating very high agreement between the two groups. Intra- and inter-rater reliability correlation coefficients were similarly high: 0.83 (SD ±0.15, range 0.54-1.00) and 0.80 (SD ±0.18, range 0.48-1.00), respectively. This user study demonstrated an excellent level of concordance between prescribing physicians and Novocure in-house clinical teams in performing transducer array layout planning. Intra-rater reliability was very high, indicating reproducible performance. Physicians prescribing TTFields, when trained on the NovoTAL System, can independently perform transducer array layout mapping required for the initiation and maintenance of patients on TTFields

  2. A Terra em Transe: o cosmopolitismo às avessas do cinema novo

    Directory of Open Access Journals (Sweden)

    Angela Prysthon

    2008-11-01

    Full Text Available Usando como referencial teórico os estudos culturais, este artigo analisa o cinema novo brasileiro como parte de uma estratégia terceiro mundista de conceber a cultura. A partir da emergência do conceito de terceiro mundo e das lutas de descolonização nos anos 1950 e 1960, a ideologia cosmopolita foi sendo vista pelos intelectuais de esquerda como a versão cultural da aliança com as forças hegemônicas da Europa e dos Estados Unidos. O projeto do cinema novo chama a atenção por suas afinidades ideológicas com o terceiro mundismo, mas, paradoxalmente, trazendo à tona uma polí­tica cosmopolita da periferia. Palavras-chave cinema novo, identidade, cultura brasileira, terceiro mundismo, estudos culturais. Abstract Using the cultural studies theoretical framework, this paper analyzes the cinema novo movement in Brazil as a part of the Third World conception of culture. Following the creation of the term "Third World" and the international politics of colonial independence of the 1950s and 1960s, a cosmopolitan attitude was seen by the intellectuals of the left as a cultural version of the alliance with the hegemonic forces of Europe and North America. Even though the cinema novo project can be associated with the ideology of an united Third World ,it brings about, paradoxically, a very cosmopolitan politics of the periphery. Key words cinema novo, identity, Brazilian culture, third world, cultural studies.

  3. Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

    Science.gov (United States)

    Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

    2015-02-01

    De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

  4. De novo autoimmune hepatitis after liver transplantation.

    Science.gov (United States)

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

    2007-10-01

    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

  5. A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

    Science.gov (United States)

    Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

    2016-08-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

  6. Arginine de novo and nitric oxide production in disease states

    OpenAIRE

    Luiking, Yvette C.; Ten Have, Gabriella A. M.; Wolfe, Robert R.; Deutz, Nicolaas E. P.

    2012-01-01

    Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin ...

  7. De novo FBXO11 mutations are associated with intellectual disability and behavioural anomalies.

    Science.gov (United States)

    Fritzen, Daniel; Kuechler, Alma; Grimmel, Mona; Becker, Jessica; Peters, Sophia; Sturm, Marc; Hundertmark, Hela; Schmidt, Axel; Kreiß, Martina; Strom, Tim M; Wieczorek, Dagmar; Haack, Tobias B; Beck-Wödl, Stefanie; Cremer, Kirsten; Engels, Hartmut

    2018-05-01

    Intellectual disability (ID) has an estimated prevalence of 1.5-2%. In most affected individuals, its genetic basis remains unclear. Whole exome sequencing (WES) studies have identified a multitude of novel causative gene defects and have shown that a large proportion of sporadic ID cases results from de novo mutations. Here, we present two unrelated individuals with similar clinical features and deleterious de novo variants in FBXO11 detected by WES. Individual 1, a 14-year-old boy, has mild ID as well as mild microcephaly, corrected cleft lip and alveolus, hyperkinetic disorder, mild brain atrophy and minor facial dysmorphism. WES detected a heterozygous de novo 1 bp insertion in the splice donor site of exon 3. Individual 2, a 3-year-old boy, showed ID and pre- and postnatal growth retardation, postnatal mild microcephaly, hyperkinetic and restless behaviour, as well as mild dysmorphism. WES detected a heterozygous de novo frameshift mutation. While ten individuals with ID and de novo variants in FBXO11 have been reported as part of larger studies, only one of the reports has some additional clinical data. Interestingly, the latter individual carries the identical mutation as our individual 2 and also displays ID, intrauterine growth retardation, microcephaly, behavioural anomalies, and dysmorphisms. Thus, we confirm deleterious de novo mutations in FBXO11 as a cause of ID and start the delineation of the associated clinical picture which may also comprise postnatal microcephaly or borderline small head size and behavioural anomalies.

  8. Angle-domain inverse scattering migration/inversion in isotropic media

    Science.gov (United States)

    Li, Wuqun; Mao, Weijian; Li, Xuelei; Ouyang, Wei; Liang, Quan

    2018-07-01

    The classical seismic asymptotic inversion can be transformed into a problem of inversion of generalized Radon transform (GRT). In such methods, the combined parameters are linearly attached to the scattered wave-field by Born approximation and recovered by applying an inverse GRT operator to the scattered wave-field data. Typical GRT-style true-amplitude inversion procedure contains an amplitude compensation process after the weighted migration via dividing an illumination associated matrix whose elements are integrals of scattering angles. It is intuitional to some extent that performs the generalized linear inversion and the inversion of GRT together by this process for direct inversion. However, it is imprecise to carry out such operation when the illumination at the image point is limited, which easily leads to the inaccuracy and instability of the matrix. This paper formulates the GRT true-amplitude inversion framework in an angle-domain version, which naturally degrades the external integral term related to the illumination in the conventional case. We solve the linearized integral equation for combined parameters of different fixed scattering angle values. With this step, we obtain high-quality angle-domain common-image gathers (CIGs) in the migration loop which provide correct amplitude-versus-angle (AVA) behavior and reasonable illumination range for subsurface image points. Then we deal with the over-determined problem to solve each parameter in the combination by a standard optimization operation. The angle-domain GRT inversion method keeps away from calculating the inaccurate and unstable illumination matrix. Compared with the conventional method, the angle-domain method can obtain more accurate amplitude information and wider amplitude-preserved range. Several model tests demonstrate the effectiveness and practicability.

  9. Airline Maintenance Manpower Optimization from the De Novo Perspective

    Science.gov (United States)

    Liou, James J. H.; Tzeng, Gwo-Hshiung

    Human resource management (HRM) is an important issue for today’s competitive airline marketing. In this paper, we discuss a multi-objective model designed from the De Novo perspective to help airlines optimize their maintenance manpower portfolio. The effectiveness of the model and solution algorithm is demonstrated in an empirical study of the optimization of the human resources needed for airline line maintenance. Both De Novo and traditional multiple objective programming (MOP) methods are analyzed. A comparison of the results with those of traditional MOP indicates that the proposed model and solution algorithm does provide better performance and an improved human resource portfolio.

  10. Modular Engineering Concept at Novo Nordisk Engineering

    DEFF Research Database (Denmark)

    Moelgaard, Gert; Miller, Thomas Dedenroth

    1997-01-01

    This report describes the concept of a new engineering method at Novo Nordisk Engineering: Modular Engineering (ME). Three tools are designed to support project phases with different levels of detailing and abstraction. ME supports a standard, cross-functional breakdown of projects that facilitates...

  11. De novo synthesis of adenine nucleotides in different skeletal muscle fiber types

    International Nuclear Information System (INIS)

    Tullson, P.C.; John-Alder, H.B.; Hood, D.A.; Terjung, R.L.

    1988-01-01

    Management of adenine nucleotide catabolism differs among skeletal muscle fiber types. This study evaluated whether there are corresponding differences in the rates of de novo synthesis of adenine nucleotide among fiber type sections of skeletal muscle using an isolated perfused rat hindquarter preparation. Label incorporation into adenine nucleotides from the [1-14C]glycine precursor was determined and used to calculate synthesis rates based on the intracellular glycine specific radioactivity. Results show that intracellular glycine is closely related to the direct precursor pool. Rates of de novo synthesis were highest in fast-twitch red muscle (57.0 +/- 4.0, 58.2 +/- 4.4 nmol.h-1.g-1; deep red gastrocnemius and vastus lateralis), relatively high in slow-twitch red muscle (47.0 +/- 3.1; soleus), and low in fast-twitch white muscle (26.1 +/- 2.0 and 21.6 +/- 2.3; superficial white gastrocnemius and vastus lateralis). Rates for four mixed muscles were intermediate, ranging between 32.3 and 37.3. Specific de novo synthesis rates exhibited a strong correlation (r = 0.986) with muscle section citrate synthase activity. Turnover rates (de novo synthesis rate/adenine nucleotide pool size) were highest in high oxidative muscle (0.82-1.06%/h), lowest in low oxidative muscle (0.30-0.35%/h), and intermediate in mixed muscle (0.44-0.55%/h). Our results demonstrate that differences in adenine nucleotide management among fiber types extends to the process of de novo adenine nucleotide synthesis

  12. Wegener's granulomatosis occurring de novo during pregnancy.

    Science.gov (United States)

    Alfhaily, F; Watts, R; Leather, A

    2009-01-01

    Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients.

  13. De novo ORFs in Drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences.

    Directory of Open Access Journals (Sweden)

    Josephine A Reinhardt

    Full Text Available How non-coding DNA gives rise to new protein-coding genes (de novo genes is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution of an open reading frame. In contrast, four other de novo genes evolved a translated open reading frame and transcription within the same evolutionary interval suggesting that nascent open reading frames (proto-ORFs, while not required, can contribute to the emergence of a new de novo gene. However, none of the genes arose from proto-ORFs that existed long before expression evolved. Sequence and structural evolution of de novo genes was rapid compared to nearby genes and the structural complexity of de novo genes steadily increases over evolutionary time. Despite the fact that these genes are transcribed at a higher level in males than females, and are most strongly expressed in testes, RNAi experiments show that most of these genes are essential in both sexes during metamorphosis. This lethality suggests that protein coding de novo genes in Drosophila quickly become functionally important.

  14. Inversions

    Science.gov (United States)

    Brown, Malcolm

    2009-01-01

    Inversions are fascinating phenomena. They are reversals of the normal or expected order. They occur across a wide variety of contexts. What do inversions have to do with learning spaces? The author suggests that they are a useful metaphor for the process that is unfolding in higher education with respect to education. On the basis of…

  15. Persistent hyperthyroidism and de novo Graves' ophthalmopathy after total thyroidectomy.

    Science.gov (United States)

    Tay, Wei Lin; Loh, Wann Jia; Lee, Lianne Ai Ling; Chng, Chiaw Ling

    2017-01-01

    We report a patient with Graves' disease who remained persistently hyperthyroid after a total thyroidectomy and also developed de novo Graves' ophthalmopathy 5 months after surgery. She was subsequently found to have a mature cystic teratoma containing struma ovarii after undergoing a total hysterectomy and salpingo-oophorectomy for an incidental ovarian lesion. It is important to investigate for other causes of primary hyperthyroidism when thyrotoxicosis persists after total thyroidectomy.TSH receptor antibody may persist after total thyroidectomy and may potentially contribute to the development of de novo Graves' ophthalmopathy.

  16. Selecting Superior De Novo Transcriptome Assemblies: Lessons Learned by Leveraging the Best Plant Genome.

    Directory of Open Access Journals (Sweden)

    Loren A Honaas

    Full Text Available Whereas de novo assemblies of RNA-Seq data are being published for a growing number of species across the tree of life, there are currently no broadly accepted methods for evaluating such assemblies. Here we present a detailed comparison of 99 transcriptome assemblies, generated with 6 de novo assemblers including CLC, Trinity, SOAP, Oases, ABySS and NextGENe. Controlled analyses of de novo assemblies for Arabidopsis thaliana and Oryza sativa transcriptomes provide new insights into the strengths and limitations of transcriptome assembly strategies. We find that the leading assemblers generate reassuringly accurate assemblies for the majority of transcripts. At the same time, we find a propensity for assemblers to fail to fully assemble highly expressed genes. Surprisingly, the instance of true chimeric assemblies is very low for all assemblers. Normalized libraries are reduced in highly abundant transcripts, but they also lack 1000s of low abundance transcripts. We conclude that the quality of de novo transcriptome assemblies is best assessed through consideration of a combination of metrics: 1 proportion of reads mapping to an assembly 2 recovery of conserved, widely expressed genes, 3 N50 length statistics, and 4 the total number of unigenes. We provide benchmark Illumina transcriptome data and introduce SCERNA, a broadly applicable modular protocol for de novo assembly improvement. Finally, our de novo assembly of the Arabidopsis leaf transcriptome revealed ~20 putative Arabidopsis genes lacking in the current annotation.

  17. Role of de novo biosynthesis in ecosystem scale monoterpene emissions from a boreal Scots pine forest

    Directory of Open Access Journals (Sweden)

    R. Taipale

    2011-08-01

    Full Text Available Monoterpene emissions from Scots pine have traditionally been assumed to originate as evaporation from specialized storage pools. More recently, the significance of de novo emissions, originating directly from monoterpene biosynthesis, has been recognized. To study the role of biosynthesis at the ecosystem scale, we measured monoterpene emissions from a Scots pine dominated forest in southern Finland using the disjunct eddy covariance method combined with proton transfer reaction mass spectrometry. The interpretation of the measurements was based on a correlation analysis and a hybrid emission algorithm describing both de novo and pool emissions. During the measurement period May–August 2007, the monthly medians of daytime emissions were 200, 290, 180, and 200 μg m−2 h−1. The emissions were partly light dependent, probably due to de novo biosynthesis. The emission potential for both de novo and pool emissions exhibited a decreasing summertime trend. The ratio of the de novo emission potential to the total emission potential varied between 30 % and 46 %. Although the monthly changes were not significant, the ratio always differed statistically from zero, suggesting that the role of de novo biosynthesis was observable. Given the uncertainties in this study, we conclude that more accurate estimates of the contribution of de novo emissions are required for improving monoterpene emission algorithms for Scots pine dominated forests.

  18. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    DEFF Research Database (Denmark)

    Hoischen, Alexander; van Bon, Bregje W M; Rodríguez-Santiago, Benjamín

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which...... is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous....

  19. Automated de novo phasing and model building of coiled-coil proteins.

    Science.gov (United States)

    Rämisch, Sebastian; Lizatović, Robert; André, Ingemar

    2015-03-01

    Models generated by de novo structure prediction can be very useful starting points for molecular replacement for systems where suitable structural homologues cannot be readily identified. Protein-protein complexes and de novo-designed proteins are examples of systems that can be challenging to phase. In this study, the potential of de novo models of protein complexes for use as starting points for molecular replacement is investigated. The approach is demonstrated using homomeric coiled-coil proteins, which are excellent model systems for oligomeric systems. Despite the stereotypical fold of coiled coils, initial phase estimation can be difficult and many structures have to be solved with experimental phasing. A method was developed for automatic structure determination of homomeric coiled coils from X-ray diffraction data. In a benchmark set of 24 coiled coils, ranging from dimers to pentamers with resolutions down to 2.5 Å, 22 systems were automatically solved, 11 of which had previously been solved by experimental phasing. The generated models contained 71-103% of the residues present in the deposited structures, had the correct sequence and had free R values that deviated on average by 0.01 from those of the respective reference structures. The electron-density maps were of sufficient quality that only minor manual editing was necessary to produce final structures. The method, named CCsolve, combines methods for de novo structure prediction, initial phase estimation and automated model building into one pipeline. CCsolve is robust against errors in the initial models and can readily be modified to make use of alternative crystallographic software. The results demonstrate the feasibility of de novo phasing of protein-protein complexes, an approach that could also be employed for other small systems beyond coiled coils.

  20. De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

    Science.gov (United States)

    Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

    2017-09-15

    The thyroid gland secretes primarily tetraiodothyronine (T 4 ), and some triiodothyronine (T 3 ). Under normal physiological circumstances, only one-fifth of circulating T 3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T 3 toxicosis. Thyroidal T 4 production results from iodination of thyroglobulin (TG) at residues Tyr 5 and Tyr 130 , whereas thyroidal T 3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T 3 is formed de novo independently of deiodination from T 4 We found that upon iodination in vitro , de novo T 3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T 3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T 3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T 3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T 3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T 3 formation, contributing to the relative T 3 toxicosis of Graves' disease.

  1. The impact of employee satisfaction on productivity in Tiskarna Novo mesto, Ltd.

    Directory of Open Access Journals (Sweden)

    Simona Cimperman

    2016-06-01

    Full Text Available Research Question: Does employee satisfaction, impact on productivity? How are these two variables associated? What is the job satisfaction in Tiskarna Novo mesto, Ltd. What needs to be done to make employees more satisfied at work and, consequently, more productive? Purpose: The purpose of the study is to determine what are the factors that influence employee satisfaction Tiskarna Novo mesto, Ltd. and check the connection between work satisfaction and employee productivity. The aim of the research is to examine what is the level of job satisfaction of employees in Tiskarna Novo mesto, Ltd. And find our reasons and factors that prevent employees were satisfied in the workplace. Method: In this study we used a descriptive method and the method of combining the study of domestic and foreign literature. Pending the results we have come to interview employees in the Tiskarna Novo mesto, Ltd. Results: We conducted a survey among employees in Tiskarna Novo mesto, Ltd and we came to the conclusion that the employees are medium satisfied – the average grade point job satisfaction of employees was 3.1 (evaluated on a 5-point Likert scale. The worst assessed was factor in job satisfaction opportunity for advancement and educational opportunities. We have found out that factors like receiving praise and awards as well as good interpersonal relations are those that affect good on job satisfaction, on the other hand conflict is the one that reduces job satisfaction. The existence of links between work satisfaction and productivity were not found (r = -0.061. Organization: The organization and managers, it is important to know which are the factors by which employees are satisfied or dissatisfied. Results of the research will give managers a clear picture of the factors of satisfaction / dissatisfaction and opinion on productivity. Society: The employees it means a lot to have your job satisfaction and consequently they are more productive. Originality: The

  2. Interplay between De Novo Biosynthesis and Sequestration of Cyanogenic Glucosides in Arthropods

    DEFF Research Database (Denmark)

    Fürstenberg-Hägg, Joel

    (Zygaenidae, Lepidoptera) both sequester (take up and accumulate) the CNglcs linamarin and lotaustralin from their food plants (Fabacea) and biosynthesize them de novo from valine and isoleucine. The presented research demonstrates that de novo biosynthesis of CNglcs in Z. filipendulae is dependent...

  3. Polytene chromosomes of monogenic and amphogenic Chrysomya species (Calliphoridae, Diptera): analysis of banding patterns and in situ hybridization with Drosophila sex determining gene sequences.

    Science.gov (United States)

    Puchalla, S

    1994-03-01

    Standard maps for the five banded polytene chromosomes found in trichogen cell nuclei of the monogenic blowfly Chrysomya rufifacies and the amphogenic Chrysomya pinguis are presented. The chromosomes are highly homologous in the two species; differences in banding patterns are predominantly caused by one pericentric and ten paracentric inversions. In chromosome 5 of the amphogenic Chrysomya phaonis, also analysed in this paper, an additional paracentric inversion was observed. The distribution of species specific inversions indicates that the monogenic C. rufifacies is phylogenetically older than the amphogenic species. The maternal sex realizer locus F'/f on polytene chromosome 5 of C. rufifacies is not associated with a structural heterozygosity. Chromosome pair 6 of C. rufifacies and the sex chromosome pair of C. pinguis are under-replicated in polytene nuclei; they consist of irregular chromatin granules, frequently associated with nucleolus material. Evolution of heteromorphic sex chromosomes in Chrysomya is probably correlated with heterochromatin accumulation. A search for sex determining genes in Chrysomya was initiated using sex determining sequences from Drosophila melanogaster for in situ hybridization. The polytene band 41A1 on chromosome 5 of monogenic and amphogenic Chrysomya species contains sequences homologous to the maternal sex determining gene daughterless (da). Homology to the zygotic gene Sex-lethal (Sxl) of Drosophila is detected in band 39A1 on chromosome 5 of C. rufifacies. The findings reported here are the first evidence for a possible homology between the da gene of Drosophila and the maternal sex realizer F' of C. rufifacies. An hypothesis for the evolution of the maternal effect sex determination of C. rufifacies is proposed.

  4. Novo Jornalismo: fronteiras litero-factuais em A sangue Frio e em Radical Chique

    Directory of Open Access Journals (Sweden)

    Francisco Aquinei Timóteo Queirós

    2012-12-01

    Full Text Available A pesquisa busca analisar de que forma fato e ficção se entrecruzam no “movimento” do Novo Jornalismo, a partir das obras A sangue Frio e Radical Chique e o Novo Jornalismo, de Truman Capote e Tom Wolfe, respectivamente. Pretende-se, a partir da investigação do corpus em estudo, revelar os aspectos que aproximam o fato jornalístico, a notícia e a reportagem às técnicas literárias do romance, do conto e da crônica. O estudo investiga o Novo Jornalismo sob o viés de textos centrais das áreas de teoria literária e estudos jornalísticos utilizando autores como Mikhail Bakhtin, Hayden White, Paul Ricoeur, Muniz Sodré; além de referenciar outros escritores que, como Tom Wolfe e Truman Capote, fizeram parte de um grande movimento renovador do jornalismo literário nos anos 1950, 1960 e 1970 chamado, genericamente, de Novo Jornalismo.

  5. Demanda dos principais metais e novos materiais : analise de tendencias

    OpenAIRE

    Wilson Trigueiro de Sousa

    1990-01-01

    Resumo: Neste trabalho são analisadas algumas tendências na área de novos materiais na tentativa de obter um melhor entendimento das repercussões das atuais inovações tecnológicas para o setor mineral. Inicialmente são revisados os principais estudos sobre as mudanças ocorridas por volta de 1972/74 no comportamento da demanda dos metais mais importantes. Entre as possíveis causas, está o progresso técnico, que tornou possível o surgimento de novos materiais e o aperfeiçoamento de outros em us...

  6. Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

    DEFF Research Database (Denmark)

    Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

    2017-01-01

    or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

  7. Generalized inverses theory and computations

    CERN Document Server

    Wang, Guorong; Qiao, Sanzheng

    2018-01-01

    This book begins with the fundamentals of the generalized inverses, then moves to more advanced topics. It presents a theoretical study of the generalization of Cramer's rule, determinant representations of the generalized inverses, reverse order law of the generalized inverses of a matrix product, structures of the generalized inverses of structured matrices, parallel computation of the generalized inverses, perturbation analysis of the generalized inverses, an algorithmic study of the computational methods for the full-rank factorization of a generalized inverse, generalized singular value decomposition, imbedding method, finite method, generalized inverses of polynomial matrices, and generalized inverses of linear operators. This book is intended for researchers, postdocs, and graduate students in the area of the generalized inverses with an undergraduate-level understanding of linear algebra.

  8. On the performance of de novo pathway enrichment

    DEFF Research Database (Denmark)

    Batra, Richa; Alcaraz, Nicolas; Gitzhofer, Kevin

    2017-01-01

    De novo pathway enrichment is a powerful approach to discover previously uncharacterized molecular mechanisms in addition to already known pathways. To achieve this, condition-specific functional modules are extracted from large interaction networks. Here, we give an overview of the state...

  9. Transferência do fator caturra para o cultivar Mundo Novo de Coffea arabica Transfer of the CT gene to Mundo Novo cultivar

    Directory of Open Access Journals (Sweden)

    A. Carvalho

    1972-01-01

    Full Text Available No presente trabalho são relatados os estudos realizados visando à introdução do gene Ct (caturra que contribui para reduzir a altura da planta, no cultivar Mundo" Novo de Coffea arabica.Estudaram-se, em ensaios de produtividade, as populações Fv F.,, F3 e F4. Nessas populações e principalmente entre os descendentes dos "caféeiros H 2077-2-5 e H 2077-2-12, foram selecionadas plantas homozigotas para os alelos Ct e também para os alelos responsáveis pela cor do fruto xc ou Xc. Essas combinações foram denominadas 'Catuaí Amarelo' e 'Catuaí Vermelho', respectivamente, e suas características são apresentadas. Os novos cultivares vêm-se mostrando de interesse econômico para as regiões cafeeiras não somente pelo porte pequeno, mas também pela produtividade, pelo vigor vegetativo e pela precocidade.The successful transfer of the Ct gene for short internode to the tall cultivar of Coffea arábica'Mundo Novo' is reported. Individual selections were carried out in the F1, F2, F3 and F4 generations. It was found that early selection in the F2 generation was quite effective. A remarkably good correlation was found between productitivity of F2 plants and the yield of the F3 and F4 generations. Plants of the F4 generation have shown reasonable uniformity and high yield in several trials. The new selections showed to be early producers. Two new cultivars were released namely 'Catuaí Amarelo' and 'Catuaí Vermelho'. The former has yellow fruits whereas the latter has red fruits. The plants are much shorter that the ones of Mundo Novo. The new cultivars have a very strong secondary and tertiary branching. Because of these characteristics Catuaí Amarelo and Catuaí Vermelho are being planted in large scale replacing the tall cultivars.

  10. De Novo Glutamine Synthesis

    Science.gov (United States)

    He, Qiao; Shi, Xinchong; Zhang, Linqi; Yi, Chang; Zhang, Xuezhen

    2016-01-01

    Purpose: The aim of this study was to investigate the role of de novo glutamine (Gln) synthesis in the proliferation of C6 glioma cells and its detection with 13N-ammonia. Methods: Chronic Gln-deprived C6 glioma (0.06C6) cells were established. The proliferation rates of C6 and 0.06C6 cells were measured under the conditions of Gln deprivation along with or without the addition of ammonia or glutamine synthetase (GS) inhibitor. 13N-ammonia uptake was assessed in C6 cells by gamma counting and in rats with C6 and 0.06C6 xenografts by micro–positron emission tomography (PET) scanning. The expression of GS in C6 cells and xenografts was assessed by Western blotting and immunohistochemistry, respectively. Results: The Gln-deprived C6 cells showed decreased proliferation ability but had a significant increase in GS expression. Furthermore, we found that low concentration of ammonia was sufficient to maintain the proliferation of Gln-deprived C6 cells, and 13N-ammonia uptake in C6 cells showed Gln-dependent decrease, whereas inhibition of GS markedly reduced the proliferation of C6 cells as well as the uptake of 13N-ammoina. Additionally, microPET/computed tomography exhibited that subcutaneous 0.06C6 xenografts had higher 13N-ammonia uptake and GS expression in contrast to C6 xenografts. Conclusion: De novo Gln synthesis through ammonia–glutamate reaction plays an important role in the proliferation of C6 cells. 13N-ammonia can be a potential metabolic PET tracer for Gln-dependent tumors. PMID:27118759

  11. Some results on inverse scattering

    International Nuclear Information System (INIS)

    Ramm, A.G.

    2008-01-01

    A review of some of the author's results in the area of inverse scattering is given. The following topics are discussed: (1) Property C and applications, (2) Stable inversion of fixed-energy 3D scattering data and its error estimate, (3) Inverse scattering with 'incomplete' data, (4) Inverse scattering for inhomogeneous Schroedinger equation, (5) Krein's inverse scattering method, (6) Invertibility of the steps in Gel'fand-Levitan, Marchenko, and Krein inversion methods, (7) The Newton-Sabatier and Cox-Thompson procedures are not inversion methods, (8) Resonances: existence, location, perturbation theory, (9) Born inversion as an ill-posed problem, (10) Inverse obstacle scattering with fixed-frequency data, (11) Inverse scattering with data at a fixed energy and a fixed incident direction, (12) Creating materials with a desired refraction coefficient and wave-focusing properties. (author)

  12. A Joint Method of Envelope Inversion Combined with Hybrid-domain Full Waveform Inversion

    Science.gov (United States)

    CUI, C.; Hou, W.

    2017-12-01

    Full waveform inversion (FWI) aims to construct high-precision subsurface models by fully using the information in seismic records, including amplitude, travel time, phase and so on. However, high non-linearity and the absence of low frequency information in seismic data lead to the well-known cycle skipping problem and make inversion easily fall into local minima. In addition, those 3D inversion methods that are based on acoustic approximation ignore the elastic effects in real seismic field, and make inversion harder. As a result, the accuracy of final inversion results highly relies on the quality of initial model. In order to improve stability and quality of inversion results, multi-scale inversion that reconstructs subsurface model from low to high frequency are applied. But, the absence of very low frequencies (time domain and inversion in the frequency domain. To accelerate the inversion, we adopt CPU/GPU heterogeneous computing techniques. There were two levels of parallelism. In the first level, the inversion tasks are decomposed and assigned to each computation node by shot number. In the second level, GPU multithreaded programming is used for the computation tasks in each node, including forward modeling, envelope extraction, DFT (discrete Fourier transform) calculation and gradients calculation. Numerical tests demonstrated that the combined envelope inversion + hybrid-domain FWI could obtain much faithful and accurate result than conventional hybrid-domain FWI. The CPU/GPU heterogeneous parallel computation could improve the performance speed.

  13. De Novo Discovery of Structured ncRNA Motifs in Genomic Sequences

    DEFF Research Database (Denmark)

    Ruzzo, Walter L; Gorodkin, Jan

    2014-01-01

    De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphas...... on an approach based on the CMfinder CMfinder program as a case study. Applications to genomic screens for novel de novo structured ncRNA ncRNA s, including structured RNA elements in untranslated portions of protein-coding genes, are presented.......De novo discovery of "motifs" capturing the commonalities among related noncoding ncRNA structured RNAs is among the most difficult problems in computational biology. This chapter outlines the challenges presented by this problem, together with some approaches towards solving them, with an emphasis...

  14. Calculation of the inverse data space via sparse inversion

    KAUST Repository

    Saragiotis, Christos; Doulgeris, Panagiotis C.; Verschuur, Dirk Jacob Eric

    2011-01-01

    The inverse data space provides a natural separation of primaries and surface-related multiples, as the surface multiples map onto the area around the origin while the primaries map elsewhere. However, the calculation of the inverse data is far from

  15. Inverse Limits

    CERN Document Server

    Ingram, WT

    2012-01-01

    Inverse limits provide a powerful tool for constructing complicated spaces from simple ones. They also turn the study of a dynamical system consisting of a space and a self-map into a study of a (likely more complicated) space and a self-homeomorphism. In four chapters along with an appendix containing background material the authors develop the theory of inverse limits. The book begins with an introduction through inverse limits on [0,1] before moving to a general treatment of the subject. Special topics in continuum theory complete the book. Although it is not a book on dynamics, the influen

  16. Inverse problems of geophysics

    International Nuclear Information System (INIS)

    Yanovskaya, T.B.

    2003-07-01

    This report gives an overview and the mathematical formulation of geophysical inverse problems. General principles of statistical estimation are explained. The maximum likelihood and least square fit methods, the Backus-Gilbert method and general approaches for solving inverse problems are discussed. General formulations of linearized inverse problems, singular value decomposition and properties of pseudo-inverse solutions are given

  17. Acute puerperal uterine inversion

    International Nuclear Information System (INIS)

    Hussain, M.; Liaquat, N.; Noorani, K.; Bhutta, S.Z; Jabeen, T.

    2004-01-01

    Objective: To determine the frequency, causes, clinical presentations, management and maternal mortality associated with acute puerperal inversion of the uterus. Materials and Methods: All the patients who developed acute puerperal inversion of the uterus either in or outside the JPMC were included in the study. Patients of chronic uterine inversion were not included in the present study. Abdominal and vaginal examination was done to confirm and classify inversion into first, second or third degrees. Results: 57036 deliveries and 36 acute uterine inversions occurred during the study period, so the frequency of uterine inversion was 1 in 1584 deliveries. Mismanagement of third stage of labour was responsible for uterine inversion in 75% of patients. Majority of the patients presented with shock, either hypovolemic (69%) or neurogenic (13%) in origin. Manual replacement of the uterus under general anaesthesia with 2% halothane was successfully done in 35 patients (97.5%). Abdominal hysterectomy was done in only one patient. There were three maternal deaths due to inversion. Conclusion: Proper education and training regarding placental delivery, diagnosis and management of uterine inversion must be imparted to the maternity care providers especially to traditional birth attendants and family physicians to prevent this potentially life-threatening condition. (author)

  18. Novo Jornalismo: fronteiras litero-factuais em A sangue Frio e em Radical Chique

    Directory of Open Access Journals (Sweden)

    Francisco Aquinei Timóteo Queirós

    2012-03-01

    Full Text Available http://dx.doi.org/10.5007/1984-784X.2012v12n18p130 A pesquisa busca analisar de que forma fato e ficção se entrecruzam no “movimento” do Novo Jornalismo, a partir das obras A sangue Frio e Radical Chique e o Novo Jornalismo, de Truman Capote e Tom Wolfe, respectivamente. Pretende-se, a partir da investigação do corpus em estudo, revelar os aspectos que aproximam o fato jornalístico, a notícia e a reportagem às técnicas literárias do romance, do conto e da crônica. O estudo investiga o Novo Jornalismo sob o viés de textos centrais das áreas de teoria literária e estudos jornalísticos utilizando autores como Mikhail Bakhtin, Hayden White, Paul Ricoeur, Muniz Sodré; além de referenciar outros escritores que, como Tom Wolfe e Truman Capote, fizeram parte de um grande movimento renovador do jornalismo literário nos anos 1950, 1960 e 1970 chamado, genericamente, de Novo Jornalismo.

  19. Facebook - Um novo espaço autobiográfico?

    Directory of Open Access Journals (Sweden)

    Maria Tereza Lima

    2015-07-01

    Full Text Available O arigo "Facebook - Um novo espaço autobiográfico?" tem como objetivo central investigar como a perspectiva autobiográfica e biográfica se configura em uma rede social. Levando em consideração esse novo espaço de exteriorização da memória, analisamos as escolhas de uma pessoa ao postar os mais diversos gêneros textuais no Facebook e verificamos até que ponto tais fragmentos textuais narram a história de um indivíduo. Quais textos são postados? O que foi escolhido e o que foi excluído desse perfil? O autor trava um pacto de leitura com o leitor? Se levarmos em consideração que os textos postados nessa rede social são textos produzidos pelo próprio autor do perfil e de autores diversos, como configuraremos esses espaços virtuais? Autobiográficos e biográficos? Quem escreve a página virtual é o próprio autor do perfil ou múltiplos autores? Com as redes sociais, surge um novo modelo de autobiografia e de biógrafo? Esses e tantos outros questionamentos nortearam nossas investigações e permitiram-nos conhecer um pouco mais sobre as estratégias autobiográficas dos autores virtuais contemporâneos.

  20. De Novo Heart Failure After Kidney Transplantation: Trends in Incidence and Outcomes.

    Science.gov (United States)

    Lenihan, Colin R; Liu, Sai; Deswal, Anita; Montez-Rath, Maria E; Winkelmayer, Wolfgang C

    2018-03-29

    Heart failure is an important cause of morbidity and mortality following kidney transplantation. Some studies in the general population have shown that the incidence of heart failure has decreased during the past 20 years. However, it is not currently known whether such a trend exists in the kidney transplantation population. Retrospective observational cohort study. Adult patients included in the US Renal Data System who underwent their first kidney transplantation in the United States between 1998 and 2010 with at least 6 months of continuous Medicare parts A and B coverage before transplantation and no prior evidence for a diagnosis of heart failure before kidney transplantation. Calendar year of transplantation and calendar year of posttransplantation heart failure diagnosis. De novo posttransplantation heart failure defined using International Classification of Diseases, Ninth Revision diagnosis codes and mortality following de novo posttransplantation heart failure diagnosis. Secular trends in de novo post-kidney transplantation heart failure were examined using Cox proportional hazards analysis. Within a study cohort of 48,771 patients, 7,269 developed de novo heart failure within 3 years of kidney transplantation, with a median time to heart failure of 0.76 years. The adjusted HR for heart failure with death as competing risk comparing patients who underwent transplantation in 2010 with those who underwent transplantation in 1998 was 0.69 (95% CI, 0.60-0.79). No temporal trend in mortality following a diagnosis of post-kidney transplantation heart failure was observed. Potential residual confounding from either incorrectly ascertained or unavailable confounders. The cohort was limited to Medicare beneficiaries. Adjusted for demographic and clinical characteristics, the risk for developing de novo post-kidney transplantation heart failure has declined significantly between 1998 and 2010, with no apparent change in subsequent mortality. Copyright © 2018

  1. Inverse feasibility problems of the inverse maximum flow problems

    Indian Academy of Sciences (India)

    199–209. c Indian Academy of Sciences. Inverse feasibility problems of the inverse maximum flow problems. ADRIAN DEACONU. ∗ and ELEONOR CIUREA. Department of Mathematics and Computer Science, Faculty of Mathematics and Informatics, Transilvania University of Brasov, Brasov, Iuliu Maniu st. 50,. Romania.

  2. Photoreactivation of conversion and de novo suppressor mutation in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Bockrath, R C; Plamer, J E [Indiana Univ., Indianapolis (USA). Dept. of Microbiology

    1977-04-01

    Studies of mutagenesis and photoreactivation in various E.coli strains have shown that conversion mutation of a mutant containing an amber suppressor to one containing an ochre suppressor is sensitive to photoreactivation. Direct photoreactivation by photoreactivating light (PRL) after uv mutagenesis reduced mutation frequencies by a factor of about 2 for each minute of exposure during the first 5 to 8 min of exposure for cells with normal repair capacity. Conversion and potential de novo suppressor mutations were about equally sensitive. For conversion, the sensitivities to PRL were identical in the repair-normal and excisions-repair-deficient strains. For de novo suppressor mutation, the rate of mutation frequency reduction by PRL in the repair-deficient strain was about one-half that in the other strains. The results suggest that ultraviolet radiation produces both de novo suppressor mutation and conversion at the sup(E,B) locus by photoreversible pyrimidine dimers in the DNA. The causative dimers could be Thy()Cyt dimers in the transcribed strand or the non-transcribed strand, respectively.

  3. The Key Drivers behind Novo Nordisk’s Growth in the Diabetes Market in China

    Directory of Open Access Journals (Sweden)

    Hind Louiza CHITOUR

    2013-12-01

    Full Text Available To enter the Chinese Pharmaceutical market, “Big Pharma” has adopted different strategies to tackle the challenges specific to the country in terms of size, demographics, specific sales channels and logistics adjustments. While the majority of Global Pharmaceutical players have opted for an aggressive M&A approach to penetrate the Chinese market and gain local insight; the Danish Novo Nordisk has instead chosen a strategy focusing on innovation and developing its R&D structure to capitalize on the local talent pool. To illustrate Novo Nordisk’s growth strategy in the Mainland, we analyzed its competitiveness in the diabetes market by demonstrating the key drivers behind this success. We applied a various set of tools for this research: Novo Nordisk, Dong Bao Pharmaceutical executives’ interviews and personal observations accounting for the primary data, we also reviewed secondary data to perform a PEST analysis in addition to Porter’s competitive advantage model in order to extract the reasons behind Novo Nordisk’s marching success in the Mainland.

  4. Identifying wrong assemblies in de novo short read primary ...

    Indian Academy of Sciences (India)

    2016-08-05

    Aug 5, 2016 ... Most of these assemblies are done using some de novo short read assemblers and other related approaches. .... benchmarking projects like Assemblathon 1, Assemblathon ... from a large insert library (at least 1000 bases).

  5. Analysis of 60 706 Exomes Questions the Role of De Novo Variants Previously Implicated in Cardiac Disease

    DEFF Research Database (Denmark)

    Paludan-Müller, Christian; Ahlberg, Gustav; Ghouse, Jonas

    2017-01-01

    BACKGROUND: De novo variants in the exome occur at a rate of 1 per individual per generation, and because of the low reproductive fitness for de novo variants causing severe disease, the likelihood of finding these as standing variations in the general population is low. Therefore, this study...... sought to evaluate the pathogenicity of de novo variants previously associated with cardiac disease based on a large population-representative exome database. METHODS AND RESULTS: We performed a literature search for previous publications on de novo variants associated with severe arrhythmias...... trio studies (>1000 subjects). Of the monogenic variants, 11% (23/211) were present in ExAC, whereas 26% (802/3050) variants believed to increase susceptibility of disease were identified in ExAC. Monogenic de novo variants in ExAC had a total allele count of 109 and with ≈844 expected cases in Ex...

  6. De novo structural modeling and computational sequence analysis ...

    African Journals Online (AJOL)

    Different bioinformatics tools and machine learning techniques were used for protein structural classification. De novo protein modeling was performed by using I-TASSER server. The final model obtained was accessed by PROCHECK and DFIRE2, which confirmed that the final model is reliable. Until complete biochemical ...

  7. Similar prognosis of transformed and de novo diffuse large B-cell lymphomas in patients treated with immunochemotherapy.

    Science.gov (United States)

    Sorigue, Marc; Garcia, Olga; Baptista, Maria Joao; Sancho, Juan-Manuel; Tapia, Gustavo; Mate, José Luis; Feliu, Evarist; Navarro, José-Tomás; Ribera, Josep-Maria

    2017-03-22

    The prognosis of diffuse large B-cell lymphomas (DLBCL) transformed from indolent lymphoma (TL) has been considered poorer than that of de novo DLBCL. However, it seems to have improved since the introduction of rituximab. We compared the characteristics (including the cell-of-origin), and the prognosis of 29 patients with TL and 101 with de novo DLBCL treated with immunochemotherapy. Patients with TL and de novo DLBCL had similar characteristics. All TL cases evolving from follicular lymphoma were germinal-center B-cell-like, while those TL from marginal zone lymphoma or chronic lymphocytic leukemia were non-germinal-center B-cell-like. The complete response rate was similar in TL and de novo DLBCL (62 vs. 66%, P=.825). The 5-year overall and progression-free survival probabilities (95% CI) were 59% (40-78) and 41% (22-60) for TL and 63% (53-73) and 60% (50-70) for de novo DLBCL, respectively (P=.732 for overall survival and P=.169 for progression-free survival). In this study, the prognosis of TL and de novo DLBCL treated with immunochemotherapy was similar. The role of intensification with stem cell transplantation in the management of TL may be questionable in the rituximab era. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  8. A Pareto Algorithm for Efficient De Novo Design of Multi-functional Molecules.

    Science.gov (United States)

    Daeyaert, Frits; Deem, Micheal W

    2017-01-01

    We have introduced a Pareto sorting algorithm into Synopsis, a de novo design program that generates synthesizable molecules with desirable properties. We give a detailed description of the algorithm and illustrate its working in 2 different de novo design settings: the design of putative dual and selective FGFR and VEGFR inhibitors, and the successful design of organic structure determining agents (OSDAs) for the synthesis of zeolites. We show that the introduction of Pareto sorting not only enables the simultaneous optimization of multiple properties but also greatly improves the performance of the algorithm to generate molecules with hard-to-meet constraints. This in turn allows us to suggest approaches to address the problem of false positive hits in de novo structure based drug design by introducing structural and physicochemical constraints in the designed molecules, and by forcing essential interactions between these molecules and their target receptor. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Rapid centriole assembly in Naegleria reveals conserved roles for both de novo and mentored assembly.

    Science.gov (United States)

    Fritz-Laylin, Lillian K; Levy, Yaron Y; Levitan, Edward; Chen, Sean; Cande, W Zacheus; Lai, Elaine Y; Fulton, Chandler

    2016-03-01

    Centrioles are eukaryotic organelles whose number and position are critical for cilia formation and mitosis. Many cell types assemble new centrioles next to existing ones ("templated" or mentored assembly). Under certain conditions, centrioles also form without pre-existing centrioles (de novo). The synchronous differentiation of Naegleria amoebae to flagellates represents a unique opportunity to study centriole assembly, as nearly 100% of the population transitions from having no centrioles to having two within minutes. Here, we find that Naegleria forms its first centriole de novo, immediately followed by mentored assembly of the second. We also find both de novo and mentored assembly distributed among all major eukaryote lineages. We therefore propose that both modes are ancestral and have been conserved because they serve complementary roles, with de novo assembly as the default when no pre-existing centriole is available, and mentored assembly allowing precise regulation of number, timing, and location of centriole assembly. © 2016 Wiley Periodicals, Inc.

  10. Identification of a novel Plasmopara halstedii elicitor protein combining de novo peptide sequencing algorithms and RACE-PCR

    Directory of Open Access Journals (Sweden)

    Madlung Johannes

    2010-05-01

    Full Text Available Abstract Background Often high-quality MS/MS spectra of tryptic peptides do not match to any database entry because of only partially sequenced genomes and therefore, protein identification requires de novo peptide sequencing. To achieve protein identification of the economically important but still unsequenced plant pathogenic oomycete Plasmopara halstedii, we first evaluated the performance of three different de novo peptide sequencing algorithms applied to a protein digests of standard proteins using a quadrupole TOF (QStar Pulsar i. Results The performance order of the algorithms was PEAKS online > PepNovo > CompNovo. In summary, PEAKS online correctly predicted 45% of measured peptides for a protein test data set. All three de novo peptide sequencing algorithms were used to identify MS/MS spectra of tryptic peptides of an unknown 57 kDa protein of P. halstedii. We found ten de novo sequenced peptides that showed homology to a Phytophthora infestans protein, a closely related organism of P. halstedii. Employing a second complementary approach, verification of peptide prediction and protein identification was performed by creation of degenerate primers for RACE-PCR and led to an ORF of 1,589 bp for a hypothetical phosphoenolpyruvate carboxykinase. Conclusions Our study demonstrated that identification of proteins within minute amounts of sample material improved significantly by combining sensitive LC-MS methods with different de novo peptide sequencing algorithms. In addition, this is the first study that verified protein prediction from MS data by also employing a second complementary approach, in which RACE-PCR led to identification of a novel elicitor protein in P. halstedii.

  11. Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    2012-09-01

    Full Text Available Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA-Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis, which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.

  12. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder

    DEFF Research Database (Denmark)

    Hamilton, P J; Campbell, N G; Sharma, S

    2013-01-01

    De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution...

  13. Novel de novo BRCA2 mutation in a patient with a family history of breast cancer

    DEFF Research Database (Denmark)

    Hansen, Thomas V O; Bisgaard, Marie Luise; Jønson, Lars

    2008-01-01

    whole blood. The paternity was determined by single nucleotide polymorphism (SNP) microarray analysis. Parental origin of the de novo mutation was determined by establishing mutation-SNP haplotypes by variant specific PCR, while de novo and mosaic status was investigated by sequencing of DNA from......BACKGROUND: BRCA2 germ-line mutations predispose to breast and ovarian cancer. Mutations are widespread and unclassified splice variants are frequently encountered. We describe the parental origin and functional characterization of a novel de novo BRCA2 splice site mutation found in a patient...... and synthesis of a truncated BRCA2 protein. The aberrant splicing was verified by RT-PCR analysis on RNA isolated from whole blood of the affected patient. The mutation was not found in any of the patient's parents or in the mother's carcinoma, showing it is a de novo mutation. Variant specific PCR indicates...

  14. De novo assembly of highly diverse viral populations

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    2012-09-01

    Full Text Available Abstract Background Extensive genetic diversity in viral populations within infected hosts and the divergence of variants from existing reference genomes impede the analysis of deep viral sequencing data. A de novo population consensus assembly is valuable both as a single linear representation of the population and as a backbone on which intra-host variants can be accurately mapped. The availability of consensus assemblies and robustly mapped variants are crucial to the genetic study of viral disease progression, transmission dynamics, and viral evolution. Existing de novo assembly techniques fail to robustly assemble ultra-deep sequence data from genetically heterogeneous populations such as viruses into full-length genomes due to the presence of extensive genetic variability, contaminants, and variable sequence coverage. Results We present VICUNA, a de novo assembly algorithm suitable for generating consensus assemblies from genetically heterogeneous populations. We demonstrate its effectiveness on Dengue, Human Immunodeficiency and West Nile viral populations, representing a range of intra-host diversity. Compared to state-of-the-art assemblers designed for haploid or diploid systems, VICUNA recovers full-length consensus and captures insertion/deletion polymorphisms in diverse samples. Final assemblies maintain a high base calling accuracy. VICUNA program is publicly available at: http://www.broadinstitute.org/scientific-community/science/projects/viral-genomics/ viral-genomics-analysis-software. Conclusions We developed VICUNA, a publicly available software tool, that enables consensus assembly of ultra-deep sequence derived from diverse viral populations. While VICUNA was developed for the analysis of viral populations, its application to other heterogeneous sequence data sets such as metagenomic or tumor cell population samples may prove beneficial in these fields of research.

  15. Intrachromosomal rearrangements in two representatives of the genus Saltator (Thraupidae, Passeriformes) and the occurrence of heteromorphic Z chromosomes.

    Science.gov (United States)

    dos Santos, Michelly da Silva; Kretschmer, Rafael; Silva, Fabio Augusto Oliveira; Ledesma, Mario Angel; O'Brien, Patricia C M; Ferguson-Smith, Malcolm A; Del Valle Garnero, Analía; de Oliveira, Edivaldo Herculano Corrêa; Gunski, Ricardo José

    2015-10-01

    Saltator is a genus within family Thraupidae, the second largest family of Passeriformes, with more than 370 species found exclusively in the New World. Despite this, only a few species have had their karyotypes analyzed, most of them only with conventional staining. The diploid number is close to 80, and chromosome morphology is similar to the usual avian karyotype. Recent studies using cross-species chromosome painting have shown that, although the chromosomal morphology and number are similar to many species of birds, Passeriformes exhibit a complex pattern of paracentric and pericentric inversions in the chromosome homologous to GGA1q in two different suborders, Oscines and Suboscines. Hence, considering the importance and species richness of Thraupidae, this study aims to analyze two species of genus Saltator, the golden-billed saltator (S. aurantiirostris) and the green-winged saltator (S. similis) by means of classical cytogenetics and cross-species chromosome painting using Gallus gallus and Leucopternis albicollis probes, and also 5S and 18S rDNA and telomeric sequences. The results show that the karyotypes of these species are similar to other species of Passeriformes. Interestingly, the Z chromosome appears heteromorphic in S. similis, varying in morphology from acrocentric to metacentric. 5S and 18S probes hybridize to one pair of microchromosomes each, and telomeric sequences produce signals only in the terminal regions of chromosomes. FISH results are very similar to the Passeriformes already analyzed by means of molecular cytogenetics (Turdus species and Elaenia spectabilis). However, the paracentric and pericentric inversions observed in Saltator are different from those detected in these species, an observation that helps to explain the probable sequence of rearrangements. As these rearrangements are found in both suborders of Passeriformes (Oscines and Suboscines), we propose that the fission of GGA1 and inversions in GGA1q have occurred very

  16. Time-reversal and Bayesian inversion

    Science.gov (United States)

    Debski, Wojciech

    2017-04-01

    Probabilistic inversion technique is superior to the classical optimization-based approach in all but one aspects. It requires quite exhaustive computations which prohibit its use in huge size inverse problems like global seismic tomography or waveform inversion to name a few. The advantages of the approach are, however, so appealing that there is an ongoing continuous afford to make the large inverse task as mentioned above manageable with the probabilistic inverse approach. One of the perspective possibility to achieve this goal relays on exploring the internal symmetry of the seismological modeling problems in hand - a time reversal and reciprocity invariance. This two basic properties of the elastic wave equation when incorporating into the probabilistic inversion schemata open a new horizons for Bayesian inversion. In this presentation we discuss the time reversal symmetry property, its mathematical aspects and propose how to combine it with the probabilistic inverse theory into a compact, fast inversion algorithm. We illustrate the proposed idea with the newly developed location algorithm TRMLOC and discuss its efficiency when applied to mining induced seismic data.

  17. A glance at quality score: implication for de novo transcriptome reconstruction of Illumina reads

    Directory of Open Access Journals (Sweden)

    Stanley Kimbung Mbandi

    2014-02-01

    Full Text Available Downstream analyses of short-reads from next-generation sequencing platforms are often preceded by a pre-processing step that removes uncalled and wrongly called bases. Standard approaches rely on their associated base quality scores to retain the read or a portion of it when the score is above a predefined threshold. It is difficult to differentiate sequencing error from biological variation without a reference using quality scores. The effects of quality score based trimming have not been systematically studied in de novo transcriptome assembly. Using RNA-Seq data produced from Illumina, we teased out the effects of quality score base filtering or trimming on de novo transcriptome reconstruction. We showed that assemblies produced from reads subjected to different quality score thresholds contain truncated and missing transfrags when compared to those from untrimmed reads. Our data supports the fact that de novo assembling of untrimmed data is challenging for de Bruijn graph assemblers. However, our results indicates that comparing the assemblies from untrimmed and trimmed read subsets can suggest appropriate filtering parameters and enable selection of the optimum de novo transcriptome assembly in non-model organisms.

  18. Efficient assembly of de novo human artificial chromosomes from large genomic loci

    Directory of Open Access Journals (Sweden)

    Stromberg Gregory

    2005-07-01

    Full Text Available Abstract Background Human Artificial Chromosomes (HACs are potentially useful vectors for gene transfer studies and for functional annotation of the genome because of their suitability for cloning, manipulating and transferring large segments of the genome. However, development of HACs for the transfer of large genomic loci into mammalian cells has been limited by difficulties in manipulating high-molecular weight DNA, as well as by the low overall frequencies of de novo HAC formation. Indeed, to date, only a small number of large (>100 kb genomic loci have been reported to be successfully packaged into de novo HACs. Results We have developed novel methodologies to enable efficient assembly of HAC vectors containing any genomic locus of interest. We report here the creation of a novel, bimolecular system based on bacterial artificial chromosomes (BACs for the construction of HACs incorporating any defined genomic region. We have utilized this vector system to rapidly design, construct and validate multiple de novo HACs containing large (100–200 kb genomic loci including therapeutically significant genes for human growth hormone (HGH, polycystic kidney disease (PKD1 and ß-globin. We report significant differences in the ability of different genomic loci to support de novo HAC formation, suggesting possible effects of cis-acting genomic elements. Finally, as a proof of principle, we have observed sustained ß-globin gene expression from HACs incorporating the entire 200 kb ß-globin genomic locus for over 90 days in the absence of selection. Conclusion Taken together, these results are significant for the development of HAC vector technology, as they enable high-throughput assembly and functional validation of HACs containing any large genomic locus. We have evaluated the impact of different genomic loci on the frequency of HAC formation and identified segments of genomic DNA that appear to facilitate de novo HAC formation. These genomic loci

  19. De novo synthesis of milk triglycerides in humans

    Science.gov (United States)

    Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk tha...

  20. 76 FR 68767 - Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification...

    Science.gov (United States)

    2011-11-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0689] Draft Guidance for Industry and Food and Drug Administration Staff; De Novo Classification Process... for Industry and Food and Drug Administration Staff; De Novo Classification Process (Evaluation of...

  1. Gravity inversion code

    International Nuclear Information System (INIS)

    Burkhard, N.R.

    1979-01-01

    The gravity inversion code applies stabilized linear inverse theory to determine the topography of a subsurface density anomaly from Bouguer gravity data. The gravity inversion program consists of four source codes: SEARCH, TREND, INVERT, and AVERAGE. TREND and INVERT are used iteratively to converge on a solution. SEARCH forms the input gravity data files for Nevada Test Site data. AVERAGE performs a covariance analysis on the solution. This document describes the necessary input files and the proper operation of the code. 2 figures, 2 tables

  2. Stratigraphic inversion of pre-stack multicomponent data; Inversion stratigraphique multicomposante avant sommation

    Energy Technology Data Exchange (ETDEWEB)

    Agullo, Y.

    2005-09-15

    This thesis present the extension of mono-component seismic pre-stack data stratigraphical inversion method to multicomponent data, with the objective of improving the determination of reservoir elastic parameters. In addiction to the PP pressure waves, the PS converted waves proved their interest for imaging under gas clouds; and their potential is highly significant for the characterization of lithologies, fluids, fractures... Nevertheless the simultaneous use ol PP and PS data remains problematic because of their different the time scales. To jointly use the information contained in PP and PS data, we propose a method in three steps first, mono-component stratigraphic inversions of PP then PS data; second, estimation of the PP to PS time conversion law; third, multicomponent stratigraphic inversion. For the second point, the estimation of the PP to PS conversion law is based on minimizing the difference between the S impedances obtained from PP and PS mono-component stratigraphic inversion. The pre-stack mono-component stratigraphic inversions was adapted to the case of multicomponent data by leaving each type of data in its own time scale in order to avoid the distortion of the seismic wavelet. The results obtained on a realistic synthetic PP-PS case show on one hand that determining PP to PS conversion law (from the mono-component inversion results) is feasible, and on the other hand that the joint inversion of PP and PS data with this conversion law improves the results compared to the mono-component inversion ones. Although this is presented within the framework of the PP and PS multi-component data, the developed methodology adapts directly to PP and SS data for example. (author)

  3. De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

    Science.gov (United States)

    Dong, Shan; Walker, Michael F.; Carriero, Nicholas J.; DiCola, Michael; Willsey, A. Jeremy; Ye, Adam Y.; Waqar, Zainulabedin; Gonzalez, Luis E.; Overton, John D.; Frahm, Stephanie; Keaney, John F.; Teran, Nicole A.; Dea, Jeanselle; Mandell, Jeffrey D.; Bal, Vanessa Hus; Sullivan, Catherine A.; DiLullo, Nicholas M.; Khalil, Rehab O.; Gockley, Jake; Yuksel, Zafer; Sertel, Sinem M.; Ercan-Sencicek, A. Gulhan; Gupta, Abha R.; Mane, Shrikant M.; Sheldon, Michael; Brooks, Andrew I.; Roeder, Kathryn; Devlin, Bernie; State, Matthew W.; Wei, Liping; Sanders, Stephan J.

    2014-01-01

    SUMMARY Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single nucleotide variants to autism spectrum disorders (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. Through the application of a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR=1.6; 95%CI=1.0-2.7; p=0.03), are more common in female probands (p=0.02), are enriched among genes encoding FMRP targets (p=6×10−9), and arise predominantly on the paternal chromosome (p<0.001). Based on mutation rates in probands versus unaffected siblings, de novo frameshift indels contribute to risk in approximately 3.0% of individuals with ASD. Finally, through observing clustering of mutations in unrelated probands, we report two novel ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. PMID:25284784

  4. De novo-based transcriptome profiling of male-sterile and fertile watermelon lines.

    Science.gov (United States)

    Rhee, Sun-Ju; Kwon, Taehyung; Seo, Minseok; Jang, Yoon Jeong; Sim, Tae Yong; Cho, Seoae; Han, Sang-Wook; Lee, Gung Pyo

    2017-01-01

    The whole-genome sequence of watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai), a valuable horticultural crop worldwide, was released in 2013. Here, we compared a de novo-based approach (DBA) to a reference-based approach (RBA) using RNA-seq data, to aid in efforts to improve the annotation of the watermelon reference genome and to obtain biological insight into male-sterility in watermelon. We applied these techniques to available data from two watermelon lines: the male-sterile line DAH3615-MS and the male-fertile line DAH3615. Using DBA, we newly annotated 855 watermelon transcripts, and found gene functional clusters predicted to be related to stimulus responses, nucleic acid binding, transmembrane transport, homeostasis, and Golgi/vesicles. Among the DBA-annotated transcripts, 138 de novo-exclusive differentially-expressed genes (DEDEGs) related to male sterility were detected. Out of 33 randomly selected newly annotated transcripts and DEDEGs, 32 were validated by RT-qPCR. This study demonstrates the usefulness and reliability of the de novo transcriptome assembly in watermelon, and provides new insights for researchers exploring transcriptional blueprints with regard to the male sterility.

  5. Inverse planning IMRT

    International Nuclear Information System (INIS)

    Rosenwald, J.-C.

    2008-01-01

    The lecture addressed the following topics: Optimizing radiotherapy dose distribution; IMRT contributes to optimization of energy deposition; Inverse vs direct planning; Main steps of IMRT; Background of inverse planning; General principle of inverse planning; The 3 main components of IMRT inverse planning; The simplest cost function (deviation from prescribed dose); The driving variable : the beamlet intensity; Minimizing a 'cost function' (or 'objective function') - the walker (or skier) analogy; Application to IMRT optimization (the gradient method); The gradient method - discussion; The simulated annealing method; The optimization criteria - discussion; Hard and soft constraints; Dose volume constraints; Typical user interface for definition of optimization criteria; Biological constraints (Equivalent Uniform Dose); The result of the optimization process; Semi-automatic solutions for IMRT; Generalisation of the optimization problem; Driving and driven variables used in RT optimization; Towards multi-criteria optimization; and Conclusions for the optimization phase. (P.A.)

  6. TRANSPORT OF PATIENTS FOR PRIMARY PTCA FROM GENERAL HOSPITAL NOVO MESTO TO LJUBLJANA IN 2002

    Directory of Open Access Journals (Sweden)

    Renata Okrajšek

    2004-12-01

    Full Text Available Background. The treatment of acute coronary syndrome (ACS with ST-segment elevation with primary percutaneous transluminal coronary angioplasty (PTCA is the best way to treat these patients. Primary PTCA is also practicable with patients who are admitted into institution without catheter laboratory. The transport of patients into the tertiary institution is safe, but it is important to keep the time of ischemia as short as possible and to reach the time interval of door-balloon as recommended by the guidelines. The ACS patients with ST-segment elevation that were directed into General Hospital Novo mesto after examination at the internistic emergency department have been redirected to KC Ljubljana for realization of PTCA since October 2001.Methods. A prospective analysis of patients with ACS with STsegment elevation, who had been transferred from General Hospital Novo mesto to KC Ljubljana in the period from January 1, 2002 to December 31, 2002 to have a primary PTCA, was performed. The analysis comprised the following: the time interval of handling the patients at Internistic department of General Hospital Novo mesto, the time of transport of patients to Ljubljana and total time interval from the arrival of patients to General Hospital Novo mesto to the first inflation of balloon in Ljubljana. We monitored the complications that occurred during the treatment of the patients.Results. In the above mentioned period 29 patients (24 males and 5 females were transported from the General Hospital Novo mesto to the KC Ljubljana to have a primary PTCA performed. The total time interval measured between the patients’ arrival to General Hospital Novo mesto to the first inflation of balloon in Ljubljana in the year 2002 was 145 minutes, which is 17 minutes better than in the previous period. The time interval recommended by the guidelines was achieved with four patients.Conclusions. By recognizing the problems that had encountered with directing the

  7. Illumina-based de novo transcriptome sequencing and analysis

    Indian Academy of Sciences (India)

    In the present study, we used Illumina HiSeq technology to perform de novo assembly of heart and musk gland transcriptomes from the Chinese forest musk deer. A total of 239,383 transcripts and 176,450 unigenes were obtained, of which 37,329 unigenes were matched to known sequences in the NCBI nonredundant ...

  8. De novo biosynthesis of anthocyanins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eichenberger, Michael; Hansson, Anders; Fischer, David; Dürr, Lara; Naesby, Michael

    2018-06-01

    Anthocyanins (ACNs) are plant secondary metabolites responsible for most of the red, purple and blue colors of flowers, fruits and vegetables. They are increasingly used in the food and beverage industry as natural alternative to artificial colorants. Production of these compounds by fermentation of microorganisms would provide an attractive alternative. In this study, Saccharomyces cerevisiae was engineered for de novo production of the three basic anthocyanins, as well as the three main trans-flavan-3-ols. Enzymes from different plant sources were screened and efficient variants found for most steps of the biosynthetic pathway. However, the anthocyanidin synthase was identified as a major obstacle to efficient production. In yeast, this enzyme converts the majority of its natural substrates leucoanthocyanidins into the off-pathway flavonols. Nonetheless, de novo biosynthesis of ACNs was shown for the first time in yeast and for the first time in a single microorganism. It provides a framework for optimizing the activity of anthocyanidin synthase and represents an important step towards sustainable industrial production of these highly relevant molecules in yeast.

  9. Uridine monophosphate synthetase enables eukaryotic de novo NAD+ biosynthesis from quinolinic acid.

    Science.gov (United States)

    McReynolds, Melanie R; Wang, Wenqing; Holleran, Lauren M; Hanna-Rose, Wendy

    2017-07-07

    NAD + biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD + biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD + biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD + biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of de novo NAD + biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact de novo biosynthesis pathway for NAD + from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD + levels and partially reversed NAD + -dependent phenotypes caused by mutation of pnc-1 , which encodes a nicotinamidase required for NAD + salvage biosynthesis, demonstrating contribution of de novo synthesis to NAD + homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD + biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD + biosynthesis creates novel possibilities for manipulating NAD + biosynthetic pathways, which is key for the future of therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Associations between Familial Rates of Psychiatric Disorders and De Novo Genetic Mutations in Autism

    Directory of Open Access Journals (Sweden)

    Kyleen Luhrs

    2017-01-01

    Full Text Available The purpose of this study was to examine the confluence of genetic and familial risk factors in children with Autism Spectrum Disorder (ASD with distinct de novo genetic events. We hypothesized that gene-disrupting mutations would be associated with reduced rates of familial psychiatric disorders relative to structural mutations. Participants included families of children with ASD in four groups: de novo duplication copy number variations (DUP, n=62, de novo deletion copy number variations (DEL, n=74, de novo likely gene-disrupting mutations (LGDM, n=267, and children without a known genetic etiology (NON, n=2111. Familial rates of psychiatric disorders were calculated from semistructured interviews. Results indicated overall increased rates of psychiatric disorders in DUP families compared to DEL and LGDM families, specific to paternal psychiatric histories, and particularly evident for depressive disorders. Higher rates of depressive disorders in maternal psychiatric histories were observed overall compared to paternal histories and higher rates of anxiety disorders were observed in paternal histories for LGDM families compared to DUP families. These findings support the notion of an additive contribution of genetic etiology and familial factors are associated with ASD risk and highlight critical need for continued work targeting these relationships.

  11. Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

    DEFF Research Database (Denmark)

    Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

    2017-01-01

    Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high...

  12. Sequencing and de novo assembly of 150 genomes from Denmark as a population reference

    DEFF Research Database (Denmark)

    Maretty, Lasse; Jensen, Jacob Malte; Petersen, Bent

    2017-01-01

    Hundreds of thousands of human genomes are now being sequenced to characterize genetic variation and use this information to augment association mapping studies of complex disorders and other phenotypic traits. Genetic variation is identified mainly by mapping short reads to the reference genome...... or by performing local assembly. However, these approaches are biased against discovery of structural variants and variation in the more complex parts of the genome. Hence, large-scale de novo assembly is needed. Here we show that it is possible to construct excellent de novo assemblies from high......-coverage sequencing with mate-pair libraries extending up to 20 kilobases. We report de novo assemblies of 150 individuals (50 trios) from the GenomeDenmark project. The quality of these assemblies is similar to those obtained using the more expensive long-read technology. We use the assemblies to identify a rich set...

  13. De novo synthesis of purine nucleotides in different fiber types of rat skeletal muscle

    International Nuclear Information System (INIS)

    Tullson, P.C.; John-Alder, H.; Hood, D.A.; Terjung, R.L.

    1986-01-01

    The contribution of de novo purine nucleotide synthesis to nucleotide metabolism in skeletal muscles is not known. The authors have determined rates of de novo synthesis in soleus (slow-twitch red), red gastrocnemius (fast-twitch red), and white gastrocnemius (fast-twitch white) using the perfused rat hindquarter. 14 C glycine incorporation into ATP was linear after 1 and 2 hours of perfusion with 0.2 mM added glycine. The intracellular (I) and extracellular (E) specific activity of 14 C glycine was determined by HPLC of phenylisothiocyanate derivatives of neutralized PCA extracts. The rates of de novo synthesis when expressed relative to muscle ATP content show slow and fast-twitch red muscles to be similar and about twice as great as fast-twitch white muscles. This could represent a greater turnover of the adenine nucleotide pool in more oxidative red muscle types

  14. De novo point mutations in patients diagnosed with ataxic cerebral palsy.

    Science.gov (United States)

    Parolin Schnekenberg, Ricardo; Perkins, Emma M; Miller, Jack W; Davies, Wayne I L; D'Adamo, Maria Cristina; Pessia, Mauro; Fawcett, Katherine A; Sims, David; Gillard, Elodie; Hudspith, Karl; Skehel, Paul; Williams, Jonathan; O'Regan, Mary; Jayawant, Sandeep; Jefferson, Rosalind; Hughes, Sarah; Lustenberger, Andrea; Ragoussis, Jiannis; Jackson, Mandy; Tucker, Stephen J; Németh, Andrea H

    2015-07-01

    Cerebral palsy is a sporadic disorder with multiple likely aetiologies, but frequently considered to be caused by birth asphyxia. Genetic investigations are rarely performed in patients with cerebral palsy and there is little proven evidence of genetic causes. As part of a large project investigating children with ataxia, we identified four patients in our cohort with a diagnosis of ataxic cerebral palsy. They were investigated using either targeted next generation sequencing or trio-based exome sequencing and were found to have mutations in three different genes, KCNC3, ITPR1 and SPTBN2. All the mutations were de novo and associated with increased paternal age. The mutations were shown to be pathogenic using a combination of bioinformatics analysis and in vitro model systems. This work is the first to report that the ataxic subtype of cerebral palsy can be caused by de novo dominant point mutations, which explains the sporadic nature of these cases. We conclude that at least some subtypes of cerebral palsy may be caused by de novo genetic mutations and patients with a clinical diagnosis of cerebral palsy should be genetically investigated before causation is ascribed to perinatal asphyxia or other aetiologies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  15. Model-Based GUI Testing Using Uppaal at Novo Nordisk

    DEFF Research Database (Denmark)

    H. Hjort, Ulrik; Rasmussen, Jacob Illum; Larsen, Kim Guldstrand

    2009-01-01

    This paper details a collaboration between Aalborg University and Novo Nordiskin developing an automatic model-based test generation tool for system testing of the graphical user interface of a medical device on an embedded platform. The tool takes as input an UML Statemachine model and generates...

  16. Towards accurate de novo assembly for genomes with repeats

    NARCIS (Netherlands)

    Bucur, Doina

    2017-01-01

    De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

  17. Engineering and introduction of de novo disulphide bridges in ...

    Indian Academy of Sciences (India)

    The engineeringof de novo disulphide bridges has been explored as a means to increase the thermal stability of enzymes in the rationalmethod of protein engineering. In this study, Disulphide by Design software, homology modelling and moleculardynamics simulations were used to select appropriate amino acid pairs for ...

  18. Sharp spatially constrained inversion

    DEFF Research Database (Denmark)

    Vignoli, Giulio G.; Fiandaca, Gianluca G.; Christiansen, Anders Vest C A.V.C.

    2013-01-01

    We present sharp reconstruction of multi-layer models using a spatially constrained inversion with minimum gradient support regularization. In particular, its application to airborne electromagnetic data is discussed. Airborne surveys produce extremely large datasets, traditionally inverted...... by using smoothly varying 1D models. Smoothness is a result of the regularization constraints applied to address the inversion ill-posedness. The standard Occam-type regularized multi-layer inversion produces results where boundaries between layers are smeared. The sharp regularization overcomes...... inversions are compared against classical smooth results and available boreholes. With the focusing approach, the obtained blocky results agree with the underlying geology and allow for easier interpretation by the end-user....

  19. Introduction to Schroedinger inverse scattering

    International Nuclear Information System (INIS)

    Roberts, T.M.

    1991-01-01

    Schroedinger inverse scattering uses scattering coefficients and bound state data to compute underlying potentials. Inverse scattering has been studied extensively for isolated potentials q(x), which tend to zero as vertical strokexvertical stroke→∞. Inverse scattering for isolated impurities in backgrounds p(x) that are periodic, are Heaviside steps, are constant for x>0 and periodic for x<0, or that tend to zero as x→∞ and tend to ∞ as x→-∞, have also been studied. This paper identifies literature for the five inverse problems just mentioned, and for four other inverse problems. Heaviside-step backgrounds are discussed at length. (orig.)

  20. A Generalization of the Spherical Inversion

    Science.gov (United States)

    Ramírez, José L.; Rubiano, Gustavo N.

    2017-01-01

    In the present article, we introduce a generalization of the spherical inversion. In particular, we define an inversion with respect to an ellipsoid, and prove several properties of this new transformation. The inversion in an ellipsoid is the generalization of the elliptic inversion to the three-dimensional space. We also study the inverse images…

  1. Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

    Directory of Open Access Journals (Sweden)

    Camila de Andrade Brum

    2015-04-01

    Full Text Available Background: Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. Objective: To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. Methods: This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Results: Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%, which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. Conclusion: It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

  2. Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

    Energy Technology Data Exchange (ETDEWEB)

    Brum, Camila de Andrade [Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS (Brazil); Stein, Airton Tetelbom [Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS (Brazil); Grupo Hospitalar Conceição (GHC), Porto Alegre, RS (Brazil); Universidade Luterana do Brasil (ULBRA), Porto Alegre, RS (Brazil); Pellanda, Lucia Campos, E-mail: luciapell.pesquisa@cardiologia.org.br [Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, RS (Brazil); Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS (Brazil)

    2015-04-15

    Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

  3. Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

    International Nuclear Information System (INIS)

    Brum, Camila de Andrade; Stein, Airton Tetelbom; Pellanda, Lucia Campos

    2015-01-01

    Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality

  4. Heterologous aggregates promote de novo prion appearance via more than one mechanism.

    Directory of Open Access Journals (Sweden)

    Fatih Arslan

    2015-01-01

    Full Text Available Prions are self-perpetuating conformational variants of particular proteins. In yeast, prions cause heritable phenotypic traits. Most known yeast prions contain a glutamine (Q/asparagine (N-rich region in their prion domains. [PSI+], the prion form of Sup35, appears de novo at dramatically enhanced rates following transient overproduction of Sup35 in the presence of [PIN+], the prion form of Rnq1. Here, we establish the temporal de novo appearance of Sup35 aggregates during such overexpression in relation to other cellular proteins. Fluorescently-labeled Sup35 initially forms one or a few dots when overexpressed in [PIN+] cells. One of the dots is perivacuolar, colocalizes with the aggregated Rnq1 dot and grows into peripheral rings/lines, some of which also colocalize with Rnq1. Sup35 dots that are not near the vacuole do not always colocalize with Rnq1 and disappear by the time rings start to grow. Bimolecular fluorescence complementation failed to detect any interaction between Sup35-VN and Rnq1-VC in [PSI+][PIN+] cells. In contrast, all Sup35 aggregates, whether newly induced or in established [PSI+], completely colocalize with the molecular chaperones Hsp104, Sis1, Ssa1 and eukaryotic release factor Sup45. In the absence of [PIN+], overexpressed aggregating proteins such as the Q/N-rich Pin4C or the non-Q/N-rich Mod5 can also promote the de novo appearance of [PSI+]. Similar to Rnq1, overexpressed Pin4C transiently colocalizes with newly appearing Sup35 aggregates. However, no interaction was detected between Mod5 and Sup35 during [PSI+] induction in the absence of [PIN+]. While the colocalization of Sup35 and aggregates of Rnq1 or Pin4C are consistent with the model that the heterologous aggregates cross-seed the de novo appearance of [PSI+], the lack of interaction between Mod5 and Sup35 leaves open the possibility of other mechanisms. We also show that Hsp104 is required in the de novo appearance of [PSI+] aggregates in a [PIN

  5. Whole-Genome de novo Sequencing Of Quail And Grey Partridge

    DEFF Research Database (Denmark)

    Holm, Lars-Erik; Panitz, Frank; Burt, Dave

    2011-01-01

    The development in sequencing methods has made it possible to perform whole genome de novo sequencing of species without large commercial interests. Within the EU-financed QUANTOMICS project (KBBE-2A-222664), we have performed de novo sequencing of quail (Coturnix coturnix) and grey partridge...... (Perdix perdix) on a Genome Analyzer GAII (Illumina) using paired-end sequencing. The amount of generated sequences amounts to 8 to 9 Gb for each species. The analysis and assembly of the generated sequences is ongoing. Access to the whole genome sequence from these two species will enable enhanced...... comparative studies towards the chicken genome and will aid in identifying evolutionarily conserved sequences within the Galliformes. The obtained sequences from quail and partridge represent a beginning of generating the whole genome sequence for these species. The continuation of establishing the genome...

  6. Wake Vortex Inverse Model User's Guide

    Science.gov (United States)

    Lai, David; Delisi, Donald

    2008-01-01

    NorthWest Research Associates (NWRA) has developed an inverse model for inverting landing aircraft vortex data. The data used for the inversion are the time evolution of the lateral transport position and vertical position of both the port and starboard vortices. The inverse model performs iterative forward model runs using various estimates of vortex parameters, vertical crosswind profiles, and vortex circulation as a function of wake age. Forward model predictions of lateral transport and altitude are then compared with the observed data. Differences between the data and model predictions guide the choice of vortex parameter values, crosswind profile and circulation evolution in the next iteration. Iterations are performed until a user-defined criterion is satisfied. Currently, the inverse model is set to stop when the improvement in the rms deviation between the data and model predictions is less than 1 percent for two consecutive iterations. The forward model used in this inverse model is a modified version of the Shear-APA model. A detailed description of this forward model, the inverse model, and its validation are presented in a different report (Lai, Mellman, Robins, and Delisi, 2007). This document is a User's Guide for the Wake Vortex Inverse Model. Section 2 presents an overview of the inverse model program. Execution of the inverse model is described in Section 3. When executing the inverse model, a user is requested to provide the name of an input file which contains the inverse model parameters, the various datasets, and directories needed for the inversion. A detailed description of the list of parameters in the inversion input file is presented in Section 4. A user has an option to save the inversion results of each lidar track in a mat-file (a condensed data file in Matlab format). These saved mat-files can be used for post-inversion analysis. A description of the contents of the saved files is given in Section 5. An example of an inversion input

  7. De novo assembly of plant body plan: a step ahead of Deadpool.

    Science.gov (United States)

    Kareem, Abdul; Radhakrishnan, Dhanya; Sondhi, Yash; Aiyaz, Mohammed; Roy, Merin V; Sugimoto, Kaoru; Prasad, Kalika

    2016-08-01

    While in the movie Deadpool it is possible for a human to recreate an arm from scratch, in reality plants can even surpass that. Not only can they regenerate lost parts, but also the whole plant body can be reborn from a few existing cells. Despite the decades old realization that plant cells possess the ability to regenerate a complete shoot and root system, it is only now that the underlying mechanisms are being unraveled. De novo plant regeneration involves the initiation of regenerative mass, acquisition of the pluripotent state, reconstitution of stem cells and assembly of regulatory interactions. Recent studies have furthered our understanding on the making of a complete plant system in the absence of embryonic positional cues. We review the recent studies probing the molecular mechanisms of de novo plant regeneration in response to external inductive cues and our current knowledge of direct reprogramming of root to shoot and vice versa. We further discuss how de novo regeneration can be exploited to meet the demands of green culture industries and to serve as a general model to address the fundamental questions of regeneration across the plant kingdom.

  8. Optimal Inversion Parameters for Full Waveform Inversion using OBS Data Set

    Science.gov (United States)

    Kim, S.; Chung, W.; Shin, S.; Kim, D.; Lee, D.

    2017-12-01

    In recent years, full Waveform Inversion (FWI) has been the most researched technique in seismic data processing. It uses the residuals between observed and modeled data as an objective function; thereafter, the final subsurface velocity model is generated through a series of iterations meant to minimize the residuals.Research on FWI has expanded from acoustic media to elastic media. In acoustic media, the subsurface property is defined by P-velocity; however, in elastic media, properties are defined by multiple parameters, such as P-velocity, S-velocity, and density. Further, the elastic media can also be defined by Lamé constants, density or impedance PI, SI; consequently, research is being carried out to ascertain the optimal parameters.From results of advanced exploration equipment and Ocean Bottom Seismic (OBS) survey, it is now possible to obtain multi-component seismic data. However, to perform FWI on these data and generate an accurate subsurface model, it is important to determine optimal inversion parameters among (Vp, Vs, ρ), (λ, μ, ρ), and (PI, SI) in elastic media. In this study, staggered grid finite difference method was applied to simulate OBS survey. As in inversion, l2-norm was set as objective function. Further, the accurate computation of gradient direction was performed using the back-propagation technique and its scaling was done using the Pseudo-hessian matrix.In acoustic media, only Vp is used as the inversion parameter. In contrast, various sets of parameters, such as (Vp, Vs, ρ) and (λ, μ, ρ) can be used to define inversion in elastic media. Therefore, it is important to ascertain the parameter that gives the most accurate result for inversion with OBS data set.In this study, we generated Vp and Vs subsurface models by using (λ, μ, ρ) and (Vp, Vs, ρ) as inversion parameters in every iteration, and compared the final two FWI results.This research was supported by the Basic Research Project(17-3312) of the Korea Institute of

  9. De novo mutations in the genome organizer CTCF cause intellectual disability

    DEFF Research Database (Denmark)

    Gregor, Anne; Oti, Martin; Kouwenhoven, Evelyn N

    2013-01-01

    An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift...... mutations and one de novo missense mutation in CTCF in individuals with intellectual disability, microcephaly, and growth retardation. Furthermore, an individual with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates...... and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three individuals with point mutations revealed deregulation of genes involved in signal transduction...

  10. De novo status epilepticus is associated with adverse outcome: An 11-year retrospective study in Hong Kong.

    Science.gov (United States)

    Lui, Hoi Ki Kate; Hui, Kwok Fai; Fong, Wing Chi; Ip, Chun Tak; Lui, Hiu Tung Colin

    2016-08-01

    To identify predictors of poor clinical outcome in patients presenting to the intensive care units with status epilepticus (SE), in particular for patients presenting with de novo status epileptics. A retrospective review was performed on patients admitted to the intensive care units with status epilepticus in two hospitals in Hong Kong over an 11-year period from 2003 to 2013. A total of 87 SE cases were analyzed. The mean age of patients was 49.3 years (SD 14.9 years). Eighteen subjects (20.7%) had breakthrough seizure, which was the most common etiology for the status epilepticus episodes. Seventy-eight subjects (89.7%) had convulsive status epilepticus (CSE) and 9 subjects (10.3%) had non-convulsive status epilepticus (NCSE) on presentation. The 30-day mortality rate of all subjects was 18.4%. Non-convulsive status epilepticus was more common in patients with de novo status epilepticus when compared to those with existing history of epilepsy (15.5% Vs. 0%, p=0.03). Patients with de novo status epilepticus were older (52 Vs 43, p=0.009). De novo status epilepticus was associated with longer status duration (median 2.5 days, IQR 5 days), longer ICU stay (median 7.5 days, IQR 9 days) and poorer outcome (OR 4.15, 95% CI 1.53-11.2). For patients presenting to intensive care units with status epilepticus, those with de novo status epileptics were older and were more likely to develop non-convulsive status epilepticus. De novo status epilepticus was associated with poorer outcome. Continuous EEG monitoring would help identifying NCSE and potentially help improving clinical outcomes. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  11. Melhoramento do cafeeiro: XXXVIII. Observações sobre progênies do cultivar Mundo-Novo de Coffea arabica na estação experimental de Mococa Coffee breeding: XXXVIII-observation on progenies of the Mundo-Novo cultivars of Coffea arabica in the Mococa experimental station

    Directory of Open Access Journals (Sweden)

    Túlio R. Rocha

    1980-01-01

    Full Text Available Os dados analisados no experimento localizado em Mococa sobre a produtividade de 112 progênies dos cultivares Mundo-Novo S1 e S2, Bourbon-Amarelo, BourbonVermelho e Caturra-Vermelho de Coffea arabica no período de 1955 a 1971, indicaram que as de Mundo-Novo S1, de prefixos MP 474, MP 502, MP 469, MP 492 e MP 475, revelaram-se como as mais produtivas, assemelhando-se a algumas progênies 'Mundo--Novo' S2. Dentre estas, destacou-se a de prefixo MP 388-6, que atingiu o nível mais elevado de produção do experimento. As progênies de 'Mundo-Novo', em conjunto, produziram 44% a mais do que as de Bourbon-Amarelo e, estas, 60% a mais do que as de Bourbon-Vermelho e Caturra-Vermelho. A altura e o diâmetro da copa atingiram valores médios mais elevados para as progênies de 'Mundo-Novo'. Verificaram-se correlações positivas e altamente significativas entre altura média da planta e diâmetro médio da copa com a produção das progênies. As progênies mais produtivas revelaram rendimento (relação entre peso de café maduro e beneficiado de aproximadamente 6,0 e porcentagem de sementes normais, do tipo chato, acima de 80. Quanto ao tamanho das sementes do tipo chato, duas progênies 'Mundo-Novo' S1, MP 474 e MP 452, apresentaram peneira média maior, permi-tindo seleção de plantas com essa característica e com elevada produção.Coffee progenies of the Mundo-Novo cultivars of Coffea arabica were studied in an experiment located at the Mococa Experimental Station of the Instituto Agronômico in comparison with Bourbon-Amarelo, Bourbon-Vermelho and Caturra-Vermelho cultivars of the same species. During a period of 17 consecutive cropping years (1955-1971, Mundo-Novo yielded approximately 44% more than Bourbon-Amarelo and this cultivars yielded 60% more than Bourbon-Vermelho and Caturra-Vermelho. Among the 89 S1 'Mundo-Novo' progenies, MP 474, MP 502, MP 469, MP 492 and MP 475 yielded as much as the two best 'Mundo-Novo' S2 progenies. Greater

  12. Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

    Directory of Open Access Journals (Sweden)

    Richard J Allen

    2017-03-01

    Full Text Available Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate of the pathway as a whole.

  13. Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

    Science.gov (United States)

    Allen, Richard J; Musante, Cynthia J

    2017-01-01

    Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

  14. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson's Progression Markers Initiative Cohort.

    Science.gov (United States)

    Holden, Samantha K; Finseth, Taylor; Sillau, Stefan H; Berman, Brian D

    2018-01-01

    The Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UDPRS) is a commonly used tool to measure Parkinson disease (PD) progression. Longitudinal changes in MDS-UPDRS scores in de novo PD have not been established. Determine progression rates of MDS-UPDRS scores in de novo PD. 362 participants from the Parkinson's Progression Markers Initiative, a multicenter longitudinal cohort study of de novo PD, were included. Longitudinal progression of MDS-UPDRS total and subscale scores were modeled using mixed model regression. MDS-UPDRS scores increased in a linear fashion over five years in de novo PD. MDS-UPDRS total score increased an estimated 4.0 points/year, Part I 0.25 points/year, Part II 1.0 points/year, and Part III 2.4 points/year. The expected average progression of MDS-UPDRS scores in de novo PD from this study can assist in clinical monitoring and provide comparative data for detection of disease modification in treatment trials.

  15. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

    DEFF Research Database (Denmark)

    Willsey, A Jeremy; Fernandez, Thomas V; Yu, Dongmei

    2017-01-01

    Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 ...

  16. De Novo Insertions and Deletions of Predominantly Paternal Origin Are Associated with Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Shan Dong

    2014-10-01

    Full Text Available Summary: Whole-exome sequencing (WES studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs to autism spectrum disorder (ASD. However, challenges in the reliable detection of de novo insertions and deletions (indels have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals, we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0–2.7; p = 0.03, are more common in female probands (p = 0.02, are enriched among genes encoding FMRP targets (p = 6 × 10−9, and arise predominantly on the paternal chromosome (p < 0.001. On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release. : Insertions and deletions (indels have proven especially difficult to detect in exome sequencing data. Dong et al. now identify indels in exome data for 787 autism spectrum disorder (ASD families. They demonstrate association between de novo indels that alter the reading frame and ASD. Furthermore, by observing clustering of indels in unrelated probands, they uncover two additional ASD-associated genes: KMT2E (MLL5, a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.

  17. De Novo Construction of Redox Active Proteins.

    Science.gov (United States)

    Moser, C C; Sheehan, M M; Ennist, N M; Kodali, G; Bialas, C; Englander, M T; Discher, B M; Dutton, P L

    2016-01-01

    Relatively simple principles can be used to plan and construct de novo proteins that bind redox cofactors and participate in a range of electron-transfer reactions analogous to those seen in natural oxidoreductase proteins. These designed redox proteins are called maquettes. Hydrophobic/hydrophilic binary patterning of heptad repeats of amino acids linked together in a single-chain self-assemble into 4-alpha-helix bundles. These bundles form a robust and adaptable frame for uncovering the default properties of protein embedded cofactors independent of the complexities introduced by generations of natural selection and allow us to better understand what factors can be exploited by man or nature to manipulate the physical chemical properties of these cofactors. Anchoring of redox cofactors such as hemes, light active tetrapyrroles, FeS clusters, and flavins by His and Cys residues allow cofactors to be placed at positions in which electron-tunneling rates between cofactors within or between proteins can be predicted in advance. The modularity of heptad repeat designs facilitates the construction of electron-transfer chains and novel combinations of redox cofactors and new redox cofactor assisted functions. Developing de novo designs that can support cofactor incorporation upon expression in a cell is needed to support a synthetic biology advance that integrates with natural bioenergetic pathways. © 2016 Elsevier Inc. All rights reserved.

  18. Novo-desenvolvimento, capital social e desigualdade social

    Directory of Open Access Journals (Sweden)

    Ana Cristina de Oliveira Oliveira

    2012-03-01

    Full Text Available Este artigo aborda a tendência de enfrentamento da desigualdade social a partir, no campo econômico, da versão do novo-desenvolvimentismo e, no campo político e ideológico, a partir da noção de capital social, na tentativa de realizar um "capitalismo com face mais humana". Discutiremos duas ordens de questões, considerando a especificidade da formação social brasileira de capitalismo dependente: 1 a “construção de Estados fortes” para

    assegurar as condições de acumulação do capital, ampliando as margens do mercado de consumo, aliviando a pobreza e controlando possíveis tensões políticas e 2 a difusão da necessidade de construir uma sociedade em harmonia, que se traduz na incorporação da ética empreendedora dos empresários em todas as esferas sociais. Entendemos que este escopo político-econômico revela uma nova pedagogia da hegemonia, sustentada numa suposta alternativa
    de gerenciamento das novas expressões da “questão social”, voltada para educar o conformismo e ocultar o conflito de classes.
    Palavras-chave:  questão social; novo-desenvolvimentismo; capital social; inclusão forçada

  19. Interplay of Nitrogen-Atom Inversion and Conformational Inversion in Enantiomerization of 1H-1-Benzazepines.

    Science.gov (United States)

    Ramig, Keith; Subramaniam, Gopal; Karimi, Sasan; Szalda, David J; Ko, Allen; Lam, Aaron; Li, Jeffrey; Coaderaj, Ani; Cavdar, Leyla; Bogdan, Lukasz; Kwon, Kitae; Greer, Edyta M

    2016-04-15

    A series of 2,4-disubstituted 1H-1-benzazepines, 2a-d, 4, and 6, were studied, varying both the substituents at C2 and C4 and at the nitrogen atom. The conformational inversion (ring-flip) and nitrogen-atom inversion (N-inversion) energetics were studied by variable-temperature NMR spectroscopy and computations. The steric bulk of the nitrogen-atom substituent was found to affect both the conformation of the azepine ring and the geometry around the nitrogen atom. Also affected were the Gibbs free energy barriers for the ring-flip and the N-inversion. When the nitrogen-atom substituent was alkyl, as in 2a-c, the geometry of the nitrogen atom was nearly planar and the azepine ring was highly puckered; the result was a relatively high-energy barrier to ring-flip and a low barrier to N-inversion. Conversely, when the nitrogen-atom substituent was a hydrogen atom, as in 2d, 4, and 6, the nitrogen atom was significantly pyramidalized and the azepine ring was less puckered; the result here was a relatively high energy barrier to N-inversion and a low barrier to ring-flip. In these N-unsubstituted compounds, it was found computationally that the lowest-energy stereodynamic process was ring-flip coupled with N-inversion, as N-inversion alone had a much higher energy barrier.

  20. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

    DEFF Research Database (Denmark)

    Heinzen, Erin L; Swoboda, Kathryn J; Hitomi, Yuki

    2012-01-01

    and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation...... affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3....

  1. Some Phenomena on Negative Inversion Constructions

    Science.gov (United States)

    Sung, Tae-Soo

    2013-01-01

    We examine the characteristics of NDI (negative degree inversion) and its relation with other inversion phenomena such as SVI (subject-verb inversion) and SAI (subject-auxiliary inversion). The negative element in the NDI construction may be" not," a negative adverbial, or a negative verb. In this respect, NDI has similar licensing…

  2. An application of sparse inversion on the calculation of the inverse data space of geophysical data

    KAUST Repository

    Saragiotis, Christos

    2011-07-01

    Multiple reflections as observed in seismic reflection measurements often hide arrivals from the deeper target reflectors and need to be removed. The inverse data space provides a natural separation of primaries and surface-related multiples, as the surface multiples map onto the area around the origin while the primaries map elsewhere. However, the calculation of the inverse data is far from trivial as theory requires infinite time and offset recording. Furthermore regularization issues arise during inversion. We perform the inversion by minimizing the least-squares norm of the misfit function and by constraining the 1 norm of the solution, being the inverse data space. In this way a sparse inversion approach is obtained. We show results on field data with an application to surface multiple removal. © 2011 IEEE.

  3. Dysplastic vs. Common Naevus-associated vs. De novo Melanomas: An Observational Retrospective Study of 1,021 Patients

    Directory of Open Access Journals (Sweden)

    Alejandro Martin-Gorgojo

    2018-03-01

    Full Text Available The aim of this case-case study was to determine the differences between dysplastic and common naevus-associated melanomas (NAM and de novo melanomas. A total of 1,021 prospectively collected patients with invasive cutaneous melanoma from an oncology referral centre were included in the study. Of these, 75.51% had de novo melanomas, 12.93% dysplastic NAM, and 11.56% common NAM. Dysplastic NAM, compared with de novo melanomas, were associated with intermittently photo-exposed sites, atypical melanocytic naevi, decreased tumour thickness, and presence of MC1R non-synonymous variants. Common NAM were more frequent on the trunk and of superficial spreading type. Comparison of dysplastic with common NAM showed significant difference only with regard to mitoses. Both subtypes of NAM shared less aggressive traits than de novo melanomas, albeit with no significant differences in survival after multivariate adjustment. In conclusion, NAM present with less aggressive traits, mostly due to a greater awareness among patients of changing moles than due to their intrinsic biological characteristics.

  4. Identification of polymorphic inversions from genotypes

    Directory of Open Access Journals (Sweden)

    Cáceres Alejandro

    2012-02-01

    Full Text Available Abstract Background Polymorphic inversions are a source of genetic variability with a direct impact on recombination frequencies. Given the difficulty of their experimental study, computational methods have been developed to infer their existence in a large number of individuals using genome-wide data of nucleotide variation. Methods based on haplotype tagging of known inversions attempt to classify individuals as having a normal or inverted allele. Other methods that measure differences between linkage disequilibrium attempt to identify regions with inversions but unable to classify subjects accurately, an essential requirement for association studies. Results We present a novel method to both identify polymorphic inversions from genome-wide genotype data and classify individuals as containing a normal or inverted allele. Our method, a generalization of a published method for haplotype data 1, utilizes linkage between groups of SNPs to partition a set of individuals into normal and inverted subpopulations. We employ a sliding window scan to identify regions likely to have an inversion, and accumulation of evidence from neighboring SNPs is used to accurately determine the inversion status of each subject. Further, our approach detects inversions directly from genotype data, thus increasing its usability to current genome-wide association studies (GWAS. Conclusions We demonstrate the accuracy of our method to detect inversions and classify individuals on principled-simulated genotypes, produced by the evolution of an inversion event within a coalescent model 2. We applied our method to real genotype data from HapMap Phase III to characterize the inversion status of two known inversions within the regions 17q21 and 8p23 across 1184 individuals. Finally, we scan the full genomes of the European Origin (CEU and Yoruba (YRI HapMap samples. We find population-based evidence for 9 out of 15 well-established autosomic inversions, and for 52 regions

  5. The NOVO Network: the original scientific basis for its establishment and our R&D vision

    OpenAIRE

    Winkel, Jørgen; Edwards, Kasper; Dellve, L.; Schiller, B.; Westgaard, Rolf H.

    2017-01-01

    The NOVO network is a Nordic non-governmental professional association whose aims are to foster the scientific progress, knowledge and development of the working environment within Healthcare as an integrated part of production system development. The vision is a “Nordic Model for Sustainable Systems” in the healthcare sector. It was founded in 2006 in Copenhagen and was financially supported by the Nordic Council of Ministers from 2007 to 2015. The motivation to establish the NOVO Network ar...

  6. Genome sequencing of bacteria: sequencing, de novo assembly and rapid analysis using open source tools.

    Science.gov (United States)

    Kisand, Veljo; Lettieri, Teresa

    2013-04-01

    De novo genome sequencing of previously uncharacterized microorganisms has the potential to open up new frontiers in microbial genomics by providing insight into both functional capabilities and biodiversity. Until recently, Roche 454 pyrosequencing was the NGS method of choice for de novo assembly because it generates hundreds of thousands of long reads (tools for processing NGS data are increasingly free and open source and are often adopted for both their high quality and role in promoting academic freedom. The error rate of pyrosequencing the Alcanivorax borkumensis genome was such that thousands of insertions and deletions were artificially introduced into the finished genome. Despite a high coverage (~30 fold), it did not allow the reference genome to be fully mapped. Reads from regions with errors had low quality, low coverage, or were missing. The main defect of the reference mapping was the introduction of artificial indels into contigs through lower than 100% consensus and distracting gene calling due to artificial stop codons. No assembler was able to perform de novo assembly comparable to reference mapping. Automated annotation tools performed similarly on reference mapped and de novo draft genomes, and annotated most CDSs in the de novo assembled draft genomes. Free and open source software (FOSS) tools for assembly and annotation of NGS data are being developed rapidly to provide accurate results with less computational effort. Usability is not high priority and these tools currently do not allow the data to be processed without manual intervention. Despite this, genome assemblers now readily assemble medium short reads into long contigs (>97-98% genome coverage). A notable gap in pyrosequencing technology is the quality of base pair calling and conflicting base pairs between single reads at the same nucleotide position. Regardless, using draft whole genomes that are not finished and remain fragmented into tens of contigs allows one to characterize

  7. Spontaneous de novo vaginal adenosis resembling Bartholin’s ...

    African Journals Online (AJOL)

    Adebayo Alade Adewole

    Spontaneous de novo vaginal adenosis resembling Bartholin's cyst: A case report ... 6 by 5 cm. The cervix, uterus, adnexa and Pouch of Douglas (POD) were normal. .... of vaginal cancer.2–4 Although, DES exposed daughters have an.

  8. Immobilization of cadmium in soils by UV-mutated Bacillus subtilis 38 bioaugmentation and NovoGro amendment

    International Nuclear Information System (INIS)

    Jiang Chunxiao; Sun Hongwen; Sun Tieheng; Zhang Qingmin; Zhang Yanfeng

    2009-01-01

    Immobilization of cadmium (10 mg Cd per kilogram soil) in soil by bioaugmentation of a UV-mutated microorganism, Bacillus subtilis 38 accompanied with amendment of a bio-fertilizer, NovoGro was investigated using extractable cadmium (E-Cd) by DTPA. B. subtilis 38, the mutant with the strongest resistance against Cd, could bioaccumulate Cd four times greater than the original wild type. Single bioaugmentation of B. subtilis 38 (SB treatment) to soil however did not reduce E-Cd significantly, while the amendment of NovoGro (SN treatment) reduced E-Cd remarkably. Simultaneous application of B. subtilis 38 and NovoGro (SNB treatment) exhibited a synergetic effect compared to the single SB and SN treatment. The immobilization effect was significantly affected by temperature, soil moisture, and pH. It seems that the immobilization on Cd reached the maximum when environmental conditions favored the activity of microorganisms. Under the optimum conditions, after 90 days incubation, E-Cd was 3.34, 3.39, 2.25 and 0.87 mg kg -1 in the control soil, SB, SN and SNB soils, respectively. NovoGro not only showed a great capacity for Cd adsorption, but also promoted the growth of B. subtilis 38. This study provides a potential cost-effective technique for in situ remediation of Cd contaminated soils with bioaugmentation.

  9. Structural variation and rates of genome evolution in the grass family seen through comparison of sequences of genomes greatly differing in size.

    Science.gov (United States)

    Dvorak, Jan; Wang, Le; Zhu, Tingting; Jorgensen, Chad M; Deal, Karin R; Dai, Xiongtao; Dawson, Matthew W; Müller, Hans-Georg; Luo, Ming-Cheng; Ramasamy, Ramesh K; Dehghani, Hamid; Gu, Yong Q; Gill, Bikram S; Distelfeld, Assaf; Devos, Katrien M; Qi, Peng; You, Frank M; Gulick, Patrick J; McGuire, Patrick E

    2018-05-16

    Homology was searched with genes annotated in the Aegilops tauschii pseudomolecules against genes annotated in the pseudomolecules of tetraploid wild emmer wheat, Brachypodium distachyon, sorghum, and rice. Similar searches were initiated with genes annotated in the rice pseudomolecules. Matrices of colinear genes and rearrangements in their order were constructed. Optical Bionano genome maps were constructed and used to validate rearrangements unique to the wild emmer and Ae. tauschii genomes. Most common rearrangements were short paracentric inversions and short intrachromosomal translocations. Intrachromosomal translocations outnumbered segmental intrachromosomal duplications. The densities of paracentric inversion lengths were approximated by exponential distributions in all six genomes. Densities of colinear genes along the Ae. tauschii chromosomes were highly correlated with meiotic recombination rates but those of rearrangements were not, suggesting different causes of the erosion of gene colinearity and evolution of major chromosome rearrangements. Frequent rearrangements sharing breakpoints suggested that chromosomes have been rearranged recurrently at some sites. The distal 4 Mb of the short arms of rice chromosomes Os11 and Os12 and corresponding regions in the sorghum, B. distachyon, and Triticeae genomes contain clusters of interstitial translocations including from 1 to 7 colinear genes. The rates of acquisition of major rearrangements were greater in the wild emmer wheat and Ae. tauschii genomes than in the lineage preceding their divergence or in the B. distachyon, rice, and sorghum lineages. It is suggested that synergy between large quantities of dynamic transposable elements and annual growth habit caused the fast evolution of the Triticeae genomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

    NARCIS (Netherlands)

    Hoischen, Alexander; van Bon, Bregje W. M.; Rodríguez-Santiago, Benjamín; Gilissen, Christian; Vissers, Lisenka E. L. M.; de Vries, Petra; Janssen, Irene; van Lier, Bart; Hastings, Rob; Smithson, Sarah F.; Newbury-Ecob, Ruth; Kjaergaard, Susanne; Goodship, Judith; McGowan, Ruth; Bartholdi, Deborah; Rauch, Anita; Peippo, Maarit; Cobben, Jan M.; Wieczorek, Dagmar; Gillessen-Kaesbach, Gabriele; Veltman, Joris A.; Brunner, Han G.; de Vries, Bert B. B. A.

    2011-01-01

    Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is

  11. Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages.

    Science.gov (United States)

    Rangel-Salazar, Rubén; Wickström-Lindholm, Marie; Aguilar-Salinas, Carlos A; Alvarado-Caudillo, Yolanda; Døssing, Kristina B V; Esteller, Manel; Labourier, Emmanuel; Lund, Gertrud; Nielsen, Finn C; Rodríguez-Ríos, Dalia; Solís-Martínez, Martha O; Wrobel, Katarzyna; Wrobel, Kazimierz; Zaina, Silvio

    2011-11-25

    We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these epigenetic responses; 2) test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1) surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2) independent of the Dicer/micro-RNA pathway. Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

  12. An 11bp region with stem formation potential is essential for de novo DNA methylation of the RPS element.

    Directory of Open Access Journals (Sweden)

    Matthew Gentry

    Full Text Available The initiation of DNA methylation in Arabidopsis is controlled by the RNA-directed DNA methylation (RdDM pathway that uses 24nt siRNAs to recruit de novo methyltransferase DRM2 to the target site. We previously described the REPETITIVE PETUNIA SEQUENCE (RPS fragment that acts as a hot spot for de novo methylation, for which it requires the cooperative activity of all three methyltransferases MET1, CMT3 and DRM2, but not the RdDM pathway. RPS contains two identical 11nt elements in inverted orientation, interrupted by a 18nt spacer, which resembles the features of a stemloop structure. The analysis of deletion/substitution derivatives of this region showed that deletion of one 11nt element RPS is sufficient to eliminate de novo methylation of RPS. In addition, deletion of a 10nt region directly adjacent to one of the 11nt elements, significantly reduced de novo methylation. When both 11nt regions were replaced by two 11nt elements with altered DNA sequence but unchanged inverted repeat homology, DNA methylation was not affected, indicating that de novo methylation was not targeted to a specific DNA sequence element. These data suggest that de novo DNA methylation is attracted by a secondary structure to which the two 11nt elements contribute, and that the adjacent 10nt region influences the stability of this structure. This resembles the recognition of structural features by DNA methyltransferases in animals and suggests that similar mechanisms exist in plants.

  13. Transmuted Generalized Inverse Weibull Distribution

    OpenAIRE

    Merovci, Faton; Elbatal, Ibrahim; Ahmed, Alaa

    2013-01-01

    A generalization of the generalized inverse Weibull distribution so-called transmuted generalized inverse Weibull dis- tribution is proposed and studied. We will use the quadratic rank transmutation map (QRTM) in order to generate a flexible family of probability distributions taking generalized inverse Weibull distribution as the base value distribution by introducing a new parameter that would offer more distributional flexibility. Various structural properties including explicit expression...

  14. De novo and salvage pathway precursor incorporation during DNA replication at the nuclear matrix

    International Nuclear Information System (INIS)

    Panzeter, P.L.

    1988-01-01

    Total nuclear DNA can be empirically subdivided into low salt-soluble (LS) DNA (75-80%), high salt-soluble (HS) DNA (18-23%), and nuclear matrix-associated (NM) DNA which remains tightly bound to the nuclear matrix (∼2%). The most-newly replicated DNA is that associated with the nuclear matrix in regenerating rat liver. Analyses of the DNA fractions after various pulse times revealed that the salvage and de novo pathway DNA precursors investigated were incorporated preferentially into NM-DNA at early pulse times, after which the radioactivity became progressively incorporated into HS- and LS-DNA, respectively. These results support two models of nuclear matrix-associated DNA replication, proposed previously, and a third model presented in this dissertation. In addition, the incorporation of de novo pathway precursors lagged significantly (> 10 minutes) behind the incorporation of precursors entering through the salvage pathway. Channeling of salvage pathway precursors to DNA replication sites would explain the more rapid uptake of salvage precursors into NM-DNA than de novo precursors. To investigate the possibility of this heretofore in vitro phenomenon, the incorporation of the salvage precursor, ( 3 H)deoxythymidine, and the de novo precursor, ( 14 C)orotic acid, into NM-DNA and dTTP was examined in regenerating rat liver. There was no significant difference between the incorporation pattern of ( 14 C)orotic acid into NM-DNA thymine and that of ( 14 C)orotic acid into soluble dTTP. Contrastingly, the salvage pathway precursor, ( 3 H)deoxythymidine, labeled NM-DNA before labeling the dTTP pool

  15. Inverse Kinematics using Quaternions

    DEFF Research Database (Denmark)

    Henriksen, Knud; Erleben, Kenny; Engell-Nørregård, Morten

    In this project I describe the status of inverse kinematics research, with the focus firmly on the methods that solve the core problem. An overview of the different methods are presented Three common methods used in inverse kinematics computation have been chosen as subject for closer inspection....

  16. Optimization and inverse problems in electromagnetism

    CERN Document Server

    Wiak, Sławomir

    2003-01-01

    From 12 to 14 September 2002, the Academy of Humanities and Economics (AHE) hosted the workshop "Optimization and Inverse Problems in Electromagnetism". After this bi-annual event, a large number of papers were assembled and combined in this book. During the workshop recent developments and applications in optimization and inverse methodologies for electromagnetic fields were discussed. The contributions selected for the present volume cover a wide spectrum of inverse and optimal electromagnetic methodologies, ranging from theoretical to practical applications. A number of new optimal and inverse methodologies were proposed. There are contributions related to dedicated software. Optimization and Inverse Problems in Electromagnetism consists of three thematic chapters, covering: -General papers (survey of specific aspects of optimization and inverse problems in electromagnetism), -Methodologies, -Industrial Applications. The book can be useful to students of electrical and electronics engineering, computer sci...

  17. Inverse Compton gamma-rays from pulsars

    International Nuclear Information System (INIS)

    Morini, M.

    1983-01-01

    A model is proposed for pulsar optical and gamma-ray emission where relativistic electrons beams: (i) scatter the blackbody photons from the polar cap surface giving inverse Compton gamma-rays and (ii) produce synchrotron optical photons in the light cylinder region which are then inverse Compton scattered giving other gamma-rays. The model is applied to the Vela pulsar, explaining the first gamma-ray pulse by inverse Compton scattering of synchrotron photons near the light cylinder and the second gamma-ray pulse partly by inverse Compton scattering of synchrotron photons and partly by inverse Compton scattering of the thermal blackbody photons near the star surface. (author)

  18. Melhoramento do cafeeiro: XLII. Produtividade de progênies derivadas de hibridação dos cultivares Laurina e Mundo Novo Coffee breeding: XLII. Yield of progenies from crosses of Laurina and Mundo Novo cultivars of Coffea arabica L.

    Directory of Open Access Journals (Sweden)

    Alcides Carvalho

    1988-01-01

    Full Text Available O cultivar Laurina de Coffea arabica L. caracteriza-se pelo pequeno porte, folhas de dimensões reduzidas, frutos afilados na base, sementes pequenas e afiladas, pequeno rendimento e reduzida produção. Apresenta, no entanto, bebida de boa qualidade e baixo teor de cafeína nas sementes. Suas principais características são controladas pela ação de um par de alelos recessivos lrlr, de acentuado efeito pleiotrópico. Devido ao atual interesse do comércio por produto de baixo teor de cafeína, iniciaram-se pesquisas tendo em vista principalmente aumentar a produtividade do 'Laurina'. Para esse fim, realizaram-se numerosas hibridações de cafeeiros do 'Laurina' com os do 'Mundo Novo' (Coffea arabica e, posteriormente, retrocruzamentos com o 'Mundo Novo'. Estudaram-se as progênies F2 e retrocruzamentos com o 'Mundo Novo' (RC em Campinas, em um experimento, anotando-se as produções por oito anos consecutivos. Separaram-se algumas progênies F2 em dois grupos, antes do plantio: normais (LrLr,Lrlr e laurina (Irlr. Como testemunhas, usaram-se progênies do 'Mundo Novo' e 'Catuaí Amarelo' de C. arabica. O conjunto de plantas F2 do grupo laurina e os retrocruzamentos tiveram produção média maior do que as plantas F2 normais, porém menor do que as testemunhas. Alguns retrocruzamentos e progênies F2 apresentaram plantas com razoável produtividade, indicando que, através de retrocruzamentos com o 'Mundo Novo', podem-se obter novos tipos comerciais com as características morfológicas do 'Laurina'. Fizeram-se considerações sobre a melhor capacidade de combinação do 'Laurina' com algumas seleções do 'Mundo Novo'.The Laurina cultivars of Coffea arabica L. has a reduced plant size, small leaves, small and pointed seeds and low yield capacity. However the seeds have a good cup quality and the desirable characteristic of low caffeine content The Laurina phenotype is supposed to be controlled by a pair of recessive alleles lrlr, with

  19. Bayesian seismic AVO inversion

    Energy Technology Data Exchange (ETDEWEB)

    Buland, Arild

    2002-07-01

    A new linearized AVO inversion technique is developed in a Bayesian framework. The objective is to obtain posterior distributions for P-wave velocity, S-wave velocity and density. Distributions for other elastic parameters can also be assessed, for example acoustic impedance, shear impedance and P-wave to S-wave velocity ratio. The inversion algorithm is based on the convolutional model and a linearized weak contrast approximation of the Zoeppritz equation. The solution is represented by a Gaussian posterior distribution with explicit expressions for the posterior expectation and covariance, hence exact prediction intervals for the inverted parameters can be computed under the specified model. The explicit analytical form of the posterior distribution provides a computationally fast inversion method. Tests on synthetic data show that all inverted parameters were almost perfectly retrieved when the noise approached zero. With realistic noise levels, acoustic impedance was the best determined parameter, while the inversion provided practically no information about the density. The inversion algorithm has also been tested on a real 3-D dataset from the Sleipner Field. The results show good agreement with well logs but the uncertainty is high. The stochastic model includes uncertainties of both the elastic parameters, the wavelet and the seismic and well log data. The posterior distribution is explored by Markov chain Monte Carlo simulation using the Gibbs sampler algorithm. The inversion algorithm has been tested on a seismic line from the Heidrun Field with two wells located on the line. The uncertainty of the estimated wavelet is low. In the Heidrun examples the effect of including uncertainty of the wavelet and the noise level was marginal with respect to the AVO inversion results. We have developed a 3-D linearized AVO inversion method with spatially coupled model parameters where the objective is to obtain posterior distributions for P-wave velocity, S

  20. Algebraic properties of generalized inverses

    CERN Document Server

    Cvetković‐Ilić, Dragana S

    2017-01-01

    This book addresses selected topics in the theory of generalized inverses. Following a discussion of the “reverse order law” problem and certain problems involving completions of operator matrices, it subsequently presents a specific approach to solving the problem of the reverse order law for {1} -generalized inverses. Particular emphasis is placed on the existence of Drazin invertible completions of an upper triangular operator matrix; on the invertibility and different types of generalized invertibility of a linear combination of operators on Hilbert spaces and Banach algebra elements; on the problem of finding representations of the Drazin inverse of a 2x2 block matrix; and on selected additive results and algebraic properties for the Drazin inverse. In addition to the clarity of its content, the book discusses the relevant open problems for each topic discussed. Comments on the latest references on generalized inverses are also included. Accordingly, the book will be useful for graduate students, Ph...

  1. De novo transcriptome assembly of Setatria italica variety Taejin

    Directory of Open Access Journals (Sweden)

    Yeonhwa Jo

    2016-06-01

    Full Text Available Foxtail millet (Setaria italica belonging to the family Poaceae is an important millet that is widely cultivated in East Asia. Of the cultivated millets, the foxtail millet has the longest history and is one of the main food crops in South India and China. Moreover, foxtail millet is a model plant system for biofuel generation utilizing the C4 photosynthetic pathway. In this study, we carried out de novo transcriptome assembly for the foxtail millet variety Taejin collected from Korea using next-generation sequencing. We obtained a total of 8.676 GB raw data by paired-end sequencing. The raw data in this study can be available in NCBI SRA database with accession number of SRR3406552. The Trinity program was used to de novo assemble 145,332 transcripts. Using the TransDecoder program, we predicted 82,925 putative proteins. BLASTP was performed against the Swiss-Prot protein sequence database to annotate the functions of identified proteins, resulting in 20,555 potentially novel proteins. Taken together, this study provides transcriptome data for the foxtail millet variety Taejin by RNA-Seq.

  2. Demonstration of de novo synthesis of enzymes by density labelling with stable isotopes

    International Nuclear Information System (INIS)

    Huebner, G.; Hirschberg, K.

    1977-01-01

    The technique of in vivo density labelling of proteins with H 2 18 O and 2 H 2 O has been used to investigate hormonal regulation and developmental expression of enzymes in plant cells. Buoyant density data obtained from isopycnic equilibrium centrifugation demonstrated that the cytokinine-induced nitrate reductase activity and the gibberellic acid-induced phosphatase activity in isolated embryos of Agrostemma githago are activities of enzymes synthesized de novo. The increase in alanine-specific aminopeptidase in germinating A. githago seeds is not due to de novo synthesis but to the release of preformed enzyme. On the basis of this result it is possible to apply the enzyme aminopeptidase as an internal density standard in equilibrium centrifugation. Density labelling experiments on proteins in pea cotyledons have been used to study the change in the activity of acid phosphatase, alanine-specific aminopeptidase, and peroxidase during germination. The activities of these enzymes increase in cotyledons of Pisum sativum. Density labelling by 18 O and 2 H demonstrates de novo synthesis of these three enzymes. The differential time course of enzyme induction shows the advantage of using H 2 18 O as labelling substance in cases when the enzyme was synthesized immediately at the beginning of germination. At this stage of development the amino-acid pool available for synthesis is formed principally by means of hydrolysis of storage proteins. The incorporation of 2 H into the new proteins takes place in a measurable amount at a stage of growth in which the amino acids are also synthesized de novo. The enzyme acid phosphatase of pea cotyledons was chosen to demonstrate the possibility of using the density labelling technique to detect protein turnover. (author)

  3. Optimizing de novo common wheat transcriptome assembly using short-read RNA-Seq data

    Directory of Open Access Journals (Sweden)

    Duan Jialei

    2012-08-01

    Full Text Available Abstract Background Rapid advances in next-generation sequencing methods have provided new opportunities for transcriptome sequencing (RNA-Seq. The unprecedented sequencing depth provided by RNA-Seq makes it a powerful and cost-efficient method for transcriptome study, and it has been widely used in model organisms and non-model organisms to identify and quantify RNA. For non-model organisms lacking well-defined genomes, de novo assembly is typically required for downstream RNA-Seq analyses, including SNP discovery and identification of genes differentially expressed by phenotypes. Although RNA-Seq has been successfully used to sequence many non-model organisms, the results of de novo assembly from short reads can still be improved by using recent bioinformatic developments. Results In this study, we used 212.6 million pair-end reads, which accounted for 16.2 Gb, to assemble the hexaploid wheat transcriptome. Two state-of-the-art assemblers, Trinity and Trans-ABySS, which use the single and multiple k-mer methods, respectively, were used, and the whole de novo assembly process was divided into the following four steps: pre-assembly, merging different samples, removal of redundancy and scaffolding. We documented every detail of these steps and how these steps influenced assembly performance to gain insight into transcriptome assembly from short reads. After optimization, the assembled transcripts were comparable to Sanger-derived ESTs in terms of both continuity and accuracy. We also provided considerable new wheat transcript data to the community. Conclusions It is feasible to assemble the hexaploid wheat transcriptome from short reads. Special attention should be paid to dealing with multiple samples to balance the spectrum of expression levels and redundancy. To obtain an accurate overview of RNA profiling, removal of redundancy may be crucial in de novo assembly.

  4. Workflow for near-surface velocity automatic estimation: Source-domain full-traveltime inversion followed by waveform inversion

    KAUST Repository

    Liu, Lu

    2017-08-17

    This paper presents a workflow for near-surface velocity automatic estimation using the early arrivals of seismic data. This workflow comprises two methods, source-domain full traveltime inversion (FTI) and early-arrival waveform inversion. Source-domain FTI is capable of automatically generating a background velocity that can kinematically match the reconstructed plane-wave sources of early arrivals with true plane-wave sources. This method does not require picking first arrivals for inversion, which is one of the most challenging aspects of ray-based first-arrival tomographic inversion. Moreover, compared with conventional Born-based methods, source-domain FTI can distinguish between slower or faster initial model errors via providing the correct sign of the model gradient. In addition, this method does not need estimation of the source wavelet, which is a requirement for receiver-domain wave-equation velocity inversion. The model derived from source-domain FTI is then used as input to early-arrival waveform inversion to obtain the short-wavelength velocity components. We have tested the workflow on synthetic and field seismic data sets. The results show source-domain FTI can generate reasonable background velocities for early-arrival waveform inversion even when subsurface velocity reversals are present and the workflow can produce a high-resolution near-surface velocity model.

  5. n-Colour even self-inverse compositions

    Indian Academy of Sciences (India)

    An -colour even self-inverse composition is defined as an -colour self-inverse composition with even parts. In this paper, we get generating functions, explicit formulas and recurrence formulas for -colour even self-inverse compositions. One new binomial identity is also obtained.

  6. Mutation studies in gamma-ray treated peas

    Energy Technology Data Exchange (ETDEWEB)

    Narsinghani, V G; Kumar, S [Jawaharlal Nehru Krishi Vishwa Vidyalaya, Jabalpur (India). Dept. of Plant Breeding

    1976-01-01

    Pea Seeds (Pisum Sativum L. 2n=14) irradiated with four doses of gamma rays viz, 10, 15, 20 and 25 kR revealed a reduction in seedling height, survival percentage, pods and seed yield and pollen fertility during X/sub 1/ and X/sub 2/ generations. Chlorophyll and leaf mutations were noted. The mitotic cells indicated chromosomal aberrations which were dose dependent. In meiosis, translocated rings and chains of 4,6 and 8 chromosomes; paracentric and pericentric inversions, fragments, laggards and unequal distribution of chromosomes were observed. Besides, the frequency of aberrations were lower during X/sub 2/ as compared to X/sub 1/.

  7. EDITORIAL: Inverse Problems in Engineering

    Science.gov (United States)

    West, Robert M.; Lesnic, Daniel

    2007-01-01

    Presented here are 11 noteworthy papers selected from the Fifth International Conference on Inverse Problems in Engineering: Theory and Practice held in Cambridge, UK during 11-15 July 2005. The papers have been peer-reviewed to the usual high standards of this journal and the contributions of reviewers are much appreciated. The conference featured a good balance of the fundamental mathematical concepts of inverse problems with a diverse range of important and interesting applications, which are represented here by the selected papers. Aspects of finite-element modelling and the performance of inverse algorithms are investigated by Autrique et al and Leduc et al. Statistical aspects are considered by Emery et al and Watzenig et al with regard to Bayesian parameter estimation and inversion using particle filters. Electrostatic applications are demonstrated by van Berkel and Lionheart and also Nakatani et al. Contributions to the applications of electrical techniques and specifically electrical tomographies are provided by Wakatsuki and Kagawa, Kim et al and Kortschak et al. Aspects of inversion in optical tomography are investigated by Wright et al and Douiri et al. The authors are representative of the worldwide interest in inverse problems relating to engineering applications and their efforts in producing these excellent papers will be appreciated by many readers of this journal.

  8. NxRepair: error correction in de novo sequence assembly using Nextera mate pairs

    Directory of Open Access Journals (Sweden)

    Rebecca R. Murphy

    2015-06-01

    Full Text Available Scaffolding errors and incorrect repeat disambiguation during de novo assembly can result in large scale misassemblies in draft genomes. Nextera mate pair sequencing data provide additional information to resolve assembly ambiguities during scaffolding. Here, we introduce NxRepair, an open source toolkit for error correction in de novo assemblies that uses Nextera mate pair libraries to identify and correct large-scale errors. We show that NxRepair can identify and correct large scaffolding errors, without use of a reference sequence, resulting in quantitative improvements in the assembly quality. NxRepair can be downloaded from GitHub or PyPI, the Python Package Index; a tutorial and user documentation are also available.

  9. Novos encontros de anofelíneos em recipientes artificiais

    Directory of Open Access Journals (Sweden)

    Oswaldo Paulo Forattini

    1998-12-01

    Full Text Available Assinalam-se novos encontros de anofelíneos em recipientes artificiais. Um deles diz respeito a formas imaturas de Anopheles bellator em criadouros experimentais e outro é concernente ao achado de An. albitarsis l.s., em recipiente abandonado. Tecem-se considerações sobre a pressão seletiva representada pela produção, cada vez maior, de objetos descartáveis.

  10. Building a better fragment library for de novo protein structure prediction.

    Directory of Open Access Journals (Sweden)

    Saulo H P de Oliveira

    Full Text Available Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10. We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. "Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources".

  11. Building a Better Fragment Library for De Novo Protein Structure Prediction

    Science.gov (United States)

    de Oliveira, Saulo H. P.; Shi, Jiye; Deane, Charlotte M.

    2015-01-01

    Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”. PMID:25901595

  12. Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

    Directory of Open Access Journals (Sweden)

    Rangel-Salazar Rubén

    2011-11-01

    Full Text Available Abstract Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces a set of repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation and histone 4 lysine 20 (H4K20 hypermethylation in THP-1 macrophages. Here, we: 1 ask what gene expression changes accompany these epigenetic responses; 2 test the involvement of candidate factors mediating the latter. We exploited genome expression arrays to identify target genes for lipoprotein-induced silencing, in addition to RNAi and expression studies to test the involvement of candidate mediating factors. The study was conducted in human THP-1 macrophages. Results Native lipoprotein-induced de novo DNA methylation was associated with a general repression of various critical genes for macrophage function, including pro-inflammatory genes. Lipoproteins showed differential effects on epigenetic marks, as de novo DNA methylation was induced by VLDL and to a lesser extent by LDL, but not by HDL, and VLDL induced H4K20 hypermethylation, while HDL caused H4 deacetylation. The analysis of candidate factors mediating VLDL-induced DNA hypermethylation revealed that this response was: 1 surprisingly, mediated exclusively by the canonical maintenance DNA methyltransferase DNMT1, and 2 independent of the Dicer/micro-RNA pathway. Conclusions Our work provides novel insights into epigenetic gene regulation by native lipoproteins. Furthermore, we provide an example of DNMT1 acting as a de novo DNA methyltransferase independently of canonical de novo enzymes, and show proof of principle that de novo DNA methylation can occur independently of a functional Dicer/micro-RNA pathway in mammals.

  13. De novo post-pollen mitosis II tobacco pollen tube transcriptome

    Czech Academy of Sciences Publication Activity Database

    Hafidh, Said; Breznenová, Katarína; Honys, David

    2012-01-01

    Roč. 7, č. 8 (2012), s. 918-921 ISSN 1559-2316 R&D Projects: GA ČR GPP501/11/P321; GA ČR GA522/09/0858 Institutional research plan: CEZ:AV0Z50380511 Keywords : de novo pollen tube transcriptome * male gametophyte development * pollen tube growth Subject RIV: ED - Physiology

  14. On the calibration process of film dosimetry: OLS inverse regression versus WLS inverse prediction

    International Nuclear Information System (INIS)

    Crop, F; Thierens, H; Rompaye, B Van; Paelinck, L; Vakaet, L; Wagter, C De

    2008-01-01

    The purpose of this study was both putting forward a statistically correct model for film calibration and the optimization of this process. A reliable calibration is needed in order to perform accurate reference dosimetry with radiographic (Gafchromic) film. Sometimes, an ordinary least squares simple linear (in the parameters) regression is applied to the dose-optical-density (OD) curve with the dose as a function of OD (inverse regression) or sometimes OD as a function of dose (inverse prediction). The application of a simple linear regression fit is an invalid method because heteroscedasticity of the data is not taken into account. This could lead to erroneous results originating from the calibration process itself and thus to a lower accuracy. In this work, we compare the ordinary least squares (OLS) inverse regression method with the correct weighted least squares (WLS) inverse prediction method to create calibration curves. We found that the OLS inverse regression method could lead to a prediction bias of up to 7.3 cGy at 300 cGy and total prediction errors of 3% or more for Gafchromic EBT film. Application of the WLS inverse prediction method resulted in a maximum prediction bias of 1.4 cGy and total prediction errors below 2% in a 0-400 cGy range. We developed a Monte-Carlo-based process to optimize calibrations, depending on the needs of the experiment. This type of thorough analysis can lead to a higher accuracy for film dosimetry

  15. Anisotropic wave-equation traveltime and waveform inversion

    KAUST Repository

    Feng, Shihang

    2016-09-06

    The wave-equation traveltime and waveform inversion (WTW) methodology is developed to invert for anisotropic parameters in a vertical transverse isotropic (VTI) meidum. The simultaneous inversion of anisotropic parameters v0, ε and δ is initially performed using the wave-equation traveltime inversion (WT) method. The WT tomograms are then used as starting background models for VTI full waveform inversion. Preliminary numerical tests on synthetic data demonstrate the feasibility of this method for multi-parameter inversion.

  16. Inverse logarithmic potential problem

    CERN Document Server

    Cherednichenko, V G

    1996-01-01

    The Inverse and Ill-Posed Problems Series is a series of monographs publishing postgraduate level information on inverse and ill-posed problems for an international readership of professional scientists and researchers. The series aims to publish works which involve both theory and applications in, e.g., physics, medicine, geophysics, acoustics, electrodynamics, tomography, and ecology.

  17. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    DEFF Research Database (Denmark)

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

    2007-01-01

    Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...... at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein...

  18. Inverse Kinematics of a Serial Robot

    Directory of Open Access Journals (Sweden)

    Amici Cinzia

    2016-01-01

    Full Text Available This work describes a technique to treat the inverse kinematics of a serial manipulator. The inverse kinematics is obtained through the numerical inversion of the Jacobian matrix, that represents the equation of motion of the manipulator. The inversion is affected by numerical errors and, in different conditions, due to the numerical nature of the solver, it does not converge to a reasonable solution. Thus a soft computing approach is adopted to mix different traditional methods to obtain an increment of algorithmic convergence.

  19. De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

    Science.gov (United States)

    Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

    2018-05-08

    Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

  20. Norgal: extraction and de novo assembly of mitochondrial DNA from whole-genome sequencing data.

    Science.gov (United States)

    Al-Nakeeb, Kosai; Petersen, Thomas Nordahl; Sicheritz-Pontén, Thomas

    2017-11-21

    Whole-genome sequencing (WGS) projects provide short read nucleotide sequences from nuclear and possibly organelle DNA depending on the source of origin. Mitochondrial DNA is present in animals and fungi, while plants contain DNA from both mitochondria and chloroplasts. Current techniques for separating organelle reads from nuclear reads in WGS data require full reference or partial seed sequences for assembling. Norgal (de Novo ORGAneLle extractor) avoids this requirement by identifying a high frequency subset of k-mers that are predominantly of mitochondrial origin and performing a de novo assembly on a subset of reads that contains these k-mers. The method was applied to WGS data from a panda, brown algae seaweed, butterfly and filamentous fungus. We were able to extract full circular mitochondrial genomes and obtained sequence identities to the reference sequences in the range from 98.5 to 99.5%. We also assembled the chloroplasts of grape vines and cucumbers using Norgal together with seed-based de novo assemblers. Norgal is a pipeline that can extract and assemble full or partial mitochondrial and chloroplast genomes from WGS short reads without prior knowledge. The program is available at: https://bitbucket.org/kosaidtu/norgal .

  1. Testing earthquake source inversion methodologies

    KAUST Repository

    Page, Morgan T.; Mai, Paul Martin; Schorlemmer, Danijel

    2011-01-01

    Source Inversion Validation Workshop; Palm Springs, California, 11-12 September 2010; Nowadays earthquake source inversions are routinely performed after large earthquakes and represent a key connection between recorded seismic and geodetic data

  2. Inverse transition radiation

    International Nuclear Information System (INIS)

    Steinhauer, L.C.; Romea, R.D.; Kimura, W.D.

    1997-01-01

    A new method for laser acceleration is proposed based upon the inverse process of transition radiation. The laser beam intersects an electron-beam traveling between two thin foils. The principle of this acceleration method is explored in terms of its classical and quantum bases and its inverse process. A closely related concept based on the inverse of diffraction radiation is also presented: this concept has the significant advantage that apertures are used to allow free passage of the electron beam. These concepts can produce net acceleration because they do not satisfy the conditions in which the Lawson-Woodward theorem applies (no net acceleration in an unbounded vacuum). Finally, practical aspects such as damage limits at optics are employed to find an optimized set of parameters. For reasonable assumptions an acceleration gradient of 200 MeV/m requiring a laser power of less than 1 GW is projected. An interesting approach to multi-staging the acceleration sections is also presented. copyright 1997 American Institute of Physics

  3. Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates.

    Directory of Open Access Journals (Sweden)

    Jia-Yu Chen

    2015-07-01

    Full Text Available While some human-specific protein-coding genes have been proposed to originate from ancestral lncRNAs, the transition process remains poorly understood. Here we identified 64 hominoid-specific de novo genes and report a mechanism for the origination of functional de novo proteins from ancestral lncRNAs with precise splicing structures and specific tissue expression profiles. Whole-genome sequencing of dozens of rhesus macaque animals revealed that these lncRNAs are generally not more selectively constrained than other lncRNA loci. The existence of these newly-originated de novo proteins is also not beyond anticipation under neutral expectation, as they generally have longer theoretical lifespan than their current age, due to their GC-rich sequence property enabling stable ORFs with lower chance of non-sense mutations. Interestingly, although the emergence and retention of these de novo genes are likely driven by neutral forces, population genetics study in 67 human individuals and 82 macaque animals revealed signatures of purifying selection on these genes specifically in human population, indicating a proportion of these newly-originated proteins are already functional in human. We thus propose a mechanism for creation of functional de novo proteins from ancestral lncRNAs during the primate evolution, which may contribute to human-specific genetic novelties by taking advantage of existed genomic contexts.

  4. Critical importance of the de novo pyrimidine biosynthesis pathway for Trypanosoma cruzi growth in the mammalian host cell cytoplasm

    International Nuclear Information System (INIS)

    Hashimoto, Muneaki; Morales, Jorge; Fukai, Yoshihisa; Suzuki, Shigeo; Takamiya, Shinzaburo; Tsubouchi, Akiko; Inoue, Syou; Inoue, Masayuki; Kita, Kiyoshi; Harada, Shigeharu; Tanaka, Akiko; Aoki, Takashi; Nara, Takeshi

    2012-01-01

    Highlights: ► We established Trypanosoma cruzi lacking the gene for carbamoyl phosphate synthetase II. ► Disruption of the cpsII gene significantly reduced the growth of epimastigotes. ► In particular, the CPSII-null mutant severely retarded intracellular growth. ► The de novo pyrimidine pathway is critical for the parasite growth in the host cell. -- Abstract: The intracellular parasitic protist Trypanosoma cruzi is the causative agent of Chagas disease in Latin America. In general, pyrimidine nucleotides are supplied by both de novo biosynthesis and salvage pathways. While epimastigotes—an insect form—possess both activities, amastigotes—an intracellular replicating form of T. cruzi—are unable to mediate the uptake of pyrimidine. However, the requirement of de novo pyrimidine biosynthesis for parasite growth and survival has not yet been elucidated. Carbamoyl-phosphate synthetase II (CPSII) is the first and rate-limiting enzyme of the de novo biosynthetic pathway, and increased CPSII activity is associated with the rapid proliferation of tumor cells. In the present study, we showed that disruption of the T. cruzicpsII gene significantly reduced parasite growth. In particular, the growth of amastigotes lacking the cpsII gene was severely suppressed. Thus, the de novo pyrimidine pathway is important for proliferation of T. cruzi in the host cell cytoplasm and represents a promising target for chemotherapy against Chagas disease.

  5. ENDOR with band-selective shaped inversion pulses

    Science.gov (United States)

    Tait, Claudia E.; Stoll, Stefan

    2017-04-01

    Electron Nuclear DOuble Resonance (ENDOR) is based on the measurement of nuclear transition frequencies through detection of changes in the polarization of electron transitions. In Davies ENDOR, the initial polarization is generated by a selective microwave inversion pulse. The rectangular inversion pulses typically used are characterized by a relatively low selectivity, with full inversion achieved only for a limited number of spin packets with small resonance offsets. With the introduction of pulse shaping to EPR, the rectangular inversion pulses can be replaced with shaped pulses with increased selectivity. Band-selective inversion pulses are characterized by almost rectangular inversion profiles, leading to full inversion for spin packets with resonance offsets within the pulse excitation bandwidth and leaving spin packets outside the excitation bandwidth largely unaffected. Here, we explore the consequences of using different band-selective amplitude-modulated pulses designed for NMR as the inversion pulse in ENDOR. We find an increased sensitivity for small hyperfine couplings compared to rectangular pulses of the same bandwidth. In echo-detected Davies-type ENDOR, finite Fourier series inversion pulses combine the advantages of increased absolute ENDOR sensitivity of short rectangular inversion pulses and increased sensitivity for small hyperfine couplings of long rectangular inversion pulses. The use of pulses with an almost rectangular frequency-domain profile also allows for increased control of the hyperfine contrast selectivity. At X-band, acquisition of echo transients as a function of radiofrequency and appropriate selection of integration windows during data processing allows efficient separation of contributions from weakly and strongly coupled nuclei in overlapping ENDOR spectra within a single experiment.

  6. Novos liberalismos e a Grande Recessão: princípios para uma política externa crítica

    Directory of Open Access Journals (Sweden)

    Igor Abdalla

    2014-06-01

    Full Text Available O artigo analisa a emergência, nas últimas décadas, de novo liberalismo internacionalista de cunho tecnocrático, que se divorcia do liberalismo clássico criado pelo filósofo crítico Immanuel Kant. O novo liberalismo, que coincide com o processo de globalização das finanças, inverte o elemento emancipatório do liberalismo kantiano para apresentar-se como instância de ratificação do poder. Como resultado, os novos liberais são incapazes de analisar criticamente eventos como a Grande Recessão. Em contraposição ao novo liberalismo tecnocrático propõem-se princípios para uma política externa crítica para o Brasil. Em termos empíricos, escrutina-se a evolução do processo de globalização das finanças do ponto de vista do poder, com enfoque sobre as crises financeiras no mundo em desenvolvimento e a Grande Recessão de 2008. Propugnam-se os seguintes argumentos: (i o novo liberalismo contradiz o liberalismo clássico; (ii o novo liberalismo legitima interesses de atores hegemônicos voltados para a liberalização e a desregulamentação financeiras sem limites, que se encontram na raiz da Grande Recessão; (iii a política externa brasileira deve resgatar elementos do liberalismo clássico no contexto de crise gerado pela Grande Recessão.

  7. Inverse problems in the Bayesian framework

    International Nuclear Information System (INIS)

    Calvetti, Daniela; Somersalo, Erkki; Kaipio, Jari P

    2014-01-01

    The history of Bayesian methods dates back to the original works of Reverend Thomas Bayes and Pierre-Simon Laplace: the former laid down some of the basic principles on inverse probability in his classic article ‘An essay towards solving a problem in the doctrine of chances’ that was read posthumously in the Royal Society in 1763. Laplace, on the other hand, in his ‘Memoirs on inverse probability’ of 1774 developed the idea of updating beliefs and wrote down the celebrated Bayes’ formula in the form we know today. Although not identified yet as a framework for investigating inverse problems, Laplace used the formalism very much in the spirit it is used today in the context of inverse problems, e.g., in his study of the distribution of comets. With the evolution of computational tools, Bayesian methods have become increasingly popular in all fields of human knowledge in which conclusions need to be drawn based on incomplete and noisy data. Needless to say, inverse problems, almost by definition, fall into this category. Systematic work for developing a Bayesian inverse problem framework can arguably be traced back to the 1980s, (the original first edition being published by Elsevier in 1987), although articles on Bayesian methodology applied to inverse problems, in particular in geophysics, had appeared much earlier. Today, as testified by the articles in this special issue, the Bayesian methodology as a framework for considering inverse problems has gained a lot of popularity, and it has integrated very successfully with many traditional inverse problems ideas and techniques, providing novel ways to interpret and implement traditional procedures in numerical analysis, computational statistics, signal analysis and data assimilation. The range of applications where the Bayesian framework has been fundamental goes from geophysics, engineering and imaging to astronomy, life sciences and economy, and continues to grow. There is no question that Bayesian

  8. Long-read sequencing and de novo assembly of a Chinese genome

    Science.gov (United States)

    Short-read sequencing has enabled the de novo assembly of several individual human genomes, but with inherent limitations in characterizing repeat elements. Here we sequence a Chinese individual HX1 by single-molecule real-time (SMRT) long-read sequencing, construct a physical map by NanoChannel arr...

  9. De novo centriole formation in human cells is error-prone and does not require SAS-6 self-assembly.

    Science.gov (United States)

    Wang, Won-Jing; Acehan, Devrim; Kao, Chien-Han; Jane, Wann-Neng; Uryu, Kunihiro; Tsou, Meng-Fu Bryan

    2015-11-26

    Vertebrate centrioles normally propagate through duplication, but in the absence of preexisting centrioles, de novo synthesis can occur. Consistently, centriole formation is thought to strictly rely on self-assembly, involving self-oligomerization of the centriolar protein SAS-6. Here, through reconstitution of de novo synthesis in human cells, we surprisingly found that normal looking centrioles capable of duplication and ciliation can arise in the absence of SAS-6 self-oligomerization. Moreover, whereas canonically duplicated centrioles always form correctly, de novo centrioles are prone to structural errors, even in the presence of SAS-6 self-oligomerization. These results indicate that centriole biogenesis does not strictly depend on SAS-6 self-assembly, and may require preexisting centrioles to ensure structural accuracy, fundamentally deviating from the current paradigm.

  10. Cinema utópico: a construção de um novo homem e um novo mundo

    OpenAIRE

    Erika Savernini Lopes

    2011-01-01

    O cinema, desde seus primórdios, prefigurou o espaço cibernético como um novo espaço imaterial construído coletivamente. A concepção desse outro lugar não físico para o qual o homem poderia migrar estabelece para o cinema e para o ciberespaço uma relação direta com as utopias. Na acepção do romance filosófico de Thomas More, a Utopia define-se como um outro espaço não-existente, irrealizável e ideal que diagnostica o atual. O cinema carregaria caracteres fundamentais da Utopia tanto no que se...

  11. Bayesian approach to inverse statistical mechanics

    Science.gov (United States)

    Habeck, Michael

    2014-05-01

    Inverse statistical mechanics aims to determine particle interactions from ensemble properties. This article looks at this inverse problem from a Bayesian perspective and discusses several statistical estimators to solve it. In addition, a sequential Monte Carlo algorithm is proposed that draws the interaction parameters from their posterior probability distribution. The posterior probability involves an intractable partition function that is estimated along with the interactions. The method is illustrated for inverse problems of varying complexity, including the estimation of a temperature, the inverse Ising problem, maximum entropy fitting, and the reconstruction of molecular interaction potentials.

  12. De novo mutations in HCN1 cause early infantile epileptic encephalopathy.

    Science.gov (United States)

    Nava, Caroline; Dalle, Carine; Rastetter, Agnès; Striano, Pasquale; de Kovel, Carolien G F; Nabbout, Rima; Cancès, Claude; Ville, Dorothée; Brilstra, Eva H; Gobbi, Giuseppe; Raffo, Emmanuel; Bouteiller, Delphine; Marie, Yannick; Trouillard, Oriane; Robbiano, Angela; Keren, Boris; Agher, Dahbia; Roze, Emmanuel; Lesage, Suzanne; Nicolas, Aude; Brice, Alexis; Baulac, Michel; Vogt, Cornelia; El Hajj, Nady; Schneider, Eberhard; Suls, Arvid; Weckhuysen, Sarah; Gormley, Padhraig; Lehesjoki, Anna-Elina; De Jonghe, Peter; Helbig, Ingo; Baulac, Stéphanie; Zara, Federico; Koeleman, Bobby P C; Haaf, Thomas; LeGuern, Eric; Depienne, Christel

    2014-06-01

    Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels contribute to cationic Ih current in neurons and regulate the excitability of neuronal networks. Studies in rat models have shown that the Hcn1 gene has a key role in epilepsy, but clinical evidence implicating HCN1 mutations in human epilepsy is lacking. We carried out exome sequencing for parent-offspring trios with fever-sensitive, intractable epileptic encephalopathy, leading to the discovery of two de novo missense HCN1 mutations. Screening of follow-up cohorts comprising 157 cases in total identified 4 additional amino acid substitutions. Patch-clamp recordings of Ih currents in cells expressing wild-type or mutant human HCN1 channels showed that the mutations had striking but divergent effects on homomeric channels. Individuals with mutations had clinical features resembling those of Dravet syndrome with progression toward atypical absences, intellectual disability and autistic traits. These findings provide clear evidence that de novo HCN1 point mutations cause a recognizable early-onset epileptic encephalopathy in humans.

  13. Reverse Universal Resolving Algorithm and inverse driving

    DEFF Research Database (Denmark)

    Pécseli, Thomas

    2012-01-01

    Inverse interpretation is a semantics based, non-standard interpretation of programs. Given a program and a value, an inverse interpreter finds all or one of the inputs, that would yield the given value as output with normal forward evaluation. The Reverse Universal Resolving Algorithm is a new...... variant of the Universal Resolving Algorithm for inverse interpretation. The new variant outperforms the original algorithm in several cases, e.g., when unpacking a list using inverse interpretation of a pack program. It uses inverse driving as its main technique, which has not been described in detail...... before. Inverse driving may find application with, e.g., supercompilation, thus suggesting a new kind of program inverter....

  14. The Source Inversion Validation (SIV) Initiative: A Collaborative Study on Uncertainty Quantification in Earthquake Source Inversions

    Science.gov (United States)

    Mai, P. M.; Schorlemmer, D.; Page, M.

    2012-04-01

    Earthquake source inversions image the spatio-temporal rupture evolution on one or more fault planes using seismic and/or geodetic data. Such studies are critically important for earthquake seismology in general, and for advancing seismic hazard analysis in particular, as they reveal earthquake source complexity and help (i) to investigate earthquake mechanics; (ii) to develop spontaneous dynamic rupture models; (iii) to build models for generating rupture realizations for ground-motion simulations. In applications (i - iii), the underlying finite-fault source models are regarded as "data" (input information), but their uncertainties are essentially unknown. After all, source models are obtained from solving an inherently ill-posed inverse problem to which many a priori assumptions and uncertain observations are applied. The Source Inversion Validation (SIV) project is a collaborative effort to better understand the variability between rupture models for a single earthquake (as manifested in the finite-source rupture model database) and to develop robust uncertainty quantification for earthquake source inversions. The SIV project highlights the need to develop a long-standing and rigorous testing platform to examine the current state-of-the-art in earthquake source inversion, and to develop and test novel source inversion approaches. We will review the current status of the SIV project, and report the findings and conclusions of the recent workshops. We will briefly discuss several source-inversion methods, how they treat uncertainties in data, and assess the posterior model uncertainty. Case studies include initial forward-modeling tests on Green's function calculations, and inversion results for synthetic data from spontaneous dynamic crack-like strike-slip earthquake on steeply dipping fault, embedded in a layered crustal velocity-density structure.

  15. De novo FGF12 mutation in 2 patients with neonatal-onset epilepsy

    Science.gov (United States)

    Guella, Ilaria; Huh, Linda; McKenzie, Marna B.; Toyota, Eric B.; Bebin, E. Martina; Thompson, Michelle L.; Cooper, Gregory M.; Evans, Daniel M.; Buerki, Sarah E.; Adam, Shelin; Van Allen, Margot I.; Nelson, Tanya N.; Connolly, Mary B.; Farrer, Matthew J.

    2016-01-01

    Objective: We describe 2 additional patients with early-onset epilepsy with a de novo FGF12 mutation. Methods: Whole-exome sequencing was performed in 2 unrelated patients with early-onset epilepsy and their unaffected parents. Genetic variants were assessed by comparative trio analysis. Clinical evolution, EEG, and neuroimaging are described. The phenotype and response to treatment was reviewed and compared to affected siblings in the original report. Results: We identified the same FGF12 de novo mutation reported previously (c.G155A, p.R52H) in 2 additional patients with early-onset epilepsy. Similar to the original brothers described, both presented with tonic seizures in the first month of life. In the first patient, seizures responded to sodium channel blockers and her development was normal at 11 months. Patient 2 is a 15-year-old girl with treatment-resistant focal epilepsy, moderate intellectual disability, and autism. Carbamazepine (sodium channel blocker) was tried later in her course but not continued due to an allergic reaction. Conclusions: The identification of a recurrent de novo mutation in 2 additional unrelated probands with early-onset epilepsy supports the role of FGF12 p.R52H in disease pathogenesis. Affected carriers presented with similar early clinical phenotypes; however, this report expands the phenotype associated with this mutation which contrasts with the progressive course and early mortality of the siblings in the original report. PMID:27872899

  16. Statistical perspectives on inverse problems

    DEFF Research Database (Denmark)

    Andersen, Kim Emil

    of the interior of an object from electrical boundary measurements. One part of this thesis concerns statistical approaches for solving, possibly non-linear, inverse problems. Thus inverse problems are recasted in a form suitable for statistical inference. In particular, a Bayesian approach for regularisation...... problem is given in terms of probability distributions. Posterior inference is obtained by Markov chain Monte Carlo methods and new, powerful simulation techniques based on e.g. coupled Markov chains and simulated tempering is developed to improve the computational efficiency of the overall simulation......Inverse problems arise in many scientific disciplines and pertain to situations where inference is to be made about a particular phenomenon from indirect measurements. A typical example, arising in diffusion tomography, is the inverse boundary value problem for non-invasive reconstruction...

  17. Identification of de novo mutations of Duchénnè/Becker muscular dystrophies in southern Spain.

    Science.gov (United States)

    Garcia, Susana; de Haro, Tomás; Zafra-Ceres, Mercedes; Poyatos, Antonio; Gomez-Capilla, Jose A; Gomez-Llorente, Carolina

    2014-01-01

    Duchénnè/Becker muscular dystrophies (DMD/BMD) are X-linked diseases, which are caused by a de novo gene mutation in one-third of affected males. The study objectives were to determine the incidence of DMD/BMD in Andalusia (Spain) and to establish the percentage of affected males in whom a de novo gene mutation was responsible. Multiplex ligation-dependent probe amplification (MLPA) technology was applied to determine the incidence of DMD/BMD in 84 males with suspicion of the disease and 106 female relatives. Dystrophin gene exon deletion (89.5%) or duplication (10.5%) was detected in 38 of the 84 males by MLPA technology; de novo mutations account for 4 (16.7%) of the 24 mother-son pairs studied. MLPA technology is adequate for the molecular diagnosis of DMD/BMD and establishes whether the mother carries the molecular alteration responsible for the disease, a highly relevant issue for genetic counseling.

  18. Management, nutrition, and lactation performance are related to bulk tank milk de novo fatty acid concentration on northeastern US dairy farms.

    Science.gov (United States)

    Woolpert, M E; Dann, H M; Cotanch, K W; Melilli, C; Chase, L E; Grant, R J; Barbano, D M

    2016-10-01

    This study investigated the relationship of management practices, dietary characteristics, milk composition, and lactation performance with de novo fatty acid (FA) concentration in bulk tank milk from commercial dairy farms with Holstein, Jersey, and mixed-breed cows. It was hypothesized that farms with higher de novo milk FA concentrations would more commonly use management and nutrition practices known to optimize ruminal conditions that enhance de novo synthesis of milk FA. Farms (n=44) located in Vermont and northeastern New York were selected based on a history of high de novo (HDN; 26.18±0.94g/100g of FA; mean ± standard deviation) or low de novo (LDN; 24.19±1.22g/100g of FA) FA in bulk tank milk. Management practices were assessed during one visit to each farm in March or April, 2014. Total mixed ration samples were collected and analyzed for chemical composition using near infrared spectroscopy. We found no differences in days in milk at the farm level. Yield of milk fat, true protein, and de novo FA per cow per day were higher for HDN versus LDN farms. The HDN farms had lower freestall stocking density (cows/stall) than LDN farms. Additionally, tiestall feeding frequency was higher for HDN than LDN farms. No differences between HDN and LDN farms were detected for dietary dry matter, crude protein, neutral detergent fiber, starch, or percentage of forage in the diet. However, dietary ether extract was lower for HDN than LDN farms. This research indicates that overcrowded freestalls, reduced feeding frequency, and greater dietary ether extract content are associated with lower de novo FA synthesis and reduced milk fat and true protein yields on commercial dairy farms. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Alternative normalization methods demonstrate widespread cortical hypometabolism in untreated de novo Parkinson's disease

    DEFF Research Database (Denmark)

    Berti, Valentina; Polito, C; Borghammer, Per

    2012-01-01

    , recent studies suggested that conventional data normalization procedures may not always be valid, and demonstrated that alternative normalization strategies better allow detection of low magnitude changes. We hypothesized that these alternative normalization procedures would disclose more widespread...... metabolic alterations in de novo PD. METHODS: [18F]FDG PET scans of 26 untreated de novo PD patients (Hoehn & Yahr stage I-II) and 21 age-matched controls were compared using voxel-based analysis. Normalization was performed using gray matter (GM), white matter (WM) reference regions and Yakushev...... normalization. RESULTS: Compared to GM normalization, WM and Yakushev normalization procedures disclosed much larger cortical regions of relative hypometabolism in the PD group with extensive involvement of frontal and parieto-temporal-occipital cortices, and several subcortical structures. Furthermore...

  20. Forward modeling. Route to electromagnetic inversion

    Energy Technology Data Exchange (ETDEWEB)

    Groom, R; Walker, P [PetRos EiKon Incorporated, Ontario (Canada)

    1996-05-01

    Inversion of electromagnetic data is a topical subject in the literature, and much time has been devoted to understanding the convergence properties of various inverse methods. The relative lack of success of electromagnetic inversion techniques is partly attributable to the difficulties in the kernel forward modeling software. These difficulties come in two broad classes: (1) Completeness and robustness, and (2) convergence, execution time and model simplicity. If such problems exist in the forward modeling kernel, it was demonstrated that inversion can fail to generate reasonable results. It was suggested that classical inversion techniques, which are based on minimizing a norm of the error between data and the simulated data, will only be successful when these difficulties in forward modeling kernels are properly dealt with. 4 refs., 5 figs.

  1. Inverse Kinematics

    Directory of Open Access Journals (Sweden)

    Joel Sereno

    2010-01-01

    Full Text Available Inverse kinematics is the process of converting a Cartesian point in space into a set of joint angles to more efficiently move the end effector of a robot to a desired orientation. This project investigates the inverse kinematics of a robotic hand with fingers under various scenarios. Assuming the parameters of a provided robot, a general equation for the end effector point was calculated and used to plot the region of space that it can reach. Further, the benefits obtained from the addition of a prismatic joint versus an extra variable angle joint were considered. The results confirmed that having more movable parts, such as prismatic points and changing angles, increases the effective reach of a robotic hand.

  2. Direct detection of common and rare inversion mutations in the genetic diagnosis of severe hemophilia A

    Energy Technology Data Exchange (ETDEWEB)

    Windsor, A.S.; Lillicrap, D.P.; Taylor, S.A.M. [Queen`s Univ., Ontario (Canada)

    1994-09-01

    Approximately 50% of the cases of severe hemophilia A (factor VIII:C < 0.01 units/ml) may be due to gross rearrangements of the factor VIII gene. The mutation involves homologous sequences upstream of the factor VIII locus and within intron 22 in an intrachromosomal recombination, inversion, event. The rearrangements can readily be detected on a Southern blot using a probe that is complementary to sequences from within intron 22. We describe here the analysis of this mutation in 71 severe hemophilia A patients. Thirty two of the patients (45%) showed evidence of a rearrangement. Five different patterns of rearrangements were seen, two of which have previously been described and account for the majority of cases (pattern 1, 70% and pattern 2, 16%). Three other abnormal patterns were observed. The inversion mechanism does not usually result in the loss or gain of any genetic material, but in one patient, in whom a unique rearrangement pattern was observed (pattern 3), we have previously documented a gross deletion which removes exons 1-22 of the factor VII gene as well as sequences 5{prime} to the gene. In another individual a fourth pattern in which an extra 19.0 kb band is present was detected. In this case it is unclear as to whether the rearrangement is responsible for the disease or is simply coincident normal variation. A fifth pattern, in which an extra 16.0 kb band was detected, was observed in a family with a new mutation causing hemophilia A. The affected individual and his mother inherited a de novo rearrangement of the factor VIII gene from his unaffected grandfather, implicating it as the cause of the disease. In conclusion, testing for the factor VIII inversion mutation was positive in approximately 45% of severe hemophiliacs, 72% of whom were isolated cases, and as such should constitute the initial stage in the genetic testing protocol for these patients` families.

  3. Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions

    DEFF Research Database (Denmark)

    Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert

    2016-01-01

    Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used...

  4. Stochastic Gabor reflectivity and acoustic impedance inversion

    Science.gov (United States)

    Hariri Naghadeh, Diako; Morley, Christopher Keith; Ferguson, Angus John

    2018-02-01

    To delineate subsurface lithology to estimate petrophysical properties of a reservoir, it is possible to use acoustic impedance (AI) which is the result of seismic inversion. To change amplitude to AI, removal of wavelet effects from the seismic signal in order to get a reflection series, and subsequently transforming those reflections to AI, is vital. To carry out seismic inversion correctly it is important to not assume that the seismic signal is stationary. However, all stationary deconvolution methods are designed following that assumption. To increase temporal resolution and interpretation ability, amplitude compensation and phase correction are inevitable. Those are pitfalls of stationary reflectivity inversion. Although stationary reflectivity inversion methods are trying to estimate reflectivity series, because of incorrect assumptions their estimations will not be correct, but may be useful. Trying to convert those reflection series to AI, also merging with the low frequency initial model, can help us. The aim of this study was to apply non-stationary deconvolution to eliminate time variant wavelet effects from the signal and to convert the estimated reflection series to the absolute AI by getting bias from well logs. To carry out this aim, stochastic Gabor inversion in the time domain was used. The Gabor transform derived the signal’s time-frequency analysis and estimated wavelet properties from different windows. Dealing with different time windows gave an ability to create a time-variant kernel matrix, which was used to remove matrix effects from seismic data. The result was a reflection series that does not follow the stationary assumption. The subsequent step was to convert those reflections to AI using well information. Synthetic and real data sets were used to show the ability of the introduced method. The results highlight that the time cost to get seismic inversion is negligible related to general Gabor inversion in the frequency domain. Also

  5. Inversion Therapy: Can It Relieve Back Pain?

    Science.gov (United States)

    Inversion therapy: Can it relieve back pain? Does inversion therapy relieve back pain? Is it safe? Answers from Edward R. Laskowski, M.D. Inversion therapy doesn't provide lasting relief from back ...

  6. On a complete topological inverse polycyclic monoid

    Directory of Open Access Journals (Sweden)

    S. O. Bardyla

    2016-12-01

    Full Text Available We give sufficient conditions when a topological inverse $\\lambda$-polycyclic monoid $P_{\\lambda}$ is absolutely $H$-closed in the class of topological inverse semigroups. For every infinite cardinal $\\lambda$ we construct the coarsest semigroup inverse topology $\\tau_{mi}$ on $P_\\lambda$ and give an example of a topological inverse monoid $S$ which contains the polycyclic monoid $P_2$ as a dense discrete subsemigroup.

  7. Laterally constrained inversion for CSAMT data interpretation

    Science.gov (United States)

    Wang, Ruo; Yin, Changchun; Wang, Miaoyue; Di, Qingyun

    2015-10-01

    Laterally constrained inversion (LCI) has been successfully applied to the inversion of dc resistivity, TEM and airborne EM data. However, it hasn't been yet applied to the interpretation of controlled-source audio-frequency magnetotelluric (CSAMT) data. In this paper, we apply the LCI method for CSAMT data inversion by preconditioning the Jacobian matrix. We apply a weighting matrix to Jacobian to balance the sensitivity of model parameters, so that the resolution with respect to different model parameters becomes more uniform. Numerical experiments confirm that this can improve the convergence of the inversion. We first invert a synthetic dataset with and without noise to investigate the effect of LCI applications to CSAMT data, for the noise free data, the results show that the LCI method can recover the true model better compared to the traditional single-station inversion; and for the noisy data, the true model is recovered even with a noise level of 8%, indicating that LCI inversions are to some extent noise insensitive. Then, we re-invert two CSAMT datasets collected respectively in a watershed and a coal mine area in Northern China and compare our results with those from previous inversions. The comparison with the previous inversion in a coal mine shows that LCI method delivers smoother layer interfaces that well correlate to seismic data, while comparison with a global searching algorithm of simulated annealing (SA) in a watershed shows that though both methods deliver very similar good results, however, LCI algorithm presented in this paper runs much faster. The inversion results for the coal mine CSAMT survey show that a conductive water-bearing zone that was not revealed by the previous inversions has been identified by the LCI. This further demonstrates that the method presented in this paper works for CSAMT data inversion.

  8. Wave-equation dispersion inversion

    KAUST Repository

    Li, Jing

    2016-12-08

    We present the theory for wave-equation inversion of dispersion curves, where the misfit function is the sum of the squared differences between the wavenumbers along the predicted and observed dispersion curves. The dispersion curves are obtained from Rayleigh waves recorded by vertical-component geophones. Similar to wave-equation traveltime tomography, the complicated surface wave arrivals in traces are skeletonized as simpler data, namely the picked dispersion curves in the phase-velocity and frequency domains. Solutions to the elastic wave equation and an iterative optimization method are then used to invert these curves for 2-D or 3-D S-wave velocity models. This procedure, denoted as wave-equation dispersion inversion (WD), does not require the assumption of a layered model and is significantly less prone to the cycle-skipping problems of full waveform inversion. The synthetic and field data examples demonstrate that WD can approximately reconstruct the S-wave velocity distributions in laterally heterogeneous media if the dispersion curves can be identified and picked. The WD method is easily extended to anisotropic data and the inversion of dispersion curves associated with Love waves.

  9. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    Science.gov (United States)

    Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G M; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M

    2014-01-01

    In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66). The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  10. Predicting survival of de novo metastatic breast cancer in Asian women: systematic review and validation study.

    Directory of Open Access Journals (Sweden)

    Hui Miao

    Full Text Available BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic. RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53 to 0.63 (95% CI, 0.60-0.66. CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.

  11. Probabilistic Geoacoustic Inversion in Complex Environments

    Science.gov (United States)

    2015-09-30

    Probabilistic Geoacoustic Inversion in Complex Environments Jan Dettmer School of Earth and Ocean Sciences, University of Victoria, Victoria BC...long-range inversion methods can fail to provide sufficient resolution. For proper quantitative examination of variability, parameter uncertainty must...project aims to advance probabilistic geoacoustic inversion methods for complex ocean environments for a range of geoacoustic data types. The work is

  12. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

    DEFF Research Database (Denmark)

    Muona, M.; Berkovic, S. F.; Dibbens, L. M.

    2015-01-01

    Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonicclonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo...

  13. A SA8000 e a responsabilidade social das empresas: a emergência de um novo paradigma?

    OpenAIRE

    Lopes, Ana Catarina Marques Figueiredo Caetano

    2004-01-01

    Mestrado em Desenvolvimento e Cooperação Internacional A Responsabilidade Social das Empresas, não é um tema novo. Durante muito tempo foi discutido e interpretado no âmbito do debate sobre as responsabilidades que uma empresa deve assumir para além daquelas que tem perante os seus accionistas, e das impostas por lei. Hoje, observamos a emergência de um novo paradigma assente no reconhecimento que o sector privado não só pode, mas deve, fazer mais para combater a pobreza, preservar o meio ...

  14. Inverse m-matrices and ultrametric matrices

    CERN Document Server

    Dellacherie, Claude; San Martin, Jaime

    2014-01-01

    The study of M-matrices, their inverses and discrete potential theory is now a well-established part of linear algebra and the theory of Markov chains. The main focus of this monograph is the so-called inverse M-matrix problem, which asks for a characterization of nonnegative matrices whose inverses are M-matrices. We present an answer in terms of discrete potential theory based on the Choquet-Deny Theorem. A distinguished subclass of inverse M-matrices is ultrametric matrices, which are important in applications such as taxonomy. Ultrametricity is revealed to be a relevant concept in linear algebra and discrete potential theory because of its relation with trees in graph theory and mean expected value matrices in probability theory. Remarkable properties of Hadamard functions and products for the class of inverse M-matrices are developed and probabilistic insights are provided throughout the monograph.

  15. Study on Strategic Planning of Road and Bridge Infrastructure Development in City Planning: Taking Porto-novo City of Benin Republic as Example

    Directory of Open Access Journals (Sweden)

    Boko-haya Dossa Didier

    2018-01-01

    Full Text Available Concern about the townlet infrastructure construction in developing country is one of the crucial part of county town planning and development. By taking the overall planning and design in a case study of Porto-novo city at Republic of Benin, this paper analyzes the characteristics and opportunities of Porto-novo city and puts forward corresponding infrastructure construction strategy. In the end, the paper comes up with specific plan of planning and design under the background of Porto-novo's planning of development strategy.

  16. Testing earthquake source inversion methodologies

    KAUST Repository

    Page, Morgan T.

    2011-01-01

    Source Inversion Validation Workshop; Palm Springs, California, 11-12 September 2010; Nowadays earthquake source inversions are routinely performed after large earthquakes and represent a key connection between recorded seismic and geodetic data and the complex rupture process at depth. The resulting earthquake source models quantify the spatiotemporal evolution of ruptures. They are also used to provide a rapid assessment of the severity of an earthquake and to estimate losses. However, because of uncertainties in the data, assumed fault geometry and velocity structure, and chosen rupture parameterization, it is not clear which features of these source models are robust. Improved understanding of the uncertainty and reliability of earthquake source inversions will allow the scientific community to use the robust features of kinematic inversions to more thoroughly investigate the complexity of the rupture process and to better constrain other earthquakerelated computations, such as ground motion simulations and static stress change calculations.

  17. A prognostic scoring model for survival after locoregional therapy in de novo stage IV breast cancer.

    Science.gov (United States)

    Kommalapati, Anuhya; Tella, Sri Harsha; Goyal, Gaurav; Ganti, Apar Kishor; Krishnamurthy, Jairam; Tandra, Pavan Kumar

    2018-05-02

    The role of locoregional treatment (LRT) remains controversial in de novo stage IV breast cancer (BC). We sought to analyze the role of LRT and prognostic factors of overall survival (OS) in de novo stage IV BC patients treated with LRT utilizing the National Cancer Data Base (NCDB). The objective of the current study is to create and internally validate a prognostic scoring model to predict the long-term OS for de novo stage IV BC patients treated with LRT. We included de novo stage IV BC patients reported to NCDB between 2004 and 2015. Patients were divided into LRT and no-LRT subsets. We randomized LRT subset to training and validation cohorts. In the training cohort, a seventeen-point prognostic scoring system was developed based on the hazard ratios calculated using Cox-proportional method. We stratified both training and validation cohorts into two "groups" [group 1 (0-7 points) and group 2 (7-17 points)]. Kaplan-Meier method and log-rank test were used to compare OS between the two groups. Our prognostic score was validated internally by comparing the OS between the respective groups in both the training and validation cohorts. Among 67,978 patients, LRT subset (21,200) had better median OS as compared to that of no-LRT (45 vs. 24 months; p < 0.0001). The group 1 and group 2 in the training cohort showed a significant difference in the 3-year OS (p < 0.0001) (68 vs. 26%). On internal validation, comparable OS was seen between the respective groups in each cohort (p = 0.77). Our prognostic scoring system will help oncologists to predict the prognosis in de novo stage IV BC patients treated with LRT. Although firm treatment-related conclusions cannot be made due to the retrospective nature of the study, LRT appears to be associated with a better OS in specific subgroups.

  18. Antimicrobial peptide capsids of de novo design.

    Science.gov (United States)

    De Santis, Emiliana; Alkassem, Hasan; Lamarre, Baptiste; Faruqui, Nilofar; Bella, Angelo; Noble, James E; Micale, Nicola; Ray, Santanu; Burns, Jonathan R; Yon, Alexander R; Hoogenboom, Bart W; Ryadnov, Maxim G

    2017-12-22

    The spread of bacterial resistance to antibiotics poses the need for antimicrobial discovery. With traditional search paradigms being exhausted, approaches that are altogether different from antibiotics may offer promising and creative solutions. Here, we introduce a de novo peptide topology that-by emulating the virus architecture-assembles into discrete antimicrobial capsids. Using the combination of high-resolution and real-time imaging, we demonstrate that these artificial capsids assemble as 20-nm hollow shells that attack bacterial membranes and upon landing on phospholipid bilayers instantaneously (seconds) convert into rapidly expanding pores causing membrane lysis (minutes). The designed capsids show broad antimicrobial activities, thus executing one primary function-they destroy bacteria on contact.

  19. Automatic Flight Controller With Model Inversion

    Science.gov (United States)

    Meyer, George; Smith, G. Allan

    1992-01-01

    Automatic digital electronic control system based on inverse-model-follower concept being developed for proposed vertical-attitude-takeoff-and-landing airplane. Inverse-model-follower control places inverse mathematical model of dynamics of controlled plant in series with control actuators of controlled plant so response of combination of model and plant to command is unity. System includes feedback to compensate for uncertainties in mathematical model and disturbances imposed from without.

  20. Parameter estimation and inverse problems

    CERN Document Server

    Aster, Richard C; Thurber, Clifford H

    2005-01-01

    Parameter Estimation and Inverse Problems primarily serves as a textbook for advanced undergraduate and introductory graduate courses. Class notes have been developed and reside on the World Wide Web for faciliting use and feedback by teaching colleagues. The authors'' treatment promotes an understanding of fundamental and practical issus associated with parameter fitting and inverse problems including basic theory of inverse problems, statistical issues, computational issues, and an understanding of how to analyze the success and limitations of solutions to these probles. The text is also a practical resource for general students and professional researchers, where techniques and concepts can be readily picked up on a chapter-by-chapter basis.Parameter Estimation and Inverse Problems is structured around a course at New Mexico Tech and is designed to be accessible to typical graduate students in the physical sciences who may not have an extensive mathematical background. It is accompanied by a Web site that...

  1. BayesMotif: de novo protein sorting motif discovery from impure datasets.

    Science.gov (United States)

    Hu, Jianjun; Zhang, Fan

    2010-01-18

    Protein sorting is the process that newly synthesized proteins are transported to their target locations within or outside of the cell. This process is precisely regulated by protein sorting signals in different forms. A major category of sorting signals are amino acid sub-sequences usually located at the N-terminals or C-terminals of protein sequences. Genome-wide experimental identification of protein sorting signals is extremely time-consuming and costly. Effective computational algorithms for de novo discovery of protein sorting signals is needed to improve the understanding of protein sorting mechanisms. We formulated the protein sorting motif discovery problem as a classification problem and proposed a Bayesian classifier based algorithm (BayesMotif) for de novo identification of a common type of protein sorting motifs in which a highly conserved anchor is present along with a less conserved motif regions. A false positive removal procedure is developed to iteratively remove sequences that are unlikely to contain true motifs so that the algorithm can identify motifs from impure input sequences. Experiments on both implanted motif datasets and real-world datasets showed that the enhanced BayesMotif algorithm can identify anchored sorting motifs from pure or impure protein sequence dataset. It also shows that the false positive removal procedure can help to identify true motifs even when there is only 20% of the input sequences containing true motif instances. We proposed BayesMotif, a novel Bayesian classification based algorithm for de novo discovery of a special category of anchored protein sorting motifs from impure datasets. Compared to conventional motif discovery algorithms such as MEME, our algorithm can find less-conserved motifs with short highly conserved anchors. Our algorithm also has the advantage of easy incorporation of additional meta-sequence features such as hydrophobicity or charge of the motifs which may help to overcome the limitations of

  2. Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling.

    Science.gov (United States)

    Scarlatti, Francesca; Sala, Giusy; Somenzi, Giulia; Signorelli, Paola; Sacchi, Nicoletta; Ghidoni, Riccardo

    2003-12-01

    Resveratrol (3,4',5-trans-trihydroxystilbene), a phytoalexin present in grapes and red wine, is emerging as a natural compound with potential anticancer properties. Here we show that resveratrol can induce growth inhibition and apoptosis in MDA-MB-231, a highly invasive and metastatic breast cancer cell line, in concomitance with a dramatic endogenous increase of growth inhibitory/proapoptotic ceramide. We found that accumulation of ceramide derives from both de novo ceramide synthesis and sphingomyelin hydrolysis. More specifically we demonstrated that ceramide accumulation induced by resveratrol can be traced to the activation of serine palmitoyltransferase (SPT), the key enzyme of de novo ceramide biosynthetic pathway, and neutral sphingomyelinase (nSMase), a main enzyme involved in the sphingomyelin/ceramide pathway. However, by using specific inhibitors of SPT, myriocin and L-cycloserine, and nSMase, gluthatione and manumycin, we found that only the SPT inhibitors could counteract the biological effects induced by resveratrol. Thus, resveratrol seems to exert its growth inhibitory/apoptotic effect on the metastatic breast cancer cell line MDA-MB-231 by activating the de novo ceramide synthesis pathway.

  3. A Swedish family with de novo alpha-synuclein A53T mutation: evidence for early cortical dysfunction

    DEFF Research Database (Denmark)

    Puschmann, Andreas; Ross, Owen A; Vilariño-Güell, Carles

    2009-01-01

    A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cog......A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria......) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected...

  4. Evaluation of effect of Ophiostoma novo-ulmi on four major wood ...

    African Journals Online (AJOL)

    Evaluation of effect of Ophiostoma novo-ulmi on four major wood species of the elm family in Rasht (North West of Iran) ... the diameter size of vessels and the number of xylary rays in four species: Ulmus carpinifolia, Ulmus glabra, Zelkova carpinifolia and Celtis australis as important factors in host resistance to elm disease.

  5. Ionizing radiation induced malignancies in man

    International Nuclear Information System (INIS)

    Dutrillaux, B.

    1997-01-01

    Using data on gene and chromosome alterations in human cancers, it is proposed that most radiation induced cancers are a consequence of recessive mutations of tumor suppressor genes. This explains the long delay between radiation exposure and the cancer onset. As a consequence, radiation induced cancers belong to groups of tumors where no specific translocations (forming or activating oncogenes) but multiple unbalanced chromosome rearrangements (deletions unmasking recessive mutations) exist. This explains why osteosarcomas, malignant fibrous histiocytoma, chondrosarcomas are frequently induced, but not liposarcoma, Ewing sarcomas and rhabdomyosarcomas, among others. A single exception confirms this rule: papillary thyroid cancer, frequently induced in exposed children, in which structural rearrangements frequently form a RET/PTC3 fusion gene. This fusion gene is the results of the inversion of a short segment of chromosome 10, and it is assumed that such rearrangement (small para-centric inversion) can easily occur after exposure to radiations, at contrast with translocations between to genes belonging to different chromosomes. (author)

  6. Inverse scale space decomposition

    DEFF Research Database (Denmark)

    Schmidt, Marie Foged; Benning, Martin; Schönlieb, Carola-Bibiane

    2018-01-01

    We investigate the inverse scale space flow as a decomposition method for decomposing data into generalised singular vectors. We show that the inverse scale space flow, based on convex and even and positively one-homogeneous regularisation functionals, can decompose data represented...... by the application of a forward operator to a linear combination of generalised singular vectors into its individual singular vectors. We verify that for this decomposition to hold true, two additional conditions on the singular vectors are sufficient: orthogonality in the data space and inclusion of partial sums...... of the subgradients of the singular vectors in the subdifferential of the regularisation functional at zero. We also address the converse question of when the inverse scale space flow returns a generalised singular vector given that the initial data is arbitrary (and therefore not necessarily in the range...

  7. Limits to Nonlinear Inversion

    DEFF Research Database (Denmark)

    Mosegaard, Klaus

    2012-01-01

    For non-linear inverse problems, the mathematical structure of the mapping from model parameters to data is usually unknown or partly unknown. Absence of information about the mathematical structure of this function prevents us from presenting an analytical solution, so our solution depends on our......-heuristics are inefficient for large-scale, non-linear inverse problems, and that the 'no-free-lunch' theorem holds. We discuss typical objections to the relevance of this theorem. A consequence of the no-free-lunch theorem is that algorithms adapted to the mathematical structure of the problem perform more efficiently than...... pure meta-heuristics. We study problem-adapted inversion algorithms that exploit the knowledge of the smoothness of the misfit function of the problem. Optimal sampling strategies exist for such problems, but many of these problems remain hard. © 2012 Springer-Verlag....

  8. Source-independent time-domain waveform inversion using convolved wavefields: Application to the encoded multisource waveform inversion

    KAUST Repository

    Choi, Yun Seok; Alkhalifah, Tariq Ali

    2011-01-01

    Full waveform inversion requires a good estimation of the source wavelet to improve our chances of a successful inversion. This is especially true for an encoded multisource time-domain implementation, which, conventionally, requires separate

  9. Inversion: A Most Useful Kind of Transformation.

    Science.gov (United States)

    Dubrovsky, Vladimir

    1992-01-01

    The transformation assigning to every point its inverse with respect to a circle with given radius and center is called an inversion. Discusses inversion with respect to points, circles, angles, distances, space, and the parallel postulate. Exercises related to these topics are included. (MDH)

  10. Inverse scattering problems with multi-frequencies

    International Nuclear Information System (INIS)

    Bao, Gang; Li, Peijun; Lin, Junshan; Triki, Faouzi

    2015-01-01

    This paper is concerned with computational approaches and mathematical analysis for solving inverse scattering problems in the frequency domain. The problems arise in a diverse set of scientific areas with significant industrial, medical, and military applications. In addition to nonlinearity, there are two common difficulties associated with the inverse problems: ill-posedness and limited resolution (diffraction limit). Due to the diffraction limit, for a given frequency, only a low spatial frequency part of the desired parameter can be observed from measurements in the far field. The main idea developed here is that if the reconstruction is restricted to only the observable part, then the inversion will become stable. The challenging task is how to design stable numerical methods for solving these inverse scattering problems inspired by the diffraction limit. Recently, novel recursive linearization based algorithms have been presented in an attempt to answer the above question. These methods require multi-frequency scattering data and proceed via a continuation procedure with respect to the frequency from low to high. The objective of this paper is to give a brief review of these methods, their error estimates, and the related mathematical analysis. More attention is paid to the inverse medium and inverse source problems. Numerical experiments are included to illustrate the effectiveness of these methods. (topical review)

  11. Population Genomics of Inversion Polymorphisms in Drosophila melanogaster

    Science.gov (United States)

    Corbett-Detig, Russell B.; Hartl, Daniel L.

    2012-01-01

    Chromosomal inversions have been an enduring interest of population geneticists since their discovery in Drosophila melanogaster. Numerous lines of evidence suggest powerful selective pressures govern the distributions of polymorphic inversions, and these observations have spurred the development of many explanatory models. However, due to a paucity of nucleotide data, little progress has been made towards investigating selective hypotheses or towards inferring the genealogical histories of inversions, which can inform models of inversion evolution and suggest selective mechanisms. Here, we utilize population genomic data to address persisting gaps in our knowledge of D. melanogaster's inversions. We develop a method, termed Reference-Assisted Reassembly, to assemble unbiased, highly accurate sequences near inversion breakpoints, which we use to estimate the age and the geographic origins of polymorphic inversions. We find that inversions are young, and most are African in origin, which is consistent with the demography of the species. The data suggest that inversions interact with polymorphism not only in breakpoint regions but also chromosome-wide. Inversions remain differentiated at low levels from standard haplotypes even in regions that are distant from breakpoints. Although genetic exchange appears fairly extensive, we identify numerous regions that are qualitatively consistent with selective hypotheses. Finally, we show that In(1)Be, which we estimate to be ∼60 years old (95% CI 5.9 to 372.8 years), has likely achieved high frequency via sex-ratio segregation distortion in males. With deeper sampling, it will be possible to build on our inferences of inversion histories to rigorously test selective models—particularly those that postulate that inversions achieve a selective advantage through the maintenance of co-adapted allele complexes. PMID:23284285

  12. High Incidence of De Novo and Subclinical Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy and Cardiac Rhythm Management Device.

    Science.gov (United States)

    Wilke, Iris; Witzel, Katrin; Münch, Julia; Pecha, Simon; Blankenberg, Stephan; Reichenspurner, Hermann; Willems, Stephan; Patten, Monica; Aydin, Ali

    2016-07-01

    Atrial fibrillation (AF) is an important prognostic parameter in patients with hypertrophic cardiomyopathy (HCM). Though cardiac rhythm management (CRM) devices (e.g., ICD, pacemaker or implantable loop recorder) can detect subclinical AF, data describing the incidence of AF are rare. We therefore investigated the incidence and clinical impact of de novo and subclinical AF detected by CRM devices in patients with HCM. In our retrospective single-center study, we included patients with HCM and need for CRM devices. The primary endpoint of the study was the incidence of clinical and subclinical de novo AF. During follow-up, patients were screened for adverse events like stroke, ventricular arrhythmia, heart failure, or death. From 192 HCM patients, 44 patients received a CRM device (38 ICDs, 5 pacemakers, 1 implantable loop recorder). In 14 of these patients (32%), AF had been documented before device implantation. Thirty (68%) patients were free from AF at the time of implantation. During a median follow-up of 595 days (interquartile range, 367-890 days), de novo AF was recorded in 16 of these 30 patients (53%). Fourteen (88%) of the 16 patients with de novo AF were free from any clinical symptoms, so these patients were classified to have subclinical AF. In logistic regression analysis, age was the only significant predictor for an increased risk of AF. AF is common in patients with HCM who need a CRM device. More than 50% of these patients develop de novo AF that was predominantly subclinical in our cohort. © 2016 Wiley Periodicals, Inc.

  13. Whole Exome Sequencing for a Patient with Rubinstein-Taybi Syndrome Reveals de Novo Variants besides an Overt CREBBP Mutation

    Directory of Open Access Journals (Sweden)

    Hee Jeong Yoo

    2015-03-01

    Full Text Available Rubinstein-Taybi syndrome (RSTS is a rare condition with a prevalence of 1 in 125,000–720,000 births and characterized by clinical features that include facial, dental, and limb dysmorphology and growth retardation. Most cases of RSTS occur sporadically and are caused by de novo mutations. Cytogenetic or molecular abnormalities are detected in only 55% of RSTS cases. Previous genetic studies have yielded inconsistent results due to the variety of methods used for genetic analysis. The purpose of this study was to use whole exome sequencing (WES to evaluate the genetic causes of RSTS in a young girl presenting with an Autism phenotype. We used the Autism diagnostic observation schedule (ADOS and Autism diagnostic interview revised (ADI-R to confirm her diagnosis of Autism. In addition, various questionnaires were used to evaluate other psychiatric features. We used WES to analyze the DNA sequences of the patient and her parents and to search for de novo variants. The patient showed all the typical features of Autism, WES revealed a de novo frameshift mutation in CREBBP and de novo sequence variants in TNC and IGFALS genes. Mutations in the CREBBP gene have been extensively reported in RSTS patients, while potential missense mutations in TNC and IGFALS genes have not previously been associated with RSTS. The TNC and IGFALS genes are involved in central nervous system development and growth. It is possible for patients with RSTS to have additional de novo variants that could account for previously unexplained phenotypes.

  14. Electron dose map inversion based on several algorithms

    International Nuclear Information System (INIS)

    Li Gui; Zheng Huaqing; Wu Yican; Fds Team

    2010-01-01

    The reconstruction to the electron dose map in radiation therapy was investigated by constructing the inversion model of electron dose map with different algorithms. The inversion model of electron dose map based on nonlinear programming was used, and this model was applied the penetration dose map to invert the total space one. The realization of this inversion model was by several inversion algorithms. The test results with seven samples show that except the NMinimize algorithm, which worked for just one sample, with great error,though,all the inversion algorithms could be realized to our inversion model rapidly and accurately. The Levenberg-Marquardt algorithm, having the greatest accuracy and speed, could be considered as the first choice in electron dose map inversion.Further tests show that more error would be created when the data close to the electron range was used (tail error). The tail error might be caused by the approximation of mean energy spectra, and this should be considered to improve the method. The time-saving and accurate algorithms could be used to achieve real-time dose map inversion. By selecting the best inversion algorithm, the clinical need in real-time dose verification can be satisfied. (authors)

  15. Workflow for near-surface velocity automatic estimation: Source-domain full-traveltime inversion followed by waveform inversion

    KAUST Repository

    Liu, Lu; Fei, Tong; Luo, Yi; Guo, Bowen

    2017-01-01

    This paper presents a workflow for near-surface velocity automatic estimation using the early arrivals of seismic data. This workflow comprises two methods, source-domain full traveltime inversion (FTI) and early-arrival waveform inversion. Source

  16. Analysis of pyrimidine synthesis "de novo" intermediates in urine and dried urine filter- paper strips with HPLC-electrospray tandem mass spectrometry

    NARCIS (Netherlands)

    van Kuilenburg, André B. P.; van Lenthe, Henk; Löffler, Monika; van Gennip, Albert H.

    2004-01-01

    BACKGROUND: The concentrations of the pyrimidine "de novo" metabolites and their degradation products in urine are useful indicators for the diagnosis of an inborn error of the pyrimidine de novo pathway or a urea-cycle defect. Until now, no procedure was available that allowed the analysis of all

  17. Support minimized inversion of acoustic and elastic wave scattering

    International Nuclear Information System (INIS)

    Safaeinili, A.

    1994-01-01

    This report discusses the following topics on support minimized inversion of acoustic and elastic wave scattering: Minimum support inversion; forward modelling of elastodynamic wave scattering; minimum support linearized acoustic inversion; support minimized nonlinear acoustic inversion without absolute phase; and support minimized nonlinear elastic inversion

  18. Lectures on the inverse scattering method

    International Nuclear Information System (INIS)

    Zakharov, V.E.

    1983-06-01

    In a series of six lectures an elementary introduction to the theory of inverse scattering is given. The first four lectures contain a detailed theory of solitons in the framework of the KdV equation, together with the inverse scattering theory of the one-dimensional Schroedinger equation. In the fifth lecture the dressing method is described, while the sixth lecture gives a brief review of the equations soluble by the inverse scattering method. (author)

  19. De novo formation of centrosomes in vertebrate cells arrested during S phase

    NARCIS (Netherlands)

    Khodjakov, A; Rieder, CL; Sluder, G; Cassels, G; Sibon, O; Wang, CL

    2002-01-01

    The centrosome usually replicates in a semiconservative fashion, i.e., new centrioles form in association with preexisting "maternal" centrioles. De novo formation of centrioles has been reported for a few highly specialized cell types but it has not been seen in vertebrate somatic cells. We find

  20. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.

    Science.gov (United States)

    Stanik, Juraj; Dusatkova, Petra; Cinek, Ondrej; Valentinova, Lucia; Huckova, Miroslava; Skopkova, Martina; Dusatkova, Lenka; Stanikova, Daniela; Pura, Mikulas; Klimes, Iwar; Lebl, Jan; Gasperikova, Daniela; Pruhova, Stepanka

    2014-03-01

    MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A). Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing. Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo. In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.

  1. A rice gene of de novo origin negatively regulates pathogen-induced defense response.

    Directory of Open Access Journals (Sweden)

    Wenfei Xiao

    Full Text Available How defense genes originated with the evolution of their specific pathogen-responsive traits remains an important problem. It is generally known that a form of duplication can generate new genes, suggesting that a new gene usually evolves from an ancestral gene. However, we show that a new defense gene in plants may evolve by de novo origination, resulting in sophisticated disease-resistant functions in rice. Analyses of gene evolution showed that this new gene, OsDR10, had homologs only in the closest relative, Leersia genus, but not other subfamilies of the grass family; therefore, it is a rice tribe-specific gene that may have originated de novo in the tribe. We further show that this gene may evolve a highly conservative rice-specific function that contributes to the regulation difference between rice and other plant species in response to pathogen infections. Biologic analyses including gene silencing, pathologic analysis, and mutant characterization by transformation showed that the OsDR10-suppressed plants enhanced resistance to a broad spectrum of Xanthomonas oryzae pv. oryzae strains, which cause bacterial blight disease. This enhanced disease resistance was accompanied by increased accumulation of endogenous salicylic acid (SA and suppressed accumulation of endogenous jasmonic acid (JA as well as modified expression of a subset of defense-responsive genes functioning both upstream and downstream of SA and JA. These data and analyses provide fresh insights into the new biologic and evolutionary processes of a de novo gene recruited rapidly.

  2. NLSE: Parameter-Based Inversion Algorithm

    Science.gov (United States)

    Sabbagh, Harold A.; Murphy, R. Kim; Sabbagh, Elias H.; Aldrin, John C.; Knopp, Jeremy S.

    Chapter 11 introduced us to the notion of an inverse problem and gave us some examples of the value of this idea to the solution of realistic industrial problems. The basic inversion algorithm described in Chap. 11 was based upon the Gauss-Newton theory of nonlinear least-squares estimation and is called NLSE in this book. In this chapter we will develop the mathematical background of this theory more fully, because this algorithm will be the foundation of inverse methods and their applications during the remainder of this book. We hope, thereby, to introduce the reader to the application of sophisticated mathematical concepts to engineering practice without introducing excessive mathematical sophistication.

  3. A rare case of de novo gigantic ovarian abscess within an endometrioma.

    Science.gov (United States)

    Hameed, Aisha; Mehta, Vaishali; Sinha, Prabha

    2010-06-01

    We are reporting a rare case of de novo ovarian abscess in an endometrioma. Ovarian abscess within an endometrioma is a rare gynecological problem, but de novo abscess in the endometrioma is even rarer. Most of the ovarian abscesses develop in the endometriomas following interventions, e.g., aspiration, pelvic surgery, and oocyte retrieval. We are presenting a case of a spontaneous giant abscess in a large ovarian cyst in a nulliparous woman who presented with acute abdomen. Patient was treated in a district general hospital with multidisciplinary approach. Thirteen liters of the pus were drained. She has had a sub total (supra cervical) hysterectomy and bilateral salpingo-oophorectomy (BSO) performed. Histology of the abscess wall confirmed endometriotic nature of the cyst. Patient made an uneventful recovery and was discharged home on the 14th postoperative day. This case highlights that endometrioma and its complication can present as a surgical emergency and should be dealt as one.

  4. Inverse and Ill-posed Problems Theory and Applications

    CERN Document Server

    Kabanikhin, S I

    2011-01-01

    The text demonstrates the methods for proving the existence (if et all) and finding of inverse and ill-posed problems solutions in linear algebra, integral and operator equations, integral geometry, spectral inverse problems, and inverse scattering problems. It is given comprehensive background material for linear ill-posed problems and for coefficient inverse problems for hyperbolic, parabolic, and elliptic equations. A lot of examples for inverse problems from physics, geophysics, biology, medicine, and other areas of application of mathematics are included.

  5. Para além do lumpen-indigenismo: novos aspectos informacionais da política indigenista brasileira

    Directory of Open Access Journals (Sweden)

    Rodrigo Piquet Saboia de Mello

    2017-06-01

    Full Text Available O artigo em tela propõe uma releitura do artigo intitulado “O lumpen-indigenismo do estado brasileiro” do antropólogo Jorge Pozzobon tendo por objetivo reelaborar alguns conceitos e propostas do autor em tempo outrora, assim como estabelecer uma ponte para os novos fenômenos informacionais que advém do conjunto político-jurídico hodierno, assim como no fortalecimento do protagonismo indígena na construção de novos modelos de participação e gerenciamento da informação indígena.

  6. Recurrent Neural Network for Computing Outer Inverse.

    Science.gov (United States)

    Živković, Ivan S; Stanimirović, Predrag S; Wei, Yimin

    2016-05-01

    Two linear recurrent neural networks for generating outer inverses with prescribed range and null space are defined. Each of the proposed recurrent neural networks is based on the matrix-valued differential equation, a generalization of dynamic equations proposed earlier for the nonsingular matrix inversion, the Moore-Penrose inversion, as well as the Drazin inversion, under the condition of zero initial state. The application of the first approach is conditioned by the properties of the spectrum of a certain matrix; the second approach eliminates this drawback, though at the cost of increasing the number of matrix operations. The cases corresponding to the most common generalized inverses are defined. The conditions that ensure stability of the proposed neural network are presented. Illustrative examples present the results of numerical simulations.

  7. Functional characterization of a rice de novo DNA methyltransferase, OsDRM2, expressed in Escherichia coli and yeast

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Jinsong, E-mail: pangjs542@nenu.edu.cn [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China); Dong, Mingyue; Li, Ning; Zhao, Yanli [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China); Liu, Bao, E-mail: baoliu@nenu.edu.cn [Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024 (China)

    2013-03-01

    Highlights: ► A rice de novo DNA methyltransferase OsDRM2 was cloned. ► In vitro methylation activity of OsDRM2 was characterized with Escherichia coli. ► Assays of OsDRM2 in vivo methylation were done with Saccharomyces cerevisiae. ► OsDRM2 methylation activity is not preferential to any type of cytosine context. ► The activity of OsDRM2 is independent of RdDM pathway. - Abstract: DNA methylation of cytosine nucleotides is an important epigenetic modification that occurs in most eukaryotic organisms and is established and maintained by various DNA methyltransferases together with their co-factors. There are two major categories of DNA methyltransferases: de novo and maintenance. Here, we report the isolation and functional characterization of a de novo methyltransferase, named OsDRM2, from rice (Oryza sativa L.). The full-length coding region of OsDRM2 was cloned and transformed into Escherichia coli and Saccharomyces cerevisiae. Both of these organisms expressed the OsDRM2 protein, which exhibited stochastic de novo methylation activity in vitro at CG, CHG, and CHH di- and tri-nucleotide patterns. Two lines of evidence demonstrated the de novo activity of OsDRM2: (1) a 5′-CCGG-3′ containing DNA fragment that had been pre-treated with OsDRM2 protein expressed in E. coli was protected from digestion by the CG-methylation-sensitive isoschizomer HpaII; (2) methylation-sensitive amplified polymorphism (MSAP) analysis of S. cerevisiae genomic DNA from transformants that had been introduced with OsDRM2 revealed CG and CHG methylation levels of 3.92–9.12%, and 2.88–6.93%, respectively, whereas the mock control S. cerevisiae DNA did not exhibit cytosine methylation. These results were further supported by bisulfite sequencing of the 18S rRNA and EAF5 genes of the transformed S. cerevisiae, which exhibited different DNA methylation patterns, which were observed in the genomic DNA. Our findings establish that OsDRM2 is an active de novo DNA

  8. Functional characterization of a rice de novo DNA methyltransferase, OsDRM2, expressed in Escherichia coli and yeast

    International Nuclear Information System (INIS)

    Pang, Jinsong; Dong, Mingyue; Li, Ning; Zhao, Yanli; Liu, Bao

    2013-01-01

    Highlights: ► A rice de novo DNA methyltransferase OsDRM2 was cloned. ► In vitro methylation activity of OsDRM2 was characterized with Escherichia coli. ► Assays of OsDRM2 in vivo methylation were done with Saccharomyces cerevisiae. ► OsDRM2 methylation activity is not preferential to any type of cytosine context. ► The activity of OsDRM2 is independent of RdDM pathway. - Abstract: DNA methylation of cytosine nucleotides is an important epigenetic modification that occurs in most eukaryotic organisms and is established and maintained by various DNA methyltransferases together with their co-factors. There are two major categories of DNA methyltransferases: de novo and maintenance. Here, we report the isolation and functional characterization of a de novo methyltransferase, named OsDRM2, from rice (Oryza sativa L.). The full-length coding region of OsDRM2 was cloned and transformed into Escherichia coli and Saccharomyces cerevisiae. Both of these organisms expressed the OsDRM2 protein, which exhibited stochastic de novo methylation activity in vitro at CG, CHG, and CHH di- and tri-nucleotide patterns. Two lines of evidence demonstrated the de novo activity of OsDRM2: (1) a 5′-CCGG-3′ containing DNA fragment that had been pre-treated with OsDRM2 protein expressed in E. coli was protected from digestion by the CG-methylation-sensitive isoschizomer HpaII; (2) methylation-sensitive amplified polymorphism (MSAP) analysis of S. cerevisiae genomic DNA from transformants that had been introduced with OsDRM2 revealed CG and CHG methylation levels of 3.92–9.12%, and 2.88–6.93%, respectively, whereas the mock control S. cerevisiae DNA did not exhibit cytosine methylation. These results were further supported by bisulfite sequencing of the 18S rRNA and EAF5 genes of the transformed S. cerevisiae, which exhibited different DNA methylation patterns, which were observed in the genomic DNA. Our findings establish that OsDRM2 is an active de novo DNA

  9. Inverse kinematic-based robot control

    Science.gov (United States)

    Wolovich, W. A.; Flueckiger, K. F.

    1987-01-01

    A fundamental problem which must be resolved in virtually all non-trivial robotic operations is the well-known inverse kinematic question. More specifically, most of the tasks which robots are called upon to perform are specified in Cartesian (x,y,z) space, such as simple tracking along one or more straight line paths or following a specified surfacer with compliant force sensors and/or visual feedback. In all cases, control is actually implemented through coordinated motion of the various links which comprise the manipulator; i.e., in link space. As a consequence, the control computer of every sophisticated anthropomorphic robot must contain provisions for solving the inverse kinematic problem which, in the case of simple, non-redundant position control, involves the determination of the first three link angles, theta sub 1, theta sub 2, and theta sub 3, which produce a desired wrist origin position P sub xw, P sub yw, and P sub zw at the end of link 3 relative to some fixed base frame. Researchers outline a new inverse kinematic solution and demonstrate its potential via some recent computer simulations. They also compare it to current inverse kinematic methods and outline some of the remaining problems which will be addressed in order to render it fully operational. Also discussed are a number of practical consequences of this technique beyond its obvious use in solving the inverse kinematic question.

  10. The Transmuted Generalized Inverse Weibull Distribution

    Directory of Open Access Journals (Sweden)

    Faton Merovci

    2014-05-01

    Full Text Available A generalization of the generalized inverse Weibull distribution the so-called transmuted generalized inverse Weibull distribution is proposed and studied. We will use the quadratic rank transmutation map (QRTM in order to generate a flexible family of probability distributions taking the generalized inverseWeibull distribution as the base value distribution by introducing a new parameter that would offer more distributional flexibility. Various structural properties including explicit expressions for the moments, quantiles, and moment generating function of the new distribution are derived. We propose the method of maximum likelihood for estimating the model parameters and obtain the observed information matrix. A real data set are used to compare the flexibility of the transmuted version versus the generalized inverse Weibull distribution.

  11. CIPESC® Curitiba: o trabalho da enfermagem no Distrito Bairro Novo CIPESC® Curitiba: el trabajo de enfermería en el Districto Bairro Novo CIPESC® Curitiba: the work of nursing at Bairro Novo District

    Directory of Open Access Journals (Sweden)

    Denise Maria Altino

    2006-08-01

    Full Text Available Curitiba implantou em rede o sistema Classificação Internacional das Práticas de Enfermagem em Saúde Coletiva - CIPESC®. O presente estudo objetivou identificar as atividades exercidas pelos profissionais de enfermagem nas unidades de saúde do distrito Bairro Novo de Curitiba. Trata-se de uma pesquisa descritiva em que foram entrevistados auxiliares e enfermeiras utilizando-se de um check-list. Os resultados mostram que: o acolhimento é realizado por todos; as auxiliares se ocupam mais das atividades assistencial-procedimentais; a totalidade das enfermeiras realiza consulta de enfermagem diariamente, recorrendo ao prontuário eletrônico de base CIPESC®. Conclui-se que, excetuando-se as atividades de pesquisa, houve intensificação e ampliação das atividades assistenciais sistematizadas e embasadas no trabalho cotidiano da enfermagem, intra e extramuros.Curitiba implantó el sistema Clasificación Internacional de las Prácticas de Enfermería en Salud Colectiva - CIPESC®. El presente estudio objetivó identificar las actividades ejercidas por personal de enfermería en la red de atención básica de la salud del distrito Bairro Novo, Curitiba. Ha hecho una investigación junto a los trabajadores de enfermería, recorriendo-se a check-list. Los resultados mostrarán: todos realizan el acogimiento; las auxiliares de enfermería se ocupan más de las actividades asistencial-procedimentales; todas las enfermeras realizan consulta de enfermería diariamente, utilizando-se del prontuario electrónico bases CIPESC®. En conclusión, excepto las actividades del investigación, hube intensificación y ampliación de las actividades asistenciales, que se ubican sistematizadas e embasadas en el trabajo cotidiano de la enfermería, así como la educación y planeamiento.Curitiba has been utilized system CIPESC® - International Nursing Practice Classification in Collective Health. This study goal identifies the activities of nursing staff in

  12. Unwrapped phase inversion for near surface seismic data

    KAUST Repository

    Choi, Yun Seok

    2012-11-04

    The Phase-wrapping is one of the main obstacles of waveform inversion. We use an inversion algorithm based on the instantaneous-traveltime that overcomes the phase-wrapping problem. With a high damping factor, the frequency-dependent instantaneous-traveltime inversion provides the stability of refraction tomography, with higher resolution results, and no arrival picking involved. We apply the instantaneous-traveltime inversion to the synthetic data generated by the elastic time-domain modeling. The synthetic data is a representative of the near surface seismic data. Although the inversion algorithm is based on the acoustic wave equation, the numerical examples show that the instantaneous-traveltime inversion generates a convergent velocity model, very similar to what we see from traveltime tomography.

  13. Integration of CpG-free DNA induces de novo methylation of CpG islands in pluripotent stem cells

    KAUST Repository

    Takahashi, Yuta

    2017-05-05

    CpG islands (CGIs) are primarily promoter-associated genomic regions and are mostly unmethylated within highly methylated mammalian genomes. The mechanisms by which CGIs are protected from de novo methylation remain elusive. Here we show that insertion of CpG-free DNA into targeted CGIs induces de novo methylation of the entire CGI in human pluripotent stem cells (PSCs). The methylation status is stably maintained even after CpG-free DNA removal, extensive passaging, and differentiation. By targeting the DNA mismatch repair gene MLH1 CGI, we could generate a PSC model of a cancer-related epimutation. Furthermore, we successfully corrected aberrant imprinting in induced PSCs derived from an Angelman syndrome patient. Our results provide insights into how CpG-free DNA induces de novo CGI methylation and broaden the application of targeted epigenome editing for a better understanding of human development and disease.

  14. Varying prior information in Bayesian inversion

    International Nuclear Information System (INIS)

    Walker, Matthew; Curtis, Andrew

    2014-01-01

    Bayes' rule is used to combine likelihood and prior probability distributions. The former represents knowledge derived from new data, the latter represents pre-existing knowledge; the Bayesian combination is the so-called posterior distribution, representing the resultant new state of knowledge. While varying the likelihood due to differing data observations is common, there are also situations where the prior distribution must be changed or replaced repeatedly. For example, in mixture density neural network (MDN) inversion, using current methods the neural network employed for inversion needs to be retrained every time prior information changes. We develop a method of prior replacement to vary the prior without re-training the network. Thus the efficiency of MDN inversions can be increased, typically by orders of magnitude when applied to geophysical problems. We demonstrate this for the inversion of seismic attributes in a synthetic subsurface geological reservoir model. We also present results which suggest that prior replacement can be used to control the statistical properties (such as variance) of the final estimate of the posterior in more general (e.g., Monte Carlo based) inverse problem solutions. (paper)

  15. Atmospheric inverse modeling via sparse reconstruction

    Science.gov (United States)

    Hase, Nils; Miller, Scot M.; Maaß, Peter; Notholt, Justus; Palm, Mathias; Warneke, Thorsten

    2017-10-01

    Many applications in atmospheric science involve ill-posed inverse problems. A crucial component of many inverse problems is the proper formulation of a priori knowledge about the unknown parameters. In most cases, this knowledge is expressed as a Gaussian prior. This formulation often performs well at capturing smoothed, large-scale processes but is often ill equipped to capture localized structures like large point sources or localized hot spots. Over the last decade, scientists from a diverse array of applied mathematics and engineering fields have developed sparse reconstruction techniques to identify localized structures. In this study, we present a new regularization approach for ill-posed inverse problems in atmospheric science. It is based on Tikhonov regularization with sparsity constraint and allows bounds on the parameters. We enforce sparsity using a dictionary representation system. We analyze its performance in an atmospheric inverse modeling scenario by estimating anthropogenic US methane (CH4) emissions from simulated atmospheric measurements. Different measures indicate that our sparse reconstruction approach is better able to capture large point sources or localized hot spots than other methods commonly used in atmospheric inversions. It captures the overall signal equally well but adds details on the grid scale. This feature can be of value for any inverse problem with point or spatially discrete sources. We show an example for source estimation of synthetic methane emissions from the Barnett shale formation.

  16. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Science.gov (United States)

    Baruffi, Marcelo Razera; de Souza, Deise Helena; Bicudo da Silva, Rosana Aparecida; Ramos, Ester Silveira; Moretti-Ferreira, Danilo

    2012-01-01

    Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process. PMID:23074688

  17. Autism Spectrum Disorder in a Girl with a De Novo X;19 Balanced Translocation

    Directory of Open Access Journals (Sweden)

    Marcelo Razera Baruffi

    2012-01-01

    Full Text Available Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with a de novo X;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed a de novo balanced translocation, with the karyotype 46,X,t(X;19(p21.2;q13.4. Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY. Although abnormal phenotypes associated with de novo balanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

  18. Inverse problems for Maxwell's equations

    CERN Document Server

    Romanov, V G

    1994-01-01

    The Inverse and Ill-Posed Problems Series is a series of monographs publishing postgraduate level information on inverse and ill-posed problems for an international readership of professional scientists and researchers. The series aims to publish works which involve both theory and applications in, e.g., physics, medicine, geophysics, acoustics, electrodynamics, tomography, and ecology.

  19. Fast wavelet based sparse approximate inverse preconditioner

    Energy Technology Data Exchange (ETDEWEB)

    Wan, W.L. [Univ. of California, Los Angeles, CA (United States)

    1996-12-31

    Incomplete LU factorization is a robust preconditioner for both general and PDE problems but unfortunately not easy to parallelize. Recent study of Huckle and Grote and Chow and Saad showed that sparse approximate inverse could be a potential alternative while readily parallelizable. However, for special class of matrix A that comes from elliptic PDE problems, their preconditioners are not optimal in the sense that independent of mesh size. A reason may be that no good sparse approximate inverse exists for the dense inverse matrix. Our observation is that for this kind of matrices, its inverse entries typically have piecewise smooth changes. We can take advantage of this fact and use wavelet compression techniques to construct a better sparse approximate inverse preconditioner. We shall show numerically that our approach is effective for this kind of matrices.

  20. Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Zhe-Ming Lu

    Full Text Available BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC samples (36/40 was significantly higher than that observed in gastritis (19/45 or normal samples (7/13 (P<0.01. Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01. In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. CONCLUSIONS/SIGNIFICANCE: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5'UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

  1. Voxel inversion of airborne EM data

    DEFF Research Database (Denmark)

    Fiandaca, Gianluca G.; Auken, Esben; Christiansen, Anders Vest C A.V.C.

    2013-01-01

    We present a geophysical inversion algorithm working directly in a voxel grid disconnected from the actual measuring points, which allows for straightforward integration of different data types in joint inversion, for informing geological/hydrogeological models directly and for easier incorporation...... of prior information. Inversion of geophysical data usually refers to a model space being linked to the actual observation points. For airborne surveys the spatial discretization of the model space reflects the flight lines. Often airborne surveys are carried out in areas where other ground......-based geophysical data are available. The model space of geophysical inversions is usually referred to the positions of the measurements, and ground-based model positions do not generally coincide with the airborne model positions. Consequently, a model space based on the measuring points is not well suited...

  2. Deep controls on intraplate basin inversion

    DEFF Research Database (Denmark)

    Nielsen, S.B.; Stephenson, Randell Alexander; Schiffer, Christian

    2014-01-01

    Basin inversion is an intermediate-scale manifestation of continental intraplate deformation, which produces earthquake activity in the interior of continents. The sedimentary basins of central Europe, inverted in the Late Cretaceous– Paleocene, represent a classic example of this phenomenon....... It is known that inversion of these basins occurred in two phases: an initial one of transpressional shortening involving reverse activation of former normal faults and a subsequent one of uplift of the earlier developed inversion axis and a shift of sedimentary depocentres, and that this is a response...... to changes in the regional intraplate stress field. This European intraplate deformation is considered in thecontext of a new model of the present-day stress field of Europe (and the North Atlantic) caused by lithospheric potential energy variations. Stresses causingbasin inversion of Europe must have been...

  3. The inverse square law of gravitation

    International Nuclear Information System (INIS)

    Cook, A.H.

    1987-01-01

    The inverse square law of gravitation is very well established over the distances of celestial mechanics, while in electrostatics the law has been shown to be followed to very high precision. However, it is only within the last century that any laboratory experiments have been made to test the inverse square law for gravitation, and all but one has been carried out in the last ten years. At the same time, there has been considerable interest in the possibility of deviations from the inverse square law, either because of a possible bearing on unified theories of forces, including gravitation or, most recently, because of a possible additional fifth force of nature. In this article the various lines of evidence for the inverse square law are summarized, with emphasis upon the recent laboratory experiments. (author)

  4. A Psicologia no novo contexto mundial Psychology in the new world context

    Directory of Open Access Journals (Sweden)

    Carla Faria Leitão

    2003-12-01

    Full Text Available Profundas alterações no mundo contemporâneo criaram um novo contexto de produção científica, caracterizado pela desconstrução de antigas teorias e pela construção de uma nova rede de conhecimentos. Neste artigo, analisamos algumas teorias recentemente desenvolvidas nas ciências sociais e na filosofia que compõem esta rede: as teorias pós-modernas, as teorias da modernização reflexiva e a teoria da Revolução da Tecnologia da Informação. Visamos com isto munir os psicólogos de conhecimentos advindos de outros campos disciplinares que sirvam como ponto de partida para a análise das mudanças subjetivas introduzidas pelo novo cenário mundial. Argumentamos que a psicologia ainda observa o homem contemporâneo a partir de categorias tradicionais, desconsiderando que transformações sociais profundas geram impactos psicológicos não menos profundos e dificilmente captáveis a partir de antigos referenciais. Concluímos que um conhecimento mais aprofundado das transformações radicais em curso no mundo atual pode ajudar os psicólogos a rever suas antigas certezas a respeito do homem e a aventurar novos olhares sobre os também novos fenômenos humanos.Profound changes in the contemporary world have created a new context for scientific work, characterised by the deconstruction of old theories and the construction of a new network of knowledge. In this article, we analyse a few theories recently developed in the social sciences and in philosophy that make up this network: post-modernist theories, reflexive modernisation theories and Information Technology Revolution theory. In this way, we aim to provide psychologists with insights produced in other fields of knowledge that can serve as a starting point for the analysis of the subjective changes introduced by the new global scenario. We argue that psychology still observes contemporary man on the basis of traditional categories, ignoring the fact that profound social changes

  5. De-novo discovery of differentially abundant transcription factor binding sites including their positional preference.

    Science.gov (United States)

    Keilwagen, Jens; Grau, Jan; Paponov, Ivan A; Posch, Stefan; Strickert, Marc; Grosse, Ivo

    2011-02-10

    Transcription factors are a main component of gene regulation as they activate or repress gene expression by binding to specific binding sites in promoters. The de-novo discovery of transcription factor binding sites in target regions obtained by wet-lab experiments is a challenging problem in computational biology, which has not been fully solved yet. Here, we present a de-novo motif discovery tool called Dispom for finding differentially abundant transcription factor binding sites that models existing positional preferences of binding sites and adjusts the length of the motif in the learning process. Evaluating Dispom, we find that its prediction performance is superior to existing tools for de-novo motif discovery for 18 benchmark data sets with planted binding sites, and for a metazoan compendium based on experimental data from micro-array, ChIP-chip, ChIP-DSL, and DamID as well as Gene Ontology data. Finally, we apply Dispom to find binding sites differentially abundant in promoters of auxin-responsive genes extracted from Arabidopsis thaliana microarray data, and we find a motif that can be interpreted as a refined auxin responsive element predominately positioned in the 250-bp region upstream of the transcription start site. Using an independent data set of auxin-responsive genes, we find in genome-wide predictions that the refined motif is more specific for auxin-responsive genes than the canonical auxin-responsive element. In general, Dispom can be used to find differentially abundant motifs in sequences of any origin. However, the positional distribution learned by Dispom is especially beneficial if all sequences are aligned to some anchor point like the transcription start site in case of promoter sequences. We demonstrate that the combination of searching for differentially abundant motifs and inferring a position distribution from the data is beneficial for de-novo motif discovery. Hence, we make the tool freely available as a component of the open

  6. Centered Differential Waveform Inversion with Minimum Support Regularization

    KAUST Repository

    Kazei, Vladimir

    2017-05-26

    Time-lapse full-waveform inversion has two major challenges. The first one is the reconstruction of a reference model (baseline model for most of approaches). The second is inversion for the time-lapse changes in the parameters. Common model approach is utilizing the information contained in all available data sets to build a better reference model for time lapse inversion. Differential (Double-difference) waveform inversion allows to reduce the artifacts introduced into estimates of time-lapse parameter changes by imperfect inversion for the baseline-reference model. We propose centered differential waveform inversion (CDWI) which combines these two approaches in order to benefit from both of their features. We apply minimum support regularization commonly used with electromagnetic methods of geophysical exploration. We test the CDWI method on synthetic dataset with random noise and show that, with Minimum support regularization, it provides better resolution of velocity changes than with total variation and Tikhonov regularizations in time-lapse full-waveform inversion.

  7. A simple method suitable to study de novo root organogenesis

    Directory of Open Access Journals (Sweden)

    Xiaodong eChen

    2014-05-01

    Full Text Available De novo root organogenesis is the process in which adventitious roots regenerate from detached or wounded plant tissues or organs. In tissue culture, appropriate types and concentrations of plant hormones in the medium are critical for inducing adventitious roots. However, in natural conditions, regeneration from detached organs is likely to rely on endogenous hormones. To investigate the actions of endogenous hormones and the molecular mechanisms guiding de novo root organogenesis, we developed a simple method to imitate natural conditions for adventitious root formation by culturing Arabidopsis thaliana leaf explants on B5 medium without additive hormones. Here we show that the ability of the leaf explants to regenerate roots depends on the age of the leaf and on certain nutrients in the medium. Based on these observations, we provide examples of how this method can be used in different situations, and how it can be optimized. This simple method could be used to investigate the effects of various physiological and molecular changes on the regeneration of adventitious roots. It is also useful for tracing cell lineage during the regeneration process by differential interference contrast observation of -glucuronidase staining, and by live imaging of proteins labeled with fluorescent tags.

  8. Use of transient elastography to predict de novo recurrence after radiofrequency ablation for hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Sang Hoon; Kim, Seung Up; Jang, Jeong Won; Bae, Si Hyun; Lee, Sanghun; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Han, Kwang-Hyub

    2015-01-01

    Liver stiffness (LS) measurement using transient elastography can accurately assess the degree of liver fibrosis, which is associated with the risk of the development of hepatocellular carcinoma (HCC). We investigated whether LS values could predict HCC de novo recurrence after radiofrequency ablation (RFA). This retrospective, multicenter study analyzed 111 patients with HCC who underwent RFA and LS measurement using transient elastography between May 2005 and April 2011. All patients were followed until March 2013 to monitor for HCC recurrence. This study included 76 men and 35 women with a mean age of 62.4 years, and the mean LS value was 21.2 kPa. During the follow-up period (median 22.4 months), 47 (42.3%) patients experienced HCC de novo recurrence, and 18 (16.2%) died. Patients with recurrence had significantly more frequent liver cirrhosis, more frequent history of previous treatment for HCC, higher total bilirubin, larger spleen size, larger total tumor size, higher tumor number, higher LS values, and lower platelet counts than those without recurrence (all P13.0 kPa were at significantly greater risk for recurrence after RFA, with a hazard ratio (HR) of 3.115 (95% confidence interval [CI], 1.238-7.842, Pmeasurement is a useful predictor of HCC de novo recurrence and overall survival after RFA.

  9. Inverse planning for x-ray rotation therapy: a general solution of the inverse problem

    International Nuclear Information System (INIS)

    Oelfke, U.; Bortfeld, T.

    1999-01-01

    Rotation therapy with photons is currently under investigation for the delivery of intensity modulated radiotherapy (IMRT). An analytical approach for inverse treatment planning of this radiotherapy technique is described. The inverse problem for the delivery of arbitrary 2D dose profiles is first formulated and then solved analytically. In contrast to previously applied strategies for solving the inverse problem, it is shown that the most general solution for the fluence profiles consists of two independent solutions of different parity. A first analytical expression for both fluence profiles is derived. The mathematical derivation includes two different strategies, an elementary expansion of fluence and dose into polynomials and a more practical approach in terms of Fourier transforms. The obtained results are discussed in the context of previous work on this problem. (author)

  10. A new hybrid-FBP inversion algorithm with inverse distance backprojection weight for CT reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Narasimhadhan, A.V.; Rajgopal, Kasi

    2011-07-01

    This paper presents a new hybrid filtered backprojection (FBP) algorithm for fan-beam and cone-beam scan. The hybrid reconstruction kernel is the sum of the ramp and Hilbert filters. We modify the redundancy weighting function to reduce the inverse square distance weighting in the backprojection to inverse distance weight. The modified weight also eliminates the derivative associated with the Hilbert filter kernel. Thus, the proposed reconstruction algorithm has the advantages of the inverse distance weight in the backprojection. We evaluate the performance of the new algorithm in terms of the magnitude level and uniformity in noise for the fan-beam geometry. The computer simulations show that the spatial resolution is nearly identical to the standard fan-beam ramp filtered algorithm while the noise is spatially uniform and the noise variance is reduced. (orig.)

  11. Lethal Ultra-Early Subarachnoid Hemorrhage Due to Rupture of De Novo Aneurysm 5 Months After Primary Aneurysmatic Subarachnoid Hemorrhage.

    Science.gov (United States)

    Walter, Johannes; Unterberg, Andreas W; Zweckberger, Klaus

    2018-05-01

    Approximately 1% of all patients surviving rupture of a cerebral aneurysm suffer from a second aneurysmatic subarachnoid hemorrhage later in their lives, 61% of which are caused by rupture of a de novo aneurysm. Latency between bleedings is usually many years, and younger patients tend to achieve better outcomes from a second subarachnoid hemorrhage. We report an unusual case of lethal ultra-early rupture of a de novo aneurysm of the anterior communicating artery only 5 months after the initial subarachnoid hemorrhage and complete coiling in a young, healthy male patient. Despite complete aneurysm obliteration, young age, and good recovery, patients may be subjected to secondary subarachnoid hemorrhages from de novo aneurysms after only a few months of the initial bleeding. Early-control magnetic resonance angiography might hence be advisable. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation

    DEFF Research Database (Denmark)

    Michaelson, Jacob J.; Shi, Yujian; Gujral, Madhusudan

    2012-01-01

    De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We...

  13. BOOK REVIEW: Inverse Problems. Activities for Undergraduates

    Science.gov (United States)

    Yamamoto, Masahiro

    2003-06-01

    This book is a valuable introduction to inverse problems. In particular, from the educational point of view, the author addresses the questions of what constitutes an inverse problem and how and why we should study them. Such an approach has been eagerly awaited for a long time. Professor Groetsch, of the University of Cincinnati, is a world-renowned specialist in inverse problems, in particular the theory of regularization. Moreover, he has made a remarkable contribution to educational activities in the field of inverse problems, which was the subject of his previous book (Groetsch C W 1993 Inverse Problems in the Mathematical Sciences (Braunschweig: Vieweg)). For this reason, he is one of the most qualified to write an introductory book on inverse problems. Without question, inverse problems are important, necessary and appear in various aspects. So it is crucial to introduce students to exercises in inverse problems. However, there are not many introductory books which are directly accessible by students in the first two undergraduate years. As a consequence, students often encounter diverse concrete inverse problems before becoming aware of their general principles. The main purpose of this book is to present activities to allow first-year undergraduates to learn inverse theory. To my knowledge, this book is a rare attempt to do this and, in my opinion, a great success. The author emphasizes that it is very important to teach inverse theory in the early years. He writes; `If students consider only the direct problem, they are not looking at the problem from all sides .... The habit of always looking at problems from the direct point of view is intellectually limiting ...' (page 21). The book is very carefully organized so that teachers will be able to use it as a textbook. After an introduction in chapter 1, sucessive chapters deal with inverse problems in precalculus, calculus, differential equations and linear algebra. In order to let one gain some insight

  14. Convex blind image deconvolution with inverse filtering

    Science.gov (United States)

    Lv, Xiao-Guang; Li, Fang; Zeng, Tieyong

    2018-03-01

    Blind image deconvolution is the process of estimating both the original image and the blur kernel from the degraded image with only partial or no information about degradation and the imaging system. It is a bilinear ill-posed inverse problem corresponding to the direct problem of convolution. Regularization methods are used to handle the ill-posedness of blind deconvolution and get meaningful solutions. In this paper, we investigate a convex regularized inverse filtering method for blind deconvolution of images. We assume that the support region of the blur object is known, as has been done in a few existing works. By studying the inverse filters of signal and image restoration problems, we observe the oscillation structure of the inverse filters. Inspired by the oscillation structure of the inverse filters, we propose to use the star norm to regularize the inverse filter. Meanwhile, we use the total variation to regularize the resulting image obtained by convolving the inverse filter with the degraded image. The proposed minimization model is shown to be convex. We employ the first-order primal-dual method for the solution of the proposed minimization model. Numerical examples for blind image restoration are given to show that the proposed method outperforms some existing methods in terms of peak signal-to-noise ratio (PSNR), structural similarity (SSIM), visual quality and time consumption.

  15. Full traveltime inversion in source domain

    KAUST Repository

    Liu, Lu

    2017-06-01

    This paper presents a new method of source-domain full traveltime inversion (FTI). The objective of this study is automatically building near-surface velocity using the early arrivals of seismic data. This method can generate the inverted velocity that can kinetically best match the reconstructed plane-wave source of early arrivals with true source in source domain. It does not require picking first arrivals for tomography, which is one of the most challenging aspects of ray-based tomographic inversion. Besides, this method does not need estimate the source wavelet, which is a necessity for receiver-domain wave-equation velocity inversion. Furthermore, we applied our method on one synthetic dataset; the results show our method could generate a reasonable background velocity even when shingling first arrivals exist and could provide a good initial velocity for the conventional full waveform inversion (FWI).

  16. Two-dimensional inversion of MT (magnetotelluric) data; MT ho no nijigen inversion kaiseki

    Energy Technology Data Exchange (ETDEWEB)

    Ito, S; Okuno, M; Ushijima, K; Mizunaga, H [Kyushu University, Fukuoka (Japan). Faculty of Engineering

    1997-05-27

    A program has been developed to conduct inversion analysis of two-dimensional model using MT data, accurately. For the developed program, finite element method (FEM) was applied to the section of sequential analysis. A method in which Jacobian matrix is calculated only one first time and is inversely analyzed by fixing this during the repetition, and a method in which Jacobian matrix is corrected at each repetition of inversion analysis, were compared mutually. As a result of the numerical simulation, it was revealed that the Jacobian correction method provided more stable convergence for the simple 2D model, and that the calculation time is almost same as that of the Jacobian fixation method. To confirm the applicability of this program to actually measured data, results obtained from this program were compared with those from the Schlumberger method analysis by using MT data obtained in the Hatchobara geothermal area. Consequently, it was demonstrated that the both are well coincided mutually. 17 refs., 7 figs.

  17. An interpretation of signature inversion

    International Nuclear Information System (INIS)

    Onishi, Naoki; Tajima, Naoki

    1988-01-01

    An interpretation in terms of the cranking model is presented to explain why signature inversion occurs for positive γ of the axially asymmetric deformation parameter and emerges into specific orbitals. By introducing a continuous variable, the eigenvalue equation can be reduced to a one dimensional Schroedinger equation by means of which one can easily understand the cause of signature inversion. (author)

  18. Inverse comptonization vs. thermal synchrotron

    International Nuclear Information System (INIS)

    Fenimore, E.E.; Klebesadel, R.W.; Laros, J.G.

    1983-01-01

    There are currently two radiation mechanisms being considered for gamma-ray bursts: thermal synchrotron and inverse comptonization. They are mutually exclusive since thermal synchrotron requires a magnetic field of approx. 10 12 Gauss whereas inverse comptonization cannot produce a monotonic spectrum if the field is larger than 10 11 and is too inefficient relative to thermal synchrotron unless the field is less than 10 9 Gauss. Neither mechanism can explain completely the observed characteristics of gamma-ray bursts. However, we conclude that thermal synchrotron is more consistent with the observations if the sources are approx. 40 kpc away whereas inverse comptonization is more consistent if they are approx. 300 pc away. Unfortunately, the source distance is still not known and, thus, the radiation mechanism is still uncertain

  19. Inversion of the star transform

    International Nuclear Information System (INIS)

    Zhao, Fan; Schotland, John C; Markel, Vadim A

    2014-01-01

    We define the star transform as a generalization of the broken ray transform introduced by us in previous work. The advantages of using the star transform include the possibility to reconstruct the absorption and the scattering coefficients of the medium separately and simultaneously (from the same data) and the possibility to utilize scattered radiation which, in the case of conventional x-ray tomography, is discarded. In this paper, we derive the star transform from physical principles, discuss its mathematical properties and analyze numerical stability of inversion. In particular, it is shown that stable inversion of the star transform can be obtained only for configurations involving odd number of rays. Several computationally-efficient inversion algorithms are derived and tested numerically. (paper)

  20. Origins of De Novo Genes in Human and Chimpanzee.

    Science.gov (United States)

    Ruiz-Orera, Jorge; Hernandez-Rodriguez, Jessica; Chiva, Cristina; Sabidó, Eduard; Kondova, Ivanela; Bontrop, Ronald; Marqués-Bonet, Tomàs; Albà, M Mar

    2015-12-01

    The birth of new genes is an important motor of evolutionary innovation. Whereas many new genes arise by gene duplication, others originate at genomic regions that did not contain any genes or gene copies. Some of these newly expressed genes may acquire coding or non-coding functions and be preserved by natural selection. However, it is yet unclear which is the prevalence and underlying mechanisms of de novo gene emergence. In order to obtain a comprehensive view of this process, we have performed in-depth sequencing of the transcriptomes of four mammalian species--human, chimpanzee, macaque, and mouse--and subsequently compared the assembled transcripts and the corresponding syntenic genomic regions. This has resulted in the identification of over five thousand new multiexonic transcriptional events in human and/or chimpanzee that are not observed in the rest of species. Using comparative genomics, we show that the expression of these transcripts is associated with the gain of regulatory motifs upstream of the transcription start site (TSS) and of U1 snRNP sites downstream of the TSS. In general, these transcripts show little evidence of purifying selection, suggesting that many of them are not functional. However, we find signatures of selection in a subset of de novo genes which have evidence of protein translation. Taken together, the data support a model in which frequently-occurring new transcriptional events in the genome provide the raw material for the evolution of new proteins.

  1. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

    International Nuclear Information System (INIS)

    Haigh, Cathryn L.; Drew, Simon C.

    2015-01-01

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation

  2. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

    Energy Technology Data Exchange (ETDEWEB)

    Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Drew, Simon C., E-mail: sdrew@unimelb.edu.au [Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010 (Australia)

    2015-06-05

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.

  3. Frequency-domain waveform inversion using the unwrapped phase

    KAUST Repository

    Choi, Yun Seok

    2011-01-01

    Phase wrapping in the frequency-domain (or cycle skipping in the time-domain) is the major cause of the local minima problem in the waveform inversion. The unwrapped phase has the potential to provide us with a robust and reliable waveform inversion, with reduced local minima. We propose a waveform inversion algorithm using the unwrapped phase objective function in the frequency-domain. The unwrapped phase, or what we call the instantaneous traveltime, is given by the imaginary part of dividing the derivative of the wavefield with respect to the angular frequency by the wavefield itself. As a result, the objective function is given a traveltime-like function, which allows us to smooth it and reduce its nonlinearity. The gradient of the objective function is computed using the back-propagation algorithm based on the adjoint-state technique. We apply both our waveform inversion algorithm using the unwrapped phase and the conventional waveform inversion and show that our inversion algorithm gives better convergence to the true model than the conventional waveform inversion. © 2011 Society of Exploration Geophysicists.

  4. De Novo Assembly and Characterization of the Transcriptome of Grasshopper Shirakiacris shirakii

    Directory of Open Access Journals (Sweden)

    Zhongying Qiu

    2016-07-01

    Full Text Available Background: The grasshopper Shirakiacris shirakii is an important agricultural pest and feeds mainly on gramineous plants, thereby causing economic damage to a wide range of crops. However, genomic information on this species is extremely limited thus far, and transcriptome data relevant to insecticide resistance and pest control are also not available. Methods: The transcriptome of S. shirakii was sequenced using the Illumina HiSeq platform, and we de novo assembled the transcriptome. Results: Its sequencing produced a total of 105,408,878 clean reads, and the de novo assembly revealed 74,657 unigenes with an average length of 680 bp and N50 of 1057 bp. A total of 28,173 unigenes were annotated for the NCBI non-redundant protein sequences (Nr, NCBI non-redundant nucleotide sequences (Nt, a manually-annotated and reviewed protein sequence database (Swiss-Prot, Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG databases. Based on the Nr annotation results, we manually identified 79 unigenes encoding cytochrome P450 monooxygenases (P450s, 36 unigenes encoding carboxylesterases (CarEs and 36 unigenes encoding glutathione S-transferases (GSTs in S. shirakii. Core RNAi components relevant to miroRNA, siRNA and piRNA pathways, including Pasha, Loquacious, Argonaute-1, Argonaute-2, Argonaute-3, Zucchini, Aubergine, enhanced RNAi-1 and Piwi, were expressed in S. shirakii. We also identified five unigenes that were homologous to the Sid-1 gene. In addition, the analysis of differential gene expressions revealed that a total of 19,764 unigenes were up-regulated and 4185 unigenes were down-regulated in larvae. In total, we predicted 7504 simple sequence repeats (SSRs from 74,657 unigenes. Conclusions: The comprehensive de novo transcriptomic data of S. shirakii will offer a series of valuable molecular resources for better studying insecticide resistance, RNAi and molecular marker discovery in the transcriptome.

  5. ESTADO E NOVOS AGENTES SOCIAIS NA RECONSTRUÇÃO DO ESPAÇO

    Directory of Open Access Journals (Sweden)

    Cláudio Barbosa da Costa

    2006-07-01

    Full Text Available Este estudo tem como objetivo principal sistematizar novas questões referentes à complexidade das ações dos agentes sociais na construção do espaço contemporâneo, e que vem interferindo, de maneira significativa, na forma como o Estado vem realizando o processo de intervenção no território. Os eixos analíticos do estudo serão constituídos pelo novo patamar de acumulação que constitui a globalização, os grandes agentes econômicos internacionais e as novas referências da chamada lógica civilizatória, na qual emergem sujeitos sociais que ao buscarem romper com idéia dominante de desenvolvimento e de crescimento, vêm construindo novas formas de lidar com a natureza, com o território e com o trabalho, estabelecendo a alteridade, a partir da luta pela sua legitimidade. A compreensão teórica dos novos movimentos sociais possibilitou um melhor entendimento do papel histórico destes agentes na construção contemporânea do espaço e das suas relações com o vetor ecológico e o desenvolvimento sustentável. Para finalizar, realizamos uma análise histórica das intervenções do Estado brasileiro na construção do território nacional, buscando identificar a complexidade dos agentes da sociedade civil, e as possibilidades e os limites da constituição de um projeto geopolítico através de um novo pacto social, que resguardando as diferenças, consideram-se as territorialidades dos setores sociais historicamente excluídos do processo de

  6. NOVOS PRODUTOS SOB O ENFOQUE DO SISTEMA DE CONSUMO E A ORIENTAÇÃO PARA O MERCADO

    OpenAIRE

    Mauro Calixta Tavares; Valéria Braga Pinto

    2009-01-01

    A orientação para o mercado tem sido abordada com suas possíveis implicações na estrutura, processos, pessoas, desenvolvimento de novos produtos, inovação e flexibilidade estratégica, entre outras possibilidades. O foco do presente capítulo é sobre sua relação com novos produtos sob a perspectiva de sistema de consumo. A partir de um estudo exploratório, os alunos de um programa de MBA, divididos em grupos, realizaram um trabalho envolvendo o consumo de vários produtos e serviços sob a perspe...

  7. Autosomal dominant cutis laxa with progeroid features due to a novel, de novo mutation in ALDH18A1.

    Science.gov (United States)

    Bhola, Priya T; Hartley, Taila; Bareke, Eric; Boycott, Kym M; Nikkel, Sarah M; Dyment, David A

    2017-06-01

    De novo dominant mutations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1) gene have recently been shown to cause autosomal dominant cutis laxa with progeroid features (MIM 616603). To date, all de novo dominant mutations have been found in a single highly conserved amino acid residue at position p.Arg138. We report an 8-year-old male with a clinical diagnosis of autosomal dominant cutis laxa (ADCL) with progeroid features and a novel de novo missense mutation in ALDH18A1 (NM_002860.3: c.377G>A (p.Arg126His)). This is the first report of an individual with ALDH18A1-ADCL due to a substitution at a residue other than p.Arg138. Knowledge of the complete spectrum of dominant-acting mutations that cause this rare syndrome will have implications for molecular diagnosis and genetic counselling of these families.

  8. Workflows for Full Waveform Inversions

    Science.gov (United States)

    Boehm, Christian; Krischer, Lion; Afanasiev, Michael; van Driel, Martin; May, Dave A.; Rietmann, Max; Fichtner, Andreas

    2017-04-01

    Despite many theoretical advances and the increasing availability of high-performance computing clusters, full seismic waveform inversions still face considerable challenges regarding data and workflow management. While the community has access to solvers which can harness modern heterogeneous computing architectures, the computational bottleneck has fallen to these often manpower-bounded issues that need to be overcome to facilitate further progress. Modern inversions involve huge amounts of data and require a tight integration between numerical PDE solvers, data acquisition and processing systems, nonlinear optimization libraries, and job orchestration frameworks. To this end we created a set of libraries and applications revolving around Salvus (http://salvus.io), a novel software package designed to solve large-scale full waveform inverse problems. This presentation focuses on solving passive source seismic full waveform inversions from local to global scales with Salvus. We discuss (i) design choices for the aforementioned components required for full waveform modeling and inversion, (ii) their implementation in the Salvus framework, and (iii) how it is all tied together by a usable workflow system. We combine state-of-the-art algorithms ranging from high-order finite-element solutions of the wave equation to quasi-Newton optimization algorithms using trust-region methods that can handle inexact derivatives. All is steered by an automated interactive graph-based workflow framework capable of orchestrating all necessary pieces. This naturally facilitates the creation of new Earth models and hopefully sparks new scientific insights. Additionally, and even more importantly, it enhances reproducibility and reliability of the final results.

  9. Differences in Recurrence Rate and De Novo Incontinence after Endoscopic Treatment of Vesicourethral Stenosis and Bladder Neck Stenosis

    Directory of Open Access Journals (Sweden)

    Jennifer Kranz

    2017-08-01

    Full Text Available ObjectivesThe objective of this study was to compare the recurrence rate and de novo incontinence after endoscopic treatment of vesicourethral stenosis (VUS after radical prostatectomy (RP and for bladder neck stenosis (BNS after transurethral resection of the prostate (TURP.MethodsRetrospective analysis of patients treated endoscopically for VUS after RP or for BNS after TURP at three German tertiary care centers between March 2009 and June 2016. Investigated endpoints were recurrence rate and de novo incontinence. Chi-squared tests and t-tests were used to model the differences between groups.ResultsA total of 147 patients underwent endoscopic therapy for VUS (59.2% or BNS (40.8%. Mean age was 68.3 years (range 44–86, mean follow-up 27.1 months (1–98. Mean time to recurrence after initial therapy was 23.9 months (1–156, mean time to recurrence after prior endoscopic therapy for VUS or BNS was 12.0 months (1–159. Patients treated for VUS underwent significantly more often radiotherapy prior to endoscopic treatment (33.3 vs. 13.3%; p = 0.006 and the recurrence rate was significantly higher (59.8 vs. 41.7%; p = 0.031. The overall success rate of TUR for VUS was 40.2%, success rate of TUR for BNS was 58.3%. TUR for BNS is significantly more successful (p = 0.031. The mean number of TUR for BNS vs. TUR for VUS in successful cases was 1.5 vs. 1.8, which was not significantly different. The rate of de novo incontinence was significantly higher in patients treated for VUS (13.8 vs. 1.7%; p = 0.011. After excluding those patients with radiotherapy prior to endoscopic treatment, the recurrence rate did not differ significantly between both groups (60.3% for VUS vs. 44.2% for BNS; p = 0.091, whereas the rate of de novo incontinence (13.8 for VUS vs. 0% for BNS; p = 0.005 stayed significantly higher in patients treated for VUS.ConclusionMost patients with BNS are successfully treated endoscopically. In patients with

  10. Resolution analysis in full waveform inversion

    NARCIS (Netherlands)

    Fichtner, A.; Trampert, J.

    2011-01-01

    We propose a new method for the quantitative resolution analysis in full seismic waveform inversion that overcomes the limitations of classical synthetic inversions while being computationally more efficient and applicable to any misfit measure. The method rests on (1) the local quadratic

  11. Novos biomateriais poliméricos para implantes ósseos

    OpenAIRE

    Ferreira, Sara Cristina Silva

    2016-01-01

    Os danos dos tecidos ósseos representam um problema importante de saúde em todo o mundo. Um dos componentes principais utilizados em engenharia de tecidos são os materiais de suporte, estruturas 3D formadas por matrizes porosas, que visam proporcionar o desenvolvimento do novo tecido. Muitas das matrizes poliméricas porosas (espumas) utilizadas em aplicações médicas são constituídas por poliuretanos, sendo estes produzidos a partir de isocianatos (produtos tóxicos) e polióis. Assim, surge a n...

  12. An inverse method for radiation transport

    Energy Technology Data Exchange (ETDEWEB)

    Favorite, J. A. (Jeffrey A.); Sanchez, R. (Richard)

    2004-01-01

    Adjoint functions have been used with forward functions to compute gradients in implicit (iterative) solution methods for inverse problems in optical tomography, geoscience, thermal science, and other fields, but only once has this approach been used for inverse solutions to the Boltzmann transport equation. In this paper, this approach is used to develop an inverse method that requires only angle-independent flux measurements, rather than angle-dependent measurements as was done previously. The method is applied to a simplified form of the transport equation that does not include scattering. The resulting procedure uses measured values of gamma-ray fluxes of discrete, characteristic energies to determine interface locations in a multilayer shield. The method was implemented with a Newton-Raphson optimization algorithm, and it worked very well in numerical one-dimensional spherical test cases. A more sophisticated optimization method would better exploit the potential of the inverse method.

  13. De novo transcriptome assembly of two different peach cultivars grown in Korea

    Directory of Open Access Journals (Sweden)

    Yeonhwa Jo

    2015-12-01

    Full Text Available Peach (Prunus persica is one of the most popular stone fruits worldwide. Next generation sequencing (NGS has facilitated genome and transcriptome analyses of several stone fruit trees. In this study, we conducted de novo transcriptome analyses of two peach cultivars grown in Korea. Leaves of two cultivars, referred to as Jangtaek and Mibaek, were harvested and used for library preparation. The two prepared libraries were paired-end sequenced by the HiSeq2000 system. We obtained 8.14 GB and 9.62 GB sequence data from Jangtaek and Mibaek (NCBI accession numbers: SRS1056585 and SRS1056587, respectively. The Trinity program was used to assemble two transcriptomes de novo, resulting in 110,477 (Jangtaek and 136,196 (Mibaek transcripts. TransDecoder identified possible coding regions in assembled transcripts. The identified proteins were subjected to BLASTP search against NCBI's non-redundant database for functional annotation. This study provides transcriptome data for two peach cultivars, which might be useful for genetic marker development and comparative transcriptome analyses.

  14. Adopting De Novo Programming Approach on IC Design Service Firms Resources Integration

    Directory of Open Access Journals (Sweden)

    James K. C. Chen

    2014-01-01

    Full Text Available The semiconductor industry has very important position in computer industry, ICT field, and new electronic technology developing. The IC design service is one of key factor of semiconductor industry development. There are more than 365 IC design service firms have been established around Hsinchu Science Park in Taiwan. Building an efficient planning model for IC design service firm resources integrating is very interest issue. This study aims to construct a planning model for IC design service firm implementation resources integration. This study uses the De Novo programming as an approach of criteria alternative to achieve optimal resource allocation on IC design firm. Results show the IC design service firm should conduct open innovation concept and utilizes design outsourcing obtains cost down and enhance IC design service business performance. This plan model of De Novo programming is not only for IC design service firm and also can apply to the other industrial implementation strategic alliance/integrating resource. This plan model is a universal model for the others industries field.

  15. 3D stochastic inversion and joint inversion of potential fields for multi scale parameters

    Science.gov (United States)

    Shamsipour, Pejman

    In this thesis we present the development of new techniques for the interpretation of potential field (gravity and magnetic data), which are the most widespread economic geophysical methods used for oil and mineral exploration. These new techniques help to address the long-standing issue with the interpretation of potential fields, namely the intrinsic non-uniqueness inversion of these types of data. The thesis takes the form of three papers (four including Appendix), which have been published, or soon to be published, in respected international journals. The purpose of the thesis is to introduce new methods based on 3D stochastical approaches for: 1) Inversion of potential field data (magnetic), 2) Multiscale Inversion using surface and borehole data and 3) Joint inversion of geophysical potential field data. We first present a stochastic inversion method based on a geostatistical approach to recover 3D susceptibility models from magnetic data. The aim of applying geostatistics is to provide quantitative descriptions of natural variables distributed in space or in time and space. We evaluate the uncertainty on the parameter model by using geostatistical unconditional simulations. The realizations are post-conditioned by cokriging to observation data. In order to avoid the natural tendency of the estimated structure to lay near the surface, depth weighting is included in the cokriging system. Then, we introduce algorithm for multiscale inversion, the presented algorithm has the capability of inverting data on multiple supports. The method involves four main steps: i. upscaling of borehole parameters (It could be density or susceptibility) to block parameters, ii. selection of block to use as constraints based on a threshold on kriging variance, iii. inversion of observation data with selected block densities as constraints, and iv. downscaling of inverted parameters to small prisms. Two modes of application are presented: estimation and simulation. Finally, a novel

  16. De novo hepatic steatosis drives atherogenic risk in liver transplantation recipients.

    Science.gov (United States)

    Idowu, Michael O; Chhatrala, Ravi; Siddiqui, M Bilal; Driscoll, Carolyn; Stravitz, R Todd; Sanyal, Arun J; Bhati, Chandra; Sargeant, Carol; Luketic, Velimir A; Sterling, Richard K; Contos, Melissa; Matherly, Scott; Puri, Puneet; Siddiqui, M Shadab

    2015-11-01

    Nonalcoholic fatty liver disease is associated with cardiovascular disease (CVD) in the general population. Despite a high prevalence of de novo hepatic steatosis after liver transplantation (LT), there are no data exploring the association between hepatic steatosis after LT and atherogenic risk. The aim of the study was to explore the impact of hepatic steatosis on serum atherogenic markers in liver transplantation recipients (LTRs). Biomarkers of CVD risk were compared in 89 LTRs with no known history of dyslipidemia, ischemic heart disease, or graft cirrhosis. To avoid potential confounders, LTRs on oral hypoglycemic agents, exogenous insulin, corticosteroids, or lipid-lowering therapy were excluded. Only patients for whom histological assessment was available after LT were included in the study. Thirty-five LTRs had de novo hepatic steatosis after LT, whereas 54 did not. Both cohorts were similar with regards to age, sex, ethnicity, and follow-up from LT. Additionally, the traditional lipid profile was similar between the 2 cohorts. LTRs with hepatic steatosis had higher serum concentrations of small-dense low-density lipoprotein cholesterol (sdLDL-C; 34.8 ± 16.9 versus 22.7 ± 11.2 mg/dL; P hepatic steatosis had higher serum insulin concentrations (27.8 ± 41.8 versus 11.7 ± 7.8 uU/mL; P Steatosis grade was directly related to sdLDL-C, sdLDL-P, insulin, VLDL-P, and VLDL-size. In multivariate analysis, the association between steatosis grade and sdLDL-C (β = 0.03; P = 0.029), VLDL-size (β = 0.316; P = 0.04), and low-density lipoprotein particle size (β = -0.27; P = 0.05) was independent of sex, body mass index, age, diabetes mellitus, time from transplant, and indication for LT. In conclusion, de novo hepatic steatosis after LT is associated with atherogenic lipoproteins and independent of traditional CVD risk factors. © 2015 American Association for the Study of Liver Diseases.

  17. Simultaneous inversion of seismic velocity and moment tensor using elastic-waveform inversion of microseismic data: Application to the Aneth CO2-EOR field

    Science.gov (United States)

    Chen, Y.; Huang, L.

    2017-12-01

    Moment tensors are key parameters for characterizing CO2-injection-induced microseismic events. Elastic-waveform inversion has the potential to providing accurate results of moment tensors. Microseismic waveforms contains information of source moment tensors and the wave propagation velocity along the wavepaths. We develop an elastic-waveform inversion method to jointly invert the seismic velocity model and moment tensor. We first use our adaptive moment-tensor joint inversion method to estimate moment tensors of microseismic events. Our adaptive moment-tensor inversion method jointly inverts multiple microseismic events with similar waveforms within a cluster to reduce inversion uncertainty for microseismic data recorded using a single borehole geophone array. We use this inversion result as the initial model for our elastic-waveform inversion to minimize the cross-correlated-based data misfit between observed data and synthetic data. We verify our method using synthetic microseismic data and obtain improved results of both moment tensors and seismic velocity model. We apply our new inversion method to microseismic data acquired at a CO2-enhanced oil recovery field in Aneth, Utah, using a single borehole geophone array. The results demonstrate that our new inversion method significantly reduces the data misfit compared to the conventional ray-theory-based moment-tensor inversion.

  18. Ética, política e direito brasileiro: reflexões para um novo senso

    Directory of Open Access Journals (Sweden)

    Adriano Monteiro Madruga

    2010-12-01

    Full Text Available O objetivo deste artigo é questionar o sentido enfático dado à ética no cenário político brasileiro na atualidade e seus reflexos no direito, já que historicamente a política e o direito estiveram sempre centralizados aos interesses dos grandes personagens e fatos (Hegel e para contrapor essa percepção é pensada a história do Brasil como tragédia repetida por farsa (Marx e o sentido de Pasárgada (Santos. A partir disso, re-pensar a ética como diálogo político (Platão e a universalidade das leis (Cícero no direito brasileiro na hodiernidade voltadas para cidadania através de movimentos de vanguarda refletidos por novos espelhos sociais para um novo senso comum (Santos.

  19. Damaging de novo mutations diminish motor skills in children on the autism spectrum.

    Science.gov (United States)

    Buja, Andreas; Volfovsky, Natalia; Krieger, Abba M; Lord, Catherine; Lash, Alex E; Wigler, Michael; Iossifov, Ivan

    2018-02-20

    In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills). Copyright © 2018 the Author(s). Published by PNAS.

  20. Synthesis of Poly pyrrole Inverse Opal in [bmim] Containing Acetonitrile and the Application of the Inverse Opal in Cell Prototype

    International Nuclear Information System (INIS)

    Yan, W.; Dong, Q.Q.; Sun, L.N.; Deng, W.; Wu, Sh.

    2013-01-01

    Most primary cells use Zn or Li as the anode, a metallic oxide as the cathode, and an acidic or alkaline solution or moist past as the electrolytic solution. In this paper, highly ordered poly pyrrole (PPy) inverse opals have been successfully synthesized in the acetonitrile solution containing [bmim]PF 6 . PPy films were prepared under the same experimental conditions. Cyclic voltammograms of the PPy film and the PPy inverse opal in neutral phosphate buffer solution (PBS) were recorded. X-ray photoelectron spectroscopy technique was used to investigate the structural surface of the PPy films and the PPy inverse opals. It is found that the PF 6 - anions kept de doping from the PPy films during the potential scanning process, resulting in the electrochemical inactivity. Although PF 6 - anions also kept de doping from the PPy inverse opals, the PO 4 3- anions from PBS could dope into the inverse opal, explaining why the PPy inverse opals kept their electrochemical activity. An environmental friendly cell prototype was constructed, using the PPy inverse opal as the anode. The electrolytes in both the cathodic and anodic half-cells were neutral PBSs. The open-circuit potential of the cell prototype reached 0.487 V and showed a stable output over several hundred hours

  1. Multiparameter Optimization for Electromagnetic Inversion Problem

    Directory of Open Access Journals (Sweden)

    M. Elkattan

    2017-10-01

    Full Text Available Electromagnetic (EM methods have been extensively used in geophysical investigations such as mineral and hydrocarbon exploration as well as in geological mapping and structural studies. In this paper, we developed an inversion methodology for Electromagnetic data to determine physical parameters of a set of horizontal layers. We conducted Forward model using transmission line method. In the inversion part, we solved multi parameter optimization problem where, the parameters are conductivity, dielectric constant, and permeability of each layer. The optimization problem was solved by simulated annealing approach. The inversion methodology was tested using a set of models representing common geological formations.

  2. Inverse problems for the Boussinesq system

    International Nuclear Information System (INIS)

    Fan, Jishan; Jiang, Yu; Nakamura, Gen

    2009-01-01

    We obtain two results on inverse problems for a 2D Boussinesq system. One is that we prove the Lipschitz stability for the inverse source problem of identifying a time-independent external force in the system with observation data in an arbitrary sub-domain over a time interval of the velocity and the data of velocity and temperature at a fixed positive time t 0 > 0 over the whole spatial domain. The other one is that we prove a conditional stability estimate for an inverse problem of identifying the two initial conditions with a single observation on a sub-domain

  3. Estudo do mecanismo de ação de novos compostos de ruténio com atividade antitumoral

    OpenAIRE

    Carvalho, Andreia Catarina Guerreiro Morais de

    2017-01-01

    Tese de mestrado, Bioquímica (Bioquímica Médica), Universidade de Lisboa, Faculdade de Ciências, 2017 A quimioterapia é um tratamento tradicional do cancro. Sua alta toxicidade, afetando tecidos saudáveis, e a resistência intrínseca a fármacos são obstáculos que precisam de ser superados. Desta forma, a identificação de novos agentes quimioterapêuticos é fundamental para novos progressos no tratamento do cancro. Uma abordagem inclui complexos de ruténio, que foram reconhecidos como uma alt...

  4. Intersections, ideals, and inversion

    International Nuclear Information System (INIS)

    Vasco, D.W.

    1998-01-01

    Techniques from computational algebra provide a framework for treating large classes of inverse problems. In particular, the discretization of many types of integral equations and of partial differential equations with undetermined coefficients lead to systems of polynomial equations. The structure of the solution set of such equations may be examined using algebraic techniques.. For example, the existence and dimensionality of the solution set may be determined. Furthermore, it is possible to bound the total number of solutions. The approach is illustrated by a numerical application to the inverse problem associated with the Helmholtz equation. The algebraic methods are used in the inversion of a set of transverse electric (TE) mode magnetotelluric data from Antarctica. The existence of solutions is demonstrated and the number of solutions is found to be finite, bounded from above at 50. The best fitting structure is dominantly one dimensional with a low crustal resistivity of about 2 ohm-m. Such a low value is compatible with studies suggesting lower surface wave velocities than found in typical stable cratons

  5. Intersections, ideals, and inversion

    Energy Technology Data Exchange (ETDEWEB)

    Vasco, D.W.

    1998-10-01

    Techniques from computational algebra provide a framework for treating large classes of inverse problems. In particular, the discretization of many types of integral equations and of partial differential equations with undetermined coefficients lead to systems of polynomial equations. The structure of the solution set of such equations may be examined using algebraic techniques.. For example, the existence and dimensionality of the solution set may be determined. Furthermore, it is possible to bound the total number of solutions. The approach is illustrated by a numerical application to the inverse problem associated with the Helmholtz equation. The algebraic methods are used in the inversion of a set of transverse electric (TE) mode magnetotelluric data from Antarctica. The existence of solutions is demonstrated and the number of solutions is found to be finite, bounded from above at 50. The best fitting structure is dominantly onedimensional with a low crustal resistivity of about 2 ohm-m. Such a low value is compatible with studies suggesting lower surface wave velocities than found in typical stable cratons.

  6. Inversions and the dynamics of eukaryotic gene order.

    NARCIS (Netherlands)

    Huynen, M.A.; Snel, B.; Bork, P.

    2001-01-01

    Comparisons of the gene order in closely related genomes reveal a major role for inversions in the genome shuffling process. In contrast to prokaryotes, where the inversions are predominantly large, half of the inversions between Saccharomyces cerevisiae and Candida albicans appear to be small,

  7. Study of the fast inversion recovery pulse sequence. With reference to fast fluid attenuated inversion recovery and fast short TI inversion recovery pulse sequence

    International Nuclear Information System (INIS)

    Tsuchihashi, Toshio; Maki, Toshio; Suzuki, Takeshi

    1997-01-01

    The fast inversion recovery (fast IR) pulse sequence was evaluated. We compared the fast fluid attenuated inversion recovery (fast FLAIR) pulse sequence in which inversion time (TI) was established as equal to the water null point for the purpose of the water-suppressed T 2 -weighted image, with the fast short TI inversion recovery (fast STIR) pulse sequence in which TI was established as equal to the fat null point for purpose of fat suppression. In the fast FLAIR pulse sequence, the water null point was increased by making TR longer. In the FLAIR pulse sequence, the longitudinal magnetization contrast is determined by TI. If TI is increased, T 2 -weighted contrast improves in the same way as increasing TR for the SE pulse sequence. Therefore, images should be taken with long TR and long TI, which are longer than TR and longer than the water null point. On the other hand, the fat null point is not affected by TR in the fast STIR pulse sequence. However, effective TE was affected by variation of the null point. This increased in proportion to the increase in effective TE. Our evaluation indicated that the fast STIR pulse sequence can control the extensive signals from fat in a short time. (author)

  8. De novo pathway-based biomarker identification

    DEFF Research Database (Denmark)

    Alcaraz, Nicolas; List, Markus; Batra, Richa

    2017-01-01

    in a large cohort of breast cancer samples from The Cancer Genome Atlas (TCGA) revealed that MGs are considerably more stable than SG models, while also providing valuable insight into the cancer hallmarks that drive them. In addition, when tested on an independent benchmark non-TCGA dataset, MG features......Gene expression profiles have been extensively discussed as an aid to guide the therapy by predicting disease outcome for the patients suffering from complex diseases, such as cancer. However, prediction models built upon single-gene (SG) features show poor stability and performance on independent...... on their molecular subtypes can provide a detailed view of the disease and lead to more personalized therapies. We propose and discuss a novel MG approach based on de novo pathways, which for the first time have been used as features in a multi-class setting to predict cancer subtypes. Comprehensive evaluation...

  9. Organ-Specific Alterations in Fatty Acid De Novo Synthesis and Desaturation in a Rat Model of Programmed Obesity

    Directory of Open Access Journals (Sweden)

    Desai Mina

    2011-05-01

    Full Text Available Abstract Background Small for gestational age (SGA leads to increased risk of adult obesity and metabolic syndrome. Offspring exposed to 50% maternal food restriction in utero are born smaller than Controls (FR, catch-up in growth by the end of the nursing period, and become obese adults. The objective of the study was to determine stearoyl-CoA desaturase activity (SCD1 and rates of de novo fatty acid synthesis in young FR and Control offspring tissues at the end of the nursing period, as possible contributors to catch-up growth. Methods From gestational day 10 to term, dams fed ad libitum (Control or were 50% food-restricted to produce small FR pups. Control dams nursed all pups. At postnatal day 1 (p1 and p21, offspring body tissues were analyzed by GC/MS, and desaturation indices of palmitoleate/palmitate and oleate/stearate were calculated. SCD1 gene expression was determined by real-time PCR on adipose and liver. Offspring were enriched with deuterium that was given to dams in drinking water during lactation and de novo synthesis of offspring body tissues was determined at p21. Primary adipocyte cell cultures were established at p21 and exposed to U13C-glucose. Results FR offspring exhibited higher desaturation index in p1 and p21 adipose tissue, but decreased desaturation index in liver at p21. SCD1 gene expression at p21 was correspondingly increased in adipose and decreased in liver. FR subcutaneous fat demonstrated increased de novo synthesis at p21. Primary cell cultures exhibited increased de novo synthesis in FR. Conclusions Adipose tissue is the first site to exhibit increased de novo synthesis and desaturase activity in FR. Therefore, abnormal lipogenesis is already present prior to onset of obesity during the period of catch-up growth. These abnormalities may contribute to future obesity development.

  10. EDUCOMUNICAÇÃO E PROTAGONISMO JUVENIL: um novo olhar para a educação

    Directory of Open Access Journals (Sweden)

    Lauro Roberto Lostada

    2016-09-01

    Full Text Available Este trabalho tem como objetivo apresentar algumas breves considerações sobre a escola tradicional, considerada por muitos como uma instituição reprodutivista, arcaica e ultrapassada, e o impacto que as tecnologias tem causado diretamente em sua estrutura e, portanto, nas práticas dos professores. Desta maneira, será apresentado um novo modo de pensar a escola: a educomunicação. Para tanto, o trabalho parte de uma pesquisa empírica, com uso de técnicas de entrevista e observações, onde será analisada a experiência de um projeto educomunicativo que oferece oportunidade de engajamento aos estudantes de uma escola do município de São José, em Santa Catarina, através da produção radiofônica, veiculada na instituição diariamente, o que tem demonstrado a possibilidade de um novo modelo pedagógico, mais participativo, onde o professor passa a exercer o papel de um mediador, cujo esforço se volta à oferta de espaços de participação e novas oportunidades de aprendizagem. Assim, as análises aqui apresentadas permitem entender, de modo geral, o protagonismo juvenil como um novo modo de olhar a educação e, destarte, a própria escola do século XXI.

  11. De novo and rare inherited copy-number variations in the hemiplegic form of cerebral palsy.

    Science.gov (United States)

    Zarrei, Mehdi; Fehlings, Darcy L; Mawjee, Karizma; Switzer, Lauren; Thiruvahindrapuram, Bhooma; Walker, Susan; Merico, Daniele; Casallo, Guillermo; Uddin, Mohammed; MacDonald, Jeffrey R; Gazzellone, Matthew J; Higginbotham, Edward J; Campbell, Craig; deVeber, Gabrielle; Frid, Pam; Gorter, Jan Willem; Hunt, Carolyn; Kawamura, Anne; Kim, Marie; McCormick, Anna; Mesterman, Ronit; Samdup, Dawa; Marshall, Christian R; Stavropoulos, Dimitri J; Wintle, Richard F; Scherer, Stephen W

    2018-02-01

    PurposeHemiplegia is a subtype of cerebral palsy (CP) in which one side of the body is affected. Our earlier study of unselected children with CP demonstrated de novo and clinically relevant rare inherited genomic copy-number variations (CNVs) in 9.6% of participants. Here, we examined the prevalence and types of CNVs specifically in hemiplegic CP.MethodsWe genotyped 97 unrelated probands with hemiplegic CP and their parents. We compared their CNVs to those of 10,851 population controls, in order to identify rare CNVs (<0.1% frequency) that might be relevant to CP. We also sequenced exomes of "CNV-positive" trios.ResultsWe detected de novo CNVs and/or sex chromosome abnormalities in 7/97 (7.2%) of probands, impacting important developmental genes such as GRIK2, LAMA1, DMD, PTPRM, and DIP2C. In 18/97 individuals (18.6%), rare inherited CNVs were found, affecting loci associated with known genomic disorders (17p12, 22q11.21) or involving genes linked to neurodevelopmental disorders.ConclusionWe found an increased rate of de novo CNVs in the hemiplegic CP subtype (7.2%) compared to controls (1%). This result is similar to that for an unselected CP group. Combined with rare inherited CNVs, the genomic data impacts the understanding of the potential etiology of hemiplegic CP in 23/97 (23.7%) of participants.

  12. De novo mutation in the dopamine transporter gene associates dopamine dysfunction with autism spectrum disorder.

    Science.gov (United States)

    Hamilton, P J; Campbell, N G; Sharma, S; Erreger, K; Herborg Hansen, F; Saunders, C; Belovich, A N; Sahai, M A; Cook, E H; Gether, U; McHaourab, H S; Matthies, H J G; Sutcliffe, J S; Galli, A

    2013-12-01

    De novo genetic variation is an important class of risk factors for autism spectrum disorder (ASD). Recently, whole-exome sequencing of ASD families has identified a novel de novo missense mutation in the human dopamine (DA) transporter (hDAT) gene, which results in a Thr to Met substitution at site 356 (hDAT T356M). The dopamine transporter (DAT) is a presynaptic membrane protein that regulates dopaminergic tone in the central nervous system by mediating the high-affinity reuptake of synaptically released DA, making it a crucial regulator of DA homeostasis. Here, we report the first functional, structural and behavioral characterization of an ASD-associated de novo mutation in the hDAT. We demonstrate that the hDAT T356M displays anomalous function, characterized as a persistent reverse transport of DA (substrate efflux). Importantly, in the bacterial homolog leucine transporter, substitution of A289 (the homologous site to T356) with a Met promotes an outward-facing conformation upon substrate binding. In the substrate-bound state, an outward-facing transporter conformation is required for substrate efflux. In Drosophila melanogaster, the expression of hDAT T356M in DA neurons-lacking Drosophila DAT leads to hyperlocomotion, a trait associated with DA dysfunction and ASD. Taken together, our findings demonstrate that alterations in DA homeostasis, mediated by aberrant DAT function, may confer risk for ASD and related neuropsychiatric conditions.

  13. Inversion effects for faces and objects in developmental prosopagnosia

    DEFF Research Database (Denmark)

    Klargaard, Solja K; Starrfelt, Randi; Gerlach, Christian

    2018-01-01

    The disproportionate face inversion effect (dFIE) concerns the finding that face recognition is more affected by inversion than recognition of non-face objects; an effect assumed to reflect that face recognition relies on special operations. Support for this notion comes from studies showing...... that face processing in developmental prosopagnosia (DP) is less affected by inversion than it is in normal subjects, and that DPs may even display face inversion superiority effects, i.e. better processing of inverted compared to upright faces. To date, however, there are no reports of direct comparisons...... between inversion effects for faces and objects, investigating whether the altered inversion effect in DP is specific to faces. We examined this question by comparing inversion effects for faces and cars in two otherwise identical recognition tasks in a group of DPs (N = 16) and a matched control group...

  14. Da família patriarcal à contemporânea. Entre o vellho e o novo: o surgimento dos novos arranjos familiares

    OpenAIRE

    Móas, Luciane da Costa

    2012-01-01

    O presente artigo propõe uma dupla abordagem da família levando em consideração o caráter socioantropológico e também histórico-evolutivo da legislação brasileira. Tem como objetivo interrogar a ideia de crise na ou da família em razão das mudanças verificadas em sua constituição: abandonou-se o modelo patriarcal, único existente no passado, que cedeu o passo aos modelos diversos, dos quais se originaram os novos arranjos familiares. O texto cuida da família como o fenômeno social que nos é m...

  15. On quasiclassical approximation in the inverse scattering method

    International Nuclear Information System (INIS)

    Geogdzhaev, V.V.

    1985-01-01

    Using as an example quasiclassical limits of the Korteweg-de Vries equation and nonlinear Schroedinger equation, the quasiclassical limiting variant of the inverse scattering problem method is presented. In quasiclassical approximation the inverse scattering problem for the Schroedinger equation is reduced to the classical inverse scattering problem

  16. Contrôle genético dos "frutos chochos" no Café "Mundo Novo" Manofactorial inheritance of "empty-locule" in the Mundo Novo coffee

    Directory of Open Access Journals (Sweden)

    A. J. T. Mendes

    1955-01-01

    Full Text Available 1. Decorre do presente trabalho que no Café Mundo Novo há dois grupos distintos de plantas : a de baixa ocorrência de frutos chochos; b de alta ocorrência de frutos chochos. 2. Há evidências de que a existência de 2 grupos distintos de plantas é devida a um par de fatores genéticos Dd. As plantas onde é baixa a ocorrência de frutos chochos são de constituição genética DD. As demais são Dd. Não há o grupo dd, pois que a combinação endosperma ddd e embrião dd é letal. 3. Segundo a hipótese, a letalidade dos fatores dd se manifesta quando o endosperma tem 2 a 3 mm de diâmetro; nesse ponto estaciona o crescimento e êle se transforma num disco (donde o símbolo d para o gen em questão. Raras vêzes a ação letal se manifesta antes dêsse estado e então nada ou quase nada resta do endosperma. Outras vezes a ação letal é tardia: o endosperma se desenvolve em semente mas esta não germina. 4. As populações de café Mundo Novo que estão se formando no Estado de São Paulo terão diferentes proporções de plantas com e sem o defeito das lojas vazias, dependendo isso da fonte onde se procurarem as sementes. 5. Limitando-se a selecionar as plantas Mundo Novo dentro do grupo de baixa ocorrência de chochos o melhorista encontra base científica para ehminar um notório defeito da variedade.It was shown in a recent paper that the occurrence of empty locules in coffee fruits of the variety Mundo Novo (Coffea arabica L. is due to an arrest in the endosperm development that takes place at a definite stage, leading to the formation of a small disc ; this rudimentary type of endosperm has been called "discoid endosperm". A suggestion was then made that this process might be controlled by genetic factors. Under this assumption, normal plants were DD; plants in which the defect occurred, Dd, and the homozygous, recessive form was lethal. The high correlation between discoid endosperm and empty locules permitted a clear

  17. Inverse scattering with supersymmetric quantum mechanics

    International Nuclear Information System (INIS)

    Baye, Daniel; Sparenberg, Jean-Marc

    2004-01-01

    The application of supersymmetric quantum mechanics to the inverse scattering problem is reviewed. The main difference with standard treatments of the inverse problem lies in the simple and natural extension to potentials with singularities at the origin and with a Coulomb behaviour at infinity. The most general form of potentials which are phase-equivalent to a given potential is discussed. The use of singular potentials allows adding or removing states from the bound spectrum without contradicting the Levinson theorem. Physical applications of phase-equivalent potentials in nuclear reactions and in three-body systems are described. Derivation of a potential from the phase shift at fixed orbital momentum can also be performed with the supersymmetric inversion by using a Bargmann-type approximation of the scattering matrix or phase shift. A unique singular potential without bound states can be obtained from any phase shift. A limited number of bound states depending on the singularity can then be added. This inversion procedure is illustrated with nucleon-nucleon scattering

  18. Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

    Science.gov (United States)

    O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

    2018-02-01

    Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

  19. Robust de novo pathway enrichment with KeyPathwayMiner 5

    DEFF Research Database (Denmark)

    Alcaraz, Nicolas; List, Markus; Dissing-Hansen, Martin

    2016-01-01

    Identifying functional modules or novel active pathways, recently termed de novo pathway enrichment, is a computational systems biology challenge that has gained much attention during the last decade. Given a large biological interaction network, KeyPathwayMiner extracts connected subnetworks tha...

  20. De novo transcriptome assembly of the mycoheterotrophic plant Monotropa hypopitys

    Directory of Open Access Journals (Sweden)

    Alexey V. Beletsky

    2017-03-01

    Full Text Available Monotropa hypopitys (pinesap is a non-photosynthetic obligately mycoheterotrophic plant of the family Ericaceae. It obtains the carbon and other nutrients from the roots of surrounding autotrophic trees through the associated mycorrhizal fungi. In order to understand the evolutionary changes in the plant genome associated with transition to a heterotrophic lifestyle, we performed de novo transcriptomic analysis of M. hypopitys using next-generation sequencing. We obtained the RNA-Seq data from flowers, flower bracts and roots with haustoria using Illumina HiSeq2500 platform. The raw data obtained in this study can be available in NCBI SRA database with accession number of SRP069226. A total of 10.3 GB raw sequence data were obtained, corresponding to 103,357,809 raw reads. A total of 103,025,683 reads were filtered after removing low-quality reads and trimming the adapter sequences. The Trinity program was used to de novo assemble 98,349 unigens with an N50 of 1342 bp. Using the TransDecoder program, we predicted 43,505 putative proteins. 38,416 unigenes were annotated in the Swiss-Prot protein sequence database using BLASTX. The obtained transcriptomic data will be useful for further studies of the evolution of plant genomes upon transition to a non-photosynthetic lifestyle and the loss of photosynthesis-related functions.

  1. A de novo Mutation in KMT2A (MLL) in monozygotic twins with Wiedemann-Steiner syndrome.

    Science.gov (United States)

    Dunkerton, Sophie; Field, Matthew; Cho, Vicki; Bertram, Edward; Whittle, Belinda; Groves, Alexandra; Goel, Himanshu

    2015-09-01

    Growth deficiency, psychomotor delay, and facial dysmorphism was originally described in a male patient in 1989 by Wiedemann et al. and later in 2000 by Steiner et al. Wiedemann-Steiner syndrome (WSS) has since been described only a few times in the literature, with the phenotypic spectrum both expanding and becoming more delineated with each patient reported. We report on the clinical and molecular features of monozygotic twins with a de novo mutation in KMT2A. Single nucleotide polymorphism (SNP) microarray was done on both twins and whole-exome sequencing was done using both parents and one of the affected twins. SNP microarray confirmed that they were monozygotic twins. A de novo heterozygous variant (p. Arg1083*) in the KMT2A gene was identified through whole-exome sequencing, confirming the diagnosis of WSS. In this study, we have identified a de novo mutation in KMT2A associated with psychomotor developmental delay, facial dysmorphism, short stature, hypertrichosis cubiti, and small kidneys. This finding in monozygotic twins gives specificity to the WSS. The description of more cases of WSS is needed for further delineation of this condition. Small kidneys with normal function have not been described in this condition in the medical literature before. © 2015 Wiley Periodicals, Inc.

  2. Superconductivity in Pb inverse opal

    International Nuclear Information System (INIS)

    Aliev, Ali E.; Lee, Sergey B.; Zakhidov, Anvar A.; Baughman, Ray H.

    2007-01-01

    Type-II superconducting behavior was observed in highly periodic three-dimensional lead inverse opal prepared by infiltration of melted Pb in blue (D = 160 nm), green (D = 220 nm) and red (D = 300 nm) opals and followed by the extraction of the SiO 2 spheres by chemical etching. The onset of a broad phase transition (ΔT = 0.3 K) was shifted from T c = 7.196 K for bulk Pb to T c = 7.325 K. The upper critical field H c2 (3150 Oe) measured from high-field hysteresis loops exceeds the critical field for bulk lead (803 Oe) fourfold. Two well resolved peaks observed in the hysteresis loops were ascribed to flux penetration into the cylindrical void space that can be found in inverse opal structure and into the periodic structure of Pb nanoparticles. The red inverse opal shows pronounced oscillations of magnetic moment in the mixed state at low temperatures, T 0.9T c has been observed for all of the samples studied. The magnetic field periodicity of resistivity modulation is in good agreement with the lattice parameter of the inverse opal structure. We attribute the failure to observe pronounced modulation in magneto-resistive measurement to difficulties in the precision orientation of the sample along the magnetic field

  3. Ensemble Kalman methods for inverse problems

    International Nuclear Information System (INIS)

    Iglesias, Marco A; Law, Kody J H; Stuart, Andrew M

    2013-01-01

    The ensemble Kalman filter (EnKF) was introduced by Evensen in 1994 (Evensen 1994 J. Geophys. Res. 99 10143–62) as a novel method for data assimilation: state estimation for noisily observed time-dependent problems. Since that time it has had enormous impact in many application domains because of its robustness and ease of implementation, and numerical evidence of its accuracy. In this paper we propose the application of an iterative ensemble Kalman method for the solution of a wide class of inverse problems. In this context we show that the estimate of the unknown function that we obtain with the ensemble Kalman method lies in a subspace A spanned by the initial ensemble. Hence the resulting error may be bounded above by the error found from the best approximation in this subspace. We provide numerical experiments which compare the error incurred by the ensemble Kalman method for inverse problems with the error of the best approximation in A, and with variants on traditional least-squares approaches, restricted to the subspace A. In so doing we demonstrate that the ensemble Kalman method for inverse problems provides a derivative-free optimization method with comparable accuracy to that achieved by traditional least-squares approaches. Furthermore, we also demonstrate that the accuracy is of the same order of magnitude as that achieved by the best approximation. Three examples are used to demonstrate these assertions: inversion of a compact linear operator; inversion of piezometric head to determine hydraulic conductivity in a Darcy model of groundwater flow; and inversion of Eulerian velocity measurements at positive times to determine the initial condition in an incompressible fluid. (paper)

  4. Trimming and procrastination as inversion techniques

    Science.gov (United States)

    Backus, George E.

    1996-12-01

    By examining the processes of truncating and approximating the model space (trimming it), and by committing to neither the objectivist nor the subjectivist interpretation of probability (procrastinating), we construct a formal scheme for solving linear and non-linear geophysical inverse problems. The necessary prior information about the correct model xE can be either a collection of inequalities or a probability measure describing where xE was likely to be in the model space X before the data vector y0 was measured. The results of the inversion are (1) a vector z0 that estimates some numerical properties zE of xE; (2) an estimate of the error δz = z0 - zE. As y0 is finite dimensional, so is z0, and hence in principle inversion cannot describe all of xE. The error δz is studied under successively more specialized assumptions about the inverse problem, culminating in a complete analysis of the linear inverse problem with a prior quadratic bound on xE. Our formalism appears to encompass and provide error estimates for many of the inversion schemes current in geomagnetism, and would be equally applicable in geodesy and seismology if adequate prior information were available there. As an idealized example we study the magnetic field at the core-mantle boundary, using satellite measurements of field elements at sites assumed to be almost uniformly distributed on a single spherical surface. Magnetospheric currents are neglected and the crustal field is idealized as a random process with rotationally invariant statistics. We find that an appropriate data compression diagonalizes the variance matrix of the crustal signal and permits an analytic trimming of the idealized problem.

  5. Inverse source problems in elastodynamics

    Science.gov (United States)

    Bao, Gang; Hu, Guanghui; Kian, Yavar; Yin, Tao

    2018-04-01

    We are concerned with time-dependent inverse source problems in elastodynamics. The source term is supposed to be the product of a spatial function and a temporal function with compact support. We present frequency-domain and time-domain approaches to show uniqueness in determining the spatial function from wave fields on a large sphere over a finite time interval. The stability estimate of the temporal function from the data of one receiver and the uniqueness result using partial boundary data are proved. Our arguments rely heavily on the use of the Fourier transform, which motivates inversion schemes that can be easily implemented. A Landweber iterative algorithm for recovering the spatial function and a non-iterative inversion scheme based on the uniqueness proof for recovering the temporal function are proposed. Numerical examples are demonstrated in both two and three dimensions.

  6. Full Waveform Inversion Using Oriented Time Migration Method

    KAUST Repository

    Zhang, Zhendong

    2016-04-12

    Full waveform inversion (FWI) for reflection events is limited by its linearized update requirements given by a process equivalent to migration. Unless the background velocity model is reasonably accurate the resulting gradient can have an inaccurate update direction leading the inversion to converge into what we refer to as local minima of the objective function. In this thesis, I first look into the subject of full model wavenumber to analysis the root of local minima and suggest the possible ways to avoid this problem. And then I analysis the possibility of recovering the corresponding wavenumber components through the existing inversion and migration algorithms. Migration can be taken as a generalized inversion method which mainly retrieves the high wavenumber part of the model. Conventional impedance inversion method gives a mapping relationship between the migration image (high wavenumber) and model parameters (full wavenumber) and thus provides a possible cascade inversion strategy to retrieve the full wavenumber components from seismic data. In the proposed approach, consider a mild lateral variation in the model, I find an analytical Frechet derivation corresponding to the new objective function. In the proposed approach, the gradient is given by the oriented time-domain imaging method. This is independent of the background velocity. Specifically, I apply the oriented time-domain imaging (which depends on the reflection slope instead of a background velocity) on the data residual to obtain the geometrical features of the velocity perturbation. Assuming that density is constant, the conventional 1D impedance inversion method is also applicable for 2D or 3D velocity inversion within the process of FWI. This method is not only capable of inverting for velocity, but it is also capable of retrieving anisotropic parameters relying on linearized representations of the reflection response. To eliminate the cross-talk artifacts between different parameters, I

  7. Jogos musicais, novos diálogos mediados pela tecnologia entre fãs e artista

    Directory of Open Access Journals (Sweden)

    Pase, André Fagundes

    2009-01-01

    Full Text Available Os recursos audiovisuais sempre estiveram próximos da produção e distribuição em massa de música. Filmes musicais e programas de televisão aproximaram o som e a imagem como uma marca, abrindo espaço para outras formas de interação entre fã e artista. Os jogos eletrônicos permitem que a história do artista seja apresentada de uma forma imersiva, com a audiência focada e ativa em um novo contexto de retenção de informação. Nestes novos espaços para a produção, trajetórias são reescritas e imaginários são reforçados

  8. Computation of inverse magnetic cascades

    International Nuclear Information System (INIS)

    Montgomery, D.

    1981-10-01

    Inverse cascades of magnetic quantities for turbulent incompressible magnetohydrodynamics are reviewed, for two and three dimensions. The theory is extended to the Strauss equations, a description intermediate between two and three dimensions appropriate to tokamak magnetofluids. Consideration of the absolute equilibrium Gibbs ensemble for the system leads to a prediction of an inverse cascade of magnetic helicity, which may manifest itself as a major disruption. An agenda for computational investigation of this conjecture is proposed

  9. X-ray induced pericentric inversions in Anopheles albimanus

    International Nuclear Information System (INIS)

    Rabbani, M.G.; Seawright, J.A.; Kitzmiller, J.B.

    1977-01-01

    Sixteen different pericentric inversions, ten on chromosome 2 and six on chromosome 3, have been isolated and characterized. The partial sterility in the inversion heterozygotes ranged from about 28 to 50%. Contrary to theoretical considerations, a curvilinear relationship exists between inversion length and partial sterility, whereby a reduction in sterility was noted for progressively longer inversions. The break-points are distributed randomly over the autosomes, but are observed more frequently in the areas of the salivary gland chromosomes where diffuse and broken bands of variable stainability are located. (author)

  10. Group inverses of M-matrices and their applications

    CERN Document Server

    Kirkland, Stephen J

    2013-01-01

    Group inverses for singular M-matrices are useful tools not only in matrix analysis, but also in the analysis of stochastic processes, graph theory, electrical networks, and demographic models. Group Inverses of M-Matrices and Their Applications highlights the importance and utility of the group inverses of M-matrices in several application areas. After introducing sample problems associated with Leslie matrices and stochastic matrices, the authors develop the basic algebraic and spectral properties of the group inverse of a general matrix. They then derive formulas for derivatives of matrix f

  11. Inflammatory bowel disease after liver transplantation : Risk factors for recurrence and De novo disease

    NARCIS (Netherlands)

    Verdonka, RC; Dijkstra, G; Haagsma, EB; Shostrom, VK; Van den Berg, AP; Kleibeuker, JH

    Inflammatory bowel disease (IBD) is associated with primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) and can recur or develop de novo after orthotopic liver transplantation (OLT). The aim of this study was to investigate the incidence and severity of IBD after liver

  12. Magnetotelluric inversion via reverse time migration algorithm of seismic data

    International Nuclear Information System (INIS)

    Ha, Taeyoung; Shin, Changsoo

    2007-01-01

    We propose a new algorithm for two-dimensional magnetotelluric (MT) inversion. Our algorithm is an MT inversion based on the steepest descent method, borrowed from the backpropagation technique of seismic inversion or reverse time migration, introduced in the middle 1980s by Lailly and Tarantola. The steepest descent direction can be calculated efficiently by using the symmetry of numerical Green's function derived from a mixed finite element method proposed by Nedelec for Maxwell's equation, without calculating the Jacobian matrix explicitly. We construct three different objective functions by taking the logarithm of the complex apparent resistivity as introduced in the recent waveform inversion algorithm by Shin and Min. These objective functions can be naturally separated into amplitude inversion, phase inversion and simultaneous inversion. We demonstrate our algorithm by showing three inversion results for synthetic data

  13. Seismic stochastic inversion identify river channel sand body

    Science.gov (United States)

    He, Z.

    2015-12-01

    The technology of seismic inversion is regarded as one of the most important part of geophysics. By using the technology of seismic inversion and the theory of stochastic simulation, the concept of seismic stochastic inversion is proposed.Seismic stochastic inversion can play an significant role in the identifying river channel sand body. Accurate sand body description is a crucial parameter to measure oilfield development and oilfield stimulation during the middle and later periods. Besides, rational well spacing density is an essential condition for efficient production. Based on the geological knowledge of a certain oilfield, in line with the use of seismic stochastic inversion, the river channel sand body in the work area is identified. In this paper, firstly, the single river channel body from the composite river channel body is subdivided. Secondly, the distribution of river channel body is ascertained in order to ascertain the direction of rivers. Morever, the superimposed relationship among the sand body is analyzed, especially among the inter-well sand body. The last but not at the least, via the analysis of inversion results of first vacuating the wells and continuous infilling later, it is meeted the most needs well spacing density that can obtain the optimal inversion result. It would serve effective guidance for oilfield stimulation.

  14. Multiscattering inversion for low-model wavenumbers

    KAUST Repository

    Alkhalifah, Tariq Ali

    2016-09-21

    A successful full-waveform inversion implementation updates the low-wavenumber model components first for a proper description of the wavefield propagation and slowly adds the high wavenumber potentially scattering parts of the model. The low-wavenumber components can be extracted from the transmission parts of the recorded wavefield emanating directly from the source or the transmission parts from the single- or double-scattered wavefield computed from a predicted scatter field acting as secondary sources.We use a combined inversion of data modeled from the source and those corresponding to single and double scattering to update the velocity model and the component of the velocity (perturbation) responsible for the single and double scattering. The combined inversion helps us access most of the potential model wavenumber information that may be embedded in the data. A scattering-angle filter is used to divide the gradient of the combined inversion, so initially the high-wavenumber (low-scattering-angle) components of the gradient are directed to the perturbation model and the low-wavenumber (highscattering- angle) components are directed to the velocity model. As our background velocity matures, the scatteringangle divide is slowly lowered to allow for more of the higher wavenumbers to contribute the velocity model. Synthetic examples including the Marmousi model are used to demonstrate the additional illumination and improved velocity inversion obtained when including multiscattered energy. © 2016 Society of Exploration Geophysicists.

  15. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin

    2016-04-27

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  16. The Earthquake‐Source Inversion Validation (SIV) Project

    KAUST Repository

    Mai, Paul Martin; Schorlemmer, Danijel; Page, Morgan; Ampuero, Jean‐Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Kä ser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran Kumar; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish Chandra; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    Finite-fault earthquake source inversions infer the (time-dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake-source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward-modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source-model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake-source imaging problem.

  17. The Earthquake‐Source Inversion Validation (SIV) Project

    Science.gov (United States)

    Mai, P. Martin; Schorlemmer, Danijel; Page, Morgan T.; Ampuero, Jean-Paul; Asano, Kimiyuki; Causse, Mathieu; Custodio, Susana; Fan, Wenyuan; Festa, Gaetano; Galis, Martin; Gallovic, Frantisek; Imperatori, Walter; Käser, Martin; Malytskyy, Dmytro; Okuwaki, Ryo; Pollitz, Fred; Passone, Luca; Razafindrakoto, Hoby N. T.; Sekiguchi, Haruko; Song, Seok Goo; Somala, Surendra N.; Thingbaijam, Kiran K. S.; Twardzik, Cedric; van Driel, Martin; Vyas, Jagdish C.; Wang, Rongjiang; Yagi, Yuji; Zielke, Olaf

    2016-01-01

    Finite‐fault earthquake source inversions infer the (time‐dependent) displacement on the rupture surface from geophysical data. The resulting earthquake source models document the complexity of the rupture process. However, multiple source models for the same earthquake, obtained by different research teams, often exhibit remarkable dissimilarities. To address the uncertainties in earthquake‐source inversion methods and to understand strengths and weaknesses of the various approaches used, the Source Inversion Validation (SIV) project conducts a set of forward‐modeling exercises and inversion benchmarks. In this article, we describe the SIV strategy, the initial benchmarks, and current SIV results. Furthermore, we apply statistical tools for quantitative waveform comparison and for investigating source‐model (dis)similarities that enable us to rank the solutions, and to identify particularly promising source inversion approaches. All SIV exercises (with related data and descriptions) and statistical comparison tools are available via an online collaboration platform, and we encourage source modelers to use the SIV benchmarks for developing and testing new methods. We envision that the SIV efforts will lead to new developments for tackling the earthquake‐source imaging problem.

  18. The limits of de novo DNA motif discovery.

    Directory of Open Access Journals (Sweden)

    David Simcha

    Full Text Available A major challenge in molecular biology is reverse-engineering the cis-regulatory logic that plays a major role in the control of gene expression. This program includes searching through DNA sequences to identify "motifs" that serve as the binding sites for transcription factors or, more generally, are predictive of gene expression across cellular conditions. Several approaches have been proposed for de novo motif discovery-searching sequences without prior knowledge of binding sites or nucleotide patterns. However, unbiased validation is not straightforward. We consider two approaches to unbiased validation of discovered motifs: testing the statistical significance of a motif using a DNA "background" sequence model to represent the null hypothesis and measuring performance in predicting membership in gene clusters. We demonstrate that the background models typically used are "too null," resulting in overly optimistic assessments of significance, and argue that performance in predicting TF binding or expression patterns from DNA motifs should be assessed by held-out data, as in predictive learning. Applying this criterion to common motif discovery methods resulted in universally poor performance, although there is a marked improvement when motifs are statistically significant against real background sequences. Moreover, on synthetic data where "ground truth" is known, discriminative performance of all algorithms is far below the theoretical upper bound, with pronounced "over-fitting" in training. A key conclusion from this work is that the failure of de novo discovery approaches to accurately identify motifs is basically due to statistical intractability resulting from the fixed size of co-regulated gene clusters, and thus such failures do not necessarily provide evidence that unfound motifs are not active biologically. Consequently, the use of prior knowledge to enhance motif discovery is not just advantageous but necessary. An implementation of

  19. Une introduction aux problèmes inverses elliptiques et paraboliques

    CERN Document Server

    Choulli, Mourad

    2009-01-01

    This book is devoted to an introduction of elliptic and parabolic inverse problems. Our goal is to present some recent methods for establishing uniqueness and stability results. We study some classical elliptic inverse problems: inverse conductivity problem, detection of corrosion or cracks and inverse spectral problems. Among the parabolic inverse problems we consider the classic problem of finding an initial distribution of heat and the location of sources. We hope that this book will interest all those who want to learn the mathematical analysis of inverse problems.

  20. Microlocal analysis of a seismic linearized inverse problem

    NARCIS (Netherlands)

    Stolk, C.C.

    1999-01-01

    The seismic inverse problem is to determine the wavespeed c x in the interior of a medium from measurements at the boundary In this paper we analyze the linearized inverse problem in general acoustic media The problem is to nd a left inverse of the linearized forward map F or equivalently to nd the

  1. Source-independent elastic waveform inversion using a logarithmic wavefield

    KAUST Repository

    Choi, Yun Seok

    2012-01-01

    The logarithmic waveform inversion has been widely developed and applied to some synthetic and real data. In most logarithmic waveform inversion algorithms, the subsurface velocities are updated along with the source estimation. To avoid estimating the source wavelet in the logarithmic waveform inversion, we developed a source-independent logarithmic waveform inversion algorithm. In this inversion algorithm, we first normalize the wavefields with the reference wavefield to remove the source wavelet, and then take the logarithm of the normalized wavefields. Based on the properties of the logarithm, we define three types of misfit functions using the following methods: combination of amplitude and phase, amplitude-only, and phase-only. In the inversion, the gradient is computed using the back-propagation formula without directly calculating the Jacobian matrix. We apply our algorithm to noise-free and noise-added synthetic data generated for the modified version of elastic Marmousi2 model, and compare the results with those of the source-estimation logarithmic waveform inversion. For the noise-free data, the source-independent algorithms yield velocity models close to true velocity models. For random-noise data, the source-estimation logarithmic waveform inversion yields better results than the source-independent method, whereas for coherent-noise data, the results are reversed. Numerical results show that the source-independent and source-estimation logarithmic waveform inversion methods have their own merits for random- and coherent-noise data. © 2011.

  2. Frequency-domain waveform inversion using the phase derivative

    KAUST Repository

    Choi, Yun Seok

    2013-09-26

    Phase wrapping in the frequency domain or cycle skipping in the time domain is the major cause of the local minima problem in the waveform inversion when the starting model is far from the true model. Since the phase derivative does not suffer from the wrapping effect, its inversion has the potential of providing a robust and reliable inversion result. We propose a new waveform inversion algorithm using the phase derivative in the frequency domain along with the exponential damping term to attenuate reflections. We estimate the phase derivative, or what we refer to as the instantaneous traveltime, by taking the derivative of the Fourier-transformed wavefield with respect to the angular frequency, dividing it by the wavefield itself and taking the imaginary part. The objective function is constructed using the phase derivative and the gradient of the objective function is computed using the back-propagation algorithm. Numerical examples show that our inversion algorithm with a strong damping generates a tomographic result even for a high ‘single’ frequency, which can be a good initial model for full waveform inversion and migration.

  3. Sequential search leads to faster, more efficient fragment-based de novo protein structure prediction.

    Science.gov (United States)

    de Oliveira, Saulo H P; Law, Eleanor C; Shi, Jiye; Deane, Charlotte M

    2018-04-01

    Most current de novo structure prediction methods randomly sample protein conformations and thus require large amounts of computational resource. Here, we consider a sequential sampling strategy, building on ideas from recent experimental work which shows that many proteins fold cotranslationally. We have investigated whether a pseudo-greedy search approach, which begins sequentially from one of the termini, can improve the performance and accuracy of de novo protein structure prediction. We observed that our sequential approach converges when fewer than 20 000 decoys have been produced, fewer than commonly expected. Using our software, SAINT2, we also compared the run time and quality of models produced in a sequential fashion against a standard, non-sequential approach. Sequential prediction produces an individual decoy 1.5-2.5 times faster than non-sequential prediction. When considering the quality of the best model, sequential prediction led to a better model being produced for 31 out of 41 soluble protein validation cases and for 18 out of 24 transmembrane protein cases. Correct models (TM-Score > 0.5) were produced for 29 of these cases by the sequential mode and for only 22 by the non-sequential mode. Our comparison reveals that a sequential search strategy can be used to drastically reduce computational time of de novo protein structure prediction and improve accuracy. Data are available for download from: http://opig.stats.ox.ac.uk/resources. SAINT2 is available for download from: https://github.com/sauloho/SAINT2. saulo.deoliveira@dtc.ox.ac.uk. Supplementary data are available at Bioinformatics online.

  4. The historical town core and traffic in Novo mesto

    Directory of Open Access Journals (Sweden)

    Lilijana Jankovič

    2001-01-01

    Full Text Available The historical town core of Novo mesto is subject to intolerable traffic conditions. Individual car use is suffocating the town core, but simultaneously good access is essential for shopkeepers and other inhabitants since buses don’t go there. The project proposes changes to the traffic regime, its basic goals are to redesign the town square into a pedestrian place and to eliminate transitory traffic by rerouting vehicles to less burdened side roads. It introduces short-term parking, smaller parking garages in the core and larger parking spaces on the edge and routes the buses through the town core.

  5. Uncovering Clinical Features of De Novo Philadelphia Positive Myelodysplasia.

    Science.gov (United States)

    Armas, Aristides; Chen, Chen; Mims, Martha; Rivero, Gustavo

    2017-01-01

    Myelodysplastic syndrome (MDS) is cytogenetically heterogeneous and retains variable risk for acute myeloid leukemia transformation. Though not yet fully understood, there is an association between genetic abnormalities and defects in gene expression. The functional role for infrequent cytogenetic alteration remains unclear. An uncommon chromosomic abnormality is the presence of the Philadelphia (Ph) chromosome. Here, we report a patient with Ph+ MDS treated with low dose Dasatinib who achieved hematologic response for 7 months. In addition, we also examined the English literature on all de novo Ph + MDS cases between 1996 and 2015 to gain insight into clinical features and outcome.

  6. Model-Based GUI Testing Using Uppaal at Novo Nordisk

    Science.gov (United States)

    Hjort, Ulrik H.; Illum, Jacob; Larsen, Kim G.; Petersen, Michael A.; Skou, Arne

    This paper details a collaboration between Aalborg University and Novo Nordiskin developing an automatic model-based test generation tool for system testing of the graphical user interface of a medical device on an embedded platform. The tool takes as input an UML Statemachine model and generates a test suite satisfying some testing criterion, such as edge or state coverage, and converts the individual test case into a scripting language that can be automatically executed against the target. The tool has significantly reduced the time required for test construction and generation, and reduced the number of test scripts while increasing the coverage.

  7. Synthesis of Polypyrrole Inverse Opal in [bmim]PF6- Containing Acetonitrile and the Application of the Inverse Opal in Cell Prototype

    Directory of Open Access Journals (Sweden)

    Wei Yan

    2013-01-01

    Full Text Available Most primary cells use Zn or Li as the anode, a metallic oxide as the cathode, and an acidic or alkaline solution or moist past as the electrolytic solution. In this paper, highly ordered polypyrrole (PPy inverse opals have been successfully synthesized in the acetonitrile solution containing [bmim]PF6. PPy films were prepared under the same experimental conditions. Cyclic voltammograms of the PPy film and the PPy inverse opal in neutral phosphate buffer solution (PBS were recorded. X-ray photoelectron spectroscopy technique was used to investigate the structural surface of the PPy films and the PPy inverse opals. It is found that the PF6- anions kept dedoping from the PPy films during the potential scanning process, resulting in the electrochemical inactivity. Although PF6- anions also kept dedoping from the PPy inverse opals, the PO43- anions from PBS could dope into the inverse opal, explaining why the PPy inverse opals kept their electrochemical activity. An environmental friendly cell prototype was constructed, using the PPy inverse opal as the anode. The electrolytes in both the cathodic and anodic half-cells were neutral PBSs. The open-circuit potential of the cell prototype reached 0.487 V and showed a stable output over several hundred hours.

  8. Off-shell T-matrices from inverse scattering

    International Nuclear Information System (INIS)

    Von Geramb, H.V.; Amos, K.A.

    1989-01-01

    Inverse scattering theory is used to determine local, energy independent, coordinate space nucleon-nucleon potentials. Inversions are made of phase shifts obtained by analyzes of data and from meson exchange theory, in particular the Paris and the Bonn parametrizations. Half off-shell T-matrices are generated to compare the exact meson theoretical results with those of inversion and it is found that phase equivalent interactions have essentially the same off-shell behaviour for any physically significant range of momenta. 8 refs., 8 figs

  9. Inverse kinematics of OWI-535 robotic arm

    OpenAIRE

    DEBENEC, PRIMOŽ

    2015-01-01

    The thesis aims to calculate the inverse kinematics for the OWI-535 robotic arm. The calculation of the inverse kinematics determines the joint parameters that provide the right pose of the end effector. The pose consists of the position and orientation, however, we will focus only on the second one. Due to arm limitations, we have created our own type of the calculation of the inverse kinematics. At first we have derived it only theoretically, and then we have transferred the derivation into...

  10. Inversion of electron-water elastic scattering data

    International Nuclear Information System (INIS)

    Lun, A.; Chen, X.J.; Allen, L.J.; Amos, K.

    1994-01-01

    Fixed energy inverse scattering theory has been used to analyse the differential cross-sections for the elastic scattering of electrons from water molecules. Both semiclassical (WKB) and fully quantal inversion methods have been used with data taken in the energy range 100 to 1000 eV. Constrained to be real, the local inversion potentials are found to be energy dependent; a dependence that can be interpreted as the local equivalence of true nonlocality in the actual interaction. 14 refs., 4 tabs., 8 figs

  11. Bayesian inversion of refraction seismic traveltime data

    Science.gov (United States)

    Ryberg, T.; Haberland, Ch

    2018-03-01

    We apply a Bayesian Markov chain Monte Carlo (McMC) formalism to the inversion of refraction seismic, traveltime data sets to derive 2-D velocity models below linear arrays (i.e. profiles) of sources and seismic receivers. Typical refraction data sets, especially when using the far-offset observations, are known as having experimental geometries which are very poor, highly ill-posed and far from being ideal. As a consequence, the structural resolution quickly degrades with depth. Conventional inversion techniques, based on regularization, potentially suffer from the choice of appropriate inversion parameters (i.e. number and distribution of cells, starting velocity models, damping and smoothing constraints, data noise level, etc.) and only local model space exploration. McMC techniques are used for exhaustive sampling of the model space without the need of prior knowledge (or assumptions) of inversion parameters, resulting in a large number of models fitting the observations. Statistical analysis of these models allows to derive an average (reference) solution and its standard deviation, thus providing uncertainty estimates of the inversion result. The highly non-linear character of the inversion problem, mainly caused by the experiment geometry, does not allow to derive a reference solution and error map by a simply averaging procedure. We present a modified averaging technique, which excludes parts of the prior distribution in the posterior values due to poor ray coverage, thus providing reliable estimates of inversion model properties even in those parts of the models. The model is discretized by a set of Voronoi polygons (with constant slowness cells) or a triangulated mesh (with interpolation within the triangles). Forward traveltime calculations are performed by a fast, finite-difference-based eikonal solver. The method is applied to a data set from a refraction seismic survey from Northern Namibia and compared to conventional tomography. An inversion test

  12. Thermal measurements and inverse techniques

    CERN Document Server

    Orlande, Helcio RB; Maillet, Denis; Cotta, Renato M

    2011-01-01

    With its uncommon presentation of instructional material regarding mathematical modeling, measurements, and solution of inverse problems, Thermal Measurements and Inverse Techniques is a one-stop reference for those dealing with various aspects of heat transfer. Progress in mathematical modeling of complex industrial and environmental systems has enabled numerical simulations of most physical phenomena. In addition, recent advances in thermal instrumentation and heat transfer modeling have improved experimental procedures and indirect measurements for heat transfer research of both natural phe

  13. Optimization for nonlinear inverse problem

    International Nuclear Information System (INIS)

    Boyadzhiev, G.; Brandmayr, E.; Pinat, T.; Panza, G.F.

    2007-06-01

    The nonlinear inversion of geophysical data in general does not yield a unique solution, but a single model, representing the investigated field, is preferred for an easy geological interpretation of the observations. The analyzed region is constituted by a number of sub-regions where the multi-valued nonlinear inversion is applied, which leads to a multi-valued solution. Therefore, combining the values of the solution in each sub-region, many acceptable models are obtained for the entire region and this complicates the geological interpretation of geophysical investigations. In this paper are presented new methodologies, capable to select one model, among all acceptable ones, that satisfies different criteria of smoothness in the explored space of solutions. In this work we focus on the non-linear inversion of surface waves dispersion curves, which gives structural models of shear-wave velocity versus depth, but the basic concepts have a general validity. (author)

  14. Support Minimized Inversion of Acoustic and Elastic Wave Scattering

    Science.gov (United States)

    Safaeinili, Ali

    Inversion of limited data is common in many areas of NDE such as X-ray Computed Tomography (CT), Ultrasonic and eddy current flaw characterization and imaging. In many applications, it is common to have a bias toward a solution with minimum (L^2)^2 norm without any physical justification. When it is a priori known that objects are compact as, say, with cracks and voids, by choosing "Minimum Support" functional instead of the minimum (L^2)^2 norm, an image can be obtained that is equally in agreement with the available data, while it is more consistent with what is most probably seen in the real world. We have utilized a minimum support functional to find a solution with the smallest volume. This inversion algorithm is most successful in reconstructing objects that are compact like voids and cracks. To verify this idea, we first performed a variational nonlinear inversion of acoustic backscatter data using minimum support objective function. A full nonlinear forward model was used to accurately study the effectiveness of the minimized support inversion without error due to the linear (Born) approximation. After successful inversions using a full nonlinear forward model, a linearized acoustic inversion was developed to increase speed and efficiency in imaging process. The results indicate that by using minimum support functional, we can accurately size and characterize voids and/or cracks which otherwise might be uncharacterizable. An extremely important feature of support minimized inversion is its ability to compensate for unknown absolute phase (zero-of-time). Zero-of-time ambiguity is a serious problem in the inversion of the pulse-echo data. The minimum support inversion was successfully used for the inversion of acoustic backscatter data due to compact scatterers without the knowledge of the zero-of-time. The main drawback to this type of inversion is its computer intensiveness. In order to make this type of constrained inversion available for common use, work

  15. QCD-instantons and conformal space-time inversion symmetry

    International Nuclear Information System (INIS)

    Klammer, D.

    2008-04-01

    In this paper, we explore the appealing possibility that the strong suppression of large-size QCD instantons - as evident from lattice data - is due to a surviving conformal space-time inversion symmetry. This symmetry is both suggested from the striking invariance of highquality lattice data for the instanton size distribution under inversion of the instanton size ρ→(left angle ρ right angle 2 )/(ρ) and from the known validity of space-time inversion symmetry in the classical instanton sector. We project the instanton calculus onto the four-dimensional surface of a five-dimensional sphere via conformal stereographic mapping, before investigating conformal inversion. This projection to a compact, curved geometry is both to avoid the occurence of divergences and to introduce the average instanton size left angle ρ right angle from the lattice data as a new length scale. The average instanton size is identified with the radius b of this 5d-sphere and acts as the conformal inversion radius. For b= left angle ρ right angle, our corresponding results are almost perfectly symmetric under space-time inversion and in good qualitative agreement with the lattice data. For (ρ)/(b)→0 we recover the familiar results of instanton perturbation theory in flat 4d-space. Moreover, we illustrate that a (weakly broken) conformal inversion symmetry would have significant consequences for QCD beyond instantons. As a further successful test for inversion symmetry, we present striking implications for another instanton dominated lattice observable, the chirality-flip ratio in the QCD vacuum. (orig.)

  16. Magnetotelluric inversion for depth-to-basement estimation

    DEFF Research Database (Denmark)

    Cai, Hongzhu; Zhdanov, Michael

    2015-01-01

    The magnetotelluric (MT) method can be effectively applied for depth-to-basement estimation, because there exists a strong contrast in resistivity between a conductive sedimentary basin and a resistive crystalline basement. Conventional inversions of MT data are usually aimed at determining...... the volumetric distribution of the conductivity within the inversion domain. By the nature of the MT method, the recovered distribution of the subsurface conductivity is typically diffusive, which makes it difficult to select the sediment-basement interface. This paper develops a novel approach to 3D MT...... inversion for the depth-to-basement estimate. The key to this approach is selection of the model parameterization with the depth to basement being the major unknown parameter. In order to estimate the depth to the basement, the inversion algorithm recovers both the thickness and the conductivities...

  17. A De novo Mutation in Dystrophin Causing Muscular Dystrophy in a Female Patient

    Directory of Open Access Journals (Sweden)

    Hao Yu

    2017-01-01

    Conclusions: We identified two novel de novo mutations of DMD gene in two Chinese pedigrees, one of which caused a female patient with muscular dystrophy. The mutational analysis is important for DMD patients and carriers in the absence of a family history. The NGS can help detect the mutations in MLPA-negative patients.

  18. Wound complications and surgical events in de novo heart transplant patients treated with everolimus

    DEFF Research Database (Denmark)

    Rashidi, Mitra; Esmaily, Sorosh; Fiane, Arnt E

    2016-01-01

    OBJECTIVES: The use of mammalian target of rapamycin (mTOR) inhibitors have been limited by adverse events (AE), including delayed wound healing. We retrospectively reviewed all AE and serious AE (SAE) in The Scandinavian heart transplant (HTx) everolimus (EVE) de novo trial with early calcineurin...

  19. Classical limit of the quantum inverse scattering problem

    International Nuclear Information System (INIS)

    Bogdanov, I.V.

    1986-01-01

    This paper studies the passage to the limit of classical mechanics which is realized in the formalism of Marchenko's method for a spherically symmetric inverse problem of quantum scattering for fixed angular momentum. The limit is considered for the general case of partial waves with arbitrary values of the orbital number 1>0 in the lowest order of perturbation theory. It is shown how in the limit h→0 in the quantum inverse problem the integral Able transformation characteristic of classical inverse problems arises. The classical inversion formula with delay time is derived from the Marchenko equation

  20. Primary intraosseous squamous cell carcinoma of the mandible arising de novo.

    Science.gov (United States)

    Shamim, Thorakkal

    2009-07-01

    Primary intraosseous squamous cell carcinoma is an odontogenic tumour with aggressive behaviour usually noticed in 6th to 7th decades of life. The tumour is characterized by progressive swelling of the jaw, pain and loosening of teeth. Microscopically, the lesion is showing foci of keratinising cells separated by collagenous connective tissue stroma. A case of primary intraosseous squamous cell carcinoma of mandible arising de novo in a 40-year-old man is reported.

  1. Testing causes for the European mid-Paleocene inversions

    DEFF Research Database (Denmark)

    Nielsen, S.B.; Stephenson, Randell; Hansen, D.L.

    2006-01-01

    For a period of approx. 20 Myr during the Late Cretaceous, the Paleozoic and Mesozoic rifts and basins on the European continent experienced compressional shortening and inversion. On the order of ~103m of erosion occurred along the inversion axes; the convergence of Africa and Europe has...... conventionally been held responsible. A second stage of inversion of the same structures occurred in the mid-Paleocene; however, this differed in structural style by being domal and non-ruptural with amplitudes on the order of ~102m. Furthermore, within the chronostratigraphic resolution, the onset of the mid......-Paleocene phase occurred synchronously at ~60 Ma. The different styles of inversion call for different explanations and, recently, the second phase of inversion has been explained by a relaxation or rotation (rather than further compression) of the in-plane stress field of the first Late Cretaceous phase...

  2. Phase and amplitude inversion of crosswell radar data

    Science.gov (United States)

    Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

    2011-01-01

    Phase and amplitude inversion of crosswell radar data estimates the logarithm of complex slowness for a 2.5D heterogeneous model. The inversion is formulated in the frequency domain using the vector Helmholtz equation. The objective function is minimized using a back-propagation method that is suitable for a 2.5D model and that accounts for the near-, intermediate-, and far-field regions of the antennas. The inversion is tested with crosswell radar data collected in a laboratory tank. The model anomalies are consistent with the known heterogeneity in the tank; the model’s relative dielectric permittivity, which is calculated from the real part of the estimated complex slowness, is consistent with independent laboratory measurements. The methodologies developed for this inversion can be adapted readily to inversions of seismic data (e.g., crosswell seismic and vertical seismic profiling data).

  3. Anisotropic wave-equation traveltime and waveform inversion

    KAUST Repository

    Feng, Shihang; Schuster, Gerard T.

    2016-01-01

    The wave-equation traveltime and waveform inversion (WTW) methodology is developed to invert for anisotropic parameters in a vertical transverse isotropic (VTI) meidum. The simultaneous inversion of anisotropic parameters v0, ε and δ is initially

  4. Elastic reflection waveform inversion with variable density

    KAUST Repository

    Li, Yuanyuan; Li, Zhenchun; Alkhalifah, Tariq Ali; Guo, Qiang

    2017-01-01

    Elastic full waveform inversion (FWI) provides a better description of the subsurface than those given by the acoustic assumption. However it suffers from a more serious cycle skipping problem compared with the latter. Reflection waveform inversion

  5. Inverse Raman effect: applications and detection techniques

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, L.J. Jr.

    1980-08-01

    The processes underlying the inverse Raman effect are qualitatively described by comparing it to the more familiar phenomena of conventional and stimulated Raman scattering. An experession is derived for the inverse Raman absorption coefficient, and its relationship to the stimulated Raman gain is obtained. The power requirements of the two fields are examined qualitatively and quantitatively. The assumption that the inverse Raman absorption coefficient is constant over the interaction length is examined. Advantages of the technique are discussed and a brief survey of reported studies is presented.

  6. Inverse Raman effect: applications and detection techniques

    International Nuclear Information System (INIS)

    Hughes, L.J. Jr.

    1980-08-01

    The processes underlying the inverse Raman effect are qualitatively described by comparing it to the more familiar phenomena of conventional and stimulated Raman scattering. An experession is derived for the inverse Raman absorption coefficient, and its relationship to the stimulated Raman gain is obtained. The power requirements of the two fields are examined qualitatively and quantitatively. The assumption that the inverse Raman absorption coefficient is constant over the interaction length is examined. Advantages of the technique are discussed and a brief survey of reported studies is presented

  7. Variability in surface inversion characteristics over India in winter ...

    Indian Academy of Sciences (India)

    inversion depth at most of the other stations show that shallow and moderate inversions occur more frequently than deep ..... processed and several checks were applied to ensure homogeneity ... simply inversions) is defined as the layer from ...

  8. Inverse Kinematics With Closed Form Solution For Denso Robot Manipulator

    Directory of Open Access Journals (Sweden)

    Ikhsan Eka Prasetia

    2015-03-01

    Full Text Available In this paper, the forward kinematics and inverse kinematics used on the Denso robot manipulator which has a 6-DOF. The forward kinematics will result in the desired position by end-effector, while inverse kinematics produce angel on each joint. Inverse kinematics problem are very difficult, therefor to obtain the solution of inverse kinematics using closed form solution with geometry approach. The simulation result obtained from forward kinematics and inverse kinematics is determining desired position by Denso robot manipulator. Forward kinematics produce the desired position by the end-effector. Inverse kinematics produce joint angle, where the inverse kinematics produce eight conditions obtained from closed form solution with geometry approach to reach the desired position by the end-effector.

  9. Wave Equation Inversion of Skeletonized SurfaceWaves

    KAUST Repository

    Zhang, Zhendong; Liu, Yike; Schuster, Gerard T.

    2015-01-01

    We present a surface-wave inversion method that inverts for the S-wave velocity from the Rayleigh dispersion curve for the fundamental-mode. We call this wave equation inversion of skeletonized surface waves because the dispersion curve

  10. The Inverse of Banded Matrices

    Science.gov (United States)

    2013-01-01

    indexed entries all zeros. In this paper, generalizing a method of Mallik (1999) [5], we give the LU factorization and the inverse of the matrix Br,n (if it...r ≤ i ≤ r, 1 ≤ j ≤ r, with the remaining un-indexed entries all zeros. In this paper generalizing a method of Mallik (1999) [5...matrices and applications to piecewise cubic approximation, J. Comput. Appl. Math. 8 (4) (1982) 285–288. [5] R.K. Mallik , The inverse of a lower

  11. Inverse transport theory and applications

    International Nuclear Information System (INIS)

    Bal, Guillaume

    2009-01-01

    Inverse transport consists of reconstructing the optical properties of a domain from measurements performed at the domain's boundary. This review concerns several types of measurements: time-dependent, time-independent, angularly resolved and angularly averaged measurements. We review recent results on the reconstruction of the optical parameters from such measurements and the stability of such reconstructions. Inverse transport finds applications e.g. in medical imaging (optical tomography, optical molecular imaging) and in geophysical imaging (remote sensing in the Earth's atmosphere). (topical review)

  12. NOVOS LETRAMENTOS NA CULTURA DIGITAL: O REMIX VEM PRA RUA - O GIGANTE ACORDOU COMO UM HÍBRIDO

    Directory of Open Access Journals (Sweden)

    Rosivaldo Gomes

    2015-07-01

    Full Text Available A utilização da internet, das mídias e redes sociais digitais e de celulares se constituiu como um diferencial importantíssimo no grande movimento social que mexeu com o País e com as visões sobre ele nas manifestações ocorridas em junho de 2013. Essas mídias e redes sociais digitais (YouTube, Flickr, Facebook, Instagram, Twitter, etc. se constituíram como canais de informação, ambientes comunicacionais, pontos de encontro, enfim, em redes e, às vezes, até em comunidades que facilitaram os relacionamentos entre os que estavam conectados e dispostos a se manifestarem de algum modo. Nessa direção, os novos letramentos digitais e o novo ethos como defendido por Lankshear e Knobel (2007 proporcionaram contribuições significativas para o uso das tecnologias digitais de informação e comunicação na propagação dessas manifestações, e, buscando compreender o modo como esses novos letramentos favoreceram isso, neste artigo buscamos, a partir das noções de hibridismo e intercalação (GARCÍA CANCLINI, 2008 [1989]; BAKHTIN, 2002 [1934-5] e  nas discussões de Lankshear e Knobel (2007; 2008 sobre remix e sobre linguagens hipermidiática e híbrido digital (SANTAELLA, 2003; 2004, realizar uma análise qualitativa do remix digita Vem pra rua - O gigante acordou,  no que diz respeito as técnicas de produção e constituição desse gênero na construção de novos significado, considerando o horizonte espacial e temporal (VOLOCHINOV/BAKHTIN, [1926]1976 nos quais foi produzido

  13. Hair Follicle and Sebaceous Gland De Novo Regeneration With Cultured Epidermal Stem Cells and Skin-Derived Precursors.

    Science.gov (United States)

    Wang, Xiaoxiao; Wang, Xusheng; Liu, Jianjun; Cai, Ting; Guo, Ling; Wang, Shujuan; Wang, Jinmei; Cao, Yanpei; Ge, Jianfeng; Jiang, Yuyang; Tredget, Edward E; Cao, Mengjun; Wu, Yaojiong

    2016-12-01

    : Stem cell-based organ regeneration is purported to enable the replacement of impaired organs in the foreseeable future. Here, we demonstrated that a combination of cultured epidermal stem cells (Epi-SCs) derived from the epidermis and skin-derived precursors (SKPs) was capable of reconstituting functional hair follicles and sebaceous glands (SG). When Epi-SCs and SKPs were mixed in a hydrogel and implanted into an excisional wound in nude mice, the Epi-SCs formed de novo epidermis along with hair follicles, and SKPs contributed to dermal papilla in the neogenic hair follicles. Notably, a combination of culture-expanded Epi-SCs and SKPs derived from the adult human scalp were sufficient to generate hair follicles and hair. Bone morphogenetic protein 4, but not Wnts, sustained the expression of alkaline phosphatase in SKPs in vitro and the hair follicle-inductive property in vivo when SKPs were engrafted with neonatal epidermal cells into excisional wounds. In addition, Epi-SCs were capable of differentiating into sebocytes and formed de novo SGs, which excreted lipids as do normal SGs. Thus our results indicate that cultured Epi-SCs and SKPs are sufficient to generate de novo hair follicles and SGs, implying great potential to develop novel bioengineered skin substitutes with appendage genesis capacity. In postpartum humans, skin appendages lost in injury are not regenerated, despite the considerable achievement made in skin bioengineering. In this study, transplantation of a combination of culture-expanded epidermal stem cells and skin-derived progenitors from mice and adult humans led to de novo regeneration of functional hair follicles and sebaceous glands. The data provide transferable knowledge for the development of novel bioengineered skin substitutes with epidermal appendage regeneration capacity. ©AlphaMed Press.

  14. Sensitivity-Informed De Novo Programming for Many-Objective Water Portfolio Planning Under Uncertainty

    Science.gov (United States)

    Kasprzyk, J. R.; Reed, P. M.; Kirsch, B. R.; Characklis, G. W.

    2009-12-01

    Risk-based water supply management presents severe cognitive, computational, and social challenges to planning in a changing world. Decision aiding frameworks must confront the cognitive biases implicit to risk, the severe uncertainties associated with long term planning horizons, and the consequent ambiguities that shape how we define and solve water resources planning and management problems. This paper proposes and demonstrates a new interactive framework for sensitivity informed de novo programming. The theoretical focus of our many-objective de novo programming is to promote learning and evolving problem formulations to enhance risk-based decision making. We have demonstrated our proposed de novo programming framework using a case study for a single city’s water supply in the Lower Rio Grande Valley (LRGV) in Texas. Key decisions in this case study include the purchase of permanent rights to reservoir inflows and anticipatory thresholds for acquiring transfers of water through optioning and spot leases. A 10-year Monte Carlo simulation driven by historical data is used to provide performance metrics for the supply portfolios. The three major components of our methodology include Sobol globoal sensitivity analysis, many-objective evolutionary optimization and interactive tradeoff visualization. The interplay between these components allows us to evaluate alternative design metrics, their decision variable controls and the consequent system vulnerabilities. Our LRGV case study measures water supply portfolios’ efficiency, reliability, and utilization of transfers in the water supply market. The sensitivity analysis is used interactively over interannual, annual, and monthly time scales to indicate how the problem controls change as a function of the timescale of interest. These results have been used then to improve our exploration and understanding of LRGV costs, vulnerabilities, and the water portfolios’ critical reliability constraints. These results

  15. Optimizing and benchmarking de novo transcriptome sequencing: from library preparation to assembly evaluation.

    Science.gov (United States)

    Hara, Yuichiro; Tatsumi, Kaori; Yoshida, Michio; Kajikawa, Eriko; Kiyonari, Hiroshi; Kuraku, Shigehiro

    2015-11-18

    RNA-seq enables gene expression profiling in selected spatiotemporal windows and yields massive sequence information with relatively low cost and time investment, even for non-model species. However, there remains a large room for optimizing its workflow, in order to take full advantage of continuously developing sequencing capacity. Transcriptome sequencing for three embryonic stages of Madagascar ground gecko (Paroedura picta) was performed with the Illumina platform. The output reads were assembled de novo for reconstructing transcript sequences. In order to evaluate the completeness of transcriptome assemblies, we prepared a reference gene set consisting of vertebrate one-to-one orthologs. To take advantage of increased read length of >150 nt, we demonstrated shortened RNA fragmentation time, which resulted in a dramatic shift of insert size distribution. To evaluate products of multiple de novo assembly runs incorporating reads with different RNA sources, read lengths, and insert sizes, we introduce a new reference gene set, core vertebrate genes (CVG), consisting of 233 genes that are shared as one-to-one orthologs by all vertebrate genomes examined (29 species)., The completeness assessment performed by the computational pipelines CEGMA and BUSCO referring to CVG, demonstrated higher accuracy and resolution than with the gene set previously established for this purpose. As a result of the assessment with CVG, we have derived the most comprehensive transcript sequence set of the Madagascar ground gecko by means of assembling individual libraries followed by clustering the assembled sequences based on their overall similarities. Our results provide several insights into optimizing de novo RNA-seq workflow, including the coordination between library insert size and read length, which manifested in improved connectivity of assemblies. The approach and assembly assessment with CVG demonstrated here would be applicable to transcriptome analysis of other species as

  16. Sorting signed permutations by inversions in O(nlogn) time.

    Science.gov (United States)

    Swenson, Krister M; Rajan, Vaibhav; Lin, Yu; Moret, Bernard M E

    2010-03-01

    The study of genomic inversions (or reversals) has been a mainstay of computational genomics for nearly 20 years. After the initial breakthrough of Hannenhalli and Pevzner, who gave the first polynomial-time algorithm for sorting signed permutations by inversions, improved algorithms have been designed, culminating with an optimal linear-time algorithm for computing the inversion distance and a subquadratic algorithm for providing a shortest sequence of inversions--also known as sorting by inversions. Remaining open was the question of whether sorting by inversions could be done in O(nlogn) time. In this article, we present a qualified answer to this question, by providing two new sorting algorithms, a simple and fast randomized algorithm and a deterministic refinement. The deterministic algorithm runs in time O(nlogn + kn), where k is a data-dependent parameter. We provide the results of extensive experiments showing that both the average and the standard deviation for k are small constants, independent of the size of the permutation. We conclude (but do not prove) that almost all signed permutations can be sorted by inversions in O(nlogn) time.

  17. Alternating minimisation for glottal inverse filtering

    International Nuclear Information System (INIS)

    Bleyer, Ismael Rodrigo; Lybeck, Lasse; Auvinen, Harri; Siltanen, Samuli; Airaksinen, Manu; Alku, Paavo

    2017-01-01

    A new method is proposed for solving the glottal inverse filtering (GIF) problem. The goal of GIF is to separate an acoustical speech signal into two parts: the glottal airflow excitation and the vocal tract filter. To recover such information one has to deal with a blind deconvolution problem. This ill-posed inverse problem is solved under a deterministic setting, considering unknowns on both sides of the underlying operator equation. A stable reconstruction is obtained using a double regularization strategy, alternating between fixing either the glottal source signal or the vocal tract filter. This enables not only splitting the nonlinear and nonconvex problem into two linear and convex problems, but also allows the use of the best parameters and constraints to recover each variable at a time. This new technique, called alternating minimization glottal inverse filtering (AM-GIF), is compared with two other approaches: Markov chain Monte Carlo glottal inverse filtering (MCMC-GIF), and iterative adaptive inverse filtering (IAIF), using synthetic speech signals. The recent MCMC-GIF has good reconstruction quality but high computational cost. The state-of-the-art IAIF method is computationally fast but its accuracy deteriorates, particularly for speech signals of high fundamental frequency ( F 0). The results show the competitive performance of the new method: With high F 0, the reconstruction quality is better than that of IAIF and close to MCMC-GIF while reducing the computational complexity by two orders of magnitude. (paper)

  18. QCD-instantons and conformal inversion symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Klammer, D.

    2006-07-15

    Instantons are an essential and non-perturbative part of Quantum Chromodynamics, the theory of strong interactions. One of the most relevant quantities in the instanton calculus is the instanton-size distribution, which can be described on the one hand within the framework of instanton perturbation theory and on the other hand investigated numerically by means of lattice computations. A rapid onset of a drastic discrepancy between these respective results indicates that the underlying physics is not yet well understood. In this work we investigate the appealing possibility of a symmetry under conformal inversion of space-time leading to this deviation. The motivation being that the lattice data seem to be invariant under an inversion of the instanton size. Since the instanton solution of a given size turns into an anti-instanton solution having an inverted size under conformal inversion of space-time, we ask in a first investigation, whether this property is transferred to the quantum level. In order to introduce a new scale, which is indicated by the lattice data and corresponds to the average instanton size as inversion radius, we project the instanton calculus onto the four-dimensional surface of a five-dimensional sphere via stereographic projection. The radius of this sphere is associated with the average instanton size. The result for the instanton size-distribution projected onto the sphere agrees surprisingly well with the lattice data at qualitative level. The resulting symmetry under an inversion of the instanton size is almost perfect. (orig.)

  19. QCD-instantons and conformal inversion symmetry

    International Nuclear Information System (INIS)

    Klammer, D.

    2006-07-01

    Instantons are an essential and non-perturbative part of Quantum Chromodynamics, the theory of strong interactions. One of the most relevant quantities in the instanton calculus is the instanton-size distribution, which can be described on the one hand within the framework of instanton perturbation theory and on the other hand investigated numerically by means of lattice computations. A rapid onset of a drastic discrepancy between these respective results indicates that the underlying physics is not yet well understood. In this work we investigate the appealing possibility of a symmetry under conformal inversion of space-time leading to this deviation. The motivation being that the lattice data seem to be invariant under an inversion of the instanton size. Since the instanton solution of a given size turns into an anti-instanton solution having an inverted size under conformal inversion of space-time, we ask in a first investigation, whether this property is transferred to the quantum level. In order to introduce a new scale, which is indicated by the lattice data and corresponds to the average instanton size as inversion radius, we project the instanton calculus onto the four-dimensional surface of a five-dimensional sphere via stereographic projection. The radius of this sphere is associated with the average instanton size. The result for the instanton size-distribution projected onto the sphere agrees surprisingly well with the lattice data at qualitative level. The resulting symmetry under an inversion of the instanton size is almost perfect. (orig.)

  20. Trans-10, cis-12 conjugated linoleic acid decreases de novo lipid synthesis in human adipocytes

    DEFF Research Database (Denmark)

    Obsen, Thomas; Faergeman, Nils J; Chung, Soonkyu

    2012-01-01

    7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA......]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10...... is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA....

  1. A Case of De Novo Anterior Condylar Dural Arteriovenous Fistula Long after Curative Transvenous Embolization of Contralateral Anterior Condylar Arteriovenous Fistula

    Directory of Open Access Journals (Sweden)

    Shinya Hagiwara

    2016-01-01

    Full Text Available We report on a 55-year-old man who developed a de novo DAVF in left ACC 5 years after curative transvenous embolization for DAVF in right ACC. Angiography revealed that the de novo lesion demonstrated more aggressive arteriovenous shunt flow than the initial lesion. Successful transvenous embolization was performed for also the second lesion. The authors describe the possible pathophysiological mechanisms and management strategies for this rare occurrence.

  2. Method and software to solution of inverse and inverse design fluid flow and heat transfer problems is compatible with CFD-software

    Energy Technology Data Exchange (ETDEWEB)

    Krukovsky, P G [Institute of Engineering Thermophysics, National Academy of Sciences of Ukraine, Kiev (Ukraine)

    1998-12-31

    The description of method and software FRIEND which provide a possibility of solution of inverse and inverse design problems on the basis of existing (base) CFD-software for solution of direct problems (in particular, heat-transfer and fluid-flow problems using software PHOENICS) are presented. FRIEND is an independent additional module that widens the operational capacities of the base software unified with this module. This unifying does not require any change or addition to the base software. Interfacing of FRIEND and the base software takes place through input and output files of the base software. A brief description of the computational technique applied for the inverse problem solution, same detailed information on the interfacing of FRIEND and CFD-software and solution results for testing inverse and inverse design problems, obtained using the tandem CFD-software PHOENICS and FRIEND, are presented. (author) 9 refs.

  3. Method and software to solution of inverse and inverse design fluid flow and heat transfer problems is compatible with CFD-software

    Energy Technology Data Exchange (ETDEWEB)

    Krukovsky, P.G. [Institute of Engineering Thermophysics, National Academy of Sciences of Ukraine, Kiev (Ukraine)

    1997-12-31

    The description of method and software FRIEND which provide a possibility of solution of inverse and inverse design problems on the basis of existing (base) CFD-software for solution of direct problems (in particular, heat-transfer and fluid-flow problems using software PHOENICS) are presented. FRIEND is an independent additional module that widens the operational capacities of the base software unified with this module. This unifying does not require any change or addition to the base software. Interfacing of FRIEND and the base software takes place through input and output files of the base software. A brief description of the computational technique applied for the inverse problem solution, same detailed information on the interfacing of FRIEND and CFD-software and solution results for testing inverse and inverse design problems, obtained using the tandem CFD-software PHOENICS and FRIEND, are presented. (author) 9 refs.

  4. Inverse reasoning processes in obsessive-compulsive disorder.

    Science.gov (United States)

    Wong, Shiu F; Grisham, Jessica R

    2017-04-01

    The inference-based approach (IBA) is one cognitive model that aims to explain the aetiology and maintenance of obsessive-compulsive disorder (OCD). The model proposes that certain reasoning processes lead an individual with OCD to confuse an imagined possibility with an actual probability, a state termed inferential confusion. One such reasoning process is inverse reasoning, in which hypothetical causes form the basis of conclusions about reality. Although previous research has found associations between a self-report measure of inferential confusion and OCD symptoms, evidence of a specific association between inverse reasoning and OCD symptoms is lacking. In the present study, we developed a task-based measure of inverse reasoning in order to investigate whether performance on this task is associated with OCD symptoms in an online sample. The results provide some evidence for the IBA assertion: greater endorsement of inverse reasoning was significantly associated with OCD symptoms, even when controlling for general distress and OCD-related beliefs. Future research is needed to replicate this result in a clinical sample and to investigate a potential causal role for inverse reasoning in OCD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

    NARCIS (Netherlands)

    de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah; Møller, Rikke S; Velinov, Milen; Dolzhanskaya, Natalia; Marsh, Eric; Helbig, Ingo; Devinsky, Orrin; Tang, Sha; Mefford, Heather C; Myers, Candace T; van Paesschen, Wim; Striano, Pasquale; van Gassen, Koen; van Kempen, Marjan; de Kovel, Carolien G F; Piard, Juliette; Minassian, Berge A; Nezarati, Marjan M; Pessoa, André; Jacquette, Aurelia; Maher, Bridget; Balestrini, Simona; Sisodiya, Sanjay; Warde, Marie Therese Abi; De St Martin, Anne; Chelly, Jamel; van 't Slot, Ruben; Van Maldergem, Lionel; Brilstra, Eva H; Koeleman, Bobby P C

    2016-01-01

    BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual

  6. De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

    DEFF Research Database (Denmark)

    de Lange, Iris M; Helbig, Katherine L; Weckhuysen, Sarah

    2016-01-01

    BACKGROUND: Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellect...

  7. Inverse Kinematics With Closed Form Solution For Denso Robot Manipulator

    OpenAIRE

    Ikhsan Eka Prasetia; Trihastuti Agustinah

    2015-01-01

    In this paper, the forward kinematics and inverse kinematics used on the Denso robot manipulator which has a 6-DOF. The forward kinematics will result in the desired position by end-effector, while inverse kinematics produce angel on each joint. Inverse kinematics problem are very difficult, therefor to obtain the solution of inverse kinematics using closed form solution with geometry approach. The simulation result obtained from forward kinematics and inverse kinematics is determining desire...

  8. The inverse conductivity problem with limited data and applications

    International Nuclear Information System (INIS)

    Isakov, Victor

    2007-01-01

    This paper describes recent uniqueness results in inverse problems for semiconductor devices and in the inverse conductivity problem. We remind basic inverse probelsm in semiconductor theory and outline use of an adjoint equation and a proof of uniqueness of piecewise constant doping profile. For the inverse conductivity problem we give a first uniqueness proof when the Dirichlet-to-Neumann map is given at an arbitrarily small part of the boundary of a three-dimensional domain

  9. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

    Science.gov (United States)

    Heinzen, Erin L.; Swoboda, Kathryn J.; Hitomi, Yuki; Gurrieri, Fiorella; Nicole, Sophie; de Vries, Boukje; Tiziano, F. Danilo; Fontaine, Bertrand; Walley, Nicole M.; Heavin, Sinéad; Panagiotakaki, Eleni; Fiori, Stefania; Abiusi, Emanuela; Di Pietro, Lorena; Sweney, Matthew T.; Newcomb, Tara M.; Viollet, Louis; Huff, Chad; Jorde, Lynn B.; Reyna, Sandra P.; Murphy, Kelley J.; Shianna, Kevin V.; Gumbs, Curtis E.; Little, Latasha; Silver, Kenneth; Ptác̆ek, Louis J.; Haan, Joost; Ferrari, Michel D.; Bye, Ann M.; Herkes, Geoffrey K.; Whitelaw, Charlotte M.; Webb, David; Lynch, Bryan J.; Uldall, Peter; King, Mary D.; Scheffer, Ingrid E.; Neri, Giovanni; Arzimanoglou, Alexis; van den Maagdenberg, Arn M.J.M.; Sisodiya, Sanjay M.; Mikati, Mohamad A.; Goldstein, David B.; Nicole, Sophie; Gurrieri, Fiorella; Neri, Giovanni; de Vries, Boukje; Koelewijn, Stephany; Kamphorst, Jessica; Geilenkirchen, Marije; Pelzer, Nadine; Laan, Laura; Haan, Joost; Ferrari, Michel; van den Maagdenberg, Arn; Zucca, Claudio; Bassi, Maria Teresa; Franchini, Filippo; Vavassori, Rosaria; Giannotta, Melania; Gobbi, Giuseppe; Granata, Tiziana; Nardocci, Nardo; De Grandis, Elisa; Veneselli, Edvige; Stagnaro, Michela; Gurrieri, Fiorella; Neri, Giovanni; Vigevano, Federico; Panagiotakaki, Eleni; Oechsler, Claudia; Arzimanoglou, Alexis; Nicole, Sophie; Giannotta, Melania; Gobbi, Giuseppe; Ninan, Miriam; Neville, Brian; Ebinger, Friedrich; Fons, Carmen; Campistol, Jaume; Kemlink, David; Nevsimalova, Sona; Laan, Laura; Peeters-Scholte, Cacha; van den Maagdenberg, Arn; Casaer, Paul; Casari, Giorgio; Sange, Guenter; Spiel, Georg; Boneschi, Filippo Martinelli; Zucca, Claudio; Bassi, Maria Teresa; Schyns, Tsveta; Crawley, Francis; Poncelin, Dominique; Vavassori, Rosaria

    2012-01-01

    Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations. AHC is usually a sporadic disorder with unknown etiology. Using exome sequencing of seven patients with AHC, and their unaffected parents, we identified de novo nonsynonymous mutations in ATP1A3 in all seven AHC patients. Subsequent sequence analysis of ATP1A3 in 98 additional patients revealed that 78% of AHC cases have a likely causal ATP1A3 mutation, including one inherited mutation in a familial case of AHC. Remarkably, six ATP1A3 mutations explain the majority of patients, including one observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset-dystonia-parkinsonism, AHC-causing mutations revealed consistent reductions in ATPase activity without effects on protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC, and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in this gene. PMID:22842232

  10. Polymer sol-gel composite inverse opal structures.

    Science.gov (United States)

    Zhang, Xiaoran; Blanchard, G J

    2015-03-25

    We report on the formation of composite inverse opal structures where the matrix used to form the inverse opal contains both silica, formed using sol-gel chemistry, and poly(ethylene glycol), PEG. We find that the morphology of the inverse opal structure depends on both the amount of PEG incorporated into the matrix and its molecular weight. The extent of organization in the inverse opal structure, which is characterized by scanning electron microscopy and optical reflectance data, is mediated by the chemical bonding interactions between the silica and PEG constituents in the hybrid matrix. Both polymer chain terminus Si-O-C bonding and hydrogen bonding between the polymer backbone oxygens and silanol functionalities can contribute, with the polymer mediating the extent to which Si-O-Si bonds can form within the silica regions of the matrix due to hydrogen-bonding interactions.

  11. Three-dimensional inversion of multisource array electromagnetic data

    Science.gov (United States)

    Tartaras, Efthimios

    Three-dimensional (3-D) inversion is increasingly important for the correct interpretation of geophysical data sets in complex environments. To this effect, several approximate solutions have been developed that allow the construction of relatively fast inversion schemes. One such method that is fast and provides satisfactory accuracy is the quasi-linear (QL) approximation. It has, however, the drawback that it is source-dependent and, therefore, impractical in situations where multiple transmitters in different positions are employed. I have, therefore, developed a localized form of the QL approximation that is source-independent. This so-called localized quasi-linear (LQL) approximation can have a scalar, a diagonal, or a full tensor form. Numerical examples of its comparison with the full integral equation solution, the Born approximation, and the original QL approximation are given. The objective behind developing this approximation is to use it in a fast 3-D inversion scheme appropriate for multisource array data such as those collected in airborne surveys, cross-well logging, and other similar geophysical applications. I have developed such an inversion scheme using the scalar and diagonal LQL approximation. It reduces the original nonlinear inverse electromagnetic (EM) problem to three linear inverse problems. The first of these problems is solved using a weighted regularized linear conjugate gradient method, whereas the last two are solved in the least squares sense. The algorithm I developed provides the option of obtaining either smooth or focused inversion images. I have applied the 3-D LQL inversion to synthetic 3-D EM data that simulate a helicopter-borne survey over different earth models. The results demonstrate the stability and efficiency of the method and show that the LQL approximation can be a practical solution to the problem of 3-D inversion of multisource array frequency-domain EM data. I have also applied the method to helicopter-borne EM

  12. Inverse photoemission of uranium oxides

    International Nuclear Information System (INIS)

    Roussel, P.; Morrall, P.; Tull, S.J.

    2009-01-01

    Understanding the itinerant-localised bonding role of the 5f electrons in the light actinides will afford an insight into their unusual physical and chemical properties. In recent years, the combination of core and valance band electron spectroscopies with theoretic modelling have already made significant progress in this area. However, information of the unoccupied density of states is still scarce. When compared to the forward photoemission techniques, measurements of the unoccupied states suffer from significantly less sensitivity and lower resolution. In this paper, we report on our experimental apparatus, which is designed to measure the inverse photoemission spectra of the light actinides. Inverse photoemission spectra of UO 2 and UO 2.2 along with the corresponding core and valance electron spectra are presented in this paper. UO 2 has been reported previously, although through its inclusion here it allows us to compare and contrast results from our experimental apparatus to the previous Bremsstrahlung Isochromat Spectroscopy and Inverse Photoemission Spectroscopy investigations

  13. Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Atsushi Takata

    2018-01-01

    Full Text Available Recent studies have established important roles of de novo mutations (DNMs in autism spectrum disorders (ASDs. Here, we analyze DNMs in 262 ASD probands of Japanese origin and confirm the “de novo paradigm” of ASDs across ethnicities. Based on this consistency, we combine the lists of damaging DNMs in our and published ASD cohorts (total number of trios, 4,244 and perform integrative bioinformatics analyses. Besides replicating the findings of previous studies, our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits. Analysis of individual genes identified 61 genes enriched for damaging DNMs, including ten genes for which our dataset now contributes to statistical significance. Screening of compounds altering the expression of genes hit by damaging DNMs reveals a global downregulating effect of valproic acid, a known risk factor for ASDs, whereas cardiac glycosides upregulate these genes. Collectively, our integrative approach provides deeper biological and potential medical insights into ASDs.

  14. Perinatal Autopsy Findings in a Case of De Novo Hypohidrotic Ectodermal Dysplasia.

    Science.gov (United States)

    Chikkannaiah, Panduranga; Nagaraju, Smitha; Kangle, Rajit; Gosavi, Mansi

    2015-01-01

    Ectodermal dysplasia are group of inherited disorders involving the developmental defects of ectodermal structures like hair, teeth, nails, sweat glands, and others. X-linked recessive inheritance is most common. Here we describe perinatal autopsy findings in a case of de novo ectodermal dysplasia in a female fetus. To the best of our knowledge, this is the first fetal autopsy description in a case of ectodermal dysplasia.

  15. Population inversion in a stationary recombining plasma

    International Nuclear Information System (INIS)

    Otsuka, M.

    1980-01-01

    Population inversion, which occurs in a recombining plasma when a stationary He plasma is brought into contact with a neutral gas, is examined. With hydrogen as a contact gas, noticeable inversion between low-lying levels of H as been found. The overpopulation density is of the order of 10 8 cm -3 , which is much higher then that (approx. =10 5 cm -3 ) obtained previously with He as a contact gas. Relations between these experimental results and the conditions for population inversion are discussed with the CR model

  16. High resolution tsunami inversion for 2010 Chile earthquake

    Directory of Open Access Journals (Sweden)

    T.-R. Wu

    2011-12-01

    Full Text Available We investigate the feasibility of inverting high-resolution vertical seafloor displacement from tsunami waveforms. An inversion method named "SUTIM" (small unit tsunami inversion method is developed to meet this goal. In addition to utilizing the conventional least-square inversion, this paper also enhances the inversion resolution by Grid-Shifting method. A smooth constraint is adopted to gain stability. After a series of validation and performance tests, SUTIM is used to study the 2010 Chile earthquake. Based upon data quality and azimuthal distribution, we select tsunami waveforms from 6 GLOSS stations and 1 DART buoy record. In total, 157 sub-faults are utilized for the high-resolution inversion. The resolution reaches 10 sub-faults per wavelength. The result is compared with the distribution of the aftershocks and waveforms at each gauge location with very good agreement. The inversion result shows that the source profile features a non-uniform distribution of the seafloor displacement. The highly elevated vertical seafloor is mainly concentrated in two areas: one is located in the northern part of the epicentre, between 34° S and 36° S; the other is in the southern part, between 37° S and 38° S.

  17. High resolution tsunami inversion for 2010 Chile earthquake

    Science.gov (United States)

    Wu, T.-R.; Ho, T.-C.

    2011-12-01

    We investigate the feasibility of inverting high-resolution vertical seafloor displacement from tsunami waveforms. An inversion method named "SUTIM" (small unit tsunami inversion method) is developed to meet this goal. In addition to utilizing the conventional least-square inversion, this paper also enhances the inversion resolution by Grid-Shifting method. A smooth constraint is adopted to gain stability. After a series of validation and performance tests, SUTIM is used to study the 2010 Chile earthquake. Based upon data quality and azimuthal distribution, we select tsunami waveforms from 6 GLOSS stations and 1 DART buoy record. In total, 157 sub-faults are utilized for the high-resolution inversion. The resolution reaches 10 sub-faults per wavelength. The result is compared with the distribution of the aftershocks and waveforms at each gauge location with very good agreement. The inversion result shows that the source profile features a non-uniform distribution of the seafloor displacement. The highly elevated vertical seafloor is mainly concentrated in two areas: one is located in the northern part of the epicentre, between 34° S and 36° S; the other is in the southern part, between 37° S and 38° S.

  18. Inverse Schroedinger equation and the exact wave function

    International Nuclear Information System (INIS)

    Nakatsuji, Hiroshi

    2002-01-01

    Using the inverse of the Hamiltonian, we introduce the inverse Schroedinger equation (ISE) that is equivalent to the ordinary Schroedinger equation (SE). The ISE has the variational principle and the H-square group of equations as the SE has. When we use a positive Hamiltonian, shifting the energy origin, the inverse energy becomes monotonic and we further have the inverse Ritz variational principle and cross-H-square equations. The concepts of the SE and the ISE are combined to generalize the theory for calculating the exact wave function that is a common eigenfunction of the SE and ISE. The Krylov sequence is extended to include the inverse Hamiltonian, and the complete Krylov sequence is introduced. The iterative configuration interaction (ICI) theory is generalized to cover both the SE and ISE concepts and four different computational methods of calculating the exact wave function are presented in both analytical and matrix representations. The exact wave-function theory based on the inverse Hamiltonian can be applied to systems that have singularities in the Hamiltonian. The generalized ICI theory is applied to the hydrogen atom, giving the exact solution without any singularity problem

  19. In-Stent Restenosis of Drug-Eluting Stents Compared With a Matched Group of Patients With De Novo Coronary Artery Stenosis.

    Science.gov (United States)

    Buchanan, Kyle D; Torguson, Rebecca; Rogers, Toby; Xu, Linzhi; Gai, Jiaxiang; Ben-Dor, Itsik; Suddath, William O; Satler, Lowell F; Waksman, Ron

    2018-03-13

    Drug-eluting stents (DES) significantly reduced the incidence of in-stent restenosis (ISR). However, ISR still exists in the contemporary DES era. Previously deemed to be a benign process, ISR leads to complex presentation and intervention. This study aimed to compare the presentation and outcome of DES-ISR versus de novo lesions. We performed a retrospective analysis of 11,666 patients receiving percutaneous coronary intervention from 2003 to 2017 and divided them into 2 groups by de novo stenosis and ISR. They were matched based on common cardiovascular risk factors at a 4:1 ratio, respectively. After matching, a total of 1,888 patients with 3,126 de novo lesions and 472 patients with 508 ISR lesions were analyzed. Patients with ISR presented more often with unstable angina (61% vs 45%, p stent technique and should motivate the continued development of fully bioresorbable scaffolds. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Cognitive impairment is associated with Hoehn and Yahr stages in early, de novo Parkinson disease patients.

    Science.gov (United States)

    Siciliano, Mattia; De Micco, Rosa; Trojano, Luigi; De Stefano, Manuela; Baiano, Chiara; Passaniti, Carla; De Mase, Antonio; Russo, Antonio; Tedeschi, Gioacchino; Tessitore, Alessandro

    2017-08-01

    The relationship between motor impairment and cognitive deterioration has long been described in Parkinson's disease (PD). The aim of the study was to compare cognitive performance of de novo PD patients in relation to the motor impairment severity according to Hoehn and Yahr (HY) stages. Forty de novo PD patients at HY stage I and 40 patients at HY stage II completed a standardized neuropsychological battery. A multivariate analysis of covariance was used to compare cognitive performance between HY groups. Odds ratios (ORs) were employed to explore the risk of cognitive impairment between HY stages. Finally, the prevalence of mild cognitive impairment (MCI) was estimated for patients in HY stage I and II. Patients at HY stage I obtained better scores on neuropsychological tests than patients at HY stage II (p = 0.001). Univariate analysis of covariance revealed significant differences between HY stages on Rey's auditory verbal learning test -immediate recall (p cognitive impairment were greater for HY stage II than stage I group. MCI occurred in 7.5% of patients in HY stage I, and in 42.5% of patients in HY stage II. In de novo PD patients, the severity of motor impairment at the diagnosis is associated to cognitive deficits and higher risk of MCI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Los "intelectuales" y el Estado Novo

    Directory of Open Access Journals (Sweden)

    Luís REIS TORGAL

    2010-02-01

    Full Text Available RESUMEN: El concepto de “intelectual” es difícil de definir y sin duda se debate constantemente. Sin embargo, es importante reflexionar sobre él a fin de comprender su significado y los problemas que implica. Sea como fuere, a un Estado autoritario “moderno” se le supone una única ideología que tiene que difundirse por medio de una propaganda bien organizada, proceso en el que los intelectuales desempeñan un papel significativo. El “Nuevo Estado” de Salazar encaja en esta categoría y sin duda el conocimiento acerca de sus “intelectuales” es fundamental. En este artículo, el objetivo es proporcionar algunos ejemplos interesantes de “intelectuales” o de simples “funcionarios políticos” con inclinación intelectual a fin de indicar el sentido y complejidad de un estudio con una dimensión distinta sobre este asunto. A este fin han sido seleccionadas tres personalidades responsables de la actividad ideológica y cultural de gran relieve en el Estado de Salazar: António Ferro, João Ameal y Costa Brochado. Palabras clave: Estado Novo; Authotitarianism; Salazar, António de Oliveira; Intellectuals; Ferro, António; Brochado, Idalino da Costa; Ameal, João. ABSTRACT: The concept of the “intellectual” is difficult to define and undoubtedly constantly debated. It is nevertheless important to reflect on it in order to understand its meaning and the problems involved with it. Be that as it may, a “modern” authoritarian State presumes a single ideology which has to be diffused by means of well-organised propaganda, in which process “intellectuals” play a significant role. Salazar’s “New State” fits this category and, undoubtedly, knowledge about its “intellectuals” is fundamental. The objective in this article is to provide some interesting examples of “intellectuals” or simple “political functionar- ies” with an intellectual bent so as to indicate the sense and complexity of a study of a

  2. De novo origin of VCY2 from autosome to Y-transposed amplicon.

    Directory of Open Access Journals (Sweden)

    Peng-Rong Cao

    Full Text Available The formation of new genes is a primary driving force of evolution in all organisms. The de novo evolution of new genes from non-protein-coding genomic regions is emerging as an important additional mechanism for novel gene creation. Y chromosomes underlie sex determination in mammals and contain genes that are required for male-specific functions. In this study, a search was undertaken for Y chromosome de novo genes derived from non-protein-coding sequences. The Y chromosome orphan gene variable charge, Y-linked (VCY2, is an autosome-derived gene that has sequence similarity to large autosomal fragments but lacks an autosomal protein-coding homolog. VCY2 locates in the amplicon containing long DNA fragments that were transposed from autosomes to the Y chromosome before the ape-monkey split. We confirmed that VCY2 cannot be encoded by autosomes due to the presence of multiple disablers that disrupt the open reading frame, such as the absence of start or stop codons and the presence of premature stop codons. Similar observations have been made for homologs in the autosomes of the chimpanzee, gorilla, rhesus macaque, baboon and out-group marmoset, which suggests that there was a non-protein-coding ancestral VCY2 that was common to apes and monkeys that predated the transposition event. Furthermore, while protein-coding orthologs are absent, a putative non-protein-coding VCY2 with conserved disablers was identified in the rhesus macaque Y chromosome male-specific region. This finding implies that VCY2 might have not acquired its protein-coding ability before the ape-monkey split. VCY2 encodes a testis-specific expressed protein and is involved in the pathologic process of male infertility, and the acquisition of this gene might improve male fertility. This is the first evidence that de novo genes can be generated from transposed autosomal non-protein-coding segments, and this evidence provides novel insights into the evolutionary history of the Y

  3. Joint Inversion of Direct Current Resistivity and Seismic Refraction Data

    International Nuclear Information System (INIS)

    Kurt, B.B.

    2007-01-01

    In this study, I assumed the underground consist of horizontal layers. I developed one-dimensional (1D) Direct Current Resistivity (DCR) and seismic refraction inversion code using MATLAB package and attempt to find velocity, resistivity and depth of the layers. The code uses damped least square technique. The code can do inversion on DCR and seismic data either individually or jointly. I tested the joint inversion code on synthetic data. Eventually, I saw that the result of joint inversion is better than the result of individual inversions. The joint inversion found depth of models of each layer and, in addition, velocity and resistivity closer to real values

  4. Inverse Interval Matrix: A Survey

    Czech Academy of Sciences Publication Activity Database

    Rohn, Jiří; Farhadsefat, R.

    2011-01-01

    Roč. 22, - (2011), s. 704-719 E-ISSN 1081-3810 R&D Projects: GA ČR GA201/09/1957; GA ČR GC201/08/J020 Institutional research plan: CEZ:AV0Z10300504 Keywords : interval matrix * inverse interval matrix * NP-hardness * enclosure * unit midpoint * inverse sign stability * nonnegative invertibility * absolute value equation * algorithm Subject RIV: BA - General Mathematics Impact factor: 0.808, year: 2010 http://www.math.technion.ac.il/iic/ ela / ela -articles/articles/vol22_pp704-719.pdf

  5. De novo alloreactive memory CD8+ T cells develop following allogeneic challenge when CNI immunosuppression is delayed.

    Science.gov (United States)

    Hart-Matyas, M; Gareau, A J; Hirsch, G M; Lee, T D G

    2015-01-01

    Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Low CLL-1 Expression Is a Novel Adverse Predictor in 123 Patients with De Novo CD34+ Acute Myeloid Leukemia.

    Science.gov (United States)

    Wang, Yan-Yu; Chen, Wen-Lian; Weng, Xiang-Qin; Sheng, Yan; Wu, Jing; Hao, Jie; Liu, Zhan-Yun; Zhu, Yong-Mei; Chen, Bing; Xiong, Shu-Min; Chen, Yu; Chen, Qiu-Sheng; Sun, Hui-Ping; Li, Jun-Min; Wang, Jin

    2017-10-15

    Recent reports state that C-type lectin-like molecule-1 (CLL-1) in acute myeloid leukemia (AML) is expressed primarily on myeloid cells, but there is still no investigation about its prognostic significance on leukemic blast compartment. Hence, this study aimed to evaluate the prognostic value of CLL-1 in 123 patients with de novo CD34 + Non-M3 AML. Multiparameter flow cytometry was used to assess the expression of CLL-1 on immature compartment in AML and control groups. We found that CLL-1 expression level on blast compartment was closely linked to clinical characteristics, treatment response, and survival outcome of patients. Decreased expression of CLL-1 was observed on immature compartment from AML patients as compared with controls (62.6% vs. 86.5%, P CLL-1 low independently predicted low complete remission rate with an odds ratio of 4.57 (2.53-6.61, P CLL-1 expression level at diagnosis was inversely correlated to the residual blast cells (residual leukemia cell) after induction chemotherapy (r = -0.423, P CLL-1 low was still an independent adverse predictor (P CLL-1 low was able to discriminate poor survival patients from intermediate- and favorable-risk groups. Taken together, CLL-1 is a novel prognostic predictor that could be exploited to supplement the current AML prognostic risk stratification system, and potentially optimize the clinical management of AML.

  7. Chromosome aberrations and oncogene alterations in atomic bomb related leukemias - different mechanisms from de novo leukemias

    International Nuclear Information System (INIS)

    Tanaka, K.; Tanaka, H.; Kamada, N.

    2003-01-01

    It is well known that leukemia occurred more frequently among atomic bomb survivors. In 132 atomic bomb related ( AB- related) leukemia patients during 1978-1999, 33 acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) patients had their exposure doses of more than 1Gy (DS86). Chromosome aberrations of the 33 patients were compared with those from 588 de novo AML/MDS patients who had been bone before August 1945 as control. No FAB M3 patient was observed in the exposed group. Most AB-related AML preceded a long term of MDS stage. Twenty seven of the 33 patients showed complex types of chromosome aberrations with more than three chromosomes involving chromosomes 5,7 and 11. The number of chromosomes abnormality per cell in the AB-related leukemia was 3.78 while 0.92 in de novo leukemia. Only one of the 33 patients had normal karyotype, while 44.1% in de novo leukemia patients. Translocations of chromosome 11 at 11q13 to 11q23 and deletion/ loss of chromosome 20 were frequently observed in AB-related leukemia. No leukemia-type specific translocations such as t(8;21),t(15;17) and 11q23 were found in the 33 AB-related leukemia patients. Furthermore, molecular analyses using FISH and PCR-SSCP revealed the presence of breakpoint located outside of MLL gene in the patients with translocations at 11q22-23 and DNA base derangements of RUNT domain of AML1(CBF β 2)gene with AML/MDS patients without t(8;21) and with a high dose of exposure. These results suggest that AB-related leukemia derives from an exposed pluripotent hematopoietic stem cell which has been preserved for a long time in the bone marrow, expressing high genetic instability such as microsatellite instability. On the other hand, de novo leukemia develops from a committed hematopoietic stem cell and shows simple and leukemia-type specific chromosome aberrations. These findings are important for understanding mechanisms for radiation-induced leukemia

  8. Multiscale Phase Inversion of Seismic Data

    KAUST Repository

    Fu, Lei

    2017-12-02

    We present a scheme for multiscale phase inversion (MPI) of seismic data that is less sensitive to the unmodeled physics of wave propagation and a poor starting model than standard full waveform inversion (FWI). To avoid cycle-skipping, the multiscale strategy temporally integrates the traces several times, i.e. high-order integration, to produce low-boost seismograms that are used as input data for the initial iterations of MPI. As the iterations proceed, higher frequencies in the data are boosted by using integrated traces of lower order as the input data. The input data are also filtered into different narrow frequency bands for the MPI implementation. At low frequencies, we show that MPI with windowed reflections approximates wave equation inversion of the reflection traveltimes, except no traveltime picking is needed. Numerical results with synthetic acoustic data show that MPI is more robust than conventional multiscale FWI when the initial model is far from the true model. Results from synthetic viscoacoustic and elastic data show that MPI is less sensitive than FWI to some of the unmodeled physics. Inversion of marine data shows that MPI is more robust and produces modestly more accurate results than FWI for this data set.

  9. Inverse modelling of European CH4 emissions during 2006-2012 using different inverse models and reassessed atmospheric observations

    Science.gov (United States)

    Bergamaschi, Peter; Karstens, Ute; Manning, Alistair J.; Saunois, Marielle; Tsuruta, Aki; Berchet, Antoine; Vermeulen, Alexander T.; Arnold, Tim; Janssens-Maenhout, Greet; Hammer, Samuel; Levin, Ingeborg; Schmidt, Martina; Ramonet, Michel; Lopez, Morgan; Lavric, Jost; Aalto, Tuula; Chen, Huilin; Feist, Dietrich G.; Gerbig, Christoph; Haszpra, László; Hermansen, Ove; Manca, Giovanni; Moncrieff, John; Meinhardt, Frank; Necki, Jaroslaw; Galkowski, Michal; O'Doherty, Simon; Paramonova, Nina; Scheeren, Hubertus A.; Steinbacher, Martin; Dlugokencky, Ed

    2018-01-01

    We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006-2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions. The inverse models infer total CH4 emissions of 26.8 (20.2-29.7) Tg CH4 yr-1 (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006-2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 Tg CH4 yr-1 (2006) to 18.8 Tg CH4 yr-1 (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3-8.2) Tg CH4 yr-1 from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain. Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon

  10. On the Duality of Forward and Inverse Light Transport.

    Science.gov (United States)

    Chandraker, Manmohan; Bai, Jiamin; Ng, Tian-Tsong; Ramamoorthi, Ravi

    2011-10-01

    Inverse light transport seeks to undo global illumination effects, such as interreflections, that pervade images of most scenes. This paper presents the theoretical and computational foundations for inverse light transport as a dual of forward rendering. Mathematically, this duality is established through the existence of underlying Neumann series expansions. Physically, it can be shown that each term of our inverse series cancels an interreflection bounce, just as the forward series adds them. While the convergence properties of the forward series are well known, we show that the oscillatory convergence of the inverse series leads to more interesting conditions on material reflectance. Conceptually, the inverse problem requires the inversion of a large light transport matrix, which is impractical for realistic resolutions using standard techniques. A natural consequence of our theoretical framework is a suite of fast computational algorithms for light transport inversion--analogous to finite element radiosity, Monte Carlo and wavelet-based methods in forward rendering--that rely at most on matrix-vector multiplications. We demonstrate two practical applications, namely, separation of individual bounces of the light transport and fast projector radiometric compensation, to display images free of global illumination artifacts in real-world environments.

  11. Molecular analysis of "de novo" purine biosynthesis in solanaceous species and in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    van der Graaff, Eric; Hooykaas, Paul; Lein, Wolfgang

    2004-01-01

    Purine nucleotides are essential components to sustain plant growth and development. In plants they are either synthesized "de novo" during the process of purine biosynthesis or are recycled from purine bases and purine nucleosides throughout the salvage pathway. Comparison between animals...... biosynthesis pathway in plants, and the in planta functional analysis of PRPP (5-phosphoribosyl-1-pyrophoshate) amidotransferase (ATase), catalyzing the first committed step of the "de novo" purine biosynthesis. The cloning of the genes involved in the purine biosynthesis pathway was attained by a screening...... strategy with heterologous cDNA probes and by using S. cerevisiae mutants for complementation. Southern hybridization showed a complex genomic organization for these genes in solanaceous species and their organ- and developmental specific expression was analyzed by Northern hybridization. The specific role...

  12. Inversion variants in human and primate genomes.

    Science.gov (United States)

    Catacchio, Claudia Rita; Maggiolini, Flavia Angela Maria; D'Addabbo, Pietro; Bitonto, Miriana; Capozzi, Oronzo; Signorile, Martina Lepore; Miroballo, Mattia; Archidiacono, Nicoletta; Eichler, Evan E; Ventura, Mario; Antonacci, Francesca

    2018-05-18

    For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies. We identified a total of 156 putative inversions, between 103 kb and 91 Mb, corresponding to 136 human loci. Combining literature, sequence, and experimental analyses, we analyzed 109 of these loci and found 67 regions inverted in one or multiple primates, including 28 newly identified inversions. These events overlap with 81 human genes at their breakpoints, and seven correspond to sites of recurrent rearrangements associated with human disease. This work doubles the number of validated primate inversions larger than 100 kb, beyond what was previously documented. We identified 74 sites of errors, where the sequence has been assembled in the wrong orientation, in the reference genomes analyzed. Our data serve two purposes: First, we generated a map of evolutionary inversions in these genomes representing a resource for interrogating differences among these species at a functional level; second, we provide a list of misassembled regions in these primate genomes, involving over 300 Mb of DNA and 1978 human genes. Accurately annotating these regions in the genome references has immediate applications for evolutionary and biomedical studies on primates. © 2018 Catacchio et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Chromatid Painting for Chromosomal Inversion Detection, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose a novel approach to the detection of chromosomal inversions. Transmissible chromosome aberrations (translocations and inversions) have profound genetic...

  14. Constraint on Parameters of Inverse Compton Scattering Model for ...

    Indian Academy of Sciences (India)

    B2319+60, two parameters of inverse Compton scattering model, the initial Lorentz factor and the factor of energy loss of relativistic particles are constrained. Key words. Pulsar—inverse Compton scattering—emission mechanism. 1. Introduction. Among various kinds of models for pulsar radio emission, the inverse ...

  15. Inverse vs. forward breast IMRT planning

    International Nuclear Information System (INIS)

    Mihai, Alina; Rakovitch, Eileen; Sixel, Katharina; Woo, Tony; Cardoso, Marlene; Bell, Chris; Ruschin, Mark; Pignol, Jean-Philippe

    2005-01-01

    Breast intensity-modulated radiation therapy (IMRT) improves dose distribution homogeneity within the whole breast. Previous publications report the use of inverse or forward dose optimization algorithms. Because the inverse technique is not widely available in commercial treatment planning systems, it is important to compare the 2 algorithms. The goal of this work is to compare them on a prospective cohort of 30 patients. Dose distributions were evaluated on differential dose-volume histograms using the volumes receiving more than 105% (V 105 ) and 110% (V 110 ) of the prescribed dose, and on the maximum dose (D max ) or hot spot and the sagittal dose gradient (SDG) being the gradient between the dose on inframammary crease and the dose prescribed. The data were analyzed using Wilcoxon signed rank test. The inverse planning significantly improves the V 105 (mean value 9.7% vs. 14.5%, p = 0.002), and the V 110 (mean value 1.4% vs. 3.2%, p = 0.006). However, the SDG is not statistically significantly different for either algorithm. Looking at the potential impact on skin acute reaction, although there is a significant reduction of V 110 using an inverse algorithm, it is unlikely this 1.6% volume reduction will present a significant clinical advantage over a forward algorithm. Both algorithms are equivalent in removing the hot spots on the inframammary fold, where acute skin reactions occur more frequently using a conventional wedge technique. Based on these results, we recommend that both forward and inverse algorithms should be considered for breast IMRT planning

  16. Size Estimates in Inverse Problems

    KAUST Repository

    Di Cristo, Michele

    2014-01-06

    Detection of inclusions or obstacles inside a body by boundary measurements is an inverse problems very useful in practical applications. When only finite numbers of measurements are available, we try to detect some information on the embedded object such as its size. In this talk we review some recent results on several inverse problems. The idea is to provide constructive upper and lower estimates of the area/volume of the unknown defect in terms of a quantity related to the work that can be expressed with the available boundary data.

  17. 3rd Annual Workshop on Inverse Problem

    CERN Document Server

    2015-01-01

    This proceeding volume is based on papers presented on the Third Annual Workshop on Inverse Problems which was organized by the Department of Mathematical Sciences, Chalmers University of Technology and University of Gothenburg, and took place in May 2013 in Stockholm. The purpose of this workshop was to present new analytical developments and numerical techniques for solution of inverse problems for a wide range of applications in acoustics, electromagnetics, optical fibers, medical imaging, geophysics, etc. The contributions in this volume reflect these themes and will be beneficial to researchers who are working in the area of applied inverse problems.

  18. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven)

    DEFF Research Database (Denmark)

    Viuff, D.; Lauritzen, B.; Pusateri, A.E.

    2008-01-01

    BACKGROUND: A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders...

  19. Outcomes of de novo and acute decompensated heart failure patients according to ejection fraction.

    Science.gov (United States)

    Choi, Ki Hong; Lee, Ga Yeon; Choi, Jin-Oh; Jeon, Eun-Seok; Lee, Hae-Young; Cho, Hyun-Jai; Lee, Sang Eun; Kim, Min-Seok; Kim, Jae-Joong; Hwang, Kyung-Kuk; Chae, Shung Chull; Baek, Sang Hong; Kang, Seok-Min; Choi, Dong-Ju; Yoo, Byung-Su; Kim, Kye Hun; Park, Hyun-Young; Cho, Myeong-Chan; Oh, Byung-Hee

    2018-03-01

    There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%). Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF. In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02). HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted

  20. Três casos de hipertensão e Fístula Arteriovenosa Renal: com uma fístula de novo Tres casos de hipertención y Fístula Arteriovenosa Renal: con una fístula de novo Three cases of hypertension and Renal Arteriovenous fistula with a de novo fistula

    Directory of Open Access Journals (Sweden)

    Natalia Correa Vieira Melo

    2009-05-01

    Full Text Available Fístula Arteriovenosa Renal (FAVR é uma causa rara e potencialmente reversível de hipertensão e insuficiência renal e/ou cardíaca. O tratamento da FAVR visa preservar o máximo de parênquima renal e, concomitantemente, erradicar os sintomas e efeitos hemodinâmicos decorrentes da FAVR. No presente estudo, serão relatados três casos de FAVR, incluindo um caso de FAVR idiopática de novo, que se apresentaram com hipertensão e insuficiência renal e/ou cardíaca, e descrever a terapêutica adotada e os resultados obtidos.La Fístula Arteriovenosa Renal (FAVR es una causa rara y potencialmente reversible de hipertensión e insuficiencia renal y/o cardíaca. El tratamiento de la FAVR busca preservar el máximo de parénquima renal y, concomitantemente, erradicar los síntomas y efectos hemodinámicos resultantes de la FAVR. En el presente estudio, se relatarán tres casos de FAVR, incluyendo un caso de FAVR idiopática de novo, que se presentaron con hipertensión e insuficiencia renal y/o cardíaca, y describir la terapéutica adoptada y los resultados obtenidos.The Renal Arteriovenous Fistula (RAVF is a rare and potentially reversible cause of hypertension and kidney and/or heart failure. The treatment of RAVF aims at preserving the most of the renal parenchyma and, concomitantly, eradicating the symptoms and hemodynamic effects caused by the RAVF. The present study reports three cases of RAVF, including one case of a de novo idiopathic RAVF, which presented with hypertension and kidney and/or heart failure and describes the therapeutic measures used to treat these patients as well as the outcomes.

  1. Inverse Function: Pre-Service Teachers' Techniques and Meanings

    Science.gov (United States)

    Paoletti, Teo; Stevens, Irma E.; Hobson, Natalie L. F.; Moore, Kevin C.; LaForest, Kevin R.

    2018-01-01

    Researchers have argued teachers and students are not developing connected meanings for function inverse, thus calling for a closer examination of teachers' and students' inverse function meanings. Responding to this call, we characterize 25 pre-service teachers' inverse function meanings as inferred from our analysis of clinical interviews. After…

  2. A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle

    DEFF Research Database (Denmark)

    Agerholm, Jørgen Steen; McEvoy, Fintan; Heegaard, Steffen

    2017-01-01

    was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Results Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial...... chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member...... of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events...

  3. Norgal: Extraction and de novo assembly of mitochondrial DNA from whole-genome sequencing data

    DEFF Research Database (Denmark)

    Al-Nakeeb, Kosai Ali Ahmed; Petersen, Thomas Nordahl; Sicheritz-Pontén, Thomas

    2017-01-01

    and performing a de novo assembly on a subset of reads that contains these k-mers. The method was applied to WGS data from a panda, brown algae seaweed, butterfly and filamentous fungus. We were able to extract full circular mitochondrial genomes and obtained sequence identities to the reference sequences...

  4. De novo assembly of human genomes with massively parallel short read sequencing

    DEFF Research Database (Denmark)

    Li, Ruiqiang; Zhu, Hongmei; Ruan, Jue

    2010-01-01

    genomes from short read sequences. We successfully assembled both the Asian and African human genome sequences, achieving an N50 contig size of 7.4 and 5.9 kilobases (kb) and scaffold of 446.3 and 61.9 kb, respectively. The development of this de novo short read assembly method creates new opportunities...... for building reference sequences and carrying out accurate analyses of unexplored genomes in a cost-effective way....

  5. Voxel inversion of airborne electromagnetic data for improved model integration

    Science.gov (United States)

    Fiandaca, Gianluca; Auken, Esben; Kirkegaard, Casper; Vest Christiansen, Anders

    2014-05-01

    Inversion of electromagnetic data has migrated from single site interpretations to inversions including entire surveys using spatial constraints to obtain geologically reasonable results. Though, the model space is usually linked to the actual observation points. For airborne electromagnetic (AEM) surveys the spatial discretization of the model space reflects the flight lines. On the contrary, geological and groundwater models most often refer to a regular voxel grid, not correlated to the geophysical model space, and the geophysical information has to be relocated for integration in (hydro)geological models. We have developed a new geophysical inversion algorithm working directly in a voxel grid disconnected from the actual measuring points, which then allows for informing directly geological/hydrogeological models. The new voxel model space defines the soil properties (like resistivity) on a set of nodes, and the distribution of the soil properties is computed everywhere by means of an interpolation function (e.g. inverse distance or kriging). Given this definition of the voxel model space, the 1D forward responses of the AEM data are computed as follows: 1) a 1D model subdivision, in terms of model thicknesses, is defined for each 1D data set, creating "virtual" layers. 2) the "virtual" 1D models at the sounding positions are finalized by interpolating the soil properties (the resistivity) in the center of the "virtual" layers. 3) the forward response is computed in 1D for each "virtual" model. We tested the new inversion scheme on an AEM survey carried out with the SkyTEM system close to Odder, in Denmark. The survey comprises 106054 dual mode AEM soundings, and covers an area of approximately 13 km X 16 km. The voxel inversion was carried out on a structured grid of 260 X 325 X 29 xyz nodes (50 m xy spacing), for a total of 2450500 inversion parameters. A classical spatially constrained inversion (SCI) was carried out on the same data set, using 106054

  6. Obtaining sparse distributions in 2D inverse problems

    OpenAIRE

    Reci, A; Sederman, Andrew John; Gladden, Lynn Faith

    2017-01-01

    The mathematics of inverse problems has relevance across numerous estimation problems in science and engineering. L1 regularization has attracted recent attention in reconstructing the system properties in the case of sparse inverse problems; i.e., when the true property sought is not adequately described by a continuous distribution, in particular in Compressed Sensing image reconstruction. In this work, we focus on the application of L1 regularization to a class of inverse problems; relaxat...

  7. Abel inverse transformation applied to plasma diagnostics

    International Nuclear Information System (INIS)

    Zhu Shiyao

    1987-01-01

    Two methods of Abel inverse transformation are applied to two different test profiles. The effects of random errors of input data, position uncertainty and number of points of input data on the accuracy of inverse transformation have been studied. The two methods are compared in each other

  8. Third Harmonic Imaging using a Pulse Inversion

    DEFF Research Database (Denmark)

    Rasmussen, Joachim; Du, Yigang; Jensen, Jørgen Arendt

    2011-01-01

    The pulse inversion (PI) technique can be utilized to separate and enhance harmonic components of a waveform for tissue harmonic imaging. While most ultrasound systems can perform pulse inversion, only few image the 3rd harmonic component. PI pulse subtraction can isolate and enhance the 3rd...

  9. 3D inversion of full tensor magnetic gradiometry (FTMG) data

    DEFF Research Database (Denmark)

    Zhdanov, Michael; Cai, Hongzhu; Wilson, Glenn

    2011-01-01

    Following recent advances in SQUID technology, full tensor magnetic gradiometry (FTMG) is emerging as a practical exploration method. We introduce 3D regularized focusing inversion for FTMG data. Our model studies show that inversion of magnetic tensor data can significantly improve resolution...... compared to inversion of magnetic vector data for the same model. We present a case study for the 3D inversion of GETMAG® FTMG data acquired over a magnetite skarn at Tallawang, Australia. The results obtained from our 3D inversion agree very well with the known geology of the area....

  10. Introduction to inverse problems for differential equations

    CERN Document Server

    Hasanov Hasanoğlu, Alemdar

    2017-01-01

    This book presents a systematic exposition of the main ideas and methods in treating inverse problems for PDEs arising in basic mathematical models, though it makes no claim to being exhaustive. Mathematical models of most physical phenomena are governed by initial and boundary value problems for PDEs, and inverse problems governed by these equations arise naturally in nearly all branches of science and engineering. The book’s content, especially in the Introduction and Part I, is self-contained and is intended to also be accessible for beginning graduate students, whose mathematical background includes only basic courses in advanced calculus, PDEs and functional analysis. Further, the book can be used as the backbone for a lecture course on inverse and ill-posed problems for partial differential equations. In turn, the second part of the book consists of six nearly-independent chapters. The choice of these chapters was motivated by the fact that the inverse coefficient and source problems considered here a...

  11. Two-dimensional probabilistic inversion of plane-wave electromagnetic data: Methodology, model constraints and joint inversion with electrical resistivity data

    NARCIS (Netherlands)

    Rosas-Carbajal, M.; Linde, N.; Kalscheuer, T.; Vrugt, J.A.

    2014-01-01

    Probabilistic inversion methods based on Markov chain Monte Carlo (MCMC) simulation are well suited to quantify parameter and model uncertainty of nonlinear inverse problems. Yet, application of such methods to CPU-intensive forward models can be a daunting task, particularly if the parameter space

  12. Locoregional symptoms in patients with de novo metastatic prostate cancer: Morbidity, management, and disease outcome.

    Science.gov (United States)

    Patrikidou, Anna; Brureau, Laurent; Casenave, Julien; Albiges, Laurence; Di Palma, Mario; Patard, Jean-Jacques; Baumert, Hervé; Blanchard, Pierre; Bossi, Alberto; Kitikidou, Kyriaki; Massard, Christophe; Fizazi, Karim; Blanchet, Pascal; Loriot, Yohann

    2015-05-01

    The paradigm change observed over the last few years in several solid tumors emphasizes the value of locoregional treatment in the presence of metastatic disease, currently ignored in de novo prostate cancer (CaP). We investigated the effect of the primary tumor that is left untreated on prostate cancer-specific morbidity and mortality, time to castration resistance, and overall survival (OS). We performed a bicentric cohort study. The overall population included de novo metastatic CaP managed at the Genito-Urinary Oncology Unit of the Gustave Roussy Institute and the Urology Clinic of the University Hospital of Pointe-à-Pitre, France. Descriptive statistical and outcome analyses were performed in the overall cohort and also separately in the N+M0 and M+subgroups. The overall cohort included 263 patients. Approximately two-thirds of patients (64%) presented with locoregional symptoms at diagnosis, and 78% throughout the disease. Of the symptomatic patients, 59% required a locoregional procedure. Median OS of patients with locoregional symptoms at diagnosis was shorter than in those who were asymptomatic (47 vs. 86 mo, P = 0.0007); this difference was maintained in the N+M0 and M+subgroups. Median OS and time to castration resistance showed a nonsignificant trend in favor of patients undergoing a locoregional treatment at diagnosis. The presence of symptoms due to locoregional disease in de novo metastatic CaP entails significant morbidity and even mortality and requires active management. Randomized prospective trials are needed to evaluate the role of initial definite locoregional treatment in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. A New Formula for the Inverse Wavelet Transform

    OpenAIRE

    Sun, Wenchang

    2010-01-01

    Finding a computationally efficient algorithm for the inverse continuous wavelet transform is a fundamental topic in applications. In this paper, we show the convergence of the inverse wavelet transform.

  14. Tectonic forward modelling of positive inversion structures

    Energy Technology Data Exchange (ETDEWEB)

    Brandes, C. [Leibniz Univ. Hannover (Germany). Inst. fuer Geologie; Schmidt, C. [Landesamt fuer Bergbau, Energie und Geologie (LBEG), Hannover (Germany)

    2013-08-01

    Positive tectonic inversion structures are common features that were recognized in many deformed sedimentary basins (Lowell, 1995). They are characterized by a two phase fault evolution, where initial normal faulting was followed by reverse faulting along the same fault, accompanied by the development of hanging wall deformation. Analysing the evolution of such inversion structures is important for understanding the tectonics of sedimentary basins and the formation of hydrocarbon traps. We used a 2D tectonic forward modelling approach to simulate the stepwise structural evolution of inversion structures in cross-section. The modelling was performed with the software FaultFold Forward v. 6, which is based on trishear kinematics (Zehnder and Allmendinger, 2000). Key aspect of the study was to derive the controlling factors for the geometry of inversion structures. The simulation results show, that the trishear approach is able to reproduce the geometry of tectonic inversion structures in a realistic way. This implies that inversion structures are simply fault-related folds that initiated as extensional fault-propagation folds, which were subsequently transformed into compressional fault-propagation folds when the stress field changed. The hanging wall deformation is a consequence of the decrease in slip towards the tip line of the fault. Trishear angle and propagation-to-slip ratio are the key controlling factors for the geometry of the fault-related deformation. We tested trishear angles in the range of 30 - 60 and propagation-to-slip ratios between 1 and 2 in increments of 0.1. Small trishear angles and low propagation-to-slip ratios produced tight folds, whereas large trishear angles and high propagation-to-slip ratios led to more open folds with concentric shapes. This has a direct effect on the size and geometry of potential hydrocarbon traps. The 2D simulations can be extended to a pseudo 3D approach, where a set of parallel cross-sections is used to describe

  15. Inverse photon-photon processes

    International Nuclear Information System (INIS)

    Carimalo, C.; Crozon, M.; Kesler, P.; Parisi, J.

    1981-12-01

    We here consider inverse photon-photon processes, i.e. AB → γγX (where A, B are hadrons, in particular protons or antiprotons), at high energies. As regards the production of a γγ continuum, we show that, under specific conditions the study of such processes might provide some information on the subprocess gg γγ, involving a quark box. It is also suggested to use those processes in order to systematically look for heavy C = + structures (quarkonium states, gluonia, etc.) showing up in the γγ channel. Inverse photon-photon processes might thus become a new and fertile area of investigation in high-energy physics, provided the difficult problem of discriminating between direct photons and indirect ones can be handled in a satisfactory way

  16. REGULARIZED D-BAR METHOD FOR THE INVERSE CONDUCTIVITY PROBLEM

    DEFF Research Database (Denmark)

    Knudsen, Kim; Lassas, Matti; Mueller, Jennifer

    2009-01-01

    A strategy for regularizing the inversion procedure for the two-dimensional D-bar reconstruction algorithm based on the global uniqueness proof of Nachman [Ann. Math. 143 (1996)] for the ill-posed inverse conductivity problem is presented. The strategy utilizes truncation of the boundary integral...... the convergence of the reconstructed conductivity to the true conductivity as the noise level tends to zero. The results provide a link between two traditions of inverse problems research: theory of regularization and inversion methods based on complex geometrical optics. Also, the procedure is a novel...

  17. Frequency domain, waveform inversion of laboratory crosswell radar data

    Science.gov (United States)

    Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

    2010-01-01

    A new waveform inversion for crosswell radar is formulated in the frequency-domain for a 2.5D model. The inversion simulates radar waves using the vector Helmholtz equation for electromagnetic waves. The objective function is minimized using a backpropagation method suitable for a 2.5D model. The inversion is tested by processing crosswell radar data collected in a laboratory tank. The estimated model is consistent with the known electromagnetic properties of the tank. The formulation for the 2.5D model can be extended to inversions of acoustic and elastic data.

  18. Decomposing Large Inverse Problems with an Augmented Lagrangian Approach: Application to Joint Inversion of Body-Wave Travel Times and Surface-Wave Dispersion Measurements

    Science.gov (United States)

    Reiter, D. T.; Rodi, W. L.

    2015-12-01

    Constructing 3D Earth models through the joint inversion of large geophysical data sets presents numerous theoretical and practical challenges, especially when diverse types of data and model parameters are involved. Among the challenges are the computational complexity associated with large data and model vectors and the need to unify differing model parameterizations, forward modeling methods and regularization schemes within a common inversion framework. The challenges can be addressed in part by decomposing the inverse problem into smaller, simpler inverse problems that can be solved separately, providing one knows how to merge the separate inversion results into an optimal solution of the full problem. We have formulated an approach to the decomposition of large inverse problems based on the augmented Lagrangian technique from optimization theory. As commonly done, we define a solution to the full inverse problem as the Earth model minimizing an objective function motivated, for example, by a Bayesian inference formulation. Our decomposition approach recasts the minimization problem equivalently as the minimization of component objective functions, corresponding to specified data subsets, subject to the constraints that the minimizing models be equal. A standard optimization algorithm solves the resulting constrained minimization problems by alternating between the separate solution of the component problems and the updating of Lagrange multipliers that serve to steer the individual solution models toward a common model solving the full problem. We are applying our inversion method to the reconstruction of the·crust and upper-mantle seismic velocity structure across Eurasia.· Data for the inversion comprise a large set of P and S body-wave travel times·and fundamental and first-higher mode Rayleigh-wave group velocities.

  19. Investigation of inversion polymorphisms in the human genome using principal components analysis.

    Science.gov (United States)

    Ma, Jianzhong; Amos, Christopher I

    2012-01-01

    Despite the significant advances made over the last few years in mapping inversions with the advent of paired-end sequencing approaches, our understanding of the prevalence and spectrum of inversions in the human genome has lagged behind other types of structural variants, mainly due to the lack of a cost-efficient method applicable to large-scale samples. We propose a novel method based on principal components analysis (PCA) to characterize inversion polymorphisms using high-density SNP genotype data. Our method applies to non-recurrent inversions for which recombination between the inverted and non-inverted segments in inversion heterozygotes is suppressed due to the loss of unbalanced gametes. Inside such an inversion region, an effect similar to population substructure is thus created: two distinct "populations" of inversion homozygotes of different orientations and their 1:1 admixture, namely the inversion heterozygotes. This kind of substructure can be readily detected by performing PCA locally in the inversion regions. Using simulations, we demonstrated that the proposed method can be used to detect and genotype inversion polymorphisms using unphased genotype data. We applied our method to the phase III HapMap data and inferred the inversion genotypes of known inversion polymorphisms at 8p23.1 and 17q21.31. These inversion genotypes were validated by comparing with literature results and by checking Mendelian consistency using the family data whenever available. Based on the PCA-approach, we also performed a preliminary genome-wide scan for inversions using the HapMap data, which resulted in 2040 candidate inversions, 169 of which overlapped with previously reported inversions. Our method can be readily applied to the abundant SNP data, and is expected to play an important role in developing human genome maps of inversions and exploring associations between inversions and susceptibility of diseases.

  20. Optimization of treatment protocols to prevent de novo development of antibiotic resistance in Pseudomonas aeruginosa

    NARCIS (Netherlands)

    Feng, Yanfang

    2016-01-01

    The ever-increasing rate of drug resistant bacteria has been one of the most challenging problem worldwide. This thesis studied the following subjects with mostly the clinically leading pathogen, P. aeruginosa, as the model strain: de novo development of antibiotic resistance in patient during the

  1. Discovery, genotyping and characterization of structural variation and novel sequence at single nucleotide resolution from de novo genome assemblies on a population scale

    DEFF Research Database (Denmark)

    Liu, Siyang; Huang, Shujia; Rao, Junhua

    2015-01-01

    present a novel approach implemented in a single software package, AsmVar, to discover, genotype and characterize different forms of structural variation and novel sequence from population-scale de novo genome assemblies up to nucleotide resolution. Application of AsmVar to several human de novo genome......) as well as large deletions. However, these approaches consistently display a substantial bias against the recovery of complex structural variants and novel sequence in individual genomes and do not provide interpretation information such as the annotation of ancestral state and formation mechanism. We...... assemblies captures a wide spectrum of structural variants and novel sequences present in the human population in high sensitivity and specificity. Our method provides a direct solution for investigating structural variants and novel sequences from de novo genome assemblies, facilitating the construction...

  2. Chromosomal inversion differences correlate with range overlap in passerine birds.

    Science.gov (United States)

    Hooper, Daniel M; Price, Trevor D

    2017-10-01

    Chromosomal inversions evolve frequently but the reasons for this remain unclear. We used cytological descriptions of 411 species of passerine birds to identify large pericentric inversion differences between species, based on the position of the centromere. Within 81 small clades comprising 284 of the species, we found 319 differences on the 9 largest autosomes combined, 56 on the Z chromosome, and 55 on the W chromosome. We also identified inversions present within 32 species. Using a new fossil-calibrated phylogeny, we examined the phylogenetic, demographic and genomic context in which these inversions have evolved. The number of inversion differences between closely related species is consistently predicted by whether the ranges of species overlap, even when time is controlled for as far as is possible. Fixation rates vary across the autosomes, but inversions are more likely to be fixed on the Z chromosome than the average autosome. Variable mutagenic input alone (estimated by chromosome size, map length, GC content or repeat density) cannot explain the differences between chromosomes in the number of inversions fixed. Together, these results support a model in which inversions increase because of their effects on recombination suppression in the face of hybridization. Other factors associated with hybridization may also contribute, including the possibility that inversions contain incompatibility alleles, making taxa less likely to collapse following secondary contact.

  3. Perception of local inhabitants regarding the socioeconomic impact of tourism focused on provisioning wild dolphins in Novo Airao, Central Amazon, Brazil

    Directory of Open Access Journals (Sweden)

    LUIZ C.P.S. ALVES

    2013-11-01

    Full Text Available Botos (Inia geoffrensis are currently provisioned for use in tourist attractions in five sites in the Brazilian Amazon. Despite the known negative effects associated with human-wild dolphin interactions, this activity has been regulated and licensed in the Anavilhanas National Park in Novo Airão, Amazonas State, Brazil. We present an updated evaluation of the perception of the local community concerning the possible socioeconomic impacts of this tourism in Novo Airão. In April 2011, 45 interviews were conducted with inhabitants. A small segment of Novo Airão perceives currently itself as being economically dependent on the botos feeding tourism. Despite that, the economic benefits of this controversial activity apparently are not shared among most inhabitants, and botos feeding tourism is perceived as generating diverse negative effects. We conclude that if the activity was banned or modified into a less impacting tourist activity, this action would probably not majorly affect the lives of the general population.

  4. De novo biosynthesis of volatiles induced by insect herbivory in cotton plants

    International Nuclear Information System (INIS)

    Pare, P.W.; Tumlinson, J.H.

    1997-01-01

    In response to insect feeding on the leaves, cotton (Gossypium hirsutum L.) plants release elevated levels of volatiles, which can serve as a chemical signal that attracts natural enemies of the herbivore to the damaged plant. Pulse-labeling experiments with [13C]CO2 demonstrated that many of the volatiles released, including the acyclic terpenes (E,E)-alpha-farnesene, (E)-beta-farnesene, (E)-beta-ocimene, linalool,(E)-4,8-dimethyl-1,3,7-nonatriene, and (E,E)-4,8,12-trimethyl-1,3,7,11-tridecatetrane, as well as the shikimate pathway product indole, are biosynthesized de novo following insect damage. However, other volatile constituents, including several cyclic terpenes, butyrates, and green leaf volatiles of the lipoxygenase pathway are released from storage or synthesized from stored intermediates. Analysis of volatiles from artificially damaged plants, with and without beet armyworm (Spodoptera exigua Hubner) oral secretions exogenously applied to the leaves, as well as volatiles from beet armyworm-damaged and -undamaged control plants, demonstrated that the application of caterpillar oral secretions increased both the production and release of several volatiles that are synthesized de novo in response to insect feeding. These results establish that the plant plays an active and dynamic role in mediating the interaction between herbivores and natural enemies of herbivores

  5. Are de novo acute heart failure and acutely worsened chronic heart failure two subgroups of the same syndrome?

    Directory of Open Access Journals (Sweden)

    Banović Marko

    2010-01-01

    Full Text Available Introduction. Acute heart failure (AHF is one of the most common diseases in emergency medicine, associated with poor prognosis and high in-hospital and long-term mortality. Objective. To investigate clinical presentation of patients with de novo AHF and acute worsening of chronic heart failure (CHF and to identify differences in blood levels of biomarkers and echocardiography findings. Methods. This prospective study comprised 64 consecutive patients being grouped according to the onset of the disease into patients with the de novo AHF (45.3%, and patients with acute worsening of CHF (54.7%. Results. Acute congestion (60% was the most common manifestation of de novo AHF, whereas pulmonary oedema (43.1% was the most common manifestation of acutely decompensated CHF. Patients with acutely decompensated CHF had significantly higher blood values of creatinine (147.10 vs 113.16 μmol/l; p<0.05, urea (12.63 vs 7.82 mmol/l; p<0.05, BNP (1440.11 vs 712.24 pg/ml; p<001 and NTproBNP (9097.00 vs 2827.70 pg/ml; p<0.01 on admission, and lower values of M-mode left ventricular ejection fraction (LVEF during hospitalization (49.44% vs 42.94%; p<0.05. The follow-up after one year revealed still significantly higher BNP (365.49 vs 164.02 pg/ ml; p<0.05 and lower average values of both LVEF in patients with acutely worsened CHF (46.62% vs 54.41% and 39.52% vs 47.88%; p<0.05. Conclusion. Considering differences in clinical severity on admission, echocardiography and natriuretic peptide values during hospitalization and after one year follow-up, de novo AHF and acutely worsened CHF are two different subgroups of the same syndrome.

  6. Fitness consequences of polymorphic inversions in the zebra finch genome.

    Science.gov (United States)

    Knief, Ulrich; Hemmrich-Stanisak, Georg; Wittig, Michael; Franke, Andre; Griffith, Simon C; Kempenaers, Bart; Forstmeier, Wolfgang

    2016-09-29

    Inversion polymorphisms constitute an evolutionary puzzle: they should increase embryo mortality in heterokaryotypic individuals but still they are widespread in some taxa. Some insect species have evolved mechanisms to reduce the cost of embryo mortality but humans have not. In birds, a detailed analysis is missing although intraspecific inversion polymorphisms are regarded as common. In Australian zebra finches (Taeniopygia guttata), two polymorphic inversions are known cytogenetically and we set out to detect these two and potentially additional inversions using genomic tools and study their effects on embryo mortality and other fitness-related and morphological traits. Using whole-genome SNP data, we screened 948 wild zebra finches for polymorphic inversions and describe four large (12-63 Mb) intraspecific inversion polymorphisms with allele frequencies close to 50 %. Using additional data from 5229 birds and 9764 eggs from wild and three captive zebra finch populations, we show that only the largest inversions increase embryo mortality in heterokaryotypic males, with surprisingly small effect sizes. We test for a heterozygote advantage on other fitness components but find no evidence for heterosis for any of the inversions. Yet, we find strong additive effects on several morphological traits. The mechanism that has carried the derived inversion haplotypes to such high allele frequencies remains elusive. It appears that selection has effectively minimized the costs associated with inversions in zebra finches. The highly skewed distribution of recombination events towards the chromosome ends in zebra finches and other estrildid species may function to minimize crossovers in the inverted regions.

  7. First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

    Science.gov (United States)

    Zago, Alexandre C; Matte, Bruno S; Reginato, Luciana; Iturry-Yamamoto, Germán; Krepsky, Ana; Bergoli, Luiz Carlos C; Balvedi, Julise; Raudales, José C; Saadi, Eduardo K; Zago, Alcides J

    2012-01-01

    Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

  8. Synthesis and inversion of Stokes spectral profiles. Thesis

    International Nuclear Information System (INIS)

    Murphy, G.A.

    1990-01-01

    Observations of Stokes spectral profiles enable the magnetic fields on the Sun's surface to be determined. Inversion is the process whereby the profiles are reduced to magnetic field vectors. One of the most robust, accurate and rapid methods available for inversion uses the least-squares fitting of analytical Stokes profiles. As this technique is suitable for the automated reduction of large sets of data, it has been adopted for use with the Advanced Stokes Polarimeter, presently under development. The limitations of inversion by analytical profile fitting have not been firmly established. Confident analysis of magnet field vectors depends upon the precise interpretation of reduced data. In this work, a framework is introduced which allows such an assessment to be made. The magnetofluid-static sunspot models presented here provide a self-consistent range of physical conditions similar to those in sunspots. Inversion can then be carried out on Stokes profiles synthesized from these known realistic conditions. The capabilities of an inversion technique can be evaluated by comparison between the models and the deduced values

  9. Applications of inverse and algebraic scattering theories

    Energy Technology Data Exchange (ETDEWEB)

    Amos, K. [Qinghua Univ., Beijing, BJ (China). Dept. of Physics

    1997-06-01

    Inverse scattering theories, algebraic scattering theory and exactly solvable scattering potentials are diverse ways by which scattering potentials can be defined from S-functions specified by fits to fixed energy, quantal scattering data. Applications have been made in nuclear (heavy ion and nucleon-nucleus scattering), atomic and molecular (electron scattering from simple molecules) systems. Three inverse scattering approaches are considered in detail; the semiclassical WKB and fully quantal Lipperheide-Fiedeldey method, than algebraic scattering theory is applied to heavy ion scattering and finally the exactly solvable Ginocchio potentials. Some nuclear results are ambiguous but the atomic and molecular inversion potentials are in good agreement with postulated forms. 21 refs., 12 figs.

  10. 3D geophysical inversion for contact surfaces

    Science.gov (United States)

    Lelièvre, Peter; Farquharson, Colin

    2014-05-01

    Geologists' interpretations about the Earth typically involve distinct rock units with contacts (interfaces) between them. In contrast, standard minimum-structure volumetric inversions (performed on meshes of space-filling cells) recover smooth models inconsistent with such interpretations. There are several approaches through which geophysical inversion can help recover models with the desired characteristics. Some authors have developed iterative strategies in which several volumetric inversions are performed with regularization parameters changing to achieve sharper interfaces at automatically determined locations. Another approach is to redesign the regularization to be consistent with the desired model characteristics, e.g. L1-like norms or compactness measures. A few researchers have taken approaches that limit the recovered values to lie within particular ranges, resulting in sharp discontinuities; these include binary inversion, level set methods and clustering strategies. In most of the approaches mentioned above, the model parameterization considers the physical properties in each of the many space-filling cells within the volume of interest. The exception are level set methods, in which a higher dimensional function is parameterized and the contact surface is determined from the zero-level of that function. However, even level-set methods rely on an underlying volumetric mesh. We are researching a fundamentally different type of inversion that parameterizes the Earth in terms of the contact surfaces between rock units. 3D geological Earth models typically comprise wireframe surfaces of tessellated triangles or other polygonal planar facets. This wireframe representation allows for flexible and efficient generation of complicated geological structures. Therefore, a natural approach for representing a geophysical model in an inversion is to parameterize the wireframe contact surfaces as the coordinates of the nodes (facet vertices). The geological and

  11. Review of ankle inversion sprain simulators in the biomechanics laboratory

    Directory of Open Access Journals (Sweden)

    Sophia Chui-Wai Ha

    2015-10-01

    Full Text Available Ankle inversion ligamentous sprain is one of the most common sports injuries. The most direct way is to investigate real injury incidents, but it is unethical and impossible to replicate on test participants. Simulators including tilt platforms, trapdoors, and fulcrum devices were designed to mimic ankle inversion movements in laboratories. Inversion angle was the only element considered in early designs; however, an ankle sprain is composed of inversion and plantarflexion in clinical observations. Inversion velocity is another parameter that increased the reality of simulation. This review summarised the simulators, and aimed to compare and contrast their features and settings.

  12. Optimized simultaneous inversion of primary and multiple reflections; Inversion linearisee simultanee des reflexions primaires et des reflexions multiples

    Energy Technology Data Exchange (ETDEWEB)

    Pelle, L.

    2003-12-01

    The removal of multiple reflections remains a real problem in seismic imaging. Many preprocessing methods have been developed to attenuate multiples in seismic data but none of them is satisfactory in 3D. The objective of this thesis is to develop a new method to remove multiples, extensible in 3D. Contrary to the existing methods, our approach is not a preprocessing step: we directly include the multiple removal in the imaging process by means of a simultaneous inversion of primaries and multiples. We then propose to improve the standard linearized inversion so as to make it insensitive to the presence of multiples in the data. We exploit kinematics differences between primaries and multiples. We propose to pick in the data the kinematics of the multiples we want to remove. The wave field is decomposed into primaries and multiples. Primaries are modeled by the Ray+Born operator from perturbations of the logarithm of impedance, given the velocity field. Multiples are modeled by the Transport operator from an initial trace, given the picking. The inverse problem simultaneously fits primaries and multiples to the data. To solve this problem with two unknowns, we take advantage of the isometric nature of the Transport operator, which allows to drastically reduce the CPU time: this simultaneous inversion is this almost as fast as the standard linearized inversion. This gain of time opens the way to different applications to multiple removal and in particular, allows to foresee the straightforward 3D extension. (author)

  13. Approximation of the inverse G-frame operator

    Indian Academy of Sciences (India)

    ... projection method for -frames which works for all conditional -Riesz frames. We also derive a method for approximation of the inverse -frame operator which is efficient for all -frames. We show how the inverse of -frame operator can be approximated as close as we like using finite-dimensional linear algebra.

  14. Probabilistic inversion for chicken processing lines

    International Nuclear Information System (INIS)

    Cooke, Roger M.; Nauta, Maarten; Havelaar, Arie H.; Fels, Ine van der

    2006-01-01

    We discuss an application of probabilistic inversion techniques to a model of campylobacter transmission in chicken processing lines. Such techniques are indicated when we wish to quantify a model which is new and perhaps unfamiliar to the expert community. In this case there are no measurements for estimating model parameters, and experts are typically unable to give a considered judgment. In such cases, experts are asked to quantify their uncertainty regarding variables which can be predicted by the model. The experts' distributions (after combination) are then pulled back onto the parameter space of the model, a process termed 'probabilistic inversion'. This study illustrates two such techniques, iterative proportional fitting (IPF) and PARmeter fitting for uncertain models (PARFUM). In addition, we illustrate how expert judgement on predicted observable quantities in combination with probabilistic inversion may be used for model validation and/or model criticism

  15. Inverse problems in linear transport theory

    International Nuclear Information System (INIS)

    Dressler, K.

    1988-01-01

    Inverse problems for a class of linear kinetic equations are investigated. The aim is to identify the scattering kernel of a transport equation (corresponding to the structure of a background medium) by observing the 'albedo' part of the solution operator for the corresponding direct initial boundary value problem. This means to get information on some integral operator in an integrodifferential equation through on overdetermined boundary value problem. We first derive a constructive method for solving direct halfspace problems and prove a new factorization theorem for the solutions. Using this result we investigate stationary inverse problems with respect to well posedness (e.g. reduce them to classical ill-posed problems, such as integral equations of first kind). In the time-dependent case we show that a quite general inverse problem is well posed and solve it constructively. (orig.)

  16. Fuzzy logic guided inverse treatment planning

    International Nuclear Information System (INIS)

    Yan Hui; Yin Fangfang; Guan Huaiqun; Kim, Jae Ho

    2003-01-01

    A fuzzy logic technique was applied to optimize the weighting factors in the objective function of an inverse treatment planning system for intensity-modulated radiation therapy (IMRT). Based on this technique, the optimization of weighting factors is guided by the fuzzy rules while the intensity spectrum is optimized by a fast-monotonic-descent method. The resultant fuzzy logic guided inverse planning system is capable of finding the optimal combination of weighting factors for different anatomical structures involved in treatment planning. This system was tested using one simulated (but clinically relevant) case and one clinical case. The results indicate that the optimal balance between the target dose and the critical organ dose is achieved by a refined combination of weighting factors. With the help of fuzzy inference, the efficiency and effectiveness of inverse planning for IMRT are substantially improved

  17. Regularized inversion of controlled source and earthquake data

    International Nuclear Information System (INIS)

    Ramachandran, Kumar

    2012-01-01

    Estimation of the seismic velocity structure of the Earth's crust and upper mantle from travel-time data has advanced greatly in recent years. Forward modelling trial-and-error methods have been superseded by tomographic methods which allow more objective analysis of large two-dimensional and three-dimensional refraction and/or reflection data sets. The fundamental purpose of travel-time tomography is to determine the velocity structure of a medium by analysing the time it takes for a wave generated at a source point within the medium to arrive at a distribution of receiver points. Tomographic inversion of first-arrival travel-time data is a nonlinear problem since both the velocity of the medium and ray paths in the medium are unknown. The solution for such a problem is typically obtained by repeated application of linearized inversion. Regularization of the nonlinear problem reduces the ill posedness inherent in the tomographic inversion due to the under-determined nature of the problem and the inconsistencies in the observed data. This paper discusses the theory of regularized inversion for joint inversion of controlled source and earthquake data, and results from synthetic data testing and application to real data. The results obtained from tomographic inversion of synthetic data and real data from the northern Cascadia subduction zone show that the velocity model and hypocentral parameters can be efficiently estimated using this approach. (paper)

  18. -Dimensional Fractional Lagrange's Inversion Theorem

    Directory of Open Access Journals (Sweden)

    F. A. Abd El-Salam

    2013-01-01

    Full Text Available Using Riemann-Liouville fractional differential operator, a fractional extension of the Lagrange inversion theorem and related formulas are developed. The required basic definitions, lemmas, and theorems in the fractional calculus are presented. A fractional form of Lagrange's expansion for one implicitly defined independent variable is obtained. Then, a fractional version of Lagrange's expansion in more than one unknown function is generalized. For extending the treatment in higher dimensions, some relevant vectors and tensors definitions and notations are presented. A fractional Taylor expansion of a function of -dimensional polyadics is derived. A fractional -dimensional Lagrange inversion theorem is proved.

  19. Unwrapped phase inversion with an exponential damping

    KAUST Repository

    Choi, Yun Seok

    2015-07-28

    Full-waveform inversion (FWI) suffers from the phase wrapping (cycle skipping) problem when the frequency of data is not low enough. Unless we obtain a good initial velocity model, the phase wrapping problem in FWI causes a result corresponding to a local minimum, usually far away from the true solution, especially at depth. Thus, we have developed an inversion algorithm based on a space-domain unwrapped phase, and we also used exponential damping to mitigate the nonlinearity associated with the reflections. We construct the 2D phase residual map, which usually contains the wrapping discontinuities, especially if the model is complex and the frequency is high. We then unwrap the phase map and remove these cycle-based jumps. However, if the phase map has several residues, the unwrapping process becomes very complicated. We apply a strong exponential damping to the wavefield to eliminate much of the residues in the phase map, thus making the unwrapping process simple. We finally invert the unwrapped phases using the back-propagation algorithm to calculate the gradient. We progressively reduce the damping factor to obtain a high-resolution image. Numerical examples determined that the unwrapped phase inversion with a strong exponential damping generated convergent long-wavelength updates without low-frequency information. This model can be used as a good starting model for a subsequent inversion with a reduced damping, eventually leading to conventional waveform inversion.

  20. Coefficient estimates of negative powers and inverse coefficients for ...

    Indian Academy of Sciences (India)

    and the inequality is sharp for the inverse of the Koebe function k(z) = z/(1 − z)2. An alternative approach to the inverse coefficient problem for functions in the class S has been investigated by Schaeffer and Spencer [27] and FitzGerald [6]. Although, the inverse coefficient problem for the class S has been completely solved ...