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Sample records for unique dynamically variant

  1. Identification of Alternative Splice Variants Using Unique Tryptic Peptide Sequences for Database Searches.

    Science.gov (United States)

    Tran, Trung T; Bollineni, Ravi C; Strozynski, Margarita; Koehler, Christian J; Thiede, Bernd

    2017-07-07

    Alternative splicing is a mechanism in eukaryotes by which different forms of mRNAs are generated from the same gene. Identification of alternative splice variants requires the identification of peptides specific for alternative splice forms. For this purpose, we generated a human database that contains only unique tryptic peptides specific for alternative splice forms from Swiss-Prot entries. Using this database allows an easy access to splice variant-specific peptide sequences that match to MS data. Furthermore, we combined this database without alternative splice variant-1-specific peptides with human Swiss-Prot. This combined database can be used as a general database for searching of LC-MS data. LC-MS data derived from in-solution digests of two different cell lines (LNCaP, HeLa) and phosphoproteomics studies were analyzed using these two databases. Several nonalternative splice variant-1-specific peptides were found in both cell lines, and some of them seemed to be cell-line-specific. Control and apoptotic phosphoproteomes from Jurkat T cells revealed several nonalternative splice variant-1-specific peptides, and some of them showed clear quantitative differences between the two states.

  2. Facial reconstruction with a unique osteomyocutaneous DCIA perforator flap variant: a case report.

    Science.gov (United States)

    Wechselberger, G; Schwaiger, K; Hachleitner, J; Oberascher, G; Ensat, F; Larcher, L

    Anatomical variance of the deep circumflex iliac artery is of high clinical value in facial reconstruction using a deep circumflex iliac artery perforator (DCIAP) flap. We present the case of a 76-year-old woman treated with an osteomyocutaneous DCIAP flap variant for facial reconstruction. We also review here the literature on DCIA perforator flaps and the different anatomical variances, which might bring clinical benefits. The observed anatomy in our patient offered the possibility to raise a free flap variant with high mobility of a large skin paddle and a long vascular pedicle combined with a variable osteomuscular portion. The characteristics of the flap thus raised help overcome the disadvantages of the conventional DCIAP flap and offer excellent options for facial reconstruction.

  3. Distinctive tropical forest variants have unique soil microbial communities, but not always low microbial diversity

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    Binu M Tripathi

    2016-04-01

    Full Text Available There has been little study of whether different variants of tropical rainforest have distinct soil microbial communities and levels of diversity. We compared bacterial and fungal community composition and diversity between primary mixed dipterocarp, secondary mixed dipterocarp, white sand heath, inland heath, and peat swamp forests in Brunei Darussalam, northwest Borneo by analyzing Illumina Miseq sequence data of 16S rRNA gene and ITS1 region. We hypothesized that white sand heath, inland heath and peat swamp forests would show lower microbial diversity and relatively distinct microbial communities (compared to MDF primary and secondary forests due to their distinctive environments. We found that soil properties together with bacterial and fungal communities varied significantly between forest types. Alpha and beta-diversity of bacteria was highest in secondary dipterocarp and white sand heath forests. Also, bacterial alpha diversity was strongly structured by pH, adding another instance of this widespread pattern in nature. The alpha diversity of fungi was equally high in all forest types except peat swamp forest, although fungal beta-diversity was highest in primary and secondary mixed dipterocarp forests. The relative abundance of ectomycorrhizal (EcM fungi varied significantly between forest types, with highest relative abundance observed in MDF primary forest. Overall, our results suggest that the soil bacterial and fungal communities in these forest types are to a certain extent predictable and structured by soil properties, but that diversity is not determined by how distinctive the conditions are. This contrasts with the diversity patterns seen in rainforest trees, where distinctive soil conditions have consistently lower tree diversity.

  4. Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements

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    Gross-Paju Katrin

    2010-03-01

    Full Text Available Abstract Background Hereditary spastic paraplegia (HSP is a clinically and genetically heterogeneous disorder that can be an autosomal-dominant, autosomal-recessive, or X-linked disease. The most common autosomal-dominant form of the disease derives from mutations in the SPAST gene. Methods The aim of this study was to analyze 49 patients diagnosed with HSP from the Estonian population for sequence variants of the SPAST gene and to describe the associated phenotypes. Healthy control individuals (n = 100 with no family history of HSP were also analyzed. All patient samples were screened using denaturing high performance liquid chromatography (DHPLC and multiplex ligation-dependent probe amplification (MLPA assay. Samples with abnormal DHPLC and MLPA profiles were sequenced, with the same regions sequenced in control samples. Results Sequence variants of SPAST were identified in 19/49 HSP patients (38.8%, twelve among them had pathogenic mutations. Within the latter group there was one sporadic case. Eight patients had pure, and four - complex HSP. The twelve variants were identified: seven pathogenic (c.1174-1G>C, c.1185delA, c.1276C>T, c.1352_1356delGAGAA, c.1378C>A, c.1518_1519insTC, c.1841_1842insA and five non-pathogenic (c.131C>T, c.484G>A, c.685A>G, c.1245+202delG, c.1245+215G>C. Only 2 of these mutations had previously been described (c.131C>T, c.1245+202delG. Three mutations, c.1174-1G>C, c.1276 C>T, c.1378C>A, showed intrafamilial segregation. Conclusion This study identified new variants of the SPAST gene which included benign missense variants and short insertions/deletions. No large rearrangements were found. Based on these data, 7 new pathogenic variants of HSP are associated with clinical phenotypes.

  5. Quantifying evolutionary dynamics from variant-frequency time series

    Science.gov (United States)

    Khatri, Bhavin S.

    2016-09-01

    From Kimura’s neutral theory of protein evolution to Hubbell’s neutral theory of biodiversity, quantifying the relative importance of neutrality versus selection has long been a basic question in evolutionary biology and ecology. With deep sequencing technologies, this question is taking on a new form: given a time-series of the frequency of different variants in a population, what is the likelihood that the observation has arisen due to selection or neutrality? To tackle the 2-variant case, we exploit Fisher’s angular transformation, which despite being discovered by Ronald Fisher a century ago, has remained an intellectual curiosity. We show together with a heuristic approach it provides a simple solution for the transition probability density at short times, including drift, selection and mutation. Our results show under that under strong selection and sufficiently frequent sampling these evolutionary parameters can be accurately determined from simulation data and so they provide a theoretical basis for techniques to detect selection from variant or polymorphism frequency time-series.

  6. Epidemiological dynamics of norovirus GII.4 variant New Orleans 2009.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; De Grazia, Simona; Calderaro, Adriana; De Conto, Flora; Terio, Valentina; Chironna, Maria; Bonura, Floriana; Pucci, Marzia; Bányai, Kristián; Martella, Vito; Giammanco, Giovanni Maurizio

    2015-09-01

    Norovirus (NoV) is one of the major causes of diarrhoeal disease with epidemic, outbreak and sporadic patterns in humans of all ages worldwide. NoVs of genotype GII.4 cause nearly 80-90 % of all NoV infections in humans. Periodically, some GII.4 strains become predominant, generating major pandemic variants. Retrospective analysis of the GII.4 NoV strains detected in Italy between 2007 and 2013 indicated that the pandemic variant New Orleans 2009 emerged in Italy in the late 2009, became predominant in 2010-2011 and continued to circulate in a sporadic fashion until April 2013. Upon phylogenetic analysis based on the small diagnostic regions A and C, the late New Orleans 2009 NoVs circulating during 2011-2013 appeared to be genetically different from the early New Orleans 2009 strains that circulated in 2010. For a selection of strains, a 3.2 kb genome portion at the 3' end was sequenced. In the partial ORF1 and in the full-length ORF2 and ORF3, the 2011-2013 New Orleans NoVs comprised at least three distinct genetic subclusters. By comparison with sequences retrieved from the databases, these subclusters were also found to circulate globally, suggesting that the local circulation reflected repeated introductions of different strains, rather than local selection of novel viruses. Phylogenetic subclustering did not correlate with changes in residues located in predicted putative capsid epitopes, although several changes affected the P2 domain in epitopes A, C, D and E.

  7. A variant of the dynamic programming algorithm for unit commitment of combined heat and power systems

    DEFF Research Database (Denmark)

    Rong, Aiying; Hakonen, Henri; Lahdelma, Risto

    2008-01-01

    introduce in this paper the DP-RSC1 algorithm, which is a variant of the dynamic programming (DP) algorithm based on linear relaxation of the ON/OFF states of the units and sequential commitment of units one by one. The time complexity of DP-RSC1 is proportional to the number of generating units...

  8. Particle spin dynamics as the grassmann variant of classical mechanics

    International Nuclear Information System (INIS)

    Berezin, F.A.; Marinov, M.S.

    1976-01-01

    A generalization of the calssical mechanics is presented. The dynamical variables are assumed to be elements of an algebra with anticommuting generators (The Grassmann algebra). The action functional and the Poisson brackets are defined. The equations of motion are deduced from the variational principle. The dynamics is described also by means of the Liouville equation for the phase-space distribution. The canonical quantization lead phase-space path integral approach to the quantum theory is also formulated. The theory is applied to describe the particle spin. Classical description of the spin precession and of the spin-orbital forces is given. The phase-space distribution and the interaction with an external field are also considered

  9. Common occurrence of a unique Cryptosporidium ryanae variant in zebu cattle and water buffaloes in the buffer zone of the Chitwan National Park, Nepal.

    Science.gov (United States)

    Feng, Yaoyu; Karna, Sandeep Raj; Dearen, Theresa K; Singh, Dinesh Kumar; Adhikari, Lekh Nath; Shrestha, Aruna; Xiao, Lihua

    2012-04-30

    There are very few studies on the diversity and public health significance of Cryptosporidium species in zebu cattle and water buffaloes in developing countries. In this study, PCR-restriction fragment length polymorphism and DNA sequence analyses of the small-subunit (SSU) rRNA gene were used to genotype Cryptosporidium specimens from 12 zebu cattle calves, 16 water buffalo calves, and four swamp deer (Cervus duvaucelii) collected from the buffer zone of the Chitwan National Park, Nepal. All Cryptosporidium specimens from cattle and buffaloes belonged to Cryptosporidium ryanae, whereas those from deer belonged to Cryptosporidium ubiquitum. Comparison of the SSU rRNA gene sequences obtained with those from earlier studies has identified a nucleotide substitution unique to all C. ryanae isolates from Nepal, in addition to some sequence heterogeneity among different copies of the gene. The finding of the dominance of a unique C. ryanae variant in both zebu cattle and water buffaloes in Nepal indicates that there is unique cryptosporidiosis transmission in bovine animals in the study area, and cross-species transmission of some Cryptosporidium spp. can occur between related animal species sharing the same habitats. Published by Elsevier B.V.

  10. Large eddy simulation of spanwise rotating turbulent channel flow with dynamic variants of eddy viscosity model

    Science.gov (United States)

    Jiang, Zhou; Xia, Zhenhua; Shi, Yipeng; Chen, Shiyi

    2018-04-01

    A fully developed spanwise rotating turbulent channel flow has been numerically investigated utilizing large-eddy simulation. Our focus is to assess the performances of the dynamic variants of eddy viscosity models, including dynamic Vreman's model (DVM), dynamic wall adapting local eddy viscosity (DWALE) model, dynamic σ (Dσ ) model, and the dynamic volumetric strain-stretching (DVSS) model, in this canonical flow. The results with dynamic Smagorinsky model (DSM) and direct numerical simulations (DNS) are used as references. Our results show that the DVM has a wrong asymptotic behavior in the near wall region, while the other three models can correctly predict it. In the high rotation case, the DWALE can get reliable mean velocity profile, but the turbulence intensities in the wall-normal and spanwise directions show clear deviations from DNS data. DVSS exhibits poor predictions on both the mean velocity profile and turbulence intensities. In all three cases, Dσ performs the best.

  11. Dynamic Allan Variance Analysis Method with Time-Variant Window Length Based on Fuzzy Control

    Directory of Open Access Journals (Sweden)

    Shanshan Gu

    2015-01-01

    Full Text Available To solve the problem that dynamic Allan variance (DAVAR with fixed length of window cannot meet the identification accuracy requirement of fiber optic gyro (FOG signal over all time domains, a dynamic Allan variance analysis method with time-variant window length based on fuzzy control is proposed. According to the characteristic of FOG signal, a fuzzy controller with the inputs of the first and second derivatives of FOG signal is designed to estimate the window length of the DAVAR. Then the Allan variances of the signals during the time-variant window are simulated to obtain the DAVAR of the FOG signal to describe the dynamic characteristic of the time-varying FOG signal. Additionally, a performance evaluation index of the algorithm based on radar chart is proposed. Experiment results show that, compared with different fixed window lengths DAVAR methods, the change of FOG signal with time can be identified effectively and the evaluation index of performance can be enhanced by 30% at least by the DAVAR method with time-variant window length based on fuzzy control.

  12. A Novel Pathogenic Variant in the MITF Gene Segregating with a Unique Spectrum of Ocular Findings in an Extended Iranian Waardenburg Syndrome Kindred.

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    Jalilian, Nazanin; Tabatabaiefar, Mohammad A; Bahrami, Tayyeb; Karbasi, Golaleh; Bahramian, Mohammad H; Salimpoor, Abdolrahman; Noori-Daloii, Mohammad R

    2017-06-01

    Waardenburg syndrome (WS) is a rare genetic disorder characterized by abnormal pigmentation of the hair, skin, and iris as well as sensorineural hearing loss. WS is subdivided into 4 major types (WS1-4), where WS2 is characterized by the absence of dystopia canthorum. This study was launched to investigate clinical and molecular characteristics of WS in an extended Iranian WS2 family. A comprehensive clinical investigation was performed. Peripheral blood samples were collected and genomic DNA was extracted. Affected members of the family were studied for possible mutations within the SOX10 , MITF , and SNAI2 genes. Six WS2 individuals affected from a large Iranian WS2 kindred were enrolled. All affected members carried the novel substitution c.877C>T at exon 9 in the MITF gene, which resulted in p.Arg293* at the protein level. None of the healthy members and also of 50 ethnically matched controls had this variant. In addition, a spectrum of unique ocular findings, including nystagmus, chorioretinal degeneration, optic disc hypoplasia, astigmatism, and myopia, was segregated with the mutant allele in the pedigree. Our data provide insight into the genotypic and phenotypic spectrum of WS2 in an Iranian family and could further expand the spectrum of MITF mutations and have implications for genetic counseling on WS in Iran.

  13. Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building.

    Science.gov (United States)

    Cha, Young-Jin; Trocha, Peter; Büyüköztürk, Oral

    2016-07-01

    Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped-mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement.

  14. Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building

    Directory of Open Access Journals (Sweden)

    Young-Jin Cha

    2016-07-01

    Full Text Available Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA, was characterized and modeled as a simplified lumped-mass beam model (SLMM, using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA. Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement.

  15. Field Measurement-Based System Identification and Dynamic Response Prediction of a Unique MIT Building

    Science.gov (United States)

    Cha, Young-Jin; Trocha, Peter; Büyüköztürk, Oral

    2016-01-01

    Tall buildings are ubiquitous in major cities and house the homes and workplaces of many individuals. However, relatively few studies have been carried out to study the dynamic characteristics of tall buildings based on field measurements. In this paper, the dynamic behavior of the Green Building, a unique 21-story tall structure located on the campus of the Massachusetts Institute of Technology (MIT, Cambridge, MA, USA), was characterized and modeled as a simplified lumped-mass beam model (SLMM), using data from a network of accelerometers. The accelerometer network was used to record structural responses due to ambient vibrations, blast loading, and the October 16th 2012 earthquake near Hollis Center (ME, USA). Spectral and signal coherence analysis of the collected data was used to identify natural frequencies, modes, foundation rocking behavior, and structural asymmetries. A relation between foundation rocking and structural natural frequencies was also found. Natural frequencies and structural acceleration from the field measurements were compared with those predicted by the SLMM which was updated by inverse solving based on advanced multiobjective optimization methods using the measured structural responses and found to have good agreement. PMID:27376303

  16. Disparity Map Generation from Illumination Variant Stereo Images Using Efficient Hierarchical Dynamic Programming

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    Viral H. Borisagar

    2014-01-01

    Full Text Available A novel hierarchical stereo matching algorithm is presented which gives disparity map as output from illumination variant stereo pair. Illumination difference between two stereo images can lead to undesirable output. Stereo image pair often experience illumination variations due to many factors like real and practical situation, spatially and temporally separated camera positions, environmental illumination fluctuation, and the change in the strength or position of the light sources. Window matching and dynamic programming techniques are employed for disparity map estimation. Good quality disparity map is obtained with the optimized path. Homomorphic filtering is used as a preprocessing step to lessen illumination variation between the stereo images. Anisotropic diffusion is used to refine disparity map to give high quality disparity map as a final output. The robust performance of the proposed approach is suitable for real life circumstances where there will be always illumination variation between the images. The matching is carried out in a sequence of images representing the same scene, however in different resolutions. The hierarchical approach adopted decreases the computation time of the stereo matching problem. This algorithm can be helpful in applications like robot navigation, extraction of information from aerial surveys, 3D scene reconstruction, and military and security applications. Similarity measure SAD is often sensitive to illumination variation. It produces unacceptable disparity map results for illumination variant left and right images. Experimental results show that our proposed algorithm produces quality disparity maps for both wide range of illumination variant and invariant stereo image pair.

  17. CALCULATION OF THE UNIQUE HIGH-RISE BUILDING FOR EARTHQUAKES IN NONLINEAR DYNAMIC FORMULATION

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    Mkrtychev Oleg Vartanovich

    2016-06-01

    Full Text Available The article contains the calculation of a 80-storey high-rise building on 3-component accelerograms with different dominant frequencies. The “Akhmat Tower” belongs to the complex “Grozny-city 2” and is classified as a unique construction, its height is 400 m. During the construction unique high-rise buildings and high-rise buildings in seismic areas an additional computational studies are required, which should take into account the nonlinear nature of the design. For the case of linear instrumental-synthesized accelerograms, it is necessary to apply nonlinear dynamic methods. The studies were conducted using the software LS-DYNA, implementing the methods of direct integration of the equations of motion by the explicit scheme. The constructive scheme of the building frame is braced, the spatial stability is ensured by load-bearing interior walls, columns and hard disks, and frame metal coatings. The choice of the type and dimensions of the finite element and the step of integration is due to the ability to perform calculations in reasonable time, and to the required accuracy of calculation. For this aim the issues of convergence of the solutions on a number of settlement schemes were investigated with the terms of thickened mesh of finite elements: 0.5 m; 1 m; 2 m; 3 m. As a result of the research it was obtained that the best is to split into finite elements with a characteristic size of 2 m. The calculation of the building is made on rigid foundation. The authors used accelerograms normalized for earthquakes of 8 and 9 points on the MSK-64 scale. The destruction of the elements in the process of loading, and the interaction of the elements during their contact was taken into account, i.e. the calculation was made taking into account physical, geometrical and structural nonlinearities. The article analyzes the results of the calculation. The authors evaluated the seismic stability of the building. Possible ways to improve the seismic

  18. Allele-dependent differences in quorum-sensing dynamics result in variant expression of virulence genes in Staphylococcus aureus.

    Science.gov (United States)

    Geisinger, Edward; Chen, John; Novick, Richard P

    2012-06-01

    Agr is an autoinducing, quorum-sensing system that functions in many Gram-positive species and is best characterized in the pathogen Staphylococcus aureus, in which it is a global regulator of virulence gene expression. Allelic variations in the agr genes have resulted in the emergence of four quorum-sensing specificity groups in S. aureus, which correlate with different strain pathotypes. The basis for these predilections is unclear but is hypothesized to involve the phenomenon of quorum-sensing interference between strains of different agr groups, which may drive S. aureus strain isolation and divergence. Whether properties intrinsic to each agr allele directly influence virulence phenotypes within S. aureus is unknown. In this study, we examined group-specific differences in agr autoinduction and virulence gene regulation by utilizing congenic strains, each harboring a unique S. aureus agr allele, enabling a dissection of agr locus-dependent versus genotype-dependent effects on quorum-sensing dynamics and virulence factor production. Employing a reporter fusion to the principal agr promoter, P3, we observed allele-dependent differences in the timing and magnitude of agr activation. These differences were mediated by polymorphisms within the agrBDCA genes and translated to significant variations in the expression of a key transcriptional regulator, Rot, and of several important exoproteins and surface factors involved in pathogenesis. This work uncovers the contribution of divergent quorum-sensing alleles to variant expression of virulence determinants within a bacterial species.

  19. Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

    Science.gov (United States)

    Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

    2015-09-01

    Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

  20. Dynamic karyotype evolution and unique sex determination systems in Leptidea wood white butterflies.

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    Šíchová, Jindra; Voleníková, Anna; Dincă, Vlad; Nguyen, Petr; Vila, Roger; Sahara, Ken; Marec, František

    2015-05-19

    Chromosomal rearrangements have the potential to limit the rate and pattern of gene flow within and between species and thus play a direct role in promoting and maintaining speciation. Wood white butterflies of the genus Leptidea are excellent models to study the role of chromosome rearrangements in speciation because they show karyotype variability not only among but also within species. In this work, we investigated genome architecture of three cryptic Leptidea species (L. juvernica, L. sinapis and L. reali) by standard and molecular cytogenetic techniques in order to reveal causes of the karyotype variability. Chromosome numbers ranged from 2n = 85 to 91 in L. juvernica and 2n = 69 to 73 in L. sinapis (both from Czech populations) to 2n = 51 to 55 in L. reali (Spanish population). We observed significant differences in chromosome numbers and localization of cytogenetic markers (rDNA and H3 histone genes) within the offspring of individual females. Using FISH with the (TTAGG) n telomeric probe we also documented the presence of multiple chromosome fusions and/or fissions and other complex rearrangements. Thus, the intraspecific karyotype variability is likely due to irregular chromosome segregation of multivalent meiotic configurations. The analysis of female meiotic chromosomes by GISH and CGH revealed multiple sex chromosomes: W1W2W3Z1Z2Z3Z4 in L. juvernica, W1W2W3Z1Z2Z3 in L. sinapis and W1W2W3W4Z1Z2Z3Z4 in L. reali. Our results suggest a dynamic karyotype evolution and point to the role of chromosomal rearrangements in the speciation of Leptidea butterflies. Moreover, our study revealed a curious sex determination system with 3-4 W and 3-4 Z chromosomes, which is unique in the Lepidoptera and which could also have played a role in the speciation process of the three Leptidea species.

  1. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

    DEFF Research Database (Denmark)

    Thompson, Bryony A; Spurdle, Amanda B; Plazzer, John-Paul

    2014-01-01

    and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary...... are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation......The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test...

  2. Quantum Dynamics of Multi Harmonic Oscillators Described by Time Variant Conic Hamiltonian and their Use in Contemporary Sciences

    International Nuclear Information System (INIS)

    Demiralp, Metin

    2010-01-01

    This work focuses on the dynamics of a system of quantum multi harmonic oscillators whose Hamiltonian is conic in positions and momenta with time variant coefficients. While it is simple, this system is useful for modeling the dynamics of a number of systems in contemporary sciences where the equations governing spatial or temporal changes are described by sets of ODEs. The dynamical causal models used readily in neuroscience can be indirectly described by these systems. In this work, we want to show that it is possible to describe these systems using quantum wave function type entities and expectations if the dynamic of the system is related to a set of ODEs.

  3. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

    NARCIS (Netherlands)

    Thompson, Bryony A.; Spurdle, Amanda B.; Plazzer, John-Paul; Greenblatt, Marc S.; Akagi, Kiwamu; Al-Mulla, Fahd; Bapat, Bharati; Bernstein, Inge; Capella, Gabriel; den Dunnen, Johan T.; du Sart, Desiree; Fabre, Aurelie; Farrell, Michael P.; Farrington, Susan M.; Frayling, Ian M.; Frebourg, Thierry; Goldgar, David E.; Heinen, Christopher D.; Holinski-Feder, Elke; Kohonen-Corish, Maija; Robinson, Kristina Lagerstedt; Leung, Suet Yi; Martins, Alexandra; Moller, Pal; Morak, Monika; Nystrom, Minna; Peltomaki, Paivi; Pineda, Marta; Qi, Ming; Ramesar, Rajkumar; Rasmussen, Lene Juel; Royer-Pokora, Brigitte; Scott, Rodney J.; Sijmons, Rolf; Tavtigian, Sean V.; Tops, Carli M.; Weber, Thomas; Wijnen, Juul; Woods, Michael O.; Macrae, Finlay; Genuardi, Maurizio

    The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and

  4. Unique contributions of dynamic versus global measures of parent-child interaction quality in predicting school adjustment.

    Science.gov (United States)

    Bardack, Sarah; Herbers, Janette E; Obradović, Jelena

    2017-09-01

    This study investigates the unique contribution of microsocial and global measures of parent-child positive coregulation (PCR) in predicting children's behavioral and social adjustment in school. Using a community sample of 102 children, ages 4-6, and their parents, we conducted nested path analytic models to identify the unique effects of 2 measures of PCR on school outcomes. Microsocial PCR independently predicted fewer externalizing and inattention/impulsive behaviors in school. Global PCR did not uniquely relate to children's behavioral and social adjustment outcomes. Household socioeconomic status was related to both microsocial and global measures of PCR, but not directly associated with school outcomes. Findings illustrate the importance of using dynamic measures of PCR based on microsocial coding to further understand how the quality of parent-child interaction is related to children's self-regulatory and social development during school transition. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  5. Characterization of Chlamydomonas reinhardtii Core Histones by Top-Down Mass Spectrometry Reveals Unique Algae-Specific Variants and Post-Translational Modifications.

    Science.gov (United States)

    Khan, Aliyya; Eikani, Carlo K; Khan, Hana; Iavarone, Anthony T; Pesavento, James J

    2018-01-05

    The unicellular microalga Chlamydomonas reinhardtii has played an instrumental role in the development of many new fields (bioproducts, biofuels, etc.) as well as the advancement of basic science (photosynthetic apparati, flagellar function, etc.). Chlamydomonas' versatility ultimately derives from the genes encoded in its genome and the way that the expression of these genes is regulated, which is largely influenced by a family of DNA binding proteins called histones. We characterize C. reinhardtii core histones, both variants and their post-translational modifications, by chromatographic separation, followed by top-down mass spectrometry (TDMS). Because TDMS has not been previously used to study Chlamydomonas proteins, we show rampant artifactual protein oxidation using established nuclei purification and histone extraction methods. After addressing oxidation, both histones H3 and H4 are found to each have a single polypeptide sequence that is minimally acetylated and methylated. Surprisingly, we uncover a novel monomethylation at lysine 79 on histone H4 present on all observed molecules. Histone H2B and H2A are found to have two and three variants, respectively, and both are minimally modified. This study provides an updated assessment of the core histone proteins in the green alga C. reinhardtii by top-down mass spectrometry and lays the foundation for further investigation of these essential proteins.

  6. Suprasellar choristoma associated with congenital hydrocephalus, anophthalmia, cleft lip and palate, and clinodactly: a proposed variant of a unique new syndrome

    Directory of Open Access Journals (Sweden)

    Alysse J. Sever, MD

    2015-12-01

    Full Text Available A male infant was born with a bilateral cleft lip and/or palate, absent nasal structures, left anophthalmos, right coloboma, and bilateral fifth digit clinodactly. Brain magnetic resonance imaging revealed severe asymmetric hydrocephalus, absent corpus callosum, a suprasellar mass with a high riding third ventricle, and no pituitary gland. He had a normal male karyotype and normal prenatal laboratory testing. He had no significant family history and no renal, vertebral, gastrointestinal, or cardiac malformations. This combination of central nervous system findings, ocular and craniofacial abnormalities, a normal karyotype, and limited skeletal abnormalities to our knowledge has only been previously described once in the literature in association with a disruption in Pax and Sonic Hedgehog protein pathways, and we conclude this patient represents a variant of this described syndrome.

  7. Full-length genome sequences of five hepatitis C virus isolates representing subtypes 3g, 3h, 3i and 3k, and a unique genotype 3 variant.

    Science.gov (United States)

    Lu, Ling; Li, Chunhua; Yuan, Jie; Lu, Teng; Okamoto, Hiroaki; Murphy, Donald G

    2013-03-01

    We characterized the full-length genomes of five distinct hepatitis C virus (HCV)-3 isolates. These represent the first complete genomes for subtypes 3g and 3h, the second such genomes for 3k and 3i, and of one novel variant presently not assigned to a subtype. Each genome was determined from 18-25 overlapping fragments. They had lengths of 9579-9660 nt and each contained a single ORF encoding 3020-3025 aa. They were isolated from five patients residing in Canada; four were of Asian origin and one was of Somali origin. Phylogenetic analysis using 64 partial NS5B sequences differentiated 10 assigned subtypes, 3a-3i and 3k, and two additional lineages within genotype 3. From the data of this study, HCV-3 full-length sequences are now available for six of the assigned subtypes and one unassigned. Our findings should add insights to HCV evolutionary studies and clinical applications.

  8. Merging spatially variant physical process models under an optimized systems dynamics framework.

    Energy Technology Data Exchange (ETDEWEB)

    Cain, William O. (University of Texas at Austin, Austin, TX); Lowry, Thomas Stephen; Pierce, Suzanne A.; Tidwell, Vincent Carroll

    2007-10-01

    The complexity of water resource issues, its interconnectedness to other systems, and the involvement of competing stakeholders often overwhelm decision-makers and inhibit the creation of clear management strategies. While a range of modeling tools and procedures exist to address these problems, they tend to be case specific and generally emphasize either a quantitative and overly analytic approach or present a qualitative dialogue-based approach lacking the ability to fully explore consequences of different policy decisions. The integration of these two approaches is needed to drive toward final decisions and engender effective outcomes. Given these limitations, the Computer Assisted Dispute Resolution system (CADRe) was developed to aid in stakeholder inclusive resource planning. This modeling and negotiation system uniquely addresses resource concerns by developing a spatially varying system dynamics model as well as innovative global optimization search techniques to maximize outcomes from participatory dialogues. Ultimately, the core system architecture of CADRe also serves as the cornerstone upon which key scientific innovation and challenges can be addressed.

  9. Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report

    Directory of Open Access Journals (Sweden)

    Stanojevic Boban

    2012-06-01

    Full Text Available Abstract Background Struma ovarii (SO is a rare form of ovarian mature teratoma in which thyroid tissue is the predominant element. Because of its rarity, the differential diagnosis between benign and malignant SO has not been clearly defined. It is believed that malignant transformation of SO has similar molecular features with and its prognosis corresponds to that of malignant tumors originating in the thyroid. Case presentation We report 35-year-old woman with bilateral ovarian cysts incidentally detected by ultrasound during the first trimester of pregnancy. Four months after delivery of a healthy child without complication she was admitted to the hospital for acute abdominal pain. Laparoscopic left adnexectomy was performed initially in a regional hospital; right cystectomy was done later in a specialized clinic. Intraoperative frozen section and a final pathology revealed that the cyst from the left ovary was composed of mature teratomatous elements, normal thyroid tissue (>50% and a non-encapsulated focus of follicular variant of papillary thyroid carcinoma (PTC. Normal and cancerous thyroid tissues were tested for BRAF and RAS mutations by direct sequencing, and for RET/PTC rearrangements by RT-PCR/Southern blotting. A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC. Conclusion To the best of our knowledge, this is the first time this mutation is described in a papillary thyroid carcinoma arising in struma in the ovarii. This finding provides further evidence that even rare mutations specific for PTC may occur in such tumors. Molecular testing may be a useful adjunct to common differential diagnostic methods of thyroid malignancy in SO.

  10. Advantages and Drawbacks of Applying Periodic Time-Variant Modal Analysis to Spur Gear Dynamics

    DEFF Research Database (Denmark)

    Pedersen, Rune; Santos, Ilmar; Hede, Ivan Arthur

    2010-01-01

    to ensure sufficient accuracy of the results. The method of time-variant modal analysis is applied, and the changes in the fundamental and the parametric resonance frequencies as a function of the rotational speed of the gears, are found. By obtaining the stationary and parametric parts of the time...... of applying the methodology to wind turbine gearboxes are addressed and elucidated....

  11. Plutonium uniqueness

    International Nuclear Information System (INIS)

    Silver, G.L.

    1984-01-01

    A standard is suggested against which the putative uniqueness of plutonium may be tested. It is common folklore that plutonium is unique among the chemical elements because its four common oxidation states can coexist in the same solution. Whether this putative uniqueness appears only during transit to equilibrium, or only at equilibrium, or all of the time, is not generally made clear. But while the folklore may contain some truth, it cannot be put to test until some measure of 'uniqueness' is agreed upon so that quantitative comparisons are possible. One way of measuring uniqueness is as the magnitude of the product of the mole fractions of the element at equilibrium. A 'coexistence index' is defined and discussed. (author)

  12. Dynamics of changes in the activation of blood coagulation tests at different variants of thromboprophylaxis

    Directory of Open Access Journals (Sweden)

    Олена Миколаївна Клигуненко

    2015-09-01

    Full Text Available Aim: To study an influence of the different variants of thromboprophylaxis on activation of blood coagulation test on the background of surgical aggression. D-dimer concentration in serum is in direct proportion to fibrinolysis activity and to an amount of lysed fibrin. At the same time fibrinolysis activation is followed with an increase of formation of products of fibrin degradation (PFD that interact with fibrin-monomers and increase the number of SFMC.Materials and methods: After informed consent 200 patients were prospectively divided into groups depending on preparation and regimen of thromboprophylaxis. 1 group (n=30 – ungraded heparin (UGH (5000 ОD for 2 hours before surgery 2 times during 7 days after it. 2 group(n=30 nadraparin calcium 9500 anti-Ха МO (0,3 ml for 2 hours before surgery 2500 МО 1 time for a day 7 days after surgery; 3 group(n=48 – endoxaparin sodium(0,2 ml for 2 hours before surgery 1 time a day 7 days; 4 group(n=29 endoxaparin sodium(0,2ml for 8 hours before surgery, 0,2 ml 1 time a day 7 days; 5 group(n=34 – bemiparin sodium(0,2 ml for 2 hours before surgery 0,2 ml 1 time a day 7 days; 6 group(n=29 bemiparin sodium(0,2ml in 6 hours after surgery 1 time a day 7 days. Patients were comparable on sex, concomitant pathology, class АSA (1-2 and type of surgical intervention. There were studied the number of thrombocytes, prothrombin time (PT, INR AFTT, fibrinogen, Х-а factor activity, antithrombin, 111 (AT111, protein C, SFMC, d-dimer before surgery, on 1,5 and 7 day after it.Results and discussions: On the 1 day of postsurgical period the most influence on D-dimer level had presurgical thromboprophylaxis (TPP with UGH and nadroparin calcium. So the D-dimer level exceeded norm respectively by 67 % (р=0,017 and 65,9 % (р<0,05. In patients of 3 and 4 groups D-dimer level was the lowest that formed deficiency by 56 % (р<0,05 and 52,7 % (р<0,05 from the norm respectively. At the same time an analysis of

  13. In vivo imaging of the dynamics of different variants of EGFR in glioblastomas.

    Science.gov (United States)

    Shah, Khalid

    2011-01-01

    A number of altered pathways in cancer cells depend on growth factor receptors. The amplification/alteration of the epidermal growth factor receptor (EGFR) has been shown to play a significant role in enhancing tumor burden in a number of tumors, including malignant glioblastomas (GBM). To dissect the role of EGFR expression in tumor progression in mouse models of cancer and ultimately evaluate targeted therapies, it is necessary to visualize the dynamics of EGFR in real time in vivo. Non-invasive imaging based on quantitative and qualitative changes in light emission by fluorescent and bioluminescent markers offers a huge potential to facilitate drug development. Multiple approaches could be used to follow a molecular target or pathway with the fusion of a bioluminescent-fluorescent marker. This unit describes a protocol for simultaneously imaging EGFR activity and progression of GBM in a mouse model. Human glioma cells transduced with lentiviral vectors bearing different combinations of fluorescent and bioluminescent proteins either fused to EGFR or expressed alone can be grown as monolayers and maintained over several passages. The unit begins with a method for transducing glioma cells with lentiviral vectors for stable expression of these fluorescent and bioluminescent markers in vitro, followed by transplantation of engineered glioma cells in mice, and, finally, sequential bioluminescent imaging of EGFR expression and GBM progression in mice. The protocol details characterization of engineered glioma cells in culture, surgical preparation, craniotomy, cell implantation, animal recovery, and imaging procedures to study kinetics of EGFR expression and GBM progression.

  14. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

    KAUST Repository

    Jackson, Andrew P.

    2014-05-05

    Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5? ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. 2014 The Author(s) 2014.

  15. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction

    KAUST Repository

    Jackson, Andrew P.; Otto, Thomas D.; Darby, Alistair; Ramaprasad, Abhinay; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B.; Moussa, Ehab; Nair, Mridul; Reid, Adam J.; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A.; Weir, William; Wastling, Jonathan M.; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R.; Pain, Arnab

    2014-01-01

    Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5? ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. 2014 The Author(s) 2014.

  16. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host–parasite interaction

    Science.gov (United States)

    Jackson, Andrew P.; Otto, Thomas D.; Darby, Alistair; Ramaprasad, Abhinay; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B.; Moussa, Ehab; Nair, Mridul; Reid, Adam J.; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A.; Weir, William; Wastling, Jonathan M.; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R.; Pain, Arnab

    2014-01-01

    Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5′ ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. PMID:24799432

  17. The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.

    Science.gov (United States)

    Jackson, Andrew P; Otto, Thomas D; Darby, Alistair; Ramaprasad, Abhinay; Xia, Dong; Echaide, Ignacio Eduardo; Farber, Marisa; Gahlot, Sunayna; Gamble, John; Gupta, Dinesh; Gupta, Yask; Jackson, Louise; Malandrin, Laurence; Malas, Tareq B; Moussa, Ehab; Nair, Mridul; Reid, Adam J; Sanders, Mandy; Sharma, Jyotsna; Tracey, Alan; Quail, Mike A; Weir, William; Wastling, Jonathan M; Hall, Neil; Willadsen, Peter; Lingelbach, Klaus; Shiels, Brian; Tait, Andy; Berriman, Matt; Allred, David R; Pain, Arnab

    2014-06-01

    Babesia spp. are tick-borne, intraerythrocytic hemoparasites that use antigenic variation to resist host immunity, through sequential modification of the parasite-derived variant erythrocyte surface antigen (VESA) expressed on the infected red blood cell surface. We identified the genomic processes driving antigenic diversity in genes encoding VESA (ves1) through comparative analysis within and between three Babesia species, (B. bigemina, B. divergens and B. bovis). Ves1 structure diverges rapidly after speciation, notably through the evolution of shortened forms (ves2) from 5' ends of canonical ves1 genes. Phylogenetic analyses show that ves1 genes are transposed between loci routinely, whereas ves2 genes are not. Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families. Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family. Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. An overview of the formulation, existence and uniqueness issues for the initial value problem raised by the dynamics of discrete systems with unilateral contact and dry friction

    Science.gov (United States)

    Ballard, Patrick; Charles, Alexandre

    2018-03-01

    In the end of the seventies, Schatzman and Moreau undertook to revisit the venerable dynamics of rigid bodies with contact and dry friction in the light of more recent mathematics. One claimed objective was to reach, for the first time, a mathematically consistent formulation of an initial value problem associated with the dynamics. The purpose of this article is to make a review of the today state-of-art concerning not only the formulation, but also the issues of existence and uniqueness of solution. xml:lang="fr"

  19. Variants of Moreau's sweeping process

    International Nuclear Information System (INIS)

    Siddiqi, A.H.; Manchanda, P.

    2001-07-01

    In this paper we prove the existence and uniqueness of two variants of Moreau's sweeping process -u'(t) is an element of Nc (t) (u(t)), where in one variant we replace u(t) by u'(t) in the right-hand side of the inclusion and in the second variant u'(t) and u(t) are respectively replaced by u''(t) and u'(t). (author)

  20. Cellulase variants

    Science.gov (United States)

    Blazej, Robert; Toriello, Nicholas; Emrich, Charles; Cohen, Richard N.; Koppel, Nitzan

    2015-07-14

    This invention provides novel variant cellulolytic enzymes having improved activity and/or stability. In certain embodiments the variant cellulotyic enzymes comprise a glycoside hydrolase with or comprising a substitution at one or more positions corresponding to one or more of residues F64, A226, and/or E246 in Thermobifida fusca Cel9A enzyme. In certain embodiments the glycoside hydrolase is a variant of a family 9 glycoside hydrolase. In certain embodiments the glycoside hydrolase is a variant of a theme B family 9 glycoside hydrolase.

  1. GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.; Delino, Nicole S.; Nakata, Hirotomo; Venkateswara Rao, Kalapala; Ghosh, Arun K.; Mitsuya, Hiroaki

    2017-09-25

    We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510 emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.

  2. In situ dynamics of O2, pH, light and photosynthesis in ikaite tufa columns (Ikka Fjord, Greenland – a unique microbial habitat.

    Directory of Open Access Journals (Sweden)

    Erik Christian Løvbjerg Trampe

    2016-05-01

    Full Text Available The Ikka Fjord (SW Greenland harbors a unique microbial habitat in the form of several hundred submarine tufa columns composed of ikaite, a special hexahydrate form of calcium carbonate that precipitates when alkaline phosphate- and carbonate-enriched spring water seeping out of the sea floor meets cold seawater. While several unique heterotrophic microbes have been isolated from the tufa columns, the microbial activity and the boundary conditions for microbial growth in ikaite have remained unexplored. We present the first detailed in situ characterization of the physico-chemical microenvironment and activity of oxygenic phototrophs thriving within the ikaite columns. In situ underwater microsensor measurements of pH, temperature, and irradiance in the porous ikaite crystal matrix, revealed an extreme microenvironment characterized by low temperatures, strong light attenuation, and gradients of pH changing from pH 9 at the outer column surface to above pH 10 over the first 1-2 cm of the ikaite. This outer layer of the freshly deposited ikaite matrix contained densely pigmented yellow and green zones harboring a diverse phototrophic community dominated by diatoms and cyanobacteria, respectively, as shown by amplicon sequencing. In situ O2 measurements, as well as underwater variable chlorophyll fluorescence measurements of photosynthetic activity, demonstrated high levels of oxygenic photosynthesis in this extreme gradient environment with strong irradiance-driven O2 dynamics ranging from anoxia to hyperoxic conditions in the ikaite matrix, albeit the local formation of gas bubbles buffered the day-night dynamics of O2 in the tufa columns. The microbial phototrophs in the ikaite matrix are embedded in exopolymers forming endolithic biofilms that may interact with mineral formation and cementing of ikaite crystals.

  3. In situ Dynamics of O2, pH, Light, and Photosynthesis in Ikaite Tufa Columns (Ikka Fjord, Greenland)-A Unique Microbial Habitat.

    Science.gov (United States)

    Trampe, Erik C L; Larsen, Jens E N; Glaring, Mikkel A; Stougaard, Peter; Kühl, Michael

    2016-01-01

    The Ikka Fjord (SW Greenland) harbors a unique microbial habitat in the form of several hundred submarine tufa columns composed of ikaite, a special hexahydrate form of calcium carbonate that precipitates when alkaline phosphate- and carbonate-enriched spring water seeping out of the sea floor meets cold seawater. While several unique heterotrophic microbes have been isolated from the tufa columns, the microbial activity, and the boundary conditions for microbial growth in ikaite have remained unexplored. We present the first detailed in situ characterization of the physico-chemical microenvironment and activity of oxygenic phototrophs thriving within the ikaite columns. In situ underwater microsensor measurements of pH, temperature, and irradiance in the porous ikaite crystal matrix, revealed an extreme microenvironment characterized by low temperatures, strong light attenuation, and gradients of pH changing from pH 9 at the outer column surface to above pH 10 over the first 1-2 cm of the ikaite. This outer layer of the freshly deposited ikaite matrix contained densely pigmented yellow and green zones harboring a diverse phototrophic community dominated by diatoms and cyanobacteria, respectively, as shown by amplicon sequencing. In situ O2 measurements, as well as underwater variable chlorophyll fluorescence measurements of photosynthetic activity, demonstrated high levels of oxygenic photosynthesis in this extreme gradient environment with strong irradiance-driven O2 dynamics ranging from anoxia to hyperoxic conditions in the ikaite matrix, albeit the local formation of gas bubbles buffered the day-night dynamics of O2 in the tufa columns. The microbial phototrophs in the ikaite matrix are embedded in exopolymers forming endolithic biofilms that may interact with mineral formation and cementing of ikaite crystals.

  4. In situ Dynamics of O2, pH, Light, and Photosynthesis in Ikaite Tufa Columns (Ikka Fjord, Greenland)—A Unique Microbial Habitat

    Science.gov (United States)

    Trampe, Erik C. L.; Larsen, Jens E. N.; Glaring, Mikkel A.; Stougaard, Peter; Kühl, Michael

    2016-01-01

    The Ikka Fjord (SW Greenland) harbors a unique microbial habitat in the form of several hundred submarine tufa columns composed of ikaite, a special hexahydrate form of calcium carbonate that precipitates when alkaline phosphate- and carbonate-enriched spring water seeping out of the sea floor meets cold seawater. While several unique heterotrophic microbes have been isolated from the tufa columns, the microbial activity, and the boundary conditions for microbial growth in ikaite have remained unexplored. We present the first detailed in situ characterization of the physico-chemical microenvironment and activity of oxygenic phototrophs thriving within the ikaite columns. In situ underwater microsensor measurements of pH, temperature, and irradiance in the porous ikaite crystal matrix, revealed an extreme microenvironment characterized by low temperatures, strong light attenuation, and gradients of pH changing from pH 9 at the outer column surface to above pH 10 over the first 1–2 cm of the ikaite. This outer layer of the freshly deposited ikaite matrix contained densely pigmented yellow and green zones harboring a diverse phototrophic community dominated by diatoms and cyanobacteria, respectively, as shown by amplicon sequencing. In situ O2 measurements, as well as underwater variable chlorophyll fluorescence measurements of photosynthetic activity, demonstrated high levels of oxygenic photosynthesis in this extreme gradient environment with strong irradiance-driven O2 dynamics ranging from anoxia to hyperoxic conditions in the ikaite matrix, albeit the local formation of gas bubbles buffered the day-night dynamics of O2 in the tufa columns. The microbial phototrophs in the ikaite matrix are embedded in exopolymers forming endolithic biofilms that may interact with mineral formation and cementing of ikaite crystals. PMID:27242741

  5. A Unique Autothermal Thermophilic Aerobic Digestion Process Showing a Dynamic Transition of Physicochemical and Bacterial Characteristics from the Mesophilic to the Thermophilic Phase.

    Science.gov (United States)

    Tashiro, Yukihiro; Kanda, Kosuke; Asakura, Yuya; Kii, Toshihiko; Cheng, Huijun; Poudel, Pramod; Okugawa, Yuki; Tashiro, Kosuke; Sakai, Kenji

    2018-03-15

    capacity, a short treatment period, and inactivation of pathogens, one of the factors limiting its broad application is the high electric power consumption for aerators with a full-scale bioreactor. We elucidated the dynamics of the bacterial community structures, as well as the physicochemical characteristics, in the ATAD process with a full-scale bioreactor from human excreta for 3 weeks. Our results indicated that this unique process can be divided into three distinguishable phases by an aerator with complete aeration and showed a possibility of shortening the digestion period to approximately 10 days. This research not only helps to identify which bacteria play significant roles and how the process can be improved and controlled but also demonstrates an efficient ATAD process with less electric power consumption for worldwide application. Copyright © 2018 American Society for Microbiology.

  6. Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function.

    Science.gov (United States)

    D'Ursi, Pasqualina; Orro, Alessandro; Morra, Giulia; Moscatelli, Marco; Trombetti, Gabriele; Milanesi, Luciano; Rovida, Ermanna

    2015-01-01

    Activated Protein C (APC) is a multifunctional serine protease, primarily known for its anticoagulant function in the coagulation system. Several studies have already elucidated its role in counteracting apoptosis and inflammation in cells, while significant effort is still ongoing for defining its involvement in sepsis. Earlier literature has shown that the antiseptic function of APC is mediated by its binding to leukocyte integrins, which is due to the presence of the integrin binding motif Arg-Gly-Asp at the N-terminus of the APC catalytic chain. Many natural mutants have been identified in patients with Protein C deficiency diagnosis including a variant of specificity pocket (Gly216Asp). In this work, we present a molecular model of the complex of APC with αVβ3 integrin obtained by protein-protein docking approach. A computational analysis of this variant is hereby presented, based on molecular dynamics and docking simulations, aiming at investigating the effects of the Gly216Asp mutation on the protein conformation and inferring its functional implications. Our study shows that such mutation is likely to impair the protease activity while preserving the overall protein fold. Moreover, superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding. Therapeutic applications could result in this APC mutant which retains antiseptic function without anticoagulant side effects.

  7. From linking of metal-oxide building blocks in a dynamic library to giant clusters with unique properties and towards adaptive chemistry.

    Science.gov (United States)

    Müller, Achim; Gouzerh, Pierre

    2012-11-21

    Following Nature's lessons, today chemists can cross the boundary of the small molecule world to construct multifunctional and highly complex molecular nano-objects up to protein size and even cell-like nanosystems showing responsive sensing. Impressive examples emerge from studies of the solutions of some oxoanions of the early transition metals especially under reducing conditions which enable the controlled linking of metal-oxide building blocks. The latter are available from constitutional dynamic libraries, thus providing the option to generate multifunctional unique nanoscale molecular systems with exquisite architectures, which even opens the way towards adaptive and evolutive (Darwinian) chemistry. The present review presents the first comprehensive report of current knowledge (including synthesis aspects not discussed before) regarding the related giant metal-oxide clusters mainly of the type {Mo(57)M'(6)} (M' = Fe(III), V(IV)) (torus structure), {M(72)M'(30)} (M = Mo, M' = V(IV), Cr(III), Fe(III), Mo(V)), {M(72)Mo(60)} (M = Mo, W) (Keplerates), {Mo(154)}, {Mo(176)}, {Mo(248)} ("big wheels"), and {Mo(368)} ("blue lemon") - all having the important transferable pentagonal {(M)M(5)} groups in common. These discoveries expanded the frontiers of inorganic chemistry to the mesoscopic world, while there is probably no collection of discrete inorganic compounds which offers such a versatile chemistry and the option to study new phenomena of interdisciplinary interest. The variety of different properties of the sphere- and wheel-type metal-oxide-based clusters can directly be related to their unique architectures: The spherical Keplerate-type capsules having 20 crown-ether-type pores and tunable internal functionalities allow the investigation of confined matter as well as that of sphere-surface-supramolecular and encapsulation chemistry - including related new aspects of the biologically important hydrophobic effects - but also of nanoscale ion transport and

  8. [Posttraumatic disturbances in patients with light craniocerebral injury and their correction via various variants of dynamic magnetotherapy].

    Science.gov (United States)

    Cherevashchenko, L A; Moliavchikova, O V; Zhuravlev, M E

    2008-01-01

    Examination of 90 patients in intermediate period of slight craniocerebral injury before and after use of curative technologies with including of dynamic magnetotherapy suboccipitally or transcranially. It is established, that choosing rehabilitation methods, it is necessary to take into consideration clinical manifestation of disease, state of cerebral blood circulation, vegetative nervous system, bioelectrogenesis of cerebrum.

  9. Holoprosencephaly Variant

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-01-01

    Full Text Available The clinical manifestations in 15 patients (6 boys and 9 girls with middle interhemispheric variant (MIH of holoprosencephaly (HPE were compared with classic subtypes (alobar, semilobar, and lobar of HPE in a multicenter study at Stanford University School of Medicine and Lucile Packard Children’s Hospital; Children’s Hospital of Philadelphia; University of California at San Francisco; Texas Scottish Rite Hospital, Dallas; and Kennedy Krieger Institute, Baltimore, MD.

  10. Distinct 3D Architecture and Dynamics of the Human HtrA2(Omi Protease and Its Mutated Variants.

    Directory of Open Access Journals (Sweden)

    Artur Gieldon

    Full Text Available HtrA2(Omi protease controls protein quality in mitochondria and plays a major role in apoptosis. Its HtrA2S306A mutant (with the catalytic serine routinely disabled for an X-ray study to avoid self-degradation is a homotrimer whose subunits contain the serine protease domain (PD and the regulatory PDZ domain. In the inactive state, a tight interdomain interface limits penetration of both PDZ-activating ligands and PD substrates into their respective target sites. We successfully crystalized HtrA2V226K/S306A, whose active counterpart HtrA2V226K has had higher proteolytic activity, suggesting higher propensity to opening the PD-PDZ interface than that of the wild type HtrA2. Yet, the crystal structure revealed the HtrA2V226K/S306A architecture typical of the inactive protein. To get a consistent interpretation of crystallographic data in the light of kinetic results, we employed molecular dynamics (MD. V325D inactivating mutant was used as a reference. Our simulations demonstrated that upon binding of a specific peptide ligand NH2-GWTMFWV-COOH, the PDZ domains open more dynamically in the wild type protease compared to the V226K mutant, whereas the movement is not observed in the V325D mutant. The movement relies on a PDZ vs. PD rotation which opens the PD-PDZ interface in a lid-like (budding flower-like in trimer fashion. The noncovalent hinges A and B are provided by two clusters of interfacing residues, harboring V325D and V226K in the C- and N-terminal PD barrels, respectively. The opening of the subunit interfaces progresses in a sequential manner during the 50 ns MD simulation. In the systems without the ligand only minor PDZ shifts relative to PD are observed, but the interface does not open. Further activation-associated events, e.g. PDZ-L3 positional swap seen in any active HtrA protein (vs. HtrA2, were not observed. In summary, this study provides hints on the mechanism of activation of wtHtrA2, the dynamics of the inactive HtrA2V325D

  11. In situ Dynamics of O2, pH, Light, and Photosynthesis in Ikaite Tufa Columns (Ikka Fjord, Greenland)?A Unique Microbial Habitat

    OpenAIRE

    Trampe, Erik C. L.; Larsen, Jens E. N.; Glaring, Mikkel A.; Stougaard, Peter; K?hl, Michael

    2016-01-01

    The Ikka Fjord (SW Greenland) harbors a unique microbial habitat in the form of several hundred submarine tufa columns composed of ikaite, a special hexahydrate form of calcium carbonate that precipitates when alkaline phosphate- and carbonate-enriched spring water seeping out of the sea floor meets cold seawater. While several unique heterotrophic microbes have been isolated from the tufa columns, the microbial activity, and the boundary conditions for microbial growth in ikaite have remaine...

  12. Functional dissociation between anterior temporal lobe and inferior frontal gyrus in the processing of dynamic body expressions: Insights from behavioral variant frontotemporal dementia.

    Science.gov (United States)

    Jastorff, Jan; De Winter, Francois-Laurent; Van den Stock, Jan; Vandenberghe, Rik; Giese, Martin A; Vandenbulcke, Mathieu

    2016-12-01

    Several brain regions are involved in the processing of emotional stimuli, however, the contribution of specific regions to emotion perception is still under debate. To investigate this issue, we combined behavioral testing, structural and resting state imaging in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and age matched controls, with task-based functional imaging in young, healthy volunteers. As expected, bvFTD patients were impaired in emotion detection as well as emotion categorization tasks, testing dynamic emotional body expressions as stimuli. Interestingly, their performance in the two tasks correlated with gray matter volume in two distinct brain regions, the left anterior temporal lobe for emotion detection and the left inferior frontal gyrus (IFG) for emotion categorization. Confirming this observation, multivoxel pattern analysis in healthy volunteers demonstrated that both ROIs contained information for emotion detection, but that emotion categorization was only possible from the pattern in the IFG. Furthermore, functional connectivity analysis showed reduced connectivity between the two regions in bvFTD patients. Our results illustrate that the mentalizing network and the action observation network perform distinct tasks during emotion processing. In bvFTD, communication between the networks is reduced, indicating one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472-4486, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Single variant bottleneck in the early dynamics of H. influenzae bacteremia in neonatal rats questions the theory of independent action

    Science.gov (United States)

    Shao, Xinxian; Levin, Bruce; Nemenman, Ilya

    2017-08-01

    There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (Sm S and Sm R ) and otherwise isogenic strains of Haemophilus influenzae type b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, Sm S or Sm R . After ruling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that ‘shuts the door’ on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We suggest possible experiments that would be able to confirm or reject our proposed modification of the early infection model.

  14. Context-dependent Dynamic Processes in Attention Deficit/Hyperactivity Disorder : Differentiating Common and Unique Effects of State Regulation Deficits and Delay Aversion

    NARCIS (Netherlands)

    Sonuga-Barke, Edmund J. S.; Wiersema, Jan R.; van der Meere, Jacob J.; Roeyers, Herbert

    The ability to specify differential predictions is a mark of a scientific models' value. State regulation deficits (SRD) and delay aversion (DAv) have both been hypothesized as context-dependent dynamic dysfunctions in ADHD. However, to date there has been no systematic comparison of their common

  15. Quantification of submarine groundwater discharge and its short-term dynamics by linking time-variant end-member mixing analysis and isotope mass balancing (222-Rn)

    Science.gov (United States)

    Petermann, Eric; Knöller, Kay; Stollberg, Reiner; Scholten, Jan; Rocha, Carlos; Weiß, Holger; Schubert, Michael

    2017-04-01

    Submarine groundwater discharge (SGD) plays a crucial role for the water quality of coastal waters due to associated fluxes of nutrients, organic compounds and/or heavy-metals. Thus, the quantification of SGD is essential for evaluating the vulnerability of coastal water bodies with regard to groundwater pollution as well as for understanding the matter cycles of the connected water bodies. Here, we present a scientific approach for quantifying discharge of fresh groundwater (GWf) and recirculated seawater (SWrec), including its short-term temporal dynamics, into the tide-affected Knysna estuary, South Africa. For a time-variant end-member mixing analysis we conducted time-series observations of radon (222Rn) and salinity within the estuary over two tidal cycles in combination with estimates of the related end-members for seawater, river water, GWf and SWrec. The mixing analysis was treated as constrained optimization problem for finding an end-member mixing ratio that simultaneously fits the observed data for radon and salinity best for every time-step. Uncertainty of each mixing ratio was quantified by Monte Carlo simulations of the optimization procedure considering uncertainty in end-member characterization. Results reveal the highest GWf and SWrec fraction in the estuary during peak low tide with averages of 0.8 % and 1.4 %, respectively. Further, we calculated a radon mass balance that revealed a daily radon flux of 4.8 * 108 Bq into the estuary equivalent to a GWf discharge of 29.000 m3/d (9.000-59.000 m3/d for 25th-75th percentile range) and a SWrec discharge of 80.000 m3/d (45.000-130.000 m3/d for 25th-75th percentile range). The uncertainty of SGD reflects the end-member uncertainty, i.e. the spatial heterogeneity of groundwater composition. The presented approach allows the calculation of mixing ratios of multiple uncertain end-members for time-series measurements of multiple parameters. Linking these results with a tracer mass balance allows conversion

  16. Unique structure and dynamics of the EphA5 ligand binding domain mediate its binding specificity as revealed by X-ray crystallography, NMR and MD simulations.

    Directory of Open Access Journals (Sweden)

    Xuelu Huan

    Full Text Available The 16 EphA and EphB receptors represent the largest family of receptor tyrosine kinases, and their interactions with 9 ephrin-A and ephrin-B ligands initiate bidirectional signals controlling many physiological and pathological processes. Most interactions occur between receptor and ephrins of the same class, and only EphA4 can bind all A and B ephrins. To understand the structural and dynamic principles that enable Eph receptors to utilize the same jellyroll β-sandwich fold to bind ephrins, the VAPB-MSP domain, peptides and small molecules, we have used crystallography, NMR and molecular dynamics (MD simulations to determine the first structure and dynamics of the EphA5 ligand-binding domain (LBD, which only binds ephrin-A ligands. Unexpectedly, despite being unbound, the high affinity ephrin-binding pocket of EphA5 resembles that of other Eph receptors bound to ephrins, with a helical conformation over the J-K loop and an open pocket. The openness of the pocket is further supported by NMR hydrogen/deuterium exchange data and MD simulations. Additionally, the EphA5 LBD undergoes significant picosecond-nanosecond conformational exchanges over the loops, as revealed by NMR and MD simulations, but lacks global conformational exchanges on the microsecond-millisecond time scale. This is markedly different from the EphA4 LBD, which shares 74% sequence identity and 87% homology. Consequently, the unbound EphA5 LBD appears to comprise an ensemble of open conformations that have only small variations over the loops and appear ready to bind ephrin-A ligands. These findings show how two proteins with high sequence homology and structural similarity are still able to achieve distinctive binding specificities through different dynamics, which may represent a general mechanism whereby the same protein fold can serve for different functions. Our findings also suggest that a promising strategy to design agonists/antagonists with high affinity and selectivity

  17. Transmission of different variants of PCV2 and viral dynamics in a research facility with pigs mingled from PMWS-affected herds and non-affected herds

    DEFF Research Database (Denmark)

    Dupont, Kitt; Hjulsager, Charlotte Kristiane; Kristensen, C.S.

    2009-01-01

    Post-weaning Multisystemic Wasting Syndrome (PMWS) has been identified in most swine-producing countries worldwide. The disease has resulted in significant health challenges and economic damage to the swine industry. The aim of this study was to determine horizontal transmission of porcine...... the aisle and pens in other compartments). By DNA sequence analysis, eight variants of genotype PCV-2b were identified in the research facility. From the spread of these PCV2-variants it was concluded that PCV2 primarily infects through close contact and nose-to-nose contact. PCV2 genome sequences were...... obtained from selected pigs at arrival to the research facility and again when the same pigs developed PMWS. This analysis showed that pigs from PMWS-affected herds developed PMWS caused by the same variant of PCV2 as they carried when entering the research facility. In contrast, pigs from non...

  18. Somatic cancer variant curation and harmonization through consensus minimum variant level data

    Directory of Open Access Journals (Sweden)

    Deborah I. Ritter

    2016-11-01

    Full Text Available Abstract Background To truly achieve personalized medicine in oncology, it is critical to catalog and curate cancer sequence variants for their clinical relevance. The Somatic Working Group (WG of the Clinical Genome Resource (ClinGen, in cooperation with ClinVar and multiple cancer variant curation stakeholders, has developed a consensus set of minimal variant level data (MVLD. MVLD is a framework of standardized data elements to curate cancer variants for clinical utility. With implementation of MVLD standards, and in a working partnership with ClinVar, we aim to streamline the somatic variant curation efforts in the community and reduce redundancy and time burden for the interpretation of cancer variants in clinical practice. Methods We developed MVLD through a consensus approach by i reviewing clinical actionability interpretations from institutions participating in the WG, ii conducting extensive literature search of clinical somatic interpretation schemas, and iii survey of cancer variant web portals. A forthcoming guideline on cancer variant interpretation, from the Association of Molecular Pathology (AMP, can be incorporated into MVLD. Results Along with harmonizing standardized terminology for allele interpretive and descriptive fields that are collected by many databases, the MVLD includes unique fields for cancer variants such as Biomarker Class, Therapeutic Context and Effect. In addition, MVLD includes recommendations for controlled semantics and ontologies. The Somatic WG is collaborating with ClinVar to evaluate MVLD use for somatic variant submissions. ClinVar is an open and centralized repository where sequencing laboratories can report summary-level variant data with clinical significance, and ClinVar accepts cancer variant data. Conclusions We expect the use of the MVLD to streamline clinical interpretation of cancer variants, enhance interoperability among multiple redundant curation efforts, and increase submission of

  19. J-aggregation, its impact on excited state dynamics and unique solvent effects on macroscopic assembly of a core-substituted naphthalenediimide

    KAUST Repository

    Kar, Haridas; Gehrig, Dominik W.; Laquai, Fré dé ric; Ghosh, Suhrit

    2015-01-01

    Herein we reveal a straightforward supramolecular design for the H-bonding driven J-aggregation of an amine-substituted cNDI in aliphatic hydrocarbons. Transient absorption spectroscopy reveals sub-ps intramolecular electron transfer in isolated NDI molecules in a THF solution followed by a fast recombination process, while a remarkable extension of the excited state lifetime by more than one order of magnitude occurred in methylcyclohexane likely owing to an increased charge-separation as a result of better delocalization of the charge-separated states in J-aggregates. We also describe unique solvent-effects on the macroscopic structure and morphology. While J-aggregation with similar photophysical characteristics was noticed in all the tested aliphatic hydrocarbons, the morphology strongly depends on the “structure” of the solvents. In linear hydrocarbons (n-hexane, n-octane, n-decane or n-dodecane), formation of an entangled fibrillar network leads to macroscopic gelation while in cyclic hydrocarbons (methylcyclohexane or cyclohexane) although having a similar polarity, the cNDI exhibits nanoscale spherical particles. These unprecedented solvent effects were rationalized by establishing structure-dependent specific interactions of the solvent molecules with the cNDI which may serve as a general guideline for solvent-induced morphology-control of structurally related self-assembled materials.

  20. J-aggregation, its impact on excited state dynamics and unique solvent effects on macroscopic assembly of a core-substituted naphthalenediimide

    KAUST Repository

    Kar, Haridas

    2015-03-12

    Herein we reveal a straightforward supramolecular design for the H-bonding driven J-aggregation of an amine-substituted cNDI in aliphatic hydrocarbons. Transient absorption spectroscopy reveals sub-ps intramolecular electron transfer in isolated NDI molecules in a THF solution followed by a fast recombination process, while a remarkable extension of the excited state lifetime by more than one order of magnitude occurred in methylcyclohexane likely owing to an increased charge-separation as a result of better delocalization of the charge-separated states in J-aggregates. We also describe unique solvent-effects on the macroscopic structure and morphology. While J-aggregation with similar photophysical characteristics was noticed in all the tested aliphatic hydrocarbons, the morphology strongly depends on the “structure” of the solvents. In linear hydrocarbons (n-hexane, n-octane, n-decane or n-dodecane), formation of an entangled fibrillar network leads to macroscopic gelation while in cyclic hydrocarbons (methylcyclohexane or cyclohexane) although having a similar polarity, the cNDI exhibits nanoscale spherical particles. These unprecedented solvent effects were rationalized by establishing structure-dependent specific interactions of the solvent molecules with the cNDI which may serve as a general guideline for solvent-induced morphology-control of structurally related self-assembled materials.

  1. Unique Path Partitions

    DEFF Research Database (Denmark)

    Bessenrodt, Christine; Olsson, Jørn Børling; Sellers, James A.

    2013-01-01

    We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions.......We give a complete classification of the unique path partitions and study congruence properties of the function which enumerates such partitions....

  2. Interconverting conformations of variants of the human amyloidogenic protein beta2-microglobulin quantitatively characterized by dynamic capillary electrophoresis and computer simulation

    DEFF Research Database (Denmark)

    Heegaard, Niels H H; Jørgensen, Thomas J D; Cheng, Lei

    2006-01-01

    Capillary electrophoretic separation profiles of cleaved variants of beta2-microglobulin (beta2m) reflect the conformational equilibria existing in solutions of these proteins. The characterization of these equilibria is of interest since beta2m is responsible for amyloid formation in dialysis-re...

  3. Proteomic Analysis of Intact Flagella of Procyclic Trypanosoma brucei Cells Identifies Novel Flagellar Proteins with Unique Sub-localization and Dynamics*

    Science.gov (United States)

    Subota, Ines; Julkowska, Daria; Vincensini, Laetitia; Reeg, Nele; Buisson, Johanna; Blisnick, Thierry; Huet, Diego; Perrot, Sylvie; Santi-Rocca, Julien; Duchateau, Magalie; Hourdel, Véronique; Rousselle, Jean-Claude; Cayet, Nadège; Namane, Abdelkader; Chamot-Rooke, Julia; Bastin, Philippe

    2014-01-01

    Cilia and flagella are complex organelles made of hundreds of proteins of highly variable structures and functions. Here we report the purification of intact flagella from the procyclic stage of Trypanosoma brucei using mechanical shearing. Structural preservation was confirmed by transmission electron microscopy that showed that flagella still contained typical elements such as the membrane, the axoneme, the paraflagellar rod, and the intraflagellar transport particles. It also revealed that flagella severed below the basal body, and were not contaminated by other cytoskeletal structures such as the flagellar pocket collar or the adhesion zone filament. Mass spectrometry analysis identified a total of 751 proteins with high confidence, including 88% of known flagellar components. Comparison with the cell debris fraction revealed that more than half of the flagellum markers were enriched in flagella and this enrichment criterion was taken into account to identify 212 proteins not previously reported to be associated to flagella. Nine of these were experimentally validated including a 14-3-3 protein not yet reported to be associated to flagella and eight novel proteins termed FLAM (FLAgellar Member). Remarkably, they localized to five different subdomains of the flagellum. For example, FLAM6 is restricted to the proximal half of the axoneme, no matter its length. In contrast, FLAM8 is progressively accumulating at the distal tip of growing flagella and half of it still needs to be added after cell division. A combination of RNA interference and Fluorescence Recovery After Photobleaching approaches demonstrated very different dynamics from one protein to the other, but also according to the stage of construction and the age of the flagellum. Structural proteins are added to the distal tip of the elongating flagellum and exhibit slow turnover whereas membrane proteins such as the arginine kinase show rapid turnover without a detectible polarity. PMID:24741115

  4. Proteomic analysis of intact flagella of procyclic Trypanosoma brucei cells identifies novel flagellar proteins with unique sub-localization and dynamics.

    Science.gov (United States)

    Subota, Ines; Julkowska, Daria; Vincensini, Laetitia; Reeg, Nele; Buisson, Johanna; Blisnick, Thierry; Huet, Diego; Perrot, Sylvie; Santi-Rocca, Julien; Duchateau, Magalie; Hourdel, Véronique; Rousselle, Jean-Claude; Cayet, Nadège; Namane, Abdelkader; Chamot-Rooke, Julia; Bastin, Philippe

    2014-07-01

    Cilia and flagella are complex organelles made of hundreds of proteins of highly variable structures and functions. Here we report the purification of intact flagella from the procyclic stage of Trypanosoma brucei using mechanical shearing. Structural preservation was confirmed by transmission electron microscopy that showed that flagella still contained typical elements such as the membrane, the axoneme, the paraflagellar rod, and the intraflagellar transport particles. It also revealed that flagella severed below the basal body, and were not contaminated by other cytoskeletal structures such as the flagellar pocket collar or the adhesion zone filament. Mass spectrometry analysis identified a total of 751 proteins with high confidence, including 88% of known flagellar components. Comparison with the cell debris fraction revealed that more than half of the flagellum markers were enriched in flagella and this enrichment criterion was taken into account to identify 212 proteins not previously reported to be associated to flagella. Nine of these were experimentally validated including a 14-3-3 protein not yet reported to be associated to flagella and eight novel proteins termed FLAM (FLAgellar Member). Remarkably, they localized to five different subdomains of the flagellum. For example, FLAM6 is restricted to the proximal half of the axoneme, no matter its length. In contrast, FLAM8 is progressively accumulating at the distal tip of growing flagella and half of it still needs to be added after cell division. A combination of RNA interference and Fluorescence Recovery After Photobleaching approaches demonstrated very different dynamics from one protein to the other, but also according to the stage of construction and the age of the flagellum. Structural proteins are added to the distal tip of the elongating flagellum and exhibit slow turnover whereas membrane proteins such as the arginine kinase show rapid turnover without a detectible polarity. © 2014 by The

  5. Uniqueness in time measurement

    International Nuclear Information System (INIS)

    Lorenzen, P.

    1981-01-01

    According to P. Janich a clock is defined as an apparatus in which a point ( hand ) is moving uniformly on a straight line ( path ). For the definition of uniformly first the scaling (as a constant ratio of velocities) is defined without clocks. Thereafter the uniqueness of the time measurement can be proved using the prove of scaling of all clocks. But the uniqueness can be defined without scaling, as it is pointed out here. (orig.) [de

  6. CDKL5 variants

    Science.gov (United States)

    Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.

    2017-01-01

    Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392

  7. Lattices with unique complements

    CERN Document Server

    Saliĭ, V N

    1988-01-01

    The class of uniquely complemented lattices properly contains all Boolean lattices. However, no explicit example of a non-Boolean lattice of this class has been found. In addition, the question of whether this class contains any complete non-Boolean lattices remains unanswered. This book focuses on these classical problems of lattice theory and the various attempts to solve them. Requiring no specialized knowledge, the book is directed at researchers and students interested in general algebra and mathematical logic.

  8. Time dependent quantum dynamics study of the O++H2(v=0,j=0)→OH++H ion-molecule reaction and isotopic variants (D2,HD)

    International Nuclear Information System (INIS)

    Martinez, Rodrigo; Sierra, Jose Daniel; Gray, Stephen K.; Gonzalez, Miguel

    2006-01-01

    The time dependent real wave packet method using the helicity decoupling approximation was used to calculate the cross section evolution with collision energy (excitation function) of the O + +H 2 (v=0,j=0)→OH + +H reaction and its isotopic variants with D 2 and HD, using the best available ab initio analytical potential energy surface. The comparison of the calculated excitation functions with exact quantum results and experimental data showed that the present quantum dynamics approach is a very useful tool for the study of the selected and related systems, in a quite wide collision energy interval (approximately 0.0-1.1 eV), involving a much lower computational cost than the quantum exact methods and without a significant loss of accuracy in the cross sections

  9. Variants of cellobiohydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Bott, Richard R.; Foukaraki, Maria; Hommes, Ronaldus Wilhelmus; Kaper, Thijs; Kelemen, Bradley R.; Kralj, Slavko; Nikolaev, Igor; Sandgren, Mats; Van Lieshout, Johannes Franciscus Thomas; Van Stigt Thans, Sander

    2018-04-10

    Disclosed are a number of homologs and variants of Hypocrea jecorina Ce17A (formerly Trichoderma reesei cellobiohydrolase I or CBH1), nucleic acids encoding the same and methods for producing the same. The homologs and variant cellulases have the amino acid sequence of a glycosyl hydrolase of family 7A wherein one or more amino acid residues are substituted and/or deleted.

  10. Is Life Unique?

    Science.gov (United States)

    Abel, David L.

    2011-01-01

    Is life physicochemically unique? No. Is life unique? Yes. Life manifests innumerable formalisms that cannot be generated or explained by physicodynamics alone. Life pursues thousands of biofunctional goals, not the least of which is staying alive. Neither physicodynamics, nor evolution, pursue goals. Life is largely directed by linear digital programming and by the Prescriptive Information (PI) instantiated particularly into physicodynamically indeterminate nucleotide sequencing. Epigenomic controls only compound the sophistication of these formalisms. Life employs representationalism through the use of symbol systems. Life manifests autonomy, homeostasis far from equilibrium in the harshest of environments, positive and negative feedback mechanisms, prevention and correction of its own errors, and organization of its components into Sustained Functional Systems (SFS). Chance and necessity—heat agitation and the cause-and-effect determinism of nature’s orderliness—cannot spawn formalisms such as mathematics, language, symbol systems, coding, decoding, logic, organization (not to be confused with mere self-ordering), integration of circuits, computational success, and the pursuit of functionality. All of these characteristics of life are formal, not physical. PMID:25382119

  11. Migraine Variants in Children

    Science.gov (United States)

    ... Headaches in Children FAQ Migraine Variants In Children Children Get Migraines Too! Learn More Migraine Information Find Help Doctors & Resources Get Connected Join the Conversation Follow Us on Social Media Company About News Resources Privacy Policy Contact Phone: ...

  12. Cancer: Unique to Older Adults

    Science.gov (United States)

    ... A to Z › Cancer › Unique to Older Adults Font size A A A Print Share Glossary Unique ... group with other older people with the same type of cancer. Researchers have found that support groups ...

  13. Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).

    Science.gov (United States)

    Nguyen, Hung; Do, Nhat; Phan, Tuyn; Pham, Tri

    2018-02-01

    The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.

  14. Analysis of the energy development variants

    International Nuclear Information System (INIS)

    Tsvetanov, P.

    1990-01-01

    Analysis of the variants of energy development is made as the third stage of a procedure of energy-economy interrelations dynamics study, the other two stages being the scenarios description and the formulation of the variants. This stage includes a research on the dimensions and the dynamics of the resources demands, the general features and the trends of the national energy development. There is a presentation of a comparative analysis of the variants in terms of economic indices and energy values, computed by the model IMPACT-B. A resource evaluation of the development variants is given in terms of investments, requirements (direct, indirect and total) and limited national resources demands of the energy system. The trends of the national energy development discussed are: trends characterizing the changes in the structure of the energy consumption, resulting from changes in the economy; trends of the energy system impact on the productivity of labor; general trends of the proportionality in the industrial, the household and services sector development. 16 refs., 16 figs., 4 tabs. (R.Ts.)

  15. Plasmodium falciparum centromeres display a unique epigenetic makeup and cluster prior to and during schizogony.

    Science.gov (United States)

    Hoeijmakers, Wieteke A M; Flueck, Christian; Françoijs, Kees-Jan; Smits, Arne H; Wetzel, Johanna; Volz, Jennifer C; Cowman, Alan F; Voss, Till; Stunnenberg, Hendrik G; Bártfai, Richárd

    2012-09-01

    Centromeres are essential for the faithful transmission of chromosomes to the next generation, therefore being essential in all eukaryotic organisms. The centromeres of Plasmodium falciparum, the causative agent of the most severe form of malaria, have been broadly mapped on most chromosomes, but their epigenetic composition remained undefined. Here, we reveal that the centromeric histone variant PfCENH3 occupies a 4-4.5 kb region on each P. falciparum chromosome, which is devoid of pericentric heterochromatin but harbours another histone variant, PfH2A.Z. These CENH3 covered regions pinpoint the exact position of the centromere on all chromosomes and revealed that all centromeric regions have similar size and sequence composition. Immunofluorescence assay of PfCENH3 strongly suggests that P. falciparum centromeres cluster to a single nuclear location prior to and during mitosis and cytokinesis but dissociate soon after invasion. In summary, we reveal a dynamic association of Plasmodium centromeres, which bear a unique epigenetic signature and conform to a strict structure. These findings suggest that DNA-associated and epigenetic elements play an important role in centromere establishment in this important human pathogen. © 2012 Blackwell Publishing Ltd.

  16. The Saccharomyces Genome Database Variant Viewer.

    Science.gov (United States)

    Sheppard, Travis K; Hitz, Benjamin C; Engel, Stacia R; Song, Giltae; Balakrishnan, Rama; Binkley, Gail; Costanzo, Maria C; Dalusag, Kyla S; Demeter, Janos; Hellerstedt, Sage T; Karra, Kalpana; Nash, Robert S; Paskov, Kelley M; Skrzypek, Marek S; Weng, Shuai; Wong, Edith D; Cherry, J Michael

    2016-01-04

    The Saccharomyces Genome Database (SGD; http://www.yeastgenome.org) is the authoritative community resource for the Saccharomyces cerevisiae reference genome sequence and its annotation. In recent years, we have moved toward increased representation of sequence variation and allelic differences within S. cerevisiae. The publication of numerous additional genomes has motivated the creation of new tools for their annotation and analysis. Here we present the Variant Viewer: a dynamic open-source web application for the visualization of genomic and proteomic differences. Multiple sequence alignments have been constructed across high quality genome sequences from 11 different S. cerevisiae strains and stored in the SGD. The alignments and summaries are encoded in JSON and used to create a two-tiered dynamic view of the budding yeast pan-genome, available at http://www.yeastgenome.org/variant-viewer. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  18. Uniquely Strongly Clean Group Rings

    Institute of Scientific and Technical Information of China (English)

    WANG XIU-LAN

    2012-01-01

    A ring R is called clean if every element is the sum of an idempotent and a unit,and R is called uniquely strongly clean (USC for short) if every element is uniquely the sum of an idempotent and a unit that commute.In this article,some conditions on a ring R and a group G such that RG is clean are given.It is also shown that if G is a locally finite group,then the group ring RG is USC if and only if R is USC,and G is a 2-group.The left uniquely exchange group ring,as a middle ring of the uniquely clean ring and the USC ring,does not possess this property,and so does the uniquely exchange group ring.

  19. Impact processes, permafrost dynamics, and climate and environmental variability in the terrestrial Arctic as inferred from the unique 3.6 Myr record of Lake El'gygytgyn, Far East Russia - A review

    Science.gov (United States)

    Wennrich, Volker; Andreev, Andrei A.; Tarasov, Pavel E.; Fedorov, Grigory; Zhao, Wenwei; Gebhardt, Catalina A.; Meyer-Jacob, Carsten; Snyder, Jeffrey A.; Nowaczyk, Norbert R.; Schwamborn, Georg; Chapligin, Bernhard; Anderson, Patricia M.; Lozhkin, Anatoly V.; Minyuk, Pavel S.; Koeberl, Christian; Melles, Martin

    2016-09-01

    Lake El'gygytgyn in Far East Russia is a 3.6 Myr old impact crater lake. Located in an area that has never been affected by Cenozoic glaciations nor desiccation, the unique sediment record of the lake represents the longest continuous sediment archive of the terrestrial Arctic. The surrounding crater is the only impact structure on Earth developed in mostly acid volcanic rocks. Recent studies on the impactite, permafrost, and sediment sequences recovered within the framework of the ICDP "El'gygytgyn Drilling Project" and multiple pre-site surveys yielded new insight into the bedrock origin and cratering processes as well as permafrost dynamics and the climate and environmental history of the terrestrial Arctic back to the mid-Pliocene. Results from the impact rock section recovered during the deep drilling clearly confirm the impact genesis of the El'gygytgyn crater, but indicate an only very reduced fallback impactite sequence without larger coherent melt bodies. Isotope and element data of impact melt samples indicate a F-type asteroid of mixed composition or an ordinary chondrite as the likely impactor. The impact event caused a long-lasting hydrothermal activity in the crater that is assumed to have persisted for c. 300 kyr. Geochemical and microbial analyses of the permafrost core indicate a subaquatic formation of the lower part during lake-level highstand, but a subaerial genesis of the upper part after a lake-level drop after the Allerød. The isotope signal and ion compositions of ground ice is overprinted by several thaw-freeze cycles due to variations in the talik underneath the lake. Modeling results suggest a modern permafrost thickness in the crater of c. 340 m, and further confirm a pervasive character of the talik below Lake El'gygytgyn. The lake sediment sequences shed new leight into the Pliocene and Pleistocene climate and environmental evolution of the Arctic. During the mid-Pliocene, significantly warmer and wetter climatic conditions in

  20. Variants of glycoside hydrolases

    Science.gov (United States)

    Teter, Sarah [Davis, CA; Ward, Connie [Hamilton, MT; Cherry, Joel [Davis, CA; Jones, Aubrey [Davis, CA; Harris, Paul [Carnation, WA; Yi, Jung [Sacramento, CA

    2011-04-26

    The present invention relates to variants of a parent glycoside hydrolase, comprising a substitution at one or more positions corresponding to positions 21, 94, 157, 205, 206, 247, 337, 350, 373, 383, 438, 455, 467, and 486 of amino acids 1 to 513 of SEQ ID NO: 2, and optionally further comprising a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2 a substitution at one or more positions corresponding to positions 8, 22, 41, 49, 57, 113, 193, 196, 226, 227, 246, 251, 255, 259, 301, 356, 371, 411, and 462 of amino acids 1 to 513 of SEQ ID NO: 2, wherein the variants have glycoside hydrolase activity. The present invention also relates to nucleotide sequences encoding the variant glycoside hydrolases and to nucleic acid constructs, vectors, and host cells comprising the nucleotide sequences.

  1. A geometric framework for evaluating rare variant tests of association.

    Science.gov (United States)

    Liu, Keli; Fast, Shannon; Zawistowski, Matthew; Tintle, Nathan L

    2013-05-01

    The wave of next-generation sequencing data has arrived. However, many questions still remain about how to best analyze sequence data, particularly the contribution of rare genetic variants to human disease. Numerous statistical methods have been proposed to aggregate association signals across multiple rare variant sites in an effort to increase statistical power; however, the precise relation between the tests is often not well understood. We present a geometric representation for rare variant data in which rare allele counts in case and control samples are treated as vectors in Euclidean space. The geometric framework facilitates a rigorous classification of existing rare variant tests into two broad categories: tests for a difference in the lengths of the case and control vectors, and joint tests for a difference in either the lengths or angles of the two vectors. We demonstrate that genetic architecture of a trait, including the number and frequency of risk alleles, directly relates to the behavior of the length and joint tests. Hence, the geometric framework allows prediction of which tests will perform best under different disease models. Furthermore, the structure of the geometric framework immediately suggests additional classes and types of rare variant tests. We consider two general classes of tests which show robustness to noncausal and protective variants. The geometric framework introduces a novel and unique method to assess current rare variant methodology and provides guidelines for both applied and theoretical researchers. © 2013 Wiley Periodicals, Inc.

  2. Diabetes: Unique to Older Adults

    Science.gov (United States)

    ... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

  3. Incidental copy-number variants identified by routine genome testing in a clinical population

    Science.gov (United States)

    Boone, Philip M.; Soens, Zachry T.; Campbell, Ian M.; Stankiewicz, Pawel; Cheung, Sau Wai; Patel, Ankita; Beaudet, Arthur L.; Plon, Sharon E.; Shaw, Chad A.; McGuire, Amy L.; Lupski, James R.

    2013-01-01

    Purpose Mutational load of susceptibility variants has not been studied on a genomic scale in a clinical population, nor has the potential to identify these mutations as incidental findings during clinical testing been systematically ascertained. Methods Array comparative genomic hybridization, a method for genome-wide detection of DNA copy-number variants, was performed clinically on DNA from 9,005 individuals. Copy-number variants encompassing or disrupting single genes were identified and analyzed for their potential to confer predisposition to dominant, adult-onset disease. Multigene copy-number variants affecting dominant, adult-onset cancer syndrome genes were also assessed. Results In our cohort, 83 single-gene copy-number variants affected 40 unique genes associated with dominant, adult-onset disorders and unrelated to the patients’ referring diagnoses (i.e., incidental) were found. Fourteen of these copy-number variants are likely disease-predisposing, 25 are likely benign, and 44 are of unknown clinical consequence. When incidental copy-number variants spanning up to 20 genes were considered, 27 copy-number variants affected 17 unique genes associated with dominant, adult-onset cancer predisposition. Conclusion Copy-number variants potentially conferring susceptibility to adult-onset disease can be identified as incidental findings during routine genome-wide testing. Some of these mutations may be medically actionable, enabling disease surveillance or prevention; however, most incidentally observed single-gene copy-number variants are currently of unclear significance to the patient. PMID:22878507

  4. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

  5. Accurate genotyping across variant classes and lengths using variant graphs

    DEFF Research Database (Denmark)

    Sibbesen, Jonas Andreas; Maretty, Lasse; Jensen, Jacob Malte

    2018-01-01

    of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used...... collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment...... to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a ‘variation-prior’ database containing already known variants significantly improves sensitivity....

  6. The liberal illusion of uniqueness.

    Science.gov (United States)

    Stern, Chadly; West, Tessa V; Schmitt, Peter G

    2014-01-01

    In two studies, we demonstrated that liberals underestimate their similarity to other liberals (i.e., display truly false uniqueness), whereas moderates and conservatives overestimate their similarity to other moderates and conservatives (i.e., display truly false consensus; Studies 1 and 2). We further demonstrated that a fundamental difference between liberals and conservatives in the motivation to feel unique explains this ideological distinction in the accuracy of estimating similarity (Study 2). Implications of the accuracy of consensus estimates for mobilizing liberal and conservative political movements are discussed.

  7. Hairy cell leukemia-variant

    International Nuclear Information System (INIS)

    Quadri, Mohammad I.; Al-Sheikh, Iman H.

    2001-01-01

    Hairy cell leukaemia variant is a very rare chronic lymphoproliferative disorder and is closely related to hairy cell leukemia. We hereby describe a case of hairy cell leukaemia variant for the first time in Saudi Arabia. An elderly Saudi man presented with pallor, massive splenomegaly, and moderate hepatomegaly. Hemoglobin was 7.7 g/dl, Platelets were 134 x109/l and white blood count was 140x10 9/l with 97% being abnormal lymphoid cells with cytoplasmic projections. The morphology, cytochemistry, and immunophenotype of the lymphoid cells were classical of hairy cell leukaemia variant. The bone marrow was easily aspirated and findings were consistent with hairy cell leukaemia variant. (author)

  8. Product Variant Master as a Means to Handle Variant Design

    DEFF Research Database (Denmark)

    Hildre, Hans Petter; Mortensen, Niels Henrik; Andreasen, Mogens Myrup

    1996-01-01

    be implemented in the CAD system I-DEAS. A precondition for high degree of computer support is identification of a product variant master from which new variants can be derived. This class platform defines how a product build up fit certain production methods and rules governing determination of modules...

  9. Unique properties of Drosophila spermatocyte primary cilia

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Riparbelli

    2013-09-01

    The primary cilium is an essential organelle required for animal development and adult homeostasis that is found on most animal cells. The primary cilium contains a microtubule-based axoneme cytoskeleton that typically grows from the mother centriole in G0/G1 phase of the cell cycle as a membrane-bound compartment that protrudes from the cell surface. A unique system of bidirectional transport, intraflagellar transport (IFT, maintains the structure and function of cilia. While the axoneme is dynamic, growing and shrinking at its tip, at the same time it is very stable to the effects of microtubule-targeting drugs. The primary cilia found on Drosophila spermatocytes diverge from the general rules of primary cilium biology in several respects. Among these unique attributes, spermatocyte cilia assemble from all four centrioles in an IFT-independent manner in G2 phase, and persist continuously through two cell divisions. Here, we show that Drosophila spermatocyte primary cilia are extremely sensitive to microtubule-targeting drugs, unlike their mammalian counterparts. Spermatocyte cilia and their axonemes fail to assemble or be maintained upon nocodazole treatment, while centriole replication appears unperturbed. On the other hand, paclitaxel (Taxol, a microtubule-stabilizing drug, disrupted transition zone assembly and anchoring to the plasma membrane while causing spermatocyte primary cilia to grow extensively long during the assembly/elongation phase, but did not overtly affect the centrioles. However, once assembled to their mature length, spermatocyte cilia appeared unaffected by Taxol. The effects of these drugs on axoneme dynamics further demonstrate that spermatocyte primary cilia are endowed with unique assembly properties.

  10. Granulomatous slack skin syndrome: Report of a unique case.

    Science.gov (United States)

    Maheswari, S Uma; Sampath, V; Ramesh, A

    2018-01-01

    Granulomatous slack skin syndrome is a rare variant of cutaneous T-cell lymphoma (mycosis fungoides). It is characterized clinically by redundant skin folds, which show a predilection towards flexural areas such as the axilla and the groin. Histologically, it shows a granulomatous T-cell infiltrate and loss of elastic tissue. It has an indolent but progressive course; and is usually refractory to treatment. We report a unique case of slack skin syndrome, sparing the classical sites with rapid and unusual involvement of non-intertriginous areas.

  11. Kosovo case: A unique arbitrariness

    Directory of Open Access Journals (Sweden)

    Nakarada Radmila

    2007-01-01

    Full Text Available The end of Cold war, contrary to expectations has brought new conflicts and forms of violence, new divisions and new relativizations of the international legal order. Taking as an example the endeavors to resolve the Kosovo conflict, the author attempts to indicate the broader implications of the international efforts to constitute an independent state on part of the territory of an existing sovereign state. The arguments used to justify the redefinition of the borders of the Serbian state without its consent, the moral, democratic, peace arguments, are reviewed. Particular attention is paid to the argument that Kosovo is a unique case and therefore unique rules should be applied. The author seeks to understand the deeper significance of these efforts, concluding that dismantling the present international legal order is not only a potential danger but a possible aim.

  12. Uniqueness theorems in linear elasticity

    CERN Document Server

    Knops, Robin John

    1971-01-01

    The classical result for uniqueness in elasticity theory is due to Kirchhoff. It states that the standard mixed boundary value problem for a homogeneous isotropic linear elastic material in equilibrium and occupying a bounded three-dimensional region of space possesses at most one solution in the classical sense, provided the Lame and shear moduli, A and J1 respectively, obey the inequalities (3 A + 2 J1) > 0 and J1>O. In linear elastodynamics the analogous result, due to Neumann, is that the initial-mixed boundary value problem possesses at most one solution provided the elastic moduli satisfy the same set of inequalities as in Kirchhoffs theorem. Most standard textbooks on the linear theory of elasticity mention only these two classical criteria for uniqueness and neglect altogether the abundant literature which has appeared since the original publications of Kirchhoff. To remedy this deficiency it seems appropriate to attempt a coherent description ofthe various contributions made to the study of uniquenes...

  13. Dynamics

    CERN Document Server

    Goodman, Lawrence E

    2001-01-01

    Beginning text presents complete theoretical treatment of mechanical model systems and deals with technological applications. Topics include introduction to calculus of vectors, particle motion, dynamics of particle systems and plane rigid bodies, technical applications in plane motions, theory of mechanical vibrations, and more. Exercises and answers appear in each chapter.

  14. The Uniqueness of Milton Friedman

    OpenAIRE

    J. Daniel Hammond

    2013-01-01

    That there is no Milton Friedman today is not a mystery; the mystery is how Milton Friedman could have been. The facts of Friedman’s biography make him unique among twentieth-century public figures. He had extensive knowledge and expertise in mathematics and statistics. Yet he became a critic of ‘formal’ theory, exemplified by mathematical economics, that failed to engage with real-world facts and data, and of econometric modeling that presumed more knowledge of economic structure than Friedm...

  15. Unique Features of Halophilic Proteins.

    Science.gov (United States)

    Arakawa, Tsutomu; Yamaguchi, Rui; Tokunaga, Hiroko; Tokunaga, Masao

    2017-01-01

    Proteins from moderate and extreme halophiles have unique characteristics. They are highly acidic and hydrophilic, similar to intrinsically disordered proteins. These characteristics make the halophilic proteins soluble in water and fold reversibly. In addition to reversible folding, the rate of refolding of halophilic proteins from denatured structure is generally slow, often taking several days, for example, for extremely halophilic proteins. This slow folding rate makes the halophilic proteins a novel model system for folding mechanism analysis. High solubility and reversible folding also make the halophilic proteins excellent fusion partners for soluble expression of recombinant proteins.

  16. A unique gesture of sharing

    International Nuclear Information System (INIS)

    Mustafa, T.

    1985-01-01

    The Atoms for Peace program was a unique gesture of sharing on the part of the leading industrialized nation, and has very few parallels in modern history. The author says one of the major advantages of the program for developing nations was the much needed stimulation of their indigenous science and technology efforts and the awakening of their governments to the multifaceted benefits of atomic energy. The author discusses how the program benefited Pakistan in the production of electrical energy and in the application of nuclear techniques in the fields of agriculture and medicine, which help to alleviate hunger and combat disease

  17. Discovering Reference Process Models by Mining Process Variants

    NARCIS (Netherlands)

    Li, C.; Reichert, M.U.; Wombacher, Andreas

    Recently, a new generation of adaptive Process-Aware Information Systems (PAIS) has emerged, which allows for dynamic process and service changes (e.g., to insert, delete, and move activities and service executions in a running process). This, in turn, has led to a large number of process variants

  18. Myxoid variant of adrenocortical tumors. Report of two cases with unique entity

    International Nuclear Information System (INIS)

    Suzuki, Rumi; Ito, Yukio; Okamoto, Takahiro; Iihara, Masatoshi; Obara, Takao; Tsuiki, Mika; Takano, Kazue; Nishikawa, Toshio; Aiba, Motohiko

    2007-01-01

    Cases in the title are reported. Case 1, a 57-year old female, had fracture and reduced limbic muscular force due to Cushing syndrome. CT image gave a big tumor in the left adrenal and 131 I-adosterol scintigraphy revealed the increased and decreased 131 I accumulation in the left and right adrenal, respectively: the carcinoma suspected. Only tumor portion was dissected out and was found to be an adenoma in histology. Case 2, a 50-year old male, had Cushing syndrome and extreme obesity. Previous CT presented a big tumor in the left adrenal; biopsy was performed under CT; and before surgery, the tumor was partly calcified in CT, which was found to be a carcinoma. In both cases, histology gave findings of the interstitial and extracellular disposition of myxoid material and of pseudoglandular pattern. (R.T.)

  19. Is physical space unique or optional

    International Nuclear Information System (INIS)

    Ekstein, H.; Centre National de la Recherche Scientifique, 13 - Marseille

    1975-02-01

    There are two concepts of the physical space-time. One, S(F), is that of a fixed arena in which events take place. The other S(D), is that of a space-time shaped by events. The second depends on the state (initial conditions) or on the external field, the first does not. The main assertions of the present paper are: 1) the fixed space-time S(F) is neither incompatibles with nor made superfluous, by Einstein's theory. S(F) is experimentally explorable, unique, and probably identical with Minkowski space M. 2) The dynamical space S(D) is largely optional. It can be chosen to be M, but the natural choice is Einstein's pseudo-Riemanian manifold [fr

  20. Prebiotic Competition between Information Variants, With Low Error Catastrophe Risks

    Directory of Open Access Journals (Sweden)

    Radu Popa

    2015-07-01

    Full Text Available During competition for resources in primitive networks increased fitness of an information variant does not necessarily equate with successful elimination of its competitors. If variability is added fast to a system, speedy replacement of pre-existing and less-efficient forms of order is required as novel information variants arrive. Otherwise, the information capacity of the system fills up with information variants (an effect referred as “error catastrophe”. As the cost for managing the system’s exceeding complexity increases, the correlation between performance capabilities of information variants and their competitive success decreases, and evolution of such systems toward increased efficiency slows down. This impasse impedes the understanding of evolution in prebiotic networks. We used the simulation platform Biotic Abstract Dual Automata (BiADA to analyze how information variants compete in a resource-limited space. We analyzed the effect of energy-related features (differences in autocatalytic efficiency, energy cost of order, energy availability, transformation rates and stability of order on this competition. We discuss circumstances and controllers allowing primitive networks acquire novel information with minimal “error catastrophe” risks. We present a primitive mechanism for maximization of energy flux in dynamic networks. This work helps evaluate controllers of evolution in prebiotic networks and other systems where information variants compete.

  1. A review of velocity-type PSO variants

    OpenAIRE

    Ivo Sousa-Ferreira; Duarte Sousa

    2017-01-01

    This paper presents a review of the particular variants of particle swarm optimization, based on the velocity-type class. The original particle swarm optimization algorithm was developed as an unconstrained optimization technique, which lacks a model that is able to handle constrained optimization problems. The particle swarm optimization and its inapplicability in constrained optimization problems are solved using the dynamic-objective constraint-handling method. The dynamic-objective constr...

  2. Thermodynamics: The Unique Universal Science

    Directory of Open Access Journals (Sweden)

    Wassim M. Haddad

    2017-11-01

    Full Text Available Thermodynamics is a physical branch of science that governs the thermal behavior of dynamical systems from those as simple as refrigerators to those as complex as our expanding universe. The laws of thermodynamics involving conservation of energy and nonconservation of entropy are, without a doubt, two of the most useful and general laws in all sciences. The first law of thermodynamics, according to which energy cannot be created or destroyed, merely transformed from one form to another, and the second law of thermodynamics, according to which the usable energy in an adiabatically isolated dynamical system is always diminishing in spite of the fact that energy is conserved, have had an impact far beyond science and engineering. In this paper, we trace the history of thermodynamics from its classical to its postmodern forms, and present a tutorial and didactic exposition of thermodynamics as it pertains to some of the deepest secrets of the universe.

  3. Unique Features of Mobile Commerce

    Institute of Scientific and Technical Information of China (English)

    DING Xiaojun; IIJIMA Junichi; HO Sho

    2004-01-01

    While the market potentials and impacts of web-based e-commerce are still in the ascendant, the advances in wireless technologies and mobile networks have brought about a new business opportunity and research attention, what is termed mobile commerce. Commonly, mobile commerce is considered to be another new application of existing web-based e-commerce onto wireless networks, but as an independent business area, mobile commerce has its own advantages and challenges as opposed to traditional e-commerce applications. This paper focuses on exploring the unique features of mobile commerce as. Compared with traditional e-commerce. Also, there are still some limitations arisen in m-commerce in contrast to web-based e-commerce. Finally, current state of mobile commerce in Japan is presented in brief, with an introduction of several cases involving mobile commerce applications in today 's marketplace.

  4. Unique features of space reactors

    International Nuclear Information System (INIS)

    Buden, D.

    1990-01-01

    This paper reports on space reactors that are designed to meet a unique set of requirements; they must be sufficiently compact to be launched in a rocket to their operational location, operate for many years without maintenance and servicing, operate in extreme environments, and reject heat by radiation to space. To meet these restrictions, operating temperatures are much greater than in terrestrial power plants, and the reactors tend to have a fast neutron spectrum. Currently, a new generation of space reactor power plants is being developed. The major effort is in the SP-100 program, where the power plant is being designed for seven years of full power, and no maintenance operation at a reactor outlet operating temperature of 1350 K

  5. The Uniqueness of Islamic Culture

    Directory of Open Access Journals (Sweden)

    Sinan YILMAZ

    2014-12-01

    Full Text Available Abstract This paper examines the main reasons behind why Islamic culture is different than other cultures. In the introduction part of the paper, the usage area of the words culture and civilization were tackled. In the first part of the paper, an evaluation of the uniqueness of Islamic culture was made and examples about this were given. In the second part of the paper, evaluations about how Islamic culture has struggled with modernization and secularization and how it has shaped itself as a result of this were made. In the third part of the paper, the situation in which Islamic civilization has regressed against the Western civilization causing emerging arguments and the current situation in Islamic civilization have been addressed by making evaluations on culture and civilization. In the final part, evaluations on thesis this paper has used were made.

  6. Unique Fock quantization of scalar cosmological perturbations

    Science.gov (United States)

    Fernández-Méndez, Mikel; Mena Marugán, Guillermo A.; Olmedo, Javier; Velhinho, José M.

    2012-05-01

    We investigate the ambiguities in the Fock quantization of the scalar perturbations of a Friedmann-Lemaître-Robertson-Walker model with a massive scalar field as matter content. We consider the case of compact spatial sections (thus avoiding infrared divergences), with the topology of a three-sphere. After expanding the perturbations in series of eigenfunctions of the Laplace-Beltrami operator, the Hamiltonian of the system is written up to quadratic order in them. We fix the gauge of the local degrees of freedom in two different ways, reaching in both cases the same qualitative results. A canonical transformation, which includes the scaling of the matter-field perturbations by the scale factor of the geometry, is performed in order to arrive at a convenient formulation of the system. We then study the quantization of these perturbations in the classical background determined by the homogeneous variables. Based on previous work, we introduce a Fock representation for the perturbations in which: (a) the complex structure is invariant under the isometries of the spatial sections and (b) the field dynamics is implemented as a unitary operator. These two properties select not only a unique unitary equivalence class of representations, but also a preferred field description, picking up a canonical pair of field variables among all those that can be obtained by means of a time-dependent scaling of the matter field (completed into a linear canonical transformation). Finally, we present an equivalent quantization constructed in terms of gauge-invariant quantities. We prove that this quantization can be attained by a mode-by-mode time-dependent linear canonical transformation which admits a unitary implementation, so that it is also uniquely determined.

  7. Data-variant kernel analysis

    CERN Document Server

    Motai, Yuichi

    2015-01-01

    Describes and discusses the variants of kernel analysis methods for data types that have been intensely studied in recent years This book covers kernel analysis topics ranging from the fundamental theory of kernel functions to its applications. The book surveys the current status, popular trends, and developments in kernel analysis studies. The author discusses multiple kernel learning algorithms and how to choose the appropriate kernels during the learning phase. Data-Variant Kernel Analysis is a new pattern analysis framework for different types of data configurations. The chapters include

  8. Heart Failure: Unique to Older Adults

    Science.gov (United States)

    ... to Z › Heart Failure › Unique to Older Adults Font size A A A Print Share Glossary Unique ... will suffer from depression at some point. This type of severe depression is more serious than the ...

  9. Detecting very low allele fraction variants using targeted DNA sequencing and a novel molecular barcode-aware variant caller.

    Science.gov (United States)

    Xu, Chang; Nezami Ranjbar, Mohammad R; Wu, Zhong; DiCarlo, John; Wang, Yexun

    2017-01-03

    Detection of DNA mutations at very low allele fractions with high accuracy will significantly improve the effectiveness of precision medicine for cancer patients. To achieve this goal through next generation sequencing, researchers need a detection method that 1) captures rare mutation-containing DNA fragments efficiently in the mix of abundant wild-type DNA; 2) sequences the DNA library extensively to deep coverage; and 3) distinguishes low level true variants from amplification and sequencing errors with high accuracy. Targeted enrichment using PCR primers provides researchers with a convenient way to achieve deep sequencing for a small, yet most relevant region using benchtop sequencers. Molecular barcoding (or indexing) provides a unique solution for reducing sequencing artifacts analytically. Although different molecular barcoding schemes have been reported in recent literature, most variant calling has been done on limited targets, using simple custom scripts. The analytical performance of barcode-aware variant calling can be significantly improved by incorporating advanced statistical models. We present here a highly efficient, simple and scalable enrichment protocol that integrates molecular barcodes in multiplex PCR amplification. In addition, we developed smCounter, an open source, generic, barcode-aware variant caller based on a Bayesian probabilistic model. smCounter was optimized and benchmarked on two independent read sets with SNVs and indels at 5 and 1% allele fractions. Variants were called with very good sensitivity and specificity within coding regions. We demonstrated that we can accurately detect somatic mutations with allele fractions as low as 1% in coding regions using our enrichment protocol and variant caller.

  10. The nucleus, a unique laboratory for quark dynamics. Theoretical challenges

    International Nuclear Information System (INIS)

    Mathiot, J.F.

    1992-01-01

    The new developments concerning high intensity and high energy (E=15-30 GeV) electron scattering, are presented in this course, focusing on the most important and most special ones. The main principles underlying this project are first reviewed; three important themes are then discussed in details: the production of heavy flavours, the concept of color transparency, and the propagation of a quark in the nuclear matter

  11. Computational topology and the Unique Games Conjecture

    OpenAIRE

    Grochow, Joshua A.; Tucker-Foltz, Jamie

    2018-01-01

    Covering spaces of graphs have long been useful for studying expanders (as "graph lifts") and unique games (as the "label-extended graph"). In this paper we advocate for the thesis that there is a much deeper relationship between computational topology and the Unique Games Conjecture. Our starting point is Linial's 2005 observation that the only known problems whose inapproximability is equivalent to the Unique Games Conjecture - Unique Games and Max-2Lin - are instances of Maximum Section of...

  12. Klebsiella pneumoniae Carbapenemase-2 (KPC-2, Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering

    Directory of Open Access Journals (Sweden)

    Melissa D. Barnes

    2017-10-01

    Full Text Available The emergence of Klebsiella pneumoniae carbapenemases (KPCs, β-lactamases that inactivate “last-line” antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ and avibactam (AVI, a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn “traps” β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii E166 is displaced by 2 ÅÅ when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases.

  13. GCPII Variants, Paralogs and Orthologs

    Czech Academy of Sciences Publication Activity Database

    Hlouchová, Klára; Navrátil, Václav; Tykvart, Jan; Šácha, Pavel; Konvalinka, Jan

    2012-01-01

    Roč. 19, č. 9 (2012), s. 1316-1322 ISSN 0929-8673 R&D Projects: GA ČR GAP304/12/0847 Institutional research plan: CEZ:AV0Z40550506 Keywords : PSMA * GCPIII * NAALADase L * splice variants * homologs * PSMAL Subject RIV: CE - Biochemistry Impact factor: 4.070, year: 2012

  14. Odontogenic keratocyst: a peripheral variant.

    Science.gov (United States)

    Vij, H; Vij, R; Gupta, V; Sengupta, S

    2011-01-01

    Odontogenic keratocyst, which is developmental in nature, is an intraosseous lesion though on rare occasions it may occur in an extraosseous location. The extraosseous variant is referred to as peripheral odontogenic keratocyst. Though, clinically, peripheral odontogenic keratocyst resembles the gingival cyst of adults, it has histologic features that are pathognomonic of odontogenic keratocyst. This article presents a case of this uncommon entity.

  15. Swine Influenza/Variant Influenza Viruses

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine Variant Pandemic Other Information on Swine Influenza/Variant Influenza Virus Language: English (US) Español Recommend ...

  16. 'Variant' angina: Evidence for small vessel coronary artery spasm

    International Nuclear Information System (INIS)

    Pfisterer, M.; Mueller-Brand, J.; Cueni, T.; Luetold, B.; Burkart, F.; Basel Univ.

    1980-01-01

    A unique case of 'variant' angina pectoris has been observed in a patient with normal coronary arteries and typical chest pain appearing spontaneously at rest, and repeatedly provoked by ergonovine maleate (0.1 mg iv) associated with large transmural perfusion defects on 201 TI-imaging (after ergonovine) and a marked increase in T wave voltage despite no demonstrable spasm of a major coronary artery after the same doses of ergonovine. While saline solution could not provoke chest pain and treatment with a beta-blocking agent increased the frequency of ischemic attacks, a calcium antangonist therapy reduced and eventually eliminated the attacks. Thus, this case provides evidence for yet another aspect of a 'variant' form of angina pectoris: small vessel coronary artery spasm. (orig.) [de

  17. Direct Correlation of Cell Toxicity to Conformational Ensembles of Genetic Aβ Variants

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2015-01-01

    We report a systematic analysis of conformational ensembles generated from multiseed molecular dynamics simulations of all 15 known genetic variants of Aβ42. We show that experimentally determined variant toxicities are largely explained by random coil content of the amyloid ensembles (correlatio...

  18. Coronary artery anatomy and variants

    Energy Technology Data Exchange (ETDEWEB)

    Malago, Roberto; Pezzato, Andrea; Barbiani, Camilla; Alfonsi, Ugolino; Nicoli, Lisa; Caliari, Giuliana; Pozzi Mucelli, Roberto [Policlinico G.B. Rossi, University of Verona, Department of Radiology, Verona (Italy)

    2011-12-15

    Variants and congenital anomalies of the coronary arteries are usually asymptomatic, but may present with severe chest pain or cardiac arrest. The introduction of multidetector CT coronary angiography (MDCT-CA) allows the detection of significant coronary artery stenosis. Improved performance with isotropic spatial resolution and higher temporal resolution provides a valid alternative to conventional coronary angiography (CCA) in many patients. MDCT-CA is now considered the ideal tool for three-dimensional visualization of the complex and tortuous anatomy of the coronary arteries. With multiplanar and volume-rendered reconstructions, MDCT-CA may even outperform CCA in determining the relative position of vessels, thus providing a better view of the coronary vascular anatomy. The purpose of this review is to describe the normal anatomy of the coronary arteries and their main variants based on MDCT-CA with appropriate reconstructions. (orig.)

  19. Unique features of glycolysis in Archaea

    NARCIS (Netherlands)

    Verhees, C.H.; Kengen, S.W.M.; Tuininga, J.E.; Schut, G.J.; Adams, M.W.W.; Vos, de W.M.; Oost, van der J.

    2003-01-01

    An early divergence in evolution has resulted in two prokaryotic domains, the Bacteria and the Archaea. Whereas the central metabolic routes of bacteria and eukaryotes are generally well-conserved, variant pathways have developed in Archaea involving several novel enzymes with a distinct control. A

  20. A Burkholderia pseudomallei colony variant necessary for gastric colonization.

    Science.gov (United States)

    Austin, C R; Goodyear, A W; Bartek, I L; Stewart, A; Sutherland, M D; Silva, E B; Zweifel, A; Vitko, N P; Tuanyok, A; Highnam, G; Mittelman, D; Keim, P; Schweizer, H P; Vázquez-Torres, A; Dow, S W C; Voskuil, M I

    2015-02-03

    Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow colony variants (YA and YB). As accumulating evidence supports the importance of B. pseudomallei enteric infection and gastric colonization, we tested the response of yellow variants to hypoxia, acidity, and stomach colonization. Yellow variants exhibited a competitive advantage under hypoxic and acidic conditions and alkalized culture media. The YB variant, although highly attenuated in acute virulence, was the only form capable of colonization and persistence in the murine stomach. The accumulation of extracellular DNA (eDNA) was a characteristic of YB as observed by 4',6-diamidino-2-phenylindole (DAPI) staining of gastric tissues, as well as in an in vitro stomach model where large amounts of eDNA were produced without cell lysis. Transposon mutagenesis identified a transcriptional regulator (BPSL1887, designated YelR) that when overexpressed produced the yellow phenotype. Deletion of yelR blocked a shift from white to the yellow forms. These data demonstrate that YB is a unique B. pseudomallei pathovariant controlled by YelR that is specifically adapted to the harsh gastric environment and necessary for persistent stomach colonization. Seemingly uniform populations of bacteria often contain subpopulations that are genetically identical but display unique characteristics which offer advantages when the population is faced with infrequent but predictable stresses. The pathogen Burkholderia pseudomallei is capable of forming several reversible colony types, and it interconverted between one white type and two yellow types under certain environmental stresses. The two yellow forms exhibited distinct advantages in low-oxygen and acidic environments. One yellow

  1. The neXtProt peptide uniqueness checker: a tool for the proteomics community.

    Science.gov (United States)

    Schaeffer, Mathieu; Gateau, Alain; Teixeira, Daniel; Michel, Pierre-André; Zahn-Zabal, Monique; Lane, Lydie

    2017-11-01

    The neXtProt peptide uniqueness checker allows scientists to define which peptides can be used to validate the existence of human proteins, i.e. map uniquely versus multiply to human protein sequences taking into account isobaric substitutions, alternative splicing and single amino acid variants. The pepx program is available at https://github.com/calipho-sib/pepx and can be launched from the command line or through a cgi web interface. Indexing requires a sequence file in FASTA format. The peptide uniqueness checker tool is freely available on the web at https://www.nextprot.org/tools/peptide-uniqueness-checker and from the neXtProt API at https://api.nextprot.org/. lydie.lane@sib.swiss. © The Author(s) 2017. Published by Oxford University Press.

  2. Microcystic Variant of Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Anthony Kodzo-Grey Venyo

    2013-01-01

    Full Text Available Background. Microcystic variant of urothelial carcinoma is one of the new variants of urothelial carcinoma that was added to the WHO classification in 2004. Aims. To review the literature on microcystic variant of urothelial carcinoma. Methods. Various internet search engines were used to identify reported cases of the tumour. Results. Microscopic features of the tumour include: (i Conspicuous intracellular and intercellular lumina/microcysts encompassed by malignant urothelial or squamous cells. (ii The lumina are usually empty; may contain granular eosinophilic debris, mucin, or necrotic cells. (iii The cysts may be variable in size; round, or oval, up to 2 mm; lined by urothelium which are either flattened cells or low columnar cells however, they do not contain colonic epithelium or goblet cells; are infiltrative; invade the muscularis propria; mimic cystitis cystica and cystitis glandularis; occasionally exhibit neuroendocrine differentiation. (iv Elongated and irregular branching spaces are usually seen. About 17 cases of the tumour have been reported with only 2 patients who have survived. The tumour tends to be of high-grade and high-stage. There is no consensus opinion on the best option of treatment of the tumour. Conclusions. It would prove difficult at the moment to be dogmatic regarding its prognosis but it is a highly aggressive tumour. New cases of the tumour should be reported in order to document its biological behaviour.

  3. Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.

    Science.gov (United States)

    Astuti, Galuh D N; van den Born, L Ingeborgh; Khan, M Imran; Hamel, Christian P; Bocquet, Béatrice; Manes, Gaël; Quinodoz, Mathieu; Ali, Manir; Toomes, Carmel; McKibbin, Martin; El-Asrag, Mohammed E; Haer-Wigman, Lonneke; Inglehearn, Chris F; Black, Graeme C M; Hoyng, Carel B; Cremers, Frans P M; Roosing, Susanne

    2018-01-10

    Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 ( SNRNP200 ) and Zinc Finger Protein 513 ( ZNF513 ), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 ( DHX32 ) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed.

  4. Peatlands as a unique climatic hotspots

    Science.gov (United States)

    Slowinska, S.; Marcisz, K.; Slowinski, M. M.; Blazejczyk, K.; Lamentowicz, M.

    2017-12-01

    Peatlands are unique environments, often acting as microrefugia of various taxa. High groundwater table, organic soils, specific vegetation and topography are important determinants of their local climatic conditions. However, relations between those determinants are not stable. For example, seasonal changes in weather patterns, hydrological dynamics, and local vegetation may alter microclimate. Additionally, long-term changes are important factor, as for example overgrowing due to significant change of microclimate conditions, what in turn changes geochemical and biological processes in the peat layer. We have been investigating interactions between abiotic and biotic factors of a small Sphagnum mire (ca. 6.0 ha) for over ten years now. The mire is located in Poland in transitional temperate climate and is the only place in polish lowlands where glacial relict Betula nana occurs. Identification of local climate of the mire, its microclimatic differentiation and its influence on surroundings were objectives of the study. We recorded water level fluctuations, photosynthetically active radiation (PAR), air temperature and humidity, and peat temperature at five monitoring plots at the mire and observed significant differences between them. We also investigated Sphagnum mosses growth and testate amoeba diversity and community structure to understand biological response of those differences. We observed that local climate of the mire was significantly different from open area reference place, it was much colder especially during nights. The average minimal temperature at the height 30 cm for growing seasons 2010-2012 was 3.7oC lower there and ground frosts occurred even in the summer. The climate of the mire affected the forest directly adjacent to it, and depending on weather conditions the strength and the distance of this interaction was different. Our results show that micro-environmental changes affects on biological processes and should be taken into consideration

  5. Unique Physician Identification Number (UPIN) Directory

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Unique Physician Identification Number (UPIN) Directory contains selected information on physicians, doctors of Osteopathy, limited licensed practitioners and...

  6. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk.

    Science.gov (United States)

    Blair, David R; Lyttle, Christopher S; Mortensen, Jonathan M; Bearden, Charles F; Jensen, Anders Boeck; Khiabanian, Hossein; Melamed, Rachel; Rabadan, Raul; Bernstam, Elmer V; Brunak, Søren; Jensen, Lars Juhl; Nicolae, Dan; Shah, Nigam H; Grossman, Robert L; Cox, Nancy J; White, Kevin P; Rzhetsky, Andrey

    2013-09-26

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to complex disease risk. We detect thousands of associations between Mendelian and complex diseases, revealing a nondegenerate, phenotypic code that links each complex disorder to a unique collection of Mendelian loci. Using genome-wide association results, we demonstrate that common variants associated with complex diseases are enriched in the genes indicated by this "Mendelian code." Finally, we detect hundreds of comorbidity associations among Mendelian disorders, and we use probabilistic genetic modeling to demonstrate that Mendelian variants likely contribute nonadditively to the risk for a subset of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Characterization of form variants of Xenorhabdus luminescens.

    Science.gov (United States)

    Gerritsen, L J; de Raay, G; Smits, P H

    1992-01-01

    From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in pigmentation and uptake of dye. Of the two other variants, one produced a yellow pigment and fewer antibiotics (XE-yellow), while the other did not produce a pigment or antibiotics (XE-white). Both were less luminescent, did not take up dye, and had small cell and colony sizes. These two variants were very unstable and shifted to the primary form after 3 to 5 days. It was not possible to separate the primary form and the white variant completely; subcultures of one colony always contained a few colonies of the other variant. The white variant was also found in several other X. luminescens strains. DNA fingerprints showed that all four variants are genetically identical and are therefore derivatives of the same parent. Protein patterns revealed a few differences among the four variants. None of the variants could be considered the secondary form. The pathogenicity of the variants decreased in the following order: XE-red, XE-pink, XE-yellow, and XE-white. The mechanism and function of this variability are discussed. Images PMID:1622273

  8. Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar.

    Science.gov (United States)

    Harrison, Steven M; Dolinsky, Jill S; Knight Johnson, Amy E; Pesaran, Tina; Azzariti, Danielle R; Bale, Sherri; Chao, Elizabeth C; Das, Soma; Vincent, Lisa; Rehm, Heidi L

    2017-10-01

    Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolve interpretation differences by analyzing a subset of variants. ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines, and then compared interpretations. At least two of the participating laboratories interpreted 6,169 variants in ClinVar, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing; 12.8% (31) of reassessed variants remained discordant owing to differences in the application of the ACMG-AMP guidelines. Participating laboratories increased their overall concordance from 88.3 to 91.7%, indicating that sharing variant interpretations in ClinVar-thereby allowing identification of differences and motivation to resolve those differences-is critical to moving toward more consistent variant interpretations.Genet Med advance online publication 09 March 2017.

  9. An isochronous variant of the Ruijsenaars-Toda model: equilibrium configurations, behavior in their neighborhood, Diophantine relations

    International Nuclear Information System (INIS)

    Droghei, R; Ragnisco, O; Calogero, F

    2009-01-01

    An isochronous variant of the Ruijsenaars-Toda integrable many-body problem is introduced, an equilibrium configuration of this dynamical system is identified and by investigating the motions in its neighborhood Diophantine relations are obtained.

  10. An isochronous variant of the Ruijsenaars-Toda model: equilibrium configurations, behavior in their neighborhood, Diophantine relations

    Energy Technology Data Exchange (ETDEWEB)

    Droghei, R; Ragnisco, O [Dipartimento di Fisica, Universita Roma Tre, Via Vasca Navale 84, I-00146 Roma (Italy); Calogero, F [Dipartimento di Fisica, Universita di Roma ' La Sapienza' , P.le A.Moro 2, I-00185 Roma (Italy)], E-mail: droghei@fis.uniroma3.it, E-mail: francesco.calogero@roma1.infn.it, E-mail: ragnisco@fis.uniroma3.it

    2009-11-06

    An isochronous variant of the Ruijsenaars-Toda integrable many-body problem is introduced, an equilibrium configuration of this dynamical system is identified and by investigating the motions in its neighborhood Diophantine relations are obtained.

  11. Uniqueness of time-independent electromagnetic fields

    DEFF Research Database (Denmark)

    Karlsson, Per W.

    1974-01-01

    As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics......As a comment on a recent paper by Steele, a more general uniqueness theorem for time-independent fields is mentioned. ©1974 American Institute of Physics...

  12. Unique specification of Yang-Mills solutions

    International Nuclear Information System (INIS)

    Campbell, W.B.; Joseph, D.W.; Morgan, T.A.

    1980-01-01

    Screened time-independent cylindrically-symmetric solutions of Yang-Mills equations are given which show that the source does not uniquely determine the field. However, these particular solutions suggest a natural way of uniquely specifying solutions in terms of a physical realization of a symmetry group. (orig.)

  13. Constructing Dense Graphs with Unique Hamiltonian Cycles

    Science.gov (United States)

    Lynch, Mark A. M.

    2012-01-01

    It is not difficult to construct dense graphs containing Hamiltonian cycles, but it is difficult to generate dense graphs that are guaranteed to contain a unique Hamiltonian cycle. This article presents an algorithm for generating arbitrarily large simple graphs containing "unique" Hamiltonian cycles. These graphs can be turned into dense graphs…

  14. Shift-Variant Multidimensional Systems.

    Science.gov (United States)

    1985-05-29

    x,y;u,v) is the system response at (x,y) to an unit impulse applied at (u,v). The presence of additive noise in the preceding input-output model of a...space model developed works very effi- ciently to deblur images affected by 2-D linear shift- varying blurs, its use, in presence of noise needs to be...causal linear shift-variant (LSV) system, whose impulse res- ponse is a K-th order degenerate sequence, a K-th order state-space model was obtained

  15. Aplicación de algoritmos de control clásico, adaptable y robusto a sistemas dinámicos de parámetros variables;Classic, adaptable and robust control algorithm application, to variant parameter dynamic system.

    Directory of Open Access Journals (Sweden)

    Orlando – Regalón Anias

    2012-11-01

    Full Text Available Existen múltiples sistemas dinámicos cuyos modelos matemáticos se caracterizan por ser de primer orden yparámetros variables con el tiempo. En estos casos las herramientas clásicas no siempre logran un sistema decontrol que sea estable, posea un buen desempeño dinámico y rechace adecuadamente las perturbaciones, cuandoel modelo de la planta se desvía del nominal, para el cual se realizó el diseño.En este trabajo se evalúa elcomportamiento de tres estrategias de control en presencia de variación de parámetros. Estas son: control clásico,control adaptable y control robusto. Se realiza un estudio comparativo de las mismas en cuanto a complejidad deldiseño, costo computacional de la implementación y sensibilidad ante variaciones en los parámetros y/o presencia dedisturbios. Se llega a conclusiones que permiten disponer de criterios para la elección más adecuada, endependencia de los requerimientos dinámicos que la aplicación demande, así como de los medios técnicos de que sedisponga.Many dynamic systems have first order mathematic models, with time variable parameters. In these cases, theclassical tools do not satisfy at all control system stability, good performance and perturbation rejection, when theplant model differs from the nominal one, for which the controller was designed.In this article, three control strategiesare evaluated in parameter variations and disturbance presence. The strategies are the followings: classical control,adaptive control and robust control. A comparative study is carried out, taking into account the design complexity, thecomputational cost and the sensitivity. The obtained conclusions helps to provide the criterion to choose the mostadequate control strategy, according to the necessary dynamic, as well as the available technical means.

  16. Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data

    DEFF Research Database (Denmark)

    Walker, Logan C; Whiley, Phillip J; Houdayer, Claude

    2013-01-01

    BRCA1 and 176 BRCA2 unique variants, from 77 publications. At least six independent reviewers from research and/or clinical settings comprehensively examined splicing assay methods and data reported for 22 variant assays of 21 variants in four publications, and classified the variants using the 5-tier......Splicing assays are commonly undertaken in the clinical setting to assess the clinical relevance of sequence variants in disease predisposition genes. A 5-tier classification system incorporating both bioinformatic and splicing assay information was previously proposed as a method to provide...... of results, and the lack of quantitative data for the aberrant transcripts. We propose suggestions for minimum reporting guidelines for splicing assays, and improvements to the 5-tier splicing classification system to allow future evaluation of its performance as a clinical tool....

  17. Unitary Evolution as a Uniqueness Criterion

    Science.gov (United States)

    Cortez, J.; Mena Marugán, G. A.; Olmedo, J.; Velhinho, J. M.

    2015-01-01

    It is well known that the process of quantizing field theories is plagued with ambiguities. First, there is ambiguity in the choice of basic variables describing the system. Second, once a choice of field variables has been made, there is ambiguity concerning the selection of a quantum representation of the corresponding canonical commutation relations. The natural strategy to remove these ambiguities is to demand positivity of energy and to invoke symmetries, namely by requiring that classical symmetries become unitarily implemented in the quantum realm. The success of this strategy depends, however, on the existence of a sufficiently large group of symmetries, usually including time-translation invariance. These criteria are therefore generally insufficient in non-stationary situations, as is typical for free fields in curved spacetimes. Recently, the criterion of unitary implementation of the dynamics has been proposed in order to select a unique quantization in the context of manifestly non-stationary systems. Specifically, the unitarity criterion, together with the requirement of invariance under spatial symmetries, has been successfully employed to remove the ambiguities in the quantization of linearly polarized Gowdy models as well as in the quantization of a scalar field with time varying mass, propagating in a static background whose spatial topology is either of a d-sphere (with d = 1, 2, 3) or a three torus. Following Ref. 3, we will see here that the symmetry and unitarity criteria allows for a complete removal of the ambiguities in the quantization of scalar fields propagating in static spacetimes with compact spatial sections, obeying field equations with an explicitly time-dependent mass, of the form ddot φ - Δ φ + s(t)φ = 0 . These results apply in particular to free fields in spacetimes which, like e.g. in the closed FRW models, are conformal to a static spacetime, by means of an exclusively time-dependent conformal factor. In fact, in such

  18. Distribution and medical impact of loss-of-function variants in the Finnish founder population.

    Directory of Open Access Journals (Sweden)

    Elaine T Lim

    2014-07-01

    Full Text Available Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5% variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸ including splice variants in LPA that lowered plasma lipoprotein(a levels (P = 1.5×10⁻¹¹⁷. Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴, demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health

  19. Uniqueness conditions for finitely dependent random fields

    International Nuclear Information System (INIS)

    Dobrushin, R.L.; Pecherski, E.A.

    1981-01-01

    The authors consider a random field for which uniqueness and some additional conditions guaranteeing that the correlations between the variables of the field decrease rapidly enough with the distance between the values of the parameter occur. The main result of the paper states that in such a case uniqueness is true for any other field with transition probabilities sufficiently close to those of the original field. Then they apply this result to some ''degenerate'' classes of random fields for which one can check this condition of correlation to decay, and thus obtain some new conditions of uniqueness. (Auth.)

  20. A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks

    DEFF Research Database (Denmark)

    Huang, Hongda; Strømme, Caroline B; Saredi, Giulia

    2015-01-01

    During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase......, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required...... for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling...

  1. A unique binding mode enables MCM2 to chaperone histones H3-H4 at replication forks.

    Science.gov (United States)

    Huang, Hongda; Strømme, Caroline B; Saredi, Giulia; Hödl, Martina; Strandsby, Anne; González-Aguilera, Cristina; Chen, Shoudeng; Groth, Anja; Patel, Dinshaw J

    2015-08-01

    During DNA replication, chromatin is reassembled by recycling of modified old histones and deposition of new ones. How histone dynamics integrates with DNA replication to maintain genome and epigenome information remains unclear. Here, we reveal how human MCM2, part of the replicative helicase, chaperones histones H3-H4. Our first structure shows an H3-H4 tetramer bound by two MCM2 histone-binding domains (HBDs), which hijack interaction sites used by nucleosomal DNA. Our second structure reveals MCM2 and ASF1 cochaperoning an H3-H4 dimer. Mutational analyses show that the MCM2 HBD is required for MCM2-7 histone-chaperone function and normal cell proliferation. Further, we show that MCM2 can chaperone both new and old canonical histones H3-H4 as well as H3.3 and CENPA variants. The unique histone-binding mode of MCM2 thus endows the replicative helicase with ideal properties for recycling histones genome wide during DNA replication.

  2. Comparative Assessment of Mediterranean Gorgonian-Associated Microbial Communities Reveals Conserved Core and Locally Variant Bacteria

    KAUST Repository

    van de Water, Jeroen A J M

    2016-10-10

    Gorgonians are key habitat-forming species of Mediterranean benthic communities, but their populations have suffered from mass mortality events linked to high summer seawater temperatures and microbial disease. However, our knowledge on the diversity, dynamics and function of gorgonian-associated microbial communities is limited. Here, we analysed the spatial variability of the microbiomes of five sympatric gorgonian species (Eunicella singularis, Eunicella cavolini, Eunicella verrucosa, Leptogorgia sarmentosa and Paramuricea clavata), collected from the Mediterranean Sea over a scale of ∼1100 km, using next-generation amplicon sequencing of the 16S rRNA gene. The microbiomes of all gorgonian species were generally dominated by members of the genus Endozoicomonas, which were at very low abundance in the surrounding seawater. Although the composition of the core microbiome (operational taxonomic units consistently present in a species) was found to be unique for each host species, significant overlap was observed. These spatially consistent associations between gorgonians and their core bacteria suggest intricate symbiotic relationships and regulation of the microbiome composition by the host. At the same time, local variations in microbiome composition were observed. Functional predictive profiling indicated that these differences could be attributed to seawater pollution. Taken together, our data indicate that gorgonian-associated microbiomes are composed of spatially conserved bacteria (core microbiome members) and locally variant members, and that local pollution may influence these local associations, potentially impacting gorgonian health.

  3. Tattoos and piercings: bodily expressions of uniqueness?

    Science.gov (United States)

    Tiggemann, Marika; Hopkins, Louise A

    2011-06-01

    The study aimed to investigate the motivations underlying the body modification practices of tattooing and piercing. There were 80 participants recruited from an Australian music store, who provided descriptions of their tattoos and piercings and completed measures of need for uniqueness, appearance investment and distinctive appearance investment. It was found that tattooed individuals scored significantly higher on need for uniqueness than non-tattooed individuals. Further, individuals with conventional ear piercings scored significantly lower on need for uniqueness than individuals with no piercings or with facial and body piercings. Neither appearance investment nor distinctive appearance investment differed significantly among tattoo or piercing status groups. Strength of identification with music was significantly correlated with number of tattoos, but not number of piercings. It was concluded that tattooing, but not body piercing, represents a bodily expression of uniqueness. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. High Blood Pressure: Unique to Older Adults

    Science.gov (United States)

    ... our e-newsletter! Aging & Health A to Z High Blood Pressure Hypertension Unique to Older Adults This section provides ... Pressure Targets are Different for Very Old Adults High blood pressure (also called hypertension) increases your chance of having ...

  5. Aplicación de algoritmos de control clásico, adaptable y robusto a sistemas dinámicos de parámetros variables; Classic, adaptable and robust control algorithm application, to variant parameter dynamic system

    Directory of Open Access Journals (Sweden)

    Orlando Regalón Anias

    2012-11-01

    Full Text Available Existen múltiples sistemas dinámicos cuyos modelos matemáticos se caracterizan por ser de primer orden y parámetros variables con el tiempo. En estos casos las herramientas clásicas no siempre logran un sistema decontrol que sea estable, posea un buen desempeño dinámico y rechace adecuadamente las perturbaciones, cuando el modelo de la planta se desvía del nominal, para el cual se realizó el diseño.En este trabajo se evalúa el comportamiento de tres estrategias de control en presencia de variación de parámetros. Estas son: control clásico, control adaptable y control robusto. Se realiza un estudio comparativo de las mismas en cuanto a complejidad del diseño, costo computacional de la implementación y sensibilidad ante variaciones en los parámetros y/o presencia de disturbios. Se llega a conclusiones que permiten disponer de criterios para la elección más adecuada, en dependencia de los requerimientos dinámicos que la aplicación demande, así como de los medios técnicos de que se disponga.  Many dynamic systems have first order mathematic models, with time variable parameters. In these cases, the classical tools do not satisfy at all control system stability, good performance and perturbation rejection, when the plant model differs from the nominal one, for which the controller was designed.In this article, three control strategies are evaluated in parameter variations and disturbance presence. The strategies are the followings: classical control, adaptive control and robust control. A comparative study is carried out, taking into account the design complexity, the computational cost and the sensitivity. The obtained conclusions helps to provide the criterion to choose the mostadequate control strategy, according to the necessary dynamic, as well as the available technical means.

  6. A dominant-negative mutant inhibits multiple prion variants through a common mechanism.

    Directory of Open Access Journals (Sweden)

    Fen Pei

    2017-10-01

    Full Text Available Prions adopt alternative, self-replicating protein conformations and thereby determine novel phenotypes that are often irreversible. Nevertheless, dominant-negative prion mutants can revert phenotypes associated with some conformations. These observations suggest that, while intervention is possible, distinct inhibitors must be developed to overcome the conformational plasticity of prions. To understand the basis of this specificity, we determined the impact of the G58D mutant of the Sup35 prion on three of its conformational variants, which form amyloids in S. cerevisiae. G58D had been previously proposed to have unique effects on these variants, but our studies suggest a common mechanism. All variants, including those reported to be resistant, are inhibited by G58D but at distinct doses. G58D lowers the kinetic stability of the associated amyloid, enhancing its fragmentation by molecular chaperones, promoting Sup35 resolubilization, and leading to amyloid clearance particularly in daughter cells. Reducing the availability or activity of the chaperone Hsp104, even transiently, reverses curing. Thus, the specificity of inhibition is determined by the sensitivity of variants to the mutant dosage rather than mode of action, challenging the view that a unique inhibitor must be developed to combat each variant.

  7. Modularity, comparative cognition and human uniqueness.

    Science.gov (United States)

    Shettleworth, Sara J

    2012-10-05

    Darwin's claim 'that the difference in mind between man and the higher animals … is certainly one of degree and not of kind' is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference in cognitive capabilities and/or mechanisms between adult humans and other animals. Dual-process theories for some cognitive domains propose that adult human cognition shares simple basic processes with that of other animals while additionally including slower-developing and more explicit uniquely human processes. These theories are consistent with a modular account of cognition and the 'core knowledge' account of children's cognitive development. A complementary proposal is that human infants have unique social and/or cognitive adaptations for uniquely human learning. A view of human cognitive architecture as a mosaic of unique and species-general modular and domain-general processes together with a focus on uniquely human developmental mechanisms is consistent with modern evolutionary-developmental biology and suggests new questions for comparative research.

  8. Locus Reference Genomic sequences: An improved basis for describing human DNA variants

    KAUST Repository

    Dalgleish, Raymond; Flicek, Paul; Cunningham, Fiona; Astashyn, Alex; Tully, Raymond E; Proctor, Glenn; Chen, Yuan; McLaren, William M; Larsson, Pontus; Vaughan, Brendan W; Bé roud, Christophe; Dobson, Glen; Lehvä slaiho, Heikki; Taschner, Peter EM; den Dunnen, Johan T; Devereau, Andrew; Birney, Ewan; Brookes, Anthony J; Maglott, Donna R

    2010-01-01

    As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specifi c purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-fi le record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)- approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants aff ecting human health. Further information can be found on the LRG web site (http://www.lrg-sequence.org). 2010 Dalgleish et al.; licensee BioMed Central Ltd.

  9. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

    Science.gov (United States)

    Lange, Leslie A.; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M.; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M.; Smith, Joshua D.; Turner, Emily H.; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A.; Holmen, Oddgeir L.; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A.; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C.; Correa, Adolfo; Griswold, Michael E.; Jakobsdottir, Johanna; Smith, Albert V.; Schreiner, Pamela J.; Feitosa, Mary F.; Zhang, Qunyuan; Huffman, Jennifer E.; Crosby, Jacy; Wassel, Christina L.; Do, Ron; Franceschini, Nora; Martin, Lisa W.; Robinson, Jennifer G.; Assimes, Themistocles L.; Crosslin, David R.; Rosenthal, Elisabeth A.; Tsai, Michael; Rieder, Mark J.; Farlow, Deborah N.; Folsom, Aaron R.; Lumley, Thomas; Fox, Ervin R.; Carlson, Christopher S.; Peters, Ulrike; Jackson, Rebecca D.; van Duijn, Cornelia M.; Uitterlinden, André G.; Levy, Daniel; Rotter, Jerome I.; Taylor, Herman A.; Gudnason, Vilmundur; Siscovick, David S.; Fornage, Myriam; Borecki, Ingrid B.; Hayward, Caroline; Rudan, Igor; Chen, Y. Eugene; Bottinger, Erwin P.; Loos, Ruth J.F.; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M.; Gabriel, Stacey B.; O’Donnell, Christopher J.; Post, Wendy S.; North, Kari E.; Reiner, Alexander P.; Boerwinkle, Eric; Psaty, Bruce M.; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P.; Cupples, L. Adrienne; Kooperberg, Charles; Wilson, James G.; Nickerson, Deborah A.; Abecasis, Goncalo R.; Rich, Stephen S.; Tracy, Russell P.; Willer, Cristen J.; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Allayee, Hooman; Cresci, Sharon; Daly, Mark J.; de Bakker, Paul I.W.; DePristo, Mark A.; Do, Ron; Donnelly, Peter; Farlow, Deborah N.; Fennell, Tim; Garimella, Kiran; Hazen, Stanley L.; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kathiresan, Sekar; Kang, Hyun Min; Kiezun, Adam; Lettre, Guillaume; Li, Bingshan; Li, Mingyao; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Rader, Daniel J.; Reich, David; Reilly, Muredach P.; Rivas, Manuel A.; Schwartz, Steve; Scott, Laura; Siscovick, David S.; Spertus, John A.; Stitziel, Nathaniel O.; Stoletzki, Nina; Sunyaev, Shamil R.; Voight, Benjamin F.; Willer, Cristen J.; Rich, Stephen S.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Boerwinkle, Eric; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; Cupples, L. Adrienne; D’Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Folsom, Aaron R.; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Gross, Myron; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Herrington, David M.; Hickson, DeMarc; Huang, Jie; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Andrew D.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Lange, Ethan M.; Lange, Leslie A.; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Liu, Yongmei; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O’Donnell, Christopher J.; O’Leary, Daniel; Ong, Frank; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Psaty, Bruce M.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Herman A.; Taylor, Kent; Thomas, Fridtjof; Tracy, Russell P.; Tsai, Michael Y.; Volcik, Kelly A.; Wassel, Chrstina L.; Watson, Karol; Wei, Gina; White, Wendy; Wiggins, Kerri L.; Wilk, Jemma B.; Williams, O. Dale; Wilson, Gregory; Wilson, James G.; Wolf, Phillip; Zakai, Neil A.; Hardy, John; Meschia, James F.; Nalls, Michael; Singleton, Andrew; Worrall, Brad; Bamshad, Michael J.; Barnes, Kathleen C.; Abdulhamid, Ibrahim; Accurso, Frank; Anbar, Ran; Beaty, Terri; Bigham, Abigail; Black, Phillip; Bleecker, Eugene; Buckingham, Kati; Cairns, Anne Marie; Caplan, Daniel; Chatfield, Barbara; Chidekel, Aaron; Cho, Michael; Christiani, David C.; Crapo, James D.; Crouch, Julia; Daley, Denise; Dang, Anthony; Dang, Hong; De Paula, Alicia; DeCelie-Germana, Joan; Drumm, Allen DozorMitch; Dyson, Maynard; Emerson, Julia; Emond, Mary J.; Ferkol, Thomas; Fink, Robert; Foster, Cassandra; Froh, Deborah; Gao, Li; Gershan, William; Gibson, Ronald L.; Godwin, Elizabeth; Gondor, Magdalen; Gutierrez, Hector; Hansel, Nadia N.; Hassoun, Paul M.; Hiatt, Peter; Hokanson, John E.; Howenstine, Michelle; Hummer, Laura K.; Kanga, Jamshed; Kim, Yoonhee; Knowles, Michael R.; Konstan, Michael; Lahiri, Thomas; Laird, Nan; Lange, Christoph; Lin, Lin; Lin, Xihong; Louie, Tin L.; Lynch, David; Make, Barry; Martin, Thomas R.; Mathai, Steve C.; Mathias, Rasika A.; McNamara, John; McNamara, Sharon; Meyers, Deborah; Millard, Susan; Mogayzel, Peter; Moss, Richard; Murray, Tanda; Nielson, Dennis; Noyes, Blakeslee; O’Neal, Wanda; Orenstein, David; O’Sullivan, Brian; Pace, Rhonda; Pare, Peter; Parker, H. Worth; Passero, Mary Ann; Perkett, Elizabeth; Prestridge, Adrienne; Rafaels, Nicholas M.; Ramsey, Bonnie; Regan, Elizabeth; Ren, Clement; Retsch-Bogart, George; Rock, Michael; Rosen, Antony; Rosenfeld, Margaret; Ruczinski, Ingo; Sanford, Andrew; Schaeffer, David; Sell, Cindy; Sheehan, Daniel; Silverman, Edwin K.; Sin, Don; Spencer, Terry; Stonebraker, Jackie; Tabor, Holly K.; Varlotta, Laurie; Vergara, Candelaria I.; Weiss, Robert; Wigley, Fred; Wise, Robert A.; Wright, Fred A.; Wurfel, Mark M.; Zanni, Robert; Zou, Fei; Nickerson, Deborah A.; Rieder, Mark J.; Green, Phil; Shendure, Jay; Akey, Joshua M.; Bustamante, Carlos D.; Crosslin, David R.; Eichler, Evan E.; Fox, P. Keolu; Fu, Wenqing; Gordon, Adam; Gravel, Simon; Jarvik, Gail P.; Johnsen, Jill M.; Kan, Mengyuan; Kenny, Eimear E.; Kidd, Jeffrey M.; Lara-Garduno, Fremiet; Leal, Suzanne M.; Liu, Dajiang J.; McGee, Sean; O’Connor, Timothy D.; Paeper, Bryan; Robertson, Peggy D.; Smith, Joshua D.; Staples, Jeffrey C.; Tennessen, Jacob A.; Turner, Emily H.; Wang, Gao; Yi, Qian; Jackson, Rebecca; Peters, Ulrike; Carlson, Christopher S.; Anderson, Garnet; Anton-Culver, Hoda; Assimes, Themistocles L.; Auer, Paul L.; Beresford, Shirley; Bizon, Chris; Black, Henry; Brunner, Robert; Brzyski, Robert; Burwen, Dale; Caan, Bette; Carty, Cara L.; Chlebowski, Rowan; Cummings, Steven; Curb, J. David; Eaton, Charles B.; Ford, Leslie; Franceschini, Nora; Fullerton, Stephanie M.; Gass, Margery; Geller, Nancy; Heiss, Gerardo; Howard, Barbara V.; Hsu, Li; Hutter, Carolyn M.; Ioannidis, John; Jiao, Shuo; Johnson, Karen C.; Kooperberg, Charles; Kuller, Lewis; LaCroix, Andrea; Lakshminarayan, Kamakshi; Lane, Dorothy; Lasser, Norman; LeBlanc, Erin; Li, Kuo-Ping; Limacher, Marian; Lin, Dan-Yu; Logsdon, Benjamin A.; Ludlam, Shari; Manson, JoAnn E.; Margolis, Karen; Martin, Lisa; McGowan, Joan; Monda, Keri L.; Kotchen, Jane Morley; Nathan, Lauren; Ockene, Judith; O’Sullivan, Mary Jo; Phillips, Lawrence S.; Prentice, Ross L.; Robbins, John; Robinson, Jennifer G.; Rossouw, Jacques E.; Sangi-Haghpeykar, Haleh; Sarto, Gloria E.; Shumaker, Sally; Simon, Michael S.; Stefanick, Marcia L.; Stein, Evan; Tang, Hua; Taylor, Kira C.; Thomson, Cynthia A.; Thornton, Timothy A.; Van Horn, Linda; Vitolins, Mara; Wactawski-Wende, Jean; Wallace, Robert; Wassertheil-Smoller, Sylvia; Zeng, Donglin; Applebaum-Bowden, Deborah; Feolo, Michael; Gan, Weiniu; Paltoo, Dina N.; Sholinsky, Phyliss; Sturcke, Anne

    2014-01-01

    Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. PMID:24507775

  10. Locus Reference Genomic sequences: An improved basis for describing human DNA variants

    KAUST Repository

    Dalgleish, Raymond

    2010-04-15

    As our knowledge of the complexity of gene architecture grows, and we increase our understanding of the subtleties of gene expression, the process of accurately describing disease-causing gene variants has become increasingly problematic. In part, this is due to current reference DNA sequence formats that do not fully meet present needs. Here we present the Locus Reference Genomic (LRG) sequence format, which has been designed for the specifi c purpose of gene variant reporting. The format builds on the successful National Center for Biotechnology Information (NCBI) RefSeqGene project and provides a single-fi le record containing a uniquely stable reference DNA sequence along with all relevant transcript and protein sequences essential to the description of gene variants. In principle, LRGs can be created for any organism, not just human. In addition, we recognize the need to respect legacy numbering systems for exons and amino acids and the LRG format takes account of these. We hope that widespread adoption of LRGs - which will be created and maintained by the NCBI and the European Bioinformatics Institute (EBI) - along with consistent use of the Human Genome Variation Society (HGVS)- approved variant nomenclature will reduce errors in the reporting of variants in the literature and improve communication about variants aff ecting human health. Further information can be found on the LRG web site (http://www.lrg-sequence.org). 2010 Dalgleish et al.; licensee BioMed Central Ltd.

  11. Developing consistent pronunciation models for phonemic variants

    CSIR Research Space (South Africa)

    Davel, M

    2006-09-01

    Full Text Available Pronunciation lexicons often contain pronunciation variants. This can create two problems: It can be difficult to define these variants in an internally consistent way and it can also be difficult to extract generalised grapheme-to-phoneme rule sets...

  12. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imene

    2017-04-17

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  13. Semantic prioritization of novel causative genomic variants

    KAUST Repository

    Boudellioua, Imene; Mohamad Razali, Rozaimi; Kulmanov, Maxat; Hashish, Yasmeen; Bajic, Vladimir B.; Goncalves-Serra, Eva; Schoenmakers, Nadia; Gkoutos, Georgios V.; Schofield, Paul N.; Hoehndorf, Robert

    2017-01-01

    Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.

  14. Fundamental Characteristics of Industrial Variant Specification Systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer; Hvam, Lars

    2004-01-01

    fundamental concepts related to this task, which are relevant to understand for academia and practitioners working with the subject. This is done through a description of variant specification tasks and typical aspects of system solutions. To support the description of variant specification tasks and systems...

  15. Characterization of form variants of Xenorhabdus luminescens.

    NARCIS (Netherlands)

    Gerritsen, L.J.M.; Raay, de G.; Smits, P.H.

    1992-01-01

    From Xenorhabdus luminescens XE-87.3 four variants were isolated. One, which produced a red pigment and antibiotics, was luminescent, and could take up dye from culture media, was considered the primary form (XE-red). A pink-pigmented variant (XE-pink) differed from the primary form only in

  16. CLEVER: Clique-Enumerating Variant Finder

    NARCIS (Netherlands)

    Marschall, T.; Costa, I.; Canzar, S.; bauer, m; Klau, G.W.; Schliep, A.; Schönhuth, A.

    2012-01-01

    Motivation: Next-generation sequencing techniques have facilitated a large-scale analysis of human genetic variation. Despite the advances in sequencing speed, the computational discovery of structural variants is not yet standard. It is likely that many variants have remained undiscovered in most

  17. Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.

    Science.gov (United States)

    Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie

    2014-11-01

    Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  18. Variant Review with the Integrative Genomics Viewer.

    Science.gov (United States)

    Robinson, James T; Thorvaldsdóttir, Helga; Wenger, Aaron M; Zehir, Ahmet; Mesirov, Jill P

    2017-11-01

    Manual review of aligned reads for confirmation and interpretation of variant calls is an important step in many variant calling pipelines for next-generation sequencing (NGS) data. Visual inspection can greatly increase the confidence in calls, reduce the risk of false positives, and help characterize complex events. The Integrative Genomics Viewer (IGV) was one of the first tools to provide NGS data visualization, and it currently provides a rich set of tools for inspection, validation, and interpretation of NGS datasets, as well as other types of genomic data. Here, we present a short overview of IGV's variant review features for both single-nucleotide variants and structural variants, with examples from both cancer and germline datasets. IGV is freely available at https://www.igv.org Cancer Res; 77(21); e31-34. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Local binary patterns new variants and applications

    CERN Document Server

    Jain, Lakhmi; Nanni, Loris; Lumini, Alessandra

    2014-01-01

    This book introduces Local Binary Patterns (LBP), arguably one of the most powerful texture descriptors, and LBP variants. This volume provides the latest reviews of the literature and a presentation of some of the best LBP variants by researchers at the forefront of textual analysis research and research on LBP descriptors and variants. The value of LBP variants is illustrated with reported experiments using many databases representing a diversity of computer vision applications in medicine, biometrics, and other areas. There is also a chapter that provides an excellent theoretical foundation for texture analysis and LBP in particular. A special section focuses on LBP and LBP variants in the area of face recognition, including thermal face recognition. This book will be of value to anyone already in the field as well as to those interested in learning more about this powerful family of texture descriptors.

  20. Congenital anomalies and normal skeletal variants

    International Nuclear Information System (INIS)

    Guebert, G.M.; Yochum, T.R.; Rowe, L.J.

    1987-01-01

    Congenital anomalies and normal skeletal variants are a common occurrence in clinical practice. In this chapter a large number of skeletal anomalies of the spine and pelvis are reviewed. Some of the more common skeletal anomalies of the extremities are also presented. The second section of this chapter deals with normal skeletal variants. Some of these variants may simulate certain disease processes. In some instances there are no clear-cut distinctions between skeletal variants and anomalies; therefore, there may be some overlap of material. The congenital anomalies are presented initially with accompanying text, photos, and references, beginning with the skull and proceeding caudally through the spine to then include the pelvis and extremities. The normal skeletal variants section is presented in an anatomical atlas format without text or references

  1. Cystinuria Associated with Different SLC7A9 Gene Variants in the Cat.

    Directory of Open Access Journals (Sweden)

    Keijiro Mizukami

    Full Text Available Cystinuria is a classical inborn error of metabolism characterized by a selective proximal renal tubular defect affecting cystine, ornithine, lysine, and arginine (COLA reabsorption, which can lead to uroliths and urinary obstruction. In humans, dogs and mice, cystinuria is caused by variants in one of two genes, SLC3A1 and SLC7A9, which encode the rBAT and bo,+AT subunits of the bo,+ basic amino acid transporter system, respectively. In this study, exons and flanking regions of the SLC3A1 and SLC7A9 genes were sequenced from genomic DNA of cats (Felis catus with COLAuria and cystine calculi. Relative to the Felis catus-6.2 reference genome sequence, DNA sequences from these affected cats revealed 3 unique homozygous SLC7A9 missense variants: one in exon 5 (p.Asp236Asn from a non-purpose-bred medium-haired cat, one in exon 7 (p.Val294Glu in a Maine Coon and a Sphinx cat, and one in exon 10 (p.Thr392Met from a non-purpose-bred long-haired cat. A genotyping assay subsequently identified another cystinuric domestic medium-haired cat that was homozygous for the variant originally identified in the purebred cats. These missense variants result in deleterious amino acid substitutions of highly conserved residues in the bo,+AT protein. A limited population survey supported that the variants found were likely causative. The remaining 2 sequenced domestic short-haired cats had a heterozygous variant at a splice donor site in intron 10 and a homozygous single nucleotide variant at a branchpoint in intron 11 of SLC7A9, respectively. This study identifies the first SLC7A9 variants causing feline cystinuria and reveals that, as in humans and dogs, this disease is genetically heterogeneous in cats.

  2. Rare human papillomavirus 16 E6 variants reveal significant oncogenic potential

    Directory of Open Access Journals (Sweden)

    Tommasino Massimo

    2011-06-01

    Full Text Available Abstract The aim of this study was to determine whether low prevalence human papillomavirus (HPV 16 E6 variants differ from high prevalence types in their functional abilities. We evaluated functions relevant to carcinogenesis for the rarely-detected European variants R8Q, R10G and R48W as compared to the commonly detected L83V. Human immortalized keratinocytes (NIKS stably transduced with the E6 variants were used in most functional assays. Low and high prevalence E6 variants displayed similar abilities in abrogation of growth arrest and inhibition of p53 elevation induced by actinomycin D. Differences were detected in the abilities to dysregulate stratification and differentiation of NIKS in organotypic raft cultures, modulate detachment induced apoptosis (anoikis and hyperactivate Wnt signaling. No distinctive phenotype could be assigned to include all rare variants. Like L83V, raft cultures derived from variants R10G and R48W similarly induced hyperplasia and aberrantly expressed keratin 5 in the suprabasal compartment with significantly lower expression of keratin 10. Unlike L83V, both variants, and particularly R48W, induced increased levels of anoikis upon suspension in semisolid medium. R8Q induced a unique phenotype characterized by thin organotypic raft cultures, low expression of keratin 10, and high expression of keratins 5 and 14 throughout all raft layers. Interestingly, in a reporter based assay R8Q exhibited a higher ability to augment TCF/β-catenin transcription. The data suggests that differences in E6 variant prevalence in cervical carcinoma may not be related to the carcinogenic potential of the E6 protein.

  3. Three novel GJB2 (connexin 26) variants associated with autosomal dominant syndromic and nonsyndromic hearing loss.

    Science.gov (United States)

    DeMille, Desiree; Carlston, Colleen M; Tam, Oliver H; Palumbos, Janice C; Stalker, Heather J; Mao, Rong; Zori, Roberto T; Viskochil, David H; Park, Albert H; Carey, John C

    2018-04-01

    Connexin 26 (Cx26), encoded by the GJB2 gene, is a key protein involved in the formation of gap junctions in epithelial organs including the inner ear and palmoplantar epidermis. Pathogenic variants in GJB2 are responsible for approximately 50% of inherited sensorineural deafness. The majority of these variants are associated with autosomal recessive inheritance; however, rare reports of dominantly co-segregating variants have been published. Since we began offering GJB2 testing in 2003, only about 2% of detected GJB2 variants from our laboratory have been classified as dominant. Here we report three novel dominant GJB2 variants (p.Thr55Ala, p.Gln57_Pro58delinsHisSer, and p.Trp44Gly); two associated with syndromic sensorineural hearing loss and one with nonsyndromic hearing loss. In the kindred with the p.Thr55Ala variant, the proband and his father present with only leukonychia as a cutaneous finding of their syndromic hearing loss. This phenotype has been previously documented in conjunction with palmoplantar hyperkeratosis, but isolated leukonychia is a novel finding likely associated with the unique threonine to alanine change at codon 55 (other variants at this codon have been reported in cases of nonsyndromic hearing loss). This report contributes to the short list of GJB2 variants associated with autosomal dominant hearing loss, highlights the variability of skin and nail findings associated with such cases, and illustrates the occurrence of both syndromic and nonsyndromic presentations with changes in the same gene. © 2018 Wiley Periodicals, Inc.

  4. [Clinical and morphological variants of diverticular disease in colon].

    Science.gov (United States)

    Levchenko, S V; Lazebnik, L B; Potapova, V B; Rogozina, V A

    2013-01-01

    Our own results of two-stage research are presented in the article. The first stage contains the retrospective analysis of 3682 X-ray examining of large bowel which were conducted in 2002-2004 to define the structure of colon disease and to determine gender differences. The second stage is prospective research which took place from 2003 to 2012 and 486 patients with diverticular disease were regularly observed. Following parameters were estimated: dynamics of complaints, life quality, clinical symptoms. Multiple X-ray and endoscopic examining were done with estimation of quantity and size of diverticula, changes of colon mucosa, comparison of X-ray and endoscopic methods in prognosis of complications. Two basic clinical morphological variants of diverticular disease (DD) of colon are made out as a result of our research. There are IBD-like and DD with ischemic component. The variants differ by pain characteristics, presence of accompanying diseases, life quality parameters and description of colon mucosa morphological research. We suppose that different ethiopathogenetic factors of development of both variants mentioned above influence the disease prognosis and selection of treatment.

  5. Unique microstructure and excellent mechanical properties of ADI

    Directory of Open Access Journals (Sweden)

    Jincheng Liu

    2006-11-01

    Full Text Available Amongst the cast iron family, ADI has a unique microstructure and an excellent, optimised combination of mechanical properties. The main microstructure of ADI is ausferrite, which is a mixture ofextremely fine acicular ferrite and stable, high carbon austenite. There are two types of austenite in ADI:(1 the coarser and more equiaxed blocks of austenite between non-parallel acicular structures, which exist mainly in the last solidified area, and (2 the thin films of ustenite between the individual ferriteplatelets in the acicular structure. It is this unique microstructure, which gives ADI its excellent static and dynamic properties, and good low temperature impact toughness. The effect of microstructure on the mechanical properties is explained in more detail by examining the microstructure at the atomic scale. Considering the nanometer grain sizes, the unique microstructure, the excellent mechanical properties,good castability, (which enables near net shape components to be produced economically and in large volumes, and the fact that it can be 100% recycled, it is not overemphasized to call ADI a high-tech,nanometer and “green” material. ADI still has the potential to be further improved and its production and the number of applications for ADI will continue to grow, driven by the resultant cost savings over alternative materials.

  6. Marketing the Uniqueness of Small Towns. Revised.

    Science.gov (United States)

    Dunn, Douglas; Hogg, David H.

    The key to marketing a town is determining and promoting the town's "differential advantage" or uniqueness that would make people want to visit or live there. Exercises to help communities gain important insights into the town's competitive edge include a brainstorming session with knowledgeable community members, a visitor…

  7. On uniqueness in evolution quasivariational inequalities

    Czech Academy of Sciences Publication Activity Database

    Brokate, M.; Krejčí, Pavel; Schnabel, H.

    2004-01-01

    Roč. 11, č. 1 (2004), s. 111-130 ISSN 0944-6532 Institutional research plan: CEZ:AV0Z1019905 Keywords : evolution quasivariational inequality * uniqueness * sweeping process Subject RIV: BA - General Mathematics Impact factor: 0.425, year: 2004 http://www.heldermann-verlag.de/jca/jca11/jca0386.pdf

  8. Esperanto: A Unique Model for General Linguistics.

    Science.gov (United States)

    Dulichenko, Aleksandr D.

    1988-01-01

    Esperanto presents a unique model for linguistic research by allowing the study of language development from project to fully functioning language. Esperanto provides insight into the growth of polysemy and redundancy, as well as into language universals and the phenomenon of social control. (Author/CB)

  9. Weeping dragon, a unique ornamenal citrus

    Science.gov (United States)

    ‘Weeping Dragon’ is a new ornamental citrus cultivar developed by intercrossing of two unusual and unique citrus types, Poncirus trifoliata cultivated variety (cv.) Flying Dragon, and Citrus sinensis cv. ‘Cipo’. This new hybrid cultivar combines strongly contorted and weeping growth traits in a smal...

  10. The end of the unique myocardial band

    DEFF Research Database (Denmark)

    MacIver, David H; Partridge, John B; Agger, Peter

    2018-01-01

    Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour th...

  11. Using Quantum Confinement to Uniquely Identify Devices

    Science.gov (United States)

    Roberts, J.; Bagci, I. E.; Zawawi, M. A. M.; Sexton, J.; Hulbert, N.; Noori, Y. J.; Young, M. P.; Woodhead, C. S.; Missous, M.; Migliorato, M. A.; Roedig, U.; Young, R. J.

    2015-11-01

    Modern technology unintentionally provides resources that enable the trust of everyday interactions to be undermined. Some authentication schemes address this issue using devices that give a unique output in response to a challenge. These signatures are generated by hard-to-predict physical responses derived from structural characteristics, which lend themselves to two different architectures, known as unique objects (UNOs) and physically unclonable functions (PUFs). The classical design of UNOs and PUFs limits their size and, in some cases, their security. Here we show that quantum confinement lends itself to the provision of unique identities at the nanoscale, by using fluctuations in tunnelling measurements through quantum wells in resonant tunnelling diodes (RTDs). This provides an uncomplicated measurement of identity without conventional resource limitations whilst providing robust security. The confined energy levels are highly sensitive to the specific nanostructure within each RTD, resulting in a distinct tunnelling spectrum for every device, as they contain a unique and unpredictable structure that is presently impossible to clone. This new class of authentication device operates with minimal resources in simple electronic structures above room temperature.

  12. Unique Results and Lessons Learned From the TSS Missions

    Science.gov (United States)

    Stone, Nobie H.

    2016-01-01

    The Tethered Satellite System (TSS) Space Shuttle missions, TSS-1 in 1993 and TSS-1R in 1996, were the height of space tether technology development in the U.S. Altogether, the investment made by NASA and the Italian Space Agency (ASI) over the thirteen-year period of the TSS Program totaled approximately $400M-exclusive of the two Space Shuttle flights provided by NASA. Since those two pioneering missions, there have been several smaller tether flight experiments, but interest in this promising technology has waned within NASA as well as the DOD agencies. This is curious in view of the unique capabilities of space tether systems and the fact that they have been flight validated in earth orbit and shown to perform better than the preflight dynamic or electrodynamic theoretical predictions. While it is true that the TSS-1 and TSS-1R missions experienced technical difficulties, the causes of these early developmental problems are now known to have been engineering design flaws, material selection, and procedural issues that (1) are unrelated to the basic viability of space tether technology, and (2) can be readily corrected. The purpose of this paper is to review the dynamic and electrodynamic fundamentals of space tethers and the unique capabilities they afford (that are enabling to certain types of space missions); to elucidate the nature, cause, and solution of the early developmental problems; and to provide an update on progress made in development of the technology.

  13. Temporal expression profiling identifies pathways mediating effect of causal variant on phenotype.

    Directory of Open Access Journals (Sweden)

    Saumya Gupta

    2015-06-01

    Full Text Available Even with identification of multiple causal genetic variants for common human diseases, understanding the molecular processes mediating the causal variants' effect on the disease remains a challenge. This understanding is crucial for the development of therapeutic strategies to prevent and treat disease. While static profiling of gene expression is primarily used to get insights into the biological bases of diseases, it makes differentiating the causative from the correlative effects difficult, as the dynamics of the underlying biological processes are not monitored. Using yeast as a model, we studied genome-wide gene expression dynamics in the presence of a causal variant as the sole genetic determinant, and performed allele-specific functional validation to delineate the causal effects of the genetic variant on the phenotype. Here, we characterized the precise genetic effects of a functional MKT1 allelic variant in sporulation efficiency variation. A mathematical model describing meiotic landmark events and conditional activation of MKT1 expression during sporulation specified an early meiotic role of this variant. By analyzing the early meiotic genome-wide transcriptional response, we demonstrate an MKT1-dependent role of novel modulators, namely, RTG1/3, regulators of mitochondrial retrograde signaling, and DAL82, regulator of nitrogen starvation, in additively effecting sporulation efficiency. In the presence of functional MKT1 allele, better respiration during early sporulation was observed, which was dependent on the mitochondrial retrograde regulator, RTG3. Furthermore, our approach showed that MKT1 contributes to sporulation independent of Puf3, an RNA-binding protein that steady-state transcription profiling studies have suggested to mediate MKT1-pleiotropic effects during mitotic growth. These results uncover interesting regulatory links between meiosis and mitochondrial retrograde signaling. In this study, we highlight the advantage

  14. Synthesis of spatially variant lattices.

    Science.gov (United States)

    Rumpf, Raymond C; Pazos, Javier

    2012-07-02

    It is often desired to functionally grade and/or spatially vary a periodic structure like a photonic crystal or metamaterial, yet no general method for doing this has been offered in the literature. A straightforward procedure is described here that allows many properties of the lattice to be spatially varied at the same time while producing a final lattice that is still smooth and continuous. Properties include unit cell orientation, lattice spacing, fill fraction, and more. This adds many degrees of freedom to a design such as spatially varying the orientation to exploit directional phenomena. The method is not a coordinate transformation technique so it can more easily produce complicated and arbitrary spatial variance. To demonstrate, the algorithm is used to synthesize a spatially variant self-collimating photonic crystal to flow a Gaussian beam around a 90° bend. The performance of the structure was confirmed through simulation and it showed virtually no scattering around the bend that would have arisen if the lattice had defects or discontinuities.

  15. Different Variants of Fundamental Portfolio

    Directory of Open Access Journals (Sweden)

    Tarczyński Waldemar

    2014-06-01

    Full Text Available The paper proposes the fundamental portfolio of securities. This portfolio is an alternative for the classic Markowitz model, which combines fundamental analysis with portfolio analysis. The method’s main idea is based on the use of the TMAI1 synthetic measure and, in limiting conditions, the use of risk and the portfolio’s rate of return in the objective function. Different variants of fundamental portfolio have been considered under an empirical study. The effectiveness of the proposed solutions has been related to the classic portfolio constructed with the help of the Markowitz model and the WIG20 market index’s rate of return. All portfolios were constructed with data on rates of return for 2005. Their effectiveness in 2006- 2013 was then evaluated. The studied period comprises the end of the bull market, the 2007-2009 crisis, the 2010 bull market and the 2011 crisis. This allows for the evaluation of the solutions’ flexibility in various extreme situations. For the construction of the fundamental portfolio’s objective function and the TMAI, the study made use of financial and economic data on selected indicators retrieved from Notoria Serwis for 2005.

  16. Constitutive homo- and hetero-oligomerization of TbetaRII-B, an alternatively spliced variant of the mouse TGF-beta type II receptor

    DEFF Research Database (Denmark)

    Krishnaveni, Manda S; Hansen, Jakob Lerche; Seeger, Werner

    2006-01-01

    , but the oligomerization pattern and dynamics of TbetaRII splice variants in live cells has not been demonstrated thus far. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET), we demonstrate that the mouse TbetaRII receptor splice variant TbetaRII-B is capable of forming ligand...

  17. Ultrasonographic imaging of papillary thyroid carcinoma variants

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Hee [Dept. of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-04-15

    Ultrasonography (US) is routinely used to evaluate thyroid nodules. The US features of papillary thyroid carcinoma (PTC), the most common thyroid malignancy, include hypoechogenicity, spiculated/microlobulated margins, microcalcifications, and a nonparallel orientation. However, many PTC variants have been identified, some of which differ from the classic type of PTC in terms of biological behavior and clinical outcomes. This review describes the US features and clinical implications of the variants of PTC. With the introduction of active surveillance replacing immediate biopsy or surgical treatment of indolent, small PTCs, an understanding of the US characteristics of PTC variants will facilitate the individualized management of patients with PTC.

  18. Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

    Directory of Open Access Journals (Sweden)

    Wan Cheol Kim

    Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

  19. [Uniqueness seeking behavior as a self-verification: an alternative approach to the study of uniqueness].

    Science.gov (United States)

    Yamaoka, S

    1995-06-01

    Uniqueness theory explains that extremely high perceived similarity between self and others evokes negative emotional reactions and causes uniqueness seeking behavior. However, the theory conceptualizes similarity so ambiguously that it appears to suffer from low predictive validity. The purpose of the current article is to propose an alternative explanation of uniqueness seeking behavior. It posits that perceived uniqueness deprivation is a threat to self-concepts, and therefore causes self-verification behavior. Two levels of self verification are conceived: one based on personal categorization and the other on social categorization. The present approach regards uniqueness seeking behavior as the personal-level self verification. To test these propositions, a 2 (very high or moderate similarity information) x 2 (with or without outgroup information) x 2 (high or low need for uniqueness) between-subject factorial-design experiment was conducted with 95 university students. Results supported the self-verification approach, and were discussed in terms of effects of uniqueness deprivation, levels of self-categorization, and individual differences in need for uniqueness.

  20. Issues in Process Variants Mining

    NARCIS (Netherlands)

    Li, C.; Reichert, M.U.; Wombacher, Andreas

    In today's dynamic business world economic success of an enterprise increasingly depends on its ability to react to internal and external changes in a quick and flexible way. In response to this need, process-aware information systems (PAIS) emerged, which support the modeling, orchestration and

  1. Multiple floating metatarsals: a unique injury

    Directory of Open Access Journals (Sweden)

    Trikha Vivek

    2013-04-01

    Full Text Available 【Abstract】Concomitant dislocation of the tar-sometatarsal and metatarsophalangeal joints of foot is an extremely rare injury. Such injuries presenting in a single or adjacent dual rays have been described in few cases previously. We describe such an injury in adjacent three metatarsals of a polytrauma patient. These injuries are likely to be missed in the initial assessment of a polytrauma patient. These patients are at risk of an overlooked diagnosis but the consequences of missing this type of injury may be Vivek Trikha*, Tarun Goyal, Amit K Agarwal quite severe. This case is presented in view of its unique-ness along with possible mechanism of injury, the sequence of reduction and follow-up. Knowledge of such injury and its proper management may be useful to the trauma surgeons. Key words: Metatarsal bones; Metatarsophalangeal joint; Wounds and injuries

  2. Consciousness: a unique way of processing information.

    Science.gov (United States)

    Marchetti, Giorgio

    2018-02-08

    In this article, I argue that consciousness is a unique way of processing information, in that: it produces information, rather than purely transmitting it; the information it produces is meaningful for us; the meaning it has is always individuated. This uniqueness allows us to process information on the basis of our personal needs and ever-changing interactions with the environment, and consequently to act autonomously. Three main basic cognitive processes contribute to realize this unique way of information processing: the self, attention and working memory. The self, which is primarily expressed via the central and peripheral nervous systems, maps our body, the environment, and our relations with the environment. It is the primary means by which the complexity inherent to our composite structure is reduced into the "single voice" of a unique individual. It provides a reference system that (albeit evolving) is sufficiently stable to define the variations that will be used as the raw material for the construction of conscious information. Attention allows for the selection of those variations in the state of the self that are most relevant in the given situation. Attention originates and is deployed from a single locus inside our body, which represents the center of the self, around which all our conscious experiences are organized. Whatever is focused by attention appears in our consciousness as possessing a spatial quality defined by this center and the direction toward which attention is focused. In addition, attention determines two other features of conscious experience: periodicity and phenomenal quality. Self and attention are necessary but not sufficient for conscious information to be produced. Complex forms of conscious experiences, such as the various modes of givenness of conscious experience and the stream of consciousness, need a working memory mechanism to assemble the basic pieces of information selected by attention.

  3. Modularity, comparative cognition and human uniqueness

    OpenAIRE

    Shettleworth, Sara J.

    2012-01-01

    Darwin's claim ‘that the difference in mind between man and the higher animals … is certainly one of degree and not of kind’ is at the core of the comparative study of cognition. Recent research provides unprecedented support for Darwin's claim as well as new reasons to question it, stimulating new theories of human cognitive uniqueness. This article compares and evaluates approaches to such theories. Some prominent theories propose sweeping domain-general characterizations of the difference ...

  4. A unique theory of all forces

    International Nuclear Information System (INIS)

    Di Vecchia, Paolo

    1997-01-01

    In discussing the construction of a consistent theory of quantum gravity unified with the gauge interactions we are naturally led to a string theory. We review its properties and the five consistent supersymmetric string theories in ten dimensions. We finally discuss the evidence that these theories are actually special limits of a unique 11-dimensional theory, called M-theory, and a recent conjecture for its explicit formulation as a supersymmetric Matrix theory

  5. HDR Image Quality Enhancement Based on Spatially Variant Retinal Response

    Directory of Open Access Journals (Sweden)

    Horiuchi Takahiko

    2010-01-01

    Full Text Available There is a growing demand for being able to display high dynamic range (HDR images on low dynamic range (LDR devices. Tone mapping is a process for enhancing HDR image quality on an LDR device by converting the tonal values of the original image from HDR to LDR. This paper proposes a new tone mapping algorithm for enhancing image quality by deriving a spatially-variant operator for imitating S-potential response in human retina, which efficiently improves local contrasts while conserving good global appearance. The proposed tone mapping operator is studied from a system construction point of view. It is found that the operator is regarded as a natural extension of the Retinex algorithm by adding a global adaptation process to the local adaptation. The feasibility of the proposed algorithm is examined in detail on experiments using standard HDR images and real HDR scene images, comparing with conventional tone mapping algorithms.

  6. Variants of social-economic and energy development of Bulgaria up to 2010

    International Nuclear Information System (INIS)

    Tsvetanov, P.

    1990-01-01

    The development variants are formulated as the second stage of a procedure of energy-economy interrelations dynamics study, the other two stages being the scenarios description and the analysis of the development variants. This stage consists of interactive studies with the complex model of the economic developments (CMED), the model of the energy demand (MED) and the energy supplies model (ENERGO). The chapter presents a considerable in its depth and scope description of the energy consumption system developments, according to the alternative social economic and technological policies and also to the studies on the energy complex structure variants and the national energy balance. The economic development variants comprise 25 economic branch structures according to 6 basic economic indices. The energy demand development variants embrace the energy consumption system (including final energy demand, final electrical power demand of the industrial, transportation, household and services sectors), the energy supply system (fuel production and energy conversion) demand and the total energy demands of the country. The dynamics of the final energy demand is considered by 14 types of energy carriers. In addition a draft study on the implementation of gas turbine and combined cycle power plants in the electricity and heat production of the country is presented. 16 refs., 28 figs., 25 tab. (R.Ts.)

  7. Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing

    Directory of Open Access Journals (Sweden)

    Jacqueline Morris

    2017-12-01

    Full Text Available Summary: A number of mitochondrial diseases arise from single-nucleotide variant (SNV accumulation in multiple mitochondria. Here, we present a method for identification of variants present at the single-mitochondrion level in individual mouse and human neuronal cells, allowing for extremely high-resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high-confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single-mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations, resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single-mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds. : Morris et al. use independent sequencing of multiple individual mitochondria from mouse and human brain cells to show high pervasiveness of mutations. The mutations are heteroplasmic within single mitochondria and within and between cells. These findings suggest mechanisms by which mutations accumulate over time, resulting in mitochondrial dysfunction and disease. Keywords: single mitochondrion, single cell, human neuron, mouse neuron, single-nucleotide variation

  8. RAGE splicing variants in mammals.

    Science.gov (United States)

    Sterenczak, Katharina Anna; Nolte, Ingo; Murua Escobar, Hugo

    2013-01-01

    The receptor for advanced glycation end products (RAGE) is a multiligand receptor of environmental stressors which plays key roles in pathophysiological processes, including immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis, tumorigenesis, and metastasis. Besides the full-length RAGE protein in humans nearly 20 natural occurring RAGE splicing variants were described on mRNA and protein level. These naturally occurring isoforms are characterized by either N-terminally or C-terminally truncations and are discussed as possible regulators of the full-length RAGE receptor either by competitive ligand binding or by displacing the full-length protein in the membrane. Accordingly, expression deregulations of the naturally occurring isoforms were supposed to have significant effect on RAGE-mediated disorders. Thereby the soluble C-truncated RAGE isoforms present in plasma and tissues are the mostly focused isoforms in research and clinics. Deregulations of the circulating levels of soluble RAGE forms were reported in several RAGE-associated pathological disorders including for example atherosclerosis, diabetes, renal failure, Alzheimer's disease, and several cancer types. Regarding other mammalian species, the canine RAGE gene showed high similarities to the corresponding human structures indicating RAGE to be evolutionary highly conserved between both species. Similar to humans the canine RAGE showed a complex and extensive splicing activity leading to a manifold pattern of RAGE isoforms. Due to the similarities seen in several canine and human diseases-including cancer-comparative structural and functional analyses allow the development of RAGE and ligand-specific therapeutic approaches beneficial for human and veterinary medicine.

  9. Global Existence and Uniqueness of Weak and Regular Solutions of Shallow Shells with Thermal Effects

    Energy Technology Data Exchange (ETDEWEB)

    Menzala, G. Perla, E-mail: perla@lncc.br [National Laboratory of Scientific Computation, (LNCC/MCTI) (Brazil); Cezaro, F. Travessini De, E-mail: fabianacezaro@furg.br [Federal University of Rio Grande (FURG/IMEF), Institute of Mathematics, Statistics and Physics (Brazil)

    2016-10-15

    We study a dynamical thin shallow shell whose elastic deformations are described by a nonlinear system of Marguerre–Vlasov’s type under the presence of thermal effects. Our main result is the proof of a global existence and uniqueness of a weak solution in the case of clamped boundary conditions. Standard techniques for uniqueness do not work directly in this case. We overcame this difficulty using recent work due to Lasiecka (Appl Anal 4:1376–1422, 1998).

  10. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-01-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell. Images PMID:6752021

  11. Isolation of a variant of Candida albicans.

    Science.gov (United States)

    Buckley, H R; Price, M R; Daneo-Moore, L

    1982-09-01

    During the course of Candida albicans antigen production, a variant of this organism was encountered which did not produce hyphae at 37 degrees C. Presented here are some of the characteristics of this variant. It produces hyphae at 25 degrees C on cornmeal agar and synthetic medium plus N-acetylglucosamine and Tween 80. At 37 degrees C, it does not produce hyphae on these media, although C. albicans normally does produce hyphae under these circumstances. In liquid synthetic medium, this variant does not produce hyphae at 37 degrees C. The variant strain was analyzed for DNA, RNA, protein content, and particle size. After 50 to 70 h in balanced exponential-phase growth, particle size distribution was narrow, and there were no differences in the DNA, RNA, or protein content per particle in the two strains. When balanced exponential-phase cultures were brought into stationary phase, both strains contained the same amount of DNA per cell.

  12. Genetic variants of ghrelin in metabolic disorders.

    Science.gov (United States)

    Ukkola, Olavi

    2011-11-01

    An increasing understanding of the role of genes in the development of obesity may reveal genetic variants that, in combination with conventional risk factors, may help to predict an individual's risk for developing metabolic disorders. Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis and it is a reasonable candidate gene for obesity-related co-morbidities. In cross-sectional studies low total ghrelin concentrations and some genetic polymorphisms of ghrelin have been associated with obesity-associated diseases. The present review highlights many of the important problems in association studies of genetic variants and complex diseases. It is known that population-specific differences in reported associations exist. We therefore conclude that more studies on variants of ghrelin gene are needed to perform in different populations to get deeper understanding on the relationship of ghrelin gene and its variants to obesity. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity.

    Directory of Open Access Journals (Sweden)

    Zhaojing Zheng

    Full Text Available To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity.Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls.A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05. However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05. None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05. One variant (L293R that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups.The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort.

  14. Asian-variant intravascular lymphoma in the African race

    Directory of Open Access Journals (Sweden)

    Holly Geyer

    2012-03-01

    Full Text Available Intravascular large B-cell lymphoma (IVLBCL is an exceptionally rare form of non- Hodgkin lymphoma (NHL distinguished by the preferential growth of neoplastic cells within blood vessel lumen. Challenging to detect and deemed disseminated at diagnosis, this condition is characterized by a highly aggressive, inconspicuous course with a high mortality rate. We describe the case of a 48 year-old African-American female presenting with a two month history of low-grade fevers and malaise. Laboratory data was notable for anemia, thrombocytopenia, elevated liver function tests, and hematuria. An extensive workup for infectious, rheumatologic and malignant causes was negative. Her symptoms progressed and within two weeks, she was admitted for disseminated intravascular coagulation (DIC. Her course was complicated by diffuse pulmonary hemorrhage and ultimately, care was withdrawn. Autopsy identified widespread CD-20 positive intravascular large B-cell lymphoma with significant hepatosplenic involvement, characteristic of the Asian variant IVLBCL. This case uniquely highlights development of the Asian variant IVLBVL in a previously undescribed race. Identified by its intraluminal vascular growth pattern, IVLBCL generally spares lymphatic channels. Diagnosis and differentiation of this condition from other hematological malignancies via skin, visceral and bone marrow biopsy is imperative as anthracycline-containing chemotherapies may significantly improve clinical outcomes. This article outlines the common presentation, natural course, and treatment options of IVLBCL, along with the histopathology, immunohistochemistry, and chromosomal aberrations common to this condition.

  15. Detonation Synthesis of Alpha-Variant Silicon Carbide

    Science.gov (United States)

    Langenderfer, Martin; Johnson, Catherine; Fahrenholtz, William; Mochalin, Vadym

    2017-06-01

    A recent research study has been undertaken to develop facilities for conducting detonation synthesis of nanomaterials. This process involves a familiar technique that has been utilized for the industrial synthesis of nanodiamonds. Developments through this study have allowed for experimentation with the concept of modifying explosive compositions to induce synthesis of new nanomaterials. Initial experimentation has been conducted with the end goal being synthesis of alpha variant silicon carbide (α-SiC) in the nano-scale. The α-SiC that can be produced through detonation synthesis methods is critical to the ceramics industry because of a number of unique properties of the material. Conventional synthesis of α-SiC results in formation of crystals greater than 100 nm in diameter, outside nano-scale. It has been theorized that the high temperature and pressure of an explosive detonation can be used for the formation of α-SiC in the sub 100 nm range. This paper will discuss in detail the process development for detonation nanomaterial synthesis facilities, optimization of explosive charge parameters to maximize nanomaterial yield, and introduction of silicon to the detonation reaction environment to achieve first synthesis of nano-sized alpha variant silicon carbide.

  16. TREM2 Variants in Alzheimer's Disease

    Science.gov (United States)

    Guerreiro, Rita; Wojtas, Aleksandra; Bras, Jose; Carrasquillo, Minerva; Rogaeva, Ekaterina; Majounie, Elisa; Cruchaga, Carlos; Sassi, Celeste; Kauwe, John S.K.; Younkin, Steven; Hazrati, Lilinaz; Collinge, John; Pocock, Jennifer; Lashley, Tammaryn; Williams, Julie; Lambert, Jean-Charles; Amouyel, Philippe; Goate, Alison; Rademakers, Rosa; Morgan, Kevin; Powell, John; St. George-Hyslop, Peter; Singleton, Andrew; Hardy, John

    2013-01-01

    BACKGROUND Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia. METHODS We used genome, exome, and Sanger sequencing to analyze the genetic variability in TREM2 in a series of 1092 patients with Alzheimer's disease and 1107 controls (the discovery set). We then performed a meta-analysis on imputed data for the TREM2 variant rs75932628 (predicted to cause a R47H substitution) from three genomewide association studies of Alzheimer's disease and tested for the association of the variant with disease. We genotyped the R47H variant in an additional 1887 cases and 4061 controls. We then assayed the expression of TREM2 across different regions of the human brain and identified genes that are differentially expressed in a mouse model of Alzheimer's disease and in control mice. RESULTS We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set (P = 0.02). There were 22 variant alleles in 1092 patients with Alzheimer's disease and 5 variant alleles in 1107 controls (P<0.001). The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001). Meta-analysis of rs75932628 genotypes imputed from genomewide association studies confirmed this association (P = 0.002), as did direct genotyping of an additional series of 1887 patients with Alzheimer's disease and 4061 controls (P<0.001). Trem2 expression differed between control mice and a mouse model of Alzheimer's disease. CONCLUSIONS Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease. (Funded by Alzheimer's Research UK and others.) PMID:23150934

  17. A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk

    DEFF Research Database (Denmark)

    Blair, David R.; Lyttle, Christopher S.; Mortensen, Jonathan M.

    2013-01-01

    Although countless highly penetrant variants have been associated with Mendelian disorders, the genetic etiologies underlying complex diseases remain largely unresolved. By mining the medical records of over 110 million patients, we examine the extent to which Mendelian variation contributes to c...... of complex diseases. Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases....

  18. Desmoplastic variant of ameloblastoma of the maxilla: A case report

    International Nuclear Information System (INIS)

    Koh, Kwang Joon; Park, Ha Na; Kim, Kyoung A

    2015-01-01

    The desmoplastic variant of ameloblastoma is a rare form of ameloblastoma characterized by unique radiographic and histologic features. A 46-year-old female was referred to our hospital, complaining of swelling in the left upper lip area. Radiographic findings revealed an ill-defined multilocular lesion with a large cystic lesion and thick sclerotic trabeculae on the left anterior maxilla. After the patient underwent partial osteotomy, histologic analysis revealed a desmoplastic ameloblastoma with no evidence of a hybrid lesion or cyst formation. The radiographic findings in the present case were different from those described in previous case reports. These findings are of special importance due to the unfamiliar radiographic and histologic features of this lesion

  19. Uniqueness and non-uniqueness of semigroups generated by singular diffusion operators

    CERN Document Server

    Eberle, Andreas

    1999-01-01

    This book addresses both probabilists working on diffusion processes and analysts interested in linear parabolic partial differential equations with singular coefficients. The central question discussed is whether a given diffusion operator, i.e., a second order linear differential operator without zeroth order term, which is a priori defined on test functions over some (finite or infinite dimensional) state space only, uniquely determines a strongly continuous semigroup on a corresponding weighted Lp space. Particular emphasis is placed on phenomena causing non-uniqueness, as well as on the relation between different notions of uniqueness appearing in analytic and probabilistic contexts.

  20. Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering.

    Science.gov (United States)

    Barnes, Melissa D; Winkler, Marisa L; Taracila, Magdalena A; Page, Malcolm G; Desarbre, Eric; Kreiswirth, Barry N; Shields, Ryan K; Nguyen, Minh-Hong; Clancy, Cornelius; Spellberg, Brad; Papp-Wallace, Krisztina M; Bonomo, Robert A

    2017-10-31

    The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn "traps" β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases. IMPORTANCE Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key

  1. Unique supply function equilibrium with capacity constraints

    International Nuclear Information System (INIS)

    Holmberg, Paer

    2008-01-01

    Consider a market where producers submit supply functions to a procurement auction with uncertain demand, e.g. an electricity auction. In the Supply Function Equilibrium (SFE), every firm commits to the supply function that maximises expected profit in the one-shot game given the supply functions of competitors. A basic weakness of the SFE is the presence of multiple equilibria. This paper shows that with (i) symmetric producers, (ii) perfectly inelastic demand, (iii) a price cap, and (iv) capacity constraints that bind with a positive probability, there exists a unique, symmetric SFE. (author)

  2. Stationary Black Holes: Uniqueness and Beyond

    Directory of Open Access Journals (Sweden)

    Heusler Markus

    1998-01-01

    Full Text Available The spectrum of known black hole solutions to the stationary Einstein equations has increased in an unexpected way during the last decade. In particular, it has turned out that not all black hole equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black hole space-times ceases to exist in self-gravitating non-linear field theories. This text aims to review some of the recent developments and to discuss them in the light of the uniqueness theorem for the Einstein-Maxwell system.

  3. Stationary Black Holes: Uniqueness and Beyond

    Directory of Open Access Journals (Sweden)

    Piotr T. Chruściel

    2012-05-01

    Full Text Available The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.

  4. On uniqueness in diffuse optical tomography

    International Nuclear Information System (INIS)

    Harrach, Bastian

    2009-01-01

    A prominent result of Arridge and Lionheart (1998 Opt. Lett. 23 882–4) demonstrates that it is in general not possible to simultaneously recover both the diffusion (aka scattering) and the absorption coefficient in steady-state (dc) diffusion-based optical tomography. In this work we show that it suffices to restrict ourselves to piecewise constant diffusion and piecewise analytic absorption coefficients to regain uniqueness. Under this condition both parameters can simultaneously be determined from complete measurement data on an arbitrarily small part of the boundary

  5. Beta-glucosidase variants and polynucleotides encoding same

    Science.gov (United States)

    Wogulis, Mark; Harris, Paul; Osborn, David

    2017-06-27

    The present invention relates to beta-glucosidase variants, e.g. beta-glucosidase variants of a parent Family GH3A beta-glucosidase from Aspergillus fumigatus. The present invention also relates to polynucleotides encoding the beta-glucosidase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the beta-glucosidase variants.

  6. Unmanned Aerial Vehicles unique cost estimating requirements

    Science.gov (United States)

    Malone, P.; Apgar, H.; Stukes, S.; Sterk, S.

    Unmanned Aerial Vehicles (UAVs), also referred to as drones, are aerial platforms that fly without a human pilot onboard. UAVs are controlled autonomously by a computer in the vehicle or under the remote control of a pilot stationed at a fixed ground location. There are a wide variety of drone shapes, sizes, configurations, complexities, and characteristics. Use of these devices by the Department of Defense (DoD), NASA, civil and commercial organizations continues to grow. UAVs are commonly used for intelligence, surveillance, reconnaissance (ISR). They are also use for combat operations, and civil applications, such as firefighting, non-military security work, surveillance of infrastructure (e.g. pipelines, power lines and country borders). UAVs are often preferred for missions that require sustained persistence (over 4 hours in duration), or are “ too dangerous, dull or dirty” for manned aircraft. Moreover, they can offer significant acquisition and operations cost savings over traditional manned aircraft. Because of these unique characteristics and missions, UAV estimates require some unique estimating methods. This paper describes a framework for estimating UAV systems total ownership cost including hardware components, software design, and operations. The challenge of collecting data, testing the sensitivities of cost drivers, and creating cost estimating relationships (CERs) for each key work breakdown structure (WBS) element is discussed. The autonomous operation of UAVs is especially challenging from a software perspective.

  7. Young children's preference for unique owned objects.

    Science.gov (United States)

    Gelman, Susan A; Davidson, Natalie S

    2016-10-01

    An important aspect of human thought is the value we place on unique individuals. Adults place higher value on authentic works of art than exact replicas, and young children at times value their original possessions over exact duplicates. What is the scope of this preference in early childhood, and when do children understand its subjective nature? On a series of trials, we asked three-year-olds (N=36) to choose between two toys for either themselves or the researcher: an old (visibly used) toy vs. a new (more attractive) toy matched in type and appearance (e.g., old vs. brand-new blanket). Focal pairs contrasted the child's own toy with a matched new object; Control pairs contrasted toys the child had never seen before. Children preferred the old toys for Focal pairs only, and treated their own preferences as not shared by the researcher. By 3years of age, young children place special value on unique individuals, and understand the subjective nature of that value. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Event segmentation ability uniquely predicts event memory.

    Science.gov (United States)

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    Science.gov (United States)

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission

  10. Deciphering the Developmental Dynamics of the Mouse Liver Transcriptome.

    Directory of Open Access Journals (Sweden)

    Sumedha S Gunewardena

    Full Text Available During development, liver undergoes a rapid transition from a hematopoietic organ to a major organ for drug metabolism and nutrient homeostasis. However, little is known on a transcriptome level of the genes and RNA-splicing variants that are differentially regulated with age, and which up-stream regulators orchestrate age-specific biological functions in liver. We used RNA-Seq to interrogate the developmental dynamics of the liver transcriptome in mice at 12 ages from late embryonic stage (2-days before birth to maturity (60-days after birth. Among 21,889 unique NCBI RefSeq-annotated genes, 9,641 were significantly expressed in at least one age, 7,289 were differently regulated with age, and 859 had multiple (> = 2 RNA splicing-variants. Factor analysis showed that the dynamics of hepatic genes fall into six distinct groups based on their temporal expression. The average expression of cytokines, ion channels, kinases, phosphatases, transcription regulators and translation regulators decreased with age, whereas the average expression of peptidases, enzymes and transmembrane receptors increased with age. The average expression of growth factors peak between Day-3 and Day-10, and decrease thereafter. We identified critical biological functions, upstream regulators, and putative transcription modules that seem to govern age-specific gene expression. We also observed differential ontogenic expression of known splicing variants of certain genes, and 1,455 novel splicing isoform candidates. In conclusion, the hepatic ontogeny of the transcriptome ontogeny has unveiled critical networks and up-stream regulators that orchestrate age-specific biological functions in liver, and suggest that age contributes to the complexity of the alternative splicing landscape of the hepatic transcriptome.

  11. Specificity of antigens on UV radiation-induced antigenic tumor cell variants measured in vitro and in vivo

    International Nuclear Information System (INIS)

    Hostetler, L.W.; Romerdahl, C.A.; Kripke, M.L.

    1989-01-01

    The purpose of this study was to determine whether antigenic variants cross-react immunologically with the parental tumor and whether the UVR-associated antigen unique to UVR-induced tumors is also present on the variants. Antigenic (regressor) variants and nonimmunogenic (progressor) clones derived from UV-irradiated cultures of the C3H K1735 melanoma and SF19 spontaneous fibrosarcoma cell lines were used to address these questions. In an in vivo immunization and challenge assay, the antigenic variants did not induce cross-protection among themselves, but each induced immunity against the immunizing variant, the parent tumor cells, and nonimmunogenic clones derived from UV-irradiated parent cultures. Therefore, the variants can be used to induce in mice a protective immunity that prevents the growth of the parent tumor and nonimmunogenic clones, but not other antigenic variants. In contrast, immunization with cells of the parental tumor or the nonimmunogenic clones induced no protective immunity against challenge with any of the cell lines. Utilizing the K1735 melanoma-derived cell lines in vitro, T-helper (Th) cells isolated from tumor-immunized mice were tested for cross-reactivity by their ability to collaborate with trinitrophenyl-primed B-cells in the presence of trinitrophenyl-conjugated tumor cells. Also, the cross-reactivity of cytotoxic T-lymphocytes from tumor-immunized mice was assessed by a 4-h 51Cr-release assay. Antigenic variants induced cytotoxic T-lymphocytes and Th activity that was higher than that induced by the parent tumor and nonimmunogenic clones from the UVR-exposed parent tumor and cross-reacted with the parental tumor cells and nonimmunogenic clones, but not with other antigenic variants

  12. Word Variant Identification in Old French

    Directory of Open Access Journals (Sweden)

    Peter Willett

    1997-01-01

    Full Text Available Increasing numbers of historical texts are available in machine-readable form, which retain the original spelling, which can be very different from the modern-day equivalents due to the natural evolution of a language, and because the concept of standardisation in spelling is comparatively modern. Among medieval vernacular writers, the same word could be spelled in different ways and the same author (or scribe might even use several alternative spellings in the same passage. Thus, we do not know,a priori, how many variant forms of a particular word there are in such texts, let alone what these variants might be. Searching on the modern equivalent, or even the commonest historical variant, of a particular word may thus fail to retrieve an appreciable number of occurrences unless the searcher already has an extensive knowledge of the language of the documents. Moreover, even specialist scholars may be unaware of some idiosyncratic variants. Here, we consider the use of computer methods to retrieve variant historical spellings.

  13. Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

    DEFF Research Database (Denmark)

    Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

    2015-01-01

    by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

  14. Detecting beer intake by unique metabolite patterns

    DEFF Research Database (Denmark)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

    2016-01-01

    Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

  15. ARAC: A unique command and control resource

    International Nuclear Information System (INIS)

    Bradley, M.M.; Baskett, R.L.; Ellis, J.S.

    1996-04-01

    The Atmospheric Release Advisory Capability (ARAC) at Lawrence Livermore National Laboratory (LLNL) is a centralized federal facility designed to provide real-time, world-wide support to military and civilian command and control centers by predicting the impacts of inadvertent or intentional releases of nuclear, biological, or chemical materials into the atmosphere. ARAC is a complete response system consisting of highly trained and experienced personnel, continually updated computer models, redundant data collection systems, and centralized and remote computer systems. With over 20 years of experience responding to domestic and international incidents, strong linkages with the Department of Defense, and the ability to conduct classified operations, ARAC is a unique command and control resource

  16. ARAC: A unique command and control resource

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, M.M.; Baskett, R.L.; Ellis, J.S. [and others

    1996-04-01

    The Atmospheric Release Advisory Capability (ARAC) at Lawrence Livermore National Laboratory (LLNL) is a centralized federal facility designed to provide real-time, world-wide support to military and civilian command and control centers by predicting the impacts of inadvertent or intentional releases of nuclear, biological, or chemical materials into the atmosphere. ARAC is a complete response system consisting of highly trained and experienced personnel, continually updated computer models, redundant data collection systems, and centralized and remote computer systems. With over 20 years of experience responding to domestic and international incidents, strong linkages with the Department of Defense, and the ability to conduct classified operations, ARAC is a unique command and control resource.

  17. Unique computer system for safeguards use

    International Nuclear Information System (INIS)

    Kuckertz, T.H.; Pratt, J.C.

    1981-01-01

    Microprocessors have been used to implement specialized scientific data processing systems since 1976. One such system, the LeCroy 3500, is presently being used by the Detection and Verification Group of the Energy Division at Los Alamos National Laboratory for a large variety of tasks involving measurement of various nuclear parameters associated with radioactive materials. The system is unique because it can do not only sophisticated pulse height and multi-scale analyses but also other analyses that are limited only by the availability fo CAMAC modules that would acquire data from exotic experiments. The system is also field portable which extends the range of experiments that it can control. Four applications of this system are described in this paper: (1) plutonium storage vault monitoring, (2) coded aperture image reconstruction, (3) spatial distribution of gamma radiation, and (4) nuclear waste management. 7 figures

  18. 2XIIB vacuum vessel: a unique design

    International Nuclear Information System (INIS)

    Hibbs, S.M.; Calderon, M.O.

    1975-01-01

    The 2XIIB mirror confinement experiment makes unique demands on its vacuum system. The confinement coil set encloses a cavity whose surface is comprised of both simple and compound curves. Within this cavity and at the core of the machine is the operating vacuum which is on the order of 10 -9 Torr. The vacuum container fits inside the cavity, presenting an inside surface suitable for titanium getter pumping and a means of removing the heat load imposed by incandescent sublimator wires. In addition, the cavity is constructed of nonmagnetic and nonconducting materials (nonmetals) to avoid distortion of the pulsed confinement field. It is also isolated from mechanical shocks induced in the machine's main structure when the coils are pulsed. This paper describes the design, construction, and operation of the 2XIIB high-vacuum vessel that has been performing successfully since early 1974

  19. The unique ethics of sports medicine.

    Science.gov (United States)

    Johnson, Rob

    2004-04-01

    The ethical code by which physicians traditionally conduct themselves is based on the relationship between the physician and the patient: both work toward the goal of improving or maintaining health. Constraints on this relationship may be behaviors of patient choice (tobacco use, excessive alcohol use, sedentary behavior, and so on). The athlete-physician relationship is ethically different. Influences such as the physician's employer, the athlete's desire to play with pain and injury, and the economic consequences of playing or not complicate medical decisions. This perspective suggests something different and even unique about the ethics of the sports medicine practitioner. This article explores the differences fostering the ethical tight ropes that sports physicians walk in their sports medicine practices.

  20. MRI: unique costing and pricing issues.

    Science.gov (United States)

    Schwartz, H W; Jarl, D F

    1985-01-01

    Acquisition of magnetic resonance imaging (MRI) involves a plethora of costs not traditionally encountered in radiology procedure cost accounting models. Experiences with MRI gained at the University of Minnesota Hospitals and Clinics during 1984 uncovered a wide variety of unique costing issues which were eventually identified at the time when the MRI hospital charge was being established. Our experience at UMHC can provide those radiology departments now acquiring MRI with an earlier awareness of these special costing issues, hopefully resulting in better and more timely data collection. Current reimbursement and pricing issues are also having a dramatic impact on MRI costs at each institution and must be assessed in terms of third-party payor intentions.

  1. Evidence of trem2 variant associated with triple risk of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Zainularifeen Abduljaleel

    Full Text Available Alzheimer's disease is one of the main causes of dementia among elderly individuals and leads to the neurodegeneration of different areas of the brain, resulting in memory impairments and loss of cognitive functions. Recently, a rare variant that is associated with 3-fold higher risk of Alzheimer's disease onset has been found. The rare variant discovered is a missense mutation in the loop region of exon 2 of Trem2 (rs75932628-T, Arg47His. The aim of this study was to investigate the evidence for potential structural and functional significance of Trem2 gene variant (Arg47His through molecular dynamics simulations. Our results showed the alteration caused due to the variant in TREM2 protein has significant effect on the ligand binding affinity as well as structural configuration. Based on molecular dynamics (MD simulation under salvation, the results confirmed that native form of the variant (Arg47His might be responsible for improved compactness, hence thereby improved protein folding. Protein simulation was carried out at different temperatures. At 300K, the deviation of the theoretical model of TREM2 protein increased from 2.0 Å at 10 ns. In contrast, the deviation of the Arg47His mutation was maintained at 1.2 Å until the end of the simulation (t = 10 ns, which indicated that Arg47His had reached its folded state. The mutant residue was a highly conserved region and was similar to "immunoglobulin V-set" and "immunoglobulin-like folds". Taken together, the result from this study provides a biophysical insight on how the studied variant could contribute to the genetic susceptibility to Alzheimer's disease.

  2. Tropical wetlands and REDD+: Three unique scientific challenges for policy

    Directory of Open Access Journals (Sweden)

    Daniel A Friess

    2013-07-01

    Full Text Available The carbon sequestration and storage value of terrestrial habitats is now increasingly appreciated, and is the basis for Payment for Ecosystem Service (PES policies such as REDD+. Tropical wetlands may be suitable for inclusion in such schemes because of the disproportionately large volume of carbon they are able to store. However, tropical wetlands offer a number of unique challenges for carbon management and policy compared to terrestrial forest systems: 1 Tropical wetlands are dynamic and subject to a wide range of physical and ecological processes that affect their long-term carbon storage potential – thus, such systems can quickly become a carbon source instead of a sink; 2 Carbon dynamics in tropical wetlands often operate over longer time-scales than are currently covered by REDD+ payments; and 3 Much of the carbon in a tropical wetland is stored in the soil, so monitoring, reporting and verification (MRV needs to adequately encapsulate the entire ecosystem and not just the vegetative component. This paper discusses these physical and biological concepts, and highlights key legal, management and policy questions that must be considered when constructing a policy framework to conserve these crucial ecosystems.

  3. Genetics in psychiatry: common variant association studies

    Directory of Open Access Journals (Sweden)

    Buxbaum Joseph D

    2010-03-01

    Full Text Available Abstract Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.

  4. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    Science.gov (United States)

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  5. [Clinico-pathogenetic variants of chronic gastritis].

    Science.gov (United States)

    Chernin, V V; Dzhulaĭ, G S

    2004-01-01

    To evaluate specific features of the course of chronic gastritis (CG), morphofunctional condition of gastric mucosa, vegetative regulation, adrenergic and cholinergic shifts, histamine metabolism and effects of exogenic and endogenic risk factors in CG patients; to study clinicopathogenetic variants of CG. A total of 311 CG patients aged from 16 to 72 years were studied. They were divided into three groups by their gastric mucosa condition. The control group consisted of 30 healthy donors. The following parameters were studied: visual and histological condition of gastric mucosa, total acidity, the levels of free hydrochloric acid, pepsin, bioelectric gastric activity, general autonomic tonicity, cholinesterase activity. Three clinicopathogenetic variants of the disease have been identified. Variant 1 was characterized by a recurrent course, subjective manifestation of the disease only in exacerbation, surface (primarily antral) mucosal affection, normal or enhanced secretory and motor functions of the stomach, adequate reaction of acid production to caffeine and histamine stimulation, parasympathicotonia, absolute hyperhistaminemia, relative hypoacetylcholinemia, subnormal urinary excretion of adrenalin. Variant 2 manifested with rare recurrences, longer and more severe exacerbations, frequent spontaneous and provoked aggravations, moderate focal atrophy of the mucosa, secretory insufficiency with adequate reaction to histamine and minor to caffeine stimuli, hypomotor gastric dyskinesia, vegetative eutonia, normohistaminemia, absolute hypoacetylcholinemia, subnormal urinary excretion of noradrenaline. Variant 3 runs without definite remissions and exacerbations, with continuous abdominal pain and dyspepsia, frequent spontaneous aggravations, marked extended mucosal atrophy with secretory insufficiency up to achlorhydria, no stimulation of acid production in response to caffeine and histamine, gastric hypomotility, sympathicotonia, absolute hypohistaminemia

  6. Uniqueness of solutions of relay systems, Special Issue on Hybrid Systems

    NARCIS (Netherlands)

    Lootsma, Y.J.; van der Schaft, Arjan; Camlıbel, M.K.

    1999-01-01

    Conditions are given for uniqueness of solutions of linear time-invariant systems under relay feedback. From a hybrid dynamical point of view this entails the deterministic specification of the discrete transition rules. The results are based on the formulation of relay systems as complementarity

  7. Unique functional properties of somatostatin-expressing GABAergic neurons in mouse barrel cortex.

    NARCIS (Netherlands)

    Gentet, L.J.; Kremer, Y.; Taniguchi, H.; Huang, Z.J.; Staiger, J.F.; Petersen, C.C.H.

    2012-01-01

    Neocortical GABAergic neurons have diverse molecular, structural and electrophysiological features, but the functional correlates of this diversity are largely unknown. We found unique membrane potential dynamics of somatostatin-expressing (SOM) neurons in layer 2/3 of the primary somatosensory

  8. Diffuse scattering as an indicator for martensitic variant selection

    International Nuclear Information System (INIS)

    Gao, Lei; Ding, Xiangdong; Zong, Hongxiang; Lookman, Turab; Sun, Jun; Ren, Xiaobing; Saxena, Avadh

    2014-01-01

    Diffuse scattering is an important precursor phenomenon prior to the martensitic transformation (MT). It is related to the correlated atomic position fluctuations prior to the MT and can provide important hints of the transformation mechanism. However, the role of this precursor phenomenon in the MT is not clear so far. Here we study the evolution of diffraction patterns prior to temperature- and stress-induced MTs and consider the evolution of atomic configurations during the whole MT process, using molecular dynamics simulations on a generic body-centered cubic–hexagonal close-packed transformation as an example. Our results show that, although the diffuse scattering changes with external fields, there exists a general relationship between the transformation pathways, the diffuse scattering streaks and the martensitic products. Two preferred transformation pathways with opposite shuffle directions lead to a single specific diffuse scattering streak prior to the MT and form one pair of anti-variants after the MT. Thus the distribution of diffuse scattering acts as an indicator of the selection of martensitic variants. In addition, we find that the applied stress can change the shear order parameter of the phase transformation, and subsequently determines the preferred transformation pathways and the distribution of diffuse scattering streaks. This work establishes a relationship between the transformation mechanism, the precursor phenomenon and the products after the MT under the influence of external fields

  9. Design of non-aggregating variants of Aβ peptide

    Energy Technology Data Exchange (ETDEWEB)

    Caine, Joanne M., E-mail: jo.caine@csiro.au [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Churches, Quentin; Waddington, Lynne [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Nigro, Julie; Breheney, Kerry [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Masters, Colin L. [CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Florey Institute for Neuroscience and Mental Health, 30 Royal Parade, Parkville, Victoria 3052 (Australia); Nuttall, Stewart D. [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia); Streltsov, Victor A., E-mail: victor.streltsov@csiro.au [CSIRO Materials Science and Engineering, 343 Royal Parade, Parkville, Victoria 3052 (Australia); Preventative Health Flagship, 343 Royal Parade, Parkville, Victoria 3052 (Australia); CRC for Mental Health, Level 2, 161 Barry Street, Carlton South, Victoria 3053 (Australia)

    2014-10-24

    Highlights: • Non-aggregating, non-toxic variants of Aβ peptide were designed using Aβ structure. • Mutations reduce aggregation by stabilising Aβ into small non-toxic oligomers. • Identification of these residues will assist the design of future therapeutic peptides. - Abstract: Self association of the amyloid-β (Aβ{sub 42}) peptide into oligomers, high molecular weight forms, fibrils and ultimately neuritic plaques, has been correlated with progressive cognitive decline in Alzheimer’s disease. Thus, insights into the drivers of the aggregation pathway have the capacity to significantly contribute to our understanding of disease mechanism. Functional assays and a three-dimensional crystal structure of the P3 amyloidogenic region 18–41 of Aβ were used to identify residues important in self-association and to design novel non-aggregating variants of the peptide. Biophysical studies (gel filtration, SDS–PAGE, dynamic light scattering, thioflavin T assay, and electron microscopy) demonstrate that in contrast to wild type Aβ these targeted mutations lose the ability to self-associate. Loss of aggregation also correlates with reduced neuronal toxicity. Our results highlight residues and regions of the Aβ peptide important for future targeting agents aimed at the amelioration of Alzheimer’s disease.

  10. Diversity and impact of rare variants in genes encoding the platelet G protein-coupled receptors.

    Science.gov (United States)

    Jones, Matthew L; Norman, Jane E; Morgan, Neil V; Mundell, Stuart J; Lordkipanidzé, Marie; Lowe, Gillian C; Daly, Martina E; Simpson, Michael A; Drake, Sian; Watson, Steve P; Mumford, Andrew D

    2015-04-01

    Platelet responses to activating agonists are influenced by common population variants within or near G protein-coupled receptor (GPCR) genes that affect receptor activity. However, the impact of rare GPCR gene variants is unknown. We describe the rare single nucleotide variants (SNVs) in the coding and splice regions of 18 GPCR genes in 7,595 exomes from the 1,000-genomes and Exome Sequencing Project databases and in 31 cases with inherited platelet function disorders (IPFDs). In the population databases, the GPCR gene target regions contained 740 SNVs (318 synonymous, 410 missense, 7 stop gain and 6 splice region) of which 70 % had global minor allele frequency (MAF) < 0.05 %. Functional annotation using six computational algorithms, experimental evidence and structural data identified 156/740 (21 %) SNVs as potentially damaging to GPCR function, most commonly in regions encoding the transmembrane and C-terminal intracellular receptor domains. In 31 index cases with IPFDs (Gi-pathway defect n=15; secretion defect n=11; thromboxane pathway defect n=3 and complex defect n=2) there were 256 SNVs in the target regions of 15 stimulatory platelet GPCRs (34 unique; 12 with MAF< 1 % and 22 with MAF≥ 1 %). These included rare variants predicting R122H, P258T and V207A substitutions in the P2Y12 receptor that were annotated as potentially damaging, but only partially explained the platelet function defects in each case. Our data highlight that potentially damaging variants in platelet GPCR genes have low individual frequencies, but are collectively abundant in the population. Potentially damaging variants are also present in pedigrees with IPFDs and may contribute to complex laboratory phenotypes.

  11. Normal variants of skin in neonates

    Directory of Open Access Journals (Sweden)

    Kulkarni M

    1996-01-01

    Full Text Available 2221 consecutive live births taking place between March 1994 and February 1995 were evaluated for a minimum period of 5 days to note for the occurrence of various normal anatomical variants specially those of skin. Birth weight, gestational age, maternal age, socio-economic status and consanguinity were carefully recorded in all the cases. Mongolian spots (72%, Epstein pearls (43.8%, Milia (26.2% and Erythema toxicum (25.2%, were the common dermatological variants noted. Maturity of the babies and possibly genetic factors (consanguinity are important factors in their causation as ordered in our study.

  12. Alpbach Summer School - a unique learning experience

    Science.gov (United States)

    Kern, K.; Aulinas, J.; Clifford, D.; Krejci, D.; Topham, R.

    2011-12-01

    The Alpbach Summer School is a ten-day program that provides a unique opportunity for young european science and engineering students, both undergraduate and graduate, to learn how to approach the entire design process of a space mission. The theme of the 2010 Summer School was "New Space Missions to Understand Climate Change", a current, challenging, very broad and complex topic. The program was established more than 35 years ago and is organised in two interrelated parts: a series of lectures held by renowned experts in the field (in the case of this specific year, climate change and space engineering experts) that provides a technical and scientific background for the workshops that follow, the core of the Summer School. For the workshops the students are split into four international, interdisciplinary teams of about 15 students. In 2010 every team had to complete a number of tasks, four in total: (1) identify climate change research gaps and design a space mission that has not yet been flown or proposed, (2) define the science objectives and requirements of the mission, (3) design a spacecraft that meets the mission requirements, which includes spacecraft design and construction, payload definition, orbit calculations, but also the satellite launch, operation and mission costs and (4) write up a short mission proposal and present the results to an expert review panel. Achieving these tasks in only a few days in a multicultural, interdisciplinary team represents a major challenge for all participants and provides an excellent practical learning experience. Over the course of the program, students do not just learn facts about climate change and space engineering, but scientists also learn from engineers and engineers from scientists. The participants have to deepen their knowledge in an often unfamiliar field, develop organisational and team-work skills and work under pressure. Moreover, teams are supported by team and roving tutors and get the opportunity to

  13. The curation of genetic variants: difficulties and possible solutions.

    Science.gov (United States)

    Pandey, Kapil Raj; Maden, Narendra; Poudel, Barsha; Pradhananga, Sailendra; Sharma, Amit Kumar

    2012-12-01

    The curation of genetic variants from biomedical articles is required for various clinical and research purposes. Nowadays, establishment of variant databases that include overall information about variants is becoming quite popular. These databases have immense utility, serving as a user-friendly information storehouse of variants for information seekers. While manual curation is the gold standard method for curation of variants, it can turn out to be time-consuming on a large scale thus necessitating the need for automation. Curation of variants described in biomedical literature may not be straightforward mainly due to various nomenclature and expression issues. Though current trends in paper writing on variants is inclined to the standard nomenclature such that variants can easily be retrieved, we have a massive store of variants in the literature that are present as non-standard names and the online search engines that are predominantly used may not be capable of finding them. For effective curation of variants, knowledge about the overall process of curation, nature and types of difficulties in curation, and ways to tackle the difficulties during the task are crucial. Only by effective curation, can variants be correctly interpreted. This paper presents the process and difficulties of curation of genetic variants with possible solutions and suggestions from our work experience in the field including literature support. The paper also highlights aspects of interpretation of genetic variants and the importance of writing papers on variants following standard and retrievable methods. Copyright © 2012. Published by Elsevier Ltd.

  14. Might "Unique" Factors Be "Common"? On the Possibility of Indeterminate Common-Unique Covariances

    Science.gov (United States)

    Grayson, Dave

    2006-01-01

    The present paper shows that the usual factor analytic structured data dispersion matrix lambda psi lambda' + delta can readily arise from a set of scores y = lambda eta + epsilon, shere the "common" (eta) and "unique" (epsilon) factors have nonzero covariance: gamma = Cov epsilon,eta) is not equal to 0. Implications of this finding are discussed…

  15. Detecting Beer Intake by Unique Metabolite Patterns.

    Science.gov (United States)

    Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

    2016-12-02

    Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

  16. Unique features in the ARIES glovebox line

    International Nuclear Information System (INIS)

    Martinez, H.E.; Brown, W.G.; Flamm, B.; James, C.A.; Laskie, R.; Nelson, T.O.; Wedman, D.E.

    1998-01-01

    A series of unique features have been incorporated into the Advanced Recovery and Integrated Extraction System (ARIES) at the Los Alamos National Laboratory, TA-55 Plutonium Facility. The features enhance the material handling in the process of the dismantlement of nuclear weapon primaries in the glovebox line. Incorporated into these features are the various plutonium process module's different ventilation zone requirements that the material handling systems must meet. These features include a conveyor system that consists of a remotely controlled cart that transverses the length of the conveyor glovebox, can be operated from a remote location and can deliver process components to the entrance of any selected module glovebox. Within the modules there exists linear motion material handling systems with lifting hoist, which are controlled via an Allen Bradley control panel or local control panels. To remove the packaged products from the hot process line, the package is processed through an air lock/electrolytic decontamination process that removes the radioactive contamination from the outside of the package container and allows the package to be removed from the process line

  17. Clinical EPR: Unique Opportunities and Some Challenges

    Science.gov (United States)

    Swartz, Harold M.; Williams, Benjamin B.; Zaki, Bassem I.; Hartford, Alan C.; Jarvis, Lesley A.; Chen, Eunice; Comi, Richard J.; Ernstoff, Marc S.; Hou, Huagang; Khan, Nadeem; Swarts, Steven G.; Flood, Ann B.; Kuppusamy, Periannan

    2014-01-01

    Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of important applications such as oxygen measurement, is challenged with several factors including the need for instrumentation customized for human subjects, probe and regulatory constraints. This paper describes the rationale and development of the first clinical EPR systems for two important clinical applications, namely, measurement of tissue oxygen (oximetry), and radiation dose (dosimetry) in humans. The clinical spectrometers operate at 1.2 GHz frequency and use surface loop resonators capable of providing topical measurements up to 1 cm depth in tissues. Tissue pO2 measurements can be carried out noninvasively and repeatedly after placement of an oxygen-sensitive paramagnetic material (currently India ink) at the site of interest. Our EPR dosimetry system is capable of measuring radiation-induced free radicals in the tooth of irradiated human subjects to determine the exposure dose. These developments offer potential opportunities for clinical dosimetry and oximetry, which include guiding therapy for individual patients with tumors or vascular disease, by monitoring of tissue oxygenation. Further work is in progress to translate this unique technology to routine clinical practice. PMID:24439333

  18. TDRSS S-shuttle unique receiver equipment

    Science.gov (United States)

    Weinberg, A.; Schwartz, J. J.; Spearing, R.

    1985-01-01

    Beginning with STS-9, the Tracking and Date Relay Satellite system (TDRSS) will start providing S- and Ku-band communications and tracking support to the Space Shuttle and its payloads. The most significant element of this support takes place at the TDRSS White Sands Ground Terminal, which processes the Shuttle return link S- and Ku-band signals. While Ku-band hardware available to other TDRSS users is also applied to Ku-Shuttle, stringent S-Shuttle link margins have precluded the application of the standard TDRSS S-band processing equipment to S-Shuttle. It was therfore found necessary to develop a unique S-Shuttle Receiver that embodies state-of-the-art digital technology and processing techniques. This receiver, developed by Motorola, Inc., enhances link margins by 1.5 dB relative to the standard S-band equipment and its bit error rate performance is within a few tenths of a dB of theory. An overview description of the Space Shuttle Receiver Equipment (SSRE) is presented which includes the presentation of block diagrams and salient design features. Selected, measured performance results are also presented.

  19. The AD: The unique anti-accelerator

    CERN Multimedia

    Slide show by Maximilien Brice. Voice (French only): Jacques Fichet. Content: Paola Catapano, Django Manglunki, CERN Bulletin

    2011-01-01

    Unlike other machines whose performance is measured in terms of energy records, AD's uniqueness resides in the fact that it can very effectively decelerate beams. At the hearth of antimatter production at CERN, the AD is making headlines in the world's press. This provides an excellent opportunity for us to retrace its history in images.   var flash_video_player=get_video_player_path(); insert_player_for_external('Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-0753-kbps-480x360-25-fps-audio-64-kbps-44-kHz-stereo', 'mms://mediastream.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-0480-kbps-384x288-25-fps-audio-128-kbps-48-kHz-stereo.wmv', 'false', 480, 360, 'http://mediaarchive.cern.ch/MediaArchive/Video/Public/Movies/2011/CERN-MOVIE-2011-083/CERN-MOVIE-2011-083-posterframe-480x360-at-5-percent.jpg', '1357551', true, '');  

  20. Hausdorff dimension of unique beta expansions

    International Nuclear Information System (INIS)

    Kong, Derong; Li, Wenxia

    2015-01-01

    Given an integer N ⩾ 2 and a real number β > 1, let Γ β, N be the set of all x=∑ i=1 ∞ d i /β i with d i  ∈ {0, 1, ···, N − 1} for all i ⩾ 1. The infinite sequence (d i ) is called a β-expansion of x. Let U β,N be the set of all x's in Γ β,N which have unique β-expansions. We give explicit formula of the Hausdorff dimension of U β,N for β in any admissible interval [β L , β U ], where β L is a purely Parry number while β U is a transcendental number whose quasi-greedy expansion of 1 is related to the classical Thue–Morse sequence. This allows us to calculate the Hausdorff dimension of U β,N for almost every β > 1. In particular, this improves the main results of Gábor Kallós (1999, 2001). Moreover, we find that the dimension function f(β) = dim H U β,N fluctuates frequently for β ∈ (1, N). (paper)

  1. Unique type of isolated cardiac valvular amyloidosis

    Directory of Open Access Journals (Sweden)

    Reehana Salma

    2006-10-01

    Full Text Available Abstract Background Amyloid deposition in heart is a common occurrence in systemic amyloidosis. But localised valvular amyloid deposits are very uncommon. It was only in 1922 that the cases of valvular amyloidosis were reported. Then in 1980, Goffin et al reported another type of valvular amyloidosis, which he called the dystrophic valvular amyloidosis. We report a case of aortic valve amyloidosis which is different from the yet described valvular amyloidosis. Case presentation A 72 years old gentleman underwent urgent aortic valve replacement. Intraoperatively, a lesion was found attached to the inferior surface of his bicuspid aortic valve. Histopathology examination of the valve revealed that the lesion contained amyloid deposits, identified as AL amyloidosis. The serum amyloid A protein (SAP scan was normal and showed no evidence of systemic amyloidosis. The ECG and echocardiogram were not consistent with cardiac amyloidosis. Conclusion Two major types of cardiac amyloidosis have been described in literature: primary-myelomatous type (occurs with systemic amyolidosis, and senile type(s. Recently, a localised cardiac dystrophic valvular amyloidosis has been described. In all previously reported cases, there was a strong association of localised valvular amyloidosis with calcific deposits. Ours is a unique case which differs from the previously reported cases of localised valvular amyloidosis. In this case, the lesion was not associated with any scar tissue. Also there was no calcific deposit found. This may well be a yet unknown type of isolated valvular amyloidosis.

  2. A Unique Civil Engineering Capstone Design Course

    Directory of Open Access Journals (Sweden)

    G Padmanabhan

    2018-02-01

    Full Text Available The North Dakota State University, USA, capstone course was developed as a unique model in response to the effort of the Accreditation Board of Engineering and Technology, USA, to streamline and improve design instruction in the curriculum and has steadily evolved to keep pace with the ever-changing technology and the expectations of the profession and the society we serve. A capstone design course by definition should be a design experience for students in the final year before graduation integrating all major design concepts they have learned up until then in the program. Carefully chosen real world projects with design content in all sub-disciplines of civil engineering are assigned in this team-taught course. Faculty and practicing professionals make presentations on design process; project management; leadership in an engineering environment; and public policy; global perspectives in engineering; and professional career and licensure. Practicing professionals also critique the final student presentations. Students work in teams with number of faculty serving as technical consultants, and a faculty mentor for each team to provide non-technical guidance and direction. The course requires students to demonstrate mastery of the curriculum and to work with others in a team environment. Course assessment includes evaluation of the final design, presentations, written technical reports, project design schedule, a project design journal, and reaction papers.

  3. Dynamic combinatorial chemistry

    NARCIS (Netherlands)

    Otto, Sijbren; Furlan, Ricardo L.E.; Sanders, Jeremy K.M.

    2002-01-01

    A combinatorial library that responds to its target by increasing the concentration of strong binders at the expense of weak binders sounds ideal. Dynamic combinatorial chemistry has the potential to achieve exactly this. In this review, we will highlight the unique features that distinguish dynamic

  4. Variants of Evolutionary Algorithms for Real-World Applications

    CERN Document Server

    Weise, Thomas; Michalewicz, Zbigniew

    2012-01-01

    Evolutionary Algorithms (EAs) are population-based, stochastic search algorithms that mimic natural evolution. Due to their ability to find excellent solutions for conventionally hard and dynamic problems within acceptable time, EAs have attracted interest from many researchers and practitioners in recent years. This book “Variants of Evolutionary Algorithms for Real-World Applications” aims to promote the practitioner’s view on EAs by providing a comprehensive discussion of how EAs can be adapted to the requirements of various applications in the real-world domains. It comprises 14 chapters, including an introductory chapter re-visiting the fundamental question of what an EA is and other chapters addressing a range of real-world problems such as production process planning, inventory system and supply chain network optimisation, task-based jobs assignment, planning for CNC-based work piece construction, mechanical/ship design tasks that involve runtime-intense simulations, data mining for the predictio...

  5. Investigation of protein selectivity in multimodal chromatography using in silico designed Fab fragment variants.

    Science.gov (United States)

    Karkov, Hanne Sophie; Krogh, Berit Olsen; Woo, James; Parimal, Siddharth; Ahmadian, Haleh; Cramer, Steven M

    2015-11-01

    In this study, a unique set of antibody Fab fragments was designed in silico and produced to examine the relationship between protein surface properties and selectivity in multimodal chromatographic systems. We hypothesized that multimodal ligands containing both hydrophobic and charged moieties would interact strongly with protein surface regions where charged groups and hydrophobic patches were in close spatial proximity. Protein surface property characterization tools were employed to identify the potential multimodal ligand binding regions on the Fab fragment of a humanized antibody and to evaluate the impact of mutations on surface charge and hydrophobicity. Twenty Fab variants were generated by site-directed mutagenesis, recombinant expression, and affinity purification. Column gradient experiments were carried out with the Fab variants in multimodal, cation-exchange, and hydrophobic interaction chromatographic systems. The results clearly indicated that selectivity in the multimodal system was different from the other chromatographic modes examined. Column retention data for the reduced charge Fab variants identified a binding site comprising light chain CDR1 as the main electrostatic interaction site for the multimodal and cation-exchange ligands. Furthermore, the multimodal ligand binding was enhanced by additional hydrophobic contributions as evident from the results obtained with hydrophobic Fab variants. The use of in silico protein surface property analyses combined with molecular biology techniques, protein expression, and chromatographic evaluations represents a previously undescribed and powerful approach for investigating multimodal selectivity with complex biomolecules. © 2015 Wiley Periodicals, Inc.

  6. Identification of Five Novel Variants in Chinese Oculocutaneous Albinism by Targeted Next-Generation Sequencing.

    Science.gov (United States)

    Qiu, Biyuan; Ma, Tao; Peng, Chunyan; Zheng, Xiaoqin; Yang, Jiyun

    2018-04-01

    The diagnosis of oculocutaneous albinism (OCA) is established using clinical signs and symptoms. OCA is, however, a highly genetically heterogeneous disease with mutations identified in at least nineteen unique genes, many of which produce overlapping phenotypic traits. Thus, differentiating genetic OCA subtypes for diagnoses and genetic counseling is challenging, based on clinical presentation alone, and would benefit from a comprehensive molecular diagnostic. To develop and validate a more comprehensive, targeted, next-generation-sequencing-based diagnostic for the identification of OCA-causing variants. The genomic DNA samples from 28 OCA probands were analyzed by targeted next-generation sequencing (NGS), and the candidate variants were confirmed through Sanger sequencing. We observed mutations in the TYR, OCA2, and SLC45A2 genes in 25/28 (89%) patients with OCA. We identified 38 pathogenic variants among these three genes, including 5 novel variants: c.1970G>T (p.Gly657Val), c.1669A>C (p.Thr557Pro), c.2339-2A>C, and c.1349C>G (p.Thr450Arg) in OCA2; c.459_470delTTTTGCTGCCGA (p.Ala155_Phe158del) in SLC45A2. Our findings expand the mutational spectrum of OCA in the Chinese population, and the assay we developed should be broadly useful as a molecular diagnostic, and as an aid for genetic counseling for OCA patients.

  7. Magnetic resonance angiography: infrequent anatomic variants

    International Nuclear Information System (INIS)

    Trejo, Mariano; Meli, Francisco; Lambre, Hector; Blessing, Ricardo; Gigy Traynor, Ignacio; Miguez, Victor

    2002-01-01

    We studied through RM angiography (3D TOF) with high magnetic field equipment (1.5 T) different infrequent intracerebral vascular anatomic variants. For their detection we emphasise the value of post-processed images obtained after conventional angiographic sequences. These post-processed images should be included in routine protocols for evaluation of the intracerebral vascular structures. (author)

  8. Report of a rare anatomic variant

    DEFF Research Database (Denmark)

    De Brucker, Y; Ilsen, B; Muylaert, C

    2015-01-01

    We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a left...

  9. Cellobiohydrolase I gene and improved variants

    Science.gov (United States)

    Adney, William S [Golden, CO; Decker, Stephen R [Berthoud, CO; Mc Carter, Suzanne [San Carlos, CA; Baker, John O [Golden, CO; Nieves, Raphael [Lakewood, CO; Himmel, Michael E [Littleton, CO; Vinzant, Todd B [Golden, CO

    2008-05-20

    The disclosure provides a method for preparing an active exoglucanase in a heterologous host of eukaryotic origin. The method includes mutagenesis to reduce glycosylation of the exoglucanase when expressed in a heterologous host. It is further disclosed a method to produce variant cellobiohydrolase that is stable at high temperature through mutagenesis.

  10. XVCL: XML-based Variant Configuration Language

    DEFF Research Database (Denmark)

    Jarzabek, Stan; Basset, Paul; Zhang, Hongyu

    2003-01-01

    XVCL (XML-based Variant Configuration Language) is a meta-programming technique and tool that provides effective reuse mechanisms. XVCL is an open source software developed at the National University of Singapore. Being a modern and versatile version of Bassett's frames, a technology that has...

  11. Glucose 6-phosphate dehydrogenase variants in Japan.

    Science.gov (United States)

    Miwa, S

    1980-01-01

    Fifty-four cases of glucose 6-phosphate dehydrogenase (G6PD) deficiency have so far been reported in Japan. Among them, 21 G6PD variants have been characterized. Nineteen out of the 21 variants were characterized in our laboratory and G6PD Heian and "Kyoto" by others. G6PD Tokyo, Tokushima, Ogikubo, Kurume, Fukushima, Yokohama, Yamaguchi, Wakayama, Akita, Heian and "Kyoto" were classified as Class 1, because all these cases showed chronic hemolytic anemia and severe enzyme deficiency. All these variants showed thermal instability. G6PD Mediterranean-like, Ogori, Gifu and Fukuoka were classified as Class 2, whereas G6PD Hofu, B(-) Chinese, Ube, Konan, Kamiube and Kiwa belonged to Class 3. All the 6 Class 3 variants were found as the results of the screening tests. The incidence of the deficiency in Japanese seems to be 0.1-0.5% but that of the cases which may slow drug-induced hemolysis would be much less. G6PD Ube and Konan appear to be relatively common in Japan.

  12. Genetic variants influencing phenotypic variance heterogeneity.

    Science.gov (United States)

    Ek, Weronica E; Rask-Andersen, Mathias; Karlsson, Torgny; Enroth, Stefan; Gyllensten, Ulf; Johansson, Åsa

    2018-03-01

    Most genetic studies identify genetic variants associated with disease risk or with the mean value of a quantitative trait. More rarely, genetic variants associated with variance heterogeneity are considered. In this study, we have identified such variance single-nucleotide polymorphisms (vSNPs) and examined if these represent biological gene × gene or gene × environment interactions or statistical artifacts caused by multiple linked genetic variants influencing the same phenotype. We have performed a genome-wide study, to identify vSNPs associated with variance heterogeneity in DNA methylation levels. Genotype data from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified vSNPs for 7195 CpG sites (P mean DNA methylation levels. We further showed that variance heterogeneity between genotypes mainly represents additional, often rare, SNPs in linkage disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low frequency variants co-segregating with one of the vSNP alleles. Therefore, our results suggest that variance heterogeneity of DNA methylation mainly represents phenotypic effects by multiple SNPs, rather than biological interactions. Such effects may also be important for interpreting variance heterogeneity of more complex clinical phenotypes.

  13. Genetic variants associated with lung function

    DEFF Research Database (Denmark)

    Thyagarajan, Bharat; Wojczynski, Mary; Minster, Ryan L

    2014-01-01

    with exceptional longevity have not been identified. METHOD: We conducted a genome wide association study (GWAS) to identify novel genetic variants associated with lung function in the Long Life Family Study (LLFS) (n = 3,899). Replication was performed using data from the CHARGE/SpiroMeta consortia...

  14. Study of Wind Effects on Unique Buildings

    Science.gov (United States)

    Olenkov, V.; Puzyrev, P.

    2017-11-01

    The article deals with a numerical simulation of wind effects on the building of the Church of the Intercession of the Holy Virgin in the village Bulzi of the Chelyabinsk region. We presented a calculation algorithm and obtained pressure fields, velocity fields and the fields of kinetic energy of a wind stream, as well as streamlines. Computational fluid dynamic (CFD) evolved three decades ago at the interfaces of calculus mathematics and theoretical hydromechanics and has become a separate branch of science the subject of which is a numerical simulation of different fluid and gas flows as well as the solution of arising problems with the help of methods that involve computer systems. This scientific field which is of a great practical value is intensively developing. The increase in CFD-calculations is caused by the improvement of computer technologies, creation of multipurpose easy-to-use CFD-packagers that are available to a wide group of researchers and cope with various tasks. Such programs are not only competitive in comparison with physical experiments but sometimes they provide the only opportunity to answer the research questions. The following advantages of computer simulation can be pointed out: a) Reduction in time spent on design and development of a model in comparison with a real experiment (variation of boundary conditions). b) Numerical experiment allows for the simulation of conditions that are not reproducible with environmental tests (use of ideal gas as environment). c) Use of computational gas dynamics methods provides a researcher with a complete and ample information that is necessary to fully describe different processes of the experiment. d) Economic efficiency of computer calculations is more attractive than an experiment. e) Possibility to modify a computational model which ensures efficient timing (change of the sizes of wall layer cells in accordance with the chosen turbulence model).

  15. Lourdes: A uniquely Catholic approach to medicine.

    Science.gov (United States)

    Dichoso, Travis Jon

    2015-02-01

    As an American medical student, I spent the summer break between my first and second year in Lourdes, France, the site where the Immaculate Conception appeared eighteen times to St. Bernadette in 1858 as proclaimed approved by the Catholic Church and whose water is associated with over seven thousand unexplained cures. During this time I volunteered with St. Joseph's Service and Poste Secour, followed several medical teams taking care of large pilgrim groups, and shadowed Dr. Alessandro de Franciscis the president of Le Bureau des Constations Médicales, the office in Lourdes charged with investigating claims of miracles. Through my experiences, I found the mission of medicine in Lourdes to be twofold: to provide the critical care needed to give sick persons the chance to transform their experience of disease through their faith; and secondly, through the efforts of the Medical Bureau, to be an instrument by which we can comprehend the wonders of the work of God. I conclude that this twofold mission should inform the work of every Catholic in health care or research, and Lourdes provides the venue par excellence to cultivate this mission. Lay Summary: Lourdes is a pilgrimage site in southern France that has been associated with medical miracles for the past 150 years. The site is unique in that throughout its history, physicians, of any or no faith, have been invited to participate in the proceedings of the investigations of each claimed cure. The investigations have formalized into a process handled by the Lourdes Medical Bureau and the Lourdes International Medical Association. Travis Dichoso, an American medical student, writes about his experiences as part of this process.

  16. Evolution of a Unique Systems Engineering Capability

    Energy Technology Data Exchange (ETDEWEB)

    Robert M. Caliva; James A. Murphy; Kyle B. Oswald

    2011-06-01

    The Idaho National Laboratory (INL) is a science-based, applied engineering laboratory dedicated to supporting U.S. Department of Energy missions in nuclear and energy research, science, and national security. The INL’s Systems Engineering organization supports all of the various programs under this wide array of missions. As with any multifaceted organization, strategic planning is essential to establishing a consistent culture and a value discipline throughout all levels of the enterprise. While an organization can pursue operational excellence, product leadership or customer intimacy, it is extremely difficult to excel or achieve best-in-class at all three. In fact, trying to do so has resulted in the demise of a number of organizations given the very intricate balancing act that is necessary. The INL’s Systems Engineering Department has chosen to focus on customer intimacy where the customer’s needs are first and foremost and a more total solution is the goal. Frequently a total solution requires the employment of specialized tools to manage system complexity. However, it is only after understanding customer needs that tool selection and use would be pursued. This results in using both commercial-off-the-shelf (COTS) tools and, in some cases, requires internal development of specialized tools. This paper describes how a unique systems engineering capability, through the development of customized tools, evolved as a result of this customer-focused culture. It also addresses the need for a common information model or analysis framework and presents an overview of the tools developed to manage and display relationships between entities, support trade studies through the application of utility theory, and facilitate the development of a technology roadmap to manage system risk and uncertainty.

  17. Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs.

    Directory of Open Access Journals (Sweden)

    Jonas Donner

    2018-04-01

    Full Text Available Knowledge on the genetic epidemiology of disorders in the dog population has implications for both veterinary medicine and sustainable breeding. Limited data on frequencies of genetic disease variants across breeds exists, and the disease heritage of mixed breed dogs remains poorly explored to date. Advances in genetic screening technologies now enable comprehensive investigations of the canine disease heritage, and generate health-related big data that can be turned into action. We pursued population screening of genetic variants implicated in Mendelian disorders in the largest canine study sample examined to date by examining over 83,000 mixed breed and 18,000 purebred dogs representing 330 breeds for 152 known variants using a custom-designed beadchip microarray. We further announce the creation of MyBreedData (www.mybreeddata.com, an online updated inherited disorder prevalence resource with its foundation in the generated data. We identified the most prevalent, and rare, disease susceptibility variants across the general dog population while providing the first extensive snapshot of the mixed breed disease heritage. Approximately two in five dogs carried at least one copy of a tested disease variant. Most disease variants are shared by both mixed breeds and purebreds, while breed- or line-specificity of others is strongly suggested. Mixed breed dogs were more likely to carry a common recessive disease, whereas purebreds were more likely to be genetically affected with one, providing DNA-based evidence for hybrid vigor. We discovered genetic presence of 22 disease variants in at least one additional breed in which they were previously undescribed. Some mutations likely manifest similarly independently of breed background; however, we emphasize the need for follow up investigations in each case and provide a suggested validation protocol for broader consideration. In conclusion, our study provides unique insight into genetic epidemiology of

  18. Kerala: a unique model of development.

    Science.gov (United States)

    Kannan, K P; Thankappan, K R; Ramankutty, V; Aravindan, K P

    1991-12-01

    This article capsules health in terms of morbidity, mortality, and maternal and child health; sex ratios, and population density in Kerala state in India from a more expanded report. Kerala state is known for its highly literate and female literate, and poor income population, but its well advanced state of demographic transition. There is a declining population growth rate, a high average marriage age, a low fertility rate, and a high degree of population mobility. One of the unique features of Kerala is the high female literacy, and the favorable position of women in decision making and a matrilineal inheritance mode. The rights of the poor and underprivileged have been upheld. The largest part of government revenue is spent on education followed by health. Traditional healing systems such the ayurveda are strong in Kerala, and Christian missionaries have contributed to a caring tradition. Morbidity is high and mortality is low because medical interventions have affected morality only. The reduction of poverty and environmentally related diseases has not been accomplished inspite of land reform, mass schooling, and general egalitarian policies. Mortality declines and a decline in birth rates have lead to a more adult and aged population, which increases the prevalence of chronic degenerative diseases. Historically, the death rate in Kerala was always lower (25/1000 in 1930 and 6.4 in 1986). The gains in mortality were made in reducing infant mortality (27/1000), which is 4 times less than India as a whole and comparable to Korea, Panama, Yugoslavia, Sri Lanka, and Colombia. Lower female mortality occurs in the 0-4 years. Life expectancy which was the same as India's in 1930 is currently 12 years higher than India's. Females have a higher expectation of life. The sex ratio in 1981 was 1032 compared to India's of 935. Kerala had almost replacement level in 1985. The crude birth rate is 21 versus 32 for India. In addition to the decline in death rates of those 5

  19. Influenza A (H3N2) Variant Virus

    Science.gov (United States)

    ... Swine Variant Pandemic Other Influenza A (H3N2) Variant Virus Language: English (US) Español Recommend on Facebook Tweet Share Compartir Influenza viruses that normally circulate in pigs are called “variant” ...

  20. Treatment of spelling variants in Setswana monolingual dictionaries

    African Journals Online (AJOL)

    user

    . ..... Table 8: Variants of Names of persons and places. Setswana variants. English. Aforika, Aferika. Africa. Baebele, Babele, Beibele. Bible. Ennyelane, Engelane ..... MWEs. As in variation amongst individual words, the MWEs such as idioms.

  1. Combined analyses of 20 common obesity susceptibility variants

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Sparsø, Thomas; Grarup, Niels

    2010-01-01

    Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes.......Genome-wide association studies and linkage studies have identified 20 validated genetic variants associated with obesity and/or related phenotypes. The variants are common, and they individually exhibit small-to-modest effect sizes....

  2. [Unique properties of highly radioresistant bacteria].

    Science.gov (United States)

    Romanovskaia, V A; Rokitko, P V; Malashenko, Iu R

    2000-01-01

    In connection with the Chernobyl Nuclear Power Plant (ChNPP) accident and the negative ecological after-effects for biota in this zone the interest has arisen to radioresistant bacteria, as to the most dynamic model of the given ecosystem, and to mechanisms which provide resistance of bacteria to ionizing radiation. The analysis of published data has shown that the radioresistant bacteria are not interrelated taxonomically and phylogenetically. The extreme radioresistant bacteria are represented by the Deinococcus species, which form a group phylogenetically close to the line Thermus-Meiothermus. Other radioresistant bacteria are the representatives of the genera Rubrobacter, Methylobacterium, Kocuria, Bacillus and some archebacteria. Data on natural habitats, of radioresistant bacteria are not numerous. In a number of cases it is difficult to distinguish their natural habitats, as they were isolated from the samples which were previously exposed to X-ray or gamma-irradiation, or from the ecosystems with the naturally raised radioactivity. To understand the strategy of survival of radioresistant bacteria, we briefly reviewed the mechanism of action of various species of radiation on cells and macromolecules; physiological signs of the cell damage caused by radiation; mechanisms eliminating (repairing) these damages. More details on mechanisms of the DNA repair in D. radiodurans are described. The extreme resistance of D. radiodurans to the DNA damaging factors is defined by 1) repair mechanisms which fundamentally differ from those in other procaryotes; 2) ability to increase the efficiency of a standard set of the DNA repairing proteins. Literary and own data on the effect of radiation on survival of various groups of bacteria in natural ecosystems are summarized. The ecological consequences of the ChNPP accident for soil bacteria in this region were estimated. The reduction of the number of soil bacteria and recession of microbial diversity under the effect of

  3. Two Galaxies for a Unique Event

    Science.gov (United States)

    2009-04-01

    To celebrate the 100 Hours of Astronomy, ESO is sharing two stunning images of unusual galaxies, both belonging to the Sculptor group of galaxies. The images, obtained at two of ESO's observatories at La Silla and Paranal in Chile, illustrate the beauty of astronomy. ESO PR Photo 14a/09 Irregular Galaxy NGC 55 ESO PR Photo 14b/09 Spiral Galaxy NGC 7793 As part of the International Year of Astronomy 2009 Cornerstone project, 100 Hours of Astronomy, the ambitious "Around the World in 80 Telescopes" event is a unique live webcast over 24 hours, following night and day around the globe to some of the most advanced observatories on and off the planet. To provide a long-lasting memory of this amazing world tour, observatories worldwide are revealing wonderful, and previously unseen, astronomical images. For its part, ESO is releasing outstanding pictures of two galaxies, observed with telescopes at the La Silla and Paranal observatories. The first of these depicts the irregular galaxy NGC 55, a member of the prominent Sculptor group of galaxies in the southern constellation of Sculptor. The galaxy is about 70 000 light-years across, that is, a little bit smaller than our own Milky Way. NGC 55 actually resembles more our galactic neighbour, the Large Magellanic Cloud (LMC), although the LMC is seen face-on, whilst NGC 55 is edge-on. By studying about 20 planetary nebulae in this image, a team of astronomers found that NGC 55 is located about 7.5 million light-years away. They also found that the galaxy might be forming a bound pair with the gorgeous spiral galaxy NGC 300 . Planetary nebulae are the final blooming of Sun-like stars before their retirement as white dwarfs. This striking image of NGC 55, obtained with the Wide Field Imager on the 2.2-metre MPG/ESO telescope at La Silla, is dusted with a flurry of reddish nebulae, created by young, hot massive stars. Some of the more extended ones are not unlike those seen in the LMC, such as the Tarantula Nebula. The quality

  4. ROSAT Discovers Unique, Distant Cluster of Galaxies

    Science.gov (United States)

    1995-06-01

    Brightest X-ray Cluster Acts as Strong Gravitational Lens Based on exciting new data obtained with the ROSAT X-ray satellite and a ground-based telescope at the ESO La Silla Observatory, a team of European astronomers [2] has just discovered a very distant cluster of galaxies with unique properties. It emits the strongest X-ray emission of any cluster ever observed by ROSAT and is accompanied by two extraordinarily luminous arcs that represent the gravitationally deflected images of even more distant objects. The combination of these unusual characteristics makes this cluster, now known as RXJ1347.5-1145, a most interesting object for further cosmological studies. DISCOVERY AND FOLLOW-UP OBSERVATIONS This strange cluster of galaxies was discovered during the All Sky Survey with the ROSAT X-ray satellite as a moderately intense X-ray source in the constellation of Virgo. It could not be identified with any already known object and additional ground-based observations were therefore soon after performed with the Max-Planck-Society/ESO 2.2-metre telescope at the La Silla observatory in Chile. These observations took place within a large--scale redshift survey of X-ray clusters of galaxies detected by the ROSAT All Sky Survey, a so-called ``ESO Key Programme'' led by astronomers from the Max-Planck-Institut fur Extraterrestrische Physik and the Osservatorio Astronomico di Brera. The main aim of this programme is to identify cluster X-ray sources, to determine the distance to the X-ray emitting clusters and to investigate their overall properties. These observations permitted to measure the redshift of the RXJ1347.5-1145 cluster as z = 0.45, i.e. it moves away from us with a velocity (about 106,000 km/sec) equal to about one-third of the velocity of light. This is an effect of the general expansion of the universe and it allows to determine the distance as about 5,000 million light-years (assuming a Hubble constant of 75 km/sec/Mpc). In other words, we see these

  5. Uniqueness of thermodynamic projector and kinetic basis of molecular individualism

    Science.gov (United States)

    Gorban, Alexander N.; Karlin, Iliya V.

    2004-05-01

    Three results are presented: First, we solve the problem of persistence of dissipation for reduction of kinetic models. Kinetic equations with thermodynamic Lyapunov functions are studied. Uniqueness of the thermodynamic projector is proven: There exists only one projector which transforms any vector field equipped with the given Lyapunov function into a vector field with the same Lyapunov function for a given anzatz manifold which is not tangent to the Lyapunov function levels. Second, we use the thermodynamic projector for developing the short memory approximation and coarse-graining for general nonlinear dynamic systems. We prove that in this approximation the entropy production increases. ( The theorem about entropy overproduction.) In example, we apply the thermodynamic projector to derive the equations of reduced kinetics for the Fokker-Planck equation. A new class of closures is developed, the kinetic multipeak polyhedra. Distributions of this type are expected in kinetic models with multidimensional instability as universally as the Gaussian distribution appears for stable systems. The number of possible relatively stable states of a nonequilibrium system grows as 2 m, and the number of macroscopic parameters is in order mn, where n is the dimension of configuration space, and m is the number of independent unstable directions in this space. The elaborated class of closures and equations pretends to describe the effects of “molecular individualism”. This is the third result.

  6. Novel criteria of uniqueness for signal reconstruction from phase

    NARCIS (Netherlands)

    Ma, C.

    1991-01-01

    An approach for ascertaining whether a signal is uniquely determined by its Fourier transform phase is proposed. It is shown that uniqueness corresponds to the nonsingularity of a matrix which can be formed from the finite-length real sequence. The criterion of uniqueness for reconstructing a

  7. Development of industrial variant specification systems

    DEFF Research Database (Denmark)

    Hansen, Benjamin Loer

    be developed from a holistic and strategically anchored point of view. Another assumption is that this is a challenge for many industrial companies. Even though the literature presents many considerations on general issues covering new information technology, little work is found on the business perspectives...... are discussed. A list of structural variables and solution components has been created. These are related to four design aspects in the holistic system design covering the aspects of process design, selection of resources (such as hardware, software and humans), the design of information structures...... solution elements and structural variables to be used in the design of variant specification systems. The thesis presents a “top-down” procedure to be used to develop variant specification systems from a strategically anchored and holistic point of view. A methodology and related task variables...

  8. Angiography of histopathologic variants of synovial sarcoma

    International Nuclear Information System (INIS)

    Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

    1986-01-01

    Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

  9. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  10. Glucose oxidase variants with improved properities

    OpenAIRE

    Fischer, Rainer; Ostafe, Raluca; Prodanovic, Radivoje

    2014-01-01

    Source: WO14173822A3 [EN] The technology provided herein relates to novel variants of microbial glucose oxidase with improved properties, more specifically to polypeptides having glucose oxidase activity as their major enzymatic activity; to nucleic acid molecules encoding said glucose oxidases; vectors and host cells containing the nucleic acids and methods for producing the glucose oxidase; compositions comprising said glucose oxidase; methods for the preparation and production of such enzy...

  11. Unusual variant of Cantrell′s pentalogy?

    Directory of Open Access Journals (Sweden)

    Kumar Basant

    2008-01-01

    Full Text Available A 12-hour-old male infant presented with prolapsed abdominal content through a defect on left side of chest wall with respiratory distress. A thorough clinical examination suggested absence of ectopia cordis, abdominal wall defect, and any bony anomaly. The child expired after 6 hours of admission because of respiratory distress and electrolyte imbalance. Is congenital defect of chest wall associated with diaphragmatic hernia without ectopia cordis and omphalocele, an unusual variant of Cantrell′s pentalogy?

  12. Random Plant Viral Variants Attain Temporal Advantages During Systemic Infections and in Turn Resist other Variants of the Same Virus.

    Science.gov (United States)

    Zhang, Xiao-Feng; Guo, Jiangbo; Zhang, Xiuchun; Meulia, Tea; Paul, Pierce; Madden, Laurence V; Li, Dawei; Qu, Feng

    2015-10-20

    Infection of plants with viruses containing multiple variants frequently leads to dominance by a few random variants in the systemically infected leaves (SLs), for which a plausible explanation is lacking. We show here that SL dominance by a given viral variant is adequately explained by its fortuitous lead in systemic spread, coupled with its resistance to superinfection by other variants. We analyzed the fate of a multi-variant turnip crinkle virus (TCV) population in Arabidopsis and N. benthamiana plants. Both wild-type and RNA silencing-defective plants displayed a similar pattern of random dominance by a few variant genotypes, thus discounting a prominent role for RNA silencing. When introduced to plants sequentially as two subpopulations, a twelve-hour head-start was sufficient for the first set to dominate. Finally, SLs of TCV-infected plants became highly resistant to secondary invasions of another TCV variant. We propose that random distribution of variant foci on inoculated leaves allows different variants to lead systemic movement in different plants. The leading variants then colonize large areas of SLs, and resist the superinfection of lagging variants in the same areas. In conclusion, superinfection resistance is the primary driver of random enrichment of viral variants in systemically infected plants.

  13. Spatially variant periodic structures in electromagnetics

    Science.gov (United States)

    Rumpf, Raymond C.; Pazos, Javier J.; Digaum, Jennefir L.; Kuebler, Stephen M.

    2015-01-01

    Spatial transforms are a popular technique for designing periodic structures that are macroscopically inhomogeneous. The structures are often required to be anisotropic, provide a magnetic response, and to have extreme values for the constitutive parameters in Maxwell's equations. Metamaterials and photonic crystals are capable of providing these, although sometimes only approximately. The problem still remains about how to generate the geometry of the final lattice when it is functionally graded, or spatially varied. This paper describes a simple numerical technique to spatially vary any periodic structure while minimizing deformations to the unit cells that would weaken or destroy the electromagnetic properties. New developments in this algorithm are disclosed that increase efficiency, improve the quality of the lattices and provide the ability to design aplanatic metasurfaces. The ability to spatially vary a lattice in this manner enables new design paradigms that are not possible using spatial transforms, three of which are discussed here. First, spatially variant self-collimating photonic crystals are shown to flow unguided waves around very tight bends using ordinary materials with low refractive index. Second, multi-mode waveguides in spatially variant band gap materials are shown to guide waves around bends without mixing power between the modes. Third, spatially variant anisotropic materials are shown to sculpt the near-field around electric components. This can be used to improve electromagnetic compatibility between components in close proximity. PMID:26217058

  14. Warty Carcinoma Penis: An Uncommon Variant

    Directory of Open Access Journals (Sweden)

    Sushma Thapa

    2017-01-01

    Full Text Available Penile carcinoma frequency varies widely in different parts of the world and comprises 1–10% of all the malignancies in males. Majority of the cases of penile carcinoma are squamous cell carcinoma of penis comprising 60% to 70% of all cases. Warty carcinoma of penis is an unusual neoplasm and a variant of penile squamous cell carcinoma comprising 5%–10% of all the variants. The other histological variants include basaloid, verrucous, papillary, sarcomatous, mixed, and adenosquamous carcinoma. The various histological entities with an exophytic papillary lesions including warty carcinoma are together referred to as the “verruciform” group of neoplasms. The warty carcinoma has to be differentiated from these lesions and is typically distinguished by histological features of hyperkeratosis, arborescent papillomatosis, acanthosis, and prominent koilocytosis with nuclear pleomorphism. We present a case of 65-year-old male with growth measuring 6×4 cm in the penis who underwent total penectomy and was diagnosed as warty carcinoma penis.

  15. Cryptanalysis of RSA and its variants

    CERN Document Server

    Hinek, M Jason

    2009-01-01

    Thirty years after RSA was first publicized, it remains an active research area. Although several good surveys exist, they are either slightly outdated or only focus on one type of attack. Offering an updated look at this field, Cryptanalysis of RSA and Its Variants presents the best known mathematical attacks on RSA and its main variants, including CRT-RSA, multi-prime RSA, and multi-power RSA. Divided into three parts, the book first introduces RSA and reviews the mathematical background needed for the majority of attacks described in the remainder of the text. It then brings together all of the most popular mathematical attacks on RSA and its variants. For each attack presented, the author includes a mathematical proof if possible or a mathematical justification for attacks that rely on assumptions. For the attacks that cannot be proven, he gives experimental evidence to illustrate their practical effectiveness. Focusing on mathematical attacks that exploit the structure of RSA and specific parameter choic...

  16. MR imaging of the ankle: Normal variants

    International Nuclear Information System (INIS)

    Noto, A.M.; Cheung, Y.; Rosenberg, Z.S.; Norman, A.; Leeds, N.E.

    1987-01-01

    Thirty asymptomatic ankles were studied with high-resolution surface coil MR imaging. The thirty ankles were reviewed for identification or normal structures. The MR appearance of the deltoid and posterior to talo-fibular ligaments, peroneous brevis and longus tendons, and posterior aspect of the tibial-talar joint demonstrated several normal variants not previously described. These should not be misinterpreted as pathologic processes. The specific findings included (1) cortical irregularity of the posterior tibial-talar joint in 27 of 30 cases which should not be mistaken for osteonecrois; (2) normal posterior talo-fibular ligament with irregular and frayed inhomogeneity, which represents a normal variant in seven of ten cases; and (3) fluid in the shared peroneal tendons sheath which may be confused for a longitudinal tendon tear in three of 30 cases. Ankle imaging with the use of MR is still a relatively new procedure. Further investigation is needed to better define normal anatomy as well as normal variants. The authors described several structures that normally present with variable MR imaging appearances. This is clinically significant in order to maintain a high sensitivity and specificity in MR imaging interpretation

  17. Establishment and Biological Characterization of a Panel of Glioblastoma Multiforme (GBM) and GBM Variant Oncosphere Cell Lines.

    Science.gov (United States)

    Binder, Zev A; Wilson, Kelli M; Salmasi, Vafi; Orr, Brent A; Eberhart, Charles G; Siu, I-Mei; Lim, Michael; Weingart, Jon D; Quinones-Hinojosa, Alfredo; Bettegowda, Chetan; Kassam, Amin B; Olivi, Alessandro; Brem, Henry; Riggins, Gregory J; Gallia, Gary L

    2016-01-01

    Human tumor cell lines form the basis of the majority of present day laboratory cancer research. These models are vital to studying the molecular biology of tumors and preclinical testing of new therapies. When compared to traditional adherent cell lines, suspension cell lines recapitulate the genetic profiles and histologic features of glioblastoma multiforme (GBM) with higher fidelity. Using a modified neural stem cell culture technique, here we report the characterization of GBM cell lines including GBM variants. Tumor tissue samples were obtained intra-operatively and cultured in neural stem cell conditions containing growth factors. Tumor lines were characterized in vitro using differentiation assays followed by immunostaining for lineage-specific markers. In vivo tumor formation was assayed by orthotopic injection in nude mice. Genetic uniqueness was confirmed via short tandem repeat (STR) DNA profiling. Thirteen oncosphere lines derived from GBM and GBM variants, including a GBM with PNET features and a GBM with oligodendroglioma component, were established. All unique lines showed distinct genetic profiles by STR profiling. The lines assayed demonstrated a range of in vitro growth rates. Multipotency was confirmed using in vitro differentiation. Tumor formation demonstrated histologic features consistent with high grade gliomas, including invasion, necrosis, abnormal vascularization, and high mitotic rate. Xenografts derived from the GBM variants maintained histopathological features of the primary tumors. We have generated and characterized GBM suspension lines derived from patients with GBMs and GBM variants. These oncosphere cell lines will expand the resources available for preclinical study.

  18. Changes in localization of human discs large (hDlg) during keratinocyte differentiation is associated with expression of alternatively spliced hDlg variants

    International Nuclear Information System (INIS)

    Roberts, S.; Calautti, E.; Vanderweil, S.; Nguyen, H.O.; Foley, A.; Baden, H.P.; Viel, A.

    2007-01-01

    Alternative spliced variants of the human discs large (hDlg) tumour suppressor are characterized by combinations of insertions. Here, using insertions I2- and I3-specific antibodies, we show that I2 and I3 variants have distinct distributions in epidermal and cervical epithelia. In skin and cervix, I3 variants are found in the cytoplasm. Cytoplasmic localization of I3 variants decreases as cervical keratinocytes differentiate, concomitant with relocalization to the cell periphery. I2 variants are found at the cell periphery of differentiated epidermal and cervical keratinocytes. Nuclear localization of I2 variants was evident in both tissues, with concentration of nuclear I2 variants in basal and parabasal cervical keratinocytes. A prominent nuclear localization of hDlg in cells of hyperproliferative layers of psoriatic lesions, but not in mature differentiated keratinocytes, together with I2 redistribution in differentiating keratinocytes, suggests that nuclear hDlg functions may be pertinent to growth of undifferentiated cells. Supporting our findings in squamous tissues, a decrease of nuclear hDlg and an increase of membrane-bound and cytoplasmic hDlg upon calcium-induced keratinocyte differentiation were not concomitant processes. Furthermore, we confirm that the exit of I2 variants from the nucleus is linked to stimulation of epithelial differentiation. The dynamic redistribution of hDlg also correlated with a marked increase in the expression of I3 variants while the level of I2 variants showed only a moderate decrease. Because changes in the intracellular distribution of hDlg splice variants, and in their expression levels, correlate with changes in differentiation state we hypothesize that the different hDlg isoforms play distinct roles at various stages of epithelial differentiation

  19. Annotating pathogenic non-coding variants in genic regions.

    Science.gov (United States)

    Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi; Ren, Zhong; La Carpia, Francesca; Halvorsen, Matt; Schoch, Kelly; Ratzon, Fanni; Heinzen, Erin L; Boland, Michael J; Petrovski, Slavé; Goldstein, David B

    2017-08-09

    Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.

  20. Variants of β-lactamase KPC-2 that are resistant to inhibition by avibactam.

    Science.gov (United States)

    Papp-Wallace, Krisztina M; Winkler, Marisa L; Taracila, Magdalena A; Bonomo, Robert A

    2015-07-01

    KPC-2 is the most prevalent class A carbapenemase in the world. Previously, KPC-2 was shown to hydrolyze the β-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam. In addition, substitutions at amino acid position R220 in the KPC-2 β-lactamase increased resistance to clavulanic acid. A novel bridged diazabicyclooctane (DBO) non-β-lactam β-lactamase inhibitor, avibactam, was shown to inactivate the KPC-2 β-lactamase. To better understand the mechanistic basis for inhibition of KPC-2 by avibactam, we tested the potency of ampicillin-avibactam and ceftazidime-avibactam against engineered variants of the KPC-2 β-lactamase that possessed single amino acid substitutions at important sites (i.e., Ambler positions 69, 130, 234, 220, and 276) that were previously shown to confer inhibitor resistance in TEM and SHV β-lactamases. To this end, we performed susceptibility testing, biochemical assays, and molecular modeling. Escherichia coli DH10B carrying KPC-2 β-lactamase variants with the substitutions S130G, K234R, and R220M demonstrated elevated MICs for only the ampicillin-avibactam combinations (e.g., 512, 64, and 32 mg/liter, respectively, versus the MICs for wild-type KPC-2 at 2 to 8 mg/liter). Steady-state kinetics revealed that the S130G variant of KPC-2 resisted inactivation by avibactam; the k2/K ratio was significantly lowered 4 logs for the S130G variant from the ratio for the wild-type enzyme (21,580 M(-1) s(-1) to 1.2 M(-1) s(-1)). Molecular modeling and molecular dynamics simulations suggested that the mobility of K73 and its ability to activate S70 (i.e., function as a general base) may be impaired in the S130G variant of KPC-2, thereby explaining the slowed acylation. Moreover, we also advance the idea that the protonation of the sulfate nitrogen of avibactam may be slowed in the S130G variant, as S130 is the likely proton donor and another residue, possibly K234, must compensate. Our findings show that residues S130 as well as K234 and R

  1. Microsatellite Instability Use in Mismatch Repair Gene Sequence Variant Classification

    Directory of Open Access Journals (Sweden)

    Bryony A. Thompson

    2015-03-01

    Full Text Available Inherited mutations in the DNA mismatch repair genes (MMR can cause MMR deficiency and increased susceptibility to colorectal and endometrial cancer. Microsatellite instability (MSI is the defining molecular signature of MMR deficiency. The clinical classification of identified MMR gene sequence variants has a direct impact on the management of patients and their families. For a significant proportion of cases sequence variants of uncertain clinical significance (also known as unclassified variants are identified, constituting a challenge for genetic counselling and clinical management of families. The effect on protein function of these variants is difficult to interpret. The presence or absence of MSI in tumours can aid in determining the pathogenicity of associated unclassified MMR gene variants. However, there are some considerations that need to be taken into account when using MSI for variant interpretation. The use of MSI and other tumour characteristics in MMR gene sequence variant classification will be explored in this review.

  2. Prions in the Urine of Patients with Variant Creutzfeldt–Jakob Disease

    Science.gov (United States)

    Moda, Fabio; Gambetti, Pierluigi; Notari, Silvio; Concha-Marambio, Luis; Catania, Marcella; Park, Kyung-Won; Maderna, Emanuela; Suardi, Silvia; Haïk, Stéphane; Brandel, Jean-Philippe; Ironside, James; Knight, Richard; Tagliavini, Fabrizio; Soto, Claudio

    2014-01-01

    BACKGROUND Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrPSc). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt–Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt–Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating. METHODS To investigate whether PrPSc can be detected in the urine of patients with variant Creutzfeldt–Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrPSc, enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt–Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons. RESULTS PrPSc was detectable only in the urine of patients with variant Creutzfeldt–Jakob disease and had the typical electrophoretic profile associated with this disease. PrPSc was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt–Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrPSc concentration in urine calculated by means of quantitative PMCA was estimated at 1×10−16 g per milliliter, or 3×10−21 mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrPSc per milliliter of urine. CONCLUSIONS Urine samples obtained from patients with variant Creutzfeldt–Jakob disease contained minute

  3. Prions in the urine of patients with variant Creutzfeldt-Jakob disease.

    Science.gov (United States)

    Moda, Fabio; Gambetti, Pierluigi; Notari, Silvio; Concha-Marambio, Luis; Catania, Marcella; Park, Kyung-Won; Maderna, Emanuela; Suardi, Silvia; Haïk, Stéphane; Brandel, Jean-Philippe; Ironside, James; Knight, Richard; Tagliavini, Fabrizio; Soto, Claudio

    2014-08-07

    Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrP(Sc)). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt-Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt-Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating. To investigate whether PrP(Sc) can be detected in the urine of patients with variant Creutzfeldt-Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrP(Sc), enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt-Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons. PrP(Sc) was detectable only in the urine of patients with variant Creutzfeldt-Jakob disease and had the typical electrophoretic profile associated with this disease. PrP(Sc) was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt-Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrP(Sc) concentration in urine calculated by means of quantitative PMCA was estimated at 1×10(-16) g per milliliter, or 3×10(-21) mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrP(Sc) per milliliter of urine. Urine samples obtained from patients with variant Creutzfeldt-Jakob disease contained minute quantities of PrP(Sc). (Funded by the

  4. Modeling and Validation of the Ecological Behavior of Wild-Type Listeria monocytogenes and Stress-Resistant Variants.

    Science.gov (United States)

    Metselaar, Karin I; Abee, Tjakko; Zwietering, Marcel H; den Besten, Heidy M W

    2016-09-01

    . monocytogenes and its stress-resistant variants. Predictions were validated under different conditions, as well as along a model food chain. This work illustrates the effects of environmental factors on population dynamics of L. monocytogenes and is a first step in evaluating the impact of population diversity on food safety. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Dirac fields in flat FLRW cosmology: Uniqueness of the Fock quantization

    Energy Technology Data Exchange (ETDEWEB)

    Cortez, Jerónimo, E-mail: jacq@ciencias.unam.mx [Departamento de Física, Facultad de Ciencias, Universidad Nacional Autónoma de México, México D.F. 04510 (Mexico); Elizaga Navascués, Beatriz, E-mail: beatriz.elizaga@iem.cfmac.csic.es [Instituto de Estructura de la Materia, IEM-CSIC, Serrano 121, 28006 Madrid (Spain); Martín-Benito, Mercedes, E-mail: m.martin@hef.ru.nl [Radboud University Nijmegen, Institute for Mathematics, Astrophysics and Particle Physics, Heyendaalseweg 135, NL-6525 AJ Nijmegen (Netherlands); Mena Marugán, Guillermo A., E-mail: mena@iem.cfmac.csic.es [Instituto de Estructura de la Materia, IEM-CSIC, Serrano 121, 28006 Madrid (Spain); Velhinho, José M., E-mail: jvelhi@ubi.pt [Universidade da Beira Interior, Rua Marquês d’Ávila e Bolama, 6201-001, Covilhã (Portugal)

    2017-01-15

    We address the issue of the infinite ambiguity that affects the construction of a Fock quantization of a Dirac field propagating in a cosmological spacetime with flat compact sections. In particular, we discuss a physical criterion that restricts to a unique possibility (up to unitary equivalence) the infinite set of available vacua. We prove that this desired uniqueness is guaranteed, for any possible choice of spin structure on the spatial sections, if we impose two conditions. The first one is that the symmetries of the classical system must be implemented quantum mechanically, so that the vacuum is invariant under the symmetry transformations. The second and more important condition is that the constructed theory must have a quantum dynamics that is implementable as a (non-trivial) unitary operator in Fock space. Actually, this unitarity of the quantum dynamics leads us to identify as explicitly time dependent some very specific contributions of the Dirac field. In doing that, we essentially characterize the part of the dynamics governed by the Dirac equation that is unitarily implementable. The uniqueness of the Fock vacuum is attained then once a physically motivated convention for the concepts of particles and antiparticles is fixed.

  6. Dirac fields in flat FLRW cosmology: Uniqueness of the Fock quantization

    International Nuclear Information System (INIS)

    Cortez, Jerónimo; Elizaga Navascués, Beatriz; Martín-Benito, Mercedes; Mena Marugán, Guillermo A.; Velhinho, José M.

    2017-01-01

    We address the issue of the infinite ambiguity that affects the construction of a Fock quantization of a Dirac field propagating in a cosmological spacetime with flat compact sections. In particular, we discuss a physical criterion that restricts to a unique possibility (up to unitary equivalence) the infinite set of available vacua. We prove that this desired uniqueness is guaranteed, for any possible choice of spin structure on the spatial sections, if we impose two conditions. The first one is that the symmetries of the classical system must be implemented quantum mechanically, so that the vacuum is invariant under the symmetry transformations. The second and more important condition is that the constructed theory must have a quantum dynamics that is implementable as a (non-trivial) unitary operator in Fock space. Actually, this unitarity of the quantum dynamics leads us to identify as explicitly time dependent some very specific contributions of the Dirac field. In doing that, we essentially characterize the part of the dynamics governed by the Dirac equation that is unitarily implementable. The uniqueness of the Fock vacuum is attained then once a physically motivated convention for the concepts of particles and antiparticles is fixed.

  7. A unique physeal injury of the distal phalanx.

    Science.gov (United States)

    Berber, Onur; Singh, Bijayendra

    2015-01-01

    An unusual Salter-Harris Type 1 fracture variant of the distal phalanx of the index finger is described. The epiphysis was dislocated, sitting dorsally over the middle phalanx head with the articular surface facing dorsal. Reduction could only be achieved through an open procedure. The reduction was stable without supplemental fixation.

  8. Clinical Relevance of Androgen Receptor Splice Variants in Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Maughan, Benjamin L; Antonarakis, Emmanuel S

    2015-12-01

    Metastatic castration-resistant prostate cancer (mCRPC) currently benefits from a wealth of treatment options, yet still remains lethal in the vast majority of patients. It is becoming increasingly understood that this disease entity continues to evolve over time, acquiring additional and diverse resistance mechanisms with each subsequent therapy used. This dynamic relationship between treatment pressure and disease resistance can be challenging for the managing clinician. The recent discovery of alternate splice variants of the androgen receptor (AR) is one potential mechanism of escape in mCRPC, and recognizing this resistance mechanism might be important for optimal treatment selection for our patients. AR-V7 appears to be the most relevant AR splice variant, and early clinical data suggest that it is a negative prognostic marker in mCRPC. Emerging evidence also suggests that detection of AR-V7 may be associated with resistance to novel hormonal therapy (abiraterone and enzalutamide) but may be compatible with sensitivity to taxane chemotherapy (docetaxel and cabazitaxel). Adding to this complexity is the observation that AR-V7 is a dynamic marker whose status may change across time and depending on selective pressures induced by different therapies. Finally, it is possible that AR-V7 may represent a therapeutic target in mCRPC if drugs can be designed that degrade or inhibit AR splice variants or block their transcriptional activity. Several such agents (including galeterone, EPI-506, and bromodomain/BET inhibitors) are now in clinical development.

  9. Genetic Variants Associated with Circulating Parathyroid Hormone.

    Science.gov (United States)

    Robinson-Cohen, Cassianne; Lutsey, Pamela L; Kleber, Marcus E; Nielson, Carrie M; Mitchell, Braxton D; Bis, Joshua C; Eny, Karen M; Portas, Laura; Eriksson, Joel; Lorentzon, Mattias; Koller, Daniel L; Milaneschi, Yuri; Teumer, Alexander; Pilz, Stefan; Nethander, Maria; Selvin, Elizabeth; Tang, Weihong; Weng, Lu-Chen; Wong, Hoi Suen; Lai, Dongbing; Peacock, Munro; Hannemann, Anke; Völker, Uwe; Homuth, Georg; Nauk, Matthias; Murgia, Federico; Pattee, Jack W; Orwoll, Eric; Zmuda, Joseph M; Riancho, Jose Antonio; Wolf, Myles; Williams, Frances; Penninx, Brenda; Econs, Michael J; Ryan, Kathleen A; Ohlsson, Claes; Paterson, Andrew D; Psaty, Bruce M; Siscovick, David S; Rotter, Jerome I; Pirastu, Mario; Streeten, Elizabeth; März, Winfried; Fox, Caroline; Coresh, Josef; Wallaschofski, Henri; Pankow, James S; de Boer, Ian H; Kestenbaum, Bryan

    2017-05-01

    Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies ( n =22,653 and n =6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 ( P =4.2 × 10 -53 ), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 ( P =6.6 × 10 -17 ), rs219779 adjacent to CLDN14 ( P =3.5 × 10 -16 ), rs4443100 near RTDR1 ( P =8.7 × 10 -9 ), and rs73186030 near CASR ( P =4.8 × 10 -8 ). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued. Copyright © 2017 by the American Society of Nephrology.

  10. Dynamical FLIC fermions

    International Nuclear Information System (INIS)

    Kamleh, W.; Leinweber, D.B.; Williams, A.G.

    2004-01-01

    The use of APE smearing or other blocking techniques in fermion actions can provide many advantages. There are many variants of these fat link actions in lattice QCD currently, such as FLIC fermions. The FLIC fermion formalism makes use of the APE blocking technique in combination with a projection of the blocked links back into the special unitary group. This reunitarisation is often performed using an iterative maximisation of a gauge invariant measure. This technique is not differentiable with respect to the gauge field and thus prevents the use of standard. Hybrid Monte Carlo simulation algorithms. The use of an alternative projection technique circumvents this difficulty and allows the simulation of dynamical fat link fermions with standard HMC and its variants

  11. Complex branchial fistula: a variant arch anomaly.

    Science.gov (United States)

    De Caluwé, D; Hayes, R; McDermott, M; Corbally, M T

    2001-07-01

    A 5-year-old boy presented with an infected left-sided branchial fistula. Despite antibiotic treatment and repeated excision of the fistula, purulent discharge from the wound persisted. Three-dimensional computed tomography (3D CT) reconstruction greatly facilitated the diagnosis and management of this case by showing the course of the fistulous tract. The complexity of the tract suggests that this represents a variant arch anomaly because it contains features of first, second, third, and fourth arch remnants. Copyright 2001 by W.B. Saunders Company.

  12. Anatomy, normal variants, and basic biomechanics

    International Nuclear Information System (INIS)

    Berquist, T.H.; Johnson, K.A.

    1989-01-01

    This paper reports on the anatomy and basic functions of the foot and ankle important to physicians involved in imaging procedures, clinical medicine, and surgery. New radiographic techniques especially magnetic resonance imaging, provide more diagnostic information owing to improved tissue contrast and the ability to obtain multiple image planes (axial, sagittal, coronal, oblique). Therefore, a thorough knowledge of skeletal and soft tissue anatomy is even more essential. Normal variants must also be understood in order to distinguish normal from pathologic changes in the foot and ankle. A basic understanding of biomechanics is also essential for selecting the proper diagnostic techniques

  13. Research progress of behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Xiao-hua GU

    2015-07-01

    Full Text Available There is no epidemiological data of frontotemporal dementia (FTD in China. The application of updated diagnostic criteria, publishing of frontotemporal lobar degeneration (FTLD consensus in China, development of multimodal imaging and biomarkers promote the clinical understanding on behavioral variant frontotemporal dementia (bvFTD. There is still no drugs treating FTD approved by U.S. Food and Drug Administration (FDA. Multidisciplinary intervention may delay the progression of bvFTD. DOI: 10.3969/j.issn.1672-6731.2015.07.006

  14. Oral fibrolipoma: A rare histological variant

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2014-01-01

    Full Text Available Lipomas are benign soft tissue mesenchymal neoplasms. Fibrolipoma is a histological variant of lipoma that mostly affects the buccal mucosa and causes functional and cosmetic disabilities. The diagnosis and differentiation of fibrolipoma with clinically similar lesions such as fibroma and pleomorphic adenoma is very essential for a correct treatment plan and complete follow-up. This article presents a case of a 35-year-old female with a fibrolipoma on the lingual marginal gingiva of the mandibular left third molar.

  15. Performance comparison of various time variant filters

    Energy Technology Data Exchange (ETDEWEB)

    Kuwata, M [JEOL Engineering Co. Ltd., Akishima, Tokyo (Japan); Husimi, K

    1996-07-01

    This paper describes the advantage of the trapezoidal filter used in semiconductor detector system comparing with the other time variant filters. The trapezoidal filter is the compose of a rectangular pre-filter and a gated integrator. We indicate that the best performance is obtained by the differential-integral summing type rectangular pre-filter. This filter is not only superior in performance, but also has the useful feature that the rising edge of the output waveform is linear. We introduce an example of this feature used in a high-energy experiment. (author)

  16. Understanding the unique assembly history of central group galaxies

    International Nuclear Information System (INIS)

    Vulcani, Benedetta; Bundy, Kevin; Lackner, Claire; Leauthaud, Alexie; Treu, Tommaso; Mei, Simona; Coccato, Lodovico; Kneib, Jean Paul; Auger, Matthew; Nipoti, Carlo

    2014-01-01

    Central galaxies (CGs) in massive halos live in unique environments with formation histories closely linked to that of the host halo. In local clusters, they have larger sizes (R e ) and lower velocity dispersions (σ) at fixed stellar mass M * , and much larger R e at a fixed σ than field and satellite galaxies (non-CGs). Using spectroscopic observations of group galaxies selected from the COSMOS survey, we compare the dynamical scaling relations of early-type CGs and non-CGs at z ∼ 0.6 to distinguish possible mechanisms that produce the required evolution. CGs are systematically offset toward larger R e at fixed σ compared to non-CGs with similar M * . The CG R e -M * relation also shows differences, primarily driven by a subpopulation (∼15%) of galaxies with large R e , while the M * -σ relations are indistinguishable. These results are accentuated when double Sérsic profiles, which better fit light in the outer regions of galaxies, are adopted. They suggest that even group-scale CGs can develop extended components by these redshifts that can increase total R e and M * estimates by factors of ∼2. To probe the evolutionary link between our sample and cluster CGs, we also analyze two cluster samples at z ∼ 0.6 and z ∼ 0. We find similar results for the more massive halos at comparable z, but much more distinct CG scaling relations at low-z. Thus, the rapid, late-time accretion of outer components, perhaps via the stripping and accretion of satellites, would appear to be a key feature that distinguishes the evolutionary history of CGs.

  17. Relevance of control theory to design and maintenance problems in time-variant reliability: The case of stochastic viability

    International Nuclear Information System (INIS)

    Rougé, Charles; Mathias, Jean-Denis; Deffuant, Guillaume

    2014-01-01

    The goal of this paper is twofold: (1) to show that time-variant reliability and a branch of control theory called stochastic viability address similar problems with different points of view, and (2) to demonstrate the relevance of concepts and methods from stochastic viability in reliability problems. On the one hand, reliability aims at evaluating the probability of failure of a system subjected to uncertainty and stochasticity. On the other hand, viability aims at maintaining a controlled dynamical system within a survival set. When the dynamical system is stochastic, this work shows that a viability problem belongs to a specific class of design and maintenance problems in time-variant reliability. Dynamic programming, which is used for solving Markovian stochastic viability problems, then yields the set of design states for which there exists a maintenance strategy which guarantees reliability with a confidence level β for a given period of time T. Besides, it leads to a straightforward computation of the date of the first outcrossing, informing on when the system is most likely to fail. We illustrate this approach with a simple example of population dynamics, including a case where load increases with time. - Highlights: • Time-variant reliability tools cannot devise complex maintenance strategies. • Stochastic viability is a control theory that computes a probability of failure. • Some design and maintenance problems are stochastic viability problems. • Used in viability, dynamic programming can find reliable maintenance actions. • Confronting reliability and control theories such as viability is promising

  18. Coexistence of uniquely ergodic subsystems of interval mapping

    International Nuclear Information System (INIS)

    Ye Xiangdong.

    1991-10-01

    The purpose of this paper is to show that uniquely ergodic subsystems of interval mapping also coexist in the same way as minimal sets do. To do this we give some notations in section 2. In section 3 we define D-function of a uniquely ergodic system and show its basic properties. We prove the coexistence of uniquely ergodic subsystems of interval mapping in section 4. Lastly we give the examples of uniquely ergodic systems with given D-functions in section 5. 27 refs

  19. TAPAS: tools to assist the targeted protein quantification of human alternative splice variants.

    Science.gov (United States)

    Yang, Jae-Seong; Sabidó, Eduard; Serrano, Luis; Kiel, Christina

    2014-10-15

    In proteomes of higher eukaryotes, many alternative splice variants can only be detected by their shared peptides. This makes it highly challenging to use peptide-centric mass spectrometry to distinguish and to quantify protein isoforms resulting from alternative splicing events. We have developed two complementary algorithms based on linear mathematical models to efficiently compute a minimal set of shared and unique peptides needed to quantify a set of isoforms and splice variants. Further, we developed a statistical method to estimate the splice variant abundances based on stable isotope labeled peptide quantities. The algorithms and databases are integrated in a web-based tool, and we have experimentally tested the limits of our quantification method using spiked proteins and cell extracts. The TAPAS server is available at URL http://davinci.crg.es/tapas/. luis.serrano@crg.eu or christina.kiel@crg.eu Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Furaldehyde substrate specificity and kinetics of Saccharomyces cerevisiae alcohol dehydrogenase 1 variants.

    Science.gov (United States)

    Laadan, Boaz; Wallace-Salinas, Valeria; Carlsson, Åsa Janfalk; Almeida, João Rm; Rådström, Peter; Gorwa-Grauslund, Marie F

    2014-08-09

    A previously discovered mutant of Saccharomyces cerevisiae alcohol dehydrogenase 1 (Adh1p) was shown to enable a unique NADH-dependent reduction of 5-hydroxymethylfurfural (HMF), a well-known inhibitor of yeast fermentation. In the present study, site-directed mutagenesis of both native and mutated ADH1 genes was performed in order to identify the key amino acids involved in this substrate shift, resulting in Adh1p-variants with different substrate specificities. In vitro activities of the Adh1p-variants using two furaldehydes, HMF and furfural, revealed that HMF reduction ability could be acquired after a single amino acid substitution (Y295C). The highest activity, however, was reached with the double mutation S110P Y295C. Kinetic characterization with both aldehydes and the in vivo primary substrate acetaldehyde also enabled to correlate the alterations in substrate affinity with the different amino acid substitutions. We demonstrated the key role of Y295C mutation in HMF reduction by Adh1p. We generated and kinetically characterized a group of protein variants using two furaldehyde compounds of industrial relevance. Also, we showed that there is a threshold after which higher in vitro HMF reduction activities do not correlate any more with faster in vivo rates of HMF conversion, indicating other cell limitations in the conversion of HMF.

  1. Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease

    Science.gov (United States)

    Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.

    2004-01-01

    Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates. PMID:14695328

  2. Common variants in Mendelian kidney disease genes and their association with renal function.

    Science.gov (United States)

    Parsa, Afshin; Fuchsberger, Christian; Köttgen, Anna; O'Seaghdha, Conall M; Pattaro, Cristian; de Andrade, Mariza; Chasman, Daniel I; Teumer, Alexander; Endlich, Karlhans; Olden, Matthias; Chen, Ming-Huei; Tin, Adrienne; Kim, Young J; Taliun, Daniel; Li, Man; Feitosa, Mary; Gorski, Mathias; Yang, Qiong; Hundertmark, Claudia; Foster, Meredith C; Glazer, Nicole; Isaacs, Aaron; Rao, Madhumathi; Smith, Albert V; O'Connell, Jeffrey R; Struchalin, Maksim; Tanaka, Toshiko; Li, Guo; Hwang, Shih-Jen; Atkinson, Elizabeth J; Lohman, Kurt; Cornelis, Marilyn C; Johansson, Asa; Tönjes, Anke; Dehghan, Abbas; Couraki, Vincent; Holliday, Elizabeth G; Sorice, Rossella; Kutalik, Zoltan; Lehtimäki, Terho; Esko, Tõnu; Deshmukh, Harshal; Ulivi, Sheila; Chu, Audrey Y; Murgia, Federico; Trompet, Stella; Imboden, Medea; Kollerits, Barbara; Pistis, Giorgio; Harris, Tamara B; Launer, Lenore J; Aspelund, Thor; Eiriksdottir, Gudny; Mitchell, Braxton D; Boerwinkle, Eric; Schmidt, Helena; Hofer, Edith; Hu, Frank; Demirkan, Ayse; Oostra, Ben A; Turner, Stephen T; Ding, Jingzhong; Andrews, Jeanette S; Freedman, Barry I; Giulianini, Franco; Koenig, Wolfgang; Illig, Thomas; Döring, Angela; Wichmann, H-Erich; Zgaga, Lina; Zemunik, Tatijana; Boban, Mladen; Minelli, Cosetta; Wheeler, Heather E; Igl, Wilmar; Zaboli, Ghazal; Wild, Sarah H; Wright, Alan F; Campbell, Harry; Ellinghaus, David; Nöthlings, Ute; Jacobs, Gunnar; Biffar, Reiner; Ernst, Florian; Homuth, Georg; Kroemer, Heyo K; Nauck, Matthias; Stracke, Sylvia; Völker, Uwe; Völzke, Henry; Kovacs, Peter; Stumvoll, Michael; Mägi, Reedik; Hofman, Albert; Uitterlinden, Andre G; Rivadeneira, Fernando; Aulchenko, Yurii S; Polasek, Ozren; Hastie, Nick; Vitart, Veronique; Helmer, Catherine; Wang, Jie Jin; Stengel, Bénédicte; Ruggiero, Daniela; Bergmann, Sven; Kähönen, Mika; Viikari, Jorma; Nikopensius, Tiit; Province, Michael; Colhoun, Helen; Doney, Alex; Robino, Antonietta; Krämer, Bernhard K; Portas, Laura; Ford, Ian; Buckley, Brendan M; Adam, Martin; Thun, Gian-Andri; Paulweber, Bernhard; Haun, Margot; Sala, Cinzia; Mitchell, Paul; Ciullo, Marina; Vollenweider, Peter; Raitakari, Olli; Metspalu, Andres; Palmer, Colin; Gasparini, Paolo; Pirastu, Mario; Jukema, J Wouter; Probst-Hensch, Nicole M; Kronenberg, Florian; Toniolo, Daniela; Gudnason, Vilmundur; Shuldiner, Alan R; Coresh, Josef; Schmidt, Reinhold; Ferrucci, Luigi; van Duijn, Cornelia M; Borecki, Ingrid; Kardia, Sharon L R; Liu, Yongmei; Curhan, Gary C; Rudan, Igor; Gyllensten, Ulf; Wilson, James F; Franke, Andre; Pramstaller, Peter P; Rettig, Rainer; Prokopenko, Inga; Witteman, Jacqueline; Hayward, Caroline; Ridker, Paul M; Bochud, Murielle; Heid, Iris M; Siscovick, David S; Fox, Caroline S; Kao, W Linda; Böger, Carsten A

    2013-12-01

    Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

  3. A novel splice variant of supervillin, SV5, promotes carcinoma cell proliferation and cell migration

    International Nuclear Information System (INIS)

    Chen, Xueran; Yang, Haoran; Zhang, Shangrong; Wang, Zhen; Ye, Fang; Liang, Chaozhao; Wang, Hongzhi; Fang, Zhiyou

    2017-01-01

    Supervillin is an actin-associated protein that regulates actin dynamics by interacting with Myosin II, F-actin, and Cortactin to promote cell contractility and cell motility. Two splicing variants of human Supervillin (SV1 and SV4) have been reported in non-muscle cells; SV1 lacks 3 exons present in the larger isoform SV4. SV2, also called archvillin, is present in striated muscle; SV3, also called smooth muscle archvillin or SmAV, was cloned from smooth muscle. In the present study, we identify a novel splicing variant of Supervillin (SV5). SV5 contains a new splicing pattern. In the mouse tissues and cell lines examined, SV5 was predominantly expressed in skeletal and cardiac muscles and in proliferating cells, but was virtually undetectable in most normal tissues. Using RNAi and rescue experiments, we show here that SV5 displays altered functional properties in cancer cells, and regulates cell proliferation and cell migration.

  4. Flavonoids as Inhibitors of Human Butyrylcholinesterase Variants

    Directory of Open Access Journals (Sweden)

    Maja Katalinić

    2014-01-01

    Full Text Available The inhibition of butyrylcholinesterase (BChE, EC 3.1.1.8 appears to be of interest in treating diseases with symptoms of reduced neurotransmitter levels, such as Alzheimer’s disease. However, BCHE gene polymorphism should not be neglected in research since it could have an effect on the expected outcome. Several well-known cholinergic drugs (e.g. galantamine, huperzine and rivastigmine originating from plants, or synthesised as derivatives of plant compounds, have shown that herbs could serve as a source of novel target-directed compounds. We focused our research on flavonoids, biologically active polyphenolic compounds found in many plants and plant-derived products, as BChE inhibitors. All of the tested flavonoids: galangin, quercetin, fisetin and luteolin reversibly inhibited usual, atypical, and fluoride-resistant variants of human BChE. The inhibition potency increased in the following order, identically for all three BChE variants: luteolin

  5. Dataset of mitochondrial genome variants in oncocytic tumors

    Directory of Open Access Journals (Sweden)

    Lihua Lyu

    2018-04-01

    Full Text Available This dataset presents the mitochondrial genome variants associated with oncocytic tumors. These data were obtained by Sanger sequencing of the whole mitochondrial genomes of oncocytic tumors and the adjacent normal tissues from 32 patients. The mtDNA variants are identified after compared with the revised Cambridge sequence, excluding those defining haplogroups of our patients. The pathogenic prediction for the novel missense variants found in this study was performed with the Mitimpact 2 program.

  6. Customization: Ideal Varieties, Product Uniqueness and Price Competition

    OpenAIRE

    Oksana Loginova; X. Henry Wang

    2009-01-01

    We study customization in the Hotelling model with two firms. In addition to providing ideal varieties, the perceived uniqueness of a customized product contributes independently to consumer utility. We show that only when consumer preferences for uniqueness are high customization occurs in equilibrium.

  7. Unique Protein Signature of Circulating Microparticles in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer; Iversen, Line V

    2013-01-01

    To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases.......To characterize the unique qualities of proteins associated with circulating subcellular material in systemic lupus erythematosus (SLE) patients compared with healthy controls and patients with other chronic autoimmune diseases....

  8. Can facial uniqueness be inferred from impostor scores?

    NARCIS (Netherlands)

    Dutta, A.; Veldhuis, Raymond N.J.; Spreeuwers, Lieuwe Jan

    2013-01-01

    In Biometrics, facial uniqueness is commonly inferred from impostor similarity scores. In this paper, we show that such uniqueness measures are highly unstable in the presence of image quality variations like pose, noise and blur. We also experimentally demonstrate the instability of a recently

  9. Novel factor VIII variants with a modified furin cleavage site improve the efficacy of gene therapy for hemophilia A.

    Science.gov (United States)

    Nguyen, G N; George, L A; Siner, J I; Davidson, R J; Zander, C B; Zheng, X L; Arruda, V R; Camire, R M; Sabatino, D E

    2017-01-01

    Essentials Factor (F) VIII is an inefficiently expressed protein. Furin deletion FVIII variants were purified and characterized using in vitro and in vivo assays. These minimally modified novel FVIII variants have enhanced function. These variants provide a strategy for increasing FVIII expression in hemophilia A gene therapy. Background The major challenge for developing gene-based therapies for hemophilia A is that human factor VIII (hFVIII) has intrinsic properties that result in inefficient biosynthesis. During intracellular processing, hFVIII is predominantly cleaved at a paired basic amino acid cleaving enzyme (PACE) or furin cleavage site to yield a heterodimer that is the major form of secreted protein. Previous studies with B-domain-deleted (BDD) canine FVIII and hFVIII-R1645H, both differing from hFVIII by a single amino acid at this site, suggested that these proteins are secreted mainly in a single polypeptide chain (SC) form and exhibit enhanced function. Objective We hypothesized that deletion(s) of the furin site modulates FVIII biology and may enhance its function. Methods A series of recombinant hFVIII-furin deletion variants were introduced into hFVIII-BDD [Δ1645, 1645-46(Δ2), 1645-47(Δ3), 1645-48(Δ4), or Δ1648] and characterized. Results In vitro, recombinant purified Δ3 and Δ4 were primarily SC and, interestingly, had 2-fold higher procoagulant activity compared with FVIII-BDD. In vivo, the variants also have improved hemostatic function. After adeno-associated viral (AAV) vector delivery, the expression of these variants is 2-4-fold higher than hFVIII-BDD. Protein challenges of each variant in mice tolerant to hFVIII-BDD showed no anti-FVIII immune response. Conclusions These data suggest that the furin deletion hFVIII variants are superior to hFVIII-BDD without increased immunogenicity. In the setting of gene-based therapeutics, these novel variants provide a unique strategy to increase FVIII expression, thus lowering the vector dose, a

  10. Differential Expression Profile of ZFX Variants Discriminates Breast Cancer Subtypes

    Science.gov (United States)

    Pourkeramati, Fatemeh; Asadi, Malek Hossein; Shakeri, Shahryar; Farsinejad, Alireza

    2018-05-13

    ZFX is a transcriptional regulator in embryonic stem cells that plays an important role in pluripotency and self-renewal. ZFX is widely expressed in pluripotent stem cells and is down-regulated during differentiation of embryonic stem cells. ZFX has five different variants that encode three different protein isoforms. While several reports have determined the overexpression of ZFX in a variety of somatic cancers, the expression of ZFX-spliced variants in cancer cells is not well-understood. We investigated the expression of ZFX variants in a series of breast cancer tissues and cell lines using quantitative PCR. The expression of ZFX variant 1/3 was higher in tumor tissue compared to marginal tissue. In contrast, the ZFX variant 5 was down-regulated in tumor tissues. While the ZFX variant 1/3 and ZFX variant 5 expression significantly increased in low-grade tumors, ZFX variant 4 was strongly expressed in high-grade tumors and demonstrating lymphatic invasion. In addition, our result revealed a significant association between the HER2 status and the expression of ZFX-spliced variants. Our data suggest that the expression of ZFX-spliced transcripts varies between different types of breast cancer and may contribute to their tumorigenesis process. Hence, ZFX-spliced transcripts could be considered as novel tumor markers with a probable value in diagnosis, prognosis, and therapy of breast cancer.

  11. Population structure analysis using rare and common functional variants

    Directory of Open Access Journals (Sweden)

    Ding Lili

    2011-11-01

    Full Text Available Abstract Next-generation sequencing technologies now make it possible to genotype and measure hundreds of thousands of rare genetic variations in individuals across the genome. Characterization of high-density genetic variation facilitates control of population genetic structure on a finer scale before large-scale genotyping in disease genetics studies. Population structure is a well-known, prevalent, and important factor in common variant genetic studies, but its relevance in rare variants is unclear. We perform an extensive population structure analysis using common and rare functional variants from the Genetic Analysis Workshop 17 mini-exome sequence. The analysis based on common functional variants required 388 principal components to account for 90% of the variation in population structure. However, an analysis based on rare variants required 532 significant principal components to account for similar levels of variation. Using rare variants, we detected fine-scale substructure beyond the population structure identified using common functional variants. Our results show that the level of population structure embedded in rare variant data is different from the level embedded in common variant data and that correcting for population structure is only as good as the level one wishes to correct.

  12. Human papillomavirus variants among Inuit women in northern Quebec, Canada.

    Science.gov (United States)

    Gauthier, Barbara; Coutlée, Francois; Franco, Eduardo L; Brassard, Paul

    2015-01-01

    Inuit communities in northern Quebec have high rates of human papillomavirus (HPV) infection, cervical cancer and cervical cancer-related mortality as compared to the Canadian population. HPV types can be further classified as intratypic variants based on the extent of homology in their nucleotide sequences. There is limited information on the distribution of intratypic variants in circumpolar areas. Our goal was to describe the HPV intratypic variants and associated baseline characteristics. We collected cervical cell samples in 2002-2006 from 676 Inuit women between the ages of 15 and 69 years in Nunavik. DNA isolates from high-risk HPVs were sequenced to determine the intratypic variant. There were 149 women that were positive for HPVs 16, 18, 31, 33, 35, 45, 52, 56 or 58 during follow-up. There were 5 different HPV16 variants, all of European lineage, among the 57 women positive for this type. There were 8 different variants of HPV18 present and all were of European lineage (n=21). The majority of samples of HPV31 (n=52) were of lineage B. The number of isolates and diversity of the other HPV types was low. Age was the only covariate associated with HPV16 variant category. These frequencies are similar to what was seen in another circumpolar region of Canada, although there appears to be less diversity as only European variants were detected. This study shows that most variants were clustered in one lineage for each HPV type.

  13. Determination of uranium by luminescent method (tablet variant)

    International Nuclear Information System (INIS)

    Sergeev, A.N.; Yufa, B.Ya.

    1985-01-01

    A new tablet variant of luminescent determination of uranium in rocks is developed. The analytical process includes the following operations: sample decomposition, uranium separation from luminescence quencher impurities, preparation of luminescent sample (tablet), photometry of the tablet. The method has two variants developed: the first one is characterized by a more hard decomposition, sample mass being 0.2 g; the second variant has a better detection limit (5x10 -6 %), the sample mass being 0.2-1 g. Procedures of the sample preparation for both variants of analysis are described

  14. Superior and inferior vena cavae: Embryology, variants, and pathology

    International Nuclear Information System (INIS)

    Mendelson, D.S.; Mitty, H.; Janus, C.; Gendal, E.; Berson, B.

    1987-01-01

    The superior and inferior venae cavae may be involved in a host of disease processes. Knowledge of the normal anatomy and variants of these structures is valuable in interpreting plain films and the results of angiographic procedures and all cross-sectional modalities. The authors review the embryology of venae cavae and proceed to describe their normal anatomy and variants. An awareness of the variants can prevent mistaking variants for pathologic processes. Finally, the authors describe pathology involving these vessels and demonstrate the radiographic manifestations

  15. Whole-Genome Sequencing and Variant Analysis of Human Papillomavirus 16 Infections.

    Science.gov (United States)

    van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J

    2017-10-01

    Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially ( P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related. IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is

  16. BigQ: a NoSQL based framework to handle genomic variants in i2b2.

    Science.gov (United States)

    Gabetta, Matteo; Limongelli, Ivan; Rizzo, Ettore; Riva, Alberto; Segagni, Daniele; Bellazzi, Riccardo

    2015-12-29

    Precision medicine requires the tight integration of clinical and molecular data. To this end, it is mandatory to define proper technological solutions able to manage the overwhelming amount of high throughput genomic data needed to test associations between genomic signatures and human phenotypes. The i2b2 Center (Informatics for Integrating Biology and the Bedside) has developed a widely internationally adopted framework to use existing clinical data for discovery research that can help the definition of precision medicine interventions when coupled with genetic data. i2b2 can be significantly advanced by designing efficient management solutions of Next Generation Sequencing data. We developed BigQ, an extension of the i2b2 framework, which integrates patient clinical phenotypes with genomic variant profiles generated by Next Generation Sequencing. A visual programming i2b2 plugin allows retrieving variants belonging to the patients in a cohort by applying filters on genomic variant annotations. We report an evaluation of the query performance of our system on more than 11 million variants, showing that the implemented solution scales linearly in terms of query time and disk space with the number of variants. In this paper we describe a new i2b2 web service composed of an efficient and scalable document-based database that manages annotations of genomic variants and of a visual programming plug-in designed to dynamically perform queries on clinical and genetic data. The system therefore allows managing the fast growing volume of genomic variants and can be used to integrate heterogeneous genomic annotations.

  17. Discovery of a Mammalian Splice Variant of Myostatin That Stimulates Myogenesis

    Science.gov (United States)

    Jeanplong, Ferenc; Falconer, Shelley J.; Oldham, Jenny M.; Thomas, Mark; Gray, Tarra S.; Hennebry, Alex; Matthews, Kenneth G.; Kemp, Frederick C.; Patel, Ketan; Berry, Carole; Nicholas, Gina; McMahon, Christopher D.

    2013-01-01

    Myostatin plays a fundamental role in regulating the size of skeletal muscles. To date, only a single myostatin gene and no splice variants have been identified in mammals. Here we describe the splicing of a cryptic intron that removes the coding sequence for the receptor binding moiety of sheep myostatin. The deduced polypeptide sequence of the myostatin splice variant (MSV) contains a 256 amino acid N-terminal domain, which is common to myostatin, and a unique C-terminus of 65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated into protein, which is present in skeletal muscles. To determine the biological role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed that it proliferated faster than that of the control line in association with an increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant protein made for the novel C-terminus of MSV also stimulated myoblast proliferation and bound to myostatin with high affinity as determined by surface plasmon resonance assay. Therefore, we postulated that MSV functions as a binding protein and antagonist of myostatin. Consistent with our postulate, myostatin protein was co-immunoprecipitated from skeletal muscle extracts with an MSV-specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin-induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the canonical myostatin pathway. Furthermore, MSV over-expression increased the abundance of MyoD, Myogenin and MRF4 proteins (Pmyostatin remained unchanged, which suggests that MSV may promote the growth of skeletal muscles. We conclude that MSV represents a unique example of intra-genic regulation in which a splice variant directly antagonizes the biological activity of the canonical gene product. PMID:24312578

  18. 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.

  19. A rabies virus vampire bat variant shows increased neuroinvasiveness in mice when compared to a carnivore variant.

    Science.gov (United States)

    Mesquita, Leonardo Pereira; Gamon, Thais Helena Martins; Cuevas, Silvia Elena Campusano; Asano, Karen Miyuki; Fahl, Willian de Oliveira; Iamamoto, Keila; Scheffer, Karin Correa; Achkar, Samira Maria; Zanatto, Dennis Albert; Mori, Cláudia Madalena Cabrera; Maiorka, Paulo César; Mori, Enio

    2017-12-01

    Rabies is one of the most important zoonotic diseases and is caused by several rabies virus (RABV) variants. These variants can exhibit differences in neurovirulence, and few studies have attempted to evaluate the neuroinvasiveness of variants derived from vampire bats and wild carnivores. The aim of this study was to evaluate the neuropathogenesis of infection with two Brazilian RABV street variants (variant 3 and crab-eating fox) in mice. BALB/c mice were inoculated with RABV through the footpad, with the 50% mouse lethal dose (LD 50 ) determined by intracranial inoculation. The morbidity of rabies in mice infected with variant 3 and the crab-eating fox strain was 100% and 50%, respectively, with an incubation period of 7 and 6 days post-inoculation (dpi), respectively. The clinical disease in mice was similar with both strains, and it was characterized initially by weight loss, ruffled fur, hunched posture, and hind limb paralysis progressing to quadriplegia and recumbency at 9 to 12 dpi. Histological lesions within the central nervous system (CNS) characterized by nonsuppurative encephalomyelitis with neuronal degeneration and necrosis were observed in mice infected with variant 3 and those infected with the crab-eating fox variant. However, lesions and the presence of RABV antigen, were more widespread within the CNS of variant-3-infected mice, whereas in crab-eating fox-variant-infected mice, RABV antigens were more restricted to caudal areas of the CNS, such as the spinal cord and brainstem. In conclusion, the results shown here demonstrate that the RABV vampire bat strain (variant 3) has a higher potential for neuroinvasiveness than the carnivore variant.

  20. The unique features of glycolytic pathways in Archaea.

    Science.gov (United States)

    Verhees, Corné H; Kengen, Servé W M; Tuininga, Judith E; Schut, Gerrit J; Adams, Michael W W; De Vos, Willem M; Van Der Oost, John

    2003-10-15

    An early divergence in evolution has resulted in two prokaryotic domains, the Bacteria and the Archaea. Whereas the central metabolic routes of bacteria and eukaryotes are generally well-conserved, variant pathways have developed in Archaea involving several novel enzymes with a distinct control. A spectacular example of convergent evolution concerns the glucose-degrading pathways of saccharolytic archaea. The identification, characterization and comparison of the glycolytic enzymes of a variety of phylogenetic lineages have revealed a mosaic of canonical and novel enzymes in the archaeal variants of the Embden-Meyerhof and the Entner-Doudoroff pathways. By means of integrating results from biochemical and genetic studies with recently obtained comparative and functional genomics data, the structure and function of the archaeal glycolytic routes, the participating enzymes and their regulation are re-evaluated.

  1. YGFP: a spectral variant of GFP

    DEFF Research Database (Denmark)

    Hansen, Flemming G.; Atlung, Tove

    2011-01-01

    We describe YGFP, a slow bleaching green fluorescent protein (GFP) with unique spectral properties. YGFP is derived from an Escherichia coli codon-optimized synthetic gfp, mutant 2 derivative. In addition to the GFP-mut 2 changes, it also carries S202F and T203I substitutions. YGFP can be used...

  2. The unique features of glycolytic pathways in Archaea.

    OpenAIRE

    Verhees, Corné H; Kengen, Servé W M; Tuininga, Judith E; Schut, Gerrit J; Adams, Michael W W; De Vos, Willem M; Van Der Oost, John

    2003-01-01

    An early divergence in evolution has resulted in two prokaryotic domains, the Bacteria and the Archaea. Whereas the central metabolic routes of bacteria and eukaryotes are generally well-conserved, variant pathways have developed in Archaea involving several novel enzymes with a distinct control. A spectacular example of convergent evolution concerns the glucose-degrading pathways of saccharolytic archaea. The identification, characterization and comparison of the glycolytic enzymes of a vari...

  3. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Science.gov (United States)

    LaRusch, Jessica; Jung, Jinsei; General, Ignacio J; Lewis, Michele D; Park, Hyun Woo; Brand, Randall E; Gelrud, Andres; Anderson, Michelle A; Banks, Peter A; Conwell, Darwin; Lawrence, Christopher; Romagnuolo, Joseph; Baillie, John; Alkaade, Samer; Cote, Gregory; Gardner, Timothy B; Amann, Stephen T; Slivka, Adam; Sandhu, Bimaljit; Aloe, Amy; Kienholz, Michelle L; Yadav, Dhiraj; Barmada, M Michael; Bahar, Ivet; Lee, Min Goo; Whitcomb, David C

    2014-07-01

    CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<0.0001). WNK1-SPAK pathway-activated increases in CFTR

  4. Mechanisms of CFTR functional variants that impair regulated bicarbonate permeation and increase risk for pancreatitis but not for cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Jessica LaRusch

    2014-07-01

    Full Text Available CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev cause complete loss of CFTR function and result in cystic fibrosis (CF, a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002. Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005 and male infertility (OR 395, p<<0.0001. WNK1-SPAK pathway-activated increases in

  5. Mnemiopsis leidyi Gut Harbors Seasonally Variant and Commensal Microbial Assemblages

    Science.gov (United States)

    Mariita, R. M.; Hossain, M. J.; Liles, M. R.; Moss, A.

    2016-02-01

    Studies have shown that with widespread use of antibiotics in human and domestic animal populations, antibiotic resistance becomes increasingly common in the environment. Estuaries provide ideal conditions for acquisition and dissemination of drug resistance genes because they serve as sinks for pollution. This study aimed to identify M. leidyi microbial diversity and richness and their potential to act as vectors for antibiotic resistance determinants (ARDs). M. leidyi, although native to study area are highly invasive. Metagenomic analyses indicate that there are temporal variations of bacterioplankton assemblages in M. leidyi gut. Overall, Proteobacteria and Actinobacteria are the most abundant phyla. Despite the temporal dynamics in the microbial assemblages in M. leidyi gut, they seem to retain Propionibacterium acnes (gut microbiota in some insects) and select proteobacteria across all seasons. The results contradict previous studies that suggest that M. leidyi does not have constant a microbiota, but only seasonally variant microbial assemblages. Here we reveal the presence of M. leidyi gut ARDs in winter and summer, probably because of the ctenophores' positive geotaxis during rough surface conditions. Genes responsible for resistance to fluoroquinolones, multidrug resistance efflux pumps, mercuric reductase, copper homeostasis and blaR1 genes were observed. This is the first study to demonstrate that M. leidyi harbors constant microbiota and provides a baseline for understanding M. leidyi gut microbial and ARDs ecology. It also suggests that M. leidyi bacterial taxonomic and functional dynamics is influenced by season. Funding: Alabama EPSCoR GRSP fellowship, AU-CMB fellowship, NSF EPS-1158862, USDA-Hatch 370225-310100 (AGM, ML).

  6. Crystal Structure of Serine Racemase that Produces Neurotransmitter font-variant:small-caps">d-Serine for Stimulation of the NMDA Receptor

    Science.gov (United States)

    Goto, Masaru

    font-variant:small-caps">d-Serine is an endogenous coagonist for the N-methyl-font-variant:small-caps">d-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5’-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of font-variant:small-caps">l-serine to yield font-variant:small-caps">d-serine and vice versa. We have determined the structures of three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe. Lys57 and Ser82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique lysino-font-variant:small-caps">d-alanyl residue at the active site, also binds the substrate serine in the active site, suggesting that the lysino-font-variant:small-caps">d-alanyl residue acts as a catalytic base in the same manner as Lys57 of the wild type enzyme.

  7. Variant facial artery in the submandibular region.

    Science.gov (United States)

    Vadgaonkar, Rajanigandha; Rai, Rajalakshmi; Prabhu, Latha V; Bv, Murlimanju; Samapriya, Neha

    2012-07-01

    Facial artery has been considered to be the most important vascular pedicle in facial rejuvenation procedures and submandibular gland (SMG) resection. It usually arises from the external carotid artery and passes from the carotid to digastric triangle, deep to the posterior belly of digastric muscle, and lodges in a groove at the posterior end of the SMG. It then passes between SMG and the mandible to reach the face after winding around the base of the mandible. During a routine dissection, in a 62-year-old female cadaver, in Kasturba Medical College Mangalore, an unusual pattern in the cervical course of facial artery was revealed. The right facial artery was found to pierce the whole substance of the SMG before winding around the lower border of the mandible to enter the facial region. Awareness of existence of such a variant and its comparison to the normal anatomy will be useful to oral and maxillofacial surgeons.

  8. Fast Ordered Sampling of DNA Sequence Variants

    Directory of Open Access Journals (Sweden)

    Anthony J. Greenberg

    2018-05-01

    Full Text Available Explosive growth in the amount of genomic data is matched by increasing power of consumer-grade computers. Even applications that require powerful servers can be quickly tested on desktop or laptop machines if we can generate representative samples from large data sets. I describe a fast and memory-efficient implementation of an on-line sampling method developed for tape drives 30 years ago. Focusing on genotype files, I test the performance of this technique on modern solid-state and spinning hard drives, and show that it performs well compared to a simple sampling scheme. I illustrate its utility by developing a method to quickly estimate genome-wide patterns of linkage disequilibrium (LD decay with distance. I provide open-source software that samples loci from several variant format files, a separate program that performs LD decay estimates, and a C++ library that lets developers incorporate these methods into their own projects.

  9. Fast Ordered Sampling of DNA Sequence Variants.

    Science.gov (United States)

    Greenberg, Anthony J

    2018-05-04

    Explosive growth in the amount of genomic data is matched by increasing power of consumer-grade computers. Even applications that require powerful servers can be quickly tested on desktop or laptop machines if we can generate representative samples from large data sets. I describe a fast and memory-efficient implementation of an on-line sampling method developed for tape drives 30 years ago. Focusing on genotype files, I test the performance of this technique on modern solid-state and spinning hard drives, and show that it performs well compared to a simple sampling scheme. I illustrate its utility by developing a method to quickly estimate genome-wide patterns of linkage disequilibrium (LD) decay with distance. I provide open-source software that samples loci from several variant format files, a separate program that performs LD decay estimates, and a C++ library that lets developers incorporate these methods into their own projects. Copyright © 2018 Greenberg.

  10. Genetic variants in periodontal health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Dumitrescu, Alexandrina L [Tromsoe Univ. (Norway). Inst. of Clinical Dentistry; Kobayashi, Junya [Kyoto Univ. (Japan). Dept. of Genome Repair Dynamics

    2010-07-01

    Periodontitis is a complex, multifactorial disease and its susceptibility is genetically determined. The present book systematically reviews the evidence of the association between the genetic variants and periodontitis progression and/or treatment outcomes. Genetic syndromes known to be associated with periodontal disease, the candidate gene polymorphisms investigated in relation to periodontitis, the heritability of chronic and aggressive periodontitis, as well as common guidelines for association studies are described. This growing understanding of the role of genetic variation in inflammation and periodontal chronic disease presents opportunities to identify healthy persons who are at increased risk of disease and to potentially modify the trajectory of disease to prolong healthy aging. The book represents a new concept in periodontology with its pronounced focus on understanding through knowledge rather than presenting the presently valid answers. Connections between genetics and periodontology are systematically reviewed and covered in detail. (orig.)

  11. Changes in unique hues induced by chromatic surrounds.

    Science.gov (United States)

    Klauke, Susanne; Wachtler, Thomas

    2016-03-01

    A chromatic surround can have a strong influence on the perceived hue of a stimulus. We investigated whether chromatic induction has similar effects on the perception of colors that appear pure and unmixed (unique red, green, blue, and yellow) as on other colors. Subjects performed unique hue settings of stimuli in isoluminant surrounds of different chromaticities. Compared with the settings in a neutral gray surround, unique hue settings altered systematically with chromatic surrounds. The amount of induced hue shift depended on the difference between stimulus and surround hues, and was similar for unique hue settings as for settings of nonunique hues. Intraindividual variability in unique hue settings was roughly twice as high as for settings obtained in asymmetric matching experiments, which may reflect the presence of a reference stimulus in the matching task. Variabilities were also larger with chromatic surrounds than with neutral gray surrounds, for both unique hue settings and matching of nonunique hues. The results suggest that the neural representations underlying unique hue percepts are influenced by the same neural processing mechanisms as the percepts of other colors.

  12. Nuclear variants of bone morphogenetic proteins

    Directory of Open Access Journals (Sweden)

    Meinhart Christopher A

    2010-03-01

    Full Text Available Abstract Background Bone morphogenetic proteins (BMPs contribute to many different aspects of development including mesoderm formation, heart development, neurogenesis, skeletal development, and axis formation. They have previously been recognized only as secreted growth factors, but the present study detected Bmp2, Bmp4, and Gdf5/CDMP1 in the nuclei of cultured cells using immunocytochemistry and immunoblotting of nuclear extracts. Results In all three proteins, a bipartite nuclear localization signal (NLS was found to overlap the site at which the proproteins are cleaved to release the mature growth factors from the propeptides. Mutational analyses indicated that the nuclear variants of these three proteins are produced by initiating translation from downstream alternative start codons. The resulting proteins lack N-terminal signal peptides and are therefore translated in the cytoplasm rather than the endoplasmic reticulum, thus avoiding proteolytic processing in the secretory pathway. Instead, the uncleaved proteins (designated nBmp2, nBmp4, and nGdf5 containing the intact NLSs are translocated to the nucleus. Immunostaining of endogenous nBmp2 in cultured cells demonstrated that the amount of nBmp2 as well as its nuclear/cytoplasmic distribution differs between cells that are in M-phase versus other phases of the cell cycle. Conclusions The observation that nBmp2 localization varies throughout the cell cycle, as well as the conservation of a nuclear localization mechanism among three different BMP family members, suggests that these novel nuclear variants of BMP family proteins play an important functional role in the cell.

  13. Unique small RNA signatures uncovered in the tammar wallaby genome

    Directory of Open Access Journals (Sweden)

    Lindsay James

    2012-10-01

    Full Text Available Abstract Background Small RNAs have proven to be essential regulatory molecules encoded within eukaryotic genomes. These short RNAs participate in a diverse array of cellular processes including gene regulation, chromatin dynamics and genome defense. The tammar wallaby, a marsupial mammal, is a powerful comparative model for studying the evolution of regulatory networks. As part of the genome sequencing initiative for the tammar, we have explored the evolution of each of the major classes of mammalian small RNAs in an Australian marsupial for the first time, including the first genome-scale analysis of the newest class of small RNAs, centromere repeat associated short interacting RNAs (crasiRNAs. Results Using next generation sequencing, we have characterized the major classes of small RNAs, micro (mi RNAs, piwi interacting (pi RNAs, and the centromere repeat associated short interacting (crasi RNAs in the tammar. We examined each of these small RNA classes with respect to the newly assembled tammar wallaby genome for gene and repeat features, salient features that define their canonical sequences, and the constitution of both highly conserved and species-specific members. Using a combination of miRNA hairpin predictions and co-mapping with miRBase entries, we identified a highly conserved cluster of miRNA genes on the X chromosome in the tammar and a total of 94 other predicted miRNA producing genes. Mapping all miRNAs to the tammar genome and comparing target genes among tammar, mouse and human, we identified 163 conserved target genes. An additional nine genes were identified in tammar that do not have an orthologous miRNA target in human and likely represent novel miRNA-regulated genes in the tammar. A survey of the tammar gonadal piRNAs shows that these small RNAs are enriched in retroelements and carry members from both marsupial and tammar-specific repeat classes. Lastly, this study includes the first in-depth analyses of the newly

  14. Non-unique Product Groups on Two Generators

    OpenAIRE

    Carter, William Paul

    2007-01-01

    The main purpose of this paper is to better understand groups that do not have the unique product property. In particular, the goal is to better understand Promislow's example, G, of such a group. In doing so, we will develop methods for generating examples of other sets that do not have the unique product property. With these methods we can show that there exists other distinct 14 element, square, non-unique product sets in G that are not inversions or translations. Also, this paper answers ...

  15. Guide to good practices for operations aspects of unique processes

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    This Guide to Good Practices is written to enhance understanding of, and provide direction for, Operations Aspects of Facility Chemistry and Unique Processes, Chapter XIII of Department of Energy (DOE) Order 5480.19, Conduct of Operations Requirements for DOE Facilities. The practices in this guide should be considered when planning or reviewing employee training and facility management programs. Contractors are advised to adopt procedures that meet the intent of DOE Order 5480.19. Operations Aspects of Unique Processes is an element of an effective Conduct of Operations program. The complexity and array of activities performed in DOE facilities dictate the necessity for all personnel to coordinate interrelated activities affecting unique processes.

  16. PET-CT in the typification of unique pulmonary injuries

    International Nuclear Information System (INIS)

    Cobos, P.; San Roman, Jose L.; Dalurzo, L.

    2007-01-01

    The objective of this document is to evaluate the usefulness of the PET-CT for the characterization of the unique pulmonary injuries. Retrospective analysis was made to patients with unique pulmonary injuries who carried out a PET-CT in the Italian Hospital between May of 2003 - March of 2005. Those patients with pulmonary outlying nodule, or unique pulmonary mass that had pathological anatomy of injury or follow-up through a computed tomography of thorax made with an interval of time not minor at 2 years of the PET-CT were included [es

  17. A unique Fock quantization for fields in non-stationary spacetimes

    International Nuclear Information System (INIS)

    Cortez, Jerónimo; Marugán, Guillermo A. Mena; Olmedo, Javier; Velhinho, José M.

    2010-01-01

    In curved spacetimes, the lack of criteria for the construction of a unique quantization is a fundamental problem undermining the significance of the predictions of quantum field theory. Inequivalent quantizations lead to different physics. Recently, however, some uniqueness results have been obtained for fields in non-stationary settings. In particular, for vacua that are invariant under the background symmetries, a unitary implementation of the classical evolution suffices to pick up a unique Fock quantization in the case of Klein-Gordon fields with time-dependent mass, propagating in a static spacetime whose spatial sections are three-spheres. In fact, the field equation can be reinterpreted as describing the propagation in a Friedmann-Robertson-Walker spacetime after a suitable scaling of the field by a function of time. For this class of fields, we prove here an even stronger result about the Fock quantization: the uniqueness persists when one allows for linear time-dependent transformations of the field in order to account for a scaling by background functions. In total, paying attention to the dynamics, there exists a preferred choice of quantum field, and only one SO(4)-invariant Fock representation for it that respects the standard probabilistic interpretation along the evolution. The result has relevant implications e.g. in cosmology

  18. Re-Ranking Sequencing Variants in the Post-GWAS Era for Accurate Causal Variant Identification

    Science.gov (United States)

    Faye, Laura L.; Machiela, Mitchell J.; Kraft, Peter; Bull, Shelley B.; Sun, Lei

    2013-01-01

    Next generation sequencing has dramatically increased our ability to localize disease-causing variants by providing base-pair level information at costs increasingly feasible for the large sample sizes required to detect complex-trait associations. Yet, identification of causal variants within an established region of association remains a challenge. Counter-intuitively, certain factors that increase power to detect an associated region can decrease power to localize the causal variant. First, combining GWAS with imputation or low coverage sequencing to achieve the large sample sizes required for high power can have the unintended effect of producing differential genotyping error among SNPs. This tends to bias the relative evidence for association toward better genotyped SNPs. Second, re-use of GWAS data for fine-mapping exploits previous findings to ensure genome-wide significance in GWAS-associated regions. However, using GWAS findings to inform fine-mapping analysis can bias evidence away from the causal SNP toward the tag SNP and SNPs in high LD with the tag. Together these factors can reduce power to localize the causal SNP by more than half. Other strategies commonly employed to increase power to detect association, namely increasing sample size and using higher density genotyping arrays, can, in certain common scenarios, actually exacerbate these effects and further decrease power to localize causal variants. We develop a re-ranking procedure that accounts for these adverse effects and substantially improves the accuracy of causal SNP identification, often doubling the probability that the causal SNP is top-ranked. Application to the NCI BPC3 aggressive prostate cancer GWAS with imputation meta-analysis identified a new top SNP at 2 of 3 associated loci and several additional possible causal SNPs at these loci that may have otherwise been overlooked. This method is simple to implement using R scripts provided on the author's website. PMID:23950724

  19. Genomewide association study identifies no major founder variant in ...

    Indian Academy of Sciences (India)

    2013-12-10

    Dec 10, 2013 ... variant in Caucasian moyamoya disease ... 1Department of Health and Environmental Sciences, Kyoto University Graduate ... a low prevalence in European countries (Goto and Yonekawa. 1992; Kuroda and Houkin 2008). We have found that the p.R4810K variant in the ring finger protein 213 (RNF213).

  20. Managing Process Variants in the Process Life Cycle

    NARCIS (Netherlands)

    Hallerbach, A.; Bauer, Th.; Reichert, M.U.

    2007-01-01

    When designing process-aware information systems, often variants of the same process have to be specified. Each variant then constitutes an adjustment of a particular process to specific requirements building the process context. Current Business Process Management (BPM) tools do not adequately

  1. Germline Variants of Prostate Cancer in Japanese Families.

    Directory of Open Access Journals (Sweden)

    Takahide Hayano

    Full Text Available Prostate cancer (PC is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family. We also found shared variants of BRCA2, HOXB13, and TRRAP from 59 additional small PC families (two patients per family. We identified two deleterious HOXB13 variants (F127C and G132E. Further exploration of the shared variants in rest of the families revealed deleterious variants of the so-called cancer genes (ATP1A1, BRIP1, FANCA, FGFR3, FLT3, HOXD11, MUTYH, PDGFRA, SMARCA4, and TCF3. The germline variant profile provides a new insight to clarify the genetic etiology and heterogeneity of PC among Japanese men.

  2. Holographic representation of space-variant systems: system theory.

    Science.gov (United States)

    Marks Ii, R J; Krile, T F

    1976-09-01

    System theory for holographic representation of linear space-variant systems is derived. The utility of the resulting piecewise isoplanatic approximation (PIA) is illustrated by example application to the invariant system, ideal magnifier, and Fourier transformer. A method previously employed to holographically represent a space-variant system, the discrete approximation, is shown to be a special case of the PIA.

  3. Detecting rare variants in case-parents association studies.

    Directory of Open Access Journals (Sweden)

    Kuang-Fu Cheng

    Full Text Available Despite the success of genome-wide association studies (GWASs in detecting common variants (minor allele frequency ≥0.05 many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT, multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

  4. Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

    Science.gov (United States)

    2017-10-01

    resistant prostate cancer ; docetaxel; cabazitaxel; chemotherapy; androgen receptor splice variants; microtubule; ligand-binding domain; microtubule... receptor splice variants (AR-Vs) are associated with resistance to taxane chemotherapy in castration- resistant prostate cancer (CRPC). However, this...androgen receptor inhibitors in prostate cancer . Nat Rev Cancer . 2015;15:701–11.

  5. Hepatitis E Virus Variant in Farmed Mink, Denmark

    DEFF Research Database (Denmark)

    Krog, Jesper Schak; Breum, Solvej Østergaard; Jensen, Trine Hammer

    2013-01-01

    Hepatitis E virus (HEV) is a zoonotic virus for which pigs are the primary animal reservoir. To investigate whether HEV occurs in mink in Denmark, we screened feces and tissues from domestic and wild mink. Our finding of a novel HEV variant supports previous findings of HEV variants in a variety...

  6. Variant Creutzfeldt-Jakob Disease (vCJD)

    Science.gov (United States)

    ... Form Controls Cancel Submit Search the CDC Variant Creutzfeldt-Jakob Disease (vCJD) Note: Javascript is disabled or is not ... gov . Recommend on Facebook Tweet Share Compartir Variant Creutzfeldt-Jakob disease (vCJD) is a prion disease that was first ...

  7. Genetics Home Reference: GM2-gangliosidosis, AB variant

    Science.gov (United States)

    ... Resources Genetic Testing (1 link) Genetic Testing Registry: Tay-Sachs disease, variant AB General Information from MedlinePlus (5 links) ... AB variant Activator Deficiency/GM2 Gangliosidosis Activator-deficient Tay-Sachs disease GM2 Activator Deficiency Disease GM2 gangliosidosis, type AB ...

  8. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    2008-01-01

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  9. Assessment of Functional Effects of Unclassified Genetic Variants

    NARCIS (Netherlands)

    Couch, Fergus J.; Rasmussen, Lene Juel; Hofstra, Robert; Monteiro, Alvaro N. A.; Greenblatt, Marc S.; de Wind, Niels

    Inherited predisposition to disease is often linked to reduced activity of a disease associated gene product. Thus, quantitation of the influence of inherited variants on gene function can potentially be used to predict the disease relevance of these variants. While many disease genes have been

  10. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  11. ADULT VARIANT BARTTER’S SYNDROME- A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Ishwar Sidappa Hasabi

    2017-02-01

    Full Text Available BACKGROUND Bartter syndrome is a group of channelopathies with different genetic origins and molecular pathophysiologies, but sharing common feature of decreased tubular transport of sodium chloride in thick ascending loop of Henle (TAL, 1 although more common in antenatal group. Classic adult variant of Bartter syndrome is a rare entity. We hereby present a rare adult variant of classic Bartter syndrome.

  12. Combinations of Genetic Variants Occurring Exclusively in Patients

    Directory of Open Access Journals (Sweden)

    Erling Mellerup

    Full Text Available In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, identifying clusters of patient-specific genetic variant combinations that are significant associated with the investigated disorders. Combinations from these clusters are found in the genomes of up to 55% of investigated patients, and are not present in the genomes of any control persons. Keywords: Genetic variants, Polygenic disorder, Combinations of genetic variants, Patient-specific combinations

  13. Golden Rule of Morphology and Variants of Word forms

    Directory of Open Access Journals (Sweden)

    Hlaváčová Jaroslava

    2017-12-01

    Full Text Available In many languages, some words can be written in several ways. We call them variants. Values of all their morphological categories are identical, which leads to an identical morphological tag. Together with the identical lemma, we have two or more wordforms with the same morphological description. This ambiguity may cause problems in various NLP applications. There are two types of variants – those affecting the whole paradigm (global variants and those affecting only wordforms sharing some combinations of morphological values (inflectional variants. In the paper, we propose means how to tag all wordforms, including their variants, unambiguously. We call this requirement “Golden rule of morphology”. The paper deals mainly with Czech, but the ideas can be applied to other languages as well.

  14. Electrophoretic variants of blood proteins in Japanese, 7

    International Nuclear Information System (INIS)

    Satoh, Chiyoko; Takahashi, Norio; Kimura, Yasukazu; Miura, Akiko; Kaneko, Junko; Fujita, Mikio; Toyama, Kyoko.

    1986-11-01

    A total of 16,835 children, of whom 11,737 are unrelated, from Hiroshima and Nagasaki were examined for erythrocyte cytoplasmic glutamate-oxaloacetate transaminase (GOT1) by starch gel electrophoresis. A variant allele named GOT1*2HR1 which seems to be identical with GOT1*2 was encountered in polymorphic frequency. Five kinds of rare variants, 3NG1, 4NG1, 5NG1, 6HR1, and 7NG1 were encountered in a total of 109 children. Except for 7NG1 for which complete family study was unable, family studies confirmed the genetic nature of these rare variants, since for all instances in which both parents could be examined, one of the parents exhibited the same variant as that of their child. Thermostability profiles of these six variants were normal. The enzyme activities of five were decreased, while the value of one was normal compared to that of GOT1 1. (author)

  15. Holistic Leadership-Nursing's Unique Contribution to Healthcare.

    Science.gov (United States)

    Clarke, Pamela N; Bleich, Michael R

    2018-04-01

    This dialogue is focused on holistic leadership from the perspective of a well-known leader in nursing. He frames the changing healthcare environment and nursing's unique contribution on the interprofessional team.

  16. The Tankwa Karoo National Park feral goat population: A unique ...

    African Journals Online (AJOL)

    The Tankwa Karoo National Park feral goat population: A unique genetic ... The feral goats from Tankwa Karoo National Park in the Northern Cape, South Africa, ... Park and former Tankwa goats, now kept on a private farm were genotyped, ...

  17. Protein nanoparticle: A unique system as drug delivery vehicles

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Nanobiotechnology Research Center, Faculty of Chemical Engineering, Babol University of Technology, Iran. ... as potential carriers with unique advantages including ..... for intracellular uptake in BT/20 human breast cancer.

  18. Unique morphology of dispersed clay particles in a polymer nanocomposite

    CSIR Research Space (South Africa)

    Malwela, T

    2011-02-01

    Full Text Available This communication reports a unique morphology of dispersed clay particles in a polymer nanocomposite. A nanocomposite of poly[butylene succinate)-co-adipate] (PBSA) with 3 wt% of organically modified montmorillonite was prepared by melt...

  19. Determining hydraulic parameters of a karst aquifer using unique ...

    African Journals Online (AJOL)

    2014-07-15

    Jul 15, 2014 ... 1 Faculty of Natural Sciences, Potchefstroom Campus, North-West University, ... a first-ever attempt to utilise various sets of unique historical data ..... Even though the aquifer shows characteristics of all major ...... Earth Sci.

  20. Uniqueness of the electrostatic solution in Schwarzschild space

    International Nuclear Information System (INIS)

    Molnar, Pal G.; Elsaesser, Klaus

    2003-01-01

    In this Brief Report we give the proof that the solution of any static test charge distribution in Schwarzschild space is unique. In order to give the proof we derive the first Green's identity written with p-forms on (pseudo) Riemannian manifolds. Moreover, the proof of uniqueness can be shown for either any purely electric or purely magnetic field configuration. The spacetime geometry is not crucial for the proof

  1. Practical relevance of pattern uniqueness in forensic science.

    Science.gov (United States)

    Jayaprakash, Paul T

    2013-09-10

    Uniqueness being unprovable, it has recently been argued that individualization in forensic science is irrelevant and, probability, as applied for DNA profiles, should be applied for all identifications. Critiques against uniqueness have omitted physical matching, a realistic and tangible individualization that supports uniqueness. Describing case examples illustrating pattern matches including physical matching, it is indicated that individualizations are practically relevant for forensic science as they establish facts on a definitive basis providing firm leads benefitting criminal investigation. As a tenet of forensic identification, uniqueness forms a fundamental paradigm relevant for individualization. Evidence on the indeterministic and stochastic causal pathways of characteristics in patterns available in the related fields of science sufficiently supports the proposition of uniqueness. Characteristics involved in physical matching and matching achieved in patterned evidence existing in the state of nature are not events amenable for counting; instead these are ensemble of visible units occupying the entire pattern area stretching the probability of re-occurrence of a verisimilitude pattern into infinity offering epistemic support to uniqueness. Observational methods are as respectable as instrumental or statistical methods since they are capable of generating results that are tangible and obviously valid as in physical matching. Applying the probabilistic interpretation used for DNA profiles to the other patterns would be unbefitting since these two are disparate, the causal pathways of the events, the loci, in the manipulated DNA profiles being determinable. While uniqueness enables individualizations, it does not vouch for eliminating errors. Instead of dismissing uniqueness and individualization, accepting errors as human or system failures and seeking remedial measures would benefit forensic science practice and criminal investigation. Copyright © 2013

  2. Investigation of unique hue setting changes with ageing

    Institute of Scientific and Technical Information of China (English)

    Chenyang Fu; Kaida Xiao; Dimosthenis Karatzas; Sophie Wuerger

    2011-01-01

    Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed. Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions. Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed. Based on the chromatic (protan, deutan, tritan) thresholds and using scaled cone signals, we predict the unique hue changes with ageing. A dependency on age for unique red and unique yellow for predicted hue angle is found. We conclude that the chromatic sensitivity deteriorates significantly with age, whereas the appearance of unique hues is much less affected, remaining almost constant despite the known changes in the ocular media.%@@ Clromatic sensitivity along the protan, deutan, and tritan lines and the loci of the unique hues (red, green,yellow, blue) for a very large sample (n = 185) of colour-normal observers ranging from 18 to 75 years of age are assessed.Visual judgments are obtained under normal viewing conditions using colour patches on self-luminous display under controlled adaptation conditions.Trivector discrimination thresholds show an increase as a function of age along the protan, deutan, and tritan axes, with the largest increase present along the tritan line, less pronounced shifts in unique hue settings are also observed.

  3. Denture identification using unique identification authority of India barcode

    OpenAIRE

    Sudhindra Mahoorkar; Anoop Jain

    2013-01-01

    Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

  4. Denture identification using unique identification authority of India barcode.

    Science.gov (United States)

    Mahoorkar, Sudhindra; Jain, Anoop

    2013-01-01

    Over the years, various denture marking systems have been reported in the literature for personal identification. They have been broadly divided into surface marking and inclusion methods. In this technique, patient's unique identification number and barcode printed in the patient's Aadhaar card issued by Unique Identification Authority of India (UIDAI) are used as denture markers. This article describes a simple, quick, and economical method for identification of individual.

  5. Unitary evolution and uniqueness of the Fock quantization in flat cosmologies

    International Nuclear Information System (INIS)

    Marugán, G A Mena; Błas, D Martín-de; Gomar, L Castelló

    2013-01-01

    We study the Fock quantization of scalar fields with a time dependent mass in cosmological scenarios with flat compact spatial sections. This framework describes physically interesting situations like, e.g., cosmological perturbations in flat Friedmann-Robertson-Walker spacetimes, generally including a suitable scaling of them by a background function. We prove that the requirements of vacuum invariance under the spatial isometries and of a unitary quantum dynamics select (a) a unique canonical pair of field variables among all those related by time dependent canonical transformations which scale the field configurations, and (b) a unique Fock representation for the canonical commutation relations of this pair of variables. The proof is generalizable to any compact spatial topology in three or less dimensions, though we focus on the case of the three-torus owing to the especially relevant implications.

  6. Eco-reliable path finding in time-variant and stochastic networks

    International Nuclear Information System (INIS)

    Li, Wenjie; Yang, Lixing; Wang, Li; Zhou, Xuesong; Liu, Ronghui; Gao, Ziyou

    2017-01-01

    This paper addresses a route guidance problem for finding the most eco-reliable path in time-variant and stochastic networks such that travelers can arrive at the destination with the maximum on-time probability while meeting vehicle emission standards imposed by government regulators. To characterize the dynamics and randomness of transportation networks, the link travel times and emissions are assumed to be time-variant random variables correlated over the entire network. A 0–1 integer mathematical programming model is formulated to minimize the probability of late arrival by simultaneously considering the least expected emission constraint. Using the Lagrangian relaxation approach, the primal model is relaxed into a dualized model which is further decomposed into two simple sub-problems. A sub-gradient method is developed to reduce gaps between upper and lower bounds. Three sets of numerical experiments are tested to demonstrate the efficiency and performance of our proposed model and algorithm. - Highlights: • The most eco-reliable path is defined in time-variant and stochastic networks. • The model is developed with on-time arrival probability and emission constraints. • The sub-gradient and label correcting algorithm are integrated to solve the model. • Numerical experiments demonstrate the effectiveness of developed approaches.

  7. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming

    2013-07-26

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  8. Bayesian detection of causal rare variants under posterior consistency.

    Directory of Open Access Journals (Sweden)

    Faming Liang

    Full Text Available Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD, to tackle this problem. The new method simultaneously addresses two issues: (i (Global association test Are there any of the variants associated with the disease, and (ii (Causal variant detection Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  9. Bayesian detection of causal rare variants under posterior consistency.

    KAUST Repository

    Liang, Faming; Xiong, Momiao

    2013-01-01

    Identification of causal rare variants that are associated with complex traits poses a central challenge on genome-wide association studies. However, most current research focuses only on testing the global association whether the rare variants in a given genomic region are collectively associated with the trait. Although some recent work, e.g., the Bayesian risk index method, have tried to address this problem, it is unclear whether the causal rare variants can be consistently identified by them in the small-n-large-P situation. We develop a new Bayesian method, the so-called Bayesian Rare Variant Detector (BRVD), to tackle this problem. The new method simultaneously addresses two issues: (i) (Global association test) Are there any of the variants associated with the disease, and (ii) (Causal variant detection) Which variants, if any, are driving the association. The BRVD ensures the causal rare variants to be consistently identified in the small-n-large-P situation by imposing some appropriate prior distributions on the model and model specific parameters. The numerical results indicate that the BRVD is more powerful for testing the global association than the existing methods, such as the combined multivariate and collapsing test, weighted sum statistic test, RARECOVER, sequence kernel association test, and Bayesian risk index, and also more powerful for identification of causal rare variants than the Bayesian risk index method. The BRVD has also been successfully applied to the Early-Onset Myocardial Infarction (EOMI) Exome Sequence Data. It identified a few causal rare variants that have been verified in the literature.

  10. Dynamic secrets in communication security

    CERN Document Server

    Xiao, Sheng; Towsley, Donald

    2013-01-01

    Dynamic secrets are constantly generated and updated from messages exchanged between two communication users. When dynamic secrets are used as a complement to existing secure communication systems, a stolen key or password can be quickly and automatically reverted to its secret status without disrupting communication. 'Dynamic Secrets in Communication Security' presents unique security properties and application studies for this technology. Password theft and key theft no longer pose serious security threats when parties frequently use dynamic secrets. This book also illustrates that a dynamic

  11. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

    NARCIS (Netherlands)

    Rivas, Manuel A.; Graham, Daniel; Sulem, Patrick; Stevens, Christine; Desch, A. Nicole; Goyette, Philippe; Gudbjartsson, Daniel; Jonsdottir, Ingileif; Thorsteinsdottir, Unnur; Degenhardt, Frauke; Mucha, Soeren; Kurki, Mitja I.; Li, Dalin; D'Amato, Mauro; Annese, Vito; Vermeire, Severine; Weersma, Rinse K.; Halfvarson, Jonas; Paavola-Sakki, Paulina; Lappalainen, Maarit; Lek, Monkol; Cummings, Beryl; Tukiainen, Taru; Haritunians, Talin; Halme, Leena; Koskinen, Lotta L. E.; Ananthakrishnan, Ashwin N.; Luo, Yang; Heap, Graham A.; Visschedijk, Marijn C.; MacArthur, Daniel G.; Neale, Benjamin M.; Ahmad, Tariq; Anderson, Carl A.; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Cho, Judy H.; Palotie, Aarno; Saavalainen, Paivi; Kontula, Kimmo; Farkkila, Martti; McGovern, Dermot P. B.; Franke, Andre; Stefansson, Kari; Rioux, John D.; Xavier, Ramnik J.; Daly, Mark J.

    Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants

  12. Genetics Home Reference: Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant

    Science.gov (United States)

    ... SBBYS variant Ohdo syndrome, Say-Barber-Biesecker-Young-Simpson variant Printable PDF Open All Close All Enable ... collapse boxes. Description The Say-Barber-Biesecker-Young-Simpson (SBBYS) variant of Ohdo syndrome is a rare ...

  13. Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants

    Directory of Open Access Journals (Sweden)

    Nagel Bert

    2012-07-01

    Full Text Available Abstract Background Left ventricular hypertrabeculation/noncompaction (LVHT is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism. Case presentation A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH detected six previously not described copy number variants (CNVs inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants. Conclusions Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.

  14. On the Uniqueness of the Fock Quantization of the Dirac Field in the Closed FRW Cosmology

    Directory of Open Access Journals (Sweden)

    Jerónimo Cortez

    2018-01-01

    Full Text Available The Fock quantization of free fields propagating in cosmological backgrounds is in general not unambiguously defined due to the nonstationarity of the space-time. For the case of a scalar field in cosmological scenarios, it is known that the criterion of unitary implementation of the dynamics serves to remove the ambiguity in the choice of Fock representation (up to unitary equivalence. Here, applying the same type of arguments and methods previously used for the scalar field case, we discuss the issue of the uniqueness of the Fock quantization of the Dirac field in the closed FRW space-time proposed by D’Eath and Halliwell.

  15. Genetic characterization of natural variants of Vpu from HIV-1 infected individuals from Northern India and their impact on virus release and cell death.

    Directory of Open Access Journals (Sweden)

    Sachin Verma

    Full Text Available BACKGROUND: Genetic studies reveal that vpu is one of the most variable regions in HIV-1 genome. Functional studies have been carried out mostly with Vpu derived from laboratory adapted subtype B pNL 4-3 virus. The rationale of this study was to characterize genetic variations that are present in the vpu gene from HIV-1 infected individuals from North-India (Punjab/Haryana and determine their functional relevance. METHODS: Functionally intact vpu gene variants were PCR amplified from genomic DNA of HIV-1 infected individuals. These variants were then subjected to genetic analysis and unique representative variants were cloned under CMV promoter containing expression vector as well as into pNL 4-3 HIV-1 virus for intracellular expression studies. These variants were characterized with respect to their ability to promote virus release as well as cell death. RESULTS: Based on phylogenetic analysis and extensive polymorphisms with respect to consensus Vpu B and C, we were able to arbitrarily assign variants into two major groups (B and C. The group B variants always showed significantly higher virus release activity and exhibited moderate levels of cell death. On the other hand, group C variants displayed lower virus release activity but greater cell death potential. Interestingly, Vpu variants with a natural S61A mutation showed greater intracellular stability. These variants also exhibited significant reduction in their intracellular ubiquitination and caused greater virus release. Another group C variant that possessed a non-functional β-TrcP binding motif due to two critical serine residues (S52 and S56 being substituted with isoleucine residues, showed reduced virus release activity but modest cytotoxic activity. CONCLUSIONS: The natural variations exhibited by our Vpu variants involve extensive polymorphism characterized by substitution and deletions that contribute toward positive selection. We identified two major groups and an extremely

  16. Genotype–phenotype correlations in individuals with pathogenic RERE variants

    Science.gov (United States)

    Jordan, Valerie K.; Fregeau, Brieana; Ge, Xiaoyan; Giordano, Jessica; Wapner, Ronald J.; Balci, Tugce B.; Carter, Melissa T.; Bernat, John A.; Moccia, Amanda N.; Srivastava, Anshika; Martin, Donna M.; Bielas, Stephanie L.; Pappas, John; Svoboda, Melissa D.; Rio, Marlène; Boddaert, Nathalie; Cantagrel, Vincent; Lewis, Andrea M.; Scaglia, Fernando; Kohler, Jennefer N.; Bernstein, Jonathan A.; Dries, Annika M.; Rosenfeld, Jill A.; DeFilippo, Colette; Thorson, Willa; Yang, Yaping; Sherr, Elliott H.; Bi, Weimin; Scott, Daryl A.

    2018-01-01

    Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype–phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7. PMID:29330883

  17. Gain-of-function HCN2 variants in genetic epilepsy.

    Science.gov (United States)

    Li, Melody; Maljevic, Snezana; Phillips, A Marie; Petrovski, Slave; Hildebrand, Michael S; Burgess, Rosemary; Mount, Therese; Zara, Federico; Striano, Pasquale; Schubert, Julian; Thiele, Holger; Nürnberg, Peter; Wong, Michael; Weisenberg, Judith L; Thio, Liu Lin; Lerche, Holger; Scheffer, Ingrid E; Berkovic, Samuel F; Petrou, Steven; Reid, Christopher A

    2018-02-01

    Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism. © 2017 Wiley Periodicals, Inc.

  18. NMNAT1 variants cause cone and cone-rod dystrophy.

    Science.gov (United States)

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  19. Behavioural-variant frontotemporal dementia: An update

    Directory of Open Access Journals (Sweden)

    Olivier Piguet

    Full Text Available ABSTRACT Behavioural-variant frontotemporal dementia (bvFTD is characterised by insidious changes in personality and interpersonal conduct that reflect progressive disintegration of the neural circuits involved in social cognition, emotion regulation, motivation and decision making. The underlying pathology is heterogeneous and classified according to the presence of intraneuronal inclusions of tau, TDP-43 or occasionally FUS. Biomarkers to detect these histopathological changes in life are increasingly important with the development of disease-modifying drugs. Gene mutations have been found which collectively account for around 10-20% of cases including a novel hexanucleotide repeat on chromosome 9 (C9orf72. The recently reviewed International Consensus Criteria for bvFTD propose three levels of diagnostic certainly: possible, probable and definite. Detailed history taking from family members to elicit behavioural features underpins the diagnostic process with support from neuropsychological testing designed to detect impairment in decision-making, emotion processing and social cognition. Brain imaging is important for increasing the level of diagnosis certainty. Carer education and support remain of paramount importance.

  20. Spatially variant morphological restoration and skeleton representation.

    Science.gov (United States)

    Bouaynaya, Nidhal; Charif-Chefchaouni, Mohammed; Schonfeld, Dan

    2006-11-01

    The theory of spatially variant (SV) mathematical morphology is used to extend and analyze two important image processing applications: morphological image restoration and skeleton representation of binary images. For morphological image restoration, we propose the SV alternating sequential filters and SV median filters. We establish the relation of SV median filters to the basic SV morphological operators (i.e., SV erosions and SV dilations). For skeleton representation, we present a general framework for the SV morphological skeleton representation of binary images. We study the properties of the SV morphological skeleton representation and derive conditions for its invertibility. We also develop an algorithm for the implementation of the SV morphological skeleton representation of binary images. The latter algorithm is based on the optimal construction of the SV structuring element mapping designed to minimize the cardinality of the SV morphological skeleton representation. Experimental results show the dramatic improvement in the performance of the SV morphological restoration and SV morphological skeleton representation algorithms in comparison to their translation-invariant counterparts.

  1. CRY2 genetic variants associate with dysthymia.

    Directory of Open Access Journals (Sweden)

    Leena Kovanen

    Full Text Available People with mood disorders often have disruptions in their circadian rhythms. Recent molecular genetics has linked circadian clock genes to mood disorders. Our objective was to study two core circadian clock genes, CRY1 and CRY2 as well as TTC1 that interacts with CRY2, in relation to depressive and anxiety disorders. Of these three genes, 48 single-nucleotide polymorphisms (SNPs whose selection was based on the linkage disequilibrium and potential functionality were genotyped in 5910 individuals from a nationwide population-based sample. The diagnoses of major depressive disorder, dysthymia and anxiety disorders were assessed with a structured interview (M-CIDI. In addition, the participants filled in self-report questionnaires on depressive and anxiety symptoms. Logistic and linear regression models were used to analyze the associations of the SNPs with the phenotypes. Four CRY2 genetic variants (rs10838524, rs7121611, rs7945565, rs1401419 associated significantly with dysthymia (false discovery rate q<0.05. This finding together with earlier CRY2 associations with winter depression and with bipolar type 1 disorder supports the view that CRY2 gene has a role in mood disorders.

  2. Variant Carvajal syndrome with additional dental anomalies.

    Science.gov (United States)

    Barber, Sophy; Day, Peter; Judge, Mary; Toole, Edell O'; Fayle, Stephen

    2012-09-01

    This paper aims to review the case of a girl who presented with a number of dental anomalies, in addition to unusual skin, nail and hair conditions. Tragically an undiagnosed cardiomyopathy caused unexpected sudden death. The case is discussed with reference to a number of dermatological and oral conditions which were considered as possible diagnoses. AW had been under long term dental care for prepubertal periodontitis, premature root resorption of primary teeth, soft tissue and dental anomalies, and angular cheilitis. Separately she had also been seen by several dermatologists with respect to palmar plantar keratosis, striae keratoderma, wiry hair and abnormal finger nails. Tragically the patient suffered a sudden unexpected death and the subsequent post mortem identified an undiagnosed dilated cardiomyopathy. The most likely diagnosis is that this case is a variant of Carvajal Syndrome with additional dental anomalies. To date we have been unable to identify mutations in the desoplakin gene. We aim to emphasise the importance of recognising these dental and dermatological signs when they present together as a potential risk factor for cardiac abnormalities. © 2012 The Authors. International Journal of Paediatric Dentistry © 2012 BSPD, IAPD and Blackwell Publishing Ltd.

  3. Identification of copy number variants in horses

    KAUST Repository

    Doan, R.

    2012-03-01

    Copy number variants (CNVs) represent a substantial source of genetic variation in mammals. However, the occurrence of CNVs in horses and their subsequent impact on phenotypic variation is unknown. We performed a study to identify CNVs in 16 horses representing 15 distinct breeds (Equus caballus) and an individual gray donkey (Equus asinus) using a whole-exome tiling array and the array comparative genomic hybridization methodology. We identified 2368 CNVs ranging in size from 197 bp to 3.5 Mb. Merging identical CNVs from each animal yielded 775 CNV regions (CNVRs), involving 1707 protein- and RNA-coding genes. The number of CNVs per animal ranged from 55 to 347, with median and mean sizes of CNVs of 5.3 kb and 99.4 kb, respectively. Approximately 6% of the genes investigated were affected by a CNV. Biological process enrichment analysis indicated CNVs primarily affected genes involved in sensory perception, signal transduction, and metabolism. CNVs also were identified in genes regulating blood group antigens, coat color, fecundity, lactation, keratin formation, neuronal homeostasis, and height in other species. Collectively, these data are the first report of copy number variation in horses and suggest that CNVs are common in the horse genome and may modulate biological processes underlying different traits observed among horses and horse breeds.

  4. Human papillomavirus type-16 variants in Quechua aboriginals from Argentina.

    Science.gov (United States)

    Picconi, María Alejandra; Alonio, Lidia Virginia; Sichero, Laura; Mbayed, Viviana; Villa, Luisa Lina; Gronda, Jorge; Campos, Rodolfo; Teyssié, Angélica

    2003-04-01

    Cervical carcinoma is the leading cause of cancer death in Quechua indians from Jujuy (northwestern Argentina). To determine the prevalence of HPV-16 variants, 106 HPV-16 positive cervical samples were studied, including 33 low-grade squamous intraepithelial lesions (LSIL), 28 high-grade squamous intraepithelial lesions (HSIL), 9 invasive cervical cancer (ICC), and 36 samples from women with normal colposcopy and cytology. HPV genome variability was examined in the L1 and E6 genes by PCR-hybridization. In a subset of 20 samples, a LCR fragment was also analyzed by PCR-sequencing. Most variants belonged to the European branch with subtle differences that depended on the viral gene fragment studied. Only about 10% of the specimens had non-European variants, including eight Asian-American, two Asian, and one North-American-1. E6 gene analysis revealed that 43% of the samples were identical to HPV-16 prototype, while 57% corresponded to variants. Interestingly, the majority (87%) of normal smears had HPV-16 prototype, whereas variants were detected mainly in SIL and ICC. LCR sequencing yielded 80% of variants, including 69% of European, 19% Asian-American, and 12% Asian. We identified a new variant, the Argentine Quechua-51 (AQ-51), similar to B-14 plus two additional changes: G7842-->A and A7837-->C; phylogenetic inference allocated it in the Asian-American branch. The high proportion of European variants may reflect Spanish colonial influence on these native Inca descendants. The predominance of HPV-16 variants in pathologic samples when compared to normal controls could have implications for the natural history of cervical lesions. Copyright 2003 Wiley-Liss, Inc.

  5. A variational Bayes discrete mixture test for rare variant association.

    Science.gov (United States)

    Logsdon, Benjamin A; Dai, James Y; Auer, Paul L; Johnsen, Jill M; Ganesh, Santhi K; Smith, Nicholas L; Wilson, James G; Tracy, Russell P; Lange, Leslie A; Jiao, Shuo; Rich, Stephen S; Lettre, Guillaume; Carlson, Christopher S; Jackson, Rebecca D; O'Donnell, Christopher J; Wurfel, Mark M; Nickerson, Deborah A; Tang, Hua; Reiner, Alexander P; Kooperberg, Charles

    2014-01-01

    Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that "aggregate" tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute's Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans.

  6. Classical many-particle systems with unique disordered ground states

    Science.gov (United States)

    Zhang, G.; Stillinger, F. H.; Torquato, S.

    2017-10-01

    Classical ground states (global energy-minimizing configurations) of many-particle systems are typically unique crystalline structures, implying zero enumeration entropy of distinct patterns (aside from trivial symmetry operations). By contrast, the few previously known disordered classical ground states of many-particle systems are all high-entropy (highly degenerate) states. Here we show computationally that our recently proposed "perfect-glass" many-particle model [Sci. Rep. 6, 36963 (2016), 10.1038/srep36963] possesses disordered classical ground states with a zero entropy: a highly counterintuitive situation . For all of the system sizes, parameters, and space dimensions that we have numerically investigated, the disordered ground states are unique such that they can always be superposed onto each other or their mirror image. At low energies, the density of states obtained from simulations matches those calculated from the harmonic approximation near a single ground state, further confirming ground-state uniqueness. Our discovery provides singular examples in which entropy and disorder are at odds with one another. The zero-entropy ground states provide a unique perspective on the celebrated Kauzmann-entropy crisis in which the extrapolated entropy of a supercooled liquid drops below that of the crystal. We expect that our disordered unique patterns to be of value in fields beyond glass physics, including applications in cryptography as pseudorandom functions with tunable computational complexity.

  7. Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

    Science.gov (United States)

    Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

    2018-01-01

    Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

  8. Dynamic karyotype evolution and unique sex determination systems in Leptidea wood white butterflies

    Czech Academy of Sciences Publication Activity Database

    Šíchová, Jindra; Voleníková, A.; Dincă, A.; Nguyen, Petr; Vila, R.; Sahara, K.; Marec, František

    2015-01-01

    Roč. 15, č. 1 (2015), article number 89 ISSN 1471-2148 R&D Projects: GA AV ČR IAA600960925; GA ČR(CZ) GP14-35819P; GA ČR(CZ) GA14-22765S Grant - others:GA JU(CZ) 063/2012/P; Spanish Ministerio de Economia y Competitividad(ES) CGL2013-48277-P; GA JU(CZ) 052/2013/P; 7th European Community Framework Programme(CZ) 625997; JSPS(JP) 23380030 Institutional support: RVO:60077344 Keywords : Lepidoptera * wood white butteflies * karyotype variability Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.406, year: 2015 http://www.biomedcentral.com/content/pdf/s12862-015-0375-4.pdf

  9. Unique and Common Mechanisms of Change across Cognitive and Dynamic Psychotherapies

    Science.gov (United States)

    Gibbons, Mary Beth Connolly; Crits-Christoph, Paul; Barber, Jacques P.; Stirman, Shannon Wiltsey; Gallop, Robert; Goldstein, Lizabeth A.; Temes, Christina M.; Ring-Kurtz, Sarah

    2009-01-01

    The goal of this article was to examine theoretically important mechanisms of change in psychotherapy outcome across different types of treatment. Specifically, the role of gains in self-understanding, acquisition of compensatory skills, and improvements in views of the self were examined. A pooled study database collected at the University of…

  10. Existence and uniqueness results for a class of dynamic elasto-plastic contact problems

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel; Petrov, A.

    2013-01-01

    Roč. 408, č. 1 (2013), s. 125-139 ISSN 0022-247X R&D Projects: GA ČR GAP201/10/2315 Institutional support: RVO:67985840 Keywords : contact with friction * elasto-plasticity * hysteresis operators Subject RIV: BA - General Mathematics Impact factor: 1.119, year: 2013 http://www.sciencedirect.com/science/article/pii/S0022247X13004952

  11. .xi. Tauri: a unique laboratory to study the dynamic interaction in a compact hierarchical quadruple system

    Czech Academy of Sciences Publication Activity Database

    Nemravová, J.; Harmanec, P.; Brož, M.; Vokrouhlický, D.; Mourard, D.; Hummel, C.A.; Cameron, C.; Matthews, J.M.; Bolton, C. T.; Božić, H.; Chini, R.; Dembsky, T.; Engle, S.; Farrington, C.D.; Grunhut, J.H.; Guenther, D.B.; Guinan, E. F.; Korčáková, D.; Koubský, Pavel; Křiček, R.; Kuschnig, R.; Mayer, P.; McCook, G.; Moffat, A.F.J.; Nardetto, N.; Prša, A.; Ribeiro, J.; Rowe, J.; Rucinski, S.M.; Škoda, Petr; Šlechta, Miroslav; Tallon-Bosc, I.; Votruba, Viktor; Weiss, W.W.; Wolf, M.; Zasche, P.; Zavala, R.T.

    2016-01-01

    Roč. 594, October (2016), A55/1-A55/47 ISSN 0004-6361 Institutional support: RVO:67985815 Keywords : close binaries * spectroscopic binaries * eclipsing binaries Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

  12. Maritime piracy situation modelling with dynamic Bayesian networks

    CSIR Research Space (South Africa)

    Dabrowski, James M

    2015-05-01

    Full Text Available A generative model for modelling maritime vessel behaviour is proposed. The model is a novel variant of the dynamic Bayesian network (DBN). The proposed DBN is in the form of a switching linear dynamic system (SLDS) that has been extended into a...

  13. Structure of chymotrypsin variant B from Atlantic cod, Gadus morhua

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Asgeirsson, B; Thórólfsson, M

    1996-01-01

    The amino-acid sequence of chymotrypsin variant B isolated from the pyloric caeca of Atlantic cod has been elucidated. The characterization of the primary structure is based on N-terminal Edman degradation and mass spectrometry of the native protein and enzymatically derived peptides. Chymotrypsi...... autolysis sites, cod variant B only contains a single autolysis site. The three-dimensional structures of the A- and B-variants of cod has been modelled on the known crystal structure of bovine alpha-chymotrypsin showing almost superimposable structures....

  14. Variant of Rett syndrome and CDKL5 gene

    DEFF Research Database (Denmark)

    Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt

    2012-01-01

    UNLABELLED: Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. AIMS: In recent years more than 60 patients with mutations in the CDKL5 gene have...... been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. METHODS: 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all...

  15. Radioimmunological activity of 22K variant of human growth hormone

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Ribela, M.T.C.P.; Rogero, J.R.

    1986-01-01

    From a preparation of human growth hormone its integral variant (hGH-22K) was isolated by isoelectric focusing, having a pI of 5,20 and relative mobility (Rm) of 0,621 in the polyacrylamide gel electrophoresis. Several experiments for the characterization of the isolated variant were carried out. The immunological properties was tested by radioimmunoassay (RIE), in which the activity of the isolated variant and the activity of the total preparation were compared. The dose response-curves obtained by RIE were found to be considered parallels (p [pt

  16. Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

    Science.gov (United States)

    Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

    2008-07-01

    A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

  17. Variante de Dandy Walker: relato de caso = Dandy Walker variant: a case report

    Directory of Open Access Journals (Sweden)

    Khan, Richard Lester

    2009-01-01

    Conclusões: este artigo procura caracterizar a variante de Dandy Walker, que é uma malformação congênita do sistema nervoso central e é o tipo mais comum da Síndrome de Dandy Walker. Seu fenótipo é variável, devendo-se sempre pesquisar malformações tanto intra quanto extracranianas, visto que o risco de mortalidade pós-natal aumenta quando existe esta associação. O tratamento envolve equipe multidisciplinar e o prognóstico é reservado, variando conforme o fenótipo

  18. Uniqueness: skews bit occurrence frequencies in randomly generated fingerprint libraries.

    Science.gov (United States)

    Chen, Nelson G

    2016-08-01

    Requiring that randomly generated chemical fingerprint libraries have unique fingerprints such that no two fingerprints are identical causes a systematic skew in bit occurrence frequencies, the proportion at which specified bits are set. Observed frequencies (O) at which each bit is set within the resulting libraries systematically differ from frequencies at which bits are set at fingerprint generation (E). Observed frequencies systematically skew toward 0.5, with the effect being more pronounced as library size approaches the compound space, which is the total number of unique possible fingerprints given the number of bit positions each fingerprint contains. The effect is quantified for varying library sizes as a fraction of the overall compound space, and for changes in the specified frequency E. The cause and implications for this systematic skew are subsequently discussed. When generating random libraries of chemical fingerprints, the imposition of a uniqueness requirement should either be avoided or taken into account.

  19. Word from the CSO - CERN’s unique scientific breadth

    CERN Multimedia

    2008-01-01

    Whilst we are all clearly focused on completion of the LHC and the detectors around it and look forward to a successful start of operations later this year, we should not forget that CERN has yet more to offer in addition to this highest priority programme ‘at the energy frontier’. Indeed, CERN also attracts a large scientific community seizing the opportunities offered by its other facilities. Sometimes I wonder whether we are not too modest and should not emphasize more CERN’s unique scientific breadth. ISOLDE, at the PS Booster, relies on innovative techniques to produce results at the forefront of nuclear physics very cost-effectively. nTOF has provided unique measurements of interest to nuclear technology, nuclear astrophysics and basic nuclear physics, and still has an ambitious programme ahead of it after refurbishment of the target. Another unique facility is the Antiproton Decelerator, at which the study of antimatter is being pursued with ingenious experiment...

  20. RUCS: Rapid identification of PCR primers for unique core sequences

    DEFF Research Database (Denmark)

    Thomsen, Martin Christen Frølund; Hasman, Henrik; Westh, Henrik

    2017-01-01

    Designing PCR primers to target a specific selection of whole genome sequenced strains can be a long, arduous, and sometimes impractical task. Such tasks would benefit greatly from an automated tool to both identify unique targets, and to validate the vast number of potential primer pairs...... for the targets in silico . Here we present RUCS, a program that will find PCR primer pairs and probes for the unique core sequences of a positive genome dataset complement to a negative genome dataset. The resulting primer pairs and probes are in addition to simple selection also validated through a complex...... in silico PCR simulation. We compared our method, which identifies the unique core sequences, against an existing tool called ssGeneFinder, and found that our method was 6.5-20 times more sensitive. We used RUCS to design primer pairs that would target a set of genomes known to contain the mcr-1 colistin...

  1. Flexible and efficient genome tiling design with penalized uniqueness score

    Directory of Open Access Journals (Sweden)

    Du Yang

    2012-12-01

    Full Text Available Abstract Background As a powerful tool in whole genome analysis, tiling array has been widely used in the answering of many genomic questions. Now it could also serve as a capture device for the library preparation in the popular high throughput sequencing experiments. Thus, a flexible and efficient tiling array design approach is still needed and could assist in various types and scales of transcriptomic experiment. Results In this paper, we address issues and challenges in designing probes suitable for tiling array applications and targeted sequencing. In particular, we define the penalized uniqueness score, which serves as a controlling criterion to eliminate potential cross-hybridization, and a flexible tiling array design pipeline. Unlike BLAST or simple suffix array based methods, computing and using our uniqueness measurement can be more efficient for large scale design and require less memory. The parameters provided could assist in various types of genomic tiling task. In addition, using both commercial array data and experiment data we show, unlike previously claimed, that palindromic sequence exhibiting relatively lower uniqueness. Conclusions Our proposed penalized uniqueness score could serve as a better indicator for cross hybridization with higher sensitivity and specificity, giving more control of expected array quality. The flexible tiling design algorithm incorporating the penalized uniqueness score was shown to give higher coverage and resolution. The package to calculate the penalized uniqueness score and the described probe selection algorithm are implemented as a Perl program, which is freely available at http://www1.fbn-dummerstorf.de/en/forschung/fbs/fb3/paper/2012-yang-1/OTAD.v1.1.tar.gz.

  2. Human uniqueness-self-interest and social cooperation.

    Science.gov (United States)

    Okada, Daijiro; Bingham, Paul M

    2008-07-21

    Humans are unique among all species of terrestrial history in both ecological dominance and individual properties. Many, or perhaps all, of the unique elements of this nonpareil status can be plausibly interpreted as evolutionary and strategic elements and consequences of the unprecedented intensity and scale of our social cooperation. Convincing explanation of this unique human social adaptation remains a central, unmet challenge to the scientific enterprise. We develop a hypothesis for the ancestral origin of expanded cooperative social behavior. Specifically, we present a game theoretic analysis demonstrating that a specific pattern of expanded social cooperation between conspecific individuals with conflicts of interest (including non-kin) can be strategically viable, but only in animals that possess a highly unusual capacity for conspecific violence (credible threat) having very specific properties that dramatically reduce the costs of coercive violence. The resulting reduced costs allow preemptive or compensated coercion to be an instantaneously self-interested behavior under diverse circumstances rather than in rare, idiosyncratic circumstances as in actors (animals) who do not have access to inexpensive coercive threat. Humans are apparently unique among terrestrial organisms in having evolved conspecific coercive capabilities that fulfill these stringent requirements. Thus, our results support the proposal that access to a novel capacity for projection of coercive threat might represent the essential initiating event for the evolution of a human-like pattern of social cooperation and the subsequent evolution of the diverse features of human uniqueness. Empirical evidence indicates that these constraints were, in fact, met only in our evolutionary lineage. The logic for the emergence of uniquely human cooperation suggested by our analysis apparently accounts simply for the human fossil record.

  3. A note on unique solvability of the absolute value equation

    Directory of Open Access Journals (Sweden)

    Taher Lotfi

    2014-05-01

    Full Text Available It is proved that applying sufficient regularity conditions to the interval matrix $[A-|B|,A+|B|]$‎, ‎we can create a new unique solvability condition for the absolute value equation $Ax+B|x|=b$‎, ‎since regularity of interval matrices implies unique solvability of their corresponding absolute value equation‎. ‎This condition is formulated in terms of positive definiteness of a certain point matrix‎. ‎Special case $B=-I$ is verified too as an application.

  4. Increasing Need for Uniqueness in Contemporary China: Empirical Evidence

    Directory of Open Access Journals (Sweden)

    Huajian Cai

    2018-05-01

    Full Text Available Past research has documented various cultural and psychological changes in contemporary China. In two studies, we examine how Chinese people’s need for uniqueness (NFU also has changed. In Study 1, we found a significant cross-generational increase in Chinese participants’ self-reported NFU. In Study 2, we sampled the names of Chinese newborn babies over the last five decades and found that parents have been increasingly likely to use unique characters to name their children. These findings suggest that the NFU has been rising in China, a historically collectivistic-oriented society. Theoretical and practical implications of our findings were discussed.

  5. Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

    Science.gov (United States)

    Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

    2018-01-23

    Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

  6. On the properties of a variant of the Riccati system of equations

    International Nuclear Information System (INIS)

    Sarkar, Amartya; Guha, Partha; Bhattacharjee, J K; Mallik, A K; Ghose-Choudhury, Anindya; Leach, P G L

    2012-01-01

    A variant of the generalized Riccati system of equations is considered. It is shown that for α = 2n + 3 the system admits a bilagrangian description and the dynamics has a node at the origin, whereas for α much smaller than a critical value the dynamics is periodic, the origin being a centre. It is found that the solution changes from being periodic to aperiodic at a critical point, α c = 2√(2(n+1)), which is independent of the initial conditions. This behaviour is explained by finding a scaling argument via which the phase trajectories corresponding to different initial conditions collapse onto a single universal orbit. Numerical evidence for the transition is shown. Further, using a perturbative renormalization group argument, it is conjectured that the oscillator exhibits isochronous oscillations. The correctness of the conjecture is established numerically. (paper)

  7. Myostatin: genetic variants, therapy and gene doping

    Directory of Open Access Journals (Sweden)

    André Katayama Yamada

    2012-09-01

    Full Text Available Since its discovery, myostatin (MSTN has been at the forefront of muscle therapy research because intrinsic mutations or inhibition of this protein, by either pharmacological or genetic means, result in muscle hypertrophy and hyperplasia. In addition to muscle growth, MSTN inhibition potentially disturbs connective tissue, leads to strength modulation, facilitates myoblast transplantation, promotes tissue regeneration, induces adipose tissue thermogenesis and increases muscle oxidative phenotype. It is also known that current advances in gene therapy have an impact on sports because of the illicit use of such methods. However, the adverse effects of these methods, their impact on athletic performance in humans and the means of detecting gene doping are as yet unknown. The aim of the present review is to discuss biosynthesis, genetic variants, pharmacological/genetic manipulation, doping and athletic performance in relation to the MSTN pathway. As will be concluded from the manuscript, MSTN emerges as a promising molecule for combating muscle wasting diseases and for triggering wide-ranging discussion in view of its possible use in gene doping.Desde sua descoberta, a miostatina (MSTN entrou na linha de frente em pesquisas relacionadas às terapias musculares porque mutações intrínsecas ou inibição desta proteína tanto por abordagens farmacológicas como genéticas resultam em hipertrofia muscular e hiperplasia. Além do aumento da massa muscular, a inibição de MSTN potencialmente prejudica o tecido conectivo, modula a força muscular, facilita o transplante de mioblastos, promove regeneração tecidual, induz termogênese no tecido adiposo e aumenta a oxidação na musculatura esquelética. É também sabido que os atuais avanços em terapia gênica têm uma relação com o esporte devido ao uso ilícito de tal método. Os efeitos adversos de tal abordagem, seus efeitos no desempenho de atletas e métodos para detectar doping genético s

  8. Adult schizophrenic-like variant of adrenoleukodystrophy.

    Science.gov (United States)

    Szpak, G M; Lewandowska, E; Schmidt-Sidor, B; Popow, J; Kozłowski, P; Lechowicz, W; Kulczycki, J; Zaremba, J; Dymecki, J

    1996-01-01

    A 35-year-old man died after 30 months following the onset of the disease. There was a history of changes in his mental condition, including disturbances of behavior as well as the evidence of progressing dementia. The patient revealed gait disturbances and finally became bed ridden. Bizarre behavior and changes of mood with concurrent growing irritability which predominated during the course of disease, may explain the initial diagnosis of schizophrenia. Then cerebellar and spastic movement disorders leading to paraparesis and sphincters disturbances developed. Clinical symptoms of adrenal failure were not found apart from episodes of arterial pressure fall. After two years a magnetic resonance imaging (MRI) revealed an extensive diffuse demyelinative process in white matter of cerebral and cerebellar hemispheres. Activity of lysosomal enzymes was normal. A general autopsy revealed atrophy of adrenal cortex and the presence of ballooned cells with striated cytoplasm in the reticular and fasciculate zones. Neuropathological examination revealed an extensive demyelination of white matter in cerebral and cerebellar hemispheres and of the long paths of the brain stem, corresponding to changes in MRI examination. Within demyelination areas damage of axons and diffuse cellular and fibrous gliosis were found as well as perivascular lymphocytic infiltrations with the presence of strong PAS (+) and Sudan (+) macrophages. Immunocytochemical reactions with HAM-56 and RCA1 in macrophages were positive. Electron microscopy examination revealed lamellar inclusions in cytoplasm of macrophages. Similar structures were present in the lysosomes of astrocytes. Morphological examination of adrenal glands as well as morphological and ultrastructural study of the brain allowed us to diagnose the cerebral form of adrenoleukodystrophy (ALD). Topography and character of the brain changes seems to be in keeping with a rare schizophrenic-like variant of ALD with progressive dementia

  9. The nonlinear dynamics of a coupled fission system

    International Nuclear Information System (INIS)

    Bilanovic, Z.; Harms, A.A.

    1993-01-01

    The dynamic properties of a nonlinear and in situ vibrationally perturbed nuclear-to-thermal coupled neutron multiplying medium are examined. Some unique self-organizational temporal patterns appear in such fission systems and suggest a complex underlying dynamic. (Author)

  10. QSAR models for prediction of chromatographic behavior of homologous Fab variants.

    Science.gov (United States)

    Robinson, Julie R; Karkov, Hanne S; Woo, James A; Krogh, Berit O; Cramer, Steven M

    2017-06-01

    While quantitative structure activity relationship (QSAR) models have been employed successfully for the prediction of small model protein chromatographic behavior, there have been few reports to date on the use of this methodology for larger, more complex proteins. Recently our group generated focused libraries of antibody Fab fragment variants with different combinations of surface hydrophobicities and electrostatic potentials, and demonstrated that the unique selectivities of multimodal resins can be exploited to separate these Fab variants. In this work, results from linear salt gradient experiments with these Fabs were employed to develop QSAR models for six chromatographic systems, including multimodal (Capto MMC, Nuvia cPrime, and two novel ligand prototypes), hydrophobic interaction chromatography (HIC; Capto Phenyl), and cation exchange (CEX; CM Sepharose FF) resins. The models utilized newly developed "local descriptors" to quantify changes around point mutations in the Fab libraries as well as novel cluster descriptors recently introduced by our group. Subsequent rounds of feature selection and linearized machine learning algorithms were used to generate robust, well-validated models with high training set correlations (R 2  > 0.70) that were well suited for predicting elution salt concentrations in the various systems. The developed models then were used to predict the retention of a deamidated Fab and isotype variants, with varying success. The results represent the first successful utilization of QSAR for the prediction of chromatographic behavior of complex proteins such as Fab fragments in multimodal chromatographic systems. The framework presented here can be employed to facilitate process development for the purification of biological products from product-related impurities by in silico screening of resin alternatives. Biotechnol. Bioeng. 2017;114: 1231-1240. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.

    Science.gov (United States)

    Wreesmann, Volkert B; Ghossein, Ronald A; Hezel, Michael; Banerjee, Debenranrath; Shaha, Ashok R; Tuttle, R Michael; Shah, Jatin P; Rao, Pulivarthi H; Singh, Bhuvanesh

    2004-08-01

    The majority of thyroid tumors are classified as papillary (papillary thyroid carcinomas; PTCs) or follicular neoplasms (follicular thyroid adenomas and carcinomas; FTA/FTC) based on nuclear features and the cellular growth pattern. However, classification of the follicular variant of papillary thyroid carcinoma (FVPTC) remains an issue of debate. These tumors contain a predominantly follicular growth pattern but display nuclear features and overall clinical behavior consistent with PTC. In this study, we used comparative genomic hybridization (CGH) to compare the global chromosomal aberrations in FVPTC to the PTC of classical variant (classical PTC) and FTA/FTC. In addition, we assessed the presence of peroxisome proliferator-activated receptor-gamma (PPARG) alteration, a genetic event specific to FTA/FTC, using Southern blot and immunohistochemistry analyses. In sharp contrast to the findings in classical PTC (4% of cases), CGH analysis demonstrated that both FVPTC (59% of cases) and FTA/FTC (36% of cases) were commonly characterized by aneuploidy (P = 0.0002). Moreover, the pattern of chromosomal aberrations (gains at chromosome arms 2q, 4q, 5q, 6q, 8q, and 13q and deletions at 1p, 9q, 16q, 17q, 19q, and 22q) in the follicular variant of PTC closely resembled that of FTA/FTC. Aberrations in PPARG were uniquely detected in FVPTC and FTA/FTC. Our findings suggest a stronger relationship between the FVPTC and FTA/FTC than previously appreciated and support further consideration of the current classification of thyroid neoplasms. Copyright 2004 Wiley-Liss, Inc.

  12. HIV-1 Variants and Drug Resistance in Pregnant Women from Bata (Equatorial Guinea): 2012-2013.

    Science.gov (United States)

    Alvarez, Patricia; Fernández McPhee, Carolina; Prieto, Luis; Martín, Leticia; Obiang, Jacinta; Avedillo, Pedro; Vargas, Antonio; Rojo, Pablo; Benito, Agustín; Ramos, José Tomás; Holguín, África

    2016-01-01

    This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence. Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses. A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each). The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.

  13. A monomeric variant of insulin degrading enzyme (IDE loses its regulatory properties.

    Directory of Open Access Journals (Sweden)

    Eun Suk Song

    2010-03-01

    Full Text Available Insulin degrading enzyme (IDE is a key enzyme in the metabolism of both insulin and amyloid beta peptides. IDE is unique in that it is subject to allosteric activation which is hypothesized to occur through an oligomeric structure.IDE is known to exist as an equilibrium mixture of monomers, dimers, and higher oligomers, with the dimer being the predominant form. Based on the crystal structure of IDE we deleted the putative dimer interface in the C-terminal region, which resulted in a monomeric variant. Monomeric IDE retained enzymatic activity, however instead of the allosteric behavior seen with wild type enzyme it displayed Michaelis-Menten kinetic behavior. With the substrate Abz-GGFLRKHGQ-EDDnp, monomeric IDE retained approximately 25% of the wild type activity. In contrast with the larger peptide substrates beta-endorphin and amyloid beta peptide 1-40, monomeric IDE retained only 1 to 0.25% of wild type activity. Unlike wild type IDE neither bradykinin nor dynorphin B-9 activated the monomeric variant of the enzyme. Similarly, monomeric IDE was not activated by polyphosphates under conditions in which the activity of wild type enzyme was increased more than 50 fold.These findings serve to establish the dimer interface in IDE and demonstrate the requirement for an oligomeric form of the enzyme for its regulatory properties. The data support a mechanism where the binding of activators to oligomeric IDE induces a conformational change that cannot occur in the monomeric variant. Since a conformational change from a closed to a more open structure is likely the rate-determining step in the IDE reaction, the subunit induced conformational change likely shifts the structure of the oligomeric enzyme to a more open conformation.

  14. Plasmodium falciparum variant STEVOR antigens are expressed in merozoites and possibly associated with erythrocyte invasion

    Directory of Open Access Journals (Sweden)

    Petter Michaela

    2008-07-01

    Full Text Available Abstract Background Plasmodium falciparum STEVOR proteins, encoded by the multicopy stevor gene family have no known biological functions. Their expression and unique locations in different parasite life cycle stages evoke multiple functionalities. Their abundance and hypervariability support a role in antigenic variation. Methods Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant antigens of this gene family and to follow changes in STEVOR expression in parasite populations panned on CSA or CD36 receptors. Immunofluorescence assays and immunoelectron microscopy were performed to study the subcellular localization of STEVOR proteins in different parasite stages. The capacity of the antibody to inhibit merozoite invasion of erythrocytes was assessed to determine whether STEVOR variants were involved in the invasion process. Results Antigenic variation of STEVORs at the protein level was observed in blood stage parasites. STEVOR variants were found to be present on the merozoite surface and in rhoptries. An insight into a participation in erythrocyte invasion was gained through an immunofluorescence analysis of a sequence of thin slides representing progressive steps in erythrocyte invasion. An interesting feature of the staining pattern was what appeared to be the release of STEVORs around the invading merozoites. Because the anti-STEVOR antibody did not inhibit invasion, the role of STEVORs in this process remains unknown. Conclusion The localization of STEVOR proteins to the merozoite surface and the rhoptries together with its prevalence as a released component in the invading merozoite suggest a role of these antigens in adhesion and/or immune evasion in the erythrocyte invasion process. These observations would also justify STEVORs for undergoing antigenic variation. Even though a role in erythrocyte invasion remains speculative, an association of members of the STEVOR protein family with

  15. Leapfrog variants of iterative methods for linear algebra equations

    Science.gov (United States)

    Saylor, Paul E.

    1988-01-01

    Two iterative methods are considered, Richardson's method and a general second order method. For both methods, a variant of the method is derived for which only even numbered iterates are computed. The variant is called a leapfrog method. Comparisons between the conventional form of the methods and the leapfrog form are made under the assumption that the number of unknowns is large. In the case of Richardson's method, it is possible to express the final iterate in terms of only the initial approximation, a variant of the iteration called the grand-leap method. In the case of the grand-leap variant, a set of parameters is required. An algorithm is presented to compute these parameters that is related to algorithms to compute the weights and abscissas for Gaussian quadrature. General algorithms to implement the leapfrog and grand-leap methods are presented. Algorithms for the important special case of the Chebyshev method are also given.

  16. Behavioral variant of frontotemporal dementia mimicking Huntington's disease

    DEFF Research Database (Denmark)

    Nielsen, T Rune; Bruhn, Peter; Nielsen, Jørgen E

    2010-01-01

    Behavioral changes and cognitive decline are the core clinical manifestations in the behavioral variant of frontotemporal dementia (bv-FTD). The behavioral changes may include characteristic stereotypic movements. These movements, although without clear purpose, are not involuntary. Involuntary...

  17. Variant Plasmodium ovale isolated from a patient infected in Ghana

    Directory of Open Access Journals (Sweden)

    Petersen Eskild

    2011-01-01

    Full Text Available Abstract Recent data have found that Plasmodium ovale can be separated in two distinct species: classic and variant P. ovale based on multilocus typing of different genes. This study presents a P. ovale isolate from a patient infected in Ghana together with an analysis of the small subunit RNA, cytochrome b, cytochrome c oxidase I, cysteine protease and lactate dehydrogenase genes, which show that the sample is a variant P. ovale and identical or highly similar to variant P. ovale isolated from humans in South-East Asia and Africa, and from a chimpanzee in Cameroon. The split between the variant and classic P. ovale is estimated to have occurred 1.7 million years ago.

  18. Genetic variant as a marker for bladder cancer therapy

    Science.gov (United States)

    Patients who have inherited a specific common genetic variant develop bladder cancer tumors that strongly express a protein known as prostate stem cell antigen (PSCA), which is also expressed in many pancreatic and prostate tumors, according to research a

  19. Efficient population-scale variant analysis and prioritization with VAPr.

    Science.gov (United States)

    Birmingham, Amanda; Mark, Adam M; Mazzaferro, Carlo; Xu, Guorong; Fisch, Kathleen M

    2018-04-06

    With the growing availability of population-scale whole-exome and whole-genome sequencing, demand for reproducible, scalable variant analysis has spread within genomic research communities. To address this need, we introduce the Python package VAPr (Variant Analysis and Prioritization). VAPr leverages existing annotation tools ANNOVAR and MyVariant.info with MongoDB-based flexible storage and filtering functionality. It offers biologists and bioinformatics generalists easy-to-use and scalable analysis and prioritization of genomic variants from large cohort studies. VAPr is developed in Python and is available for free use and extension under the MIT License. An install package is available on PyPi at https://pypi.python.org/pypi/VAPr, while source code and extensive documentation are on GitHub at https://github.com/ucsd-ccbb/VAPr. kfisch@ucsd.edu.

  20. Genetic variants influencing lipid levels and risk of dyslipidemia in ...

    Indian Academy of Sciences (India)

    HUAICHAO LUO

    2017-12-18

    Dec 18, 2017 ... total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. (TG) in 1900 ... in Chinese population, especially relationship between these genetic variants ...

  1. Common Gene Variants Account for Most Genetic Risk for Autism

    Science.gov (United States)

    ... gene variants account for most genetic risk for autism Roles of heritability, mutations, environment estimated – NIH-funded study. The bulk of risk, or liability, for autism spectrum disorders (ASD) was traced to inherited variations ...

  2. Method of generating ploynucleotides encoding enhanced folding variants

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.; Kiss, Csaba; Waldo, Geoffrey S.

    2017-05-02

    The invention provides directed evolution methods for improving the folding, solubility and stability (including thermostability) characteristics of polypeptides. In one aspect, the invention provides a method for generating folding and stability-enhanced variants of proteins, including but not limited to fluorescent proteins, chromophoric proteins and enzymes. In another aspect, the invention provides methods for generating thermostable variants of a target protein or polypeptide via an internal destabilization baiting strategy. Internally destabilization a protein of interest is achieved by inserting a heterologous, folding-destabilizing sequence (folding interference domain) within DNA encoding the protein of interest, evolving the protein sequences adjacent to the heterologous insertion to overcome the destabilization (using any number of mutagenesis methods), thereby creating a library of variants. The variants in the library are expressed, and those with enhanced folding characteristics selected.

  3. Genotype and phenotype spectrum of NRAS germline variants

    NARCIS (Netherlands)

    Altmuller, F.; Lissewski, C.; Bertola, D.; Flex, E.; Stark, Z.; Spranger, S.; Baynam, G.; Buscarilli, M.; Dyack, S.; Gillis, J.; Yntema, H.G.; Pantaleoni, F.; Loon, R.L. van; MacKay, S.; Mina, K.; Schanze, I.; Tan, T.Y.; Walsh, M.; White, S.M.; Niewisch, M.R.; Garcia-Minaur, S.; Plaza, D.; Ahmadian, M.R.; Cave, H.; Tartaglia, M.; Zenker, M.

    2017-01-01

    RASopathies comprise a group of disorders clinically characterized by short stature, heart defects, facial dysmorphism, and varying degrees of intellectual disability and cancer predisposition. They are caused by germline variants in genes encoding key components or modulators of the highly

  4. Characterization of Canine parvovirus 2 variants circulating in Greece.

    Science.gov (United States)

    Ntafis, Vasileios; Xylouri, Eftychia; Kalli, Iris; Desario, Costantina; Mari, Viviana; Decaro, Nicola; Buonavoglia, Canio

    2010-09-01

    The aim of the present study was to characterize Canine parvovirus 2 (CPV-2) variants currently circulating in Greece. Between March 2008 and March 2009, 167 fecal samples were collected from diarrheic dogs from different regions of Greece. Canine parvovirus 2 was detected by standard polymerase chain reaction, whereas minor groove binder probe assays were used to distinguish genetic variants and discriminate between vaccine and field strains. Of 84 CPV-2-positive samples, 81 CPV-2a, 1 CPV-2b, and 2 CPV-2c were detected. Vaccine strains were not detected in any sample. Sequence analysis of the VP2 gene of the 2 CPV-2c viruses revealed up to 100% amino acid identity with the CPV-2c strains previously detected in Europe. The results indicated that, unlike other European countries, CPV-2a remains the most common variant in Greece, and that the CPV-2c variant found in Europe is also present in Greece.

  5. COMPARISON OF THE TEST VARIANTS IN ENTRANCE EXAMINATIONS

    Directory of Open Access Journals (Sweden)

    KLŮFA, Jindřich

    2016-12-01

    Full Text Available The paper contains an analysis of the differences of number of points in the test in mathematics between test variants, which were used in the entrance examinations at the Faculty of Business Administration at University of Economics in Prague in 2015. The differences may arise due to the varying difficulty of variants for students, but also because of the different level of knowledge of students who write these variants. This problem we shall study in present paper. The aim of this paper is to study dependence of the results of entrance examinations in mathematics on test variants. The results obtained will be used for further improvement of the admission process at University of Economics.

  6. Reversion in variants from a duplication strain of Aspergillus nidulans

    International Nuclear Information System (INIS)

    Menezes, E.M.; Azevedo, J.L.

    1978-01-01

    Strains of Aspergillus nidulans with a chromosome segment in duplicate, one in normal position and one translocated to another chromosome, are unstable at mitosis. In addition to variants which result from deletions in either of the duplicate segments, which usually have improved morphology, they produce variants with deteriorated morphology. Three deteriorated variants reverted frequently to parental type morphology, both spontaneously and after ultra-violet treatment. Of six reversions analysed genetically, five were due to suppressors and one was probably due to back mutation. The suppressors segregated as single genes and were not linked to the mutation which they suppress. The instability of these so-called 'deteriorated' variants is discussed in relation to mitotic instability phenomena in A. nidulans. (orig.) [de

  7. Leucine 208 in human histamine N-methyltransferase emerges as a hotspot for protein stability rationalizing the role of the L208P variant in intellectual disability.

    Science.gov (United States)

    Tongsook, Chanakan; Niederhauser, Johannes; Kronegger, Elena; Straganz, Grit; Macheroux, Peter

    2017-01-01

    The degradation of histamine catalyzed by the SAM-dependent histamine N-methyltransferase (HNMT) is critically important for the maintenance of neurological processes. Recently, two mutations in the encoding human gene were reported to give rise to dysfunctional protein variants (G60D and L208P) leading to intellectual disability. In the present study, we have expressed eight L208 variants with either apolar (L208F and L208V), polar (L208N and L208T) or charged (L208D, L208H, L208K and L208R) amino acids to define the impact of side chain variations on protein structure and function. We found that the variants L208N, L208T, L208D and L208H were severely compromised in their stability. The other four variants were obtained in lower amounts in the order wild-type HNMT>L208F=L208V>L208K=L208R. Biochemical characterization of the two variants L208F and L208V exhibited similar Michaelis-Menten parameters for SAM and histamine while the enzymatic activity was reduced to 21% and 48%, respectively. A substantial loss of enzymatic activity and binding affinity for histamine was seen for the L208K and L208R variants. Similarly the thermal stability for the latter variants was reduced by 8 and 13°C, respectively. These findings demonstrate that position 208 is extremely sensitive to side chain variations and even conservative replacements affect enzymatic function. Molecular dynamics simulations showed that amino acid replacements in position 208 perturb the helical character and disrupt interactions with the adjacent β-strand, which is involved in the binding and correct positioning of histamine. This finding rationalizes the gradual loss of enzymatic activity observed in the L208 variants. Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.

  8. Protein variants in Hiroshima and Nagasaki: tales of two cities.

    Science.gov (United States)

    Neel, J V; Satoh, C; Smouse, P; Asakawa, J; Takahashi, N; Goriki, K; Fujita, M; Kageoka, T; Hazama, R

    1988-12-01

    The results of 1,465,423 allele product determinations based on blood samples from Hiroshima and Nagasaki, involving 30 different proteins representing 32 different gene products, are analyzed in a variety of ways, with the following conclusions: (1) Sibships and their parents are included in the sample. Our analysis reveals that statistical procedures designed to reduce the sample to equivalent independent genomes do not in population comparisons compensate for the familial cluster effect of rare variants. Accordingly, the data set was reduced to one representative of each sibship (937,427 allele products). (2) Both chi 2-type contrasts and a genetic distance measure (delta) reveal that rare variants (P less than .01) are collectively as effective as polymorphisms in establishing genetic differences between the two cities. (3) We suggest that rare variants that individually exhibit significant intercity differences are probably the legacy of tribal private polymorphisms that occurred during prehistoric times. (4) Despite the great differences in the known histories of the two cities, both the overall frequency of rare variants and the number of different rare variants are essentially identical in the two cities. (5) The well-known differences in locus variability are confirmed, now after adjustment for sample size differences for the various locus products; in this large series we failed to detect variants at only three of 29 loci for which sample size exceeded 23,000. (6) The number of alleles identified per locus correlates positively with subunit molecular weight. (7) Loci supporting genetic polymorphisms are characterized by more rare variants than are loci at which polymorphisms were not encountered. (8) Loci whose products do not appear to be essential for health support more variants than do loci the absence of whose product is detrimental to health. (9) There is a striking excess of rare variants over the expectation under the neutral mutation

  9. Family studies to find rare high risk variants in migraine.

    Science.gov (United States)

    Hansen, Rikke Dyhr; Christensen, Anne Francke; Olesen, Jes

    2017-12-01

    Migraine has long been known as a common complex disease caused by genetic and environmental factors. The pathophysiology and the specific genetic susceptibility are poorly understood. Common variants only explain a small part of the heritability of migraine. It is thought that rare genetic variants with bigger effect size may be involved in the disease. Since migraine has a tendency to cluster in families, a family approach might be the way to find these variants. This is also indicated by identification of migraine-associated loci in classical linkage-analyses in migraine families. A single migraine study using a candidate-gene approach was performed in 2010 identifying a rare mutation in the TRESK potassium channel segregating in a large family with migraine with aura, but this finding has later become questioned. The technologies of next-generation sequencing (NGS) now provides an affordable tool to investigate the genetic variation in the entire exome or genome. The family-based study design using NGS is described in this paper. We also review family studies using NGS that have been successful in finding rare variants in other common complex diseases in order to argue the promising application of a family approach to migraine. PubMed was searched to find studies that looked for rare genetic variants in common complex diseases through a family-based design using NGS, excluding studies looking for de-novo mutations, or using a candidate-gene approach and studies on cancer. All issues from Nature Genetics and PLOS genetics 2014, 2015 and 2016 (UTAI June) were screened for relevant papers. Reference lists from included and other relevant papers were also searched. For the description of the family-based study design using NGS an in-house protocol was used. Thirty-two successful studies, which covered 16 different common complex diseases, were included in this paper. We also found a single migraine study. Twenty-three studies found one or a few family specific

  10. Structural and Functional Characterization of a New Double Variant Haemoglobin (HbG-Philadelphia/Duarte α(2)β(2)).

    Science.gov (United States)

    Fais, Antonella; Casu, Mariano; Ruggerone, Paolo; Ceccarelli, Matteo; Porcu, Simona; Era, Benedetta; Anedda, Roberto; Sollaino, Maria Carla; Galanello, Renzo; Corda, Marcella

    2011-01-01

    WE REPORT THE FIRST CASE OF COSEGREGATION OF TWO HAEMOGLOBINS (HBS): HbG-Philadelphia [α68(E17)Asn → Lys] and HbDuarte [β62(E6)Ala → Pro]. The proband is a young patient heterozygous also for β°-thalassaemia. We detected exclusively two haemoglobin variants: HbDuarte and HbG-Philadelphia/Duarte. Functional study of the new double variant HbG-Philadelphia/Duarte exhibited an increase in oxygen affinity, with a slight decrease of cooperativity and Bohr effect. This functional behaviour is attributed to β62Ala → Pro instead of α68Asn → Lys substitution. Indeed, HbG-Philadelphia isolated in our laboratory from blood cells donor carrier for this variant is not affected by any functional modification, whereas purified Hb Duarte showed functional properties very similar to the double variant. NMR and MD simulation studies confirmed that the presence of Pro instead of Ala at the β62 position produces displacement of the E helix and modifications of the tertiary structure. The substitution α68(E17)Asn → Lys does not cause significant structural and dynamical modifications of the protein. A possible structure-based rational of substitution effects is suggested.

  11. De novo assembly and next-generation sequencing to analyse full-length gene variants from codon-barcoded libraries.

    Science.gov (United States)

    Cho, Namjin; Hwang, Byungjin; Yoon, Jung-ki; Park, Sangun; Lee, Joongoo; Seo, Han Na; Lee, Jeewon; Huh, Sunghoon; Chung, Jinsoo; Bang, Duhee

    2015-09-21

    Interpreting epistatic interactions is crucial for understanding evolutionary dynamics of complex genetic systems and unveiling structure and function of genetic pathways. Although high resolution mapping of en masse variant libraries renders molecular biologists to address genotype-phenotype relationships, long-read sequencing technology remains indispensable to assess functional relationship between mutations that lie far apart. Here, we introduce JigsawSeq for multiplexed sequence identification of pooled gene variant libraries by combining a codon-based molecular barcoding strategy and de novo assembly of short-read data. We first validate JigsawSeq on small sub-pools and observed high precision and recall at various experimental settings. With extensive simulations, we then apply JigsawSeq to large-scale gene variant libraries to show that our method can be reliably scaled using next-generation sequencing. JigsawSeq may serve as a rapid screening tool for functional genomics and offer the opportunity to explore evolutionary trajectories of protein variants.

  12. A case report of the clear cell variant of gallbladder carcinoma.

    Science.gov (United States)

    Maharaj, Ravi; Cave, Christo; Sarran, Kevin; Bascombe, Nigel; Dan, Dilip; Greaves, Wesley; Warner, Wayne A

    2017-01-01

    Clear cell gallbladder carcinoma accounts for less than 1% of all gallbladder malignancies and demonstrates its unique histopathological characteristics in patients with no prior medical illness or familial predisposition. Here we present a case of a 56-year-old female, with no prior medical conditions presented with a 2-month history of upper abdominal pain. Routine hematological and biochemical tests were unremarkable. An abdominal ultrasound revealed the presence of a gallbladder calculi, and a fundic mass while magnetic resonance cholangiopancreatography revealed a 8.0cm×3.5cm gallbladder mass. Computed tomography imaging excluded any distant haematogenous metastases. An open cholecystectomy with lymphadenectomy was proceeded by staging laparoscopy. Upon pathologic investigation, the morphologic and immunophenotypic features supported a diagnosis of clear cell variant of gallbladder carcinoma. Pathological prognostications for primary clear cell gall bladder carcinomas are not well defined due to the rarity of cases and possible misidentification as secondary metastases. Foci of adenocarcinoma within the tumor along with immunohistochemical staining probes can be informative in consideration of differential diagnosis. In these cases, clinical case management should be personalized for increased survival with the possible incorporation of next generation sequencing approaches to guide therapeutic algorithms. We discuss this exceedingly rare case of the clear cell variant of gallbladder carcinoma in detail, highlighting some of the diagnostic, and clinical challenges. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. IRAK1 variant is protective for orthodontic-induced external apical root resorption.

    Science.gov (United States)

    Pereira, S; Nogueira, L; Canova, F; Lopez, M; Silva, H C

    2016-10-01

    Interleukin-1 beta (IL1B) pathway is a key player in orthodontic-induced external apical root resorption (EARR). The aim of this work was to identify the genes related to the IL1 pathway as possible candidate genes for EARR, which might be included in an integrative predictive model of this complex phenotype. Using a stepwise multiple linear regression model, 195 patients who had undergone orthodontic treatment were assessed for clinical and genetic factors associated with %EARRmax (maximum %EARR value obtained for each patient). The four maxillary incisors and the two maxillary canines were assessed. Three functional single nucleotide polymorphisms (SNPs) were genotyped: rs1143634 in IL1B gene, rs315952 in IL1RN gene, and rs1059703 in X-linked IRAK1 gene. The model showed that four of the nine clinical variables and one SNP explained 30% of the %EARRmax variability. The most significant unique contributions to the model were gender (P = 0.001), treatment duration (P < 0.001), premolar extractions (P = 0.003), Hyrax appliance (P < 0.001), and homozygosity/hemizygosity for variant C from IRAK1 gene (P = 0.018), which proved to be a protective factor. IRAK1 polymorphism is proposed as a protective variant for EARR. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. al mena: a comprehensive resource of human genetic variants integrating genomes and exomes from Arab, Middle Eastern and North African populations.

    Science.gov (United States)

    Koshy, Remya; Ranawat, Anop; Scaria, Vinod

    2017-10-01

    Middle East and North Africa (MENA) encompass very unique populations, with a rich history and encompasses characteristic ethnic, linguistic and genetic diversity. The genetic diversity of MENA region has been largely unknown. The recent availability of whole-exome and whole-genome sequences from the region has made it possible to collect population-specific allele frequencies. The integration of data sets from this region would provide insights into the landscape of genetic variants in this region. We integrated genetic variants from multiple data sets systematically, available from this region to create a compendium of over 26 million genetic variations. The variants were systematically annotated and their allele frequencies in the data sets were computed and available as a web interface which enables quick query. As a proof of principle for application of the compendium for genetic epidemiology, we analyzed the allele frequencies for variants in transglutaminase 1 (TGM1) gene, associated with autosomal recessive lamellar ichthyosis. Our analysis revealed that the carrier frequency of selected variants differed widely with significant interethnic differences. To the best of our knowledge, al mena is the first and most comprehensive repertoire of genetic variations from the Arab, Middle Eastern and North African region. We hope al mena would accelerate Precision Medicine in the region.

  15. Variants at the 9p21 locus and melanoma risk

    International Nuclear Information System (INIS)

    Maccioni, Livia; Rachakonda, Panduranga Sivaramakrishna; Bermejo, Justo Lorenzo; Planelles, Dolores; Requena, Celia; Hemminki, Kari; Nagore, Eduardo; Kumar, Rajiv

    2013-01-01

    The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS). In the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region. All the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3’ UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A–allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54). Our data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes

  16. Evaluating how variants of floristic quality assessment indicate wetland condition.

    Science.gov (United States)

    Kutcher, Thomas E; Forrester, Graham E

    2018-03-28

    Biological indicators are useful tools for the assessment of ecosystem condition. Multi-metric and multi-taxa indicators may respond to a broader range of disturbances than simpler indicators, but their complexity can make them difficult to interpret, which is critical to indicator utility for ecosystem management. Floristic Quality Assessment (FQA) is an example of a biological assessment approach that has been widely tested for indicating freshwater wetland condition, but less attention has been given to clarifying the factors controlling its response. FQA quantifies the aggregate of vascular plant species tolerance to habitat degradation (conservatism), and model variants have incorporated species richness, abundance, and indigenity (native or non-native). To assess bias, we tested FQA variants in open-canopy freshwater wetlands against three independent reference measures, using practical vegetation sampling methods. FQA variants incorporating species richness did not correlate with our reference measures and were influenced by wetland size and hydrogeomorphic class. In contrast, FQA variants lacking measures of species richness responded linearly to reference measures quantifying individual and aggregate stresses, suggesting a broad response to cumulative degradation. FQA variants incorporating non-native species, and a variant additionally incorporating relative species abundance, improved performance over using only native species. We relate our empirical findings to ecological theory to clarify the functional properties and implications of the FQA variants. Our analysis indicates that (1) aggregate conservatism reliably declines with increased disturbance; (2) species richness has varying relationships with disturbance and increases with site area, confounding FQA response; and (3) non-native species signal human disturbance. We propose that incorporating species abundance can improve FQA site-level relevance with little extra sampling effort. Using our

  17. Functional significance of SPINK1 promoter variants in chronic pancreatitis.

    Science.gov (United States)

    Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

    2015-05-01

    Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

  18. Mouse ribosomal RNA genes contain multiple differentially regulated variants.

    Directory of Open Access Journals (Sweden)

    Hung Tseng

    2008-03-01

    Full Text Available Previous cytogenetic studies suggest that various rDNA chromosomal loci are not equally active in different cell types. Consistent with this variability, rDNA polymorphism is well documented in human and mouse. However, attempts to identify molecularly rDNA variant types, which are regulated individually (i.e., independent of other rDNA variants and tissue-specifically, have not been successful. We report here the molecular cloning and characterization of seven mouse rDNA variants (v-rDNA. The identification of these v-rDNAs was based on restriction fragment length polymorphisms (RFLPs, which are conserved among individuals and mouse strains. The total copy number of the identified variants is less than 100 and the copy number of each individual variant ranges from 4 to 15. Sequence analysis of the cloned v-rDNA identified variant-specific single nucleotide polymorphisms (SNPs in the transcribed region. These SNPs were used to develop a set of variant-specific PCR assays, which permitted analysis of the v-rDNAs' expression profiles in various tissues. These profiles show that three v-rDNAs are expressed in all tissues (constitutively active, two are expressed in some tissues (selectively active, and two are not expressed (silent. These expression profiles were observed in six individuals from three mouse strains, suggesting the pattern is not randomly determined. Thus, the mouse rDNA array likely consists of genetically distinct variants, and some are regulated tissue-specifically. Our results provide the first molecular evidence for cell-type-specific regulation of a subset of rDNA.

  19. Identifying structural variants using linked-read sequencing data.

    Science.gov (United States)

    Elyanow, Rebecca; Wu, Hsin-Ta; Raphael, Benjamin J

    2017-11-03

    Structural variation, including large deletions, duplications, inversions, translocations, and other rearrangements, is common in human and cancer genomes. A number of methods have been developed to identify structural variants from Illumina short-read sequencing data. However, reliable identification of structural variants remains challenging because many variants have breakpoints in repetitive regions of the genome and thus are difficult to identify with short reads. The recently developed linked-read sequencing technology from 10X Genomics combines a novel barcoding strategy with Illumina sequencing. This technology labels all reads that originate from a small number (~5-10) DNA molecules ~50Kbp in length with the same molecular barcode. These barcoded reads contain long-range sequence information that is advantageous for identification of structural variants. We present Novel Adjacency Identification with Barcoded Reads (NAIBR), an algorithm to identify structural variants in linked-read sequencing data. NAIBR predicts novel adjacencies in a individual genome resulting from structural variants using a probabilistic model that combines multiple signals in barcoded reads. We show that NAIBR outperforms several existing methods for structural variant identification - including two recent methods that also analyze linked-reads - on simulated sequencing data and 10X whole-genome sequencing data from the NA12878 human genome and the HCC1954 breast cancer cell line. Several of the novel somatic structural variants identified in HCC1954 overlap known cancer genes. Software is available at compbio.cs.brown.edu/software. braphael@princeton.edu. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  20. [Approach to diagnosis and management of myeloproliferative neoplasm variants].

    Science.gov (United States)

    Mitsumori, Toru; Kirito, Keita

    2015-08-01

    Myeloproliferative neoplasm (MPN) variants are defined as relatively uncommon myeloid neoplasms which do not meet the criteria for either classical MPN or myelodysplastic syndrome. Due to the lack of specific markers, it has been challenging to accurately diagnose these malignant diseases. Recent studies have revealed new genetic abnormalities in MPN variants. These research advances are anticipated to open new approaches to not only achieving accurate diagnosis but also novel therapeutic options for these diseases.

  1. Y-type urethral duplication with posterior perineal fistula: A new variant

    Directory of Open Access Journals (Sweden)

    Sandesh V Parelkar

    2017-05-01

    Full Text Available 13 months old boy presented with constipation and straining during micturition with poor urinary stream and voiding of urine per rectum. Perineal examination revealed posterior perineal fistula. Voiding cysto-urethrogram showed bilateral vesicoureteral reflux with bladder diverticuli, normal dorsal urethra and dye going from urethra to rectum suggestive of Y type urethral duplication. Under stoma cover, he underwent excision of posterior perineal fistula with accessory ventral urethra and anorectoplasty was done. At present patient is passing urine in good stream without straining. The uniqueness of our case is the presence of Y type of urethral duplication with normal calibre dorsal urethra and presence of posterior perineal fistula. Therefore, we consider our case to be an unusual variant of Y type of urethral duplication that has not been described before.

  2. Pediatric and adult MRI atlas of bone marrow. Normal appearances, variants and diffuse disease states

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Sundaram, Murali [Cleveland Clinic Lerner College of Medicine, OH (United States); Cleveland Clinic Department of Radiology, OH (United States)

    2016-08-01

    This comprehensive atlas is unique in being devoted to the MRI appearances of bone marrow in the axial and appendicular skeleton of adults and children. Normal MRI findings, including common variants and degenerative changes, are first documented. MRI appearances in the entire spectrum of neoplastic and non-neoplastic infiltrative marrow disorders are then presented, with accompanying explanatory text. Among the conditions considered are multiple myeloma, the acute and chronic leukemias, diffuse metastases, diffuse lymphomas, the anemias, polycythemia vera, myelofibrosis, storage disorders, and infections. Characteristic changes to bone marrow following various forms of treatment are also displayed and discussed. The selected images reflect the use of a variety of sequences and techniques, such as fat suppression, and contrast-enhanced imaging.

  3. Regional cluster policy between best practices and cultural uniqueness

    NARCIS (Netherlands)

    Hospers, Gerrit J.; Beugelsdijk, S.; Boneschansker, E.; van Dijk, J.; Jansma, L.G.J.; Verhaar, K.H.A.

    2004-01-01

    This chapter deals with an intriguing paradox in current regional economic policy: whereas unique local factors are increasingly seen as the determinants of regional economic success, more and more governments simultaneously try to copy policy experiences that have proved successful in a particular

  4. Teen camp: a unique approach to recruit future nurses.

    Science.gov (United States)

    Redding, Donna A; Riech, Sandy; Prater, Marsha A

    2004-01-01

    A collaborative and unique approach to interest high school students in nursing. To inform educators and nursing departments about an innovative approach to recruit future nurses. Professional literature and authors' experience. All students related positive experiences. The initial camp evaluation produced innovative input from the students, and each camp met its goal of creating career interest in the nursing profession.

  5. Differentiating Performance Approach Goals and Their Unique Effects

    Science.gov (United States)

    Edwards, Ordene V.

    2014-01-01

    The study differentiates between two types of performance approach goals (competence demonstration performance approach goal and normative performance approach goal) by examining their unique effects on self-efficacy, interest, and fear of failure. Seventy-nine students completed questionnaires that measure performance approach goals,…

  6. Sufficient conditions for uniqueness of the weak value

    International Nuclear Information System (INIS)

    Dressel, J; Jordan, A N

    2012-01-01

    We review and clarify the sufficient conditions for uniquely defining the generalized weak value as the weak limit of a conditioned average using the contextual values formalism introduced in Dressel, Agarwal and Jordan (2010 Phys. Rev. Lett. http://dx.doi.org/10.1103/PhysRevLett.104.240401). We also respond to criticism of our work by Parrott (arXiv:1105.4188v1) concerning a proposed counter-example to the uniqueness of the definition of the generalized weak value. The counter-example does not satisfy our prescription in the case of an underspecified measurement context. We show that when the contextual values formalism is properly applied to this example, a natural interpretation of the measurement emerges and the unique definition in the weak limit holds. We also prove a theorem regarding the uniqueness of the definition under our sufficient conditions for the general case. Finally, a second proposed counter-example by Parrott (arXiv:1105.4188v6) is shown not to satisfy the sufficiency conditions for the provided theorem. (paper)

  7. On the Existence of Unique Equilibria in Location Models

    NARCIS (Netherlands)

    Webers, H.M.

    1996-01-01

    In this paper, we study a two-stage location-then-price game where consumers are distributed piecewise uniformly, each piece being referred to as an interval.Although the firms face a coordination problem, it is obvious that, for any given locations and prices, there is a unique indifferent

  8. Marketing the Uniqueness of Small Towns. Small Town Strategy.

    Science.gov (United States)

    Hogg, David H.; Dunn, Douglas

    A small town can strengthen its local economy as a result of business people and concerned citizens collectively identifying that community's uniqueness and then capitalizing on it via advertising, personal selling, sales promotion, or publicity. This publication relates the science of marketing to communities. Seven simple techniques are provided…

  9. Secondary metabolites from the unique bamboo, Melocanna baccifera.

    Science.gov (United States)

    Govindan, Balaji; Johnson, Anil John; Viswanathan, Gayathri; Ramaswamy, Venkataraman; Koshy, Konnath Chacko; Baby, Sabulal

    2018-02-15

    Phytochemistry of fruits and leaves of the unique bamboo Melocanna baccifera resulted in the isolation of 27 secondary metabolites, including 4-Oxabicyclo[3.2.2]nona-1(7),5,8-triene and Verbacine. Biological activity studies of Verbacine revealed it as an inhibitor of acetylcholinesterase and as cytotoxic against C6 cancer cells.

  10. Uniqueness in inverse elastic scattering with finitely many incident waves

    International Nuclear Information System (INIS)

    Elschner, Johannes; Yamamoto, Masahiro

    2009-01-01

    We consider the third and fourth exterior boundary value problems of linear isotropic elasticity and present uniqueness results for the corresponding inverse scattering problems with polyhedral-type obstacles and a finite number of incident plane elastic waves. Our approach is based on a reflection principle for the Navier equation. (orig.)

  11. Unique case of esophageal rupture after a fall from height

    NARCIS (Netherlands)

    van Heijl, Mark; Saltzherr, Teun P.; van Berge Henegouwen, Mark I.; Goslings, J. Carel

    2009-01-01

    ABSTRACT: BACKGROUND: Traumatic ruptures of the esophagus are relatively rare. This condition is associated with high morbidity and mortality. Most traumatic ruptures occur after motor vehicle accidents. Case Presentation: We describe a unique case of a 23 year old woman that presented at our trauma

  12. DECISIONS ET COMPETITIVITE SUR LE MARCHE UNIQUE EUROPEEN

    Directory of Open Access Journals (Sweden)

    Sirghi Nicoleta

    2008-05-01

    Full Text Available L’un des traits importants du marché unique européen, a comme source le męme énoncé du principal objectif de l’intégration européenne ainsi que: l’harmonisation des niveaux du développement des Etats Membres et l’augmentation du niveau de vie dans l’ensemble de la communauté. Pour le marché unique européen, cet aspect se traduit par une permanente et soutenue augmentation de la demande. Cet ouvrage présente au début une analyse des éléments spécifiques du marché européen. Ensuite on identifie les opportunités et les risques au niveau macroéconomique adjointes aux perspectives du marché unique européen. Comme fondement on présente des stratégies du développement réalisables au niveau microéconomique que puissent assurer l’augmentation du niveau sur la compétitivité des sociétés sur le marché unique européen.

  13. Is Self-Assessment in Religious Education Unique?

    Science.gov (United States)

    Brooks, Val; Fancourt, Nigel

    2012-01-01

    This paper addresses the question: is self-assessment in religious education unique? It first presents an overview of some challenges for assessment from subject differences, and then reviews the generic literature on self-assessment. It builds on earlier empirical research on self-assessment in religious education, carried out in an English state…

  14. Three Unique Implementations of Processes for PyCSP

    DEFF Research Database (Denmark)

    Friborg, Rune Møllegaard; Bjørndalen, John Markus; Vinter, Brian

    2009-01-01

    In this work we motivate and describe three unique implementations of processes for PyCSP: process, thread and greenlet based. The overall purpose is to demonstrate the feasibility of Communicating Sequential Processes as a framework for different application types and target platforms. The result...

  15. Zeros and uniqueness of Q-difference polynomials of meromorphic ...

    Indian Academy of Sciences (India)

    Meromorphic functions; Nevanlinna theory; logarithmic order; uniqueness problem; difference-differential polynomial. Abstract. In this paper, we investigate the value distribution of -difference polynomials of meromorphic function of finite logarithmic order, and study the zero distribution of difference-differential polynomials ...

  16. Why Is Family Firms' Internationalization Unique? : A Meta-Analysis

    NARCIS (Netherlands)

    Arregle, Jean-Luc; Duran, Patricio; Hitt, Michael A.; van Essen, M.

    Despite its importance, there is no clear understanding of the uniqueness of family firms' internationalization. This article sheds new light on this issue with a meta-analysis of 76 studies covering 41 countries. We show that the considerable study and cross-country differences in the relationship

  17. Meeting Each Student's Unique Potential: One Approach to Education.

    Science.gov (United States)

    Gauld, Joseph W.

    1996-01-01

    By championing extrinsic motivation, the achievement-reward system short-circuits individuals' innate inner power. Achievement-oriented adults rely on their knowledge, skills, and abilities, not their deeper potential. Hyde School, in Bath, Maine, solves this problem by committing the entire school community to development of unique potential via…

  18. Determining hydraulic parameters of a karst aquifer using unique ...

    African Journals Online (AJOL)

    Although karst aquifers constitute some of the most important water resources worldwide, generally accepted methods for reliably characterising their hydraulic properties are still elusive. This paper aims at contributing to the discussion by a first-ever attempt to utilise various sets of unique historical data derived from ...

  19. Uniqueness and zeros of q-shift difference polynomials

    Indian Academy of Sciences (India)

    In this paper, we consider the zero distributions of -shift difference polynomials of meromorphic functions with zero order, and obtain two theorems that extend the classical Hayman results on the zeros of differential polynomials to -shift difference polynomials. We also investigate the uniqueness problem of -shift ...

  20. Crossover Can Be Constructive When Computing Unique Input Output Sequences

    DEFF Research Database (Denmark)

    Lehre, Per Kristian; Yao, Xin

    2010-01-01

    Unique input output (UIO) sequences have important applications in conformance testing of finite state machines (FSMs). Previous experimental and theoretical research has shown that evolutionary algorithms (EAs) can compute UIOs efficiently on many FSM instance classes, but fail on others. However...

  1. review article how unique is south african military integration?

    African Journals Online (AJOL)

    Roy Licklider

    Rutgers University. The study of civil war ... South Africa has a strong case to be the poster child of military integration after civil violence.6 In a .... One aspect of the South African response to this problem was unique: a. Defence White Paper ...

  2. Uniqueness of inverse scattering problem in local quantum physics

    Energy Technology Data Exchange (ETDEWEB)

    Schroer, Bert [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mail: schroer@cbpf.br

    2001-06-01

    It is shown that the a Bisognano-Wichmann-Unruh inspired formulation of local quantum physics which starts from wedge-localized algebras, leads to a uniqueness proof for the scattering problem. The important mathematical tool is the thermal KMS aspect of localization and its strengthening by the requirement of crossing symmetry for generalized formfactors. (author)

  3. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Directory of Open Access Journals (Sweden)

    Ralph W Pridmore

    Full Text Available This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0 in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones. Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  4. Cone photoreceptor sensitivities and unique hue chromatic responses: correlation and causation imply the physiological basis of unique hues.

    Science.gov (United States)

    Pridmore, Ralph W

    2013-01-01

    This paper relates major functions at the start and end of the color vision process. The process starts with three cone photoreceptors transducing light into electrical responses. Cone sensitivities were once expected to be Red Green Blue color matching functions (to mix colors) but microspectrometry proved otherwise: they instead peak in yellowish, greenish, and blueish hues. These physiological functions are an enigma, unmatched with any set of psychophysical (behavioral) functions. The end-result of the visual process is color sensation, whose essential percepts are unique (or pure) hues red, yellow, green, blue. Unique hues cannot be described by other hues, but can describe all other hues, e.g., that hue is reddish-blue. They are carried by four opponent chromatic response curves but the literature does not specify whether each curve represents a range of hues or only one hue (a unique) over its wavelength range. Here the latter is demonstrated, confirming that opponent chromatic responses define, and may be termed, unique hue chromatic responses. These psychophysical functions also are an enigma, unmatched with any physiological functions or basis. Here both enigmas are solved by demonstrating the three cone sensitivity curves and the three spectral chromatic response curves are almost identical sets (Pearson correlation coefficients r from 0.95-1.0) in peak wavelengths, curve shapes, math functions, and curve crossover wavelengths, though previously unrecognized due to presentation of curves in different formats, e.g., log, linear. (Red chromatic response curve is largely nonspectral and thus derives from two cones.) Close correlation combined with deterministic causation implies cones are the physiological basis of unique hues. This match of three physiological and three psychophysical functions is unique in color vision.

  5. EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

    Science.gov (United States)

    Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

    2014-01-01

    For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

  6. Unique rheological behavior of chitosan-modified nanoclay at highly hydrated state.

    Science.gov (United States)

    Liang, Songmiao; Liu, Linshu; Huang, Qingrong; Yam, Kit L

    2009-04-30

    This work attempts to explore the dynamic and steady-state rheological properties of chitosan modified clay (CMCs) at highly hydrated state. CMCs with different initial chitosan/clay weight ratios (s) were prepared from pre-exfoliated clay via electrostatic adsorption process. Thermogravimetric analysis and optical microscopy were used to determine the adsorbed content of chitosan (m) in CMCs and the microstructure of CMCs at highly hydrated state, respectively. Dynamic rheological results indicate that both stress-strain behavior and moduli of CMCs exhibit strong dependence on m. Shear-thinning behavior for all of CMCs is observed and further confirmed by steady-state shear test. Interestingly, two unique transitions, denoted as a small peak region of the shear viscosity for CMCs with m > 2.1% and a sharp drop region of the shear viscosity for CMCs with m unique transitions. Thixotropic effect was observed in CMCs and showed strong dependence on m and the preshearing history. Failure to Cox-Merz rule of the rheological behavior of CMCs suggests that some preferential orientation of the initial quiescent random arrangement of CMCs particles or their tactoids occurs under the applied shearing.

  7. Electrophoretic variants of blood proteins in japanese, 5

    International Nuclear Information System (INIS)

    Fujita, Mikio; Satoh, Chiyoko; Asakawa, Jun-ichi; Nagahata, Yuko; Tanaka, Yoshiko; Hazama, Ryuji; Goriki, Kazuaki.

    1985-08-01

    The plasma ceruloplasmin (CP) of 22,367 children of atomic bomb survivors in Hiroshima and Nagasaki was examined for variants by electrophoresis. The sample was composed of 14,964 unrelated children and 7,403 siblings of the unrelated persons. A total of seven types of electrophoretic variants were detected; four migrating anodally and three cathodally to the normal B band. We have reported two of these variants, CP A sub(NG1) and CP C sub(NG1), previously but the other five, CP A sub(NG2), CP A sub(HR1), CP A sub(HR2), CP C sub(HR1), and CP C sub(HR2), are newly identified. The allelic frequency of CP*CNG1 was 0.00916, so that the variant is considered to be a polymorphic allele. Homozygosity for the CP*CNG1 allele was detected in five individuals. This is the first report of a homozygous phenotype for a CP variant in a Japanese population. Family study of the new five variants all demonstrated patterns of codominant inheritance. (author)

  8. [Hemoglobin variants in Colombian patients referred to discard hemoglobinopathies].

    Science.gov (United States)

    Romero-Sánchez, Consuelo; Gómez Gutiérrez, Alberto; Duarte, Yurani; Amazo, Constanza; Manosalva, Clara; Chila M, Lorena; Casas-Gómez, María Consuelo; Briceño Balcázar, Ignacio

    2015-10-01

    Oxygen transport is altered in hemoglobinopathies. To study the distribution of hemoglobinopathies in Andean subjects without African ancestry. We analyzed blood samples of 1,407 subjects aged 18 to 59 years (58% females), living in the central Andean region of Colombia, referred to discard hemoglobinopathies. The frequency and type of hemoglobinopathy was established by capillary and agarose gel electrophoresis. The frequency of hemoglobinopathies was 34.5% and higher among females. The structural variants found were: AS-heterozygous hemoglobin (8.1%), homozygous SS (3.7%), heterozygous SC (2.2%), AC heterozygotes (0.5%) and heterozygous AE (0.3%). Quantitative variants found were Hb A-Beta thalassemia (13.91%) and Hb H (0.06%), Beta-thalassemia heterozygotes C (0.88%), S-Beta thalassemia heterozygotes (6.07%) and compound heterozygous SC/Beta thalassemia (0.25%), with a persistence of fetal hemoglobin 0. Composite thalassemia was also found in 31%. All techniques showed good correlation and capillary electrophoresis demonstrated a greater detection of hemoglobin variants. The frequency of hemoglobin variants in the analyzed population was high, which is an important public health indicator. The most common hemoglobin variant was HbA/Increased structural Hb A2 and the mos frequent structural hemoglobinopathy was sickle cell trait. Capillary electrophoresis can discern any Hb variants present in the population.

  9. Uniqueness of the Fock quantization of the Gowdy T3 model

    International Nuclear Information System (INIS)

    Cortez, Jeronimo; Marugan, Guillermo A. Mena; Velhinho, Jose M.

    2007-01-01

    After its reduction by a gauge-fixing procedure, the family of linearly polarized Gowdy T 3 cosmologies admits a scalar field description whose evolution is governed by a Klein-Gordon type equation in a flat background in 1+1 dimensions with the spatial topology of S 1 , though in the presence of a time-dependent potential. The model is still subject to a homogeneous constraint, which generates S 1 -translations. Recently, a Fock quantization of this scalar field was introduced and shown to be unique under the requirements of unitarity of the dynamics and invariance under the gauge group of S 1 -translations. In this work, we extend and complete this uniqueness result by considering other possible scalar field descriptions, resulting from reasonable field reparametrizations of the induced metric of the reduced model. In the reduced phase space, these alternate descriptions can be obtained by means of a time-dependent scaling of the field, the inverse scaling of its canonical momentum, and the possible addition of a time-dependent, linear contribution of the field to this momentum. Demanding again unitarity of the field dynamics and invariance under the gauge group, we prove that the alternate canonical pairs of fieldlike variables admit a Fock representation if and only if the scaling of the field is constant in time. In this case, there exists essentially a unique Fock representation, provided by the quantization constructed by Corichi, Cortez, and Mena Marugan. In particular, our analysis shows that the scalar field description proposed by Pierri does not admit a Fock quantization with the above unitarity and invariance properties

  10. Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind.

    Science.gov (United States)

    Chan, S Y; Ho, L; Ong, C K; Chow, V; Drescher, B; Dürst, M; ter Meulen, J; Villa, L; Luande, J; Mgaya, H N

    1992-04-01

    We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The

  11. Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications

    Directory of Open Access Journals (Sweden)

    Lam Hon-Ming

    2009-07-01

    Full Text Available Abstract Background Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. Results In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1 and T31Y41H87L90 (HISTONE variant H3.2, respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2 were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. Conclusion This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone

  12. Psychosis in behavioral variant frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Gossink FT

    2017-04-01

    Full Text Available Flora T Gossink,1,2 Everard GB Vijverberg,2,3 Welmoed Krudop,2 Philip Scheltens,2 Max L Stek,1 Yolande AL Pijnenburg,1,2 Annemiek Dols1,2 1Department of Old Age Psychiatry, GGZinGeest, 2Alzheimer Center & Department of Neurology, VU University Medical Center, Amsterdam, 3Department of Neurology, HagaZiekenhuis, The Hague, the Netherlands Background: Dementia is generally characterized by cognitive impairment that can be accompanied by psychotic symptoms; for example, visual hallucinations are a core feature of dementia with Lewy bodies, and delusions are often seen in Alzheimer’s disease. However, for behavioral variant of frontotemporal dementia (bvFTD, studies on the broad spectrum of psychotic symptoms are still lacking. The aim of this study was to systematically and prospectively subtype the wide spectrum of psychotic symptoms in probable and definite bvFTD.Methods: In this study, a commonly used and validated clinical scale that quantifies the broad spectrum of psychotic symptoms (Positive and Negative Symptom Scale was used in patients with probable and definite bvFTD (n=22 and with a primary psychiatric disorder (n=35 in a late-onset frontal lobe cohort. Median symptom duration was 2.8 years, and the patients were prospectively followed for 2 years.Results: In total, 22.7% of bvFTD patients suffered from delusions, hallucinatory behavior, and suspiciousness, although the majority of the patients exhibited negative psychotic symptoms such as social and emotional withdrawal and blunted affect (95.5% and formal thought disorders (81.8%. “Difficulty in abstract thinking” and “stereotypical thinking” (formal thought disorders differentiated bvFTD from psychiatric disorders. The combined predictors difficulty in abstract thinking, stereotypical thinking, “anxiety”, “guilt feelings,” and “tension” explained 75.4% of variance in the diagnosis of bvFTD versus psychiatric diagnoses (P<0.001.Conclusion: Delusions

  13. Increased expression of MERTK is associated with a unique form of canine retinopathy.

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    Saija J Ahonen

    Full Text Available Progressive retinal degenerations are among the most common causes of blindness both in human and in dogs. Canine progressive retinal atrophy (PRA resembles human retinitis pigmentosa (RP and is typically characterized by a progressive loss of rod photoreceptors followed by a loss of cone function. The disease gradually progress from the loss of night and day vision to a complete blindness. We have recently described a unique form of retinopathy characterized by the multifocal gray/brown discoloration and thinning of the retina in the Swedish Vallhund (SV breed. We aimed to identify the genetic cause by performing a genome wide association analysis in a cohort of 18 affected and 10 healthy control dogs using Illumina's canine 22k SNP array. We mapped the disease to canine chromosome 17 (p = 7.7×10(-5 and found a 6.1 Mb shared homozygous region in the affected dogs. A combined analysis of the GWAS and replication data with additional 60 dogs confirmed the association (p = 4.3×10(-8, OR = 11.2 for homozygosity. A targeted resequencing of the entire associated region in four cases and four controls with opposite risk haplotypes identified several variants in the coding region of functional candidate genes, such as a known retinopathy gene, MERTK. However, none of the identified coding variants followed a compelling case- or breed-specific segregation pattern. The expression analyses of four candidate genes in the region, MERTK, NPHP1, ANAPC1 and KRCC1, revealed specific upregulation of MERTK in the retina of the affected dogs. Collectively, these results indicate that the retinopathy is associated with overexpression of MERTK, however further investigation is needed to discover the regulatory mutation for the better understanding of the disease pathogenesis. Our study establishes a novel gain-of-function model for the MERTK biology and provides a therapy model for retinopathy MERTK inhibitors. Meanwhile, a marker-based genetic

  14. The Influenza A(H1N1)v Pandemic : An Exploratory System Dynamics Approach

    NARCIS (Netherlands)

    Pruyt, E.; Hamarat, C.

    2010-01-01

    This paper presents a small exploratory System Dynamics model related to the dynamics of the 2009 flu pandemic, also known as the Mexican flu, swine flu, or A(H1N1)v. The model was developed in May 2009 in order to quickly foster understanding about the possible dynamics of this new flu variant and

  15. Quantum dynamical semigroups and approach to equilibrium

    International Nuclear Information System (INIS)

    Frigerio, A.

    1977-01-01

    For a quantum dynamical semigroup possessing a faithful normal stationary state, some conditions are discussed, which ensure the uniqueness of the equilibrium state and/or the approach to equilibrium for arbitrary initial condition. (Auth.)

  16. Amino acid changes in disease-associated variants differ radically from variants observed in the 1000 genomes project dataset.

    Directory of Open Access Journals (Sweden)

    Tjaart A P de Beer

    Full Text Available The 1000 Genomes Project data provides a natural background dataset for amino acid germline mutations in humans. Since the direction of mutation is known, the amino acid exchange matrix generated from the observed nucleotide variants is asymmetric and the mutabilities of the different amino acids are very different. These differences predominantly reflect preferences for nucleotide mutations in the DNA (especially the high mutation rate of the CpG dinucleotide, which makes arginine mutability very much higher than other amino acids rather than selection imposed by protein structure constraints, although there is evidence for the latter as well. The variants occur predominantly on the surface of proteins (82%, with a slight preference for sites which are more exposed and less well conserved than random. Mutations to functional residues occur about half as often as expected by chance. The disease-associated amino acid variant distributions in OMIM are radically different from those expected on the basis of the 1000 Genomes dataset. The disease-associated variants preferentially occur in more conserved sites, compared to 1000 Genomes mutations. Many of the amino acid exchange profiles appear to exhibit an anti-correlation, with common exchanges in one dataset being rare in the other. Disease-associated variants exhibit more extreme differences in amino acid size and hydrophobicity. More modelling of the mutational processes at the nucleotide level is needed, but these observations should contribute to an improved prediction of the effects of specific variants in humans.

  17. Cellulase variants with improved expression, activity and stability, and use thereof

    Science.gov (United States)

    Aehle, Wolfgang; Bott, Richard R; Bower, Benjamin; Caspi, Jonathan; Estell, David A; Goedegebuur, Frits; Hommes, Ronaldus W.J.; Kaper, Thijs; Kelemen, Bradley; Kralj, Slavko; Van Lieshout, Johan; Nikolaev, Igor; Van Stigt Thans, Sander; Wallace, Louise; Vogtentanz, Gudrun; Sandgren, Mats

    2014-03-25

    The present disclosure relates to cellulase variants. In particular the present disclosure relates to cellulase variants having improved expression, activity and/or stability. Also described are nucleic acids encoding the cellulase variants, compositions comprising the cellulase variants, and methods of use thereof.

  18. Cellulase variants with improved expression, activity and stability, and use thereof

    Energy Technology Data Exchange (ETDEWEB)

    Aehle, Wolfgang; Bott, Richard R.; Bower, Benjamin S.; Caspi, Jonathan; Goedegebuur, Frits; Hommes, Ronaldus Wilhelmus Joannes; Kaper, Thijs; Kelemen, Bradley R.; Kralj, Slavko; Van Lieshout, Johannes Franciscus Thomas; Nikolaev, Igor; Wallace, Louise; Van Stigt Thans, Sander; Vogtentanz, Gudrun; Sandgren, Mats

    2016-12-20

    The present disclosure relates to cellulase variants. In particular the present disclosure relates to cellulase variants having improved expression, activity and/or stability. Also described are nucleic acids encoding the cellulase variants, compositions comprising the cellulase variants, and methods of use thereof.

  19. Quasistatic Dynamics with Intermittency

    International Nuclear Information System (INIS)

    Leppänen, Juho; Stenlund, Mikko

    2016-01-01

    We study an intermittent quasistatic dynamical system composed of nonuniformly hyperbolic Pomeau–Manneville maps with time-dependent parameters. We prove an ergodic theorem which shows almost sure convergence of time averages in a certain parameter range, and identify the unique physical family of measures. The theorem also shows convergence in probability in a larger parameter range. In the process, we establish other results that will be useful for further analysis of the statistical properties of the model.

  20. Quasistatic Dynamics with Intermittency

    Energy Technology Data Exchange (ETDEWEB)

    Leppänen, Juho; Stenlund, Mikko, E-mail: mikko.stenlund@helsinki.fi [University of Helsinki, Department of Mathematics and Statistics (Finland)

    2016-06-15

    We study an intermittent quasistatic dynamical system composed of nonuniformly hyperbolic Pomeau–Manneville maps with time-dependent parameters. We prove an ergodic theorem which shows almost sure convergence of time averages in a certain parameter range, and identify the unique physical family of measures. The theorem also shows convergence in probability in a larger parameter range. In the process, we establish other results that will be useful for further analysis of the statistical properties of the model.

  1. Discovery of novel variants in genotyping arrays improves genotype retention and reduces ascertainment bias

    Directory of Open Access Journals (Sweden)

    Didion John P

    2012-01-01

    Full Text Available Abstract Background High-density genotyping arrays that measure hybridization of genomic DNA fragments to allele-specific oligonucleotide probes are widely used to genotype single nucleotide polymorphisms (SNPs in genetic studies, including human genome-wide association studies. Hybridization intensities are converted to genotype calls by clustering algorithms that assign each sample to a genotype class at each SNP. Data for SNP probes that do not conform to the expected pattern of clustering are often discarded, contributing to ascertainment bias and resulting in lost information - as much as 50% in a recent genome-wide association study in dogs. Results We identified atypical patterns of hybridization intensities that were highly reproducible and demonstrated that these patterns represent genetic variants that were not accounted for in the design of the array platform. We characterized variable intensity oligonucleotide (VINO probes that display such patterns and are found in all hybridization-based genotyping platforms, including those developed for human, dog, cattle, and mouse. When recognized and properly interpreted, VINOs recovered a substantial fraction of discarded probes and counteracted SNP ascertainment bias. We developed software (MouseDivGeno that identifies VINOs and improves the accuracy of genotype calling. MouseDivGeno produced highly concordant genotype calls when compared with other methods but it uniquely identified more than 786000 VINOs in 351 mouse samples. We used whole-genome sequence from 14 mouse strains to confirm the presence of novel variants explaining 28000 VINOs in those strains. We also identified VINOs in human HapMap 3 samples, many of which were specific to an African population. Incorporating VINOs in phylogenetic analyses substantially improved the accuracy of a Mus species tree and local haplotype assignment in laboratory mouse strains. Conclusion The problems of ascertainment bias and missing

  2. Discovery of a mammalian splice variant of myostatin that stimulates myogenesis.

    Directory of Open Access Journals (Sweden)

    Ferenc Jeanplong

    Full Text Available Myostatin plays a fundamental role in regulating the size of skeletal muscles. To date, only a single myostatin gene and no splice variants have been identified in mammals. Here we describe the splicing of a cryptic intron that removes the coding sequence for the receptor binding moiety of sheep myostatin. The deduced polypeptide sequence of the myostatin splice variant (MSV contains a 256 amino acid N-terminal domain, which is common to myostatin, and a unique C-terminus of 65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated into protein, which is present in skeletal muscles. To determine the biological role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed that it proliferated faster than that of the control line in association with an increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant protein made for the novel C-terminus of MSV also stimulated myoblast proliferation and bound to myostatin with high affinity as determined by surface plasmon resonance assay. Therefore, we postulated that MSV functions as a binding protein and antagonist of myostatin. Consistent with our postulate, myostatin protein was co-immunoprecipitated from skeletal muscle extracts with an MSV-specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin-induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the canonical myostatin pathway. Furthermore, MSV over-expression increased the abundance of MyoD, Myogenin and MRF4 proteins (P<0.05, which indicates that MSV stimulates myogenesis through the induction of myogenic regulatory factors. To help elucidate a possible role in vivo, we observed that MSV protein was more abundant during early post-natal muscle development, while myostatin remained unchanged, which suggests that MSV may promote the growth of skeletal muscles. We conclude that MSV represents a unique example of intra-genic regulation in which a

  3. Target Choice and Unique Synergies in Global Mobile Telephony

    DEFF Research Database (Denmark)

    Claussen, Jörg; Köhler, Rebecca; Kretschmer, Tobias

    2018-01-01

    their foresight to select specific targets: First, they lower integration costs by selecting geographically close targets. This effect is stronger when buyer and target are in the same country, but only if the market is not so concentrated that it provokes regulatory interventions. Second, they select targets......The success of acquisitions rests on detecting and realizing unique synergies between buyer and target through their dyadic relationships. We study the role of unique dyad-specific synergies in the selection of takeover targets in the global mobile telecommunications industry. Firms use...... that can be acquired at a modest bid premium because they have asymmetric bargaining power. Finally, they select targets which can generate significant synergies due to technological synergies. Our work expands the existing target selection literature by studying dyad-specific factors within a single...

  4. Unique Migraine Subtypes, Rare Headache Disorders, and Other Disturbances.

    Science.gov (United States)

    Goadsby, Peter J

    2015-08-01

    The medical aphorism that common things happen commonly makes unique (and less common) migraine subtypes especially appropriate to review for the general neurologist. This article also identifies some rare headache disorders and other disturbances, and offers strategies to manage them. This article discusses migraine with brainstem aura, which is troublesome clinically and has had a change in terminology in the International Classification of Headache Disorders, Third Edition, beta version (ICHD-3 beta), and hemiplegic migraine, which is also troublesome in practice. The rare headache disorder hypnic headache and the exploding head syndrome are also discussed. When hypnic headache is recognized, it is eminently treatable, while exploding head syndrome is a benign condition with no reported consequences. Unique migraine subtypes, rare headache disorders, and other disturbances present to neurologists. When recognized, they can often be managed very well, which offers significant benefits to patients and practice satisfaction to neurologists.

  5. Solitary intraosseous neurofibroma: Report of a unique case

    Directory of Open Access Journals (Sweden)

    Sagar Satish Jangam

    2014-01-01

    Full Text Available Neural tumors located centrally in jaw bones are relatively rare compared with soft tissue neurofibromas. Less than 50 cases have been reported in the literature with a predilection for mandible. This article aims to elucidate a unique case of intraosseous neurofibroma of mandible in a 62-year-old edentulous female patient associated with facial asymmetry due to the swelling extending from the right body of mandible to left body of mandible. The uniqueness of this case is related to the age and extensiveness of this lesion. A review of clinical, radiographic, histological, and immunohistochemical features, and the surgical management pertaining to this case are discussed along with a review of the literature.

  6. Unique Approach to Dental Management of Children with Hearing Impairment.

    Science.gov (United States)

    Renahan, Navanith; Varma, R Balagopal; Kumaran, Parvathy; Xavier, Arun M

    2017-01-01

    The number of deaf children has dramatically increased in the past few decades. These children present to the pediatric dentist a unique set of challenges mostly pertaining to the establishment of communication with them. There have been very few attempts in the past to break down these challenges and formulate a strategy on how to manage them effectively. This is a case report of a child who was successfully managed using two different modes of communication. Finally, the advantages and disadvantages are mentioned, and a common strategy incorporating the positives of both the methods has been devised. Renahan N, Varma RB, Kumaran P, Xavier AM. Unique Approach to Dental Management of Children with Hearing Impairment. Int J Clin Pediatr Dent 2017;10(1):107-110.

  7. Concentration and mindfulness meditations: unique forms of consciousness?

    Science.gov (United States)

    Dunn, B R; Hartigan, J A; Mikulas, W L

    1999-09-01

    Electroencephalographic (EEG) recordings from 19 scalp recording sites were used to differentiate among two posited unique forms of mediation, concentration and mindfulness, and a normal relaxation control condition. Analyzes of all traditional frequency bandwidth data (i.e., delta 1-3 Hz; theta, 4-7 Hz; alpha, 8-12 Hz; beta 1, 13-25 Hz; beta 2, 26-32 Hz) showed strong mean amplitude frequency differences between the two meditation conditions and relaxation over numerous cortical sites. Furthermore, significant differences were obtained between concentration and mindfulness states at all bandwidths. Taken together, our results suggest that concentration and mindfulness "meditations" may be unique forms of consciousness and are not merely degrees of a state of relaxation.

  8. On the Existence and Uniqueness of the Scientific Method.

    Science.gov (United States)

    Wagensberg, Jorge

    2014-01-01

    The ultimate utility of science is widely agreed upon: the comprehension of reality. But there is much controversy about what scientific understanding actually means, and how we should proceed in order to gain new scientific understanding. Is there a method for acquiring new scientific knowledge? Is this method unique and universal? There has been no shortage of proposals, but neither has there been a shortage of skeptics about these proposals. This article proffers for discussion a potential scientific method that aspires to be unique and universal and is rooted in the recent and ancient history of scientific thinking. Curiously, conclusions can be inferred from this scientific method that also concern education and the transmission of science to others.

  9. Being and feeling unique: statistical deviance and psychological marginality.

    Science.gov (United States)

    Frable, D E

    1993-03-01

    Two studies tested the hypothesis that people with culturally stigmatized and concealable conditions (e.g., gays, epileptics, juvenile delinquents, and incest victims) would be more likely to feel unique than people with culturally valued or conspicuous conditions (e.g., the physically attractive, the intellectually gifted, the obese, and the facially scarred). In Study 1, culturally stigmatized individuals with concealable conditions were least likely to perceive consensus between their personal preferences and those of others. In Study 2, they were most likely to describe themselves as unique and to make these self-relevant decisions quickly. Marginality is a psychological reality, not just a statistical one, for those with stigmatized and concealable "master status" conditions.

  10. Non-unique factorizations algebraic, combinatorial and analytic theory

    CERN Document Server

    Geroldinger, Alfred

    2006-01-01

    From its origins in algebraic number theory, the theory of non-unique factorizations has emerged as an independent branch of algebra and number theory. Focused efforts over the past few decades have wrought a great number and variety of results. However, these remain dispersed throughout the vast literature. For the first time, Non-Unique Factorizations: Algebraic, Combinatorial, and Analytic Theory offers a look at the present state of the theory in a single, unified resource.Taking a broad look at the algebraic, combinatorial, and analytic fundamentals, this book derives factorization results and applies them in concrete arithmetical situations using appropriate transfer principles. It begins with a basic introduction that can be understood with knowledge of standard basic algebra. The authors then move to the algebraic theory of monoids, arithmetic theory of monoids, the structure of sets of lengths, additive group theory, arithmetical invariants, and the arithmetic of Krull monoids. They also provide a s...

  11. HABP2 G534E Variant in Papillary Thyroid Carcinoma.

    Directory of Open Access Journals (Sweden)

    Jerneja Tomsic

    Full Text Available The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC that accounts for 80-90% of all thyroid malignancies. Only 3-10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536 was genotyped in blood DNA from 179 PTC families (one affected individual per family, 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.

  12. Functionally significant, rare transcription factor variants in tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Ana Töpf

    Full Text Available Rare variants in certain transcription factors involved in cardiac development cause Mendelian forms of congenital heart disease. The purpose of this study was to systematically assess the frequency of rare transcription factor variants in sporadic patients with the cardiac outflow tract malformation tetralogy of Fallot (TOF.We sequenced the coding, 5'UTR, and 3'UTR regions of twelve transcription factor genes implicated in cardiac outflow tract development (NKX2.5, GATA4, ISL1, TBX20, MEF2C, BOP/SMYD1, HAND2, FOXC1, FOXC2, FOXH, FOXA2 and TBX1 in 93 non-syndromic, non-Mendelian TOF cases. We also analysed Illumina Human 660W-Quad SNP Array data for copy number variants in these genes; none were detected. Four of the rare variants detected have previously been shown to affect transactivation in in vitro reporter assays: FOXC1 p.P297S, FOXC2 p.Q444R, FOXH1 p.S113T and TBX1 p.P43_G61del PPPPRYDPCAAAAPGAPGP. Two further rare variants, HAND2 p.A25_A26insAA and FOXC1 p.G378_G380delGGG, A488_491delAAAA, affected transactivation in in vitro reporter assays. Each of these six functionally significant variants was present in a single patient in the heterozygous state; each of the four for which parental samples were available were maternally inherited. Thus in the 93 TOF cases we identified six functionally significant mutations in the secondary heart field transcriptional network.This study indicates that rare genetic variants in the secondary heart field transcriptional network with functional effects on protein function occur in 3-13% of patients with TOF. This is the first report of a functionally significant HAND2 mutation in a patient with congenital heart disease.

  13. HFE gene variants affect iron in the brain.

    Science.gov (United States)

    Nandar, Wint; Connor, James R

    2011-04-01

    Iron accumulation in the brain and increased oxidative stress are consistent observations in many neurodegenerative diseases. Thus, we have begun examination into gene mutations or allelic variants that could be associated with loss of iron homeostasis. One of the mechanisms leading to iron overload is a mutation in the HFE gene, which is involved in iron metabolism. The 2 most common HFE gene variants are C282Y (1.9%) and H63D (8.9%). The C282Y HFE variant is more commonly associated with hereditary hemochromatosis, which is an autosomal recessive disorder, characterized by iron overload in a number of systemic organs. The H63D HFE variant appears less frequently associated with hemochromatosis, but its role in the neurodegenerative diseases has received more attention. At the cellular level, the HFE mutant protein resulting from the H63D HFE gene variant is associated with iron dyshomeostasis, increased oxidative stress, glutamate release, tau phosphorylation, and alteration in inflammatory response, each of which is under investigation as a contributing factor to neurodegenerative diseases. Therefore, the HFE gene variants are proposed to be genetic modifiers or a risk factor for neurodegenerative diseases by establishing an enabling milieu for pathogenic agents. This review will discuss the current knowledge of the association of the HFE gene variants with neurodegenerative diseases: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and ischemic stroke. Importantly, the data herein also begin to dispel the long-held view that the brain is protected from iron accumulation associated with the HFE mutations.

  14. Biochemical characterization of the GM2 gangliosidosis B1 variant

    Directory of Open Access Journals (Sweden)

    Tutor J.C.

    2004-01-01

    Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

  15. Genomic constitution of an H-2:Tla variant leukemia.

    Science.gov (United States)

    Shen, F W; Chaganti, R S; Doucette, L A; Litman, G W; Steinmetz, M; Hood, L; Boyse, E A

    1984-10-01

    A TL+ leukemia of a (B6 X A)F1 hybrid mouse (H-2b/H-2a) was previously subjected to immunoselection against H-2a by passage in (B6 X A.SW)F1 mice (H-2b/H-2s). A variant leukemia line was obtained that serologically lacked not only the H-2a phenotype but also the TL phenotype determined by the linked cis Tlaa allele of strain A. The H-2b phenotype and the TL phenotype of the Tlab allele of the B6 strain, which is expressed only by leukemia cells, were retained by the variant. Southern blotting with an H-2 cDNA probe that identifies restriction fragment polymorphisms distinguishing alleles of the H-2 and Tla regions of the B6 and A strains indicates that both the H-2a and Tlaa alleles are missing from the genome of this H-2a:Tlaa negative variant. Since the variant has two apparently unaltered chromosomes 17, where the H-2:Tla complex is situated, and since the intensity of bands in Southern blotting is suggestive of H-2b homozygosity, it is considered that loss of the H-2a:Tlaa haplotype by the variant was accompanied by duplication of the H-2b:Tlab haplotype. The implied change from heterozygosity to homozygosity that the variant has undergone with respect to H-2:Tla was not paralleled by a similar change at the three other loci tested, since the variant retained heterozygosity for Pep-3 (chromosome 1), Gpi-1 (chromosome 7), and Es-1 (chromosome 8).

  16. Diverse Functional Properties of Wilson Disease ATP7B Variants

    Science.gov (United States)

    Huster, Dominik; Kühne, Angelika; Bhattacharjee, Ashima; Raines, Lily; Jantsch, Vanessa; Noe, Johannes; Schirrmeister, Wiebke; Sommerer, Ines; Sabri, Osama; Berr, Frieder; Mössner, Joachim; Stieger, Bruno; Caca, Karel; Lutsenko, Svetlana

    2012-01-01

    BACKGROUND & AIMS Wilson disease is a severe disorder of copper metabolism caused by mutations in ATP7B, which encodes a copper-transporting adenosine triphosphatase. The disease presents with a variable phenotype that complicates the diagnostic process and treatment. Little is known about the mechanisms that contribute to the different phenotypes of the disease. METHODS We analyzed 28 variants of ATP7B from patients with Wilson disease that affected different functional domains; the gene products were expressed using the baculovirus expression system in Sf9 cells. Protein function was analyzed by measuring catalytic activity and copper (64Cu) transport into vesicles. We studied intracellular localization of variants of ATP7B that had measurable transport activities and were tagged with green fluorescent protein in mammalian cells using confocal laser scanning microscopy. RESULTS Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. In mammalian cells, transport-competent variants differed in stability and subcellular localization. CONCLUSIONS Variants in ATP7B associated with Wilson disease disrupt the protein’s transport activity, result in its mislocalization, and reduce its stability. Single assays are insufficient to accurately predict the effects of ATP7B variants the function of its product and development of Wilson disease. These findings will contribute to our understanding of genotype–phenotype correlation and mechanisms of disease pathogenesis. PMID:22240481

  17. Forward and backward dynamics in implicitly defined overlapping generations models

    NARCIS (Netherlands)

    Gardini, L.; Hommes, C.; Tramontana, F.; de Vilder, R.

    2009-01-01

    In dynamic economic models derived from optimization principles, the forward equilibrium dynamics may not be uniquely defined, while the backward dynamics is well defined. We derive properties of the global forward equilibrium paths based on properties of the backward dynamics. We propose the

  18. Uniqueness of rarefaction waves in multidimensional compressible Euler system

    Czech Academy of Sciences Publication Activity Database

    Feireisl, Eduard; Kreml, Ondřej

    2015-01-01

    Roč. 12, č. 3 (2015), s. 489-499 ISSN 0219-8916 R&D Projects: GA ČR GA13-00522S EU Projects: European Commission(XE) 320078 - MATHEF Institutional support: RVO:67985840 Keywords : compressible Euler system * uniqueness * rarefaction wave * Riemann problem Subject RIV: BA - General Mathematics Impact factor: 0.556, year: 2015 http://www.worldscientific.com/doi/abs/10.1142/S0219891615500149

  19. Common processes at unique volcanoes – a volcanological conundrum

    OpenAIRE

    Katharine eCashman; Juliet eBiggs

    2014-01-01

    An emerging challenge in modern volcanology is the apparent contradiction between the perception that every volcano is unique, and classification systems based on commonalities among volcano morphology and eruptive style. On the one hand, detailed studies of individual volcanoes show that a single volcano often exhibits similar patterns of behavior over multiple eruptive episodes; this observation has led to the idea that each volcano has its own distinctive pattern of behavior (or “personali...

  20. Social Capital and Institutions in Rural Kenya: Is Machakos Unique?

    OpenAIRE

    Nyangena, Wilfred; Sterner, Thomas

    2008-01-01

    In Eastern Africa, the experience of Machakos has been heavily debated between Malthusians and the more optimistic Boserupians. Machakos was the epitome of overpopulation and resource degradation in the 1950s, but has since thrived. The Boserupians view Machakos as an illustration of how population growth can solve rather than exacerbate the vicious cycle of poverty and resource degradation. The question arises whether Machakos is unique. This study investigates the role of social capital in ...