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Sample records for null allele strains

  1. Population estimators or progeny tests: what is the best method to assess null allele frequencies at SSR loci?

    NARCIS (Netherlands)

    Oddou-Muratorio, S.; Vendramin, G.G.; Buiteveld, J.; Fady, B.

    2009-01-01

    Nuclear SSRs are notorious for having relatively high frequencies of null alleles, i.e. alleles that fail to amplify and are thus recessive and undetected in heterozygotes. In this paper, we compare two kinds of approaches for estimating null allele frequencies at seven nuclear microsatellite

  2. Null alleles and sequence variations at primer binding sites of STR loci within multiplex typing systems.

    Science.gov (United States)

    Yao, Yining; Yang, Qinrui; Shao, Chengchen; Liu, Baonian; Zhou, Yuxiang; Xu, Hongmei; Zhou, Yueqin; Tang, Qiqun; Xie, Jianhui

    2018-01-01

    Rare variants are widely observed in human genome and sequence variations at primer binding sites might impair the process of PCR amplification resulting in dropouts of alleles, named as null alleles. In this study, 5 cases from routine paternity testing using PowerPlex ® 21 System for STR genotyping were considered to harbor null alleles at TH01, FGA, D5S818, D8S1179, and D16S539, respectively. The dropout of alleles was confirmed by using alternative commercial kits AGCU Expressmarker 22 PCR amplification kit and AmpFℓSTR ® . Identifiler ® Plus Kit, and sequencing results revealed a single base variation at the primer binding site of each STR locus. Results from the collection of previous reports show that null alleles at D5S818 were frequently observed in population detected by two PowerPlex ® typing systems and null alleles at D19S433 were mostly observed in Japanese population detected by two AmpFℓSTR™ typing systems. Furthermore, the most popular mutation type appeared the transition from C to T with G to A, which might have a potential relationship with DNA methylation. Altogether, these results can provide helpful information in forensic practice to the elimination of genotyping discrepancy and the development of primer sets. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

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    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  4. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G locus in subjects to recurrent miscarriage

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    Nazila Alizadeh

    2016-07-01

    Full Text Available Background: Human leukocyte antigen-G (HLA-G is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR. Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele.

  5. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

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    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-01-01

    Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

  6. Fibrillin levels in a severely affected Marfan syndrome patient with a null allele

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    Boxer, M.; Withers, A.P.; Al-Ghaban, Z. [Univ. of Wales, Cardiff (United Kingdom)]|[Ninewells Hospital and Medical School, Dundee (United Kingdom)] [and others

    1994-09-01

    Marfan syndrome is an autosomal dominantly inherited connective tissue disorder characterized by defects in the cardiovascular, skeletal and ocular systems. A patient was first examined in 1992 having survived an acute sortic dissection with subsequent composite repair and insertion of a prosthetic aortic valve. Clinical examination revealed arachnodactyly, narrow, high arched palate with dental crowding, an arm span exceeding her height by 10.5 cm, joint laxity and bilateral lens subluxation. Analysis of the family showed affected members in three generations and the fibrillin gene, FBN1, was shown to segregate with the disease when using polymorphic markers including an RsaI polymorphism in the 3{prime}-untranslated region of the gene. Analysis of patient mRNA for this RsaI polymorphism by RT-PCR (reverse transcriptase-PCR) amplification and restriction enzyme digestion of the PCR products showed that the copy of the gene segregating with the disease was not transcribed. No low level expression of this allele was observed despite RT-PCR amplification incorporating radioactively labelled dCTP, thus revealing a null allele phenotype. Western blotting analysis of fibrillin secreted by the patient`s dermal fibroblasts using fibrillin-specific antibodies showed only normal sized fibrillin protein. However, immunohistochemical studies of the patient`s tissue and fibroblasts showed markedly lowered levels in staining of microfibrillar structures compared with age-matched controls. This low level of expression of the protein affected in Marfan syndrome in a patient with such severe clinical manifestations is surprising since current understanding would suggest that this molecular phenotype should lead to a mild clinical disorder.

  7. Compound heterozygosity of the functionally null Cdh23(v-ngt) and hypomorphic Cdh23(ahl) alleles leads to early-onset progressive hearing loss in mice.

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    Miyasaka, Yuki; Suzuki, Sari; Ohshiba, Yasuhiro; Watanabe, Kei; Sagara, Yoshihiko; Yasuda, Shumpei P; Matsuoka, Kunie; Shitara, Hiroshi; Yonekawa, Hiromichi; Kominami, Ryo; Kikkawa, Yoshiaki

    2013-01-01

    The waltzer (v) mouse mutant harbors a mutation in Cadherin 23 (Cdh23) and is a model for Usher syndrome type 1D, which is characterized by congenital deafness, vestibular dysfunction, and prepubertal onset of progressive retinitis pigmentosa. In mice, functionally null Cdh23 mutations affect stereociliary morphogenesis and the polarity of both cochlear and vestibular hair cells. In contrast, the murine Cdh23(ahl) allele, which harbors a hypomorphic mutation, causes an increase in susceptibility to age-related hearing loss in many inbred strains. We produced congenic mice by crossing mice carrying the v niigata (Cdh23(v-ngt)) null allele with mice carrying the hypomorphic Cdh23(ahl) allele on the C57BL/6J background, and we then analyzed the animals' balance and hearing phenotypes. Although the Cdh23(v-ngt/ahl) compound heterozygous mice exhibited normal vestibular function, their hearing ability was abnormal: the mice exhibited higher thresholds of auditory brainstem response (ABR) and rapid age-dependent elevation of ABR thresholds compared with Cdh23(ahl/ahl) homozygous mice. We found that the stereocilia developed normally but were progressively disrupted in Cdh23(v-ngt/ahl) mice. In hair cells, CDH23 localizes to the tip links of stereocilia, which are thought to gate the mechanoelectrical transduction channels in hair cells. We hypothesize that the reduction of Cdh23 gene dosage in Cdh23(v-ngt/ahl) mice leads to the degeneration of stereocilia, which consequently reduces tip link tension. These findings indicate that CDH23 plays an important role in the maintenance of tip links during the aging process.

  8. Analysis of a lin-42/period Null Allele Implicates All Three Isoforms in Regulation of Caenorhabditis elegans Molting and Developmental Timing

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    Theresa L. B. Edelman

    2016-12-01

    Full Text Available The Caenorhabditis elegans heterochronic gene pathway regulates the relative timing of events during postembryonic development. lin-42, the worm homolog of the circadian clock gene, period, is a critical element of this pathway. lin-42 function has been defined by a set of hypomorphic alleles that cause precocious phenotypes, in which later developmental events, such as the terminal differentiation of hypodermal cells, occur too early. A subset of alleles also reveals a significant role for lin-42 in molting; larval stages are lengthened and ecdysis often fails in these mutant animals. lin-42 is a complex locus, encoding overlapping and nonoverlapping isoforms. Although existing alleles that affect subsets of isoforms have illuminated important and distinct roles for this gene in developmental timing, molting, and the decision to enter the alternative dauer state, it is essential to have a null allele to understand all of the roles of lin-42 and its individual isoforms. To remedy this problem and discover the null phenotype, we engineered an allele that deletes the entire lin-42 protein-coding region. lin-42 null mutants are homozygously viable, but have more severe phenotypes than observed in previously characterized hypomorphic alleles. We also provide additional evidence for this conclusion by using the null allele as a base for reintroducing different isoforms, showing that each isoform can provide heterochronic and molting pathway activities. Transcript levels of the nonoverlapping isoforms appear to be under coordinate temporal regulation, despite being driven by independent promoters. The lin-42 null allele will continue to be an important tool for dissecting the functions of lin-42 in molting and developmental timing.

  9. Characterization of a null allelic mutant of the rice NAL1 gene reveals its role in regulating cell division.

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    Dan Jiang

    Full Text Available Leaf morphology is closely associated with cell division. In rice, mutations in Narrow leaf 1 (NAL1 show narrow leaf phenotypes. Previous studies have shown that NAL1 plays a role in regulating vein patterning and increasing grain yield in indica cultivars, but its role in leaf growth and development remains unknown. In this report, we characterized two allelic mutants of NARROW LEAF1 (NAL1, nal1-2 and nal1-3, both of which showed a 50% reduction in leaf width and length, as well as a dwarf culm. Longitudinal and transverse histological analyses of leaves and internodes revealed that cell division was suppressed in the anticlinal orientation but enhanced in the periclinal orientation in the mutants, while cell size remained unaltered. In addition to defects in cell proliferation, the mutants showed abnormal midrib in leaves. Map-based cloning revealed that nal1-2 is a null allelic mutant of NAL1 since both the whole promoter and a 404-bp fragment in the first exon of NAL1 were deleted, and that a 6-bp fragment was deleted in the mutant nal1-3. We demonstrated that NAL1 functions in the regulation of cell division as early as during leaf primordia initiation. The altered transcript level of G1- and S-phase-specific genes suggested that NAL1 affects cell cycle regulation. Heterogeneous expression of NAL1 in fission yeast (Schizosaccharomyces pombe further supported that NAL1 affects cell division. These results suggest that NAL1 controls leaf width and plant height through its effects on cell division.

  10. A new AQP1 null allele identified in a Gypsy woman who developed an anti-CO3 during her first pregnancy.

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    Saison, C; Peyrard, T; Landre, C; Ballif, B A; Schlosser, K A; Dettori, I; Chicheportiche, C; Nemeth, P; Cartron, J-P; Arnaud, L

    2012-08-01

    The Colton blood group antigens are carried by the AQP1 water channel. AQP1(-/-) individuals, also known as Colton-null since they express no Colton antigens, do not suffer any apparent clinical consequence but may develop a clinically significant alloantibody (anti-CO3) induced by transfusion or pregnancy. Identification and transfusion support of Colton-null patients are highly challenging, not only due to the extreme rarity of this phenotype, the lack of appropriate reagents in most laboratories, as well as the possibility of confusing it with the recently described CO:-1,-2,3,-4 phenotype where AQP1 is present. This study investigated a new Colton-null case and evaluated three commercially available anti-AQP1s to identify Colton-null red blood cell samples. The Colton-null phenotype was investigated by standard serological techniques, AQP1 sequencing, immunoblot and flow cytometry analyses. We identified and characterized the Colton-null phenotype in a Gypsy woman who developed an anti-CO3 during her first pregnancy. After developing a simple and robust method to sequence AQP1, we showed that she was apparently homozygous for a new AQP1 null allele, AQP1 601delG, whose product is not expressed in her red blood cells. We also established the Colton specificity of three commercially available anti-AQP1s in immunoblot and/or flow cytometry analyses. This Gypsy woman represents the sixth Colton-null case characterized at the serological, genetic and biochemical levels. The validation here of new reagents and methods should facilitate the identification of Colton-null individuals. © 2012 The Author(s). Vox Sanguinis © 2012 International Society of Blood Transfusion.

  11. An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers.

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    Fisher, Cynthia L; Marks, Hendrik; Cho, Lily Ting-Yin; Andrews, Robert; Wormald, Sam; Carroll, Thomas; Iyer, Vivek; Tate, Peri; Rosen, Barry; Stunnenberg, Hendrik G; Fisher, Amanda G; Skarnes, William C

    2017-12-01

    Mouse embryonic stem (ES) cells are a popular model system to study biological processes, though uncovering recessive phenotypes requires inactivating both alleles. Building upon resources from the International Knockout Mouse Consortium (IKMC), we developed a targeting vector for second allele inactivation in conditional-ready IKMC 'knockout-first' ES cell lines. We applied our technology to several epigenetic regulators, recovering bi-allelic targeted clones with a high efficiency of 60% and used Flp recombinase to restore expression in two null cell lines to demonstrate how our system confirms causality through mutant phenotype reversion. We designed our strategy to select against re-targeting the 'knockout-first' allele and identify essential genes in ES cells, including the histone methyltransferase Setdb1. For confirmation, we exploited the flexibility of our system, enabling tamoxifen inducible conditional gene ablation while controlling for genetic background and tamoxifen effects. Setdb1 ablated ES cells exhibit severe growth inhibition, which is not rescued by exogenous Nanog expression or culturing in naive pluripotency '2i' media, suggesting that the self-renewal defect is mediated through pluripotency network independent pathways. Our strategy to generate null mutant mouse ES cells is applicable to thousands of genes and repurposes existing IKMC Intermediate Vectors. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Characterization of a New Pink-Fruited Tomato Mutant Results in the Identification of a Null Allele of the SlMYB12 Transcription Factor.

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    Fernandez-Moreno, Josefina-Patricia; Tzfadia, Oren; Forment, Javier; Presa, Silvia; Rogachev, Ilana; Meir, Sagit; Orzaez, Diego; Aharoni, Aspah; Granell, Antonio

    2016-07-01

    The identification and characterization of new tomato (Solanum lycopersicum) mutants affected in fruit pigmentation and nutritional content can provide valuable insights into the underlying biology, as well as a source of new alleles for breeding programs. To date, all characterized pink-pigmented tomato fruit mutants appear to result from low SlMYB12 transcript levels in the fruit skin. Two new mutant lines displaying a pink fruit phenotype (pf1 and pf2) were characterized in this study. In the pf mutants, SlMYB12 transcripts accumulated to wild-type levels but exhibited the same truncation, which resulted in the absence of the essential MYB activation domain coding region. Allelism and complementation tests revealed that both pf mutants were allelic to the y locus and showed the same recessive null allele in homozygosis: Δy A set of molecular and metabolic effects, reminiscent of those observed in the Arabidopsis (Arabidopsis thaliana) myb11 myb12 myb111 triple mutant, were found in the tomato Δy mutants. To our knowledge, these have not been described previously, and our data support the idea of their being null mutants, in contrast to previously described transcriptional hypomorphic pink fruit lines. We detected a reduction in the expression of several flavonol glycosides and some associated glycosyl transferases. Transcriptome analysis further revealed that the effects of the pf mutations extended beyond the flavonoid pathway into the interface between primary and secondary metabolism. Finally, screening for Myb-binding sites in the candidate gene promoter sequences revealed that 141 of the 152 co-down-regulated genes may be direct targets of SlMYB12 regulation. © 2016 American Society of Plant Biologists. All Rights Reserved.

  13. A Common LPA Null Allele Associates With Lower Lipoprotein(a) Levels and Coronary Artery Disease Risk

    NARCIS (Netherlands)

    Kyriakou, Theodosios; Seedorf, Udo; Goel, Anuj; Hopewell, Jemma C.; Clarke, Robert; Watkins, Hugh; Farrall, Martin; van der Hout, A.H.

    Objective-Increased levels of lipoprotein(a) are a highly heritable risk factor for coronary artery disease (CAD). The genetic determinants of lipoprotein(a) levels are mainly because of genetic variation in the apolipoprotein(a) gene (LPA). We have tested the association of a relatively common null

  14. Genotyping of vacA alleles of Helicobacter pylori strains recovered ...

    African Journals Online (AJOL)

    Genotyping of vacA alleles of Helicobacter pylori strains recovered from some Iranian food items. ... Tropical Journal of Pharmaceutical Research ... Conclusion: The presence of similar genotypes in H. pylori strains of foods and those of human clinical samples suggest that contaminated foods may be the source of bacteria ...

  15. Population genetics for 23 Y-STR loci in Tibetan in China and confirmation of DYS448 null allele.

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    Ye, Yi; Gao, Jingshang; Fan, Guangyao; Liao, Linchuan; Hou, Yiping

    2015-05-01

    Tibetan is one of 56 ethnic groups in China, where a level of genetic sub-structure might be expected. Although a global analysis of Y-chromosomal haplotype diversity for 23 STR loci and Y-STR databases with PPY23 kit were created with collaborative effort, there was a lack of data for Tibetan population. In this study we evaluated 248 unrelated male individuals of Chinese Tibetan living in the Tibet Autonomous Region to explore the underlying genetic structure of Tibetan populations. These samples were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) by using PPY23 kit. A total of 224 different haplotypes were found. Haplotype diversity was 0.9990. Both Rst pairwise analyses and multidimensional scaling plot showed the genetic structure of Tibetan population was significantly different from some of Chinese ethnic groups and neighboring populations. There were few interesting null features at DYS448 observed by PPY23 that deserved some comment. It revealed that PPY23 marker set provided substantially stronger discriminatory power in Tibetan population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev 3 mutant strains

    International Nuclear Information System (INIS)

    Lawrence, C.W.; Crhistensen, R.B.

    1979-01-01

    The role of rev3 gene function in uv-induced mutagenesis in the yeast Saccharomyces cerevisiae has been examined by determining the reversion of 12 well-defined cyc1 mutations in diploid strains homozygous for the rev3-1 or rev3-3 allale. The 12 cyc1 alleles include one ochre, one amber, four initiation, two proline missense, and four frameshift mutations. We find that the rev3 mutations reduce the frequency of UV-induced reversion of all of the cyc1 alleles, though different classes of alleles respond to a different extent. These results imply that the rev3 gene function is required for the production of a wide variety of mutational events, though probably not all, and show that each of the three rev loci have different mutational phenotypes. Such diverse phenotypes are not predicted by the unitary model for bacterial mutagenes, suggesting that this is at best an incomplete description of eukaryotic mutagenesis

  17. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

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    Stewart I Head

    Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

  18. High-efficiency genome editing and allele replacement in prototrophic and wild strains of Saccharomyces.

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    Alexander, William G; Doering, Drew T; Hittinger, Chris Todd

    2014-11-01

    Current genome editing techniques available for Saccharomyces yeast species rely on auxotrophic markers, limiting their use in wild and industrial strains and species. Taking advantage of the ancient loss of thymidine kinase in the fungal kingdom, we have developed the herpes simplex virus thymidine kinase gene as a selectable and counterselectable marker that forms the core of novel genome engineering tools called the H: aploid E: ngineering and R: eplacement P: rotocol (HERP) cassettes. Here we show that these cassettes allow a researcher to rapidly generate heterogeneous populations of cells with thousands of independent chromosomal allele replacements using mixed PCR products. We further show that the high efficiency of this approach enables the simultaneous replacement of both alleles in diploid cells. Using these new techniques, many of the most powerful yeast genetic manipulation strategies are now available in wild, industrial, and other prototrophic strains from across the diverse Saccharomyces genus. Copyright © 2014 by the Genetics Society of America.

  19. Molecular strain typing of Brucella abortus isolates from Italy by two VNTR allele sizing technologies.

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    De Santis, Riccardo; Ancora, Massimo; De Massis, Fabrizio; Ciammaruconi, Andrea; Zilli, Katiuscia; Di Giannatale, Elisabetta; Pittiglio, Valentina; Fillo, Silvia; Lista, Florigio

    2013-10-01

    Brucellosis, one of the most important re-emerging zoonoses in many countries, is caused by bacteria belonging to the genus Brucella. Furthermore these bacteria represent potential biological warfare agents and the identification of species and biovars of field strains may be crucial for tracing back source of infection, allowing to discriminate naturally occurring outbreaks instead of bioterrorist events. In the last years, multiple-locus variable-number tandem repeat analysis (MLVA) has been proposed as complement of the classical biotyping methods and it has been applied for genotyping large collections of Brucella spp. At present, the MLVA band profiles may be resolved by automated or manual procedures. The Lab on a chip technology represents a valid alternative to standard genotyping techniques (as agarose gel electrophoresis) and it has been previously used for Brucella genotyping. Recently, a new high-throughput genotyping analysis system based on capillary gel electrophoresis, the QIAxcel, has been described. The aim of the study was to evaluate the ability of two DNA sizing equipments, the QIAxcel System and the Lab chip GX, to correctly call alleles at the sixteen loci including one frequently used MLVA assay for Brucella genotyping. The results confirmed that these technologies represent a meaningful advancement in high-throughput Brucella genotyping. Considering the accuracy required to confidently resolve loci discrimination, QIAxcel shows a better ability to measure VNTR allele sizes compared to LabChip GX.

  20. Identification and Genetic Diversity of Etambutol Resistant Strains of Mycobacterium Tuberculosis by Allelic-Specific PCR and Spologiotyping

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    Zahra Derakhshani Nezhad

    2012-09-01

    Full Text Available Background & Objectives: Ethambutol is one of the four main drugs in treatment of tuberculosis. The most common mutation associated with this drug resistance usually occurs in codon 306 of embB. The aim of this study was to detect ethambutol resistance using Allele-Specific PCR and Spoligotyping in various subtypes of Mycobacterium tuberculosis.   Methods : 140 sputum specimens were collected from suspected TB patients. They were digested and decontaminated using Pettrof method before culturing them on LJ medium. Drug susceptibility testing was performed on 106 culture positive specimens using proportional method. DNA was extracted from the isolated organisms and subsequently subjected to Allele-Specific PCR to detect any mutationin embB306. Spoligotyping was then used to determine the subtypes.   Results: Out of 106 cultures positive samples, 36 samples (33.9% showed resistance to ethambutol using proportional method. Allele-Specific PCR assay identified 93 as sensitive and 13 (27.6% as resistant strains. The results of PCR were in agreement with result of proportional method. The PCR method revealed that 61.5% of mutation occurred in the first and 38.5% in third nucleotides. Spoligotyping differentiated Mycobacterium tuberculosis strains into Beijing (10 9.4%, Bovis (2 1.8%, CAS (24 22.6%, EAI (1 0.9%, Haarlem (27 25.4%, LAM (5 4.7%, Manu (5 4.7%, T (27 25.4% and U( 2 1,8% families. The high frequency of mutation in embB gene was belonged to Haarlem, CAS and T subfamilies.   Conclusion: Based on results current study, mutations in the genes other than embB might have occurred in the resistant strains that gave negative result in Allele-Specific PCR assay. Therefore other mechanisms of resistance to this antibiotic should be investigated.

  1. Novel ethyl methanesulfonate (EMS-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo

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    Mark W. Dodson

    2014-12-01

    Full Text Available Mutations in LRRK2 cause a dominantly inherited form of Parkinson’s disease (PD and are the most common known genetic determinant of PD. Inhibitor-based therapies targeting LRRK2 have emerged as a key therapeutic strategy in PD; thus, understanding the consequences of inhibiting the normal cellular functions of this protein is vital. Despite much interest, the physiological functions of LRRK2 remain unclear. Several recent studies have linked the toxicity caused by overexpression of pathogenic mutant forms of LRRK2 to defects in the endolysosomal and autophagy pathways, raising the question of whether endogenous LRRK2 might play a role in these processes. Here, we report the characterization of multiple novel ethyl methanesulfonate (EMS-induced nonsense alleles in the Drosophila LRRK2 homolog, lrrk. Using these alleles, we show that lrrk loss-of-function causes striking defects in the endolysosomal and autophagy pathways, including the accumulation of markedly enlarged lysosomes that are laden with undigested contents, consistent with a defect in lysosomal degradation. lrrk loss-of-function also results in the accumulation of autophagosomes, as well as the presence of enlarged early endosomes laden with mono-ubiquitylated cargo proteins, suggesting an additional defect in lysosomal substrate delivery. Interestingly, the lysosomal abnormalities in these lrrk mutants can be suppressed by a constitutively active form of the small GTPase rab9, which promotes retromer-dependent recycling from late endosomes to the Golgi. Collectively, our data provides compelling evidence of a vital role for lrrk in lysosomal function and endolysosomal membrane transport in vivo, and suggests a link between lrrk and retromer-mediated endosomal recycling.

  2. Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo.

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    Dodson, Mark W; Leung, Lok K; Lone, Mohiddin; Lizzio, Michael A; Guo, Ming

    2014-12-01

    Mutations in LRRK2 cause a dominantly inherited form of Parkinson's disease (PD) and are the most common known genetic determinant of PD. Inhibitor-based therapies targeting LRRK2 have emerged as a key therapeutic strategy in PD; thus, understanding the consequences of inhibiting the normal cellular functions of this protein is vital. Despite much interest, the physiological functions of LRRK2 remain unclear. Several recent studies have linked the toxicity caused by overexpression of pathogenic mutant forms of LRRK2 to defects in the endolysosomal and autophagy pathways, raising the question of whether endogenous LRRK2 might play a role in these processes. Here, we report the characterization of multiple novel ethyl methanesulfonate (EMS)-induced nonsense alleles in the Drosophila LRRK2 homolog, lrrk. Using these alleles, we show that lrrk loss-of-function causes striking defects in the endolysosomal and autophagy pathways, including the accumulation of markedly enlarged lysosomes that are laden with undigested contents, consistent with a defect in lysosomal degradation. lrrk loss-of-function also results in the accumulation of autophagosomes, as well as the presence of enlarged early endosomes laden with mono-ubiquitylated cargo proteins, suggesting an additional defect in lysosomal substrate delivery. Interestingly, the lysosomal abnormalities in these lrrk mutants can be suppressed by a constitutively active form of the small GTPase rab9, which promotes retromer-dependent recycling from late endosomes to the Golgi. Collectively, our data provides compelling evidence of a vital role for lrrk in lysosomal function and endolysosomal membrane transport in vivo, and suggests a link between lrrk and retromer-mediated endosomal recycling. © 2014. Published by The Company of Biologists Ltd.

  3. Using the Textpresso Site-Specific Recombinases Web server to identify Cre expressing mouse strains and floxed alleles.

    Science.gov (United States)

    Condie, Brian G; Urbanski, William M

    2014-01-01

    Effective tools for searching the biomedical literature are essential for identifying reagents or mouse strains as well as for effective experimental design and informed interpretation of experimental results. We have built the Textpresso Site Specific Recombinases (Textpresso SSR) Web server to enable researchers who use mice to perform in-depth searches of a rapidly growing and complex part of the mouse literature. Our Textpresso Web server provides an interface for searching the full text of most of the peer-reviewed publications that report the characterization or use of mouse strains that express Cre or Flp recombinase. The database also contains most of the publications that describe the characterization or analysis of strains carrying conditional alleles or transgenes that can be inactivated or activated by site-specific recombinases such as Cre or Flp. Textpresso SSR complements the existing online databases that catalog Cre and Flp expression patterns by providing a unique online interface for the in-depth text mining of the site specific recombinase literature.

  4. Trichoderma reesei xylanase 5 is defective in the reference strain QM6a but functional alleles are present in other wild-type strains.

    Science.gov (United States)

    Ramoni, Jonas; Marchetti-Deschmann, Martina; Seidl-Seiboth, Verena; Seiboth, Bernhard

    2017-05-01

    Trichoderma reesei is a paradigm for the regulation and industrial production of plant cell wall-degrading enzymes. Among these, five xylanases, including the glycoside hydrolase (GH) family 11 XYN1 and XYN2, the GH10 XYN3, and the GH30 XYN4 and XYN6, were described. By genome mining and transcriptome analysis, a further putative xylanase, encoded by xyn5, was identified. Analysis of xyn5 from the genome-sequenced reference strain T. reesei QM6a shows that it encodes a non-functional, truncated form of XYN5. However, non-truncated orthologues are present in other genome sequenced Trichoderma spp., and sequencing of xyn5 in other T. reesei wild-type isolates shows that they harbor a putative functional xyn5 allele. In silico analysis and 3D modeling revealed that the encoded XYN5 has significant structural similarities to xylanases of the GH11 family, including a GH-typical substrate binding groove and a carboxylate pair in the active site. The xyn5 of wild-type strain TUCIM1282 was recombinantly expressed in a T. reesei strain with a (hemi)cellulase-free background and the corresponding protein purified to apparent homogeneity. The pH and temperature optima and the kinetic parameters of the purified XYN5 were pH 4, 50 °C, and V max  = 2646 nkat/mg with a K m of 9.68 mg/ml. This functional xyn5 allele was used to replace the mutated version which led to an overall increase of the xylanolytic activity. These findings are of particular importance as GH11 xylanases are of high biotechnological relevance, and T. reesei is one of the main industrial producers of such lignocellulose-degrading enzymes.

  5. Novel polymorphisms within the Dlk1-Dio3 imprinted locus in rat: a putative genetic basis for strain-specific allelic gene expression

    Directory of Open Access Journals (Sweden)

    Laura J Sittig

    2012-12-01

    Full Text Available The imprinted iodothyronine deiodinase-III (Dio3 thyroid hormone metabolizing gene exhibits paternal expression in most fetal tissues, yet exhibits aberrant, maternal expression in the hippocampus in F1 offspring of Sprague Dawley (SD x Brown Norway (BN rats. The maternal hippocampal expression is associated with lower Dio3 mRNA levels specifically in the hippocampus. Here, we tested the hypothesis that genetic polymorphisms between the SD and BN parent strains cause this aberrant allelic Dio3 expression and contribute to behavioral sequelae of higher thyroid hormone levels locally in the hippocampus, including anxiety-related behavior. We mapped and sequenced the Dio3 gene and several previously unmapped regions in the Dlk1-Dio3 locus that could regulate imprinting of the Dio3 gene. In the Dio3 promoter we identified four novel polymorphisms between the BN and SD strains. Next we took advantage of the fact that the Long Evans (LE strain exhibits identical polymorphisms as the SD strain in the region 5’ and including the Dio3 gene. By reciprocally crossing LE and BN strains we tested the relationship among Dio3 promoter region polymorphisms and Dio3 mRNA expression in the hippocampus. Aberrant strain-specific hippocampal Dio3 allelic expression replicated in the LE-BN reciprocal crosses, suggesting that hippocampal-specific imprinting of the Dio3 gene is not the result of a unique genetic or epigenetic characteristic of the SD rat strain, or a unique epistatic interaction between SD and BN. To our knowledge no other studies have reported a genetic x epigenetic interaction of genetic origin in the brain.

  6. Association of H2A{sup b} with resistance to collagen-induced arthritis in H2-recombinant mouse strains: An allele associated with reduction of several apparently unrelated responses

    Energy Technology Data Exchange (ETDEWEB)

    Mitchison, N.A.; Brunner, M.C. [Deutsches Rheuma-Forschungszentrum, Berlin (Germany)

    1995-02-01

    HLA class II alleles can protect against immunological diseases. Seeking an animal model for a naturally occurring protective allele, we screened a panel of H2-congenic and recombinant mouse strains for ability to protect against collagen-induced arthritis. The strains were crossed with the susceptible strain DBA/1, and the F{sub 1} hybrids immunized with cattle and chicken type II collagen. Hybrids having the H2A{sup b} allele displayed a reduced incidence and duration of the disease. They also had a reduced level of pre-disease inflammation, but not of anti-collagen antibodies. The allele is already known to be associated with reduction of other apparently unrelated immune responses, suggesting that some form of functional differentiation may operate that is not exclusively related to epitope-binding. It is suggested that this may reflect allelic variation in the class II major histocompatibility complex promoter region. 42 refs., 7 figs., 1 tab.

  7. Human rotavirus strains bearing VP4 gene P[6] allele recovered from asymptomatic or symptomatic infections share similar, if not identical, VP4 neutralization specificities

    International Nuclear Information System (INIS)

    Hoshino, Yasutaka; Jones, Ronald W.; Ross, Jerri; Santos, Norma; Kapikian, Albert Z.

    2003-01-01

    A rotavirus VP4 gene P[6] allele has been documented in a number of countries to be characteristically associated with an endemic predominantly asymptomatic infection in neonates in maternity hospital nurseries. The mechanisms underlying the endemicity and asymptomatic nature of such neonatal infections remain unknown. Rotavirus strains sharing this same P genotype, however, have more recently been recovered from an increasing number of symptomatic diarrheal episodes in infants and young children in various parts of the world. Previously, we have shown that an asymptomatic P[6] rotavirus neonatal infection is not associated with a unique VP7 (G) serotype but may occur in conjunction with various G types. Although amino acid sequence comparisons of the VP4 gene between selected 'asymptomatic' and 'symptomatic' P[6] rotavirus strains have been reported and yielded information concerning their VP4 genotypes, serotypic comparisons of the outer capsid spike protein VP4 of such viruses have not been studied systematically by two-way cross-neutralizations. We determined the VP4 neutralization specificities of four asymptomatic and four symptomatic P[6] strains: two each of asymptomatic and symptomatic strains by two-way tests, and two each of additional asymptomatic and symptomatic strains by one-way tests. Both asymptomatic and symptomatic P[6] strains were shown to bear similar, if not identical, VP4 neutralization specificities. Thus, P[6] rotavirus strains causing asymptomatic or symptomatic infections did not appear to belong to unique P (VP4) serotypes. In addition, a close VP4 serotypic relationship between human P[6] rotavirus strains and the porcine P[6] rotavirus Gottfried strain was confirmed

  8. Superoxide dismutase 1-mediated production of ethanol- and DNA-derived radicals in yeasts challenged with hydrogen peroxide: molecular insights into the genome instability of peroxiredoxin-null strains.

    Science.gov (United States)

    Ogusucu, Renata; Rettori, Daniel; Netto, Luis E S; Augusto, Ohara

    2009-02-27

    Peroxiredoxins are receiving increasing attention as defenders against oxidative damage and sensors of hydrogen peroxide-mediated signaling events. In the yeast Saccharomyces cerevisiae, deletion of one or more isoforms of the peroxiredoxins is not lethal but compromises genome stability by mechanisms that remain under scrutiny. Here, we show that cytosolic peroxiredoxin-null cells (tsa1Deltatsa2Delta) are more resistant to hydrogen peroxide than wild-type (WT) cells and consume it faster under fermentative conditions. Also, tsa1Deltatsa2Delta cells produced higher yields of the 1-hydroxyethyl radical from oxidation of the glucose metabolite ethanol, as proved by spin-trapping experiments. A major role for Fenton chemistry in radical formation was excluded by comparing WT and tsa1Deltatsa2Delta cells with respect to their levels of total and chelatable metal ions and of radical produced in the presence of chelators. The main route for 1-hydroxyethyl radical formation was ascribed to the peroxidase activity of Cu,Zn-superoxide dismutase (Sod1), whose expression and activity increased approximately 5- and 2-fold, respectively, in tsa1Deltatsa2Delta compared with WT cells. Accordingly, overexpression of human Sod1 in WT yeasts led to increased 1-hydroxyethyl radical production. Relevantly, tsa1Deltatsa2Delta cells challenged with hydrogen peroxide contained higher levels of DNA-derived radicals and adducts as monitored by immuno-spin trapping and incorporation of (14)C from glucose into DNA, respectively. The results indicate that part of hydrogen peroxide consumption by tsa1Deltatsa2Delta cells is mediated by induced Sod1, which oxidizes ethanol to the 1-hydroxyethyl radical, which, in turn, leads to increased DNA damage. Overall, our studies provide a pathway to account for the hypermutability of peroxiredoxin-null strains.

  9. Generation of mice with a conditional Foxp2 null allele

    OpenAIRE

    French, C.; Groszer, M.; Preece, C.; Coupe, A.; Rajewsky, K.; Fisher, S.

    2007-01-01

    Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12?14 of Foxp2; these exons encode the DNA-bindi...

  10. Development of an allele-specific PCR assay for simultaneous sero-typing of avian pathogenic Escherichia coli predominant O1, O2, O18 and O78 strains.

    Science.gov (United States)

    Wang, Shaohui; Meng, Qingmei; Dai, Jianjun; Han, Xiangan; Han, Yue; Ding, Chan; Liu, Haiwen; Yu, Shengqing

    2014-01-01

    Systemic infections by avian pathogenic Escherichia coli (APEC) are economically devastating to poultry industries worldwide. E. coli strains belonging to serotypes O1, O2, O18 and O78 are preferentially associated with avian colibacillosis. The rfb gene cluster controlling O antigen synthesis is usually various among different E. coli serotypes. In present study, the rfb gene clusters of E. coli serotypes O1, O2, O18 and O78 were characterized and compared. Based on the serotype-specific genes in rfb gene cluster, an allele-specific polymerase chain reaction (PCR) assay was developed. This PCR assay was highly specific and reliable for sero-typing of APEC O1, O2, O18 and O78 strains. The sensitivity of the assay was determined as 10 pg DNA or 10 colony forming units (CFUs) bacteria for serotypes O2 and O18 strains, and 500 pg DNA or 1,000 CFUs bacteria for serotypes O1 and O78 strains. Using this PCR system, APEC isolates and the infected tissue samples were categorized successfully. Furthermore, it was able to differentiate the serotypes for the samples with multi-agglutination in the traditional serum agglutination assay. Therefore, the allele-specific PCR is more simple, rapid and accurate assay for APEC diagnosis, epidemiologic study and vaccine development.

  11. Development of an allele-specific PCR assay for simultaneous sero-typing of avian pathogenic Escherichia coli predominant O1, O2, O18 and O78 strains.

    Directory of Open Access Journals (Sweden)

    Shaohui Wang

    Full Text Available Systemic infections by avian pathogenic Escherichia coli (APEC are economically devastating to poultry industries worldwide. E. coli strains belonging to serotypes O1, O2, O18 and O78 are preferentially associated with avian colibacillosis. The rfb gene cluster controlling O antigen synthesis is usually various among different E. coli serotypes. In present study, the rfb gene clusters of E. coli serotypes O1, O2, O18 and O78 were characterized and compared. Based on the serotype-specific genes in rfb gene cluster, an allele-specific polymerase chain reaction (PCR assay was developed. This PCR assay was highly specific and reliable for sero-typing of APEC O1, O2, O18 and O78 strains. The sensitivity of the assay was determined as 10 pg DNA or 10 colony forming units (CFUs bacteria for serotypes O2 and O18 strains, and 500 pg DNA or 1,000 CFUs bacteria for serotypes O1 and O78 strains. Using this PCR system, APEC isolates and the infected tissue samples were categorized successfully. Furthermore, it was able to differentiate the serotypes for the samples with multi-agglutination in the traditional serum agglutination assay. Therefore, the allele-specific PCR is more simple, rapid and accurate assay for APEC diagnosis, epidemiologic study and vaccine development.

  12. Null cone superspace supergravity

    International Nuclear Information System (INIS)

    Downes-Martin, S.G.

    1980-03-01

    The null cone formalism is used to derive a 2(N-1) parameter family of constraints for O(N) extended superspace supergravity. The invariance groups of these constraints is analysed and is found to be [subgroup U submanifold] contains GL(4,R) for N = 1, the submanifold being eliminated for N > 1. The invariance group defines non-Weyl rotations on the superbein which combine to form Weyl transformations on the supertangent space metric. The invariance of the supergravity Lagrangian under these transformations is discussed. (Auth.)

  13. Red hair is the null phenotype of MC1R.

    Science.gov (United States)

    Beaumont, Kimberley A; Shekar, Sri N; Cook, Anthony L; Duffy, David L; Sturm, Richard A

    2008-08-01

    The Melanocortin-1 Receptor (MC1R) is a G-protein coupled receptor, which is responsible for production of the darker eumelanin pigment and the tanning response. The MC1R gene has many polymorphisms, some of which have been linked to variation in pigmentation phenotypes within human populations. In particular, the p.D84E, p.R151C, p.R160W and p.D294 H alleles have been strongly associated with red hair, fair skin and increased skin cancer risk. These red hair colour (RHC) variants are relatively well described and are thought to result in altered receptor function, while still retaining varying levels of signaling ability in vitro. The mouse Mc1r null phenotype is yellow fur colour, the p.R151C, p.R160W and p.D294 H alleles were able to partially rescue this phenotype, leading to the question of what the true null phenotype of MC1R would be in humans. Due to the rarity of MC1R null alleles in human populations, they have only been found in the heterozygous state until now. We report here the first case of a homozygous MC1R null individual, phenotypic analysis indicates that red hair and fair skin is found in the absence of MC1R function.

  14. The new allelic variant of the subtilase cytotoxin (subAB2) is common among Shiga toxin-producing Escherichia coli strains from large game animals and their meat and meat products.

    Science.gov (United States)

    Sánchez, Sergio; Díaz-Sánchez, Sandra; Martínez, Remigio; Llorente, María Teresa; Herrera-León, Silvia; Vidal, Dolors

    2013-10-25

    Subtilase cytotoxin (SubAB) is an AB5 toxin produced by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains usually lacking the eae gene product intimin. Two allelic variants of SubAB encoding genes have been described: subAB1, located on a plasmid, and subAB2, located on a pathogenicity island (PAI) together with tia gene. While subAB1 has been reported to be more frequent among bovine strains, subAB2 has been mainly associated with strains from small ruminants. We investigated the presence of the two variants of subAB among 59 eae-negative STEC from large game animals (deer and wild boar) and their meat and meat products in order to assess the role of other species in the epidemiology of subAB-positive, eae-negative STEC. For this approach, the strains were PCR-screened for the presence of subAB, including the specific detection of both allelic variants, for the presence of saa, tia and sab, and for stx subtyping. Overall, subAB genes were detected in 71.2% of the strains: 84.1% of the strains from deer and 33.3% of the strains from wild boar. Most of them (97.6%) possessed subAB2 and most of these subAB2-positive strains (92.7%) were also positive for tia and negative for saa, suggesting the presence of the subAB2-harbouring PAI. Subtype stx2b was present in most of the strains (67.8%) and a statistically significant association could be established between subAB2 and stx2b. Our results suggest that large game animals, mainly deer, may represent an important animal reservoir of subAB2-positive, eae-negative STEC, and also highlight the risk of human infection posed by the consumption of large game meat and meat products. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. sirt1-null mice develop an autoimmune-like condition

    International Nuclear Information System (INIS)

    Sequeira, Jedon; Boily, Gino; Bazinet, Stephanie; Saliba, Sarah; He Xiaohong; Jardine, Karen; Kennedy, Christopher; Staines, William; Rousseaux, Colin; Mueller, Rudi; McBurney, Michael W.

    2008-01-01

    The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease

  16. Visible Nulling Coronagraph Progress Report

    Science.gov (United States)

    Lyon, R. G.; Clampin, M.; Woodruff, R. A.; Vasudevan, G.; Thompson, P.; Petrone, P.; Madison, T.; Rizzo, M.; Melnick, G.; Tolls, V.

    2010-10-01

    We report on recent laboratory results with the NASA Goddard Space Flight Center Visible Nulling Coronagraph (VNC) testbed. We have achieved focal plane contrasts of 108 and approaching 109 at inner working angles of 2 λ/D and 4 λ/D, respectively. Results were obtained with a broadband source and 40 nm filter centered on 630 nm. A null control breadboard (NCB) was also developed to assess and quantify MEMS based deformable mirror technology (DM), and to develop and assess closed-loop null control algorithms. We have demonstrated closed-loop performance at 27 Hz.

  17. Fitness differences due to allelic variation at Esterase-4 locus in ...

    Indian Academy of Sciences (India)

    KAVITA KRISHNAMOORTI

    2017-08-31

    Aug 31, 2017 ... Keywords. esterases; null allele; reproductive fitness; natural selection; Drosophila ananassae. .... cific substrate (1-naphthylacetate AR) and stain (fast blue. RR). On the ... transferred to fresh food vials and eggs were counted.

  18. Null lifts and projective dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Cariglia, Marco, E-mail: marco@iceb.ufop.br

    2015-11-15

    We describe natural Hamiltonian systems using projective geometry. The null lift procedure endows the tangent bundle with a projective structure where the null Hamiltonian is identified with a projective conic and induces a Weyl geometry. Projective transformations generate a set of known and new dualities between Hamiltonian systems, as for example the phenomenon of coupling-constant metamorphosis. We conclude outlining how this construction can be extended to the quantum case for Eisenhart–Duval lifts.

  19. Insight into stereochemistry of a new IMP allelic variant (IMP-55) metallo-β-lactamase identified in a clinical strain of Acinetobacter baumannii.

    Science.gov (United States)

    Shakibaie, Mohammad Reza; Azizi, Omid; Shahcheraghi, Fereshteh

    2017-07-01

    Metallo-β-lactamases (MBLs) such as IMPs are broad-spectrum β-lactamases that inactivate virtually all β-lactam antibiotics including carbapenems. In this study, we investigated the hydrolytic activity, phylogenetic relationship, three dimensional (3D) structure including zinc binding motif of a new IMP variant (IMP-55) identified in a clinical strain of Acinetobacter baumannii (AB). AB strain 56 was isolated from an adult ICU of a teaching hospital in Kerman, Iran. It exhibited MIC 32μg/ml to imipenem and showed MBL activity. Hydrolytic property of the MBL enzyme was measured phenotypically. Presence of bla IMP gene encoded by class 1 integrons was detected by PCR-sequencing. Phylogenetic tree of IMP protein was constructed using the Unweighted Pair Group Method with Arithmetic Mean (UPGMA) and 3D model including zinc binding motif was predicted by bioinformatics softwares. Analysis of IMP sequence led to the identification of a novel IMP-type designated as IMP-55 (GenBank: KU299753.1; UniprotKB: A0A0S2MTX2). Impact in term of hydrolytic activity compared to the closest variants suggested efficient imipenem hydrolysis by this enzyme. Evolutionary distance matrix assessment indicated that IMP-55 protein is not closely related to other A. baumannii IMPs, however, shared 98% homology with Escherichia coli IMP-30 (UniprotKB: A0A0C5PJR0) and Pseudomonas aeruginosa IMP-1 (UniprotKB: Q19KT1). It consisted of five α-helices, ten β-sheets and six loops. A monovalent zinc ion attached to core of enzyme via His95, His97, His157 and Cys176. Multiple amino acid sequence alignments and mutational trajectory with reported IMPs showed 4 amino acid substitutions at positions 12(Phe→Ile), 31(Asp→Glu), 172(Leu→Phe) and 185(Asn→Lys). We suggest that the pleiotropic effect of mutations due to frequent administration of imipenem is responsible for emergence of new IMP variant in our hospitals. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Bare Quantum Null Energy Condition.

    Science.gov (United States)

    Fu, Zicao; Marolf, Donald

    2018-02-16

    The quantum null energy condition (QNEC) is a conjectured relation between a null version of quantum field theory energy and derivatives of quantum field theory von Neumann entropy. In some cases, divergences cancel between these two terms and the QNEC is intrinsically finite. We study the more general case here where they do not and argue that a QNEC can still hold for bare (unrenormalized) quantities. While the original QNEC applied only to locally stationary null congruences in backgrounds that solve semiclassical theories of quantum gravity, at least in the formal perturbation theory at a small Planck length, the quantum focusing conjecture can be viewed as the special case of our bare QNEC for which the metric is on shell.

  1. Visible nulling coronagraph testbed results

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Petrone, Peter; Madison, Timothy; Rizzo, Maxime; Melnick, Gary; Tolls, Volker

    2009-08-01

    We report on our recent laboratory results with the NASA/Goddard Space Flight Center (GSFC) Visible Nulling Coronagraph (VNC) testbed. We have experimentally achieved focal plane contrasts of 1 x 108 and approaching 109 at inner working angles of 2 * wavelength/D and 4 * wavelength/D respectively where D is the aperture diameter. The result was obtained using a broadband source with a narrowband spectral filter of width 10 nm centered on 630 nm. To date this is the deepest nulling result with a visible nulling coronagraph yet obtained. Developed also is a Null Control Breadboard (NCB) to assess and quantify MEMS based segmented deformable mirror technology and develop and assess closed-loop null sensing and control algorithm performance from both the pupil and focal planes. We have demonstrated closed-loop control at 27 Hz in the laboratory environment. Efforts are underway to first bring the contrast to > 109 necessary for the direct detection and characterization of jovian (Jupiter-like) and then to > 1010 necessary for terrestrial (Earth-like) exosolar planets. Short term advancements are expected to both broaden the spectral passband from 10 nm to 100 nm and to increase both the long-term stability to > 2 hours and the extent of the null out to a ~ 10 * wavelength / D via the use of MEMS based segmented deformable mirror technology, a coherent fiber bundle, achromatic phase shifters, all in a vacuum chamber at the GSFC VNC facility. Additionally an extreme stability textbook sized compact VNC is under development.

  2. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

    Directory of Open Access Journals (Sweden)

    Erin E Cummings

    Full Text Available α1-antitrypsin deficiency (ATD predisposes patients to both loss-of-function (emphysema and gain-of-function (liver cirrhosis phenotypes depending on the type of mutation. Although the Z mutation (ATZ is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels or null (<1% normal levels alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS, showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of

  3. Standard and Null Weak Values

    OpenAIRE

    Zilberberg, Oded; Romito, Alessandro; Gefen, Yuval

    2013-01-01

    Weak value (WV) is a quantum mechanical measurement protocol, proposed by Aharonov, Albert, and Vaidman. It consists of a weak measurement, which is weighed in, conditional on the outcome of a later, strong measurement. Here we define another two-step measurement protocol, null weak value (NVW), and point out its advantages as compared to WV. We present two alternative derivations of NWVs and compare them to the corresponding derivations of WVs.

  4. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  5. Impairment of Infectivity and Immunoprotective Effect of a LYT1 Null Mutant of Trypanosoma cruzi▿

    Science.gov (United States)

    Zago, M. Paola; Barrio, Alejandra B.; Cardozo, Rubén M.; Duffy, Tomás; Schijman, Alejandro G.; Basombrío, Miguel A.

    2008-01-01

    Trypanosoma cruzi infection of host cells is a complex process in which many proteins participate but only a few of these proteins have been identified experimentally. One parasite factor likely to be involved is the protein product of LYT1, a single-copy gene cloned, sequenced, and characterized by Manning-Cela et al. (Infect. Immun. 69:3916-3923, 2001). This gene was potentially associated with infectivity, since the deletion of both LYT1 alleles in the CL Brenner strain (the wild type [WT]) resulted in a null mutant T. cruzi clone (L16) that shows an attenuated phenotype in cell culture models. The aim of this work was to characterize the infective behavior of L16 in the insect vector and murine models. The infection of adult Swiss mice with 103 trypomastigotes of both clones revealed a significant reduction in infective behavior of L16, as shown by direct parasitemia, spleen index, and quantitation of tissue parasite burden, suggesting the loss of virulence in the null mutant clone. Although L16 blood counts were almost undetectable, blood-based PCRs indicated the presence of latent and persistent infection during all of the study period and epimastigotes were reisolated from hemocultures until 12 months postinfection. Nevertheless, virulence was not restored in L16 by serial passages in mice, and reisolated parasites lacking the LYT1 gene and bearing the antibiotic resistance genes revealed the stability of the genetic manipulation. Histopathological studies showed a strong diminution in the muscle inflammatory response triggered by L16 compared to that triggered by the WT group, consistent with a lower tissue parasite load. A strong protection against a virulent challenge in both L16- and WT-infected mice was observed; however, the immunizing infection by the genetically modified parasite was highly attenuated. PMID:17938222

  6. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Science.gov (United States)

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  7. The Importance of Proving the Null

    Science.gov (United States)

    Gallistel, C. R.

    2009-01-01

    Null hypotheses are simple, precise, and theoretically important. Conventional statistical analysis cannot support them; Bayesian analysis can. The challenge in a Bayesian analysis is to formulate a suitably vague alternative, because the vaguer the alternative is (the more it spreads out the unit mass of prior probability), the more the null is…

  8. Seleção de linhagens de feijoeiro com tipo de grão carioca e com os alelos co-4 e co-5 de resistência à antracnose Selection of common bean strains with carioca grain type, and with the alleles co-4 and co-5 for anthracnose resistance

    Directory of Open Access Journals (Sweden)

    Eduardo Henrique Keller Marcondes

    2010-08-01

    Full Text Available Objetivou-se, neste trabalho, identificar linhagens de feijão que reúnam, além da resistência à antracnose, alta produtividade de grãos do tipo carioca e resistência à mancha angular. Foram utilizadas 194 linhagens F5:6 extraídas de sete famílias segregantes, selecionadas do cruzamento entre os genitores H147 e B1. A linhagem H147 possui grãos tipo carioca, portadora do alelo Co-5, que confere resistência a várias raças de Colletotrichum lindemuthianum. A linhagem B1 também possui grãos tipo carioca e é portadora do alelo Co-4, que confere resistência a outro grupo de raças do mesmo patógeno. As linhagens foram avaliadas na safra das águas 2005/2006, em Lavras, com a cultivar Talismã e H147 como testemunhas, com base na produtividade e tipo de grãos. Foram selecionadas 99 linhagens, as quais foram avaliadas na safra da seca/2006, juntamente com a testemunha Talismã, com base na produtividade, tipo de grão e resistência à mancha angular. Dessas 99 linhagens, foram selecionadas 24, as quais foram avaliadas na safra de inverno/2006 em Lavras e Lambari, com base no tipo de grão e produtividade. Essas 24 linhagens foram inoculadas com a raça 321 de C. lindemuthianum, que quebra a resistência conferida pelo alelo Co-4, mas não o Co-5. Para verificar a presença do alelo Co4 foi utilizado um marcador SCAR que amplifica um fragmento de 950 pb por meio do primer SAS 13. Foi possível identificar 14 linhagens que possuem a pirâmide de alelos Co-4/Co-5 e entre elas, quatro destacaram-se em todos os caracteres avaliados.The objective of the research was to identify bean strains that possess at the same time resistance to anthracnose, high grain yield of Carioca grain type and resistance to angular leaf spot. 194 strains F5:6 were taken from seven segregating families derived from the cross H147 x B1. The H147 line has Carioca grain type and Co-5 resistance allele to several races of C. lindemuthianum. The B1 line also has the

  9. Conformal symmetry inheritance in null fluid spacetimes

    International Nuclear Information System (INIS)

    Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

    2003-01-01

    We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

  10. Null solution of the Yang-Mills equations

    International Nuclear Information System (INIS)

    Tafel, J.

    1986-05-01

    We investigate the correspondence between null solutions of the Yang-Mills equations and shearfree geodesic null congruences. We give an example of a non-Abelian null solution with twisting rays. (orig.)

  11. Null-strut calculus. II. Dynamics

    International Nuclear Information System (INIS)

    Kheyfets, A.; LaFave, N.J.; Miller, W.A.

    1990-01-01

    In this paper, we continue from the preceding paper to develop a fully functional Regge calculus geometrodynamic algorithm from the null-strut-calculus construction. The developments discussed include (a) the identification of the Regge calculus analogue of the constraint and evolution equations on the null-strut lattice, (b) a description of the Minkowski solid geometry for the simplicial blocks of the null-strut lattice, (c) a description of the evolution algorithm for the geometrodynamic scheme and an analysis of its consistency, and (d) a presentation of the dynamical degrees of freedom for a simplicial hypersurface and the description of an initial-value prescription. To demonstrate qualitatively this new approach to geometrodynamics, we present the most simple application of null-strut calculus that we know of---the Friedmann cosmology using the three-boundary of a 600-cell simplicial polytope to model the simplicial hypersurface

  12. Null structure groups in eleven dimensions

    International Nuclear Information System (INIS)

    Cariglia, Marco; Mac Conamhna, Oisin A. P.

    2006-01-01

    We classify all the structure groups which arise as subgroups of the isotropy group (Spin(7)xR 8 )xR, of a single null Killing spinor in 11 dimensions. We construct the spaces of spinors fixed by these groups. We determine the conditions under which structure subgroups of the maximal null structure group (Spin(7)xR 8 )xR may also be embedded in SU(5), and hence the conditions under which a supersymmetric spacetime admits only null, or both timelike and null, Killing spinors. We discuss how this purely algebraic material will facilitate the direct analysis of the Killing spinor equation of 11 dimensional supergravity, and the classification of supersymmetric spacetimes therein

  13. On smoothness-asymmetric null infinities

    International Nuclear Information System (INIS)

    Valiente Kroon, Juan Antonio

    2006-01-01

    We discuss the existence of asymptotically Euclidean initial data sets for the vacuum Einstein field equations which would give rise (modulo an existence result for the evolution equations near spatial infinity) to developments with a past and a future null infinity of different smoothness. For simplicity, the analysis is restricted to the class of conformally flat, axially symmetric initial data sets. It is shown how the free parameters in the second fundamental form of the data can be used to satisfy certain obstructions to the smoothness of null infinity. The resulting initial data sets could be interpreted as those of some sort of (nonlinearly) distorted Schwarzschild black hole. Their developments would be that they admit a peeling future null infinity, but at the same time have a polyhomogeneous (non-peeling) past null infinity

  14. High-contrast Nulling Interferometry Techniques Project

    Data.gov (United States)

    National Aeronautics and Space Administration — "We are developing rotating-baseline nulling-interferometry techniques and algorithms on the single-aperture Hale and Keck telescopes at near-infrared wavelengths,...

  15. Null-plane quantization of fermions

    International Nuclear Information System (INIS)

    Mustaki, D.

    1990-01-01

    Massive Dirac fermions are canonically quantized on the null plane using the Dirac-Bergmann algorithm. The procedure is carried out in the framework of quantum electrodynamics as an illustration of a rigorous treatment of interacting fermion fields

  16. Several classical mouse inbred strains, including DBA/2, NOD/Lt, FVB/N, and SJL/J, carry a putative loss-of-function allele of Gpr84.

    Science.gov (United States)

    Perez, Carlos J; Dumas, Aline; Vallières, Luc; Guénet, Jean-Louis; Benavides, Fernando

    2013-01-01

    G protein-coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in the mouse family tree and found that 14 strains are homozygous for the deletion. Some of these strains are DBA/1J, DBA/2J, FVB/NJ, LG/J, MRL/MpJ, NOD/LtJ, and SJL/J. However, the deletion was not found in any of the wild-derived inbred strains analyzed. Haplotype analysis suggested that the deletion originates from a unique mutation event that occurred more than 100 years ago, preceding the development of the first inbred strain (DBA), from a Mus musculus domesticus source. As GPR84 ostensibly plays a role in the biology of myeloid cells, it could be relevant 1) to consider the existence of this Gpr84 nonsense mutation in several mouse strains when choosing a mouse model to study immune processes and 2) to consider reevaluating data obtained using such strains.

  17. Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

    Directory of Open Access Journals (Sweden)

    Gerhard Sengle

    2015-06-01

    Full Text Available Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that

  18. On the Penrose inequality along null hypersurfaces

    International Nuclear Information System (INIS)

    Mars, Marc; Soria, Alberto

    2016-01-01

    The null Penrose inequality, i.e. the Penrose inequality in terms of the Bondi energy, is studied by introducing a functional on surfaces and studying its properties along a null hypersurface Ω extending to past null infinity. We prove a general Penrose-type inequality which involves the limit at infinity of the Hawking energy along a specific class of geodesic foliations called Geodesic Asymptotically Bondi (GAB), which are shown to always exist. Whenever this foliation approaches large spheres, this inequality becomes the null Penrose inequality and we recover the results of Ludvigsen–Vickers (1983 J. Phys. A: Math. Gen. 16 3349–53) and Bergqvist (1997 Class. Quantum Grav. 14 2577–83). By exploiting further properties of the functional along general geodesic foliations, we introduce an approach to the null Penrose inequality called the Renormalized Area Method and find a set of two conditions which imply the validity of the null Penrose inequality. One of the conditions involves a limit at infinity and the other a restriction on the spacetime curvature along the flow. We investigate their range of applicability in two particular but interesting cases, namely the shear-free and vacuum case, where the null Penrose inequality is known to hold from the results by Sauter (2008 PhD Thesis Zürich ETH ), and the case of null shells propagating in the Minkowski spacetime. Finally, a general inequality bounding the area of the quasi-local black hole in terms of an asymptotic quantity intrinsic of Ω is derived. (paper)

  19. Latex allergy and filaggrin null mutations

    DEFF Research Database (Denmark)

    Carlsen, Berit C; Meldgaard, Michael; Hamann, Dathan

    2011-01-01

    to aeroallergens and it is possible that filaggrin null mutations also increase the risk of latex allergy. The aim of this paper was to examine the association between filaggrin null mutations and type I latex allergy. Methods Twenty latex allergic and 24 non-latex allergic dentists and dental assistants...... in the cases in this study may not have occurred through direct skin contact but through the respiratory organs via latex proteins that are absorbed in glove powder and aerosolized...

  20. Quality of synthetic hexaploid wheat containing null alleles at Glu-A1 ...

    Indian Academy of Sciences (India)

    2013-08-02

    Aug 2, 2013 ... Xinkun Hu and Shoufen Dai contributed equally to this work. been recognized ... 87 (PE company, USA) in 50 μL reaction volumes contain- ing 200–300 ng .... flours for the food industry and the balance between these.

  1. Generation of Mice With a Conditional Null Allele For Tbx2

    NARCIS (Netherlands)

    Wakker, Vincent; Brons, Janynke F.; Aanhaanen, Wim T. J.; van Roon, Marian A.; Moorman, Antoon F. M.; Christoffels, Vincent M.

    2010-01-01

    The T-box transcription factor Tbx2 plays important roles in patterning and development, and has been implicated in cell-cycle regulation and cancer. Conventional disruption of Tbx2 results in abnormalities of the heart, limbs, eye and other structures, and early fetal lethality. To gain insight

  2. Quality of synthetic hexaploid wheat containing null alleles at Glu-A1

    Indian Academy of Sciences (India)

    GSs. However, incorporation of HMW-GS from Ae. tauschii in six synthetic hexaploid wheat lines significantly increased most quality related parameters. The potential values of these wheat lines in improving the quality of wheat are discussed.

  3. Null Subjects in European and Brazilian Portuguese

    Directory of Open Access Journals (Sweden)

    Pilar Barbosa

    2005-12-01

    Full Text Available The goals of this paper are twofold: a to provide a structural account of the effects of the informal ‘Avoid Pronoun Principle’, proposed in Chomsky (1981: 65 for the Null Subject Languages (NSLs, and b to compare, in European and Brazilian Portuguese (EP and BP, the distribution of the third person pronouns in its full and null forms, to check whether in written corpora BP incorporates signs of the ongoing loss of the null subject, largely attested in its contemporary spoken language. The strong theoretical claim is that in the Romance non-NSLs the pre-verbal subject is sitting in Spec of IP, while in the Romance NSLs it is Clitic Left-Dislocated (or is extracted by A-bar movement if it belongs to a restricted set of non-referential quantified expressions. The paper provides quantitative evidence that BP is losing the properties associated with the Null Subject Parameter. In its qualitative analysis, it shows that the contrasts between EP and BP are easily accounted for if the two derivations are assumed and if the null subjects in the two varieties are considered to be of a different nature: a pronoun in EP and a pronominal anaphor in BP.

  4. A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

    Science.gov (United States)

    Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

    2011-01-01

    The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

  5. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  6. Several Classical Mouse Inbred Strains, Including DBA/2, NOD/Lt, FVB/N, and SJL/J, Carry a Putative Loss-of-Function Allele of Gpr84

    OpenAIRE

    Perez, Carlos J.; Dumas, Aline; Vallières, Luc; Guénet, Jean-Louis; Benavides, Fernando

    2013-01-01

    G protein–coupled receptor 84 (GPR84) is a 7-transmembrane protein expressed on myeloid cells that can bind to medium-chain free fatty acids in vitro. Here, we report the discovery of a 2-bp frameshift deletion in the second exon of the Gpr84 gene in several classical mouse inbred strains. This deletion generates a premature stop codon predicted to result in a truncated protein lacking the transmembrane domains 4-7. We sequenced Gpr84 exon 2 from 58 strains representing different groups in th...

  7. Supersymmetric null-like holographic cosmologies

    International Nuclear Information System (INIS)

    Lin Fengli; Wen Wenyu

    2006-01-01

    We construct a new class of 1/4-BPS time dependent domain-wall solutions with null-like metric and dilaton in type II supergravities, which admit a null-like big bang singularity. Based on the domain-wall/QFT correspondence, these solutions are dual to 1/4-supersymmetric quantum field theories living on a boundary cosmological background with time dependent coupling constant and UV cutoff. In particular we evaluate the holographic c function for the 2-dimensional dual field theory living on the corresponding null-like cosmology. We find that this c function runs in accordance with the c-theorem as the boundary universe evolves, this means that the number of degrees of freedom is divergent at big bang and suggests the possible resolution of big bang singularity

  8. Null-strut calculus. I. Kinematics

    International Nuclear Information System (INIS)

    Kheyfets, A.; LaFave, N.J.; Miller, W.A.

    1990-01-01

    This paper describes the kinematics of null-strut calculus---a 3+1 Regge calculus approach to general relativity. We show how to model the geometry of spacetime with simplicial spacelike three-geometries (TET's) linked to ''earlier'' and ''later'' momentumlike lattice surfaces (TET * ) entirely by light rays or ''null struts.'' These three-layered lattice spacetime geometries are defined and analyzed using combinatorial formulas for the structure of polytopes. The following paper in this series describes how these three-layered spacetime lattices are used to model spacetimes in full conformity with Einstein's theory of gravity

  9. Apoptosis in spermatogonia irradiated P53 null mice

    International Nuclear Information System (INIS)

    Streit-Bianchi, M.; Hendry, J.H.; Roberts, S.A.; Morris, J.D.; Durgaryan, A.A.

    2007-01-01

    irradiation and may contribute to a greater mutational burden with respect to transgenerational effects. Split-dose data when compared to single dose also shows for p53 null mice a very high rate of spermatogonia survival. The strain +/+ indicates a large mortality rate when the second dose is given at the time mitotic radiation induced delay is highest whereas the strain +/- shows intermediate values. In the +/+ mice efficient apoptosis activity is shown by a first and second wave appearance whereas in p53 null mice only a second wave is clearly visible. These data seems to indicate that in +/+ mice repair mechanisms in spermatogonial cell are extremely low and that poor cellular damage proofreading exists in p53 null mice. The deficiencies in apoptosis related to the p53 status contribute to the high cancer-proneness of individual with p53 deficiency in the Li-Fraumeni syndrome.

  10. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  11. Fine art of computing nulling interferometer maps

    Science.gov (United States)

    Hénault, F.

    2008-07-01

    Spaceborne nulling interferometers are often characterized by means of their nulling ratio, which is defined as the deepest possible extinction of one target star supposed to harbor an extra-solar system. Herein is shown that another parameter, which is the transmitting efficiency of nearby bright fringes, is also of prime importance. More generally, "nulling maps" formed by the whole destructive and constructive fringe pattern projected on-sky, are found to be very sensitive on the design of some subsystems constituting the interferometer. In particular, we consider Spatial Filtering (SF) and Achromatic Phase Shifter (APS) devices, both required achieving planet detection and characterization. Consequences of the SF choice (pinhole or single-mode optical fiber) and APS properties (with or without induced pupil-flip) are discussed, for both monochromatic and polychromatic cases. Examples of numerical simulations are provided for single Bracewell interferometer, Angel cross and X-array configurations, demonstrating noticeable differences in the aspect of resulting nulling maps. It is concluded that both FS and APS designs exhibit variable capacities for serendipitous planet discovery.

  12. Matter sources for a null big bang

    International Nuclear Information System (INIS)

    Bronnikov, K A; Zaslavskii, O B

    2008-01-01

    We consider the properties of stress-energy tensors compatible with a null big bang, i.e., cosmological evolution starting from a Killing horizon rather than a singularity. For Kantowski-Sachs cosmologies, it is shown that if matter satisfies the null energy condition, then (i) regular cosmological evolution can only start from a Killing horizon, (ii) matter is absent at the horizon and (iii) matter can only appear in the cosmological region due to interaction with vacuum. The latter is understood phenomenologically as a fluid whose stress tensor is insensitive to boosts in a particular direction. We also argue that matter is absent in a static region beyond the horizon. All this generalizes the observations recently obtained for a mixture of dust and a vacuum fluid. If, however, we admit the existence of phantom matter, its certain special kinds (with the parameter w ≤ -3) are consistent with a null big bang without interaction with vacuum (or without vacuum fluid at all). Then in the static region there is matter with w ≥ -1/3. Alternatively, the evolution can begin from a horizon in an infinitely remote past, leading to a scenario combining the features of a null big bang and an emergent universe

  13. Instabilities and the null energy condition

    International Nuclear Information System (INIS)

    Buniy, Roman V.; Hsu, Stephen D.H.

    2006-01-01

    We show that violation of the null energy condition implies instability in a broad class of models, including gauge theories with scalar and fermionic matter as well as any perfect fluid. When applied to the dark energy, our results imply that w=p/ρ is unlikely to be less than -1. than -1

  14. Covariant quantum mechanics on a null plane

    International Nuclear Information System (INIS)

    Leutwyler, H.; Stern, J.

    1977-03-01

    Lorentz invariance implies that the null plane wave functions factorize into a kinematical part describing the motion of the system as a whole and an inner wave function that involves the specific dynamical properties of the system - in complete correspondence with the non-relativistic situation. Covariance is equivalent to an angular condition which admits non-trivial solutions

  15. Null vectors in superconformal quantum field theory

    International Nuclear Information System (INIS)

    Huang Chaoshang

    1993-01-01

    The superspace formulation of the N=1 superconformal field theory and superconformal Ward identities are used to give a precise definition of fusion. Using the fusion procedure, superconformally covariant differential equations are derived and consequently a complete and straightforward algorithm for finding null vectors in Verma modules of the Neveu-Schwarz algebra is given. (orig.)

  16. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  17. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  18. Gravitational collapse of a cylindrical null shell in vacuum

    Directory of Open Access Journals (Sweden)

    S. Khakshournia

    2008-03-01

    Full Text Available   Barrabès-Israel null shell formalism is used to study the gravitational collapse of a thin cylindrical null shell in vacuum. In general the lightlike matter shell whose history coincides with a null hypersurface is characterized by a surface energy density. In addition, a gravitational impulsive wave is present on this null hypersurface whose generators admit both the shear and expansion. In the case of imposing the cylindrical flatness the surface energy-momentum tensor of the matter shell on the null hypersurface vanishes and the null hyper- surface is just the history of the gravitational wave .

  19. Nulling tomography with weak gravitational lensing

    International Nuclear Information System (INIS)

    Huterer, Dragan; White, Martin

    2005-01-01

    We explore several strategies of eliminating (or nulling) the small-scale information in weak lensing convergence power spectrum measurements in order to protect against undesirable effects, for example, the effects of baryonic cooling and pressure forces on the distribution of large-scale structures. We selectively throw out the small-scale information in the convergence power spectrum that is most sensitive to the unwanted bias, while trying to retain most of the sensitivity to cosmological parameters. The strategies are effective in the difficult but realistic situations when we are able to guess the form of the contaminating effect only approximately. However, we also find that the simplest scheme of simply not using information from the largest multipoles works about as well as the proposed techniques in most, although not all, realistic cases. We advocate further exploration of nulling techniques and believe that they will find important applications in the weak lensing data mining

  20. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  1. Collapse and bounce of null fluids

    OpenAIRE

    Creelman, Bradley; Booth, Ivan

    2016-01-01

    Exact solutions describing the spherical collapse of null fluids can contain regions which violate the energy conditions. Physically the violations occur when the infalling matter continues to move inwards even when non-gravitational repulsive forces become stronger than gravity. In 1991 Ori proposed a resolution for these violations: spacetime surgery should be used to replace the energy condition violating region with an outgoing solution. The matter bounces. We revisit and implement this p...

  2. Null balance type electrostatic generating voltmeters

    International Nuclear Information System (INIS)

    Mahant, A.K.; Sidhu, N.P.S.; Gupta, U.C.

    1977-01-01

    A description is given of a null balance type generating voltmeter for measuring high D.C. voltage upto about 400 kV. The paper discusses the principle of operation, design, calibration and performance of the instrument. Main advantages of the device are: (1) it does not load the high voltage source, (2) no physical connection is required with the H.T. terminal and (3) calibration is independent of the rotor's frequency and amplifier's gain. (author)

  3. QuASAR: quantitative allele-specific analysis of reads.

    Science.gov (United States)

    Harvey, Chris T; Moyerbrailean, Gregory A; Davis, Gordon O; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2015-04-15

    Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. http://github.com/piquelab/QuASAR. fluca@wayne.edu or rpique@wayne.edu Supplementary Material is available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Null missense ABCR (ABCA4) mutations in a family with stargardt disease and retinitis pigmentosa.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Lupski, J R

    2001-11-01

    To determine the type of ABCR mutations that segregate in a family that manifests both Stargardt disease (STGD) and retinitis pigmentosa (RP), and the functional consequences of the underlying mutations. Direct sequencing of all 50 exons and flanking intronic regions of ABCR was performed for the STGD- and RP-affected relatives. RNA hybridization, Western blot analysis, and azido-adenosine triphosphate (ATP) labeling was used to determine the effect of disease-associated ABCR mutations in an in vitro assay system. Compound heterozygous missense mutations were identified in patients with STGD and RP. STGD-affected individual AR682-03 was compound heterozygous for the mutation 2588G-->C and a complex allele, [W1408R; R1640W]. RP-affected individuals AR682-04 and-05 were compound heterozygous for the complex allele [W1408R; R1640W] and the missense mutation V767D. Functional analysis of the mutation V767D by Western blot and ATP binding revealed a severe reduction in protein expression. In vitro analysis of ABCR protein with the mutations W1408R and R1640W showed a moderate effect of these individual mutations on expression and ATP-binding; the complex allele [W1408R; R1640W] caused a severe reduction in protein expression. These data reveal that missense ABCR mutations may be associated with RP. Functional analysis reveals that the RP-associated missense ABCR mutations are likely to be functionally null. These studies of the complex allele W1408R; R1640W suggest a synergistic effect of the individual mutations. These data are congruent with a model in which RP is associated with homozygous null mutations and with the notion that severity of retinal disease is inversely related to residual ABCR activity.

  5. Null controllability of the viscous Camassa–Holm equation with ...

    Indian Academy of Sciences (India)

    In this paper, we study the null controllability of the viscous Camassa–. Holm equation on the one-dimensional torus. By using a moving distributed control, we obtain that the system is null controllable for a given data with certain regularity. Keywords. Viscous Camassa–Holm equation; null controllability; moving control;.

  6. Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

    Science.gov (United States)

    Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

    2015-07-01

    Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population

  7. A mycobacterial smc null mutant is proficient in DNA repair and long-term survival.

    Science.gov (United States)

    Güthlein, Carolin; Wanner, Roger M; Sander, Peter; Böttger, Erik C; Springer, Burkhard

    2008-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  8. A Mycobacterial smc Null Mutant Is Proficient in DNA Repair and Long-Term Survival▿

    OpenAIRE

    Güthlein, Carolin; Wanner, Roger M.; Sander, Peter; Böttger, Erik C.; Springer, Burkhard

    2007-01-01

    SMC (structural maintenance of chromosomes) proteins play fundamental roles in various aspects of chromosome organization and dynamics, including repair of DNA damage. Mutant strains of Mycobacterium smegmatis and Mycobacterium tuberculosis defective in SMC were constructed. Surprisingly, inactivation of smc did not result in recognizable phenotypes in hallmark assays characteristic for the function of these genes. This is in contrast to data for smc null mutants in other species.

  9. A strategy to discover genes that carry multi-allelic or mono-allelic risk for common diseases: A cohort allelic sums test (CAST)

    International Nuclear Information System (INIS)

    Morgenthaler, Stephan; Thilly, William G.

    2007-01-01

    A method is described to discover if a gene carries one or more allelic mutations that confer risk for any specified common disease. The method does not depend upon genetic linkage of risk-conferring mutations to high frequency genetic markers such as single nucleotide polymorphisms. Instead, the sums of allelic mutation frequencies in case and control cohorts are determined and a statistical test is applied to discover if the difference in these sums is greater than would be expected by chance. A statistical model is presented that defines the ability of such tests to detect significant gene-disease relationships as a function of case and control cohort sizes and key confounding variables: zygosity and genicity, environmental risk factors, errors in diagnosis, limits to mutant detection, linkage of neutral and risk-conferring mutations, ethnic diversity in the general population and the expectation that among all exonic mutants in the human genome greater than 90% will be neutral with regard to any effect on disease risk. Means to test the null hypothesis for, and determine the statistical power of, each test are provided. For this 'cohort allelic sums test' or 'CAST', the statistical model and test are provided as an Excel (TM) program, CASTAT (C) at http://epidemiology.mit.edu. Based on genetics, technology and statistics, a strategy of enumerating the mutant alleles carried in the exons and splice sites of the estimated ∼25,000 human genes in case cohort samples of 10,000 persons for each of 100 common diseases is proposed and evaluated: A wide range of possible conditions of multi-allelic or mono-allelic and monogenic, multigenic or polygenic (including epistatic) risk are found to be detectable using the statistical criteria of 1 or 10 ''false positive'' gene associations per 25,000 gene-disease pair-wise trials and a statistical power of >0.8. Using estimates of the distribution of both neutral and gene-inactivating nondeleterious mutations in humans and

  10. Percentiles of the null distribution of 2 maximum lod score tests.

    Science.gov (United States)

    Ulgen, Ayse; Yoo, Yun Joo; Gordon, Derek; Finch, Stephen J; Mendell, Nancy R

    2004-01-01

    We here consider the null distribution of the maximum lod score (LOD-M) obtained upon maximizing over transmission model parameters (penetrance values, dominance, and allele frequency) as well as the recombination fraction. Also considered is the lod score maximized over a fixed choice of genetic model parameters and recombination-fraction values set prior to the analysis (MMLS) as proposed by Hodge et al. The objective is to fit parametric distributions to MMLS and LOD-M. Our results are based on 3,600 simulations of samples of n = 100 nuclear families ascertained for having one affected member and at least one other sibling available for linkage analysis. Each null distribution is approximately a mixture p(2)(0) + (1 - p)(2)(v). The values of MMLS appear to fit the mixture 0.20(2)(0) + 0.80chi(2)(1.6). The mixture distribution 0.13(2)(0) + 0.87chi(2)(2.8). appears to describe the null distribution of LOD-M. From these results we derive a simple method for obtaining critical values of LOD-M and MMLS. Copyright 2004 S. Karger AG, Basel

  11. Clausius entropy for arbitrary bifurcate null surfaces

    International Nuclear Information System (INIS)

    Baccetti, Valentina; Visser, Matt

    2014-01-01

    Jacobson’s thermodynamic derivation of the Einstein equations was originally applied only to local Rindler horizons. But at least some parts of that construction can usefully be extended to give meaningful results for arbitrary bifurcate null surfaces. As presaged in Jacobson’s original article, this more general construction sharply brings into focus the questions: is entropy objectively ‘real’? Or is entropy in some sense subjective and observer-dependent? These innocent questions open a Pandora’s box of often inconclusive debate. A consensus opinion, though certainly not universally held, seems to be that Clausius entropy (thermodynamic entropy, defined via a Clausius relation dS=đQ/T) should be objectively real, but that the ontological status of statistical entropy (Shannon or von Neumann entropy) is much more ambiguous, and much more likely to be observer-dependent. This question is particularly pressing when it comes to understanding Bekenstein entropy (black hole entropy). To perhaps further add to the confusion, we shall argue that even the Clausius entropy can often be observer-dependent. In the current article we shall conclusively demonstrate that one can meaningfully assign a notion of Clausius entropy to arbitrary bifurcate null surfaces—effectively defining a ‘virtual Clausius entropy’ for arbitrary ‘virtual (local) causal horizons’. As an application, we see that we can implement a version of the generalized second law (GSL) for this virtual Clausius entropy. This version of GSL can be related to certain (nonstandard) integral variants of the null energy condition. Because the concepts involved are rather subtle, we take some effort in being careful and explicit in developing our framework. In future work we will apply this construction to generalize Jacobson’s derivation of the Einstein equations. (paper)

  12. Generalized frame of reference with null congruence

    International Nuclear Information System (INIS)

    Ferrarese, G.; Antonelli, R.

    2000-01-01

    The paper derives the main properties of a generalized frame of reference with a null congruence (light flux), by means of adapted non-holonomic techniques; then it studies the geometry of the space-time in terms of non-orthogonal projection: longitudinal and transverse covariant derivatives and corresponding commutation formulae, decomposition of the Riemann and gravitational tensors, lie derivatives of the Ricci rotation coefficients, transverse Bianchi identity. Application to the (absolute and relative) light flux: kinematical characteristics and screen, Sachs theorems etc. are also given

  13. Dall-Null tester for spaceborne applications

    Science.gov (United States)

    Wingler, R. L.

    1984-12-01

    This is a study to design a self correcting primary mirror system for a space telescope. The design is centered around a Dall-Null tester (a Foucault knife-edge tester with compensating lens). An indepth study of the theory of the Foucault test from Foucault's original publications to current work is presented. Also short comings of the diffraction approach are shown. The findings of a simple experiment showed the way to the correct explanation as to the workings of the test. Based on this new explanation, a computer program to find the error in the surface of the mirror from the irradiance pattern provided by the Dall-Null tester was developed. The computer program with a sample run is included in the appendixes A and B. The basic design of an adaptive optic system for a spaceborne application is also presented in the paper. This design has the desired quality of being able to correct the mirror while the telescope is in use. The equations being independent of wavelength allows for the design to be applied to systems working outside of the visible spectrum as well as the systems working in the visible.

  14. Averaged null energy condition from causality

    Science.gov (United States)

    Hartman, Thomas; Kundu, Sandipan; Tajdini, Amirhossein

    2017-07-01

    Unitary, Lorentz-invariant quantum field theories in flat spacetime obey mi-crocausality: commutators vanish at spacelike separation. For interacting theories in more than two dimensions, we show that this implies that the averaged null energy, ∫ duT uu , must be non-negative. This non-local operator appears in the operator product expansion of local operators in the lightcone limit, and therefore contributes to n-point functions. We derive a sum rule that isolates this contribution and is manifestly positive. The argument also applies to certain higher spin operators other than the stress tensor, generating an infinite family of new constraints of the form ∫ duX uuu··· u ≥ 0. These lead to new inequalities for the coupling constants of spinning operators in conformal field theory, which include as special cases (but are generally stronger than) the existing constraints from the lightcone bootstrap, deep inelastic scattering, conformal collider methods, and relative entropy. We also comment on the relation to the recent derivation of the averaged null energy condition from relative entropy, and suggest a more general connection between causality and information-theoretic inequalities in QFT.

  15. Recent developments with the visible nulling coronagraph

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter; Helmbrecht, Michael A.; Howard, Joseph M.; Miller, Ian J.

    2016-08-01

    A wide array of general astrophysics studies including detecting and characterizing habitable exoplanets could be enabled by a future large segmented telescope with sensitivity in the UV, optical, and infrared bands. When paired with a starshade or coronagraph, such an observatory could enable direct imaging and detailed spectroscopic observations of nearby Earth-like habitable zone planets. Over the past several years, a laboratory-based Visible Nulling Coronagraph (VNC) has evolved to reach requisite contrasts over a 1 nm bandwidth at narrow source angle separation using a segmented deformable mirror in one arm of a Mach-Zehnder layout. More recent efforts targeted broadband performance following the addition of two sets of half-wave Fresnel rhomb achromatic phase shifters (APS) with the goal of reaching 10-9 contrast, at a separation of 2λ/D, using a 40 nm (6%) bandwidth single mode fiber source. Here we present updates on the VNC broadband nulling effort, including approaches to addressing system contrast limitations.

  16. Singular Null Hypersurfaces in General Relativity

    International Nuclear Information System (INIS)

    Dray, T

    2006-01-01

    Null hypersurfaces are a mathematical consequence of the Lorentzian signature of general relativity; singularities in mathematical models usually indicate where the interesting physics takes place. This book discusses what happens when you combine these ideas. Right from the preface, this is a no-nonsense book. There are two principal approaches to singular shells, one distributional and the other 'cut and paste'; both are treated in detail. A working knowledge of GR is assumed, including familiarity with null tetrads, differential forms, and 3 + 1 decompositions. Despite my own reasonably extensive, closely related knowledge, there was material unfamiliar to me already in chapter 3, although I was reunited with some old friends in later chapters. The exposition is crisp, with a minimum of transition from chapter to chapter. In fact, my main criticism is that there is no clear statement of the organization of the book, nor is there an index. Everything is here, and the story is compelling if you know what to look for, although it is less easy to follow the story if you are not already familiar with it. But this is really a book for experts, and the authors certainly qualify, having played a significant role in developing and extending the results they describe. It is also entirely appropriate that the book is dedicated to Werner Israel, who pioneered the thin-shell approach to (non-null) singular surfaces and later championed the use of similar methods for analysing null shells. After an introductory chapter on impulsive signals, the authors show how the Bianchi identities can be used to classify spacetimes with singular null hypersurfaces. This approach, due to the authors, generalizes the framework originally proposed by Penrose. While astrophysical applications are discussed only briefly, the authors point out that detailed physical characteristics of signals from isolated sources can be determined in this manner. In particular, they describe the behaviour of

  17. Abnormal nociception and opiate sensitivity of STOP null mice exhibiting elevated levels of the endogenous alkaloid morphine

    Directory of Open Access Journals (Sweden)

    Aunis Dominique

    2010-12-01

    Full Text Available Abstract Background- Mice deficient for the stable tubule only peptide (STOP display altered dopaminergic neurotransmission associated with severe behavioural defects including disorganized locomotor activity. Endogenous morphine, which is present in nervous tissues and synthesized from dopamine, may contribute to these behavioral alterations since it is thought to play a role in normal and pathological neurotransmission. Results- In this study, we showed that STOP null brain structures, including cortex, hippocampus, cerebellum and spinal cord, contain high endogenous morphine amounts. The presence of elevated levels of morphine was associated with the presence of a higher density of mu opioid receptor with a higher affinity for morphine in STOP null brains. Interestingly, STOP null mice exhibited significantly lower nociceptive thresholds to thermal and mechanical stimulations. They also had abnormal behavioural responses to the administration of exogenous morphine and naloxone. Low dose of morphine (1 mg/kg, i.p. produced a significant mechanical antinociception in STOP null mice whereas it has no effect on wild-type mice. High concentration of naloxone (1 mg/kg was pronociceptive for both mice strain, a lower concentration (0.1 mg/kg was found to increase the mean mechanical nociceptive threshold only in the case of STOP null mice. Conclusions- Together, our data show that STOP null mice displayed elevated levels of endogenous morphine, as well as an increase of morphine receptor affinity and density in brain. This was correlated with hypernociception and impaired pharmacological sensitivity to mu opioid receptor ligands.

  18. Differential allelic expression of a fibrillin gene (FBNI) in patients with Marfan syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hewett, D.; Lynch, J.; Sykes, B. [Univ. of Oxford (United Kingdom); Firth, H. [Churchill Hospital, Oxford (United Kingdom); Child, A. [St. George`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. The authors identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3{prime} UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce <5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines. 26 refs., 4 figs.

  19. On the null origin of the ambitwistor string

    Energy Technology Data Exchange (ETDEWEB)

    Casali, Eduardo [Mathematical Institute, University of Oxford,Woodstock Road, Oxford, OX2 6GG (United Kingdom); Tourkine, Piotr [Department of Applied Mathematics and Theoretical Physics,Wilberforce Road, Cambridge, CB3 0WA (United Kingdom)

    2016-11-07

    In this paper we present the null string origin of the ambitwistor string. Classically, the null string is the tensionless limit of string theory, and so too is the ambitwistor string. Both have as constraint algebra the Galilean Conformal Algebra in two dimensions. But something interesting happens in the quantum theory since there is an ambiguity in quantizing the null string. We show that, given a particular choice of quantization scheme and a particular gauge, the null string coincides with the ambitwistor string both classically and quantum mechanically. We also show that the same holds for the spinning versions of the null string and ambitwistor string. With these results we clarify the relationship between the ambitwistor string, the null string, the usual string and the Hohm-Siegel-Zwiebach theory.

  20. Molecular analyses of the agouti allele in the Japanese house mouse identify a novel variant of the agouti gene.

    Science.gov (United States)

    Iwasa, Masahiro A; Kawamura, Sayaka; Myoshu, Hikari; Suzuki, Taichi A

    2018-03-01

    It has been thought that the Japanese house mouse carries the A w allele at the agouti locus causing light-colored bellies, but they do not always show this coloration. Thus, the presence of the A w allele seems to be doubtful in them. To ascertain whether the A w allele is present, a two-pronged approach was used. First, we compared lengths of DNA fragments obtained from three PCRs conducted on them to the known fragment sizes generated from mouse strains exhibiting homozygosities of either a/a, A/A, or A w /A w . PCR I, PCR II, and PCR III amplify only in the A and A w alleles, the a and A w alleles, and the a allele, respectively, and we detected amplifications in strains with A/A and A w /A w by PCR I, in those with a/a and the Japanese house mouse by PCR II, and in those with a/a by PCR III. Second, we sequenced the exon 1A region of the agouti gene and obtained sequences corresponding to the above strains and the Japanese house mouse, but their sequences were similar to those of the a allele. We concluded that their agouti allele is not identical to the A w allele and seems to be a novel type similar to the a allele.

  1. Technology Advancement of the Visible Nulling Coronagraph

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Thompson, Patrick; Bolcar, Matt; Madison, Timothy; Woodruff, Robert; Noecker, Charley; Kendrick, Steve

    2010-01-01

    The critical high contrast imaging technology for the Extrasolar Planetary Imaging Coronagraph (EPIC) mission concept is the visible nulling coronagraph (VNC). EPIC would be capable of imaging jovian planets, dust/debris disks, and potentially super-Earths and contribute to answering how bright the debris disks are for candidate stars. The contrast requirement for EPIC is 10(exp 9) contrast at 125 milli-arseconds inner working angle. To advance the VNC technology NASA/Goddard Space Flight Center, in collaboration with Lockheed-Martin, previously developed a vacuum VNC testbed, and achieved narrowband and broadband suppression of the core of the Airy disk. Recently our group was awarded a NASA Technology Development for Exoplanet Missions to achieve two milestones: (i) 10(exp 8) contrast in narrowband light, and, (ii) 10(ecp 9) contrast in broader band light; one milestone per year, and both at 2 Lambda/D inner working angle. These will be achieved with our 2nd generation testbed known as the visible nulling testbed (VNT). It contains a MEMS based hex-packed segmented deformable mirror known as the multiple mirror array (MMA) and coherent fiber bundle, i.e. a spatial filter array (SFA). The MMA is in one interferometric arm and works to set the wavefront differences between the arms to zero. Each of the MMA segments is optically mapped to a single mode fiber of the SFA, and the SFA passively cleans the sub-aperture wavefront error leaving only piston, tip and tilt error to be controlled. The piston degree of freedom on each segment is used to correct the wavefront errors, while the tip/tilt is used to simultaneously correct the amplitude errors. Thus the VNT controls both amplitude and wavefront errors with a single MMA in closed-loop in a vacuum tank at approx.20 Hz. Herein we will discuss our ongoing progress with the VNT.

  2. [Dilemma of null hypothesis in ecological hypothesis's experiment test.

    Science.gov (United States)

    Li, Ji

    2016-06-01

    Experimental test is one of the major test methods of ecological hypothesis, though there are many arguments due to null hypothesis. Quinn and Dunham (1983) analyzed the hypothesis deduction model from Platt (1964) and thus stated that there is no null hypothesis in ecology that can be strictly tested by experiments. Fisher's falsificationism and Neyman-Pearson (N-P)'s non-decisivity inhibit statistical null hypothesis from being strictly tested. Moreover, since the null hypothesis H 0 (α=1, β=0) and alternative hypothesis H 1 '(α'=1, β'=0) in ecological progresses are diffe-rent from classic physics, the ecological null hypothesis can neither be strictly tested experimentally. These dilemmas of null hypothesis could be relieved via the reduction of P value, careful selection of null hypothesis, non-centralization of non-null hypothesis, and two-tailed test. However, the statistical null hypothesis significance testing (NHST) should not to be equivalent to the causality logistical test in ecological hypothesis. Hence, the findings and conclusions about methodological studies and experimental tests based on NHST are not always logically reliable.

  3. Broadband Active Segmented Aperture and Radial Shear Nulling

    Data.gov (United States)

    National Aeronautics and Space Administration — The Visible Nulling Coronagraph (VNC) is a starlight suppression system for enabling exoplanet detectionand atmospheric measurement. Conceptual space telescope...

  4. Cloning of an E. coli RecA and yeast RAD51 homolog, radA, an allele of the uvsC in Aspergillus nidulans and its mutator effects.

    Science.gov (United States)

    Seong, K Y; Chae, S K; Kang, H S

    1997-04-30

    An E. coli RecA and yeast RAD51 homolog from Aspergillus nidulans, radA, has been cloned by screening genomic and cDNA libraries with a PCR-amplified probe. This probe was generated using primers carrying the conserved sequences of eukaryotic RecA homologs. The deduced amino acid sequence revealed two conserved Walker-A and -B type nucleotide-binding domains and exhibited 88%, 60%, and 53% identity with Mei-3 of Neurospora crassa, rhp51+ of Schizosaccharomyces pombe, and Rad51 of Saccharomyces cerevisiae, respectively. radA null mutants constructed by replacing the whole coding region with a selection marker showed high methyl methanesulfonate (MMS) sensitivity. Heterozygous diploids of radA disruptant with the uvsC114 mutant failed to complement with respect to MMS-sensitivity, indicating that radA is an allele of uvsC. In selecting spontaneous forward selenate resistant mutations, mutator effects were observed in radA null mutants similarly to those shown in uvsC114 mutant strains.

  5. Analysis of FBN1 allele expression by dermal fibroblasts from Marfan syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Putman, E.A.; Cao, S.N.; Milewicz, D.M. [Univ. of Texas Medical School, Houston, TX (United States)

    1994-09-01

    Screening for mutations in the FBN1 cDNA from Marfan patient cell strains has detected mutations in only 10-15% of patients. In an attempt to explain this poor detection rate, we examined FBN1 allele expression and fibrillin synthesis by 26 cell strains from Marfan patients. DNA from the patients and 10 controls was assessed for the presence of a polymorphic Rsa I restriction site in the 3{prime} untranslated region of the FBN1 gene. Twelve of 26 patient and 5 of 10 control DNAs were heterozygous. Fibroblast RNA from the heterozygous cell strains was reverse-transcribed and subsequently PCR amplified using a [{sup 32}P]-labelled primer, digested with Rsa I and analyzed. Although 3 samples showed no transcript from one allele by ethidium bromide staining, a Betagen scanner detected low levels (10-15%) of that allele. In addition, there was unequal expression of the two alleles in three other patients; for example, only 30% expression from one allele. The remaining patients and the controls had equal expression of each allele. Fibrillin protein synthesis by fibroblasts from these heterozygous patients was also examined. After a 30 minute pulse with [{sup 35}S]-cysteine, cell lysates were collected and proteins analyzed by SDS-PAGE. The amount of fibrillin produced relative to a reference protein was determined using a Betagen scanner. Fibrillin protein synthesis was reduced in 2 of the 3 patients with very low RNA production from one of the FBN1 alleles. All other Marfan and control cell strains showed normal amounts of fibrillin synthesized. The low expression levels from one allele may contribute to, but not fully account for, the low detection rate of FBN1 mutations. Interestingly, protein synthesis levels were not affected in 4 of 6 cell strains demonstrating low levels of RNA expression.

  6. Allelic variation of bile salt hydrolase genes in Lactobacillus salivarius does not determine bile resistance levels.

    LENUS (Irish Health Repository)

    Fang, Fang

    2009-09-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host.

  7. MAGNETIC NULL POINTS IN KINETIC SIMULATIONS OF SPACE PLASMAS

    International Nuclear Information System (INIS)

    Olshevsky, Vyacheslav; Innocenti, Maria Elena; Cazzola, Emanuele; Lapenta, Giovanni; Deca, Jan; Divin, Andrey; Peng, Ivy Bo; Markidis, Stefano

    2016-01-01

    We present a systematic attempt to study magnetic null points and the associated magnetic energy conversion in kinetic particle-in-cell simulations of various plasma configurations. We address three-dimensional simulations performed with the semi-implicit kinetic electromagnetic code iPic3D in different setups: variations of a Harris current sheet, dipolar and quadrupolar magnetospheres interacting with the solar wind, and a relaxing turbulent configuration with multiple null points. Spiral nulls are more likely created in space plasmas: in all our simulations except lunar magnetic anomaly (LMA) and quadrupolar mini-magnetosphere the number of spiral nulls prevails over the number of radial nulls by a factor of 3–9. We show that often magnetic nulls do not indicate the regions of intensive energy dissipation. Energy dissipation events caused by topological bifurcations at radial nulls are rather rare and short-lived. The so-called X-lines formed by the radial nulls in the Harris current sheet and LMA simulations are rather stable and do not exhibit any energy dissipation. Energy dissipation is more powerful in the vicinity of spiral nulls enclosed by magnetic flux ropes with strong currents at their axes (their cross sections resemble 2D magnetic islands). These null lines reminiscent of Z-pinches efficiently dissipate magnetic energy due to secondary instabilities such as the two-stream or kinking instability, accompanied by changes in magnetic topology. Current enhancements accompanied by spiral nulls may signal magnetic energy conversion sites in the observational data

  8. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    Science.gov (United States)

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  9. QuASAR-MPRA: accurate allele-specific analysis for massively parallel reporter assays.

    Science.gov (United States)

    Kalita, Cynthia A; Moyerbrailean, Gregory A; Brown, Christopher; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2018-03-01

    The majority of the human genome is composed of non-coding regions containing regulatory elements such as enhancers, which are crucial for controlling gene expression. Many variants associated with complex traits are in these regions, and may disrupt gene regulatory sequences. Consequently, it is important to not only identify true enhancers but also to test if a variant within an enhancer affects gene regulation. Recently, allele-specific analysis in high-throughput reporter assays, such as massively parallel reporter assays (MPRAs), have been used to functionally validate non-coding variants. However, we are still missing high-quality and robust data analysis tools for these datasets. We have further developed our method for allele-specific analysis QuASAR (quantitative allele-specific analysis of reads) to analyze allele-specific signals in barcoded read counts data from MPRA. Using this approach, we can take into account the uncertainty on the original plasmid proportions, over-dispersion, and sequencing errors. The provided allelic skew estimate and its standard error also simplifies meta-analysis of replicate experiments. Additionally, we show that a beta-binomial distribution better models the variability present in the allelic imbalance of these synthetic reporters and results in a test that is statistically well calibrated under the null. Applying this approach to the MPRA data, we found 602 SNPs with significant (false discovery rate 10%) allele-specific regulatory function in LCLs. We also show that we can combine MPRA with QuASAR estimates to validate existing experimental and computational annotations of regulatory variants. Our study shows that with appropriate data analysis tools, we can improve the power to detect allelic effects in high-throughput reporter assays. http://github.com/piquelab/QuASAR/tree/master/mpra. fluca@wayne.edu or rpique@wayne.edu. Supplementary data are available online at Bioinformatics. © The Author (2017). Published by

  10. Visual and Plastic Arts in Teaching Literacy: Null Curricula?

    Science.gov (United States)

    Wakeland, Robin Gay

    2010-01-01

    Visual and plastic arts in contemporary literacy instruction equal null curricula. Studies show that painting and sculpture facilitate teaching reading and writing (literacy), yet such pedagogy has not been formally adopted into USA curriculum. An example of null curriculum can be found in late 19th - early 20th century education the USA…

  11. Euclidean null controllability of nonlinear infinite delay systems with ...

    African Journals Online (AJOL)

    Sufficient conditions for the Euclidean null controllability of non-linear delay systems with time varying multiple delays in the control and implicit derivative are derived. If the uncontrolled system is uniformly asymptotically stable and if the control system is controllable, then the non-linear infinite delay system is Euclidean null ...

  12. Null infinity and extremal horizons in AdS-CFT

    International Nuclear Information System (INIS)

    Hickling, Andrew; Wiseman, Toby; Lucietti, James

    2015-01-01

    We consider AdS gravity duals to CFT on background spacetimes with a null infinity. Null infinity on the conformal boundary may extend to an extremal horizon in the bulk. For example it does so for Poincaré–AdS, although does not for planar Schwarzschild–AdS. If null infinity does extend into an extremal horizon in the bulk, we show that the bulk near-horizon geometry is determined by the geometry of the boundary null infinity. Hence the ‘infra-red’ geometry of the bulk is fixed by the large scale behaviour of the CFT spacetime. In addition the boundary stress tensor must have a particular decay at null infinity. As an application, we argue that for CFT on asymptotically flat backgrounds, any static bulk dual containing an extremal horizon extending from the boundary null infinity, must have the near-horizon geometry of Poincaré–AdS. We also discuss a class of boundary null infinity that cannot extend to a bulk extremal horizon, although we give evidence that they can extend to an analogous null surface in the bulk which possesses an associated scale-invariant ‘near-geometry’. (paper)

  13. Logarithmic corrections to gravitational entropy and the null energy condition

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Maulik, E-mail: maulik.parikh@asu.edu; Svesko, Andrew

    2016-10-10

    Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein–Hawking entropy.

  14. Logarithmic corrections to gravitational entropy and the null energy condition

    Directory of Open Access Journals (Sweden)

    Maulik Parikh

    2016-10-01

    Full Text Available Using a relation between the thermodynamics of local horizons and the null energy condition, we consider the effects of quantum corrections to the gravitational entropy. In particular, we find that the geometric form of the null energy condition is not affected by the inclusion of logarithmic corrections to the Bekenstein–Hawking entropy.

  15. A new dynamic null model for phylogenetic community structure

    NARCIS (Netherlands)

    Pigot, Alex L; Etienne, Rampal S

    Phylogenies are increasingly applied to identify the mechanisms structuring ecological communities but progress has been hindered by a reliance on statistical null models that ignore the historical process of community assembly. Here, we address this, and develop a dynamic null model of assembly by

  16. ENERGY DISSIPATION IN MAGNETIC NULL POINTS AT KINETIC SCALES

    International Nuclear Information System (INIS)

    Olshevsky, Vyacheslav; Lapenta, Giovanni; Divin, Andrey; Eriksson, Elin; Markidis, Stefano

    2015-01-01

    We use kinetic particle-in-cell and MHD simulations supported by an observational data set to investigate magnetic reconnection in clusters of null points in space plasma. The magnetic configuration under investigation is driven by fast adiabatic flux rope compression that dissipates almost half of the initial magnetic field energy. In this phase powerful currents are excited producing secondary instabilities, and the system is brought into a state of “intermittent turbulence” within a few ion gyro-periods. Reconnection events are distributed all over the simulation domain and energy dissipation is rather volume-filling. Numerous spiral null points interconnected via their spines form null lines embedded into magnetic flux ropes; null point pairs demonstrate the signatures of torsional spine reconnection. However, energy dissipation mainly happens in the shear layers formed by adjacent flux ropes with oppositely directed currents. In these regions radial null pairs are spontaneously emerging and vanishing, associated with electron streams and small-scale current sheets. The number of spiral nulls in the simulation outweighs the number of radial nulls by a factor of 5–10, in accordance with Cluster observations in the Earth's magnetosheath. Twisted magnetic fields with embedded spiral null points might indicate the regions of major energy dissipation for future space missions such as the Magnetospheric Multiscale Mission

  17. On the Robinson theorem and shearfree geodesic null congruences

    International Nuclear Information System (INIS)

    Tafel, J.

    1985-01-01

    Null electromagnetic fields and shearfree geodesic null congruences in curved and flat spacetimes are studied. We point out some mathematical problems connected with the validity of the Robinson theorem. The problem of finding nonanalytic twisting congruences in the Minkowski space is reduced to the construction of holomorphic functions with specific boundary conditions. (orig.)

  18. Assessment of the myostatin Q204X allele using an allelic discrimination assay

    OpenAIRE

    Sifuentes-Rincón,Ana M.; Puentes-Montiel,Herlinda E.; Moreno-Medina,Víctor R.; Rosa-Reyna,Xóchitl F. de la

    2006-01-01

    An allelic discrimination assay was designed and used to determine the genotypic and allelic frequencies of the myostatin (MSTN) gene Q204X allele from two Mexican Full-French herds. The assay is a simple high throughput genotyping method that could be applied to investigate the effect of the Q204X allele on the Charolais breed.

  19. An omnibus test for the global null hypothesis.

    Science.gov (United States)

    Futschik, Andreas; Taus, Thomas; Zehetmayer, Sonja

    2018-01-01

    Global hypothesis tests are a useful tool in the context of clinical trials, genetic studies, or meta-analyses, when researchers are not interested in testing individual hypotheses, but in testing whether none of the hypotheses is false. There are several possibilities how to test the global null hypothesis when the individual null hypotheses are independent. If it is assumed that many of the individual null hypotheses are false, combination tests have been recommended to maximize power. If, however, it is assumed that only one or a few null hypotheses are false, global tests based on individual test statistics are more powerful (e.g. Bonferroni or Simes test). However, usually there is no a priori knowledge on the number of false individual null hypotheses. We therefore propose an omnibus test based on cumulative sums of the transformed p-values. We show that this test yields an impressive overall performance. The proposed method is implemented in an R-package called omnibus.

  20. The Visible Nulling Coronagraph--Architecture Definition and Technology Development

    Science.gov (United States)

    Shao, Michael; Levine, B. Martin; Wallace, J. Kent; Liu, Duncan T.; Schmidtlin, Edouard; Serabyn, Eugene; Mennesson, Bertrand; Green, Joseph J.; Aguayo, Francisco; Fregoso, S. Felipe; hide

    2005-01-01

    This paper describes the advantages of visible direct detection and spectroscopy of Earth-like extrasolar planets using a nulling coronagraph instrument behind a moderately sized single aperture space telescope. Our concept synthesizes a nulling interferometer by shearing the telescope pupil, with the resultant producing a deep null. We describe nulling configurations that also include methods to mitigate stellar leakage, such as spatial filtering by a coherent array of single mode fibers, and post-starlight suppression wavefront sensing and control. With diffraction limited telescope optics and similar quality components in the optical train (lambda/20), suppression of the starlight to 1e-10 is readily achievable. We describe key features of the architecture and analysis, present latest results of laboratory measurements demonstrating achievable null depth and component development, and discuss future key technical milestones.

  1. N-ethyl-N-nitrosourea-induced null mutation at the mouse Car-2 locus: An animal model for human carbonic anhydrase II deficiency syndrome

    International Nuclear Information System (INIS)

    Lewis, S.E.; Barnett, L.B.; Erickson, R.P.; Venta, P.J.; Tashian, R.E.

    1988-01-01

    Electrophoretic screening of (C57BL/6J x DBA/2J)F 1 progeny of male mice treated with N-ethyl-N-nitrosourea revealed a mouse that lacked the paternal carbonic anhydrase II (Ca II). Breeding tests showed that this trait was heritable and due to a null mutation at the Car-2 locus on chromosome 3. Like humans with the same inherited enzyme defect, animals homozygous for the new null allele are runted and have renal tubular acidosis. However, the prominent osteopetrosis found in humans with CA II deficiency could be detected even in very old homozygous null mice. A molecular analysis of the deficient mice shows that the mutant gene is not deleted and is transcribed. The CA II protein, which is normally expressed in most tissues, could not be detected by immunodiffusion analysis in any tissues of the CA II-deficient mice, suggesting a nonsense or a missense mutation at the Car-2 locus

  2. Wormholes minimally violating the null energy condition

    Energy Technology Data Exchange (ETDEWEB)

    Bouhmadi-López, Mariam [Departamento de Física, Universidade da Beira Interior, 6200 Covilhã (Portugal); Lobo, Francisco S N; Martín-Moruno, Prado, E-mail: mariam.bouhmadi@ehu.es, E-mail: fslobo@fc.ul.pt, E-mail: pmmoruno@fc.ul.pt [Centro de Astronomia e Astrofísica da Universidade de Lisboa, Campo Grande, Edifício C8, 1749-016 Lisboa (Portugal)

    2014-11-01

    We consider novel wormhole solutions supported by a matter content that minimally violates the null energy condition. More specifically, we consider an equation of state in which the sum of the energy density and radial pressure is proportional to a constant with a value smaller than that of the inverse area characterising the system, i.e., the area of the wormhole mouth. This approach is motivated by a recently proposed cosmological event, denoted {sup t}he little sibling of the big rip{sup ,} where the Hubble rate and the scale factor blow up but the cosmic derivative of the Hubble rate does not [1]. By using the cut-and-paste approach, we match interior spherically symmetric wormhole solutions to an exterior Schwarzschild geometry, and analyse the stability of the thin-shell to linearized spherically symmetric perturbations around static solutions, by choosing suitable properties for the exotic material residing on the junction interface radius. Furthermore, we also consider an inhomogeneous generalization of the equation of state considered above and analyse the respective stability regions. In particular, we obtain a specific wormhole solution with an asymptotic behaviour corresponding to a global monopole.

  3. Bodyweight Assessment of Enamelin Null Mice

    Directory of Open Access Journals (Sweden)

    Albert H.-L. Chan

    2013-01-01

    Full Text Available The Enam null mice appear to be smaller than wild-type mice, which prompted the hypothesis that enamel defects negatively influence nutritional intake and bodyweight gain (BWG. We compared the BWG of Enam−/− and wild-type mice from birth (D0 to Day 42 (D42. Wild-type (WT and Enam−/− (N mice were given either hard chow (HC or soft chow (SC. Four experimental groups were studied: WTHC, WTSC, NHC, and NSC. The mother’s bodyweight (DBW and the average litter bodyweight (ALBW were obtained from D0 to D21. After D21, the pups were separated from the mother and provided the same type of food. Litter bodyweights were measured until D42. ALBW was compared at 7-day intervals using one-way ANOVA, while the influence of DBW on ALBW was analyzed by mixed-model analyses. The ALBW of Enam−/− mice maintained on hard chow (NHC was significantly lower than the two WT groups at D21 and the differences persisted into young adulthood. The ALBW of Enam−/− mice maintained on soft chow (NSC trended lower, but was not significantly different than that of the WT groups. We conclude that genotype, which affects enamel integrity, and food hardness influence bodyweight gain in postnatal and young adult mice.

  4. Characterization of ROP18 alleles in human toxoplasmosis.

    Science.gov (United States)

    Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

    2014-04-01

    The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis. © 2013.

  5. Improvements to a Markerless Allelic Exchange System for Bacillus anthracis.

    Directory of Open Access Journals (Sweden)

    Roger D Plaut

    Full Text Available A system was previously developed for conducting I-SceI-mediated allelic exchange in Bacillus anthracis. In this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease I-SceI. Although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in B. anthracis, researchers are nonetheless required to "pick and patch" colonies in order to identify candidate "exchangeants." In the present study, a number of improvements have been made to this system: 1 an improved I-SceI-producing plasmid includes oriT so that both plasmids can now be introduced by conjugation, thus avoiding the need for preparing electro-competent cells of each integration intermediate; 2 antibiotic markers have been changed to allow the use of the system in select agent strains; and 3 both plasmids have been marked with fluorescent proteins, allowing the visualization of plasmid segregation on a plate and obviating the need for "picking and patching." These modifications have made the process easier, faster, and more efficient, allowing for parallel construction of larger numbers of mutant strains. Using this improved system, the genes encoding the tripartite anthrax toxin were deleted singly and in combination from plasmid pXO1 of Sterne strain 34F2. In the course of this study, we determined that DNA transfer to B. anthracis could be accomplished by conjugation directly from a methylation-competent E. coli strain.

  6. Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related Alleles in Botrytis cinerea

    OpenAIRE

    Zhang, Xin; Xie, Fei; Lv, Baobei; Zhao, Pengxiang; Ma, Xuemei

    2016-01-01

    A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension (ASPE) assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA), H272 and 272Y of the Succinate dehydrogenase iron–sulfur...

  7. Identification, genetic localization, and allelic diversity of selectively amplified microsatellite polymorphic loci in lettuce and wild relatives (Lactuca spp.).

    Science.gov (United States)

    Witsenboer, H; Michelmore, R W; Vogel, J

    1997-12-01

    Selectively amplified microsatellite polymorphic locus (SAMPL) analysis is a method of amplifying microsatellite loci using generic PCR primers. SAMPL analysis uses one AFLP primer in combination with a primer complementary to microsatellite sequences. SAMPL primers based on compound microsatellite sequences provided the clearest amplification patterns. We explored the potential of SAMPL analysis in lettuce to detect PCR-based codominant microsatellite markers. Fifty-eight SAMPLs were identified and placed on the genetic map. Seventeen were codominant. SAMPLs were dispersed with RFLP markers on 11 of the 12 main linkage groups in lettuce, indicating that they have a similar genomic distribution. Some but not all fragments amplified by SAMPL analysis were confirmed to contain microsatellite sequences by Southern hybridization. Forty-five cultivars of lettuce and five wild species of Lactuca were analyzed to determine the allelic diversity for codominant SAMPLs. From 3 to 11 putative alleles were found for each SAMPL; 2-6 alleles were found within Lactuca sativa and 1-3 alleles were found among the crisphead genotypes, the most genetically homogeneous plant type of L. sativa. This allelic diversity is greater than that found for RFLP markers. Numerous new alleles were observed in the wild species; however, there were frequent null alleles. Therefore, SAMPL analysis is more applicable to intraspecific than to interspecific comparisons. A phenetic analysis based on SAMPLs resulted in a dendrogram similar to those based on RFLP and AFLP markers.

  8. Tensionless branes and the null string critical dimension

    International Nuclear Information System (INIS)

    Bozhilov, P.

    1998-01-01

    BRST quantization is carried out for a model of p-branes with second class constraints. After extension of the phase space the constraint algebra coincides with the one of null string when p=1. It is shown that in this case one can or cannot obtain critical dimension for the null string, depending on the choice of the operator ordering and corresponding vacuum states. When p>1, operator orderings leading to critical dimension in the p=1 case are not allowed. Admissible orderings give no restrictions on the dimension of the embedding space-time. Finally, a generalization to supersymmetric null branes is proposed

  9. An Updated Collection of Sequence Barcoded Temperature-Sensitive Alleles of Yeast Essential Genes.

    Science.gov (United States)

    Kofoed, Megan; Milbury, Karissa L; Chiang, Jennifer H; Sinha, Sunita; Ben-Aroya, Shay; Giaever, Guri; Nislow, Corey; Hieter, Philip; Stirling, Peter C

    2015-07-14

    Systematic analyses of essential gene function using mutant collections in Saccharomyces cerevisiae have been conducted using collections of heterozygous diploids, promoter shut-off alleles, through alleles with destabilized mRNA, destabilized protein, or bearing mutations that lead to a temperature-sensitive (ts) phenotype. We previously described a method for construction of barcoded ts alleles in a systematic fashion. Here we report the completion of this collection of alleles covering 600 essential yeast genes. This resource covers a larger gene repertoire than previous collections and provides a complementary set of strains suitable for single gene and genomic analyses. We use deep sequencing to characterize the amino acid changes leading to the ts phenotype in half of the alleles. We also use high-throughput approaches to describe the relative ts behavior of the alleles. Finally, we demonstrate the experimental usefulness of the collection in a high-content, functional genomic screen for ts alleles that increase spontaneous P-body formation. By increasing the number of alleles and improving the annotation, this ts collection will serve as a community resource for probing new aspects of biology for essential yeast genes. Copyright © 2015 Kofoed et al.

  10. Emission and null coordinates: geometrical properties and physical construction

    International Nuclear Information System (INIS)

    Coll, Bartolome; Ferrando, Joan J; Morales-Lladosa, Juan A

    2011-01-01

    A Relativistic Positioning System is defined by four clocks (emitters) broadcasting their proper time. Then, every event reached by the signals is naturally labeled by these four times which are the emission coordinates of this event. The coordinate hypersurfaces of the emission coordinates are the future light cones based on the emitter trajectories. For this reason the emission coordinates have been also named null coordinates or light coordinates. Nevertheless, other coordinate systems used in different relativistic contexts have the own right to be named null or light coordinates. Here we analyze when one can say that a coordinate is a null coordinate and when one can say that a coordinate system is null. Moreover, we examine the physical construction and the geometrical properties of several n ull coordinate systems : the emission and the reception coordinates, the radar coordinates, and the Bondi-Sachs coordinates, among others.

  11. Relative null controllability of linear systems with multiple delays in ...

    African Journals Online (AJOL)

    varying multiple delays in state and control are developed. If the uncontrolled system is uniformly asymptotically stable, and if the linear system is controllable, then the linear system is null controllable. Journal of the Nigerian Association of ...

  12. Null canonical formalism 1, Maxwell field. [Poisson brackets, boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Wodkiewicz, K [Warsaw Univ. (Poland). Inst. Fizyki Teoretycznej

    1975-01-01

    The purpose of this paper is to formulate the canonical formalism on null hypersurfaces for the Maxwell electrodynamics. The set of the Poisson brackets relations for null variables of the Maxwell field is obtained. The asymptotic properties of the theory are investigated. The Poisson bracket relations for the news-functions of the Maxwell field are computed. The Hamiltonian form of the asymptotic Maxwell equations in terms of these news-functions is obtained.

  13. Null controllability of a cascade system of Schrodinger equations

    Directory of Open Access Journals (Sweden)

    Marcos Lopez-Garcia

    2016-03-01

    Full Text Available This article presents a control problem for a cascade system of two linear N-dimensional Schrodinger equations. We address the problem of null controllability by means of a control supported in a region not satisfying the classical geometrical control condition. The proof is based on the application of a Carleman estimate with degenerate weights to each one of the equations and a careful analysis of the system in order to prove null controllability with only one control force.

  14. Sequential weak continuity of null Lagrangians at the boundary

    Czech Academy of Sciences Publication Activity Database

    Kalamajska, A.; Kraemer, S.; Kružík, Martin

    2014-01-01

    Roč. 49, 3/4 (2014), s. 1263-1278 ISSN 0944-2669 R&D Projects: GA ČR GAP201/10/0357 Institutional support: RVO:67985556 Keywords : null Lagrangians * nonhomogeneous nonlinear mappings * sequential weak/in measure continuity Subject RIV: BA - General Mathematics Impact factor: 1.518, year: 2014 http://library.utia.cas.cz/separaty/2013/MTR/kruzik-sequential weak continuity of null lagrangians at the boundary.pdf

  15. On the geometry of null congruences in general relativity

    International Nuclear Information System (INIS)

    Ahsan, Zafar; Malik, N.P.

    1977-01-01

    Some theorems for the null congruences within the framework of general theory of relativity are given. These theorems are important in themselves as they illustrate the geometric meaning of the spin coefficients. The newly developed Geroch-Held-Penrose (GHP) formalism has been used throughout the investigations. The salient features of GHP formalism that are necessary for the present work are given and these techniques are applied to a pair of null congruences C(l) and C(n). (author)

  16. A parameter set for a double-null DEMO reactor

    International Nuclear Information System (INIS)

    Cooke, P.I.H.

    1987-01-01

    The present study is aimed at commenting on the reactor-relevance of the design principles and technology being proposed for NET. The authors propose that a double-null device serve as a basis for a NET-based demonstration reactor. Calculations are carried out to determine the parameter set for reactors based on the double-null NET design, and the results are presented in tabular form. (U.K.)

  17. Vortical null orbits, repulsive barriers, energy confinement in Kerr metric

    Energy Technology Data Exchange (ETDEWEB)

    Calvani, M [Padua Univ. (Italy). Ist. di Astronomia; De Felice, F

    1978-10-01

    The complete analytical description of the null trajectories in the field of a Kerr naked singularity is given. Two peculiar phenomena are described: the existence of repulsive barriers in the r < O world and the existence of null circular bound orbits which surround the singularity in 'shells'. They distribute around the surface at r = m, which is the position of the horizon in the extreme black-hole case; this suggests that a naked singularity 'remembers' the position of the last horizon.

  18. Ambitwistor strings at null infinity and (subleading) soft limits

    International Nuclear Information System (INIS)

    Geyer, Yvonne; Lipstein, Arthur E; Mason, Lionel

    2015-01-01

    The relationship between BMS symmetries at null infinity and Weinberg's soft theorems for gravitons and photons together with their subleading extensions are developed using ambitwistor string theory. Ambitwistor space is the phase space of complex null geodesics in complexified space-time. We show how it can be canonically identified with the cotangent bundle of complexified null infinity. BMS symmetries of null infinity lift to give a Hamiltonian action on ambitwistor space, both in general dimension and in its twistorial four-dimensional representation. General vertex operators arise from Hamiltonians generating diffeomorphisms of ambitwistor space that determine the scattering from past to future null infinity. When a momentum eigenstate goes soft, the diffeomorphism defined by its leading and its subleading part are extended BMS generators realized in the world sheet conformal field theory of the ambitwistor string. More generally, this gives an explicit perturbative correspondence between the scattering of null geodesics and that of the gravitational field via ambitwistor string theory. (paper)

  19. Absence of the HLA-G*0113N allele in Amerindian populations from the Brazilian Amazon region.

    Science.gov (United States)

    Mendes-Junior, Celso T; Castelli, Erick C; Moreau, Philippe; Simões, Aguinaldo L; Donadi, Eduardo A

    2010-04-01

    The HLA-G gene is predominantly expressed at the maternal-fetal interface and has been associated with maternal-fetal tolerance. The HLA-G*0113N is a null allele defined by the insertion of a premature stop codon at exon 2, observed in a single Ghanaian individual. Likewise the G*0105N allele, the occurrence of the HLA-G*0113N in a population from an area with high pathogen load suggests that the reduced HLA-G expression in G*0113N heterozygous placentas could improve the intrauterine defense against infections. The presence of the G*0113N allele here was investigated in 150 Amerindians from five isolated tribes that inhabit the Central Amazon and in 295 admixed individuals from the State of São Paulo, Southeastern Brazil, previously genotyped for HLA-G. No copy of the G*0113N null allele was found in both population samples by exon 2 sequence-based analysis, reinforcing its restricted occurrence in Africa.

  20. Compound Heterozygosity for Null Mutations and a Common Hypomorphic Risk Haplotype in TBX6 Causes Congenital Scoliosis.

    Science.gov (United States)

    Takeda, Kazuki; Kou, Ikuyo; Kawakami, Noriaki; Iida, Aritoshi; Nakajima, Masahiro; Ogura, Yoji; Imagawa, Eri; Miyake, Noriko; Matsumoto, Naomichi; Yasuhiko, Yukuto; Sudo, Hideki; Kotani, Toshiaki; Nakamura, Masaya; Matsumoto, Morio; Watanabe, Kota; Ikegawa, Shiro

    2017-03-01

    Congenital scoliosis (CS) occurs as a result of vertebral malformations and has an incidence of 0.5-1/1,000 births. Recently, TBX6 on chromosome 16p11.2 was reported as a disease gene for CS; about 10% of Chinese CS patients were compound heterozygotes for rare null mutations and a common haplotype defined by three SNPs in TBX6. All patients had hemivertebrae. We recruited 94 Japanese CS patients, investigated the TBX6 locus for both mutations and the risk haplotype, examined transcriptional activities of mutant TBX6 in vitro, and evaluated clinical and radiographic features. We identified TBX6 null mutations in nine patients, including a missense mutation that had a loss of function in vitro. All had the risk haplotype in the opposite allele. One of the mutations showed dominant negative effect. Although all Chinese patients had one or more hemivertebrae, two Japanese patients did not have hemivertebra. The compound heterozygosity of null mutations and the common risk haplotype in TBX6 also causes CS in Japanese patients with similar incidence. Hemivertebra was not a specific type of spinal malformation in TBX6-associated CS (TACS). A heterozygous TBX6 loss-of-function mutation has been reported in a family with autosomal-dominant spondylocostal dysostosis, but it may represent a spectrum of the same disease with TACS. © 2017 WILEY PERIODICALS, INC.

  1. Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

    Directory of Open Access Journals (Sweden)

    Jennifer E Kerr

    Full Text Available Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions.

  2. Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

    Science.gov (United States)

    Kerr, Jennifer E; Abramian, Jared R; Dao, Doan-Hieu V; Rigney, Todd W; Fritz, Jamie; Pham, Tan; Gay, Isabel; Parthasarathy, Kavitha; Wang, Bing-yan; Zhang, Wenjian; Tribble, Gena D

    2014-01-01

    Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions.

  3. Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

    Directory of Open Access Journals (Sweden)

    Elissa J. Chesler

    2016-12-01

    Full Text Available Multi-parent populations (MPPs capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

  4. Resistivity at the field null of the FRC plasma

    International Nuclear Information System (INIS)

    Gerwin, R.A.

    1989-01-01

    In the absence of the major destructive instabilities, the configuration time is ultimately determined by particle and flux containment. If the profiles are ''gentle,'' then the anomalous flux-loss rate depends essentially on the anomalous resistivity at the field null. Conventional electrostatic quasi-linear models of anomalous cross-field resistive diffusivity are based upon the use of rvec E x rvec B drift velocities, and hence break down at the magnetic field null. In this paper, an electromagnetic treatment valid at the field null is developed, based upon the presence of flute-parity perturbations. An expression for anomalous resistivity at the field null in the quasi-linear approximation is derived by averaging in the ignorable direction over the random phases of the perturbations. The expression is valid for arbitrary (non-local) radial shapes of the perturbing modes (for example, the eigenfunctions need not be centered at the field null), and for an arbitrary ratio of real frequency to growth rate. The effective resistivity due to flute perturbations of the MHD type will be considered. 1 ref

  5. Evaluation of null-point detection methods on simulation data

    Science.gov (United States)

    Olshevsky, Vyacheslav; Fu, Huishan; Vaivads, Andris; Khotyaintsev, Yuri; Lapenta, Giovanni; Markidis, Stefano

    2014-05-01

    We model the measurements of artificial spacecraft that resemble the configuration of CLUSTER propagating in the particle-in-cell simulation of turbulent magnetic reconnection. The simulation domain contains multiple isolated X-type null-points, but the majority are O-type null-points. Simulations show that current pinches surrounded by twisted fields, analogous to laboratory pinches, are formed along the sequences of O-type nulls. In the simulation, the magnetic reconnection is mainly driven by the kinking of the pinches, at spatial scales of several ion inertial lentghs. We compute the locations of magnetic null-points and detect their type. When the satellites are separated by the fractions of ion inertial length, as it is for CLUSTER, they are able to locate both the isolated null-points, and the pinches. We apply the method to the real CLUSTER data and speculate how common are pinches in the magnetosphere, and whether they play a dominant role in the dissipation of magnetic energy.

  6. Visible nulling coronagraphy testbed development for exoplanet detection

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert A.; Vasudevan, Gopal; Thompson, Patrick; Chen, Andrew; Petrone, Peter; Booth, Andrew; Madison, Timothy; Bolcar, Matthew; Noecker, M. Charley; Kendrick, Stephen; Melnick, Gary; Tolls, Volker

    2010-07-01

    Three of the recently completed NASA Astrophysics Strategic Mission Concept (ASMC) studies addressed the feasibility of using a Visible Nulling Coronagraph (VNC) as the prime instrument for exoplanet science. The VNC approach is one of the few approaches that works with filled, segmented and sparse or diluted aperture telescope systems and thus spans the space of potential ASMC exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies and has developed an incremental sequence of VNC testbeds to advance the this approach and the technologies associated with it. Herein we report on the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under high bandwidth closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible light nulling milestones of sequentially higher contrasts of 108, 109 and 1010 at an inner working angle of 2*λ/D and ultimately culminate in spectrally broadband (>20%) high contrast imaging. Each of the milestones, one per year, is traceable to one or more of the ASMC studies. The VNT uses a modified Mach-Zehnder nulling interferometer, modified with a modified "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. Discussed will be the optical configuration laboratory results, critical technologies and the null sensing and control approach.

  7. Tolerance analysis of null lenses using an end-use system performance criterion

    Science.gov (United States)

    Rodgers, J. Michael

    2000-07-01

    An effective method of assigning tolerances to a null lens is to determine the effects of null-lens fabrication and alignment errors on the end-use system itself, not simply the null lens. This paper describes a method to assign null- lens tolerances based on their effect on any performance parameter of the end-use system.

  8. Null but not void: considerations for hypothesis testing.

    Science.gov (United States)

    Shaw, Pamela A; Proschan, Michael A

    2013-01-30

    Standard statistical theory teaches us that once the null and alternative hypotheses have been defined for a parameter, the choice of the statistical test is clear. Standard theory does not teach us how to choose the null or alternative hypothesis appropriate to the scientific question of interest. Neither does it tell us that in some cases, depending on which alternatives are realistic, we may want to define our null hypothesis differently. Problems in statistical practice are frequently not as pristinely summarized as the classic theory in our textbooks. In this article, we present examples in statistical hypothesis testing in which seemingly simple choices are in fact rich with nuance that, when given full consideration, make the choice of the right hypothesis test much less straightforward. Published 2012. This article is a US Government work and is in the public domain in the USA.

  9. Unicorns do exist: a tutorial on "proving" the null hypothesis.

    Science.gov (United States)

    Streiner, David L

    2003-12-01

    Introductory statistics classes teach us that we can never prove the null hypothesis; all we can do is reject or fail to reject it. However, there are times when it is necessary to try to prove the nonexistence of a difference between groups. This most often happens within the context of comparing a new treatment against an established one and showing that the new intervention is not inferior to the standard. This article first outlines the logic of "noninferiority" testing by differentiating between the null hypothesis (that which we are trying to nullify) and the "nill" hypothesis (there is no difference), reversing the role of the null and alternate hypotheses, and defining an interval within which groups are said to be equivalent. We then work through an example and show how to calculate sample sizes for noninferiority studies.

  10. ISCO and Principal Null Congruences in Extremal Kerr Spacetime

    International Nuclear Information System (INIS)

    Pradhan, Parthapratim

    2012-01-01

    The effective potential in universal like coordinates(U, V, θ, φ), which are smooth across the event horizon is derived and investigated the ISCO(Innermost Stable Circular Orbits) explicitly in these coordinates for extremal Kerr spacetime. Extremization of the effective potential for timelike circular orbit shows that the existence of a stable circular geodesics in the extremal spacetime for direct orbit, precisely on the event horizon in terms of the radial coordinate which coincides with the principal null geodesic congruences of the event horizon. These null geodesic congruences mold themselves to the spacetime curvature in such a way that Weyl conformal tensor and its dual are vanished, that is why they are in-fact doubly degenerate principal null congruences.

  11. Phase-space lagrangians for null spinning strings

    International Nuclear Information System (INIS)

    Barcelos-Neto, J.; Ruiz-Altaba, M.; Ramirez, C.

    1990-01-01

    The striking fact that normal-ordered null strings have the same critical dimension as their usual non-zero tension siblings can be understood from the observation that one must, in the tensionless case, keep all the conjugate momenta as independent dynamical variables, thus doubling the number of physical degrees of freedom. The fermionic momenta give rise to a second-class constraint which cannot be solved covariantly, but can be successfully incorporated into the first-class constraint algebra after gauge-fixing. The ghost contributions to the anomaly consist of two b-c (and also two β-γ systems in the supersymmetric case), of the single Virasoro sub(super)algebra for the closed null (spinning) string. In the appropriate gauge, the null (super)string is (super)chiral. (orig.)

  12. Allelic Variation of Bile Salt Hydrolase Genes in Lactobacillus salivarius Does Not Determine Bile Resistance Levels▿ †

    Science.gov (United States)

    Fang, Fang; Li, Yin; Bumann, Mario; Raftis, Emma J.; Casey, Pat G.; Cooney, Jakki C.; Walsh, Martin A.; O'Toole, Paul W.

    2009-01-01

    Commensal lactobacilli frequently produce bile salt hydrolase (Bsh) enzymes whose roles in intestinal survival are unclear. Twenty-six Lactobacillus salivarius strains from different sources all harbored a bsh1 allele on their respective megaplasmids. This allele was related to the plasmid-borne bsh1 gene of the probiotic strain UCC118. A second locus (bsh2) was found in the chromosomes of two strains that had higher bile resistance levels. Four Bsh1-encoding allele groups were identified, defined by truncations or deletions involving a conserved residue. In vitro analyses showed that this allelic variation was correlated with widely varying bile deconjugation phenotypes. Despite very low activity of the UCC118 Bsh1 enzyme, a mutant lacking this protein had significantly lower bile resistance, both in vitro and during intestinal transit in mice. However, the overall bile resistance phenotype of this and other strains was independent of the bsh1 allele type. Analysis of the L. salivarius transcriptome upon exposure to bile and cholate identified a multiplicity of stress response proteins and putative efflux proteins that appear to broadly compensate for, or mask, the effects of allelic variation of bsh genes. Bsh enzymes with different bile-degrading kinetics, though apparently not the primary determinants of bile resistance in L. salivarius, may have additional biological importance because of varying effects upon bile as a signaling molecule in the host. PMID:19592587

  13. Microangiopathic complications related to different alleles of ...

    African Journals Online (AJOL)

    Egyptian Journal of Biochemistry and Molecular Biology. Journal Home ... Microangiopathic complications related to different alleles of manganese superoxide dismutase gene in diabetes mellitus type 1. TM EL Masry ... 23(2) 2005: 155-167 ...

  14. Evidence for complete epistasis of null mutations in murine Fanconi anemia genes Fanca and Fancg.

    Science.gov (United States)

    van de Vrugt, Henri J; Koomen, Mireille; Bakker, Sietske; Berns, Mariska A D; Cheng, Ngan Ching; van der Valk, Martin A; de Vries, Yne; Rooimans, Martin A; Oostra, Anneke B; Hoatlin, Maureen E; Te Riele, Hein; Joenje, Hans; Arwert, Fré

    2011-12-10

    Fanconi anemia (FA) is a heritable disease characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. The 15 identified FA genes operate in a molecular pathway to preserve genomic integrity. Within this pathway the FA core complex operates as an ubiquitin ligase that activates the complex of FANCD2 and FANCI to coordinate DNA repair. The FA core complex is formed by at least 12 proteins. However, only the FANCL subunit displays ubiquitin ligase activity. FANCA and FANCG are members of the FA core complex for which no other functions have been described than to participate in protein interactions. In this study we generated mice with combined null alleles for Fanca and Fancg to identify extended functions for these genes by characterizing the double mutant mice and cells. Double mutant a(-/-)/g(-/-) mice were born at near Mendelian frequencies without apparent developmental abnormalities. Histological analysis of a(-/-)/g(-/-) mice revealed a Leydig cell hyperplasia and frequent vacuolization of Sertoli cells in testes, while ovaries were depleted from developing follicles and displayed an interstitial cell hyperplasia. These gonadal aberrations were associated with a compromised fertility of a(-/-)/g(-/-) males and females. During the first year of life a(-/-)/g(-/-) did not develop malignancies or bone marrow failure. At the cellular level a(-/-)/g(-/-), Fanca(-/-), and Fancg(-/-) cells proved equally compromised in DNA crosslink and homology-directed repair. Overall the phenotype of a(-/-)/g(-/-) double knockout mice and cells appeared highly similar to the phenotype of Fanca or Fancg single knockouts. The lack of an augmented phenotype suggest that null mutations in Fanca or Fancg are fully epistatic, making additional important functions outside of the FA core complex highly unlikely. 2011 Elsevier B.V. All rights reserved.

  15. Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA.

    Science.gov (United States)

    Royle, N J; Armour, J A; Crosier, M; Jeffreys, A J

    1993-01-01

    Somatic events that result in the reduction to hemi- or homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis.

  16. Alpha-1 antitrypsin deficiency caused by a novel mutation (p.Leu263Pro: Pi*ZQ0gaia – Q0gaia allele

    Directory of Open Access Journals (Sweden)

    M.J. Oliveira

    2015-11-01

    Full Text Available Severe alpha-1 antitrypsin deficiency (AATD is generally associated with PI*ZZ genotype and less often with combinations of PI*Z, PI*S, and other rarer deficiency or null (Q0 alleles. Severe AATD predisposes patients to various diseases, including pulmonary emphysema. Presented here is a case report of a young man with COPD and AATD. The investigation of the AATD showed a novel mutation p.Leu263Pro (c.860T>C, which was named Q0gaia (Pi*ZQ0gaia. Q0gaia is associated with very low or no detectable serum concentrations of AAT. Keywords: Alpha-1 antitrypsin deficiency, Null allele, COPD

  17. Testing the null hypothesis: the forgotten legacy of Karl Popper?

    Science.gov (United States)

    Wilkinson, Mick

    2013-01-01

    Testing of the null hypothesis is a fundamental aspect of the scientific method and has its basis in the falsification theory of Karl Popper. Null hypothesis testing makes use of deductive reasoning to ensure that the truth of conclusions is irrefutable. In contrast, attempting to demonstrate the new facts on the basis of testing the experimental or research hypothesis makes use of inductive reasoning and is prone to the problem of the Uniformity of Nature assumption described by David Hume in the eighteenth century. Despite this issue and the well documented solution provided by Popper's falsification theory, the majority of publications are still written such that they suggest the research hypothesis is being tested. This is contrary to accepted scientific convention and possibly highlights a poor understanding of the application of conventional significance-based data analysis approaches. Our work should remain driven by conjecture and attempted falsification such that it is always the null hypothesis that is tested. The write up of our studies should make it clear that we are indeed testing the null hypothesis and conforming to the established and accepted philosophical conventions of the scientific method.

  18. Euclidean null controllability of perturbed infinite delay systems with ...

    African Journals Online (AJOL)

    Euclidean null controllability of perturbed infinite delay systems with limited control. ... Open Access DOWNLOAD FULL TEXT ... The results are established by placing conditions on the perturbation function which guarantee that, if the linear control base system is completely Euclidean controllable, then the perturbed system ...

  19. Euclidean null controllability of linear systems with delays in state ...

    African Journals Online (AJOL)

    Sufficient conditions are developed for the Euclidean controllability of linear systems with delay in state and in control. Namely, if the uncontrolled system is uniformly asymptotically stable and the control equation proper, then the control system is Euclidean null controllable. Journal of the Nigerian Association of ...

  20. Future null infinity of Robertson-Walker spacetimes

    International Nuclear Information System (INIS)

    Moreschi, O.M.

    1988-08-01

    The future null infinity for all non-contracting Robertson-Walker space time is studied systematically. A theorem is proved which establishes the expected relation between the nature of J + and the appearance or absence of cosmic event horizons. (author). 7 refs, 1 tab

  1. The Many Null Distributions of Person Fit Indices.

    Science.gov (United States)

    Molenaar, Ivo W.; Hoijtink, Herbert

    1990-01-01

    Statistical properties of person fit indices are reviewed as indicators of the extent to which a person's score pattern is in agreement with a measurement model. Distribution of a fit index and ability-free fit evaluation are discussed. The null distribution was simulated for a test of 20 items. (SLD)

  2. Spatial and null infinity via advanced and retarded conformal factors

    International Nuclear Information System (INIS)

    Hayward, Sean A.

    2003-01-01

    A new approach to space-time asymptotics is presented, refining Penrose's idea of conformal transformations with infinity represented by the conformal boundary of space-time. It is proposed that the Penrose conformal factor be a product of advanced and retarded conformal factors, which asymptotically relate physical and conformal null coordinates and vanish at future and past null infinity respectively. A refined definition of asymptotic flatness at both spatial and null infinity is given, including that the conformal boundary is locally a light cone, with spatial infinity as the vertex. It is shown how to choose the conformal factors so that this asymptotic light cone is locally a metric light cone. The theory is implemented in the spin-coefficient (or null-tetrad) formalism by a joint transformation of the spin-metric and spin-basis (or metric and tetrad). Asymptotic regularity conditions are proposed, based on the conformal boundary locally being a smoothly embedded metric light cone. These conditions ensure that the Bondi-Sachs energy-flux integrals of ingoing and outgoing gravitational radiation decay at spatial infinity such that the total radiated energy is finite, and that the Bondi-Sachs energy-momentum has a unique limit at spatial infinity, coinciding with the uniquely rendered ADM energy-momentum

  3. On the null distribution of Bayes factors in linear regression

    Science.gov (United States)

    We show that under the null, the 2 log (Bayes factor) is asymptotically distributed as a weighted sum of chi-squared random variables with a shifted mean. This claim holds for Bayesian multi-linear regression with a family of conjugate priors, namely, the normal-inverse-gamma prior, the g-prior, and...

  4. Magnetic Reconnection at a Three-dimensional Solar Null Point

    DEFF Research Database (Denmark)

    Frederiksen, Jacob Trier; Baumann, Gisela; Galsgaard, Klaus

    2012-01-01

    Using a specific solar null point reconnection case studied by Masson et al (2009; ApJ 700, 559) we investigate the dependence of the reconnection rate on boundary driving speed, numerical resolution, type of resistivity (constant or numerical), and assumed stratification (constant density or sol...

  5. Null point of discrimination in crustacean polarisation vision.

    Science.gov (United States)

    How, Martin J; Christy, John; Roberts, Nicholas W; Marshall, N Justin

    2014-07-15

    The polarisation of light is used by many species of cephalopods and crustaceans to discriminate objects or to communicate. Most visual systems with this ability, such as that of the fiddler crab, include receptors with photopigments that are oriented horizontally and vertically relative to the outside world. Photoreceptors in such an orthogonal array are maximally sensitive to polarised light with the same fixed e-vector orientation. Using opponent neural connections, this two-channel system may produce a single value of polarisation contrast and, consequently, it may suffer from null points of discrimination. Stomatopod crustaceans use a different system for polarisation vision, comprising at least four types of polarisation-sensitive photoreceptor arranged at 0, 45, 90 and 135 deg relative to each other, in conjunction with extensive rotational eye movements. This anatomical arrangement should not suffer from equivalent null points of discrimination. To test whether these two systems were vulnerable to null points, we presented the fiddler crab Uca heteropleura and the stomatopod Haptosquilla trispinosa with polarised looming stimuli on a modified LCD monitor. The fiddler crab was less sensitive to differences in the degree of polarised light when the e-vector was at -45 deg than when the e-vector was horizontal. In comparison, stomatopods showed no difference in sensitivity between the two stimulus types. The results suggest that fiddler crabs suffer from a null point of sensitivity, while stomatopods do not. © 2014. Published by The Company of Biologists Ltd.

  6. Null Lens Assembly for X-Ray Mirror Segments

    Science.gov (United States)

    Robinson, David W.

    2011-01-01

    A document discusses a null lens assembly that allows laser interferometry of 60 deg. slumped glass mirror segments used in x-ray mirrors. The assembly consists of four lenses in precise alignment to each other, with incorporated piezoelectric nanometer stepping actuators to position the lenses in six degrees of freedom for positioning relative to each other.

  7. Self-Nulling Beam Combiner Using No External Phase Inverter

    Science.gov (United States)

    Bloemhof, Eric E.

    2010-01-01

    A self-nulling beam combiner is proposed that completely eliminates the phase inversion subsystem from the nulling interferometer, and instead uses the intrinsic phase shifts in the beam splitters. Simplifying the flight instrument in this way will be a valuable enhancement of mission reliability. The tighter tolerances on R = T (R being reflection and T being transmission coefficients) required by the self-nulling configuration actually impose no new constraints on the architecture, as two adaptive nullers must be situated between beam splitters to correct small errors in the coatings. The new feature is exploiting the natural phase shifts in beam combiners to achieve the 180 phase inversion necessary for nulling. The advantage over prior art is that an entire subsystem, the field-flipping optics, can be eliminated. For ultimate simplicity in the flight instrument, one might fabricate coatings to very high tolerances and dispense with the adaptive nullers altogether, with all their moving parts, along with the field flipper subsystem. A single adaptive nuller upstream of the beam combiner may be required to correct beam train errors (systematic noise), but in some circumstances phase chopping reduces these errors substantially, and there may be ways to further reduce the chop residuals. Though such coatings are beyond the current state of the art, the mechanical simplicity and robustness of a flight system without field flipper or adaptive nullers would perhaps justify considerable effort on coating fabrication.

  8. Visible Nulling Coronagraphy for Exo-Planetary Detection and Characterization

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Woodruff, Robert; Vasudevan, Gopal; Shao, Mike; Levine, Martin; Melnick, Gary; Tolls, Volker; Petrone, Peter; Dogoda, Peter; Duval, Julia; Ge, Jian

    Visible Nulling Coronagraphy (VNC) is the proposed method of detecting and characterizing exo-solar Jovian planets (null depth 10-9) for the proposed NASA's Extrasolar Planetary Imaging Coronagraph (EPIC) Clampin & Lyon 2004 and is an approach under evaluation for NASA's Terrestrial Planet Finder (TPF) mission. The VNC approach uses a single unobscured filled-aperture telescope and splits, via a 50:50 beamsplitter, its re-imaged pupil into two paths within a Mach-Zender interferometer. An achromatic PI phase shift is imposed onto one beam path and the two paths are laterally sheared with respect to each other. The two beams are recombined at a second 50:50 beamsplitter. The net effect is that the on axis (stellar) light is transmitted out of the bright interferometer arm while the off-axis (planetary) light is transmitted out of the nulled interferometer arm. The bright output is used for fine pointing control and coarse wavefront control. The nulled output is relayed to the science camera for science imagery and fine wavefront control. The actual transmission pattern, projected on the sky, follows a θ^2 pattern for a single shear, θ^4 for a double shear, with the spacing of the successive maxima proportional to the inverse of the relative lateral shear. Combinations of shears and spacecraft rolls build up the spatial frequency content of the sky transmission pattern in the same manner as imaging interferometer builds up the spatial frequency content of the image.

  9. Shaping Up the Practice of Null Hypothesis Significance Testing.

    Science.gov (United States)

    Wainer, Howard; Robinson, Daniel H.

    2003-01-01

    Discusses criticisms of null hypothesis significance testing (NHST), suggesting that historical use of NHST was reasonable, and current users should read Sir Ronald Fisher's applied work. Notes that modifications to NHST and interpretations of its outcomes might better suit the needs of modern science. Concludes that NHST is most often useful as…

  10. Relative controllability and null controllability of linear delay systems ...

    African Journals Online (AJOL)

    Necessary and sufficient conditions are established for the relative, absolute controllability and null controllability of the generalized linear delay system and its discrete prototype. The paper presents illuminating examples on previous controllability results by Manitius and Olbrot [7] and carries over the results of Onwuatu [8] ...

  11. A model for electron currents near a field null

    International Nuclear Information System (INIS)

    Stark, R.A.; Miley, G.H.

    1987-01-01

    The fluid approximation is invalid near a field null, since the local electron orbit size and the magnetic scale length are comparable. To model the electron currents in this region we propose a single equation of motion describing the bulk electron dynamics. The equation applies to the plasma within one thermal orbit size of the null. The region is treated as unmagnetized; electrons are accelerated by the inductive electric field and drag on ions; damping is provided by viscosity due to electrons and collisions with ions. Through variational calculations and a particle tracking code for electrons, the size of the terms in the equation of motion have been estimated. The resulting equation of motion combines with Faraday's Law to produce a governing equation which implicitly contains the self inductive field of the electrons. This governing equation predicts that viscosity prevents complete cancellation of the ion current density by the electrons in the null region. Thus electron dynamics near the field null should not prevent the formation and deepening of field reversal using neutral-beam injection

  12. A comment on the null geodesic equations in Schwarzschild geometry

    International Nuclear Information System (INIS)

    Rosa, M.A.F.; Rodrigues Junior, W.A.

    1986-01-01

    An integration of the null geodesic equations in the Schwarzschild geometry, which is valid to first order in GM/Rc 2 is presented. The solution is compared with others published in the literature and their range of validity is analysed. Some misunderstandings are also clarified. (Author) [pt

  13. Maxwell fields and shear-free null geodesic congruences

    International Nuclear Information System (INIS)

    Newman, Ezra T

    2004-01-01

    We study and report on the class of vacuum Maxwell fields in Minkowski space that possess a non-degenerate, diverging, principal null vector field (null eigenvector field of the Maxwell tensor) that is tangent to a shear-free null geodesics congruence. These congruences can be either surface forming (the tangent vectors being proportional to gradients) or not, i.e., the twisting congruences. In the non-twisting case, the associated Maxwell fields are precisely the Lienard-Wiechert fields, i.e., those Maxwell fields arising from an electric monopole moving on an arbitrary worldline. The null geodesic congruence is given by the generators of the light-cones with apex on the worldline. The twisting case is much richer, more interesting and far more complicated. In a twisting subcase, where our main interests lie, the following strange interpretation can be given. If we allow the real Minkowski space to be complexified so that the real Minkowski coordinates x a take complex values, i.e., x a → z a = x a + iy a with complex metric g η ab dz a dz b , the real vacuum Maxwell equations can be extended into the complex space and rewritten as curl W=i W radical, div W=0 with W=E+iB. This subcase of Maxwell fields can then be extended into the complex space so as to have as source, a complex analytic worldline, i.e., to now become complex Lienard-Wiechart fields. When viewed as real fields on the real Minkowski space (z a = x a ), they possess a real principal null vector that is shear-free but twisting and diverging. The twist is a measure of how far the complex worldline is from the real 'slice'. Most Maxwell fields in this subcase are asymptotically flat with a time-varying set of electric and magnetic moments, all depending on the complex displacements and the complex velocities

  14. The murine Cd48 gene: allelic polymorphism in the IgV-like region.

    Science.gov (United States)

    Cabrero, J G; Freeman, G J; Reiser, H

    1998-12-01

    The murine CD48 molecule is a member of the immunoglobulin superfamily which regulates the activation of T lymphocytes. prior cloning experiments using mRNA from two different mouse strains had yielded discrepant sequences within the IgV-like domain of murine CD48. To resolve this issue, we have directly sequenced genomic DNA of 10 laboratory strains and two inbred strains of wild origin. The results of our analysis reveal an allelic polymorphism within the IgV-like domain of murine CD48.

  15. Reversal of the ΔdegP Phenotypes by a Novel rpoE Allele of Escherichia coli

    Science.gov (United States)

    Leiser, Owen P.; Charlson, Emily S.; Gerken, Henri; Misra, Rajeev

    2012-01-01

    RseA sequesters RpoE (σE) to the inner membrane of Escherichia coli when envelope stress is low. Elevated envelope stress triggers RseA cleavage by the sequential action of two membrane proteases, DegS and RseP, releasing σE to activate an envelope stress reducing pathway. Revertants of a ΔdegP ΔbamB strain, which fails to grow at 37°C due to high envelope stress, harbored mutations in the rseA and rpoE genes. Null and missense rseA mutations constitutively hyper-activated the σE regulon and significantly reduced the major outer membrane protein (OMP) levels. In contrast, a novel rpoE allele, rpoE3, resulting from the partial duplication of the rpoE gene, increased σE levels greater than that seen in the rseA mutant background but did not reduce OMP levels. A σE-dependent RybB::LacZ construct showed only a weak activation of the σE pathway by rpoE3. Despite this, rpoE3 fully reversed the growth and envelope vesiculation phenotypes of ΔdegP. Interestingly, rpoE3 also brought down the modestly activated Cpx envelope stress pathway in the ΔdegP strain to the wild type level, showing the complementary nature of the σE and Cpx pathways. Through employing a labile mutant periplasmic protein, AcrAL222Q, it was determined that the rpoE3 mutation overcomes the ΔdegP phenotypes, in part, by activating a σE-dependent proteolytic pathway. Our data suggest that a reduction in the OMP levels is not intrinsic to the σE-mediated mechanism of lowering envelope stress. They also suggest that under extreme envelope stress, a tight homeostasis loop between RseA and σE may partly be responsible for cell death, and this loop can be broken by mutations that either lower RseA activity or increase σE levels. PMID:22439016

  16. A Comparison of Plasma Performance Between Single-Null and Double-Null Configurations During Elming H-Mode

    International Nuclear Information System (INIS)

    Petrie, T.W.; Fenstermacher, M.E.; Allen, S.L.; Carlstrom, T.N.; Gohil, P.; Groebner, R.J.; Greenfield, C.M.; Hyatt, A.W.; Lasnier, C.J.; La Haye, R.J.; Leonard, A.W.; Mahdavi, M.A.; Osborne, T.H.; Porter, G.D.; Rhodes, T.L.; Thomas, D.M.; Watkins, J.G.; West, W.P.; Wolf, N.S.

    1999-01-01

    Tokamak plasma performance generally improves with increased shaping of the plasma cross section, such as higher elongation and higher triangularity. The stronger shaping, especially higher triangularity, leads to changes in the magnetic topology of the divertor. Because there are engineering and divertor physics issues associated with changes in the details of the divertor flux geometry, especially as the configuration transitions from a single-null (SN) divertor to a marginally balanced double-null (DN) divertor, we have undertaken a systematic evaluation of the plasma characteristics as the magnetic geometry is varied, particularly with respect to (1) energy confinement, (2) the response of the plasma to deuterium gas fueling, (3) the operational density range for the ELMing H-mode, and (4) heat flux sharing by the diverters. To quantify the degree of divertor imbalance (or equivalently, to what degree the shape is double-null or single-null), we define a parameter DRSEP. DRSEP is taken as the radial distance between the upper divertor separatrix and the lower divertor separatrix, as determined at the outboard midplane. For example, if DRSEP=O, the configuration is a magnetically balanced DN; if DRSEP = +1.0 cm, the divertor configuration is biased toward the upper divertor. Three examples are shown in Fig. 1. In the following discussions, VB drift is directed toward the lower divertor

  17. Estimated allele substitution effects underlying genomic evaluation models depend on the scaling of allele counts

    NARCIS (Netherlands)

    Bouwman, Aniek C.; Hayes, Ben J.; Calus, Mario P.L.

    2017-01-01

    Background: Genomic evaluation is used to predict direct genomic values (DGV) for selection candidates in breeding programs, but also to estimate allele substitution effects (ASE) of single nucleotide polymorphisms (SNPs). Scaling of allele counts influences the estimated ASE, because scaling of

  18. Detection of long nulls in PSR B1706-16, a pulsar with large timing irregularities

    Science.gov (United States)

    Naidu, Arun; Joshi, Bhal Chandra; Manoharan, P. K.; Krishnakumar, M. A.

    2018-04-01

    Single pulse observations, characterizing in detail, the nulling behaviour of PSR B1706-16 are being reported for the first time in this paper. Our regular long duration monitoring of this pulsar reveals long nulls of 2-5 h with an overall nulling fraction of 31 ± 2 per cent. The pulsar shows two distinct phases of emission. It is usually in an active phase, characterized by pulsations interspersed with shorter nulls, with a nulling fraction of about 15 per cent, but it also rarely switches to an inactive phase, consisting of long nulls. The nulls in this pulsar are concurrent between 326.5 and 610 MHz. Profile mode changes accompanied by changes in fluctuation properties are seen in this pulsar, which switches from mode A before a null to mode B after the null. The distribution of null durations in this pulsar is bimodal. With its occasional long nulls, PSR B1706-16 joins the small group of intermediate nullers, which lie between the classical nullers and the intermittent pulsars. Similar to other intermediate nullers, PSR B1706-16 shows high timing noise, which could be due to its rare long nulls if one assumes that the slowdown rate during such nulls is different from that during the bursts.

  19. High frequency induction of mitotic recombination by ionizing radiation in Mlh1 null mouse cells

    International Nuclear Information System (INIS)

    Wang Qi; Ponomareva, Olga N.; Lasarev, Michael; Turker, Mitchell S.

    2006-01-01

    Mitotic recombination in somatic cells involves crossover events between homologous autosomal chromosomes. This process can convert a cell with a heterozygous deficiency to one with a homozygous deficiency if a mutant allele is present on one of the two homologous autosomes. Thus mitotic recombination often represents the second mutational step in tumor suppressor gene inactivation. In this study we examined the frequency and spectrum of ionizing radiation (IR)-induced autosomal mutations affecting Aprt expression in a mouse kidney cell line null for the Mlh1 mismatch repair (MMR) gene. The mutant frequency results demonstrated high frequency induction of mutations by IR exposure and the spectral analysis revealed that most of this response was due to the induction of mitotic recombinational events. High frequency induction of mitotic recombination was not observed in a DNA repair-proficient cell line or in a cell line with an MMR-independent mutator phenotype. These results demonstrate that IR exposure can initiate a process leading to mitotic recombinational events and that MMR function suppresses these events from occurring

  20. Allelic genealogies in sporophytic self-incompatibility systems in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1998-01-01

    , alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self...

  1. 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.

  2. The loss-of-allele assay for ES cell screening and mouse genotyping.

    Science.gov (United States)

    Frendewey, David; Chernomorsky, Rostislav; Esau, Lakeisha; Om, Jinsop; Xue, Yingzi; Murphy, Andrew J; Yancopoulos, George D; Valenzuela, David M

    2010-01-01

    Targeting vectors used to create directed mutations in mouse embryonic stem (ES) cells consist, in their simplest form, of a gene for drug selection flanked by mouse genomic sequences, the so-called homology arms that promote site-directed homologous recombination between the vector and the target gene. The VelociGene method for the creation of targeted mutations in ES cells employs targeting vectors, called BACVecs, that are based on bacterial artificial chromosomes. Compared with conventional short targeting vectors, BacVecs provide two major advantages: (1) their much larger homology arms promote high targeting efficiencies without the need for isogenicity or negative selection strategies; and (2) they enable deletions and insertions of up to 100kb in a single targeting event, making possible gene-ablating definitive null alleles and other large-scale genomic modifications. Because of their large arm sizes, however, BACVecs do not permit screening by conventional assays, such as long-range PCR or Southern blotting, that link the inserted targeting vector to the targeted locus. To exploit the advantages of BACVecs for gene targeting, we inverted the conventional screening logic in developing the loss-of-allele (LOA) assay, which quantifies the number of copies of the native locus to which the mutation was directed. In a correctly targeted ES cell clone, the LOA assay detects one of the two native alleles (for genes not on the X or Y chromosome), the other allele being disrupted by the targeted modification. We apply the same principle in reverse as a gain-of-allele assay to quantify the copy number of the inserted targeting vector. The LOA assay reveals a correctly targeted clone as having lost one copy of the native target gene and gained one copy of the drug resistance gene or other inserted marker. The combination of these quantitative assays makes LOA genotyping unequivocal and amenable to automated scoring. We use the quantitative polymerase chain reaction

  3. Nonparametric Regression Estimation for Multivariate Null Recurrent Processes

    Directory of Open Access Journals (Sweden)

    Biqing Cai

    2015-04-01

    Full Text Available This paper discusses nonparametric kernel regression with the regressor being a \\(d\\-dimensional \\(\\beta\\-null recurrent process in presence of conditional heteroscedasticity. We show that the mean function estimator is consistent with convergence rate \\(\\sqrt{n(Th^{d}}\\, where \\(n(T\\ is the number of regenerations for a \\(\\beta\\-null recurrent process and the limiting distribution (with proper normalization is normal. Furthermore, we show that the two-step estimator for the volatility function is consistent. The finite sample performance of the estimate is quite reasonable when the leave-one-out cross validation method is used for bandwidth selection. We apply the proposed method to study the relationship of Federal funds rate with 3-month and 5-year T-bill rates and discover the existence of nonlinearity of the relationship. Furthermore, the in-sample and out-of-sample performance of the nonparametric model is far better than the linear model.

  4. Pair of null gravitating shells: III. Algebra of Dirac's observables

    International Nuclear Information System (INIS)

    Kouletsis, I; Hajicek, P

    2002-01-01

    The study of the two-shell system started in 'pair of null gravitating shells I and II' is continued. The pull back of the Liouville form to the constraint surface, which contains complete information about the Poisson brackets of Dirac observables, is computed in the singular double-null Eddington-Finkelstein (DNEF) gauge. The resulting formula shows that the variables conjugate to the Schwarzschild masses of the intershell spacetimes are simple combinations of the values of the DNEF coordinates on these spacetimes at the shells. The formula is valid for any number of in- and outgoing shells. After applying it to the two-shell system, the symplectic form is calculated for each component of the physical phase space; regular coordinates are found, defining it as a symplectic manifold. The symplectic transformation between the initial and final values of observables for the shell-crossing case is given

  5. Local modular Hamiltonians from the quantum null energy condition

    Science.gov (United States)

    Koeller, Jason; Leichenauer, Stefan; Levine, Adam; Shahbazi-Moghaddam, Arvin

    2018-03-01

    The vacuum modular Hamiltonian K of the Rindler wedge in any relativistic quantum field theory is given by the boost generator. Here we investigate the modular Hamiltonian for more general half-spaces which are bounded by an arbitrary smooth cut of a null plane. We derive a formula for the second derivative of the modular Hamiltonian with respect to the coordinates of the cut which schematically reads K''=Tv v . This formula can be integrated twice to obtain a simple expression for the modular Hamiltonian. The result naturally generalizes the standard expression for the Rindler modular Hamiltonian to this larger class of regions. Our primary assumptions are the quantum null energy condition—an inequality between the second derivative of the von Neumann entropy of a region and the stress tensor—and its saturation in the vacuum for these regions. We discuss the validity of these assumptions in free theories and holographic theories to all orders in 1 /N .

  6. Segmented Aperture Interferometric Nulling Testbed (SAINT) II: component systems update

    Science.gov (United States)

    Hicks, Brian A.; Bolcar, Matthew R.; Helmbrecht, Michael A.; Petrone, Peter; Burke, Elliot; Corsetti, James; Dillon, Thomas; Lea, Andrew; Pellicori, Samuel; Sheets, Teresa; Shiri, Ron; Agolli, Jack; DeVries, John; Eberhardt, Andrew; McCabe, Tyler

    2017-09-01

    This work presents updates to the coronagraph and telescope components of the Segmented Aperture Interferometric Nulling Testbed (SAINT). The project pairs an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC) towards demonstrating capabilities for the future space observatories needed to directly detect and characterize a significant sample of Earth-sized worlds around nearby stars in the quest for identifying those which may be habitable and possibly harbor life. Efforts to improve the VNC wavefront control optics and mechanisms towards repeating narrowband results are described. A narrative is provided for the design of new optical components aimed at enabling broadband performance. Initial work with the hardware and software interface for controlling the segmented telescope mirror is also presented.

  7. Lovelock vacua with a recurrent null vector field

    Czech Academy of Sciences Publication Activity Database

    Ortaggio, Marcello

    2018-01-01

    Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals.aps.org/prd/abstract/10.1103/PhysRevD.97.044051

  8. Spherical null geodesics of rotating Kerr black holes

    International Nuclear Information System (INIS)

    Hod, Shahar

    2013-01-01

    The non-equatorial spherical null geodesics of rotating Kerr black holes are studied analytically. Unlike the extensively studied equatorial circular orbits whose radii are known analytically, no closed-form formula exists in the literature for the radii of generic (non-equatorial) spherical geodesics. We provide here an approximate formula for the radii r ph (a/M;cosi) of these spherical null geodesics, where a/M is the dimensionless angular momentum of the black hole and cos i is an effective inclination angle (with respect to the black-hole equatorial plane) of the orbit. It is well-known that the equatorial circular geodesics of the Kerr spacetime (the prograde and the retrograde orbits with cosi=±1) are characterized by a monotonic dependence of their radii r ph (a/M;cosi=±1) on the dimensionless spin-parameter a/M of the black hole. We use here our novel analytical formula to reveal that this well-known property of the equatorial circular geodesics is actually not a generic property of the Kerr spacetime. In particular, we find that counter-rotating spherical null orbits in the range (3√(3)−√(59))/4≲cosi ph (a/M;cosi=const) on the dimensionless rotation-parameter a/M of the black hole. Furthermore, it is shown that spherical photon orbits of rapidly-rotating black holes are characterized by a critical inclination angle, cosi=√(4/7), above which the coordinate radii of the orbits approach the black-hole radius in the extremal limit. We prove that this critical inclination angle signals a transition in the physical properties of the spherical null geodesics: in particular, it separates orbits which are characterized by finite proper distances to the black-hole horizon from orbits which are characterized by infinite proper distances to the horizon.

  9. The quantum null energy condition in curved space

    Science.gov (United States)

    Fu, Zicao; Koeller, Jason; Marolf, Donald

    2017-11-01

    The quantum null energy condition (QNEC) is a conjectured bound on components (Tkk = Tab ka k^b) of the stress tensor along a null vector k a at a point p in terms of a second k-derivative of the von Neumann entropy S on one side of a null congruence N through p generated by k a . The conjecture has been established for super-renormalizeable field theories at points p that lie on a bifurcate Killing horizon with null tangent k a and for large-N holographic theories on flat space. While the Koeller-Leichenauer holographic argument clearly yields an inequality for general ( p, k^a) , more conditions are generally required for this inequality to be a useful QNEC. For d≤slant 3 , for arbitrary backgroud metric we show that the QNEC is naturally finite and independent of renormalization scheme when the expansion θ of N at the point p vanishes. This is consistent with the original QNEC conjecture which required θ and the shear σab to satisfy θ \\vert _p= \\dotθ\\vert p =0 , σab\\vert _p=0 . But for d=4, 5 more conditions than even these are required. In particular, we also require the vanishing of additional derivatives and a dominant energy condition. In the above cases the holographic argument does indeed yield a finite QNEC, though for d≥slant6 we argue these properties to fail even for weakly isolated horizons (where all derivatives of θ, σab vanish) that also satisfy a dominant energy condition. On the positive side, a corrollary to our work is that, when coupled to Einstein-Hilbert gravity, d ≤slant 3 holographic theories at large N satisfy the generalized second law (GSL) of thermodynamics at leading order in Newton’s constant G. This is the first GSL proof which does not require the quantum fields to be perturbations to a Killing horizon.

  10. Null half-supersymmetric solutions in five-dimensional supergravity

    International Nuclear Information System (INIS)

    Grover, Jai; Gutowski, Jan B.; Sabra, Wafic

    2008-01-01

    We classify half-supersymmetric solutions of gauged N = 2, D = 5 supergravity coupled to an arbitrary number of abelian vector multiplets for which all of the Killing spinors generate null Killing vectors. We show that there are four classes of solutions, and in each class we find the metric, scalars and gauge field strengths. When the scalar manifold is symmetric, the solutions correspond to a class of local near horizon geometries recently found by Kunduri and Lucietti.

  11. Yang-Mills theory in null path space

    International Nuclear Information System (INIS)

    Kent, S.L.

    1982-01-01

    A reformulation of classical GL(n,c) Yang-Mills theory is presented. The reformulation is in terms of a single matrix-valued function G on a six-dimensional subspace of the space of paths in Minkowski space, M. This subspace is defined as the null paths beginning at each point, (X/sup a/), of M and ending at future null infinity. A convenient parametrization of these paths is to give the Minkowski coordinates x/sup a/ of the starting point and the (complex) stereographic coordinates (xi, antixi) on S 2 which label the light cone generators of x/sup a/. A path is thus labeled by (x/sup a/,xi, antixi). The function G(x/sup a/,xi, antixi) is defined by the parallel propagation (with a given connection) of n linearly independent fiber vectors from x/sup a/ to null infinity along the (xi, antixi) generator. From knowledge of G(x/sup a/,xi, antixi) the connection one-form γ/sub a/ at the point x/sup a/ can be obtained is shown. Furthermore how the vacuum Yang-Mills equations can be imposed on the G is shown. This results in a rather complicated integro-differential equation for G which involves the characteristic initial data (essentially the radiation field) acting as the driving term. Two simple special cases are immediately obtainable; in the case of self-dual (or anti-self dual) fields the author obtains a simple derivation of the Sparling equation, namely delta G = -GA, while for Abelian (Maxwell) theories obtained the equation delta anti delta log G = -anti delta A-anti delta A, where A and its conjugate anti A are the characteristic free data given on null infinity. The latter equation is equivalent to the vacuum Maxwell equations

  12. Shearfree congruences of null geodesics and Killing tensors

    International Nuclear Information System (INIS)

    Dietz, W.; Ruediger, R.

    1980-01-01

    In this communication, the mutual connections between quantities that are generalizations of the notion of a a Killing vector field are investigated. A classification of these quantities in terms of a complex vector field αsub(a) is given. A common feature of all these quantities is that they imply the existence of a pair of shearfree geodetic null congruences. There are no explicit restrictions posed on the Ricci tensor. (author)

  13. Lovelock vacua with a recurrent null vector field

    Czech Academy of Sciences Publication Activity Database

    Ortaggio, Marcello

    2018-01-01

    Roč. 97, č. 4 (2018), č. článku 044051. ISSN 2470-0010 R&D Projects: GA ČR GA13-10042S Institutional support: RVO:67985840 Keywords : Lovelock gravity * recurrent null vector field Subject RIV: BA - General Mathematics OBOR OECD: Applied mathematics Impact factor: 4.568, year: 2016 https://journals. aps .org/prd/abstract/10.1103/PhysRevD.97.044051

  14. In Search of the Null: The NCSA 2003 Presidential Address

    Directory of Open Access Journals (Sweden)

    Beth Davison

    2003-10-01

    Full Text Available Sociologists usually publish articles where the results show statistically significant differences between two groups of people. Results which show the opposite are generally called 'negative findings,' and are not considered publishable. Davison argues that we really ought to be looking for and encouraging the null finding, especially when social inequality and poverty are the issue. In addition, society as a whole should be working to eliminate poverty and inequality

  15. Toll-like receptor 4 mutant and null mice retain morphine-induced tolerance, hyperalgesia, and physical dependence.

    Directory of Open Access Journals (Sweden)

    Theresa Alexandra Mattioli

    Full Text Available The innate immune system modulates opioid-induced effects within the central nervous system and one target that has received considerable attention is the toll-like receptor 4 (TLR4. Here, we examined the contribution of TLR4 in the development of morphine tolerance, hyperalgesia, and physical dependence in two inbred mouse strains: C3H/HeJ mice which have a dominant negative point mutation in the Tlr4 gene rendering the receptor non-functional, and B10ScNJ mice which are TLR4 null mutants. We found that neither acute antinociceptive response to a single dose of morphine, nor the development of analgesic tolerance to repeated morphine treatment, was affected by TLR4 genotype. Likewise, opioid induced hyperalgesia and opioid physical dependence (assessed by naloxone precipitated withdrawal were not altered in TLR4 mutant or null mice. We also examined the behavioural consequence of two stereoisomers of naloxone: (- naloxone, an opioid receptor antagonist, and (+ naloxone, a purported antagonist of TLR4. Both stereoisomers of naloxone suppressed opioid induced hyperalgesia in wild-type control, TLR4 mutant, and TLR4 null mice. Collectively, our data suggest that TLR4 is not required for opioid-induced analgesic tolerance, hyperalgesia, or physical dependence.

  16. Zero emission city. Preliminary study; Null-Emissions-Stadt. Sondierungsstudie

    Energy Technology Data Exchange (ETDEWEB)

    Diefenbach, N; Enseling, A; Werner, P; Flade, A; Greiff, R; Hennings, D; Muehlich, E; Wullkopf, U; Sturm, P; Kieslich, W; Born, R; Grossklos, M; Hatteh, R; Mueller, K; Ratschow, A; Valouch-Fornoff, C

    2002-10-01

    The idea of a 'zero emission city' is investigated by the Institut Wohnen und Umwelt on behalf of the Federal Minister of Education and Research. After describing the current situation and defining the key parameters of a 'zero emission city', settlement structures, power supply, production processes and transportation are analyzed and linked with the communal action level to obtain a framework for research, activities and actions. The study ends with recommendations for a research programme 'zero emission city'. (orig.) [German] Die von den Staedten der Industrielaender ausgehenden Emissionen stellen im Hinblick auf die globalen Belastungen wie z.B. Treibhauseffekt, Ozonabbau und Versauerung das Hauptproblem dar. Aus diesem Grunde bietet es sich an, den Gedanken der 'Null-Emissions-Stadt', der Vision einer moeglichst emissionsfreien Stadt, aufzugreifen und auf seine Tragfaehigkeit fuer innovative Handlungsmodelle forschungsstrategisch zu ueberpruefen. Das Bundesministerium fuer Bildung und Forschung hat das Institut Wohnen und Umwelt beauftragt, in einer Sondierungsstudie dieser Fragestellung nachzugehen. Nach der Festlegung der Ausgangsbedingungen und Eckpunkte der Vision 'Null-Emissions-Stadt' und der Analyse der vier Handlungsfelder Siedlungsstrukturen, Energieversorgung, Produktionsprozesse (Kreislaufwirtschaft) und Verkehr werden diese aufgegriffen und mit der kommunalen Handlungsebene verknuepft und zu einem Forschungs-, Handlungs- und moeglichen Aktionsrahmen zusammengefuegt. Die Studie schliesst mit Hinweisen fuer die Gestaltung eines Forschungsprogramms 'Null-Emissions-Stadt'. (orig.)

  17. The Quantum Focussing Conjecture and Quantum Null Energy Condition

    Science.gov (United States)

    Koeller, Jason

    Evidence has been gathering over the decades that spacetime and gravity are best understood as emergent phenomenon, especially in the context of a unified description of quantum mechanics and gravity. The Quantum Focussing Conjecture (QFC) and Quantum Null Energy Condition (QNEC) are two recently-proposed relationships between entropy and geometry, and energy and entropy, respectively, which further strengthen this idea. In this thesis, we study the QFC and the QNEC. We prove the QNEC in a variety of contexts, including free field theories on Killing horizons, holographic theories on Killing horizons, and in more general curved spacetimes. We also consider the implications of the QFC and QNEC in asymptotically flat space, where they constrain the information content of gravitational radiation arriving at null infinity, and in AdS/CFT, where they are related to other semiclassical inequalities and properties of boundary-anchored extremal area surfaces. It is shown that the assumption of validity and vacuum-state saturation of the QNEC for regions of flat space defined by smooth cuts of null planes implies a local formula for the modular Hamiltonian of these regions. We also demonstrate that the QFC as originally conjectured can be violated in generic theories in d ≥ 5, which led the way to an improved formulation subsequently suggested by Stefan Leichenauer.

  18. Zero emission city. Preliminary study; Null-Emissions-Stadt. Sondierungsstudie

    Energy Technology Data Exchange (ETDEWEB)

    Diefenbach, N.; Enseling, A.; Werner, P.; Flade, A.; Greiff, R.; Hennings, D.; Muehlich, E.; Wullkopf, U.; Sturm, P.; Kieslich, W.; Born, R.; Grossklos, M.; Hatteh, R.; Mueller, K.; Ratschow, A.; Valouch-Fornoff, C.

    2002-10-01

    The idea of a 'zero emission city' is investigated by the Institut Wohnen und Umwelt on behalf of the Federal Minister of Education and Research. After describing the current situation and defining the key parameters of a 'zero emission city', settlement structures, power supply, production processes and transportation are analyzed and linked with the communal action level to obtain a framework for research, activities and actions. The study ends with recommendations for a research programme 'zero emission city'. (orig.) [German] Die von den Staedten der Industrielaender ausgehenden Emissionen stellen im Hinblick auf die globalen Belastungen wie z.B. Treibhauseffekt, Ozonabbau und Versauerung das Hauptproblem dar. Aus diesem Grunde bietet es sich an, den Gedanken der 'Null-Emissions-Stadt', der Vision einer moeglichst emissionsfreien Stadt, aufzugreifen und auf seine Tragfaehigkeit fuer innovative Handlungsmodelle forschungsstrategisch zu ueberpruefen. Das Bundesministerium fuer Bildung und Forschung hat das Institut Wohnen und Umwelt beauftragt, in einer Sondierungsstudie dieser Fragestellung nachzugehen. Nach der Festlegung der Ausgangsbedingungen und Eckpunkte der Vision 'Null-Emissions-Stadt' und der Analyse der vier Handlungsfelder Siedlungsstrukturen, Energieversorgung, Produktionsprozesse (Kreislaufwirtschaft) und Verkehr werden diese aufgegriffen und mit der kommunalen Handlungsebene verknuepft und zu einem Forschungs-, Handlungs- und moeglichen Aktionsrahmen zusammengefuegt. Die Studie schliesst mit Hinweisen fuer die Gestaltung eines Forschungsprogramms 'Null-Emissions-Stadt'. (orig.)

  19. PERSEE: a nulling interferometer with dynamic correction of external perturbations

    Science.gov (United States)

    Jacquinod, S.; Houairi, K.; Le Duigou, J.-M.; Barillot, M.; Cassaing, F.; Réess, J.-M.; Hénault, F.; Sorrente, B.; Morinaud, G.; Amans, J.-P.; Coudé du Foresto, V.; Ollivier, M.

    2017-11-01

    Nulling interferometry is one of the direct detection methods assessed to find and characterize extrasolar planets and particularly telluric ones. Several projects such as Darwin [1;2], TPF-I [3;4], PEGASE [5;6] or FKSI [7], are currently considered. One of the main issues is the feasibility of a stable polychromatic null despite the presence of significant disturbances, induced by vibrations, atmospheric turbulence on the ground or satellite drift. Satisfying all these requirements is a great challenge and a key issue of these missions. In the context of the PEGASE mission, it was decided (in 2006), to build a laboratory demonstrator named PERSEE. It is the first laboratory setup which couples deep nulling interferometry with a free flying GNC simulator [8]. It is developed by a consortium composed of CNES, IAS, LESIA, OCA, ONERA, and TAS. In this paper, we detail the main objectives, the set-up and the function of the bench. We describe all the subsystems and we focus particularly on two key points of PERSEE: the beam combiner and the Fringe tracker.

  20. Kastor-Traschen black holes, null geodesics and conformal circles

    International Nuclear Information System (INIS)

    Casey, Stephen

    2012-01-01

    The Kastor-Traschen metric is a time-dependent solution of the Einstein-Maxwell equations with positive cosmological constant Λ which can be used to describe an arbitrary number of charged dynamical black holes. In this paper, we consider the null geodesic structure of this solution, in particular, focusing on the projection to the space of orbits of the timelike conformal retraction. It is found that these projected light rays arise as integral curves of a system of third-order ordinary differential equations. This system is not uniquely defined, however, and we use the inherent freedom to construct a new system whose integral curves coincide with the projection of distinguished null curves of Kastor-Traschen arising from a magnetic flow. We discuss our results in the one-centre case and demonstrate a link to conformal circles in the limit Λ → 0. We also show how to construct analytic expressions for the projected null geodesics of this metric by exploiting a well-known diffeomorphism between the K-T metric and extremal Reissner-Nordstrom-de Sitter. We make some remarks about the two-centre solution and demonstrate a link with the one-centre case. (paper)

  1. "Time sweet time": circadian characterization of galectin-1 null mice

    Directory of Open Access Journals (Sweden)

    Rabinovich Gabriel A

    2010-04-01

    Full Text Available Abstract Background Recent evidence suggests a two-way interaction between the immune and circadian systems. Circadian control of immune factors, as well as the effect of immunological variables on circadian rhythms, might be key elements in both physiological and pathological responses to the environment. Among these relevant factors, galectin-1 is a member of a family of evolutionarily-conserved glycan-binding proteins with both extracellular and intracellular effects, playing important roles in immune cell processes and inflammatory responses. Many of these actions have been studied through the use of mice with a null mutation in the galectin-1 (Lgals1 gene. To further analyze the role of endogenous galectin-1 in vivo, we aimed to characterize the circadian behavior of galectin-1 null (Lgals1-/- mice. Methods We analyzed wheel-running activity in light-dark conditions, constant darkness, phase responses to light pulses (LP at circadian time 15, and reentrainment to 6 hour shifts in light-dark schedule in wild-type (WT and Lgals1-/- mice. Results We found significant differences in free-running period, which was longer in mutant than in WT mice (24.02 vs 23.57 h, p alpha (14.88 vs. 12.35 circadian h, p Conclusions Given the effect of a null mutation on circadian period and entrainment, we indicate that galectin-1 could be involved in the regulation of murine circadian rhythmicity. This is the first study implicating galectin-1 in the mammalian circadian system.

  2. RHD alleles in the Tunisian population

    Science.gov (United States)

    Ouchari, Mouna; Jemni-Yaacoub, Saloua; Chakroun, Taher; Abdelkefi, Saida; Houissa, Batoul; Hmida, Slama

    2013-01-01

    Background: A comprehensive survey of RHD alleles in Tunisia population was lacking. The aim of this study was to use a multiplex RHD typing assay for simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic acid (DNA) sequence exchange mechanism and some weak D alleles. Materials and Methods: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5, 6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions was selected for RHD genotyping using a PCR multiplex assay. Further molecular investigations were done to characterize the RHD variants that were identified by the PCR multiplex assay. Results: In the 1777 D+ samples, only 10 individuals showed the absence of amplification of exons 4 and 5 that were subsequently identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected. In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4 individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5. These samples were then screened by PCR-SSPs on d(C) ces and weak D type 4, respectively. Conclusion: The weak D type 4 appears to be the most common D variant allele. We have not found any partial D variant. Findings also indicated that RHD gene deletion is the most prevalent cause of the D- phenotype in the Tunisian population. PMID:24014941

  3. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene ...

  4. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  5. Generation of New Hairless Alleles by Genomic Engineering at the Hairless Locus in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Heiko Praxenthaler

    Full Text Available Hairless (H is the major antagonist within the Notch signalling pathway of Drosophila melanogaster. By binding to Suppressor of Hairless [Su(H] and two co-repressors, H induces silencing of Notch target genes in the absence of Notch signals. We have applied genomic engineering to create several new H alleles. To this end the endogenous H locus was replaced with an attP site by homologous recombination, serving as a landing platform for subsequent site directed integration of different H constructs. This way we generated a complete H knock out allele HattP, reintroduced a wild type H genomic and a cDNA-construct (Hgwt, Hcwt as well as two constructs encoding H proteins defective of Su(H binding (HLD, HiD. Phenotypes regarding viability, bristle and wing development were recorded, and the expression of Notch target genes wingless and cut was analysed in mutant wing discs or in mutant cell clones. Moreover, genetic interactions with Notch (N5419 and Delta (DlB2 mutants were addressed. Overall, phenotypes were largely as expected: both HLD and HiD were similar to the HattP null allele, indicating that most of H activity requires the binding of Su(H. Both rescue constructs Hgwt and Hcwt were homozygous viable without phenotype. Unexpectedly, the hemizygous condition uncovered that they were not identical to the wild type allele: notably Hcwt showed a markedly reduced activity, suggesting the presence of as yet unidentified regulatory or stabilizing elements in untranslated regions of the H gene. Interestingly, Hgwt homozygous cells expressed higher levels of H protein, perhaps unravelling gene-by-environment interactions.

  6. Variational principle for gravity with null and non-null boundaries: a unified boundary counter-term

    Energy Technology Data Exchange (ETDEWEB)

    Parattu, Krishnamohan; Chakraborty, Sumanta; Padmanabhan, T. [IUCAA, Post Bag 4, Pune (India)

    2016-03-15

    It is common knowledge that the Einstein-Hilbert action does not furnish a well-posed variational principle. The usual solution to this problem is to add an extra boundary term to the action, called a counter-term, so that the variational principle becomes well-posed. When the boundary is spacelike or timelike, the Gibbons-Hawking-York counter-term is the most widely used. For null boundaries, we had proposed a counter-term in a previous paper. In this paper, we extend the previous analysis and propose a counter-term that can be used to eliminate variations of the ''off-the-surface'' derivatives of the metric on any boundary, regardless of its spacelike, timelike or null nature. (orig.)

  7. Left cardiac isomerism in the Sonic hedgehog null mouse.

    Science.gov (United States)

    Hildreth, Victoria; Webb, Sandra; Chaudhry, Bill; Peat, Jonathan D; Phillips, Helen M; Brown, Nigel; Anderson, Robert H; Henderson, Deborah J

    2009-06-01

    Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from

  8. An allele of an ancestral transcription factor dependent on a horizontally acquired gene product.

    Science.gov (United States)

    Chen, H Deborah; Jewett, Mollie W; Groisman, Eduardo A

    2012-01-01

    Changes in gene regulatory circuits often give rise to phenotypic differences among closely related organisms. In bacteria, these changes can result from alterations in the ancestral genome and/or be brought about by genes acquired by horizontal transfer. Here, we identify an allele of the ancestral transcription factor PmrA that requires the horizontally acquired pmrD gene product to promote gene expression. We determined that a single amino acid difference between the PmrA proteins from the human adapted Salmonella enterica serovar Paratyphi B and the broad host range S. enterica serovar Typhimurium rendered transcription of PmrA-activated genes dependent on the PmrD protein in the former but not the latter serovar. Bacteria harboring the serovar Typhimurium allele exhibited polymyxin B resistance under PmrA- or under PmrA- and PmrD-inducing conditions. By contrast, isogenic strains with the serovar Paratyphi B allele displayed PmrA-regulated polymyxin B resistance only when experiencing activating conditions for both PmrA and PmrD. We establish that the two PmrA orthologs display quantitative differences in several biochemical properties. Strains harboring the serovar Paratyphi B allele showed enhanced biofilm formation, a property that might promote serovar Paratyphi B's chronic infection of the gallbladder. Our findings illustrate how subtle differences in ancestral genes can impact the ability of horizontally acquired genes to confer new properties.

  9. Allelic hierarchy of CDH23 mutations causing non-syndromic deafness DFNB12 or Usher syndrome USH1D in compound heterozygotes.

    Science.gov (United States)

    Schultz, Julie M; Bhatti, Rashid; Madeo, Anne C; Turriff, Amy; Muskett, Julie A; Zalewski, Christopher K; King, Kelly A; Ahmed, Zubair M; Riazuddin, Saima; Ahmad, Nazir; Hussain, Zawar; Qasim, Muhammad; Kahn, Shaheen N; Meltzer, Meira R; Liu, Xue Z; Munisamy, Murali; Ghosh, Manju; Rehm, Heidi L; Tsilou, Ekaterini T; Griffith, Andrew J; Zein, Wadih M; Brewer, Carmen C; Riazuddin, Sheikh; Friedman, Thomas B

    2011-11-01

    Recessive mutant alleles of MYO7A, USH1C, CDH23, and PCDH15 cause non-syndromic deafness or type 1 Usher syndrome (USH1) characterised by deafness, vestibular areflexia, and vision loss due to retinitis pigmentosa. For CDH23, encoding cadherin 23, non-syndromic DFNB12 deafness is associated primarily with missense mutations hypothesised to have residual function. In contrast, homozygous nonsense, frame shift, splice site, and some missense mutations of CDH23, all of which are presumably functional null alleles, cause USH1D. The phenotype of a CDH23 compound heterozygote for a DFNB12 allele in trans configuration to an USH1D allele is not known and cannot be predicted from current understanding of cadherin 23 function in the retina and vestibular labyrinth. To address this issue, this study sought CDH23 compound heterozygotes by sequencing this gene in USH1 probands, and families segregating USH1D or DFNB12. Five non-syndromic deaf individuals were identified with normal retinal and vestibular phenotypes that segregate compound heterozygous mutations of CDH23, where one mutation is a known or predicted USH1 allele. One DFNB12 allele in trans configuration to an USH1D allele of CDH23 preserves vision and balance in deaf individuals, indicating that the DFNB12 allele is phenotypically dominant to an USH1D allele. This finding has implications for genetic counselling and the development of therapies for retinitis pigmentosa in Usher syndrome. ACCESSION NUMBERS: The cDNA and protein Genbank accession numbers for CDH23 and cadherin 23 used in this paper are AY010111.2 and AAG27034.2, respectively.

  10. Analysis of nucleotide diversity among alleles of the major bacterial blight resistance gene Xa27 in cultivars of rice (Oryza sativa) and its wild relatives.

    Science.gov (United States)

    Bimolata, Waikhom; Kumar, Anirudh; Sundaram, Raman Meenakshi; Laha, Gouri Shankar; Qureshi, Insaf Ahmed; Reddy, Gajjala Ashok; Ghazi, Irfan Ahmad

    2013-08-01

    Xa27 is one of the important R-genes, effective against bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo). Using natural population of Oryza, we analyzed the sequence variation in the functionally important domains of Xa27 across the Oryza species. DNA sequences of Xa27 alleles from 27 rice accessions revealed higher nucleotide diversity among the reported R-genes of rice. Sequence polymorphism analysis revealed synonymous and non-synonymous mutations in addition to a number of InDels in non-coding regions of the gene. High sequence variation was observed in the promoter region including the 5'UTR with 'π' value 0.00916 and 'θ w ' = 0.01785. Comparative analysis of the identified Xa27 alleles with that of IRBB27 and IR24 indicated the operation of both positive selection (Ka/Ks > 1) and neutral selection (Ka/Ks ≈ 0). The genetic distances of alleles of the gene from Oryza nivara were nearer to IRBB27 as compared to IR24. We also found the presence of conserved and null UPT (upregulated by transcriptional activator) box in the isolated alleles. Considerable amino acid polymorphism was localized in the trans-membrane domain for which the functional significance is yet to be elucidated. However, the absence of functional UPT box in all the alleles except IRBB27 suggests the maintenance of single resistant allele throughout the natural population.

  11. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

    1999-01-01

    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  12. Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

    Science.gov (United States)

    Faure, Eric

    2008-01-01

    Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of

  13. Vacuum Nuller Testbed Performance, Characterization and Null Control

    Science.gov (United States)

    Lyon, R. G.; Clampin, M.; Petrone, P.; Mallik, U.; Madison, T.; Bolcar, M.; Noecker, C.; Kendrick, S.; Helmbrecht, M. A.

    2011-01-01

    The Visible Nulling Coronagraph (VNC) can detect and characterize exoplanets with filled, segmented and sparse aperture telescopes, thereby spanning the choice of future internal coronagraph exoplanet missions. NASA/Goddard Space Flight Center (GSFC) has developed a Vacuum Nuller Testbed (VNT) to advance this approach, and assess and advance technologies needed to realize a VNC as a flight instrument. The VNT is an ultra-stable testbed operating at 15 Hz in vacuum. It consists of a MachZehnder nulling interferometer; modified with a "W" configuration to accommodate a hexpacked MEMS based deformable mirror (DM), coherent fiber bundle and achromatic phase shifters. The 2-output channels are imaged with a vacuum photon counting camera and conventional camera. Error-sensing and feedback to DM and delay line with control algorithms are implemented in a real-time architecture. The inherent advantage of the VNC is that it is its own interferometer and directly controls its errors by exploiting images from bright and dark channels simultaneously. Conservation of energy requires the sum total of the photon counts be conserved independent of the VNC state. Thus sensing and control bandwidth is limited by the target stars throughput, with the net effect that the higher bandwidth offloads stressing stability tolerances within the telescope. We report our recent progress with the VNT towards achieving an incremental sequence of contrast milestones of 10(exp 8) , 10(exp 9) and 10(exp 10) respectively at inner working angles approaching 2A/D. Discussed will be the optics, lab results, technologies, and null control. Shown will be evidence that the milestones have been achieved.

  14. A visualization of null geodesics for the bonnor massive dipole

    Directory of Open Access Journals (Sweden)

    G. Andree Oliva Mercado

    2015-08-01

    Full Text Available In this work we simulate null geodesics for the Bonnor massive dipole metric by implementing a symbolic-numerical algorithm in Sage and Python. This program is also capable of visualizing in 3D, in principle, the geodesics for any given metric. Geodesics are launched from a common point, collectively forming a cone of light beams, simulating a solid-angle section of a point source in front of a massive object with a magnetic field. Parallel light beams also were considered, and their bending due to the curvature of the space-time was simulated.

  15. Do electromagnetic waves always propagate along null geodesics?

    International Nuclear Information System (INIS)

    Asenjo, Felipe A; Hojman, Sergio A

    2017-01-01

    We find exact solutions to Maxwell equations written in terms of four-vector potentials in non–rotating, as well as in Gödel and Kerr spacetimes. We show that Maxwell equations can be reduced to two uncoupled second-order differential equations for combinations of the components of the four-vector potential. Exact electromagnetic waves solutions are written on given gravitational field backgrounds where they evolve. We find that in non–rotating spherical symmetric spacetimes, electromagnetic waves travel along null geodesics. However, electromagnetic waves on Gödel and Kerr spacetimes do not exhibit that behavior. (paper)

  16. Two-loop string theory on null compactifications

    International Nuclear Information System (INIS)

    Cove, Henry C.D.; Szabo, Richard J.

    2006-01-01

    We compute the two-loop contributions to the free energy in the null compactification of perturbative string theory at finite temperature. The cases of bosonic, type II and heterotic strings are all treated. The calculation exploits an explicit reductive parametrization of the moduli space of infinite-momentum frame string worldsheets in terms of branched cover instantons. Various arithmetic and physical properties of the instanton sums are described. Applications to symmetric product orbifold conformal field theories and to the matrix string theory conjecture are also briefly discussed

  17. Twisting null geodesic congruences and the Einstein-Maxwell equations

    International Nuclear Information System (INIS)

    Newman, Ezra T; Silva-Ortigoza, Gilberto

    2006-01-01

    In a recent article, we returned to the study of asymptotically flat solutions of the vacuum Einstein equations with a rather unconventional point of view. The essential observation in that work was that from a given asymptotically flat vacuum spacetime with a given Bondi shear, one can find a class of asymptotically shear-free (but, in general, twisting) null geodesic congruences where the class was uniquely given up to the arbitrary choice of a complex analytic 'worldline' in a four-dimensional complex space. By imitating certain terms in the Weyl tensor that are found in the algebraically special type II metrics, this complex worldline could be made unique and given-or assigned-the physical meaning as the complex centre of mass. Equations of motion for this case were found. The purpose of the present work is to extend those results to asymptotically flat solutions of the Einstein-Maxwell equations. Once again, in this case, we get a class of asymptotically shear-free null geodesic congruences depending on a complex worldline in the same four-dimensional complex space. However in this case there will be, in general, two distinct but uniquely chosen worldlines, one of which can be assigned as the complex centre of charge while the other could be called the complex centre of mass. Rather than investigating the situation where there are two distinct complex worldlines, we study instead the special degenerate case where the two worldlines coincide, i.e., where there is a single unique worldline. This mimics the case of algebraically special Einstein-Maxwell fields where the degenerate principle null vector of the Weyl tensor coincides with a Maxwell principle null vector. Again we obtain equations of motion for this worldline-but explicitly found here only in an approximation. Though there are ambiguities in assigning physical meaning to different terms it appears as if reliance on the Kerr and charged Kerr metrics and classical electromagnetic radiation theory helps

  18. The null-event method in computer simulation

    International Nuclear Information System (INIS)

    Lin, S.L.

    1978-01-01

    The simulation of collisions of ions moving under the influence of an external field through a neutral gas to non-zero temperatures is discussed as an example of computer models of processes in which a probe particle undergoes a series of interactions with an ensemble of other particles, such that the frequency and outcome of the events depends on internal properties of the second particles. The introduction of null events removes the need for much complicated algebra, leads to a more efficient simulation and reduces the likelihood of logical error. (Auth.)

  19. Null geodesic deviation II. Conformally flat space--times

    International Nuclear Information System (INIS)

    Peters, P.C.

    1975-01-01

    The equation of geodesic deviation is solved in conformally flat space--time in a covariant manner. The solution is given as an integral equation for general geodesics. The solution is then used to evaluate second derivatives of the world function and derivatives of the parallel propagator, which need to be known in order to find the Green's function for wave equations in curved space--time. A method of null geodesic limits of two-point functions is discussed, and used to find the scalar Green's function as an iterative series

  20. Lichenysin production is improved in codY null Bacillus licheniformis by addition of precursor amino acids.

    Science.gov (United States)

    Zhu, Chengjun; Xiao, Fang; Qiu, Yimin; Wang, Qin; He, Zhili; Chen, Shouwen

    2017-08-01

    Lichenysin is categorized into the family of lipopeptide biosurfactants and has a variety of applications in the petroleum industry, bioremediation, pharmaceuticals, and the food industry. Currently, large-scale production is limited due to the low yield. This study found that lichenysin production was repressed by supplementation of extracellular amino acids. The global transcriptional factor CodY was hypothesized to prevent lichenysin biosynthesis under an amino acid-rich condition in Bacillus licheniformis. Thus, the codY null strain was constructed, and lichenysin production was increased by 31.0% to 2356 mg/L with the addition of precursor amino acids, and the lichenysin production efficiency was improved by 42.8% to 98.2 mg/L• h. Correspondingly, the transcription levels of the lichenysin synthetase gene lchAA, and its corresponding regulator genes comA, degQ, and degU, were upregulated. Also, the codY deletion enhanced biosynthesis of lichenysin precursor amino acids (Gln, Ile, Leu, and Val) and reduced the formation of byproducts, acetate, acetoin, and 2,3-butanediol. This study firstly reported that lichenysin biosynthesis was negatively regulated by CodY and lichenysin production could be further improved with the precursor amino acid amendment in the codY null strain.

  1. Segregation of genes from donor strain during the production of recombinant congenic strains.

    Science.gov (United States)

    van Zutphen, L F; Den Bieman, M; Lankhorst, A; Demant, P

    1991-07-01

    Recombinant congenic strains (RCS) constitute a set of inbred strains which are designed to dissect the genetic control of multigenic traits, such as tumour susceptibility or disease resistance. Each RCS contains a small fraction of the genome of a common donor strain, while the majority of genes stem from a common background strain. We tested at two stages of the inbreeding process in 20 RCS, derived from BALB/cHeA and STS/A, to see whether alleles from the STS/A donor strain are distributed over the RCS in a ratio as would theoretically be expected. Four marker genes (Pep-3; Pgm-1; Gpi-1 and Es-3) located at 4 different chromosomes were selected and the allelic distribution was tested after 3-4 and after 12 generations of inbreeding. The data obtained do not significantly deviate from the expected pattern, thus supporting the validity of the concept of RCS.

  2. Determination of allele frequencies in nine short tandem repeat loci ...

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... the normal cellular process of replication of DNA molecules. ... probability of a certain genetic variant (alleles) occuring in ... have preservatives that hinder spoilage and are easily packaged .... Allele distribution at Nine STR.

  3. A new electrophoresis technique to separate microsatellite alleles ...

    African Journals Online (AJOL)

    A new electrophoresis technique to separate microsatellite alleles* ... African Journal of Biotechnology ... with the CEQTM 8000 Genetic Analysis System and ABI 3130xl DNA Sequencer easily separated products and determined allelic size, ...

  4. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  5. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Gourab Dewan

    2015-02-18

    Feb 18, 2015 ... desh and having borders with India and Myanmar (Fig. 1). It is a hilly area with ..... calculated allelic frequencies for ABO/Rh systems previously. Therefore, allelic .... in backward caste population of Uttar Pradesh, India. Not Sci.

  6. Association mapping and favourable QTL alleles for fibre quality ...

    Indian Academy of Sciences (India)

    Cheng-Guang Dong

    A total of 201 markers were polymorphic and generated 394 allele loci, and 403 ... identified as containing favourable allele loci related to fibre quality traits. The identified .... environment. Field management followed respective local practices.

  7. Prevalence of Helicobacter pylori vacuolating cytotoxin and its allelic mosaicism as a predictive marker for Iranian dyspeptic patients

    DEFF Research Database (Denmark)

    Mohammadi, M; Oghalaie, A; Mohajerani, N

    2003-01-01

    can serve as screening markers for such a population, H. pylori strains were isolated from one hundred and thirty two dyspeptic patients. H. pylori genomic DNA was extracted and underwent PCR-amplification for the cytotoxin alleles. Genotyping of the signal sequence region of the vacA gene identified...

  8. The new null testing method for the special optical window

    Science.gov (United States)

    Huang, Changchun

    2009-07-01

    The high speed, high precision and wide range specifications are requirement for the modern aircraft, which the traditional hemispherical dome can't achieve now, and the novel conformal window instead can enhance the aerodynamic performance of the aircraft obviously. To reduce the aerodynamic drag and radar cross-section, the window geometry is generally aspheric in shape. As a result, the involved fabrication and testing processes are much more challenging than that of conventional optics and must be mastered before these windows and systems can be implemented at an acceptable cost and risk. Metrology is one of the critical areas required to advance the conformal window technology. But as the surface of these conformal windows is not the traditional sphere lens, the measurement method for it is infeasible with the conventional optics measurement processes. This paper we express the development of testing technology for the special conformal windows in brief, and emphatically introduces one available novel testing method- a new null testing, and here based on the theory of compensation methods, The principle of Offner's refractive null lens has been extended to test the transmission wavefront through conformal window optics and provide feedback during surface fabrication. a compensator system for the was designed for the conformal window is given which parameters are 100mm for its aperture and two parabolic surface as conformal window, the final residual wavefront error(RMS) of which is less than 1/20λ(λ=632.8nm).

  9. Pituitary null cell adenoma in a domestic llama (Lama glama).

    Science.gov (United States)

    Chalkley, M D; Kiupel, M; Draper, A C E

    2014-07-01

    Pituitary gland neoplasia has been reported rarely in camelids. A 12-year-old neutered male llama (Lama glama) presented with lethargy, inappetence and neurological signs. On physical examination, the llama was mentally dull and exhibited compulsive pacing and circling to the left. Complete blood count and serum biochemistry revealed haemoconcentration, mild hypophosphataemia, hyperglycaemia, hypercreatininaemia and hyperalbuminaemia. Humane destruction was elected due to rapid clinical deterioration and poor prognosis. Post-mortem examination revealed a pituitary macroadenoma and bilateral internal hydrocephalus. Microscopically, the pituitary tumour was composed of neoplastic chromophobic pituitary cells. Ultrastructural studies revealed similar neoplastic cells to those previously described in human null cell adenomas. Immunohistochemically, the neoplastic cells were strongly immunoreactive for neuroendocrine markers (synaptophysin and chromogranin A), but did not exhibit immunoreactivity for epithelial, mesenchymal, neuronal and all major pituitary hormone markers (adrenocorticotropic hormone, follicle stimulating hormone, growth hormone, luteinizing hormone, melanocyte-stimulating hormone, prolactin and thyroid stimulating hormone), consistent with the diagnosis of a pituitary null cell adenoma. This is the first report of pituitary neoplasia in a llama. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Randomizing growing networks with a time-respecting null model

    Science.gov (United States)

    Ren, Zhuo-Ming; Mariani, Manuel Sebastian; Zhang, Yi-Cheng; Medo, Matúš

    2018-05-01

    Complex networks are often used to represent systems that are not static but grow with time: People make new friendships, new papers are published and refer to the existing ones, and so forth. To assess the statistical significance of measurements made on such networks, we propose a randomization methodology—a time-respecting null model—that preserves both the network's degree sequence and the time evolution of individual nodes' degree values. By preserving the temporal linking patterns of the analyzed system, the proposed model is able to factor out the effect of the system's temporal patterns on its structure. We apply the model to the citation network of Physical Review scholarly papers and the citation network of US movies. The model reveals that the two data sets are strikingly different with respect to their degree-degree correlations, and we discuss the important implications of this finding on the information provided by paradigmatic node centrality metrics such as indegree and Google's PageRank. The randomization methodology proposed here can be used to assess the significance of any structural property in growing networks, which could bring new insights into the problems where null models play a critical role, such as the detection of communities and network motifs.

  11. Geometry of extended null supersymmetry in M theory

    International Nuclear Information System (INIS)

    Conamhna, Oisin A.P. Mac

    2006-01-01

    For supersymmetric spacetimes in 11 dimensions admitting a null Killing spinor, a set of explicit necessary and sufficient conditions for the existence of any number of arbitrary additional Killing spinors is derived. The necessary and sufficient conditions are comprised of algebraic relationships, linear in the spinorial components, between the spinorial components and their first derivatives, and the components of the spin connection and four-form. The integrability conditions for the Killing spinor equation are also analyzed in detail, to determine which components of the field equations are implied by arbitrary additional supersymmetries and the four-form Bianchi identity. This provides a complete formalism for the systematic and exhaustive investigation of all spacetimes with extended null supersymmetry in 11 dimensions. The formalism is employed to show that the general bosonic solution of 11 dimensional supergravity admitting a G 2 structure defined by four Killing spinors is either locally the direct product of R 1,3 with a seven-manifold of G 2 holonomy, or locally the Freund-Rubin direct product of AdS 4 with a seven-manifold of weak G 2 holonomy. In addition, all supersymmetric spacetimes admitting a (G 2 xR 7 )xR 2 structure are classified

  12. Extrasolar Planetary Imaging Coronagraph (EPIC): visible nulling cornagraph testbed results

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Melnick, Gary; Tolls, Volker; Woodruff, Robert; Vasudevan, Gopal

    2008-07-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a NASA Astrophysics Strategic Mission Concept under study for the upcoming Exoplanet Probe. EPIC's mission would be to image and characterize extrasolar giant planets, and potential super-Earths, in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys and potentially some transits, determine orbital inclinations and masses, characterize the atmospheres of gas giants around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched into a heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime (5 year goal) and will revisit planets at least three times. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA/Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed.

  13. Extrasolar Planetary Imaging Coronagraph: Visible Nulling Coronagraph Testbed Results

    Science.gov (United States)

    Lyon, Richard G.

    2008-01-01

    The Extrasolar Planetary Imaging Coronagraph (EPIC) is a proposed NASA Discovery mission to image and characterize extrasolar giant planets in orbits with semi-major axes between 2 and 10 AU. EPIC will provide insights into the physical nature of a variety of planets in other solar systems complimenting radial velocity (RV) and astrometric planet searches. It will detect and characterize the atmospheres of planets identified by radial velocity surveys, determine orbital inclinations and masses, characterize the atmospheres around A and F stars, observed the inner spatial structure and colors of inner Spitzer selected debris disks. EPIC would be launched to heliocentric Earth trailing drift-away orbit, with a 3-year mission lifetime ( 5 year goal) and will revisit planets at least three times at intervals of 9 months. The starlight suppression approach consists of a visible nulling coronagraph (VNC) that enables high order starlight suppression in broadband light. To demonstrate the VNC approach and advance it's technology readiness the NASA Goddard Space Flight Center and Lockheed-Martin have developed a laboratory VNC and have demonstrated white light nulling. We will discuss our ongoing VNC work and show the latest results from the VNC testbed,

  14. Non-dissipative electromagnetic media with two Lorentz null cones

    International Nuclear Information System (INIS)

    Dahl, Matias F.

    2013-01-01

    We study Maxwell’s equations on a 4-manifold where the electromagnetic medium is modeled by an antisymmetric (2/2 )-tensor with 21 real coefficients. In this setting the Fresnel surface is a fourth-order polynomial surface that describes the dynamical response of the medium in the geometric optics limit. For example, in an isotropic medium the Fresnel surface is a Lorentz null cone. The contribution of this paper is the pointwise description of all electromagnetic medium tensors κ with real coefficients that satisfy the following three conditions: (i)medium κ is invertible, (ii)medium κ is skewon-free, or non-dissipative, (iii)the Fresnel surface of κ is the union of two distinct Lorentz null cones. We show that there are only three classes of media with these properties and give explicit expressions in local coordinates for each class. - Highlights: ► We find two new electromagnetic media classes for which the Fresnel surface decomposes into two light cones. ► In a suitable setting we classify all electromagnetic media where this is the case. ► We find an electromagnetic medium tensor with three different signal speeds in one direction. ► The work is related to [5], which classifies all media with one light cone (in a suitable setting).

  15. Plate with a hole obeys the averaged null energy condition

    International Nuclear Information System (INIS)

    Graham, Noah; Olum, Ken D.

    2005-01-01

    The negative energy density of Casimir systems appears to violate general relativity energy conditions. However, one cannot test the averaged null energy condition (ANEC) using standard calculations for perfectly reflecting plates, because the null geodesic would have to pass through the plates, where the calculation breaks down. To avoid this problem, we compute the contribution to ANEC for a geodesic that passes through a hole in a single plate. We consider both Dirichlet and Neumann boundary conditions in two and three space dimensions. We use a Babinet's principle argument to reduce the problem to a complementary finite disk correction to the perfect mirror result, which we then compute using scattering theory in elliptical and spheroidal coordinates. In the Dirichlet case, we find that the positive correction due to the hole overwhelms the negative contribution of the infinite plate. In the Neumann case, where the infinite plate gives a positive contribution, the hole contribution is smaller in magnitude, so again ANEC is obeyed. These results can be extended to the case of two plates in the limits of large and small hole radii. This system thus provides another example of a situation where ANEC turns out to be obeyed when one might expect it to be violated

  16. Allele and genotype frequencies of -β lactoglobulin gene in Iranian ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... Blood samples were supplied from 80 Najdi cattle and 80 buffalo from different cities of Khouzestan province. ... The allele B of β-Lactoglobulin occurred at a higher frequency than the allele A in both. Najdi cattle and buffalo. .... that of the B allele in both groups of animals studied. Expected heterozygosity ...

  17. Directional Positive Selection on an Allele of Arbitrary Dominance

    OpenAIRE

    Teshima, Kosuke M.; Przeworski, Molly

    2006-01-01

    Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

  18. Meterwavelength Single-pulse Polarimetric Emission Survey. III. The Phenomenon of Nulling in Pulsars

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Rahul; Mitra, Dipanjan; Melikidze, George I., E-mail: rahulbasu.astro@gmail.com [Janusz Gil Institute of Astronomy, University of Zielona Góra, ul. Szafrana 2, 65–516 Zielona Góra (Poland)

    2017-09-10

    A detailed analysis of nulling was conducted for the pulsars studied in the Meterwavelength Single-pulse Polarimetric Emission Survey. We characterized nulling in 36 pulsars including 17 pulsars where the phenomenon was reported for the first time. The most dominant nulls lasted for a short duration, less than five periods. Longer duration nulls extending to hundreds of periods were also seen in some cases. A careful analysis showed the presence of periodicities in the transition from the null to the burst states in 11 pulsars. In our earlier work, fluctuation spectrum analysis showed multiple periodicities in 6 of these 11 pulsars. We demonstrate that the longer periodicity in each case was associated with nulling. The shorter periodicities usually originate from subpulse drifting. The nulling periodicities were more aligned with the periodic amplitude modulation, indicating a possible common origin for both. The most prevalent nulls last for a single period and can be potentially explained using random variations affecting the plasma processes in the pulsar magnetosphere. On the other hand, longer-duration nulls require changes in the pair-production processes, which need an external triggering mechanism for the changes. The presence of periodic nulling puts an added constraint on the triggering mechanism, which also needs to be periodic.

  19. Mice null for the deubiquitinase USP18 spontaneously develop leiomyosarcomas

    International Nuclear Information System (INIS)

    Chinyengetere, Fadzai; Sekula, David J.; Lu, Yun; Giustini, Andrew J.; Sanglikar, Aarti; Kawakami, Masanori; Ma, Tian; Burkett, Sandra S.; Eisenberg, Burton L.; Wells, Wendy A.; Hoopes, Paul J.; Demicco, Elizabeth G.; Lazar, Alexander J; Torres, Keila E.; Memoli, Vincent; Freemantle, Sarah J.; Dmitrovsky, Ethan

    2015-01-01

    USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease. Heterozygous USP18 +/− FVB/N mice were bred to generate wild-type, heterozygous and homozygous cohorts. Tumors were characterized immunohistochemically and two cell lines were derived from independent tumors. Cell lines were karyotyped and their responses to restoration of USP18 activity assessed. Drug testing and tumorigenic assays were also performed. USP18 immunohistochemical staining in a large series of human leiomyosacomas was examined. USP18 −/− FVB/N mice spontaneously develop tumors predominantly on the back of the neck with most tumors evident between 6–12 months (80 % penetrance). Immunohistochemical characterization of the tumors confirmed they were leiomyosarcomas, which originate from smooth muscle. Restoration of USP18 activity in sarcoma-derived cell lines did not reduce anchorage dependent or independent growth or xenograft tumor formation demonstrating that these cells no longer require USP18 suppression for tumorigenesis. Karyotyping revealed that both tumor-derived cell lines were aneuploid with extra copies of chromosomes 3 and 15. Chromosome 15 contains the Myc locus and MYC is also amplified in human leiomyosarcomas. MYC protein levels were elevated in both murine leiomyosarcoma cell lines. Stabilized P53 protein was detected in a subset of these murine tumors, another feature of human leiomyosarcomas. Immunohistochemical analyses of USP18 in human leiomyosarcomas revealed a range of staining intensities with the highest USP18 expression in normal vascular smooth muscle. USP18 tissue array analysis of primary leiomyosarcomas from 89 patients with a clinical database revealed cases with reduced USP18 levels had a significantly

  20. Radiation Hardened NULL Convention Logic Asynchronous Circuit Design

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    2015-10-01

    Full Text Available This paper proposes a radiation hardened NULL Convention Logic (NCL architecture that can recover from a single event latchup (SEL or single event upset (SEU fault without deadlock or any data loss. The proposed architecture is analytically proved to be SEL resistant, and by extension, proved to be SEU resistant. The SEL/SEU resistant version of a 3-stage full-word pipelined NCL 4 × 4 unsigned multiplier was implemented using the IBM cmrf8sf 130 nm 1.2 V process at the transistor level and simulated exhaustively with SEL fault injection to validate the proposed architectures. Compared with the original version, the SEL/SEU resilient version has 1.31× speed overhead, 2.74× area overhead, and 2.79× energy per operation overhead.

  1. The simple map for a single-null divertor tokamak

    International Nuclear Information System (INIS)

    Punjabi, A.; Verma, A.; Boozer, A.

    1996-01-01

    We present the simple map for a single-null divertor tokamak. The simple map is an area-preserving map based on the idea that magnetic field lines are a single-degree-of-freedom time-dependent Hamiltonian system, and that the basic features of such systems near the X-point are generic. We obtain the properties of this map and the resulting footprints of field lines on the divertor plate. These include the width of the stochastic layer, the edge safety factor, the area of the footprint and the amount of magnetic flux diverted. We give the safety factor profile, the average and median values of strike angles, lengths and the Liapunov exponents. We describe how the effects of magnetic perturbations can be included in the simple map. We show how the map can be applied to the problem of the determination of heat flux on the divertor plate in tokamaks. (Author)

  2. Status of the Visible Nulling Coronagraph Technology Demonstration Program

    Science.gov (United States)

    Clampin, M.; Lyon, R.

    2012-01-01

    We report on the development, sensing and control of the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraphy (VNC) for exoplanet detection and characterization. The VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center has an established effort to develop VNC technologies, and an incremental sequence of testbeds to advance this approach and its critical technologies. We will highlight results demonstrating the achievement of our TDEM contrast milestones, and highlight the performance of our wavefront sensing and control concept.

  3. Horizons in Matter:. Black Hole Hair Versus Null Big Bang

    Science.gov (United States)

    Bronnikov, K. A.; Zaslavskii, Oleg B.

    It is shown that only particular kinds of matter (in terms of the "radial" pressure-to-density ratio w) can coexist with Killing horizons in black hole or cosmological space-times. Thus, for arbitrary (not necessarily spherically symmetric) static black holes, admissible are vacuum matter (w = -1, i.e. the cosmological constant or its generalization with the same value of w) and matter with certain values of w between 0 and -1, in particular a gas of disordered cosmic strings (w = -1/3). If the cosmological evolution starts from a horizon (the so-called null big bang scenarios), this horizon can coexist with vacuum matter and certain kinds of phantom matter with w ≤ -3. It is concluded that normal matter in such scenarios is entirely created from vacuum.

  4. Cadmium modulates adipocyte functions in metallothionein-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  5. Dinucleotide controlled null models for comparative RNA gene prediction

    Directory of Open Access Journals (Sweden)

    Gesell Tanja

    2008-05-01

    Full Text Available Abstract Background Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak et al. [BMC Bioinformatics. 8:33] that RNA gene prediction programs can be biased by the genomic dinucleotide content, in particular those programs using a thermodynamic folding model including stacking energies. As a consequence, there is need for dinucleotide-preserving control strategies to assess the significance of such predictions. While there have been randomization algorithms for single sequences for many years, the problem has remained challenging for multiple alignments and there is currently no algorithm available. Results We present a program called SISSIz that simulates multiple alignments of a given average dinucleotide content. Meeting additional requirements of an accurate null model, the randomized alignments are on average of the same sequence diversity and preserve local conservation and gap patterns. We make use of a phylogenetic substitution model that includes overlapping dependencies and site-specific rates. Using fast heuristics and a distance based approach, a tree is estimated under this model which is used to guide the simulations. The new algorithm is tested on vertebrate genomic alignments and the effect on RNA structure predictions is studied. In addition, we directly combined the new null model with the RNAalifold consensus folding algorithm giving a new variant of a thermodynamic structure based RNA gene finding program that is not biased by the dinucleotide content. Conclusion SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require

  6. Dinucleotide controlled null models for comparative RNA gene prediction.

    Science.gov (United States)

    Gesell, Tanja; Washietl, Stefan

    2008-05-27

    Comparative prediction of RNA structures can be used to identify functional noncoding RNAs in genomic screens. It was shown recently by Babak et al. [BMC Bioinformatics. 8:33] that RNA gene prediction programs can be biased by the genomic dinucleotide content, in particular those programs using a thermodynamic folding model including stacking energies. As a consequence, there is need for dinucleotide-preserving control strategies to assess the significance of such predictions. While there have been randomization algorithms for single sequences for many years, the problem has remained challenging for multiple alignments and there is currently no algorithm available. We present a program called SISSIz that simulates multiple alignments of a given average dinucleotide content. Meeting additional requirements of an accurate null model, the randomized alignments are on average of the same sequence diversity and preserve local conservation and gap patterns. We make use of a phylogenetic substitution model that includes overlapping dependencies and site-specific rates. Using fast heuristics and a distance based approach, a tree is estimated under this model which is used to guide the simulations. The new algorithm is tested on vertebrate genomic alignments and the effect on RNA structure predictions is studied. In addition, we directly combined the new null model with the RNAalifold consensus folding algorithm giving a new variant of a thermodynamic structure based RNA gene finding program that is not biased by the dinucleotide content. SISSIz implements an efficient algorithm to randomize multiple alignments preserving dinucleotide content. It can be used to get more accurate estimates of false positive rates of existing programs, to produce negative controls for the training of machine learning based programs, or as standalone RNA gene finding program. Other applications in comparative genomics that require randomization of multiple alignments can be considered. SISSIz

  7. Does horizon entropy satisfy a quantum null energy conjecture?

    Science.gov (United States)

    Fu, Zicao; Marolf, Donald

    2016-12-01

    A modern version of the idea that the area of event horizons gives 4G times an entropy is the Hubeny-Rangamani causal holographic information (CHI) proposal for holographic field theories. Given a region R of a holographic QFTs, CHI computes A/4G on a certain cut of an event horizon in the gravitational dual. The result is naturally interpreted as a coarse-grained entropy for the QFT. CHI is known to be finitely greater than the fine-grained Hubeny-Rangamani-Takayanagi (HRT) entropy when \\partial R lies on a Killing horizon of the QFT spacetime, and in this context satisfies other non-trivial properties expected of an entropy. Here we present evidence that it also satisfies the quantum null energy condition (QNEC), which bounds the second derivative of the entropy of a quantum field theory on one side of a non-expanding null surface by the flux of stress-energy across the surface. In particular, we show CHI to satisfy the QNEC in 1  +  1 holographic CFTs when evaluated in states dual to conical defects in AdS3. This surprising result further supports the idea that CHI defines a useful notion of coarse-grained holographic entropy, and suggests unprecedented bounds on the rate at which bulk horizon generators emerge from a caustic. To supplement our motivation, we include an appendix deriving a corresponding coarse-grained generalized second law for 1  +  1 holographic CFTs perturbatively coupled to dilaton gravity.

  8. 3D Solar Null Point Reconnection MHD Simulations

    Science.gov (United States)

    Baumann, G.; Galsgaard, K.; Nordlund, Å.

    2013-06-01

    Numerical MHD simulations of 3D reconnection events in the solar corona have improved enormously over the last few years, not only in resolution, but also in their complexity, enabling more and more realistic modeling. Various ways to obtain the initial magnetic field, different forms of solar atmospheric models as well as diverse driving speeds and patterns have been employed. This study considers differences between simulations with stratified and non-stratified solar atmospheres, addresses the influence of the driving speed on the plasma flow and energetics, and provides quantitative formulas for mapping electric fields and dissipation levels obtained in numerical simulations to the corresponding solar quantities. The simulations start out from a potential magnetic field containing a null-point, obtained from a Solar and Heliospheric Observatory (SOHO) Michelson Doppler Imager (MDI) magnetogram magnetogram extrapolation approximately 8 hours before a C-class flare was observed. The magnetic field is stressed with a boundary motion pattern similar to - although simpler than - horizontal motions observed by SOHO during the period preceding the flare. The general behavior is nearly independent of the driving speed, and is also very similar in stratified and non-stratified models, provided only that the boundary motions are slow enough. The boundary motions cause a build-up of current sheets, mainly in the fan-plane of the magnetic null-point, but do not result in a flare-like energy release. The additional free energy required for the flare could have been partly present in non-potential form at the initial state, with subsequent additions from magnetic flux emergence or from components of the boundary motion that were not represented by the idealized driving pattern.

  9. Molecular bass for a malic enzyme null mutation

    International Nuclear Information System (INIS)

    Brown, M.L.; Wise, L.S.; Rubin, C.S.

    1987-01-01

    Many tissues from normal (wt) mice have cytosolic malic enzyme (ME) activity and express two mRNAs (2 and 3.1 kb) that code for a single ME polypeptide. Mod-1 null (M-n) mice lack cytosolic ME activity, but express 2.5 and 3.6 kb mRNAs that hybridize with wt ME cDNAs. To investigate the basis for the ME deficiency cDNAs corresponding to M-n ME RNA were cloned. A λgt11 library was prepared using M-n liver mRNA as a template. Wt ME cDNA probes hybridized with several recombinant phages and a 2kb insert with an atypical (non-wt) restriction pattern was subcloned in pGEM 1 and sequenced. The M-n ME cDNA contains an internal directly repeated sequence that corresponds to nts 1109-1617 in the coding region of wt ME cDNA. A restriction fragment from M-n ME cDNA that includes the first 204 bp of repeated sequence and 306 bp of contiguous 5' sequence was subcloned into pGEM 1 and used as a template for synthesizing 32 P-labeled anti-sense RNA. After hybridization with M-n liver RNA the 510 nt transcript was resistant to RNA digestion; after hybridization with wt RNA only fragments corresponding to the normally non-contiguous 204 bp and 306 bp segments of the insert were protected. Thus the partial duplication of coding sequence in M-n ME mRNA is confirmed. Analyses of intron-exon organization in the relevant regions of the wt and M-n ME genes will provide further insights into the mechanism underlying the ME null mutation

  10. Surprising structures hiding in Penrose’s future null infinity

    Science.gov (United States)

    Newman, Ezra T.

    2017-07-01

    Since the late1950s, almost all discussions of asymptotically flat (Einstein-Maxwell) space-times have taken place in the context of Penrose’s null infinity, I+. In addition, almost all calculations have used the Bondi coordinate and tetrad systems. Beginning with a known asymptotically flat solution to the Einstein-Maxwell equations, we show first, that there are other natural coordinate systems, near I+, (analogous to light-cones in flat-space) that are based on (asymptotically) shear-free null geodesic congruences (analogous to the flat-space case). Using these new coordinates and their associated tetrad, we define the complex dipole moment, (the mass dipole plus i times angular momentum), from the l  =  1 harmonic coefficient of a component of the asymptotic Weyl tensor. Second, from this definition, from the Bianchi identities and from the Bondi-Sachs mass and linear momentum, we show that there exists a large number of results—identifications and dynamics—identical to those of classical mechanics and electrodynamics. They include, among many others, {P}=M{v}+..., {L}= {r} × {P} , spin, Newton’s second law with the rocket force term (\\dotM v) and radiation reaction, angular momentum conservation and others. All these relations take place in the rather mysterious H-space rather than in space-time. This leads to the enigma: ‘why do these well known relations of classical mechanics take place in H-space?’ and ‘What is the physical meaning of H-space?’

  11. Is PMI the Hypothesis or the Null Hypothesis?

    Science.gov (United States)

    Tarone, Aaron M; Sanford, Michelle R

    2017-09-01

    Over the past several decades, there have been several strident exchanges regarding whether forensic entomologists estimate the postmortem interval (PMI), minimum PMI, or something else. During that time, there has been a proliferation of terminology reflecting this concern regarding "what we do." This has been a frustrating conversation for some in the community because much of this debate appears to be centered on what assumptions are acknowledged directly and which are embedded within a list of assumptions (or ignored altogether) in the literature and in case reports. An additional component of the conversation centers on a concern that moving away from the use of certain terminology like PMI acknowledges limitations and problems that would make the application of entomology appear less useful in court-a problem for lawyers, but one that should not be problematic for scientists in the forensic entomology community, as uncertainty is part of science that should and can be presented effectively in the courtroom (e.g., population genetic concepts in forensics). Unfortunately, a consequence of the way this conversation is conducted is that even as all involved in the debate acknowledge the concerns of their colleagues, parties continue to talk past one another advocating their preferred terminology. Progress will not be made until the community recognizes that all of the terms under consideration take the form of null hypothesis statements and that thinking about "what we do" as a null hypothesis has useful legal and scientific ramifications that transcend arguments over the usage of preferred terminology. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Observation of a 3D Magnetic Null Point

    Energy Technology Data Exchange (ETDEWEB)

    Romano, P.; Falco, M. [INAF—Osservatorio Astrofisico di Catania, Via S. Sofia 78, I-95123 Catania (Italy); Guglielmino, S. L.; Murabito, M., E-mail: prom@oact.inaf.it [Dipartimento di Fisica e Astronomia—Sezione Astrofisica, Università di Catania, Via S. Sofia 78, I-95123 Catania (Italy)

    2017-03-10

    We describe high-resolution observations of a GOES B-class flare characterized by a circular ribbon at the chromospheric level, corresponding to the network at the photospheric level. We interpret the flare as a consequence of a magnetic reconnection event that occurred at a three-dimensional (3D) coronal null point located above the supergranular cell. The potential field extrapolation of the photospheric magnetic field indicates that the circular chromospheric ribbon is cospatial with the fan footpoints, while the ribbons of the inner and outer spines look like compact kernels. We found new interesting observational aspects that need to be explained by models: (1) a loop corresponding to the outer spine became brighter a few minutes before the onset of the flare; (2) the circular ribbon was formed by several adjacent compact kernels characterized by a size of 1″–2″; (3) the kernels with a stronger intensity emission were located at the outer footpoint of the darker filaments, departing radially from the center of the supergranular cell; (4) these kernels started to brighten sequentially in clockwise direction; and (5) the site of the 3D null point and the shape of the outer spine were detected by RHESSI in the low-energy channel between 6.0 and 12.0 keV. Taking into account all these features and the length scales of the magnetic systems involved in the event, we argue that the low intensity of the flare may be ascribed to the low amount of magnetic flux and to its symmetric configuration.

  13. Allelic Imbalance Is a Prevalent and Tissue-Specific Feature of the Mouse Transcriptome

    Science.gov (United States)

    Pinter, Stefan F.; Colognori, David; Beliveau, Brian J.; Sadreyev, Ruslan I.; Payer, Bernhard; Yildirim, Eda; Wu, Chao-ting; Lee, Jeannie T.

    2015-01-01

    In mammals, several classes of monoallelic genes have been identified, including those subject to X-chromosome inactivation (XCI), genomic imprinting, and random monoallelic expression (RMAE). However, the extent to which these epigenetic phenomena are influenced by underlying genetic variation is unknown. Here we perform a systematic classification of allelic imbalance in mouse hybrids derived from reciprocal crosses of divergent strains. We observe that deviation from balanced biallelic expression is common, occurring in ∼20% of the mouse transcriptome in a given tissue. Allelic imbalance attributed to genotypic variation is by far the most prevalent class and typically is tissue-specific. However, some genotype-based imbalance is maintained across tissues and is associated with greater genetic variation, especially in 5′ and 3′ termini of transcripts. We further identify novel random monoallelic and imprinted genes and find that genotype can modify penetrance of parental origin even in the setting of large imprinted regions. Examination of nascent transcripts in single cells from inbred parental strains reveals that genes showing genotype-based imbalance in hybrids can also exhibit monoallelic expression in isogenic backgrounds. This surprising observation may suggest a competition between alleles and/or reflect the combined impact of cis- and trans-acting variation on expression of a given gene. Our findings provide novel insights into gene regulation and may be relevant to human genetic variation and disease. PMID:25858912

  14. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...

  15. Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.

    Directory of Open Access Journals (Sweden)

    Laura Jeacock

    2017-03-01

    Full Text Available Aquaglyceroporins (AQPs transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM, octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.

  16. Nitric oxide synthase gene G298 allele

    International Nuclear Information System (INIS)

    Nagib El-Kilany, Galal E.; Nayel, Ehab; Hazzaa, Sahar

    2004-01-01

    Background: Nitric oxide (NO) has an important effect on blood pressure, arterial wall, and the basal release of endothelial NO in hypertension (HPN) may be reduced. Until now, there is no solid data revealing the potential role of the polymorphism of the nitric oxide synthase gene (NOS) in patients with HPN and microvascular angina. Aim: The aim of the present study is to investigate the gene of endothelial nitric oxide synthase (eNOS), as the polymorphism of this gene may be a putative candidate for HPN and initiate the process of atherosclerosis. Methods: Sixty participants were recruited for this study; 50 were hypertensive patients complaining of chest pain [30 of them have electrocardiogram (EKG) changes of ischemia], 20 had isolated HPN, and 10 healthy volunteers served as control. All patients underwent stress myocardial perfusion imaging (MPI) and coronary angiography. Genotyping of eNOS for all patients and controls was performed. The linkages between HPN, microvascular angina and eNOS gene polymorphism were investigated. Results: MPI and coronary angiography revealed that 15 patients had chest pain with true ischemia and reversible myocardial perfusion defects (multiple and mild) but normal epicardial coronary arteries (microvascular angina), while 15 patients had significant coronary artery disease (CAD), and 20 hypertensive patients showed normal perfusion scan and coronary angiography. The prevalence of the NOS G 298 allele was higher in the hypertensive group with microvascular angina (documented by MPI) than it was among the control participants (P<.005). The eNOS allele was significantly higher in the hypertensive group than in the control participants, but there was no significant difference in homozygote mutants among hypertensive participants, x-syndrome and patients with CAD. Conclusion: eNOS gene polymorphism is proved to be an important etiology in microvascular angina (x-syndrome) among hypertensive patients. In addition, the eNOS mutant

  17. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

    Science.gov (United States)

    Ali, Niwa; Flutter, Barry; Sanchez Rodriguez, Robert; Sharif-Paghaleh, Ehsan; Barber, Linda D; Lombardi, Giovanna; Nestle, Frank O

    2012-01-01

    The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.

  18. Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

    Directory of Open Access Journals (Sweden)

    Niwa Ali

    Full Text Available The occurrence of Graft-versus-Host Disease (GvHD is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice" are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null, notably the NOD-scid IL-2Rγ(null (NSG and BALB/c-Rag2(null IL-2Rγ(null (BRG mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+ compartment and higher engraftment levels of CD3(+ T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM phenotype and high levels of cutaneous lymphocyte antigen (CLA expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM-cell driven GvHD.

  19. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution.

    Science.gov (United States)

    Marez, D; Legrand, M; Sabbagh, N; Lo Guidice, J M; Spire, C; Lafitte, J J; Meyer, U A; Broly, F

    1997-06-01

    The polymorphic cytochrome P450 CYP2D6 is involved in the metabolism of various drugs of wide therapeutic use and is a presumed susceptibility factor for certain environmentally-induced diseases. Our aim was to define the mutations and alleles of the CYP2D6 gene and to evaluate their frequencies in the European population. Using polymerase chain reaction-single strand conformation polymorphism analysis, 672 unrelated subjects were screened for mutations in the 9 exons of the gene and their exon-intron boundaries. A total of 48 point mutations were identified, of which 29 were novel. Mutations 1749 G-->C, 2938 C-->T and 4268 G-->C represented 52.6%, 34.3% and 52.9% of the mutations in the total population, respectively. Of the eight detrimental mutations detected, the 1934 G-->A, the 1795 Tdel and the 2637 Adel accounted for 65.8%, 6.2% and 4.8% respectively, within the poor metabolizer subgroup. Fifty-three different alleles were characterized from the mutation pattern and by allele-specific sequencing. They are derived from three major alleles, namely the wild-type CYP2D6*1A, the functional CYP2D6*2 and the null CYP2D6*4A. Five allelic variants (CYP2D6*1A, *2, *2B, *4A and *5) account for about 87% of all alleles, while the remaining alleles occur with a frequency of 0.1%-2.7%. These data provide a solid basis for future epidemiological, clinical as well as interethnic studies of the CYP2D6 polymorphism and highlight that the described single strand conformation polymorphism method can be successfully used in designing such studies.

  20. Qualification of a Null Lens Using Image-Based Phase Retrieval

    Science.gov (United States)

    Bolcar, Matthew R.; Aronstein, David L.; Hill, Peter C.; Smith, J. Scott; Zielinski, Thomas P.

    2012-01-01

    In measuring the figure error of an aspheric optic using a null lens, the wavefront contribution from the null lens must be independently and accurately characterized in order to isolate the optical performance of the aspheric optic alone. Various techniques can be used to characterize such a null lens, including interferometry, profilometry and image-based methods. Only image-based methods, such as phase retrieval, can measure the null-lens wavefront in situ - in single-pass, and at the same conjugates and in the same alignment state in which the null lens will ultimately be used - with no additional optical components. Due to the intended purpose of a Dull lens (e.g., to null a large aspheric wavefront with a near-equal-but-opposite spherical wavefront), characterizing a null-lens wavefront presents several challenges to image-based phase retrieval: Large wavefront slopes and high-dynamic-range data decrease the capture range of phase-retrieval algorithms, increase the requirements on the fidelity of the forward model of the optical system, and make it difficult to extract diagnostic information (e.g., the system F/#) from the image data. In this paper, we present a study of these effects on phase-retrieval algorithms in the context of a null lens used in component development for the Climate Absolute Radiance and Refractivity Observatory (CLARREO) mission. Approaches for mitigation are also discussed.

  1. An equation satisfied by the tangent to a shear-free, geodesic, null congruence

    International Nuclear Information System (INIS)

    Hogan, P.A.; Dublin Inst. for Advanced Studies

    1987-01-01

    A tensorial equation satisfied by the tangent to a shear-free geodesic, null congruence is presented. If the congruence is neither twist-free nor expansion-free then the equation defines a second, unique, null direction previously obtained, using the spinor formalism, by Somers. Some further properties of the equation are discussed. (orig.)

  2. Allele Frequency - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available nd 39 SNPs are assayed in three (POP_*) and two (RIKEN_japanese_*) panels, respectively. Derived from Flat f... assay (JBIC-allele and RIKEN_japanese_*), TaqMan assay (RIKEN-allele) or direct sequencing / allelic discri...unteers under informed consent RIKEN_japanese_normal_weight - 711 unrelated japanese normal weight volunteer...s ( body mass index RIKEN_japanese_obese - 796 unrelated japanese obese patients

  3. Database for the ampC alleles in Acinetobacter baumannii.

    Directory of Open Access Journals (Sweden)

    Nabil Karah

    Full Text Available Acinetobacter baumannii is a troublesome opportunistic pathogen with a high capacity for clonal dissemination. We announce the establishment of a database for the ampC locus in A. baumannii, in which novel ampC alleles are differentiated based on the occurrence of ≥ 1 nucleotide change, regardless of whether it is silent or missense. The database is openly accessible at the pubmlst platform for A. baumannii (http://pubmlst.org/abaumannii/. Forty-eight distinctive alleles of the ampC locus have so far been identified and deposited in the database. Isolates from clonal complex 1 (CC1, according to the Pasteur multilocus sequence typing scheme, had a variety of the ampC locus alleles, including alleles 1, 3, 4, 5, 6, 7, 8, 13, 14, 17, and 18. On the other hand, isolates from CC2 had the ampC alleles 2, 3, 19, 20, 21, 22, 23, 24, 26, 27, 28, and 46. Allele 3 was characteristic for sequence types ST3 or ST32. The ampC alleles 10, 16, and 25 were characteristic for CC10, ST16, and CC25, respectively. Our study points out that novel gene databases, in which alleles are numbered based on differences in their nucleotide identities, should replace traditional records that use amino acid substitutions to define new alleles.

  4. Causal null hypotheses of sustained treatment strategies: What can be tested with an instrumental variable?

    Science.gov (United States)

    Swanson, Sonja A; Labrecque, Jeremy; Hernán, Miguel A

    2018-05-02

    Sometimes instrumental variable methods are used to test whether a causal effect is null rather than to estimate the magnitude of a causal effect. However, when instrumental variable methods are applied to time-varying exposures, as in many Mendelian randomization studies, it is unclear what causal null hypothesis is tested. Here, we consider different versions of causal null hypotheses for time-varying exposures, show that the instrumental variable conditions alone are insufficient to test some of them, and describe additional assumptions that can be made to test a wider range of causal null hypotheses, including both sharp and average causal null hypotheses. Implications for interpretation and reporting of instrumental variable results are discussed.

  5. Continuous development of current sheets near and away from magnetic nulls

    International Nuclear Information System (INIS)

    Kumar, Sanjay; Bhattacharyya, R.

    2016-01-01

    The presented computations compare the strength of current sheets which develop near and away from the magnetic nulls. To ensure the spontaneous generation of current sheets, the computations are performed congruently with Parker's magnetostatic theorem. The simulations evince current sheets near two dimensional and three dimensional magnetic nulls as well as away from them. An important finding of this work is in the demonstration of comparative scaling of peak current density with numerical resolution, for these different types of current sheets. The results document current sheets near two dimensional magnetic nulls to have larger strength while exhibiting a stronger scaling than the current sheets close to three dimensional magnetic nulls or away from any magnetic null. The comparative scaling points to a scenario where the magnetic topology near a developing current sheet is important for energetics of the subsequent reconnection.

  6. Nulling interferometry for the darwin mission: laboratory demonstration experiment

    Science.gov (United States)

    Ollivier, Marc; Léger, Alain; Sekulic, Predrag; Labèque, Alain; Michel, Guy

    2017-11-01

    The DARWIN mission is a project of the European Space Agency that should allow around 2012 the search for extrasolar planets and a spectral analysis of their potential atmosphere in order to evidence gases and particularly tracers of life. The principle of the instrument is based on the Bracewell nulling interferometer. It allows high angular resolution and high dynamic range. However, this concept, proposed more than 20 years ago, has never been experimentally demonstrated in the thermal infrared with high levels of extinction. We present here a laboratory monochromatic experiment dedicated to this goal. A theoretical and numerical approach of the question highlights a strong difficulty: the need for very clean and homogeneous wavefronts, in terms of intensity, phase and polarisation distribution. A classical interferometric approach appears to be insufficient to reach our goals. We have shown theoretically then numerically that this difficulty can be surpassed if we perform an optical filtering of the interfering beams. This technique allows us to decrease strongly the optical requirements and to view very high interferometric contrast measurements with commercial optical pieces. We present here a laboratory interferometer working at 10,6 microns, and implementing several techniques of optical filtering (pinholes and single-mode waveguides), its realisation, and its first promising results. We particularly present measurements that exhibit stable visibility levels better than 99,9% that is to say extinction levels better than 1000.

  7. Constrained Null Space Component Analysis for Semiblind Source Separation Problem.

    Science.gov (United States)

    Hwang, Wen-Liang; Lu, Keng-Shih; Ho, Jinn

    2018-02-01

    The blind source separation (BSS) problem extracts unknown sources from observations of their unknown mixtures. A current trend in BSS is the semiblind approach, which incorporates prior information on sources or how the sources are mixed. The constrained independent component analysis (ICA) approach has been studied to impose constraints on the famous ICA framework. We introduced an alternative approach based on the null space component (NCA) framework and referred to the approach as the c-NCA approach. We also presented the c-NCA algorithm that uses signal-dependent semidefinite operators, which is a bilinear mapping, as signatures for operator design in the c-NCA approach. Theoretically, we showed that the source estimation of the c-NCA algorithm converges with a convergence rate dependent on the decay of the sequence, obtained by applying the estimated operators on corresponding sources. The c-NCA can be formulated as a deterministic constrained optimization method, and thus, it can take advantage of solvers developed in optimization society for solving the BSS problem. As examples, we demonstrated electroencephalogram interference rejection problems can be solved by the c-NCA with proximal splitting algorithms by incorporating a sparsity-enforcing separation model and considering the case when reference signals are available.

  8. A null relationship between media multitasking and well-being.

    Directory of Open Access Journals (Sweden)

    Shui-I Shih

    Full Text Available There is a rapidly increasing trend in media-media multitasking or MMM (using two or more media concurrently. In a recent conference, scholars from diverse disciplines expressed concerns that indulgence in MMM may compromise well-being and/or cognitive abilities. However, research on MMM's impacts is too sparse to inform the general public and policy makers whether MMM should be encouraged, managed, or minimized. The primary purpose of the present study was to develop an innovative computerized instrument--the Survey of the Previous Day (SPD--to quantify MMM as well as media-nonmedia and nonmedia-nonmedia multitasking and sole-tasking. The secondary purpose was to examine whether these indices could predict a sample of well-being related, psychosocial measures. In the SPD, participants first recalled (typed what they did during each hour of the previous day. In later parts of the SPD, participants analysed activities and their timing and duration for each hour of the previous day, while relevant recall was on display. Participants also completed the Media Use Questionnaire. The results showed non-significant relationship between tasking measures and well-being related measures. Given how little is known about the associations between MMM and well-being, the null results may offer some general reassurance to those who are apprehensive about negative impacts of MMM.

  9. A Null Relationship between Media Multitasking and Well-Being

    Science.gov (United States)

    Shih, Shui-I

    2013-01-01

    There is a rapidly increasing trend in media-media multitasking or MMM (using two or more media concurrently). In a recent conference, scholars from diverse disciplines expressed concerns that indulgence in MMM may compromise well-being and/or cognitive abilities. However, research on MMM's impacts is too sparse to inform the general public and policy makers whether MMM should be encouraged, managed, or minimized. The primary purpose of the present study was to develop an innovative computerized instrument – the Survey of the Previous Day (SPD) – to quantify MMM as well as media-nonmedia and nonmedia-nonmedia multitasking and sole-tasking. The secondary purpose was to examine whether these indices could predict a sample of well-being related, psychosocial measures. In the SPD, participants first recalled (typed) what they did during each hour of the previous day. In later parts of the SPD, participants analysed activities and their timing and duration for each hour of the previous day, while relevant recall was on display. Participants also completed the Media Use Questionnaire. The results showed non-significant relationship between tasking measures and well-being related measures. Given how little is known about the associations between MMM and well-being, the null results may offer some general reassurance to those who are apprehensive about negative impacts of MMM. PMID:23691236

  10. Conical twist fields and null polygonal Wilson loops

    Science.gov (United States)

    Castro-Alvaredo, Olalla A.; Doyon, Benjamin; Fioravanti, Davide

    2018-06-01

    Using an extension of the concept of twist field in QFT to space-time (external) symmetries, we study conical twist fields in two-dimensional integrable QFT. These create conical singularities of arbitrary excess angle. We show that, upon appropriate identification between the excess angle and the number of sheets, they have the same conformal dimension as branch-point twist fields commonly used to represent partition functions on Riemann surfaces, and that both fields have closely related form factors. However, we show that conical twist fields are truly different from branch-point twist fields. They generate different operator product expansions (short distance expansions) and form factor expansions (large distance expansions). In fact, we verify in free field theories, by re-summing form factors, that the conical twist fields operator product expansions are correctly reproduced. We propose that conical twist fields are the correct fields in order to understand null polygonal Wilson loops/gluon scattering amplitudes of planar maximally supersymmetric Yang-Mills theory.

  11. Lovelock vacua with a recurrent null vector field

    Science.gov (United States)

    Ortaggio, Marcello

    2018-02-01

    Vacuum solutions of Lovelock gravity in the presence of a recurrent null vector field (a subset of Kundt spacetimes) are studied. We first discuss the general field equations, which constrain both the base space and the profile functions. While choosing a "generic" base space puts stronger constraints on the profile, in special cases there also exist solutions containing arbitrary functions (at least for certain values of the coupling constants). These and other properties (such as the p p - waves subclass and the overlap with VSI, CSI and universal spacetimes) are subsequently analyzed in more detail in lower dimensions n =5 , 6 as well as for particular choices of the base manifold. The obtained solutions describe various classes of nonexpanding gravitational waves propagating, e.g., in Nariai-like backgrounds M2×Σn -2. An Appendix contains some results about general (i.e., not necessarily Kundt) Lovelock vacua of Riemann type III/N and of Weyl and traceless-Ricci type III/N. For example, it is pointed out that for theories admitting a triply degenerate maximally symmetric vacuum, all the (reduced) field equations are satisfied identically, giving rise to large classes of exact solutions.

  12. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

    2015-01-01

    the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...... of RNA sequencing. The visualization features can reveal notable, non-trivial allelic imbalance behavior over specific regions, such as exons. Conclusions: The software provides a complete framework to perform allelic imbalance analyses of aligned RNA sequencing data, from detection to visualization...

  13. Identification of Novel Alleles Conferring Superior Production of Rose Flavor Phenylethyl Acetate Using Polygenic Analysis in Yeast

    Directory of Open Access Journals (Sweden)

    Bruna Trindade de Carvalho

    2017-11-01

    Full Text Available Flavor compound metabolism is one of the last areas in metabolism where multiple genes encoding biosynthetic enzymes are still unknown. A major challenge is the involvement of side activities of enzymes having their main function in other areas of metabolism. We have applied pooled-segregant whole-genome sequence analysis to identify novel Saccharomyces cerevisiae genes affecting production of phenylethyl acetate (2-PEAc. This is a desirable flavor compound of major importance in alcoholic beverages imparting rose- and honey-like aromas, with production of high 2-PEAc levels considered a superior trait. Four quantitative trait loci (QTLs responsible for high 2-PEAc production were identified, with two loci each showing linkage to the genomes of the BTC.1D and ER18 parents. The first two loci were investigated further. The causative genes were identified by reciprocal allele swapping into both parents using clustered regularly interspaced short palindromic repeat (CRISPR/Cas9. The superior allele of the first major causative gene, FAS2, was dominant and contained two unique single nucleotide polymorphisms (SNPs responsible for high 2-PEAc production that were not present in other sequenced yeast strains. FAS2 encodes the alpha subunit of the fatty acid synthetase complex. Surprisingly, the second causative gene was a mutant allele of TOR1, a gene involved in nitrogen regulation. Exchange of both superior alleles in the ER18 parent strain increased 2-PEAc production 70%, nearly to the same level as in the best superior segregant. Our results show that polygenic analysis combined with CRISPR/Cas9-mediated allele exchange is a powerful tool for identification of genes encoding missing metabolic enzymes and for development of industrial yeast strains generating novel flavor profiles in alcoholic beverages.

  14. An extensive allelic series of Drosophila kae1 mutants reveals diverse and tissue-specific requirements for t6A biogenesis

    Science.gov (United States)

    Lin, Ching-Jung; Smibert, Peter; Zhao, Xiaoyu; Hu, Jennifer F.; Ramroop, Johnny; Kellner, Stefanie M.; Benton, Matthew A.; Govind, Shubha; Dedon, Peter C.; Sternglanz, Rolf; Lai, Eric C.

    2015-01-01

    N6-threonylcarbamoyl-adenosine (t6A) is one of the few RNA modifications that is universally present in life. This modification occurs at high frequency at position 37 of most tRNAs that decode ANN codons, and stabilizes cognate anticodon–codon interactions. Nearly all genetic studies of the t6A pathway have focused on single-celled organisms. In this study, we report the isolation of an extensive allelic series in the Drosophila ortholog of the core t6A biosynthesis factor Kae1. kae1 hemizygous larvae exhibit decreases in t6A that correlate with allele strength; however, we still detect substantial t6A-modified tRNAs even during the extended larval phase of null alleles. Nevertheless, complementation of Drosophila Kae1 and other t6A factors in corresponding yeast null mutants demonstrates that these metazoan genes execute t6A synthesis. Turning to the biological consequences of t6A loss, we characterize prominent kae1 melanotic masses and show that they are associated with lymph gland overgrowth and ectopic generation of lamellocytes. On the other hand, kae1 mutants exhibit other phenotypes that reflect insufficient tissue growth. Interestingly, whole-tissue and clonal analyses show that strongly mitotic tissues such as imaginal discs are exquisitely sensitive to loss of kae1, whereas nonproliferating tissues are less affected. Indeed, despite overt requirements of t6A for growth of many tissues, certain strong kae1 alleles achieve and sustain enlarged body size during their extended larval phase. Our studies highlight tissue-specific requirements of the t6A pathway in a metazoan context and provide insights into the diverse biological roles of this fundamental RNA modification during animal development and disease. PMID:26516084

  15. Estimating and testing the effect of allelic recombination on the ...

    African Journals Online (AJOL)

    Jane

    2011-01-21

    Jan 21, 2011 ... The significance of the correlation coefficient as well as the fitted regression model was obtained using. Analysis of Variance method. Key words: Allele, genotype, regression, correlation, F-ratio, analysis of variance. INTRODUCTION .... while if the allelic replacement is being made on an Aa individual the ...

  16. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These

  17. Comparison of bovine lymphocyte antigen DRB3.2 allele ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-08-04

    Aug 4, 2008 ... The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell ... alleles were more resistant to clinical mastitis. ... DRB3.2 allele pattern in two Iranian Holstein cow .... observed and the number of immune parameters with.

  18. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    DEFF Research Database (Denmark)

    Schierup, Mikkel Heide; Vekemans, Xavier; Christiansen, Freddy Bugge

    1997-01-01

    codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model...

  19. Human minisatellite alleles detectable only after PCR amplification.

    Science.gov (United States)

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  20. Comparative frequency and allelic distribution of ABO and Rh (D ...

    African Journals Online (AJOL)

    Background: Allelic distribution of major blood groups (ABO and rhesus) has not been defined in Bangladeshi population. Determinants of blood group frequency in this region have not been studied properly. Aim: To determine ABO and rhesus blood group frequency and allelic distribution in a multiethnic area of ...

  1. Apolipoprotein E4 allele does not influence serum triglyceride ...

    African Journals Online (AJOL)

    This study investigated how the APOε4 allele affects the serum triglyceride response after a fatmeal in apparently healthy black South African young adults. Sixty students were successfully screened for APOE genotype using Restriction Fragment Length Polymorphism (RFLP) and were divided into four groups; the ε2 allele ...

  2. Measurement of high-departure aspheres using subaperture stitching with the Variable Optical Null (VON)

    Science.gov (United States)

    Kulawiec, Andrew; Murphy, Paul; DeMarco, Michael

    2010-10-01

    Aspheric surfaces are proven to provide significant benefits to a wide variety of optical systems, but the ability to produce high-precision aspheric surfaces has historically been limited by the ability (or lack thereof) to measure them. Traditionally, aspheric measurements have required dedicated null optics, but the cost, lead time, and calibration difficulty of using null optics has made the use of aspheres more challenging and less attractive. In the past three years, QED has developed the Subaperture Stitching Interferometer for Aspheres (SSI-A®) to help address this limitation, providing flexible aspheric measurement capability of up to 200 waves of aspheric departure from best-fit sphere. Some aspheres, however, have thousands of waves of departure. We have recently developed Variable Optical Null (VON) technology that can null much of the aspheric departure in a subaperture. The VON is automatically configurable and is adjusted to nearly null each specific subaperture of an asphere. This ability to nearly null a local subaperture of an asphere provides a significant boost in aspheric measurement capability, enabling aspheres with up to 1000 waves of departure to be measured, without the use of dedicated null optics. We outline the basic principles of subaperture stitching and VON technology, demonstrate the extended capability provided by the VON, and present measurement results from the new Aspheric Stitching Interferometer (ASI®).

  3. Shocks and currents in stratified atmospheres with a magnetic null point

    Science.gov (United States)

    Tarr, Lucas A.; Linton, Mark

    2017-08-01

    We use the resistive MHD code LARE (Arber et al 2001) to inject a compressive MHD wavepacket into a stratified atmosphere that has a single magnetic null point, as recently described in Tarr et al 2017. The 2.5D simulation represents a slice through a small ephemeral region or area of plage. The strong gradients in field strength and connectivity related to the presence of the null produce substantially different dynamics compared to the more slowly varying fields typically used in simple sunspot models. The wave-null interaction produces a fast mode shock that collapses the null into a current sheet and generates a set of outward propagating (from the null) slow mode shocks confined to field lines near each separatrix. A combination of oscillatory reconnection and shock dissipation ultimately raise the plasma's internal energy at the null and along each separatrix by 25-50% above the background. The resulting pressure gradients must be balanced by Lorentz forces, so that the final state has contact discontinuities along each separatrix and a persistent current at the null. The simulation demonstrates that fast and slow mode waves localize currents to the topologically important locations of the field, just as their Alfvenic counterparts do, and also illustrates the necessity of treating waves and reconnection as coupled phenomena.

  4. Modular Hamiltonians on the null plane and the Markov property of the vacuum state

    Science.gov (United States)

    Casini, Horacio; Testé, Eduardo; Torroba, Gonzalo

    2017-09-01

    We compute the modular Hamiltonians of regions having the future horizon lying on a null plane. For a CFT this is equivalent to regions with a boundary of arbitrary shape lying on the null cone. These Hamiltonians have a local expression on the horizon formed by integrals of the stress tensor. We prove this result in two different ways, and show that the modular Hamiltonians of these regions form an infinite dimensional Lie algebra. The corresponding group of unitary transformations moves the fields on the null surface locally along the null generators with arbitrary null line dependent velocities, but act non-locally outside the null plane. We regain this result in greater generality using more abstract tools on the algebraic quantum field theory. Finally, we show that modular Hamiltonians on the null surface satisfy a Markov property that leads to the saturation of the strong sub-additive inequality for the entropies and to the strong super-additivity of the relative entropy.

  5. Mechanical Forces Exacerbate Periodontal Defects in Bsp-null Mice

    Science.gov (United States)

    Soenjaya, Y.; Foster, B.L.; Nociti, F.H.; Ao, M.; Holdsworth, D.W.; Hunter, G.K.; Somerman, M.J.

    2015-01-01

    Bone sialoprotein (BSP) is an acidic phosphoprotein with collagen-binding, cell attachment, and hydroxyapatite-nucleating properties. BSP expression in mineralized tissues is upregulated at onset of mineralization. Bsp-null (Bsp-/-) mice exhibit reductions in bone mineral density, bone turnover, osteoclast activation, and impaired bone healing. Furthermore, Bsp-/- mice have marked periodontal tissue breakdown, with a lack of acellular cementum leading to periodontal ligament detachment, extensive alveolar bone and tooth root resorption, and incisor malocclusion. We hypothesized that altered mechanical stress from mastication contributes to periodontal destruction observed in Bsp-/- mice. This hypothesis was tested by comparing Bsp-/- and wild-type mice fed with standard hard pellet diet or soft powder diet. Dentoalveolar tissues were analyzed using histology and micro–computed tomography. By 8 wk of age, Bsp-/- mice exhibited molar and incisor malocclusion regardless of diet. Bsp-/- mice with hard pellet diet exhibited high incidence (30%) of severe incisor malocclusion, 10% lower body weight, 3% reduced femur length, and 30% elevated serum alkaline phosphatase activity compared to wild type. Soft powder diet reduced severe incisor malocclusion incidence to 3% in Bsp-/- mice, supporting the hypothesis that occlusal loading contributed to the malocclusion phenotype. Furthermore, Bsp-/- mice in the soft powder diet group featured normal body weight, long bone length, and serum alkaline phosphatase activity, suggesting that tooth dysfunction and malnutrition contribute to growth and skeletal defects reported in Bsp-/- mice. Bsp-/- incisors also erupt at a slower rate, which likely leads to the observed thickened dentin and enhanced mineralization of dentin and enamel toward the apical end. We propose that the decrease in eruption rate is due to a lack of acellular cementum and associated defective periodontal attachment. These data demonstrate the importance of BSP

  6. Magnetoacoustic Waves in a Stratified Atmosphere with a Magnetic Null Point

    Energy Technology Data Exchange (ETDEWEB)

    Tarr, Lucas A.; Linton, Mark; Leake, James, E-mail: lucas.tarr.ctr@nrl.navy.mil [U.S. Naval Research Laboratory, 4555 Overlook Ave. SW, Washington, DC 20375 (United States)

    2017-03-01

    We perform nonlinear MHD simulations to study the propagation of magnetoacoustic waves from the photosphere to the low corona. We focus on a 2D system with a gravitationally stratified atmosphere and three photospheric concentrations of magnetic flux that produce a magnetic null point with a magnetic dome topology. We find that a single wavepacket introduced at the lower boundary splits into multiple secondary wavepackets. A portion of the packet refracts toward the null owing to the varying Alfvén speed. Waves incident on the equipartition contour surrounding the null, where the sound and Alfvén speeds coincide, partially transmit, reflect, and mode-convert between branches of the local dispersion relation. Approximately 15.5% of the wavepacket’s initial energy ( E {sub input}) converges on the null, mostly as a fast magnetoacoustic wave. Conversion is very efficient: 70% of the energy incident on the null is converted to slow modes propagating away from the null, 7% leaves as a fast wave, and the remaining 23% (0.036 E {sub input}) is locally dissipated. The acoustic energy leaving the null is strongly concentrated along field lines near each of the null’s four separatrices. The portion of the wavepacket that refracts toward the null, and the amount of current accumulation, depends on the vertical and horizontal wavenumbers and the centroid position of the wavepacket as it crosses the photosphere. Regions that refract toward or away from the null do not simply coincide with regions of open versus closed magnetic field or regions of particular field orientation. We also model wavepacket propagation using a WKB method and find that it agrees qualitatively, though not quantitatively, with the results of the numerical simulation.

  7. An improved null model for assessing the net effects of multiple stressors on communities.

    Science.gov (United States)

    Thompson, Patrick L; MacLennan, Megan M; Vinebrooke, Rolf D

    2018-01-01

    Ecological stressors (i.e., environmental factors outside their normal range of variation) can mediate each other through their interactions, leading to unexpected combined effects on communities. Determining whether the net effect of stressors is ecologically surprising requires comparing their cumulative impact to a null model that represents the linear combination of their individual effects (i.e., an additive expectation). However, we show that standard additive and multiplicative null models that base their predictions on the effects of single stressors on community properties (e.g., species richness or biomass) do not provide this linear expectation, leading to incorrect interpretations of antagonistic and synergistic responses by communities. We present an alternative, the compositional null model, which instead bases its predictions on the effects of stressors on individual species, and then aggregates them to the community level. Simulations demonstrate the improved ability of the compositional null model to accurately provide a linear expectation of the net effect of stressors. We simulate the response of communities to paired stressors that affect species in a purely additive fashion and compare the relative abilities of the compositional null model and two standard community property null models (additive and multiplicative) to predict these linear changes in species richness and community biomass across different combinations (both positive, negative, or opposite) and intensities of stressors. The compositional model predicts the linear effects of multiple stressors under almost all scenarios, allowing for proper classification of net effects, whereas the standard null models do not. Our findings suggest that current estimates of the prevalence of ecological surprises on communities based on community property null models are unreliable, and should be improved by integrating the responses of individual species to the community level as does our

  8. OBSERVATION OF MAGNETIC RECONNECTION AT A 3D NULL POINT ASSOCIATED WITH A SOLAR ERUPTION

    International Nuclear Information System (INIS)

    Sun, J. Q.; Yang, K.; Cheng, X.; Ding, M. D.; Zhang, J.

    2016-01-01

    Magnetic null has long been recognized as a special structure serving as a preferential site for magnetic reconnection (MR). However, the direct observational study of MR at null-points is largely lacking. Here, we show the observations of MR around a magnetic null associated with an eruption that resulted in an M1.7 flare and a coronal mass ejection. The Geostationary Operational Environmental Satellites X-ray profile of the flare exhibited two peaks at ∼02:23 UT and ∼02:40 UT on 2012 November 8, respectively. Based on the imaging observations, we find that the first and also primary X-ray peak was originated from MR in the current sheet (CS) underneath the erupting magnetic flux rope (MFR). On the other hand, the second and also weaker X-ray peak was caused by MR around a null point located above the pre-eruption MFR. The interaction of the null point and the erupting MFR can be described as a two-step process. During the first step, the erupting and fast expanding MFR passed through the null point, resulting in a significant displacement of the magnetic field surrounding the null. During the second step, the displaced magnetic field started to move back, resulting in a converging inflow and subsequently the MR around the null. The null-point reconnection is a different process from the current sheet reconnection in this flare; the latter is the cause of the main peak of the flare, while the former is the cause of the secondary peak of the flare and the conspicuous high-lying cusp structure.

  9. Assigning breed origin to alleles in crossbred animals.

    Science.gov (United States)

    Vandenplas, Jérémie; Calus, Mario P L; Sevillano, Claudia A; Windig, Jack J; Bastiaansen, John W M

    2016-08-22

    For some species, animal production systems are based on the use of crossbreeding to take advantage of the increased performance of crossbred compared to purebred animals. Effects of single nucleotide polymorphisms (SNPs) may differ between purebred and crossbred animals for several reasons: (1) differences in linkage disequilibrium between SNP alleles and a quantitative trait locus; (2) differences in genetic backgrounds (e.g., dominance and epistatic interactions); and (3) differences in environmental conditions, which result in genotype-by-environment interactions. Thus, SNP effects may be breed-specific, which has led to the development of genomic evaluations for crossbred performance that take such effects into account. However, to estimate breed-specific effects, it is necessary to know breed origin of alleles in crossbred animals. Therefore, our aim was to develop an approach for assigning breed origin to alleles of crossbred animals (termed BOA) without information on pedigree and to study its accuracy by considering various factors, including distance between breeds. The BOA approach consists of: (1) phasing genotypes of purebred and crossbred animals; (2) assigning breed origin to phased haplotypes; and (3) assigning breed origin to alleles of crossbred animals based on a library of assigned haplotypes, the breed composition of crossbred animals, and their SNP genotypes. The accuracy of allele assignments was determined for simulated datasets that include crosses between closely-related, distantly-related and unrelated breeds. Across these scenarios, the percentage of alleles of a crossbred animal that were correctly assigned to their breed origin was greater than 90 %, and increased with increasing distance between breeds, while the percentage of incorrectly assigned alleles was always less than 2 %. For the remaining alleles, i.e. 0 to 10 % of all alleles of a crossbred animal, breed origin could not be assigned. The BOA approach accurately assigns

  10. Sortilin-Related Receptor Expression in Human Neural Stem Cells Derived from Alzheimer’s Disease Patients Carrying the APOE Epsilon 4 Allele

    Directory of Open Access Journals (Sweden)

    Alen Zollo

    2017-01-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia in the elderly; important risk factors are old age and inheritance of the apolipoprotein E4 (APOE4 allele. Changes in amyloid precursor protein (APP binding, trafficking, and sorting may be important AD causative factors. Secretase-mediated APP cleavage produces neurotoxic amyloid-beta (Aβ peptides, which form lethal deposits in the brain. In vivo and in vitro studies have implicated sortilin-related receptor (SORL1 as an important factor in APP trafficking and processing. Recent in vitro evidence has associated the APOE4 allele and alterations in the SORL1 pathway with AD development and progression. Here, we analyzed SORL1 expression in neural stem cells (NSCs from AD patients carrying null, one, or two copies of the APOE4 allele. We show reduced SORL1 expression only in NSCs of a patient carrying two copies of APOE4 allele with increased Aβ/SORL1 localization along the degenerated neurites. Interestingly, SORL1 binding to APP was largely compromised; this could be almost completely reversed by γ-secretase (but not β-secretase inhibitor treatment. These findings may yield new insights into the complex interplay of SORL1 and AD pathology and point to NSCs as a valuable tool to address unsolved AD-related questions in vitro.

  11. A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence.

    Science.gov (United States)

    Grucza, Richard A; Wang, Jen C; Stitzel, Jerry A; Hinrichs, Anthony L; Saccone, Scott F; Saccone, Nancy L; Bucholz, Kathleen K; Cloninger, C Robert; Neuman, Rosalind J; Budde, John P; Fox, Louis; Bertelsen, Sarah; Kramer, John; Hesselbrock, Victor; Tischfield, Jay; Nurnberger, John I; Almasy, Laura; Porjesz, Bernice; Kuperman, Samuel; Schuckit, Marc A; Edenberg, Howard J; Rice, John P; Goate, Alison M; Bierut, Laura J

    2008-12-01

    A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence. Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA). In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD. The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.

  12. Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors

    KAUST Repository

    Joffré, Enrique

    2015-01-15

    Enterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.

  13. Allele Variants of Enterotoxigenic Escherichia coli Heat-Labile Toxin Are Globally Transmitted and Associated with Colonization Factors

    KAUST Repository

    Joffré , Enrique; von Mentzer, Astrid; Abd El Ghany, Moataz; Oezguen, Numan; Savidge, Tor; Dougan, Gordon; Svennerholm, Ann-Mari; Sjö ling, Å sa

    2015-01-01

    Enterotoxigenic Escherichia coli (ETEC) is a significant cause of morbidity and mortality in the developing world. ETEC-mediated diarrhea is orchestrated by heat-labile toxin (LT) and heat-stable toxins (STp and STh), acting in concert with a repertoire of more than 25 colonization factors (CFs). LT, the major virulence factor, induces fluid secretion after delivery of a monomeric ADP-ribosylase (LTA) and its pentameric carrier B subunit (LTB). A study of ETEC isolates from humans in Brazil reported the existence of natural LT variants. In the present study, analysis of predicted amino acid sequences showed that the LT amino acid polymorphisms are associated with a geographically and temporally diverse set of 192 clinical ETEC strains and identified 12 novel LT variants. Twenty distinct LT amino acid variants were observed in the globally distributed strains, and phylogenetic analysis showed these to be associated with different CF profiles. Notably, the most prevalent LT1 allele variants were correlated with major ETEC lineages expressing CS1 + CS3 or CS2 + CS3, and the most prevalent LT2 allele variants were correlated with major ETEC lineages expressing CS5 + CS6 or CFA/I. LTB allele variants generally exhibited more-stringent amino acid sequence conservation (2 substitutions identified) than LTA allele variants (22 substitutions identified). The functional impact of LT1 and LT2 polymorphisms on virulence was investigated by measuring total-toxin production, secretion, and stability using GM1-enzyme-linked immunosorbent assays (GM1-ELISA) and in silico protein modeling. Our data show that LT2 strains produce 5-fold more toxin than LT1 strains (P < 0.001), which may suggest greater virulence potential for this genetic variant. Our data suggest that functionally distinct LT-CF variants with increased fitness have persisted during the evolution of ETEC and have spread globally.

  14. Impaired Uptake and/or Utilization of Leucine by Saccharomyces cerevisiae Is Suppressed by the SPT15-300 Allele of the TATA-Binding Protein Gene

    DEFF Research Database (Denmark)

    Baerends, RJ; Qiu, Jin-Long; Rasmussen, Simon

    2009-01-01

    Successful fermentations to produce ethanol require microbial strains that have a high tolerance to glucose and ethanol. Enhanced glucose/ethanol tolerance of the laboratory yeast Saccharomyces cerevisiae strain BY4741 under certain growth conditions as a consequence of the expression of a dominant...... us to examine the effect of expression of the SPT15-300 allele in various yeast species of industrial importance. Expression of SPT15-300 in leucine-prototrophic strains of S. cerevisiae, Saccharomyces bayanus, or Saccharomyces pastorianus (lager brewing yeast), however, did not improve tolerance...... to ethanol on complex rich medium (yeast extract-peptone-dextrose). The enhanced growth of the laboratory yeast strain BY4741 expressing the SPT15-300 mutant allele was seen only on defined media with low concentrations of leucine, indicating that the apparent improved growth in the presence of ethanol...

  15. Argonaute-2-null embryonic stem cells are retarded in self-renewal ...

    Indian Academy of Sciences (India)

    Present address: Institute of Stem Cells and Regenerative Medicine, Bangalore, India ... [Chandra Shekar P, Naim A, Partha Sarathi D and Kumar S 2011 Argonaute-2-null embryonic stem cells are retarded in self-renewal ..... Research, India.

  16. Possible Solution to Publication Bias Through Bayesian Statistics, Including Proper Null Hypothesis Testing

    NARCIS (Netherlands)

    Konijn, Elly A.; van de Schoot, Rens; Winter, Sonja D.; Ferguson, Christopher J.

    2015-01-01

    The present paper argues that an important cause of publication bias resides in traditional frequentist statistics forcing binary decisions. An alternative approach through Bayesian statistics provides various degrees of support for any hypothesis allowing balanced decisions and proper null

  17. Vacuum non-expanding horizons and shear-free null geodesic congruences

    International Nuclear Information System (INIS)

    Adamo, T M; Newman, E T

    2009-01-01

    We investigate the geometry of a particular class of null surfaces in spacetime called vacuum non-expanding horizons (NEHs). Using the spin-coefficient equation, we provide a complete description of the horizon geometry, as well as fixing a canonical choice of null tetrad and coordinates on a NEH. By looking for particular classes of null geodesic congruences which live exterior to NEHs but have the special property that their shear vanishes at the intersection with the horizon, a good cut formalism for NEHs is developed which closely mirrors asymptotic theory. In particular, we show that such null geodesic congruences are generated by arbitrary choice of a complex worldline in a complex four-dimensional space, each such choice induces a CR structure on the horizon, and a particular worldline (and hence CR structure) may be chosen by transforming to a privileged tetrad frame.

  18. ON THE NATURE OF RECONNECTION AT A SOLAR CORONAL NULL POINT ABOVE A SEPARATRIX DOME

    International Nuclear Information System (INIS)

    Pontin, D. I.; Priest, E. R.; Galsgaard, K.

    2013-01-01

    Three-dimensional magnetic null points are ubiquitous in the solar corona and in any generic mixed-polarity magnetic field. We consider magnetic reconnection at an isolated coronal null point whose fan field lines form a dome structure. Using analytical and computational models, we demonstrate several features of spine-fan reconnection at such a null, including the fact that substantial magnetic flux transfer from one region of field line connectivity to another can occur. The flux transfer occurs across the current sheet that forms around the null point during spine-fan reconnection, and there is no separator present. Also, flipping of magnetic field lines takes place in a manner similar to that observed in the quasi-separatrix layer or slip-running reconnection

  19. Are eikonal quasinormal modes linked to the unstable circular null geodesics?

    Directory of Open Access Journals (Sweden)

    R.A. Konoplya

    2017-08-01

    Full Text Available In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein–Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein–Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

  20. Are eikonal quasinormal modes linked to the unstable circular null geodesics?

    Science.gov (United States)

    Konoplya, R. A.; Stuchlík, Z.

    2017-08-01

    In Cardoso et al. [6] it was claimed that quasinormal modes which any stationary, spherically symmetric and asymptotically flat black hole emits in the eikonal regime are determined by the parameters of the circular null geodesic: the real and imaginary parts of the quasinormal mode are multiples of the frequency and instability timescale of the circular null geodesics respectively. We shall consider asymptotically flat black hole in the Einstein-Lovelock theory, find analytical expressions for gravitational quasinormal modes in the eikonal regime and analyze the null geodesics. Comparison of the both phenomena shows that the expected link between the null geodesics and quasinormal modes is violated in the Einstein-Lovelock theory. Nevertheless, the correspondence exists for a number of other cases and here we formulate its actual limits.

  1. Vlasov Fluid stability of a 2-D plasma with a linear magnetic field null

    International Nuclear Information System (INIS)

    Kim, J.S.

    1984-01-01

    Vlasov Fluid stability of a 2-dimensional plasma near an O type magnetic null is investigated. Specifically, an elongated Z-pinch is considered, and applied to Field Reversed Configurations at Los Alamos National Laboratory by making a cylindrical approximation of the compact torus. The orbits near an elliptical O type null are found to be very complicated; the orbits are large and some are stochastic. The kinetic corrections to magnetohydrodynamics (MHD) are investigated by evaluating the expectation values of the growth rates of a Vlasov Fluid dispersion functional by using a set of trial functions based on ideal MHD. The dispersion functional involves fluid parts and orbit dependent parts. The latter involves phase integral of two time correlations. The phase integral is replaced by the time integral both for the regular and for the stochastic orbits. Two trial functions are used; one has a large displacement near the null and the other away from the null

  2. Development of a High Resolution Virulence Allelic Profiling (HReVAP) Approach Based on the Accessory Genome of Escherichia coli to Characterize Shiga-Toxin Producing E. coli (STEC)

    Science.gov (United States)

    Michelacci, Valeria; Orsini, Massimiliano; Knijn, Arnold; Delannoy, Sabine; Fach, Patrick; Caprioli, Alfredo; Morabito, Stefano

    2016-01-01

    Shiga-toxin producing Escherichia coli (STEC) strains possess a large accessory genome composed of virulence genes existing in multiple allelic variants, which sometimes segregate with specific STEC subpopulations. We analyzed the allelic variability of 91 virulence genes of STEC by Real Time PCR followed by melting curves analysis in 713 E. coli strains including 358 STEC. The 91 genes investigated were located on the locus of enterocyte effacement (LEE), OI-57, and OI-122 pathogenicity islands and displayed a total of 476 alleles in the study population. The combinations of the 91 alleles of each strain were termed allelic signatures and used to perform cluster analyses. We termed such an approach High Resolution Virulence Allelic Profiling (HReVAP) and used it to investigate the phylogeny of STEC of multiple serogroups. The dendrograms obtained identified groups of STEC segregating approximately with the serogroups and allowed the identification of subpopulations within the single groups. The study of the allelic signatures provided further evidence of the coevolution of the LEE and OI-122, reflecting the occurrence of their acquisition through a single event. The HReVAP analysis represents a sensitive tool for studying the evolution of LEE-positive STEC. PMID:26941726

  3. Allele-specific marker generation and linkage mapping on the Xiphophorus sex chromosomes.

    Science.gov (United States)

    Woolcock, B; Kazianis, S; Lucito, R; Walter, R B; Kallman, K D; Morizot, D C; Vielkind, J R

    2006-01-01

    There is great interest in the sex chromosomes of Xiphophorus fishes because both WY/YY and XX/XY sex-determining mechanisms function in these species, with at least one taxon possessing all three types of sex chromosomes, and because in certain interspecific hybrids melanoma arises as a consequence of inheritance of the sex-linked macromelanophore determining locus (MDL). Representational difference analysis (RDA) has been used to clone two sequences from the sex-determining region of X. maculatus, including a cholinergic receptor, nicotinic, delta polypeptide (CHRND) orthologue. Allele-specific assays for these sequences, as well as for the sex-linked XMRK1 and XMRK2 genes, were developed to distinguish W, X, and Y chromosomes derived from a X. maculatus (XX/XY) strain and a X. helleri (WY/YY) strain. Linkage mapping localized these markers to linkage group (LG) 24. No recombinants were observed between XMRK2 and MDL, confirming a role for XMRK2 in macromelanophore development. Although the master sex-determining (SD) locus certainly resides on Xiphophorus LG 24, autosomal loci are probably involved in sex determination as well, as indicated by the abnormal sex ratios in the backcross hybrids that contrast theoretical predictions based on LG 24 genotyping. Marker development and allelic discrimination on the Xiphophorus sex chromosomes should prove highly useful for studies that utilize this genus as an animal model.

  4. Identification of tms-26 as an allele of the gcaD gene, which encodes N-acetylglucosamine 1-phosphate uridyltransferase in Bacillus subtilis

    DEFF Research Database (Denmark)

    Hove-Jensen, Bjarne

    1992-01-01

    -acetylglucosamine 1-phosphate, the substrate of the uridyltransferase activity, was elevated more than 40-fold in the mutant strain at the permissive temperature compared with the level in the wild-type strain. During a temperature shift, the level of UDP-N-acetylglucosamine, the product of the uridyltransferase...... activity, decreased much more in the mutant strain than in the wild-type strain. An Escherichia coli strain harboring the wild-type version of the tms-26 allele on a plasmid contained increased N-acetylglucosamine 1-phosphate uridyltransferase activity compared with that in the haploid strain...

  5. Hypersensitivities for acetaldehyde and other agents among cancer cells null for clinically relevant Fanconi anemia genes.

    Science.gov (United States)

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R; Rago, Carlo; Bhunia, Anil K; Hossain, M Zulfiquer; Paun, Bogdan C; Ren, Yunzhao R; Iacobuzio-Donahue, Christine A; Azad, Nilofer A; Kern, Scott E

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, including the engineering of new PALB2/FANCN-null cancer cells by homologous recombination. A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phenotypes was confirmed by uniform tumor regression on single-dose cross-linker therapy in mice and by shared chemical hypersensitivities to various inter-strand cross-linking agents and γ-radiation in vitro. Some compounds, however, had contrasting magnitudes of sensitivity; a strikingly high (19- to 22-fold) hypersensitivity was seen among PALB2-null and BRCA2-null cells for the ethanol metabolite, acetaldehyde, associated with widespread chromosomal breakage at a concentration not producing breaks in parental cells. Because FANC-defective cancer cells can share or differ in their chemical sensitivities, patterns of selective hypersensitivity hold implications for the evolutionary understanding of this pathway. Clinical decisions for cancer-relevant prevention and management of FANC-mutation carriers could be modified by expanded studies of high-magnitude sensitivities. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Null geodesics and embedding diagrams of the interior Schwarzschild--de Sitter spacetimes with uniform density

    International Nuclear Information System (INIS)

    Stuchlik, Zdenek; Hledik, Stanislav; Soltes, Jiri; Ostgaard, Erlend

    2001-01-01

    Null geodesics and embedding diagrams of central planes in the ordinary space geometry and the optical reference geometry of the interior Schwarzschild--de Sitter spacetimes with uniform density are studied. For completeness, both positive and negative values of the cosmological constant are considered. The null geodesics are restricted to the central planes of these spacetimes, and their properties can be reflected by an 'effective potential.' If the interior spacetime is extremely compact, the effective potential has a local maximum corresponding to a stable circular null geodesic around which bound null geodesics are concentrated. The upper limit on the size of the interior spacetimes containing bound null geodesics is R=3M, independently of the value of the cosmological constant. The embedding diagrams of the central planes of the ordinary geometry into three-dimensional Euclidean space are well defined for the complete interior of all spacetimes with a repulsive cosmological constant, but the planes cannot be embedded into the Euclidean space in the case of spacetimes with subcritical values of an attractive cosmological constant. On the other hand, the embedding diagrams of the optical geometry are well defined for all of the spacetimes, and the turning points of these diagrams correspond to the radii of the circular null geodesics. All the embedding diagrams, for both the ordinary and optical geometry, are smoothly matched to the corresponding embedding diagrams of the external vacuum Schwarzschild--de Sitter spacetimes

  7. pyNSMC: A Python Module for Null-Space Monte Carlo Uncertainty Analysis

    Science.gov (United States)

    White, J.; Brakefield, L. K.

    2015-12-01

    The null-space monte carlo technique is a non-linear uncertainty analyses technique that is well-suited to high-dimensional inverse problems. While the technique is powerful, the existing workflow for completing null-space monte carlo is cumbersome, requiring the use of multiple commandline utilities, several sets of intermediate files and even a text editor. pyNSMC is an open-source python module that automates the workflow of null-space monte carlo uncertainty analyses. The module is fully compatible with the PEST and PEST++ software suites and leverages existing functionality of pyEMU, a python framework for linear-based uncertainty analyses. pyNSMC greatly simplifies the existing workflow for null-space monte carlo by taking advantage of object oriented design facilities in python. The core of pyNSMC is the ensemble class, which draws and stores realized random vectors and also provides functionality for exporting and visualizing results. By relieving users of the tedium associated with file handling and command line utility execution, pyNSMC instead focuses the user on the important steps and assumptions of null-space monte carlo analysis. Furthermore, pyNSMC facilitates learning through flow charts and results visualization, which are available at many points in the algorithm. The ease-of-use of the pyNSMC workflow is compared to the existing workflow for null-space monte carlo for a synthetic groundwater model with hundreds of estimable parameters.

  8. The data-driven null models for information dissemination tree in social networks

    Science.gov (United States)

    Zhang, Zhiwei; Wang, Zhenyu

    2017-10-01

    For the purpose of detecting relatedness and co-occurrence between users, as well as the distribution features of nodes in spreading path of a social network, this paper explores topological characteristics of information dissemination trees (IDT) that can be employed indirectly to probe the information dissemination laws within social networks. Hence, three different null models of IDT are presented in this article, including the statistical-constrained 0-order IDT null model, the random-rewire-broken-edge 0-order IDT null model and the random-rewire-broken-edge 2-order IDT null model. These null models firstly generate the corresponding randomized copy of an actual IDT; then the extended significance profile, which is developed by adding the cascade ratio of information dissemination path, is exploited not only to evaluate degree correlation of two nodes associated with an edge, but also to assess the cascade ratio of different length of information dissemination paths. The experimental correspondences of the empirical analysis for several SinaWeibo IDTs and Twitter IDTs indicate that the IDT null models presented in this paper perform well in terms of degree correlation of nodes and dissemination path cascade ratio, which can be better to reveal the features of information dissemination and to fit the situation of real social networks.

  9. Losses at magnetic nulls in pulsed-power transmission line systems

    International Nuclear Information System (INIS)

    Mendel, C.W. Jr.; Pointon, T.D.; Savage, M.E.; Seidel, D.B.; Magne, I.; Vezinet, R.

    2006-01-01

    Pulsed-power systems operating in the terawatt regime must deal with large electron flows in vacuum transmission lines. In most parts of these transmission lines the electrons are constrained by the self-magnetic field to flow parallel to the conductors. In very low impedance systems, such as those used to drive Z-pinch radiation sources, the currents from multiple transmission lines are added together. This addition necessarily involves magnetic nulls that connect the positive and negative electrodes. The resultant local loss of magnetic insulation results in electron losses at the anode in the vicinity of the nulls. The lost current due to the magnetic null might or might not be appreciable. In some cases the lost current due to the null is not large, but is spatially localized, and may create a gas and plasma release from the anode that can lead to an excessive loss, and possibly to catastrophic damage to the hardware. In this paper we describe an analytic model that uses one geometric parameter (aside from straightforward hardware size measurements) that determines the loss to the anode, and the extent of the loss region when the driving source and load are known. The parameter can be calculated in terms of the magnetic field in the region of the null calculated when no electron flow is present. The model is compared to some experimental data, and to simulations of several different hardware geometries, including some cases with multiple nulls, and unbalanced feeds

  10. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

    International Nuclear Information System (INIS)

    Takubo, Keiyo; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio

    2006-01-01

    Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16 Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16 Ink4a -mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16 Ink4a -mediated senescence

  11. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    /GCA, MBL variant alleles were associated with signs of increased inflammatory activity and clinical signs of arteritic manifestations. This was not found for HLA-DR4 alleles. These findings indicate that HLA-DR4 and MBL are contributing to the pathophysiology of GCA at different levels in the disease...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...... not associated with any clinical phenotypes of PMR/GCA, whereas MBL variant alleles were associated with cranial arteritis, high erythrocyte sedimentation rate, and low B-hemoglobin. CONCLUSION: We found MBL variant alleles and HLA-DR4 alleles to be weak susceptibility markers for GCA. In patients with PMR...

  12. Ancient DNA Investigation of a Medieval German Cemetery Confirms Long-Term Stability of CCR5-Δ32 Allele Frequencies in Central Europe.

    Science.gov (United States)

    Bouwman, Abigail; Shved, Natallia; Akgül, Gülfirde; Rühli, Frank; Warinner, Christina

    2017-04-01

    The CCR5-Δ32 mutation present in European populations is among the most prominently debated cases of recent positive selection in humans. This allele, a 32-bp deletion that renders the T-cell CCR5 receptor nonfunctional, has important epidemiological and public health significance, as homozygous carriers are resistant to several HIV strains. However, although the function of this allele in preventing HIV infection is now well described, its human evolutionary origin is poorly understood. Initial attempts to determine the emergence of the CCR5-Δ32 allele pointed to selection during the 14th-century Black Death pandemic; however, subsequent analyses suggest that the allele rose in frequency more than 5,000 years ago, possibly through drift. Recently, three studies have identified populations predating the 14th century CE that are positive for the CCR5-Δ32 allele, supporting the claim for a more ancient origin. However, these studies also suggest poorly understood regional differences in the recent evolutionary history of the CCR5-Δ32 allele. Here a new hydrolysis-probe-based real-time PCR assay was designed to ascertain CCR5 allele frequency in 53 individuals from a 10th- to 12th-century CE church and convent complex in central Germany that predates outbreaks of the Black Death pandemic. High-confidence genotypes were obtained for 32 individuals, and results show that CCR5-Δ32 allele frequency has remained unchanged in this region of Central Europe over the last millennium, suggesting that there has been no strong positive selective pressure over this time period and confirming a more ancient origin for the allele.

  13. allelic variation of hmw glutenin subunits of ethiopian bread wheat

    African Journals Online (AJOL)

    journal

    High molecular weight glutenins are often effective in identifying wheat (Triticum ... There were highly significant differences between genotypes and banding ... was without deliberate selection pressure towards high Glu-1 scoring alleles ...

  14. Association mapping and favorable QTL alleles for fiber quality traits ...

    Indian Academy of Sciences (India)

    A total of 201 markers were polymorphic and generated 394 ... identified favorable QTL alleles and typical accessions for fiber quality are excellent genetic resources for future cotton .... Field management followed respective local practices.

  15. Apolipoprotein e4 allele and cognitive decline in elderly men

    NARCIS (Netherlands)

    Feskens, E.J.M.; Havekes, L.M.; Kalmijn, S.; Knijff, P. de; Launer, L.J.; Kromhout, D.

    1994-01-01

    Objectives - To determine whether polymorphism of apolipoprotein E - notably, the e4 allele - predicts cognitive deterioration in the general population. Design - Population based cohort investigated in 1990 and in 1993. Setting - Zutphen, the Netherlands. Subjects - Representative cohort of 538

  16. DRD4 dopamine receptor allelic diversity in various primate species

    Energy Technology Data Exchange (ETDEWEB)

    Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

    1994-09-01

    The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

  17. Allele frequency distribution for 21 autosomal STR loci in Nepal.

    Science.gov (United States)

    Kraaijenbrink, T; van Driem, G L; Opgenort, J R M L; Tuladhar, N M; de Knijff, P

    2007-05-24

    The allele frequency distributions of 21 autosomal loci contained in the AmpFlSTR Identifiler, the Powerplex 16 and the FFFL multiplex PCR kits, was studied in 953 unrelated individuals from Nepal. Several new alleles (i.e. not yet reported in the NIST Short Tandem Repeat DNA Internet DataBase [http://www.cstl.nist.gov/biotech/strbase/]) have been detected in the process.

  18. [Multilocus sequence-typing for characterization of Moscow strains of Haemophilus influenzae type b].

    Science.gov (United States)

    Platonov, A E; Mironov, K O; Iatsyshina, S B; Koroleva, I S; Platonova, O V; Gushchin, A E; Shipulin, G A

    2003-01-01

    Haemophilius influenzae, type b (Hib) bacteria, were genotyped by multilocus sequence typing (MLST) using 5 loci (adk, fucK, mdh, pgi, recA). 42 Moscow Hib strains (including 38 isolates form cerebrospinal fluid of children, who had purulent meningitis in 1999-2001, and 4 strains isolated from healthy carriers of Hib), as well as 2 strains from Yekaterinburg were studied. In MLST a strain is characterized, by alleles and their combinations (an allele profile) referred to also as sequence-type (ST). 9 Sts were identified within the Russian Hib bacteria: ST-1 was found in 25 strains (57%), ST-12 was found in 8 strains (18%), ST-11 was found in 4 strains (9%) and ST-15 was found in 2 strains (4.5%); all other STs strains (13, 14, 16, 17, 51) were found in isolated cases (2.3%). A comparison of allelic profiles and of nucleotide sequences showed that 93% of Russian isolates, i.e. strain with ST-1, 11, 12, 13, 15 and 17, belong to one and the same clonal complex. 2 isolates from Norway and Sweden from among 7 foreign Hib strains studied up to now can be described as belonging to the same clonal complex; 5 Hib strains were different from the Russian ones.

  19. Genotyping of vacA alleles of Helicobacter pylori strains recovered ...

    African Journals Online (AJOL)

    commonly detected genotypes in the meat-based foods, viz, vegetable sandwich and ready to eat fish, were vacA ... Keywords: Helicobacter pylori, VacA genotypes, Genotyping, Food items ..... Microbiology and Quality Control, Islamic Azad.

  20. Na{sup +}/H{sup +} exchanger-1 alleles: Strain distribution and correlation with activity

    Energy Technology Data Exchange (ETDEWEB)

    McClive, P.J.; Morahan, G. [Walter and Eliza Hall Inst. of Medical Research, Parkville, Victoria (Australia); Little, P.J. [Baker Medical Research Inst., Victoria (Australia)

    1996-12-31

    The Na{sup +}/H{sup +} exchanger-1 molecule (NHE1) regulates intracellular pH, cell volume, and cell growth. NHE1 is a phosphoprotein of approximately M{sub r} 110000 with 10 or 12 transmembrane domains. NHE1 is ubiquitously expressed. Three other family members have been identified which show close similarity to NHE1 but are significantly more restricted in their expression: all are found in the gastrointestinal tract, while NHE2 and NHE3 are also expressed in the kidney. 14 refs., 2 figs.

  1. ALEA: a toolbox for allele-specific epigenomics analysis.

    Science.gov (United States)

    Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

    2014-04-15

    The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data. The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea CONTACT: : mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Allele-specific MMP-3 transcription under in vivo conditions

    Energy Technology Data Exchange (ETDEWEB)

    Chaoyong, Zhu [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Odeberg, Jacob [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm (Sweden); Hamsten, Anders [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Eriksson, Per [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden)

    2006-09-29

    A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

  3. SSR allelic variation in almond (Prunus dulcis Mill.).

    Science.gov (United States)

    Xie, Hua; Sui, Yi; Chang, Feng-Qi; Xu, Yong; Ma, Rong-Cai

    2006-01-01

    Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

  4. Origin of allelic diversity in antirrhinum S locus RNases.

    Science.gov (United States)

    Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

    1996-01-01

    In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate. PMID:8672882

  5. Influence of choice of null network on small-world parameters of structural correlation networks.

    Directory of Open Access Journals (Sweden)

    S M Hadi Hosseini

    Full Text Available In recent years, coordinated variations in brain morphology (e.g., volume, thickness have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1 networks constructed by topology randomization (TOP, 2 networks matched to the distributional properties of the observed covariance matrix (HQS, and 3 networks generated from correlation of randomized input data (COR. The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures.

  6. Influence of Choice of Null Network on Small-World Parameters of Structural Correlation Networks

    Science.gov (United States)

    Hosseini, S. M. Hadi; Kesler, Shelli R.

    2013-01-01

    In recent years, coordinated variations in brain morphology (e.g., volume, thickness) have been employed as a measure of structural association between brain regions to infer large-scale structural correlation networks. Recent evidence suggests that brain networks constructed in this manner are inherently more clustered than random networks of the same size and degree. Thus, null networks constructed by randomizing topology are not a good choice for benchmarking small-world parameters of these networks. In the present report, we investigated the influence of choice of null networks on small-world parameters of gray matter correlation networks in healthy individuals and survivors of acute lymphoblastic leukemia. Three types of null networks were studied: 1) networks constructed by topology randomization (TOP), 2) networks matched to the distributional properties of the observed covariance matrix (HQS), and 3) networks generated from correlation of randomized input data (COR). The results revealed that the choice of null network not only influences the estimated small-world parameters, it also influences the results of between-group differences in small-world parameters. In addition, at higher network densities, the choice of null network influences the direction of group differences in network measures. Our data suggest that the choice of null network is quite crucial for interpretation of group differences in small-world parameters of structural correlation networks. We argue that none of the available null models is perfect for estimation of small-world parameters for correlation networks and the relative strengths and weaknesses of the selected model should be carefully considered with respect to obtained network measures. PMID:23840672

  7. Averaged null energy condition and difference inequalities in quantum field theory

    International Nuclear Information System (INIS)

    Yurtsever, U.

    1995-01-01

    For a large class of quantum states, all local (pointwise) energy conditions widely used in relativity are violated by the renormalized stress-energy tensor of a quantum field. In contrast, certain nonlocal positivity constraints on the quantum stress-energy tensor might hold quite generally, and this possibility has received considerable attention in recent years. In particular, it is now known that the averaged null energy condition, the condition that the null-null component of the stress-energy tensor integrated along a complete null geodesic is non-negative for all states, holds quite generally in a wide class of spacetimes for a minimally coupled scalar field. Apart from the specific class of spacetimes considered (mainly two-dimensional spacetimes and four-dimensional Minkowski space), the most significant restriction on this result is that the null geodesic over which the average is taken must be achronal. Recently, Ford and Roman have explored this restriction in two-dimensional flat spacetime, and discovered that in a flat cylindrical space, although the stress energy tensor itself fails to satisfy the averaged null energy condition (ANEC) along the (nonachronal) null geodesics, when the ''Casimir-vacuum'' contribution is subtracted from the stress-energy the resulting tensor does satisfy the ANEC inequality. Ford and Roman name this class of constraints on the quantum stress-energy tensor ''difference inequalities.'' Here I give a proof of the difference inequality for a minimally coupled massless scalar field in an arbitrary (globally hyperbolic) two-dimensional spacetime, using the same techniques as those we relied on to prove the ANEC in an earlier paper with Wald. I begin with an overview of averaged energy conditions in quantum field theory

  8. Procedures for identifying S-allele genotypes of Brassica.

    Science.gov (United States)

    Wallace, D H

    1979-11-01

    Procedures are described for efficient selection of: (1) homozygous and heterozygous S-allele genotypes; (2) homozygous inbreds with the strong self- and sib-incompatibility required for effective seed production of single-cross F1 hybrids; (3) heterozygous genotypes with the high self- and sib-incompatibility required for effective seed production of 3- and 4-way hybrids.From reciprocal crosses between two first generation inbred (I1) plants there are three potential results: both crosses are incompatible; one is incompatible and the other compatible; and both are compatible. Incompatibility of both crosses is useful information only when combined with data from other reciprocal crosses. Each compatible cross, depending on whether its reciprocal is incompatible or compatible, dictates alternative reasoning and additional reciprocal crosses for efficiently and simultaneously identifying: (A) the S-allele genotype of all individual I1 plants, and (B) the expressions of dominance or codominance in pollen and stigma (sexual organs) of an S-allele heterozygous genotype. Reciprocal crosses provide the only efficient means of identifying S-allele genotypes and also the sexual-organ x S-allele-interaction types.Fluorescent microscope assay of pollen tube penetration into the style facilitates quantitation within 24-48 hours of incompatibility and compatibility of the reciprocal crosses. A procedure for quantitating the reciprocal difference is described that maximizes informational content of the data about interactions between S alleles in pollen and stigma of the S-allele-heterozygous genotype.Use of the non-inbred Io generation parent as a 'known' heterozygous S-allele genotype in crosses with its first generation selfed (I1) progeny usually reduces at least 7 fold the effort required for achieving objectives 1, 2, and 3, compared to the method of making reciprocal crosses only among I1 plants.Identifying the heterozygous and both homozygous S-allele genotypes during

  9. Allelic heterogeneity and genetic modifier loci contribute to clinical variation in males with X-linked retinitis pigmentosa due to RPGR mutations.

    Directory of Open Access Journals (Sweden)

    Abigail T Fahim

    Full Text Available Mutations in RPGR account for over 70% of X-linked retinitis pigmentosa (XlRP, characterized by retinal degeneration and eventual blindness. The clinical consequences of RPGR mutations are highly varied, even among individuals with the same mutation: males demonstrate a wide range of clinical severity, and female carriers may or may not be affected. This study describes the phenotypic diversity in a cohort of 98 affected males from 56 families with RPGR mutations, and demonstrates the contribution of genetic factors (i.e., allelic heterogeneity and genetic modifiers to this diversity. Patients were categorized as grade 1 (mild, 2 (moderate or 3 (severe according to specific clinical criteria. Patient DNAs were genotyped for coding SNPs in 4 candidate modifier genes with products known to interact with RPGR protein: RPGRIP1, RPGRIP1L, CEP290, and IQCB1. Family-based association testing was performed using PLINK. A wide range of clinical severity was observed both between and within families. Patients with mutations in exons 1-14 were more severely affected than those with ORF15 mutations, and patients with predicted null alleles were more severely affected than those predicted to make RPGR protein. Two SNPs showed association with severe disease: the minor allele (N of I393N in IQCB1 (p = 0.044 and the common allele (R of R744Q in RPGRIP1L (p = 0.049. These data demonstrate that allelic heterogeneity contributes to phenotypic diversity in XlRP and suggest that this may depend on the presence or absence of RPGR protein. In addition, common variants in 2 proteins known to interact with RPGR are associated with severe disease in this cohort.

  10. A Δ11 desaturase gene genealogy reveals two divergent allelic classes within the European corn borer (Ostrinia nubilalis

    Directory of Open Access Journals (Sweden)

    Harrison Richard G

    2010-04-01

    Full Text Available Abstract Background Moth pheromone mating systems have been characterized at the molecular level, allowing evolutionary biologists to study how changes in protein sequence or gene expression affect pheromone phenotype, patterns of mating, and ultimately, the formation of barriers to gene exchange. Recent studies of Ostrinia pheromones have focused on the diversity of sex pheromone desaturases and their role in the specificity of pheromone production. Here we produce a Δ11 desaturase genealogy within Ostrinia nubilalis. We ask what has been the history of this gene, and whether this history suggests that changes in Δ11 desaturase have been involved in the divergence of the E and Z O. nubilalis pheromone strains. Results The Δ11 desaturase gene genealogy does not differentiate O. nubilalis pheromone strains. However, we find two distinct clades, separated by 2.9% sequence divergence, that do not sort with pheromone strain, geographic origin, or emergence time. We demonstrate that these clades do not represent gene duplicates, but rather allelic variation at a single gene locus. Conclusions Analyses of patterns of variation at the Δ11 desaturase gene in ECB suggest that this enzyme does not contribute to reproductive isolation between pheromone strains (E and Z. However, our genealogy reveals two deeply divergent allelic classes. Standing variation at loci that contribute to mate choice phenotypes may permit novel pheromone mating systems to arise in the presence of strong stabilizing selection.

  11. Increased trabecular bone and improved biomechanics in an osteocalcin-null rat model created by CRISPR/Cas9 technology

    Directory of Open Access Journals (Sweden)

    Laura J. Lambert

    2016-10-01

    Full Text Available Osteocalcin, also known as bone γ-carboxyglutamate protein (Bglap, is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover. A mouse model of osteocalcin deficiency has implicated osteocalcin as a mediator of changes to the skeleton, endocrine system, reproductive organs and central nervous system. However, differences between mouse and human osteocalcin at both the genome and protein levels have challenged the validity of extrapolating findings from the osteocalcin-deficient mouse model to human disease. The rat osteocalcin (Bglap gene locus shares greater synteny with that of humans. To further examine the role of osteocalcin in disease, we created a rat model with complete loss of osteocalcin using the CRISPR/Cas9 system. Rat osteocalcin was modified by injection of CRISPR/Cas9 mRNA into the pronuclei of fertilized single cell Sprague-Dawley embryos, and animals were bred to homozygosity and compound heterozygosity for the mutant alleles. Dual-energy X-ray absorptiometry (DXA, glucose tolerance testing (GTT, insulin tolerance testing (ITT, microcomputed tomography (µCT, and a three-point break biomechanical assay were performed on the excised femurs at 5 months of age. Complete loss of osteocalcin resulted in bones with significantly increased trabecular thickness, density and volume. Cortical bone volume and density were not increased in null animals. The bones had improved functional quality as evidenced by an increase in failure load during the biomechanical stress assay. Differences in glucose homeostasis were observed between groups, but there were no differences in body weight or composition. This rat model of complete loss of osteocalcin provides a platform for further understanding the role of osteocalcin in disease, and it is a novel model of increased bone formation with potential utility in osteoporosis and osteoarthritis research.

  12. Genetic analysis of Saccharomyces cerevisiae strains isolated from palm wine in eastern Nigeria. Comparison with other African strains.

    Science.gov (United States)

    Ezeronye, O U; Legras, J-L

    2009-05-01

    To study the yeast diversity of Nigerian palm wines by comparison with other African strains. Twenty-three Saccharomyces cerevisiae strains were obtained from palm wine samples collected at four locations in eastern Nigeria, and characterized using different molecular techniques: internal transcribed spacer restriction fragment length polymorphism and sequence analysis, pulsed field gel electrophoresis, inter delta typing and microsatellite multilocus analysis. These techniques revealed that palm wine yeasts represent a group of closely related strains that includes other West African isolates (CBS400, NCYC110, DVPG6044). Population analysis revealed an excess of homozygote strains and an allelic richness similar to wine suggestive of local domestication. Several other African yeast strains were not connected to this group. Ghana sorghum beer strains and other African strains (DBVPG1853 and MUCL28071) displayed strikingly high relatedness with European bread, beer or wine strains, and the genome of strain MUCL30909 contained African and wine-type alleles, indicating its hybrid origin. Nigerian palm wine yeast represents a local specific yeast flora, whereas a European origin or hybrid was suspected for several other Africa isolates. This study presents the first genetic characterization of an autochthonous African palm wine yeast population and confirms the idea that human intervention has favoured yeast migration.

  13. A modified Janus cassette (Sweet Janus to improve allelic replacement efficiency by high-stringency negative selection in Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Yuan Li

    Full Text Available The Janus cassette permits marker-free allelic replacement or knockout in streptomycin-resistant Streptococcus pneumoniae (pneumococcus through sequential positive and negative selection. Spontaneous revertants of Janus can lead to high level of false-positives during negative selection, which necessitate a time-consuming post-selection screening process. We hypothesized that an additional counter-selectable marker in Janus would decrease the revertant frequency and reduce false-positives, since simultaneous reversion of both counter-selectable makers is much less likely. Here we report a modified cassette, Sweet Janus (SJ, in which the sacB gene from Bacillus subtilis conferring sucrose sensitivity is added to Janus. By using streptomycin and sucrose simultaneously as selective agents, the frequency of SJ double revertants was about 105-fold lower than the frequency of Janus revertants. Accordingly, the frequency of false-positives in the SJ-mediated negative selection was about 100-fold lower than what was seen for Janus. Thus, SJ enhances negative selection stringency and can accelerate allelic replacement in pneumococcus, especially when transformation frequency is low due to strain background or suboptimal transformation conditions. Results also suggested the sacB gene alone can function as a counter-selectable marker in the Gram-positive pneumococcus, which will have the advantage of not requiring a streptomycin-resistant strain for allelic replacement.

  14. Vacuum Nuller Testbed (VNT) Performance, Characterization and Null Control: Progress Report

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

    2011-01-01

    Herein we report on the development. sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled. segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be Hown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies. and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). Tbe VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 10(sup 8), 10(sup 9) and ideally 10(sup 10) at an inner working angle of 2*lambda/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

  15. A Null Space Control of Two Wheels Driven Mobile Manipulator Using Passivity Theory

    Science.gov (United States)

    Shibata, Tsuyoshi; Murakami, Toshiyuki

    This paper describes a control strategy of null space motion of a two wheels driven mobile manipulator. Recently, robot is utilized in various industrial fields and it is preferable for the robot manipulator to have multiple degrees of freedom motion. Several studies of kinematics for null space motion have been proposed. However stability analysis of null space motion is not enough. Furthermore, these approaches apply to stable systems, but they do not apply unstable systems. Then, in this research, base of manipulator equips with two wheels driven mobile robot. This robot is called two wheels driven mobile manipulator, which becomes unstable system. In the proposed approach, a control design of null space uses passivity based stabilizing. A proposed controller is decided so that closed-loop system of robot dynamics satisfies passivity. This is passivity based control. Then, control strategy is that stabilizing of the robot system applies to work space observer based approach and null space control while keeping end-effector position. The validity of the proposed approach is verified by simulations and experiments of two wheels driven mobile manipulator.

  16. Time asymmetric spacetimes near null and spatial infinity: I. Expansions of developments of conformally flat data

    International Nuclear Information System (INIS)

    Kroon, Juan Antonio Valiente

    2004-01-01

    The conformal Einstein equations and the representation of spatial infinity as a cylinder introduced by Friedrich are used to analyse the behaviour of the gravitational field near null and spatial infinity for the development of data which are asymptotically Euclidean, conformally flat and time asymmetric. Our analysis allows for initial data whose second fundamental form is more general than the one given by the standard Bowen-York ansatz. The conformal Einstein equations imply, upon evaluation on the cylinder at spatial infinity, a hierarchy of transport equations which can be used to calculate asymptotic expansions for the gravitational field in a recursive way. It is found that the solutions to these transport equations develop logarithmic divergences at the critical sets where null infinity meets spatial infinity. Associated with these, there is a series of quantities expressible in terms of the initial data (obstructions), which if zero, preclude the appearance of some of the logarithmic divergences. The obstructions are, in general, time asymmetric. That is, the obstructions at the intersection of future null infinity with spatial infinity are in general different from those obtained at the intersection of past null infinity with spatial infinity. The latter allows for the possibility of having spacetimes where future and past null infinity have different degrees of smoothness. Finally, it is shown that if both sets of obstructions vanish up to a certain order, then the initial data have to be asymptotically Schwarzschildean in a certain sense

  17. Vacuum nuller testbed (VNT) performance, characterization and null control: progress report

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.; Noecker, M. Charley; Kendrick, Stephen; Helmbrecht, Michael

    2011-10-01

    Herein we report on the development, sensing and control and our first results with the Vacuum Nuller Testbed to realize a Visible Nulling Coronagraph (VNC) for exoplanet coronagraphy. The VNC is one of the few approaches that works with filled, segmented and sparse or diluted-aperture telescope systems. It thus spans a range of potential future NASA telescopes and could be flown as a separate instrument on such a future mission. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop VNC technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and the enabling technologies associated with it. We discuss the continued development of the vacuum Visible Nulling Coronagraph testbed (VNT). The VNT is an ultra-stable vibration isolated testbed that operates under closed-loop control within a vacuum chamber. It will be used to achieve an incremental sequence of three visible-light nulling milestones with sequentially higher contrasts of 108, 109, and ideally 1010 at an inner working angle of 2*λ/D. The VNT is based on a modified Mach-Zehnder nulling interferometer, with a "W" configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We discuss the initial laboratory results, the optical configuration, critical technologies and the null sensing and control approach.

  18. Current singularities at finitely compressible three-dimensional magnetic null points

    International Nuclear Information System (INIS)

    Pontin, D.I.; Craig, I.J.D.

    2005-01-01

    The formation of current singularities at line-tied two- and three-dimensional (2D and 3D, respectively) magnetic null points in a nonresistive magnetohydrodynamic environment is explored. It is shown that, despite the different separatrix structures of 2D and 3D null points, current singularities may be initiated in a formally equivalent manner. This is true no matter whether the collapse is triggered by flux imbalance within closed, line-tied null points or driven by externally imposed velocity fields in open, incompressible geometries. A Lagrangian numerical code is used to investigate the finite amplitude perturbations that lead to singular current sheets in collapsing 2D and 3D null points. The form of the singular current distribution is analyzed as a function of the spatial anisotropy of the null point, and the effects of finite gas pressure are quantified. It is pointed out that the pressure force, while never stopping the formation of the singularity, significantly alters the morphology of the current distribution as well as dramatically weakening its strength. The impact of these findings on 2D and 3D magnetic reconnection models is discussed

  19. An assessment of Wx microsatellite allele, alkali degradation and differentiation of chloroplast DNA in traditional black rice (Oryza sativa L.) from Thailand and Lao PDR.

    Science.gov (United States)

    Prathepha, Preecha

    2007-01-15

    Thailand and Lao PDR are the country's rich rice diversity. To contribute a significant knowledge for development new rice varieties, a collection of 142 black rice (Oryza sativa) accessions were determined for variation of physico-chemical properties, Wx microsatellite allele, Wx allele and chloroplast DNA type. The results showed that amylose content of black rice accessions were ranged from 1.9 to 6.8%. All of the alkali disintegration types (high, intermediate and low) was observed in these rice with average of 1.75 on the 1-3 digestibility scale. The unique Wx microsatellite allele (CT)17 was found in these samples and all black rice strains carried Wx(b) allele. In addition, all black rice accessions were found the duplication of the 23 bp sequence motif in the exon 2 of the wx gene. This evidence is a common phenomenon in glutinous rice. Based on two growing condition for black rice, rainfed lowland and rainfed upland, chloroplast DNA type was distinct from each other. All rice strains from rainfed lowland was deletion plastotype, but all other rainfed upland strains were non-deletion types.

  20. Inheritance of Cry1F resistance, cross-resistance and frequency of resistant alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Vélez, A M; Spencer, T A; Alves, A P; Moellenbeck, D; Meagher, R L; Chirakkal, H; Siegfried, B D

    2013-12-01

    Transgenic maize, Zea maize L., expressing the Cry1F protein from Bacillus thuringiensis has been registered for Spodoptera frugiperda (J. E. Smith) control since 2003. Unexpected damage to Cry1F maize was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain originating from Puerto Rico, which displayed >289-fold resistance to purified Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F1 generation crossed with the resistant parental strain suggest that a single locus is responsible for resistance. In addition, cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry2Aa and Vip3Aa was assessed in the Cry1F-resistant strain. There was no significant cross-resistance to Cry1Aa, Cry1Ba and Cry2Aa, although only limited effects were observed in the susceptible strain. Vip3Aa was highly effective against susceptible and resistant insects indicating no cross-resistance with Cry1F. In contrast, low levels of cross-resistance were observed for both Cry1Ab and Cry1Ac. Because the resistance is recessive and conferred by a single locus, an F1 screening assay was used to measure the frequency of Cry1F-resistant alleles from populations of Florida and Texas in 2010 and 2011. A total frequency of resistant alleles of 0.13 and 0.02 was found for Florida and Texas populations, respectively, indicating resistant alleles could be found in US populations, although there have been no reports of reduced efficacy of Cry1F-expressing plants.

  1. Detecting imbalanced expression of SNP alleles by minisequencing on microarrays

    Directory of Open Access Journals (Sweden)

    Dahlgren Andreas

    2004-10-01

    Full Text Available Abstract Background Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system. Results The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1–9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and

  2. Anti-optic-null medium: Achieving the optic-null medium effect by enclosing an air region with relatively low-anisotropy media

    Science.gov (United States)

    Sun, Fei; Liu, Yichao; He, Sailing

    2016-07-01

    A so-called anti-optic-null medium (anti-ONM), which can be utilized to cancel the optic-null medium (ONM) and create many novel optical illusions, is introduced and designed by transformation optics (TO). Optical separation illusions can be achieved with an anti-ONM. With the help of the anti-ONM, we can achieve the same optical illusions where ONM is required via a shelled structure filled with low anisotropic medium, which is easier to realize for some novel optical devices designed by TO and optical surface transformation. The special function of the anti-ONM will lead to a new way to design optical devices or simplify the material requirements. Overlapping illusions, and wave-front reshapers are designed to demonstrate the function of the proposed method.

  3. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt

    2013-01-01

    In certain crime cases, information about a perpetrator's phenotype, including eye colour, may be a valuable tool if no DNA profile of any suspect or individual in the DNA database matches the DNA profile found at the crime scene. Often, the available DNA material is sparse and allelic drop-out...... of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop-out...... when the amount of DNA was greater than 125 pg for 29 cycles of PCR and greater than 62 pg for 30 cycles of PCR. With the use of a logistic regression model, we estimated the allele specific probability of drop-out in heterozygote systems based on the signal strength of the observed allele...

  4. Common breast cancer risk alleles and risk assessment

    DEFF Research Database (Denmark)

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...... ratio for the 5(th) vs. 1(st) allele sum quintile was 1.82(95% confidence interval;1.53-2.18). Corresponding hazard ratios per allele were 1.04(1.03-1.05) and 1.05(1.02-1.08) for breast cancer incidence and mortality, similar across risk factors. In 50-year old women, the starting age for screening...

  5. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

    2001-11-01

    Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

  6. Molecular analysis of two mouse dilute locus deletion mutations: Spontaneous dilute lethal20J and radiation-induced dilute prenatal lethal Aa2 alleles

    International Nuclear Information System (INIS)

    Strobel, M.C.; Seperack, P.K.; Copeland, N.G.; Jenkins, N.A.

    1990-01-01

    The dilute (d) coat color locus of mouse chromosome 9 has been identified by more than 200 spontaneous and mutagen-induced recessive mutations. With the advent of molecular probes for this locus, the molecular lesion associated with different dilute alleles can be recognized and precisely defined. In this study, two dilute mutations, dilute-lethal20J (dl20J) and dilute prenatal lethal Aa2, have been examined. Using a dilute locus genomic probe in Southern blot analysis, we detected unique restriction fragments in dl20J and Aa2 DNA. Subsequent analysis of these fragments showed that they represented deletion breakpoint fusion fragments. DNA sequence analysis of each mutation-associated deletion breakpoint fusion fragment suggests that both genomic deletions were generated by nonhomologous recombination events. The spontaneous dl20J mutation is caused by an interstitial deletion that removes a single coding exon of the dilute gene. The correlation between this discrete deletion and the expression of all dilute-associated phenotypes in dl20J homozygotes defines the dl20J mutation as a functional null allele of the dilute gene. The radiation-induced Aa2 allele is a multilocus deletion that, by complementation analysis, affects both the dilute locus and the proximal prenatal lethal-3 (pl-3) functional unit. Molecular analysis of the Aa2 deletion breakpoint fusion fragment has provided access to a previously undefined gene proximal to d. Initial characterization of this new gene suggests that it may represent the genetically defined pl-3 functional unit

  7. The null hypothesis of GSEA, and a novel statistical model for competitive gene set analysis

    DEFF Research Database (Denmark)

    Debrabant, Birgit

    2017-01-01

    MOTIVATION: Competitive gene set analysis intends to assess whether a specific set of genes is more associated with a trait than the remaining genes. However, the statistical models assumed to date to underly these methods do not enable a clear cut formulation of the competitive null hypothesis....... This is a major handicap to the interpretation of results obtained from a gene set analysis. RESULTS: This work presents a hierarchical statistical model based on the notion of dependence measures, which overcomes this problem. The two levels of the model naturally reflect the modular structure of many gene set...... analysis methods. We apply the model to show that the popular GSEA method, which recently has been claimed to test the self-contained null hypothesis, actually tests the competitive null if the weight parameter is zero. However, for this result to hold strictly, the choice of the dependence measures...

  8. A few insights into the nature of classical and quantum gravity via null-strut calculus

    International Nuclear Information System (INIS)

    Kheyfets, Arkady

    1989-01-01

    Null-strut calculus is a 3 + 1 formulation of standard Regge calculus, wherein the dynamics of 3-geometry is propagated in time along light rays, or 'null struts'. However, just as Regge calculus is a discrete and geometric tool for the description of Einstein's theory of gravitation, so too NSC offers itself as a discrete and geometric tool for the description of Einstein's spacetime as the dynamics of discrete spacelike 3-geometries in time, or discrete geometrodynamics. It has for its objectives to provide a discrete model of a 3 + 1 split of spacetime into space plus time, while in so doing to preserve and illuminate the geometric content of Einstein's theory of gravity. The feature of 'light-cone-produced duality' is central to null-strut calculus. This paper will capitalise on this feature, and will attempt to provide some insights into the nature of classical and quantum gravity. (Author)

  9. Maxwell, Yang-Mills, Weyl and eikonal fields defined by any null shear-free congruence

    Science.gov (United States)

    Kassandrov, Vladimir V.; Rizcallah, Joseph A.

    We show that (specifically scaled) equations of shear-free null geodesic congruences on the Minkowski space-time possess intrinsic self-dual, restricted gauge and algebraic structures. The complex eikonal, Weyl 2-spinor, SL(2, ℂ) Yang-Mills and complex Maxwell fields, the latter produced by integer-valued electric charges (“elementary” for the Kerr-like congruences), can all be explicitly associated with any shear-free null geodesic congruence. Using twistor variables, we derive the general solution of the equations of the shear-free null geodesic congruence (as a modification of the Kerr theorem) and analyze the corresponding “particle-like” field distributions, with bounded singularities of the associated physical fields. These can be obtained in a straightforward algebraic way and exhibit nontrivial collective dynamics simulating physical interactions.

  10. The (2, 0) superalgebra, null M-branes and Hitchin's system

    Science.gov (United States)

    Kucharski, P.; Lambert, N.; Owen, M.

    2017-10-01

    We present an interacting system of equations with sixteen supersymmetries and an SO(2) × SO(6) R-symmetry where the fields depend on two space and one null dimensions that is derived from a representation of the six-dimensional (2, 0) superalgebra. The system can be viewed as two M5-branes compactified on {S}-^1× T^2 or equivalently as M2-branes on R+× R^2 , where ± refer to null directions. We show that for a particular choice of fields the dynamics can be reduced to motion on the moduli space of solutions to the Hitchin system. We argue that this provides a description of intersecting null M2-branes and is also related by U-duality to a DLCQ description of four-dimensional maximally supersymmetric Yang-Mills.

  11. In Vivo-Selected Compensatory Mutations Restore the Fitness Cost of Mosaic penA Alleles That Confer Ceftriaxone Resistance in Neisseria gonorrhoeae

    Directory of Open Access Journals (Sweden)

    Leah R. Vincent

    2018-04-01

    Full Text Available Resistance to ceftriaxone in Neisseria gonorrhoeae is mainly conferred by mosaic penA alleles that encode penicillin-binding protein 2 (PBP2 variants with markedly lower rates of acylation by ceftriaxone. To assess the impact of these mosaic penA alleles on gonococcal fitness, we introduced the mosaic penA alleles from two ceftriaxone-resistant (Cror clinical isolates (H041 and F89 into a Cros strain (FA19 by allelic exchange and showed that the resultant Cror mutants were significantly outcompeted by the Cros parent strain in vitro and in a murine infection model. Four Cror compensatory mutants of FA19 penA41 were isolated independently from mice that outcompeted the parent strain both in vitro and in vivo. One of these compensatory mutants (LV41C displayed a unique growth profile, with rapid log growth followed by a sharp plateau/gradual decline at stationary phase. Genome sequencing of LV41C revealed a mutation (G348D in the acnB gene encoding the bifunctional aconitate hydratase 2/2 methylisocitrate dehydratase. Introduction of the acnBG348D allele into FA19 penA41 conferred both a growth profile that phenocopied that of LV41C and a fitness advantage, although not as strongly as that exhibited by the original compensatory mutant, suggesting the existence of additional compensatory mutations. The mutant aconitase appears to be a functional knockout with lower activity and expression than wild-type aconitase. Transcriptome sequencing (RNA-seq analysis of FA19 penA41 acnBG348D revealed a large set of upregulated genes involved in carbon and energy metabolism. We conclude that compensatory mutations can be selected in Cror gonococcal strains that increase metabolism to ameliorate their fitness deficit.

  12. Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related Alleles in Botrytis cinerea

    Directory of Open Access Journals (Sweden)

    Xin Zhang

    2016-09-01

    Full Text Available A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension (ASPE assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA, H272 and 272Y of the Succinate dehydrogenase iron–sulfur subunit gene (SdhB, I365 and 365S of the putative osmosensor histidine kinase gene (BcOS1, and F412 and 412S of the 3-ketoreductase gene (erg27. This assay was first established and optimized with eight plasmid templates containing the DNA sequence variants BenA-E198, BenA-198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S. Results indicated that none of the probes showed cross-reactivity with one another. The minimum limit of detection for these genotypes was one copy per test. Four mutant plasmids were mixed with 10 ng/μL wild-type genomic DNA in different ratios. Detection sensitivity of mutant loci was 0.45% for BenA-E198A, BcOS1-I365S, and erg27-F412S, and was 4.5% for SdhB-H272Y. A minimum quantity of 0.1 ng of genomic DNA was necessary to obtain reliable results. This is the first reported assay that can simultaneously detect mutations in BenA, SdhB, BcOS1, and erg27.

  13. Suspension Array for Multiplex Detection of Eight Fungicide-Resistance Related Alleles in Botrytis cinerea.

    Science.gov (United States)

    Zhang, Xin; Xie, Fei; Lv, Baobei; Zhao, Pengxiang; Ma, Xuemei

    2016-01-01

    A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea . Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene ( BenA ), H272 and 272Y of the Succinate dehydrogenase iron-sulfur subunit gene ( SdhB) , I365 and 365S of the putative osmosensor histidine kinase gene ( BcOS1 ), and F412 and 412S of the 3-ketoreductase gene ( erg27 ). This assay was first established and optimized with eight plasmid templates containing the DNA sequence variants BenA- E198, BenA- 198A, SdhB- H272, SdhB- 272Y, BcOS1- I365, BcOS1- 365S, erg27 -F412, and erg27 -412S. Results indicated that none of the probes showed cross-reactivity with one another. The minimum limit of detection for these genotypes was one copy per test. Four mutant plasmids were mixed with 10 ng/μL wild-type genomic DNA in different ratios. Detection sensitivity of mutant loci was 0.45% for BenA- E198A, BcOS1- I365S, and erg27 -F412S, and was 4.5% for SdhB- H272Y. A minimum quantity of 0.1 ng of genomic DNA was necessary to obtain reliable results. This is the first reported assay that can simultaneously detect mutations in BenA , SdhB , BcOS1 , and erg27 .

  14. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  15. From GLC to double-null coordinates and illustration with static black holes

    Energy Technology Data Exchange (ETDEWEB)

    Nugier, Fabien, E-mail: fnugier@ntu.edu.tw [Leung Center for Cosmology and Particle Astrophysics, National Taiwan University, Taipei, 10617 Taiwan (China)

    2016-09-01

    We present a system of coordinates deriving directly from the so-called Geodesic Light-Cone (GLC) coordinates and made of two null scalars intersecting on a 2-dimensional sphere parameterized by two constant angles along geodesics. These coordinates are shown to be equivalent to the well-known double-null coordinates. As GLC, they present interesting properties for cosmology and astrophysics. We discuss this latter topic for static black holes, showing simple descriptions for the metric or particles and photons trajectories. We also briefly comment on the time of flight of ultra-relativistic particles.

  16. The Segmented Aperture Interferometric Nulling Testbed (SAINT) I: overview and air-side system description

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Petrone, Peter; Ballard, Marlin; Bolcar, Matthew R.; Bolognese, Jeff; Clampin, Mark; Dogoda, Peter; Dworzanski, Daniel; Helmbrecht, Michael A.; Koca, Corina; Shiri, Ron

    2016-07-01

    This work presents an overview of the Segmented Aperture Interferometric Nulling Testbed (SAINT), a project that will pair an actively-controlled macro-scale segmented mirror with the Visible Nulling Coronagraph (VNC). SAINT will incorporate the VNC's demonstrated wavefront sensing and control system to refine and quantify end-to-end high-contrast starlight suppression performance. This pathfinder testbed will be used as a tool to study and refine approaches to mitigating instabilities and complex diffraction expected from future large segmented aperture telescopes.

  17. Noncolocated Time-Reversal MUSIC: High-SNR Distribution of Null Spectrum

    Science.gov (United States)

    Ciuonzo, Domenico; Rossi, Pierluigi Salvo

    2017-04-01

    We derive the asymptotic distribution of the null spectrum of the well-known Multiple Signal Classification (MUSIC) in its computational Time-Reversal (TR) form. The result pertains to a single-frequency non-colocated multistatic scenario and several TR-MUSIC variants are here investigated. The analysis builds upon the 1st-order perturbation of the singular value decomposition and allows a simple characterization of null-spectrum moments (up to the 2nd order). This enables a comparison in terms of spectrums stability. Finally, a numerical analysis is provided to confirm the theoretical findings.

  18. In vivo time-gated diffuse correlation spectroscopy at quasi-null source-detector separation.

    Science.gov (United States)

    Pagliazzi, M; Sekar, S Konugolu Venkata; Di Sieno, L; Colombo, L; Durduran, T; Contini, D; Torricelli, A; Pifferi, A; Mora, A Dalla

    2018-06-01

    We demonstrate time domain diffuse correlation spectroscopy at quasi-null source-detector separation by using a fast time-gated single-photon avalanche diode without the need of time-tagging electronics. This approach allows for increased photon collection, simplified real-time instrumentation, and reduced probe dimensions. Depth discriminating, quasi-null distance measurement of blood flow in a human subject is presented. We envision the miniaturization and integration of matrices of optical sensors of increased spatial resolution and the enhancement of the contrast of local blood flow changes.

  19. A class of algebraically general solutions of the Einstein-Maxwell equations for non-null electromagnetic fields

    International Nuclear Information System (INIS)

    Tupper, B.O.J.

    1976-01-01

    In a previous article (Gen. Rel. Grav.; 6 : 345 (1975)) the Einstein-Maxwell field equations for non-null electromagnetic fields were studied under the conditions that the null tetrad is parallel-propagated along both principal null congruences. A solution with twist and shear, but no expansion, was found and was conjectured to be the only expansion-free solution. Here it is shown that this conjecture is false; the general expansion-free solution is found to be a family of space-times depending on a single constant parameter which is the ratio of the (constant) twists of the two principal null congruences. (author)

  20. Population differentiation in allele frequencies of obesity-associated SNPs.

    Science.gov (United States)

    Mao, Linyong; Fang, Yayin; Campbell, Michael; Southerland, William M

    2017-11-10

    Obesity is emerging as a global health problem, with more than one-third of the world's adult population being overweight or obese. In this study, we investigated worldwide population differentiation in allele frequencies of obesity-associated SNPs (single nucleotide polymorphisms). We collected a total of 225 obesity-associated SNPs from a public database. Their population-level allele frequencies were derived based on the genotype data from 1000 Genomes Project (phase 3). We used hypergeometric model to assess whether the effect allele at a given SNP is significantly enriched or depleted in each of the 26 populations surveyed in the 1000 Genomes Project with respect to the overall pooled population. Our results indicate that 195 out of 225 SNPs (86.7%) possess effect alleles significantly enriched or depleted in at least one of the 26 populations. Populations within the same continental group exhibit similar allele enrichment/depletion patterns whereas inter-continental populations show distinct patterns. Among the 225 SNPs, 15 SNPs cluster in the first intron region of the FTO gene, which is a major gene associated with body-mass index (BMI) and fat mass. African populations exhibit much smaller blocks of LD (linkage disequilibrium) among these15 SNPs while European and Asian populations have larger blocks. To estimate the cumulative effect of all variants associated with obesity, we developed the personal composite genetic risk score for obesity. Our results indicate that the East Asian populations have the lowest averages of the composite risk scores, whereas three European populations have the highest averages. In addition, the population-level average of composite genetic risk scores is significantly correlated (R 2 = 0.35, P = 0.0060) with obesity prevalence. We have detected substantial population differentiation in allele frequencies of obesity-associated SNPs. The results will help elucidate the genetic basis which may contribute to population

  1. A common mutation associated with the Duarte galactosemia allele

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  2. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    Energy Technology Data Exchange (ETDEWEB)

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  3. Reduced Height (Rht Alleles Affect Wheat Grain Quality.

    Directory of Open Access Journals (Sweden)

    Richard Casebow

    Full Text Available The effects of dwarfing alleles (reduced height, Rht in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c as well as those that retained GA-sensitivity (rht(tall, Rht8, Rht8 + Ppd-D1a, Rht12. Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (P<0.05 reduced grain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there

  4. Reduced Height (Rht) Alleles Affect Wheat Grain Quality.

    Science.gov (United States)

    Casebow, Richard; Hadley, Caroline; Uppal, Rajneet; Addisu, Molla; Loddo, Stefano; Kowalski, Ania; Griffiths, Simon; Gooding, Mike

    2016-01-01

    The effects of dwarfing alleles (reduced height, Rht) in near isogenic lines on wheat grain quality are characterised in field experiments and related to effects on crop height, grain yield and GA-sensitivity. Alleles included those that conferred GA-insensitivity (Rht-B1b, Rht-B1c, Rht-D1b, Rht-D1c) as well as those that retained GA-sensitivity (rht(tall), Rht8, Rht8 + Ppd-D1a, Rht12). Full characterisation was facilitated by including factors with which the effects of Rht alleles are known to interact for grain yield (i.e. system, [conventional or organic]; tillage intensity [plough-based, minimum or zero]; nitrogen fertilizer level [0-450 kg N/ha]; and genetic backgrounds varying in height [cvs Maris Huntsman, Maris Widgeon, and Mercia]. Allele effects on mean grain weight and grain specific weight were positively associated with final crop height: dwarfing reduced these quality criteria irrespective of crop management or GA-sensitivity. In all but two experiments the effects of dwarfing alleles on grain nitrogen and sulphur concentrations were closely and negatively related to effects on grain yield, e.g. a quadratic relationship between grain yield and crop height manipulated by the GA-insensitive alleles was mirrored by quadratic relationships for nitrogen and sulphur concentrations: the highest yields and most dilute concentrations occurred around 80cm. In one of the two exceptional experiments the GA-insensitive Rht-B1b and Rht-B1c significantly (Pgrain nitrogen concentration in the absence of an effect on yield, and in the remaining experiment the GA-sensitive Rht8 significantly reduced both grain yield and grain nitrogen concentration simultaneously. When Rht alleles diluted grain nitrogen concentration, N:S ratios and SDS-sedimentation volumes were often improved. Hagberg falling number (HFN) was negatively related to crop height but benefits from dwarfing were only seen for GA-insensitive alleles. For HFN, therefore, there was the strongest evidence for

  5. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  6. Novel allelic mutations in murine Serca2 induce differential development of squamous cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Toki, Hideaki; Minowa, Osamu; Inoue, Maki; Motegi, Hiromi; Karashima, Yuko; Ikeda, Ami [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Kaneda, Hideki [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Sakuraba, Yoshiyuki [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Saiki, Yuriko [Department of Molecular Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi (Japan); Wakana, Shigeharu [Technology and Development Team for Mouse Phenotype Analysis, Riken BRC, Tsukuba, Ibaraki (Japan); Suzuki, Hiroshi [Department of Biochemistry, Asahikawa Medical University, Asahikawa, Hokkaido (Japan); Gondo, Yoichi [Mutagenesis and Genomics Team, Riken BRC, Tsukuba, Ibaraki (Japan); Shiroishi, Toshihiko [Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka (Japan); Noda, Tetsuo, E-mail: tnoda@jfcr.or.jp [Team for Advanced Development and Evaluation of Human Disease Models, Riken BioResource Center (BRC), Tsukuba, Ibaraki (Japan); Department of Cell Biology, Cancer Institute, The Japanese Foundation for Cancer Research, Tokyo (Japan)

    2016-08-05

    Dominant mutations in the Serca2 gene, which encodes sarco(endo)plasmic reticulum calcium-ATPase, predispose mice to gastrointestinal epithelial carcinoma [1–4] and humans to Darier disease (DD) [14–17]. In this study, we generated mice harboring N-ethyl-N-nitrosourea (ENU)-induced allelic mutations in Serca2: three missense mutations and one nonsense mutation. Mice harboring these Serca2 mutations developed tumors that were categorized as either early onset squamous cell tumors (SCT), with development similar to null-type knockout mice [2,4] (aggressive form; M682, M814), or late onset tumors (mild form; M1049, M1162). Molecular analysis showed no aberration in Serca2 mRNA or protein expression levels in normal esophageal cells of any of the four mutant heterozygotes. There was no loss of heterozygosity at the Serca2 locus in the squamous cell carcinomas in any of the four lines. The effect of each mutation on Ca{sup 2+}-ATPase activity was predicted using atomic-structure models and accumulated mutated protein studies, suggesting that putative complete loss of Serca2 enzymatic activity may lead to early tumor onset, whereas mutations in which Serca2 retains residual enzymatic activity result in late onset. We propose that impaired Serca2 gene product activity has a long-term effect on squamous cell carcinogenesis from onset to the final carcinoma stage through an as-yet unrecognized but common regulatory pathway. -- Highlights: •Novel mutations in murine Serca2 caused early onset or late onset of tumorigenesis. •They also caused higher or lower incidence of Darier Disease phenotype. •3D structure model suggested the former mutations led to severer defect on ATPase. •Driver gene mutations via long-range effect on Ca2+ distributions are suggested.

  7. Molecular typing of Brucella melitensis endemic strains and differentiation from the vaccine strain Rev-1.

    Science.gov (United States)

    Noutsios, Georgios T; Papi, Rigini M; Ekateriniadou, Loukia V; Minas, Anastasios; Kyriakidis, Dimitrios A

    2012-03-01

    In the present study forty-four Greek endemic strains of Br. melitensis and three reference strains were genotyped by Multi locus Variable Number Tandem Repeat (ML-VNTR) analysis based on an eight-base pair tandem repeat sequence that was revealed in eight loci of Br. melitensis genome. The forty-four strains were discriminated from the vaccine strain Rev-1 by Restriction Fragment Length Polymorphism (RFLP) and Denaturant Gradient Gel Electrophoresis (DGGE). The ML-VNTR analysis revealed that endemic, reference and vaccine strains are genetically closely related, while most of the loci tested (1, 2, 4, 5 and 7) are highly polymorphic with Hunter-Gaston Genetic Diversity Index (HGDI) values in the range of 0.939 to 0.775. Analysis of ML-VNTRs loci stability through in vitro passages proved that loci 1 and 5 are non stable. Therefore, vaccine strain can be discriminated from endemic strains by allele's clusters of loci 2, 4, 6 and 7. RFLP and DGGE were also employed to analyse omp2 gene and reveled different patterns among Rev-1 and endemic strains. In RFLP, Rev-1 revealed three fragments (282, 238 and 44 bp), while endemic strains two fragments (238 and 44 bp). As for DGGE, the electrophoretic mobility of Rev-1 is different from the endemic strains due to heterologous binding of DNA chains of omp2a and omp2b gene. Overall, our data show clearly that it is feasible to genotype endemic strains of Br. melitensis and differentiate them from vaccine strain Rev-1 with ML-VNTR, RFLP and DGGE techniques. These tools can be used for conventional investigations in brucellosis outbreaks.

  8. Propagation of errors from a null balance terahertz reflectometer to a sample's relative water content

    International Nuclear Information System (INIS)

    Hadjiloucas, S; Walker, G C; Bowen, J W; Zafiropoulos, A

    2009-01-01

    The THz water content index of a sample is defined and advantages in using such metric in estimating a sample's relative water content are discussed. The errors from reflectance measurements performed at two different THz frequencies using a quasi-optical null-balance reflectometer are propagated to the errors in estimating the sample water content index.

  9. Partial null astigmatism-compensated interferometry for a concave freeform Zernike mirror

    Science.gov (United States)

    Dou, Yimeng; Yuan, Qun; Gao, Zhishan; Yin, Huimin; Chen, Lu; Yao, Yanxia; Cheng, Jinlong

    2018-06-01

    Partial null interferometry without using any null optics is proposed to measure a concave freeform Zernike mirror. Oblique incidence on the freeform mirror is used to compensate for astigmatism as the main component in its figure, and to constrain the divergence of the test beam as well. The phase demodulated from the partial nulled interferograms is divided into low-frequency phase and high-frequency phase by Zernike polynomial fitting. The low-frequency surface figure error of the freeform mirror represented by the coefficients of Zernike polynomials is reconstructed from the low-frequency phase, applying the reverse optimization reconstruction technology in the accurate model of the interferometric system. The high-frequency surface figure error of the freeform mirror is retrieved from the high-frequency phase adopting back propagating technology, according to the updated model in which the low-frequency surface figure error has been superimposed on the sag of the freeform mirror. Simulations verified that this method is capable of testing a wide variety of astigmatism-dominated freeform mirrors due to the high dynamic range. The experimental result using our proposed method for a concave freeform Zernike mirror is consistent with the null test result employing the computer-generated hologram.

  10. The Harm Done to Reproducibility by the Culture of Null Hypothesis Significance Testing.

    Science.gov (United States)

    Lash, Timothy L

    2017-09-15

    In the last few years, stakeholders in the scientific community have raised alarms about a perceived lack of reproducibility of scientific results. In reaction, guidelines for journals have been promulgated and grant applicants have been asked to address the rigor and reproducibility of their proposed projects. Neither solution addresses a primary culprit, which is the culture of null hypothesis significance testing that dominates statistical analysis and inference. In an innovative research enterprise, selection of results for further evaluation based on null hypothesis significance testing is doomed to yield a low proportion of reproducible results and a high proportion of effects that are initially overestimated. In addition, the culture of null hypothesis significance testing discourages quantitative adjustments to account for systematic errors and quantitative incorporation of prior information. These strategies would otherwise improve reproducibility and have not been previously proposed in the widely cited literature on this topic. Without discarding the culture of null hypothesis significance testing and implementing these alternative methods for statistical analysis and inference, all other strategies for improving reproducibility will yield marginal gains at best. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. High Contrast Vacuum Nuller Testbed (VNT) Contrast, Performance and Null Control

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-01-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal planeregion extending from 14 D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. TheVNC is a hybrid interferometriccoronagraphic approach for exoplanet science. It operates with high Lyot stopefficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential futureNASA flight telescopes. NASAGoddard Space Flight Center (GSFC) has a well-established effort to develop the VNCand its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and itsenabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry tounprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a W configurationto accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters.We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, criticaltechnologies and null sensing and control.

  12. Modelling the electromechanical interactions in a null-flux EDS Maglev system

    NARCIS (Netherlands)

    Boeij, de J.; Steinbuch, M.; Gutierrez, H.M.; Fair, H.D.

    2004-01-01

    The fundamental electromechanical interactionsin a passive null-ux EDS maglev system aremediated by the voltages induced in the levita-tion coils by the sled magnets, and by the forcesexerted on the sled as a result of the inducedcurrents. This paper presents a reliable andcompact method to

  13. Parallel-propagated frame along null geodesics in higher-dimensional black hole spacetimes

    International Nuclear Information System (INIS)

    Kubiznak, David; Frolov, Valeri P.; Connell, Patrick; Krtous, Pavel

    2009-01-01

    In [arXiv:0803.3259] the equations describing the parallel transport of orthonormal frames along timelike (spacelike) geodesics in a spacetime admitting a nondegenerate principal conformal Killing-Yano 2-form h were solved. The construction employed is based on studying the Darboux subspaces of the 2-form F obtained as a projection of h along the geodesic trajectory. In this paper we demonstrate that, although slightly modified, a similar construction is possible also in the case of null geodesics. In particular, we explicitly construct the parallel-transported frames along null geodesics in D=4, 5, 6 Kerr-NUT-(A)dS spacetimes. We further discuss the parallel transport along principal null directions in these spacetimes. Such directions coincide with the eigenvectors of the principal conformal Killing-Yano tensor. Finally, we show how to obtain a parallel-transported frame along null geodesics in the background of the 4D Plebanski-Demianski metric which admits only a conformal generalization of the Killing-Yano tensor.

  14. Diversity-Multiplexing-Nulling Trade-Off Analysis of Multiuser MIMO System for Intercell Interference Coordination

    Directory of Open Access Journals (Sweden)

    Jinwoo Kim

    2017-01-01

    Full Text Available A fundamental performance trade-off of multicell multiuser multiple-input multiple-output (MU-MIMO systems is explored for achieving intercell and intracell interference-free conditions. In particular, we analyze the three-dimensional diversity-multiplexing-nulling trade-off (DMNT among the diversity order (i.e., the slope of the error performance curve, multiplexing order (i.e., the number of users that are simultaneously served by MU-MIMO, and nulling order (i.e., the number of users with zero interference in a victim cell. This trade-off quantifies the performance of MU-MIMO in terms of its diversity and multiplexing order, while nulling the intercell interference toward the victim cell in the neighbor. First, we design a precoding matrix to mitigate both intercell and intracell interference for a linear precoding-based MU-MIMO system. Then, the trade-off relationship is obtained by analyzing the distribution of the signal-to-noise ratio (SNR at the user terminals. Furthermore, we demonstrate how DMNT can be applied to estimate the long-term throughput for each mobile station, which allows for determining the optimal number of multiplexing order and throughput loss due to the interference nulling.

  15. Exact null distributions of quadratic distribution-free statistics for two-way classification

    NARCIS (Netherlands)

    Wiel, van de M.A.

    2004-01-01

    Abstract We present new techniques for computing exact distributions of `Friedman-type¿ statistics. Representing the null distribution by a generating function allows for the use of general, not necessarily integer-valued rank scores. Moreover, we use symmetry properties of the multivariate

  16. Pattern Nulling of Linear Antenna Arrays Using Backtracking Search Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Kerim Guney

    2015-01-01

    Full Text Available An evolutionary method based on backtracking search optimization algorithm (BSA is proposed for linear antenna array pattern synthesis with prescribed nulls at interference directions. Pattern nulling is obtained by controlling only the amplitude, position, and phase of the antenna array elements. BSA is an innovative metaheuristic technique based on an iterative process. Various numerical examples of linear array patterns with the prescribed single, multiple, and wide nulls are given to illustrate the performance and flexibility of BSA. The results obtained by BSA are compared with the results of the following seventeen algorithms: particle swarm optimization (PSO, genetic algorithm (GA, modified touring ant colony algorithm (MTACO, quadratic programming method (QPM, bacterial foraging algorithm (BFA, bees algorithm (BA, clonal selection algorithm (CLONALG, plant growth simulation algorithm (PGSA, tabu search algorithm (TSA, memetic algorithm (MA, nondominated sorting GA-2 (NSGA-2, multiobjective differential evolution (MODE, decomposition with differential evolution (MOEA/D-DE, comprehensive learning PSO (CLPSO, harmony search algorithm (HSA, seeker optimization algorithm (SOA, and mean variance mapping optimization (MVMO. The simulation results show that the linear antenna array synthesis using BSA provides low side-lobe levels and deep null levels.

  17. On the geometry of null cones to infinity under curvature flux bounds

    International Nuclear Information System (INIS)

    Alexakis, Spyros; Shao, Arick

    2014-01-01

    The main objective of this paper is to control the geometry of a future outgoing truncated null cone extending smoothly toward infinity in an Einstein-vacuum spacetime. In particular, we wish to do this under minimal regularity assumptions, namely, at the (weighted) L 2 -curvature level. We show that if the curvature flux and the data on an initial sphere of the cone are sufficiently close to the corresponding values in a standard Minkowski or Schwarzschild null cone, then we can obtain quantitative bounds on the geometry of the entire infinite cone. The same bounds also imply the existence of limits at infinity, along the null cone, of naturally scaled geometric quantities. In Alexakis and Shao (2013 Bounds on the Bondi energy by a flux of curvature arXiv:1308.4170), we will apply these results in order to control various physical quantities—e.g., the Bondi energy and (linear and angular) momenta—associated with such infinite null cones in vacuum spacetimes. (paper)

  18. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice.

    Science.gov (United States)

    Kyriakides, T R; Zhu, Y H; Yang, Z; Huynh, G; Bornstein, P

    2001-10-01

    The matricellular angiogenesis inhibitor, thrombospondin (TSP) 2, has been shown to be an important modulator of wound healing and the foreign body response. Specifically, TSP2-null mice display improved healing with minimal scarring and form well-vascularized foreign body capsules. In this study we performed subcutaneous implantation of sponges and investigated the resulting angiogenic and fibrogenic responses. Histological and immunohistochemical analysis of sponges, excised at 7, 14, and 21 days after implantation, revealed significant differences between TSP2-null and wild-type mice. Most notably, TSP2-null mice exhibited increased angiogenesis and fibrotic encapsulation of the sponge. However, invasion of dense tissue was compromised, even though its overall density was increased. Furthermore, histomorphometry and biochemical assays demonstrated a significant increase in the extracellular distribution of matrix metalloproteinase (MMP) 2, but no change in the levels of active transforming growth factor-beta(1). The alterations in neovascularization, dense tissue invasion, and MMP2 in TSP2-null mice coincided with the deposition of TSP2 in the extracellular matrix of wild-type animals. These observations support the proposed role of TSP2 as a modulator of angiogenesis and matrix remodeling during tissue repair. In addition, they provide in vivo evidence for a newly proposed function of TSP2 as a modulator of extracellular MMP2 levels.

  19. A Coding of Real Null Four-Momenta into World-Sheet Coordinates

    Directory of Open Access Journals (Sweden)

    David B. Fairlie

    2009-01-01

    Full Text Available The results of minimizing the action for string-like systems on a simply connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into coordinates on the world sheet. This identification arises consistently from different approaches to the problem.

  20. A Coding of Real Null Four-Momenta into World-Sheet Co-ordinates

    OpenAIRE

    Fairlie, David B.

    2008-01-01

    The results of minimizing the action for string-like systems on a simply-connected world sheet are shown to encode the Cartesian components of real null momentum four-vectors into co-ordinates on the world sheet. This identification arises consistently from different approaches to the problem.

  1. A Panel Test of Purchasing Power Parity Under the Null of Stationarity

    OpenAIRE

    Hunter, J; Simpson, M

    2001-01-01

    Purchasing Power Parity (PPP) is tested using a sample of real exchange rate data for twelve European countries. Acknowledging that Augmented Dickey Fuller tests have low power, we apply a Panel test that considers the null of stationarity and corrects for serial dependence using a non-parametric kernel based method.

  2. Stitching interferometry of high numerical aperture cylindrical optics without using a fringe-nulling routine.

    Science.gov (United States)

    Peng, Junzheng; Wang, Qingquan; Peng, Xiang; Yu, Yingjie

    2015-11-01

    Stitching interferometry is a common method for measuring the figure error of high numerical aperture optics. However, subaperture measurement usually requires a fringe-nulling routine, thus making the stitching procedure complex and time-consuming. The challenge when measuring a surface without a fringe-nulling routine is that the rays no longer perpendicularly hit the surface. This violation of the null-test condition can lead to high fringe density and introduce high-order misalignment aberrations into the measurement result. This paper demonstrates that the high-order misalignment aberrations can be characterized by low-order misalignment aberrations; then, an efficient method is proposed to separate the high-order misalignment aberrations from subaperture data. With the proposed method, the fringe-nulling routine is not required. Instead, the subaperture data is measured under a nonzero fringe pattern. Then, all possible misalignment aberrations are removed with the proposed method. Finally, the full aperture map is acquired by connecting all subaperture data together. Experimental results showing the feasibility of the proposed procedure are presented.

  3. No association of GSTM1 null polymorphism with endometriosis in women from central and southern Iran

    Directory of Open Access Journals (Sweden)

    Razieh Dehghani Firouzabadi

    2012-01-01

    Full Text Available Background: Endometriosis is one of the most common gynecologic disorders. It is a complex trait and both genetic and environmental factors have been implicated in its pathogenesis. There is growing evidence indicating that exposure to environmental contaminants is a risk factor for endometriosis. Glutathione-S-Transferase M1 (GSTM1 is one of the genes involved in detoxification of endogenous and exogenous compounds. Objective: Several studies have indicated an association between GSTM1 null mutation and endometriosis. In this study, the possible association between the GSTM1 gene null genotype and susceptibility to endometriosis in woman from central and southern Iran was investigated.Materials and Methods: One hundred and one unrelated premenopausal women with endometriosis and 142 unrelated healthy premenopausal women without endometriosis were enrolled in the study. Genomic DNA was extracted from Peripheral blood in all subjects. GSTM1 null genotyping was performed by polymerase chain reaction (PCR.Results: There was no significant difference between frequencies of GSTM1 null genotype in case and control groups (50.5% Vs. 52.1%, p=0.804. Furthermore, this genotype was not associated with severity of endometriosis in our sample (p=0.77. Conclusion: further studies involving gene-environment and gene-gene interactions, particularly combination of GSTM1 and other GST gene family polymorphisms are needed.

  4. High contrast vacuum nuller testbed (VNT) contrast, performance, and null control

    Science.gov (United States)

    Lyon, Richard G.; Clampin, Mark; Petrone, Peter; Mallik, Udayan; Madison, Timothy; Bolcar, Matthew R.

    2012-09-01

    Herein we report on our Visible Nulling Coronagraph high-contrast result of 109 contrast averaged over a focal plane region extending from 1 - 4 λ/D with the Vacuum Nuller Testbed (VNT) in a vibration isolated vacuum chamber. The VNC is a hybrid interferometric/coronagraphic approach for exoplanet science. It operates with high Lyot stop efficiency for filled, segmented and sparse or diluted-aperture telescopes, thereby spanning the range of potential future NASA flight telescopes. NASA/Goddard Space Flight Center (GSFC) has a well-established effort to develop the VNC and its technologies, and has developed an incremental sequence of VNC testbeds to advance this approach and its enabling technologies. These testbeds have enabled advancement of high-contrast, visible light, nulling interferometry to unprecedented levels. The VNC is based on a modified Mach-Zehnder nulling interferometer, with a “W” configuration to accommodate a hex-packed MEMS based deformable mirror, a coherent fiber bundle and achromatic phase shifters. We give an overview of the VNT and discuss the high-contrast laboratory results, the optical configuration, critical technologies and null sensing and control.

  5. Cell therapy of congenital corneal diseases with umbilical mesenchymal stem cells: lumican null mice.

    Directory of Open Access Journals (Sweden)

    Hongshan Liu

    Full Text Available BACKGROUND: Keratoplasty is the most effective treatment for corneal blindness, but suboptimal medical conditions and lack of qualified medical personnel and donated cornea often prevent the performance of corneal transplantation in developing countries. Our study aims to develop alternative treatment regimens for congenital corneal diseases of genetic mutation. METHODOLOGY/PRINCIPAL FINDINGS: Human mesenchymal stem cells isolated from neonatal umbilical cords were transplanted to treat thin and cloudy corneas of lumican null mice. Transplantation of umbilical mesenchymal stem cells significantly improved corneal transparency and increased stromal thickness of lumican null mice, but human umbilical hematopoietic stem cells failed to do the same. Further studies revealed that collagen lamellae were re-organized in corneal stroma of lumican null mice after mesenchymal stem cell transplantation. Transplanted umbilical mesenchymal stem cells survived in the mouse corneal stroma for more than 3 months with little or no graft rejection. In addition, these cells assumed a keratocyte phenotype, e.g., dendritic morphology, quiescence, expression of keratocyte unique keratan sulfated keratocan and lumican, and CD34. Moreover, umbilical mesenchymal stem cell transplantation improved host keratocyte functions, which was verified by enhanced expression of keratocan and aldehyde dehydrogenase class 3A1 in lumican null mice. CONCLUSIONS/SIGNIFICANCE: Umbilical mesenchymal stem cell transplantation is a promising treatment for congenital corneal diseases involving keratocyte dysfunction. Unlike donated corneas, umbilical mesenchymal stem cells are easily isolated, expanded, stored, and can be quickly recovered from liquid nitrogen when a patient is in urgent need.

  6. Development of IR single mode optical fibers for DARWIN-nulling interferometry

    NARCIS (Netherlands)

    Chakkalakkal Abdulla, S.M.; Cheng, L.K.; Bosch, B. van den; Dijkhuizen, N.; Nieuwland, R.A.; Gielesen, W.L.M.; Lucas, J.; Boussard-Plédel, C.; Conseil, C.; Bureau, B.; Carmo, J.P. do

    2014-01-01

    The DARWIN mission aims to detect weak infra-red emission lines from distant orbiting earth-like planets using nulling interferometry. This requires filtering of wavefront errors using single mode waveguides operating at a wavelength range of 6.5-20 μm. This article describes the optical design of

  7. The Need for Nuance in the Null Hypothesis Significance Testing Debate

    Science.gov (United States)

    Häggström, Olle

    2017-01-01

    Null hypothesis significance testing (NHST) provides an important statistical toolbox, but there are a number of ways in which it is often abused and misinterpreted, with bad consequences for the reliability and progress of science. Parts of contemporary NHST debate, especially in the psychological sciences, is reviewed, and a suggestion is made…

  8. Integrable structures and the quantization of free null initial data for gravity

    Science.gov (United States)

    Fuchs, Andreas; Reisenberger, Michael P.

    2017-09-01

    Variables for constraint free null canonical vacuum general relativity are presented which have simple Poisson brackets that facilitate quantization. Free initial data for vacuum general relativity on a pair of intersecting null hypersurfaces has been known since the 1960s. These consist of the ‘main’ data which are set on the bulk of the two null hypersurfaces, and additional ‘surface’ data set only on their intersection 2-surface. More recently the complete set of Poisson brackets of such data has been obtained. However the complexity of these brackets is an obstacle to their quantization. Part of this difficulty may be overcome using methods from the treatment of cylindrically symmetric gravity. Specializing from general to cylindrically symmetric solutions changes the Poisson algebra of the null initial data surprisingly little, but cylindrically symmetric vacuum general relativity is an integrable system, making powerful tools available. Here a transformation is constructed at the cylindrically symmetric level which maps the main initial data to new data forming a Poisson algebra for which an exact deformation quantization is known. (Although an auxiliary condition on the data has been quantized only in the asymptotically flat case, and a suitable representation of the algebra of quantum data by operators on a Hilbert space has not yet been found.) The definition of the new main data generalizes naturally to arbitrary, symmetryless gravitational fields, with the Poisson brackets retaining their simplicity. The corresponding generalization of the quantization is however ambiguous and requires further analysis.

  9. Reduced infarct size in neuroglobin-null mice after experimental stroke in vivo

    DEFF Research Database (Denmark)

    Raida, Zindy; Hundahl, Christian Ansgar; Kelsen, Jesper

    2012-01-01

    Neuroglobin is considered to be a novel important pharmacological target in combating stroke and neurodegenerative disorders, although the mechanism by which this protection is accomplished remains an enigma. We hypothesized that if neuroglobin is directly involved in neuroprotection, then perman......, then permanent cerebral ischemia would lead to larger infarct volumes in neuroglobin-null mice than in wild-type mice....

  10. Interpretation of Chinese Overt and Null Embedded Arguments by English-Speaking Learners

    Science.gov (United States)

    Zhao, Lucy Xia

    2012-01-01

    It has been proposed that external interfaces are vulnerable to residue optionality, whereas pure syntax and internal interfaces are acquirable in second language (L2) acquisition (Sorace, 2005, 2011; Sorace and Filiaci, 2006). The proposal was tested in this article through the interpretation of overt and null embedded arguments in L2 Chinese…

  11. Simple Fourier optics formalism for high-angular-resolution systems and nulling interferometry.

    Science.gov (United States)

    Hénault, François

    2010-03-01

    Reviewed are various designs of advanced, multiaperture optical systems dedicated to high-angular-resolution imaging or to the detection of exoplanets by nulling interferometry. A simple Fourier optics formalism applicable to both imaging arrays and nulling interferometers is presented, allowing their basic theoretical relationships to be derived as convolution or cross-correlation products suitable for fast and accurate computation. Several unusual designs, such as a "superresolving telescope" utilizing a mosaicking observation procedure or a free-flying, axially recombined interferometer are examined, and their performance in terms of imaging and nulling capacity are assessed. In all considered cases, it is found that the limiting parameter is the diameter of the individual telescopes. A final section devoted to nulling interferometry shows an apparent superiority of axial versus multiaxial recombining schemes. The entire study is valid only in the framework of first-order geometrical optics and scalar diffraction theory. Furthermore, it is assumed that all entrance subapertures are optically conjugated with their associated exit pupils.

  12. Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane

    Science.gov (United States)

    Bertin, M. C.; Pimentel, B. M.; Valcárcel, C. E.; Zambrano, G. E. R.

    2017-08-01

    We develop the Hamilton-Jacobi formalism for Podolsky's electromagnetic theory on the null-plane. The main goal is to build the complete set of Hamiltonian generators of the system as well as to study the canonical and gauge transformations of the theory.

  13. What Constitutes Science and Scientific Evidence: Roles of Null Hypothesis Testing

    Science.gov (United States)

    Chang, Mark

    2017-01-01

    We briefly discuss the philosophical basis of science, causality, and scientific evidence, by introducing the hidden but most fundamental principle of science: the similarity principle. The principle's use in scientific discovery is illustrated with Simpson's paradox and other examples. In discussing the value of null hypothesis statistical…

  14. Novel HLA Class I Alleles Associated with Indian Leprosy Patients

    Directory of Open Access Journals (Sweden)

    U. Shankarkumar

    2003-01-01

    A*0101, Cw*04011, and Cw*0602 leprosy patients was observed when compared to the controls. Further haplotype A*1102-B*4006-Cw*1502 was significantly increased among the lepromatous leprosy patients when compared to the controls. It seems that HLA class I alleles play vital roles in disease association/pathogenesis with leprosy among Indians.

  15. Molecular monitoring of resistant dhfr and dhps allelic haplotypes in ...

    African Journals Online (AJOL)

    Objective: The present study assesses the frequency of resistant dhfr and dhps alleles in Morogoro-Mvomero district in south eastern Tanzania and contrast their rate of change during 17 years of SP second line use against five years of SP first line use. Methodology: Cross sectional surveys of asymptomatic infections were ...

  16. Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis

    Science.gov (United States)

    Brock, M.K.; White, B.N.

    1991-01-01

    Human DNA probes that identify variable numbers of tandem repeat loci are being used to generate DNA fingerprints in many animal and plant species. In most species the majority of the sc rable autoradiographic bands of the DNA fingerprint represent alleles from numerous unlinked loci. This study was initiated to use DNA fingerprints to determine the amount of band-sharing among captive Hispaniolan parrots (Amazona ventralis) with known genetic relationships. This would form the data base to examine DNA fingerprints of the closely related and endangered Puerto Rican parrot (A. vittata) and to estimate the degree of inbreeding in the relic population. We found by segregation analysis of the bands scored in the DNA fingerprints of the Hispaniolan parrots that there may be as few as two to five loci identified by the human 33.15 probe. Furthermore, at one locus we identified seven alleles, one of which is represented by as many as 19 cosegregating bands. It is unknown how common multiband alleles might be in natural populations, and their existence will cause problems in the assessment of relatedness by band-sharing analysis. We believe, therefore, that a pedigree analysis should be included in all DNA fingerprinting studies, where possible, in order to estimate the number of loci identified by a minisatellite DNA probe and to examine the nature of their alleles.

  17. Allele frequency distribution for 21 autosomal STR loci in Bhutan.

    Science.gov (United States)

    Kraaijenbrink, Thirsa; van Driem, George L; Tshering of Gaselô, Karma; de Knijff, Peter

    2007-07-20

    We studied the allele frequency distribution of 21 autosomal STR loci contained in the AmpFlSTR Identifiler (Applied Biosystems), the Powerplex 16 (Promega) and the FFFL (Promega) multiplex PCR kits among 936 individuals from the Royal Kingdom of Bhutan. As such these are the first published autosomal DNA results from this country.

  18. Allelic prevalence of intron 3 insertion/deletion genetic ...

    African Journals Online (AJOL)

    Leila Fallahzadeh-Abarghooei

    2015-03-18

    Mar 18, 2015 ... Tabriz (East Azerbaijan province; belong to Azaris), and Yasuj (Kohgiluyeh va Boyer-Ahmad pro- vince; belong to Lurs), respectively. Genotypic analysis of the Ins/Del XRCC4 polymorphism was detected by the PCR method. Results: The prevalence of the Del allele in Shiraz, Abarku, Tabriz, and Yasuj was ...

  19. Allele frequency analysis of Chinese chestnut ( Castanea mollissima ...

    African Journals Online (AJOL)

    The aim of this study was to establish a method for allele frequency detection in bulk samples. The abundance of polymerase chain reaction (PCR) products in bulk leaf samples was detected using fluorescent labeled Simple sequence repeat (SSR) primers and an Applied biosystems (AB) automatic DNA analyzer.

  20. Association of LEI0258 microsatellite alleles with antibody response ...

    African Journals Online (AJOL)

    SERVER

    2008-03-18

    Mar 18, 2008 ... (MHC) B region on chicken Micro-chromosome 16 has been demonstrated by many workers to be ... promising DNA markers in characterizing MHC B genes. Identifying marker alleles (bands) ..... SAS/STAT Users' Guide,. Release 6.12 Edition, SAS Institute Inc, Cary, North Carolina. USA. Taylor RL (2004).

  1. Distribution of HIV-1 resistance-conferring polymorphic alleles SDF ...

    Indian Academy of Sciences (India)

    Polymorphic allelic variants of chemokine receptors CCR2 and CCR5, as well as of stromal-derived factor-1 SDF-1, the ligand for the chemokine receptor CXCR4, are known to have protective effects against HIV-1 infection and to be involved with delay in disease progression. We have studied the DNA polymorphisms at ...

  2. HLA-A alleles differentially associate with severity to Plasmodium ...

    African Journals Online (AJOL)

    Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A ...

  3. Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

    Science.gov (United States)

    Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

    1993-04-01

    Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

  4. THE NATURE OF FLARE RIBBONS IN CORONAL NULL-POINT TOPOLOGY

    International Nuclear Information System (INIS)

    Masson, S.; Aulanier, G.; Pariat, E.; Schrijver, C. J.

    2009-01-01

    Flare ribbons are commonly attributed to the low-altitude impact, along the footprints of separatrices or quasi-separatrix layers (QSLs), of particle beams accelerated through magnetic reconnection. If reconnection occurs at a three-dimensional coronal magnetic null point, the footprint of the dome-shaped fan surface would map a closed circular ribbon. This paper addresses the following issues: does the entire circular ribbon brighten simultaneously, as expected because all fan field lines pass through the null point? And since the spine separatrices are singular field lines, do spine-related ribbons look like compact kernels? What can we learn from these observations about current sheet formation and magnetic reconnection in a null-point topology? The present study addresses these questions by analyzing Transition Region and Coronal Explorer and Solar and Heliospheric Observatory/Michelson Doppler Imager observations of a confined flare presenting a circular ribbon. Using a potential field extrapolation, we linked the circular shape of the ribbon with the photospheric mapping of the fan field lines originating from a coronal null point. Observations show that the flare ribbon outlining the fan lines brightens sequentially along the counterclockwise direction and that the spine-related ribbons are elongated. Using the potential field extrapolation as initial condition, we conduct a low-β resistive magnetohydrodynamics simulation of this observed event. We drive the coronal evolution by line-tied diverging boundary motions, so as to emulate the observed photospheric flow pattern associated with some magnetic flux emergence. The numerical analysis allows us to explain several observed features of the confined flare. The vorticity induced in the fan by the prescribed motions causes the spines to tear apart along the fan. This leads to formation of a thin current sheet and induces null-point reconnection. We also find that the null point and its associated topological

  5. Strain-based HLA association analysis identified HLA-DRB1*09:01 associated with modern strain tuberculosis.

    Science.gov (United States)

    Toyo-Oka, L; Mahasirimongkol, S; Yanai, H; Mushiroda, T; Wattanapokayakit, S; Wichukchinda, N; Yamada, N; Smittipat, N; Juthayothin, T; Palittapongarnpim, P; Nedsuwan, S; Kantipong, P; Takahashi, A; Kubo, M; Sawanpanyalert, P; Tokunaga, K

    2017-09-01

    Tuberculosis (TB) occurs as a result of complex interactions between the host immune system and pathogen virulence factors. Human leukocyte antigen (HLA) class II molecules play an important role in the host immune system. However, no study has assessed the association between HLA class II genes and susceptibility to TB caused by specific strains. This study investigated the possible association of HLA class II genes with TB caused by modern and ancient Mycobacterium tuberculosis (MTB). The study included 682 patients with TB and 836 control subjects who were typed for HLA-DRB1 and HLA-DQB1 alleles. MTB strains were classified using a large sequence polymorphism typing method. Association analysis was performed using common HLA alleles and haplotypes in different MTB strains. HLA association analysis of patients infected with modern MTB strains showed significant association for HLA-DRB1*09:01 (odds ratio [OR] = 1.82; P-value = 9.88 × 10 -4 ) and HLA-DQB1*03:03 alleles (OR = 1.76; P-value = 1.31 × 10 -3 ) with susceptibility to TB. Haplotype analysis confirmed that these alleles were in strong linkage disequilibrium and did not exert an interactive effect. Thus, the results of this study showed an association between HLA class II genes and susceptibility to TB caused by modern MTB strains, suggesting the importance of strain-specific analysis to determine susceptibility genes associated with TB. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Segregation of male-sterility alleles across a species boundary.

    Science.gov (United States)

    Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

    2014-02-01

    Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  7. Reversing hypomyelination in BACE1-null mice with Akt-DD overexpression.

    Science.gov (United States)

    Hu, Xiangyou; Schlanger, Rita; He, Wanxia; Macklin, Wendy B; Yan, Riqiang

    2013-05-01

    β-Site amyloid precursor protein convertase enzyme 1 (BACE1), a type I transmembrane aspartyl protease required to cleave amyloid precursor protein for releasing a toxic amyloid peptide, also cleaves type I and type III neuregulin-1 (Nrg-1). BACE1 deficiency in mice causes hypomyelination during development and impairs remyelination if injured. In BACE1-null mice, the abolished cleavage of neuregulin-1 by BACE1 is speculated to cause reduced myelin sheath thickness in both the central nervous system and peripheral nervous system because reduced cleavage of Nrg-1 correlates with reduced Akt phosphorylation, a downstream signaling molecule of the Nrg-1/ErbB pathway. Here we tested specifically whether increasing Akt activity alone in oligodendrocytes would be sufficient to reverse the hypomyelination phenotype in BACE1-null mice. BACE1-null mice were bred with transgenic mice expressing constitutively active Akt (Akt-DD; mutations with D(308)T and D(473)S) in oligodendrocytes. Relative to littermate BACE1-null controls, BACE1(-/-)/Akt-DD mice exhibited enhanced expression of myelin basic protein and promoter of proteolipid protein. The elevated expression of myelin proteins correlated with a thicker myelin sheath in optic nerves; comparison of quantified g ratios with statistic significance was used to confirm this reversion. However, it appeared that myelin sheath thickness in the sciatic nerves was not increased in BACE1(-/-)/Akt-DD mice, as the g ratio was not significantly different from the control. Hence, increased Akt activity in BACE1-null myelinating cells only compensates for the loss of BACE1 activity in the central nervous system, which is consistent with the observation that overexpression of Akt-DD in Schwann cells did not induce hypermyelination. Our results suggest that signaling activity other than Akt may also contribute to proper myelination in peripheral nerves.

  8. Orexin Receptor Antagonism Improves Sleep and Reduces Seizures in Kcna1-null Mice.

    Science.gov (United States)

    Roundtree, Harrison M; Simeone, Timothy A; Johnson, Chaz; Matthews, Stephanie A; Samson, Kaeli K; Simeone, Kristina A

    2016-02-01

    Comorbid sleep disorders occur in approximately one-third of people with epilepsy. Seizures and sleep disorders have an interdependent relationship where the occurrence of one can exacerbate the other. Orexin, a wake-promoting neuropeptide, is associated with sleep disorder symptoms. Here, we tested the hypothesis that orexin dysregulation plays a role in the comorbid sleep disorder symptoms in the Kcna1-null mouse model of temporal lobe epilepsy. Rest-activity was assessed using infrared beam actigraphy. Sleep architecture and seizures were assessed using continuous video-electroencephalography-electromyography recordings in Kcna1-null mice treated with vehicle or the dual orexin receptor antagonist, almorexant (100 mg/kg, intraperitoneally). Orexin levels in the lateral hypothalamus/perifornical region (LH/P) and hypothalamic pathology were assessed with immunohistochemistry and oxygen polarography. Kcna1-null mice have increased latency to rapid eye movement (REM) sleep onset, sleep fragmentation, and number of wake epochs. The numbers of REM and non-REM (NREM) sleep epochs are significantly reduced in Kcna1-null mice. Severe seizures propagate to the wake-promoting LH/P where injury is apparent (indicated by astrogliosis, blood-brain barrier permeability, and impaired mitochondrial function). The number of orexin-positive neurons is increased in the LH/P compared to wild-type LH/P. Treatment with a dual orexin receptor antagonist significantly increases the number and duration of NREM sleep epochs and reduces the latency to REM sleep onset. Further, almorexant treatment reduces the incidence of severe seizures and overall seizure burden. Interestingly, we report a significant positive correlation between latency to REM onset and seizure burden in Kcna1-null mice. Dual orexin receptor antagonists may be an effective sleeping aid in epilepsy, and warrants further study on their somnogenic and ant-seizure effects in other epilepsy models. © 2016 Associated

  9. Isolation of two independent allyl alcohol resistant Adh-1 null mutants following selection of pollen and seeds.

    NARCIS (Netherlands)

    Wisman, E.; Ramanna, M.S.; Zabel, P.

    1993-01-01

    The Adh-1 null mutant (B15-1-8) isolated previously was used to establish conditions that allow the selection of ADH-deficient pollen grains and seeds of tomato. New Adh-1 null mutants were then selected among the progenies derived from crosses between the genetically unstable tomato lines Yvms,

  10. Increased Oocyte Degeneration and Follicular Atresia during the Estrous Cycle in Anti-Müllerian Hormone Null Mice

    NARCIS (Netherlands)

    Visser, Jenny A.; Durlinger, Alexandra L.L.; Peters, Isolde J.J.; Heuvel, Edwin R. van den; Rose, Ursula M.; Kramer, Piet; Jong, Frank H. de; Themmen, Axel P.N.

    2007-01-01

    Anti-Müllerian hormone (AMH) plays an important role in folliculogenesis. AMH null mice display an increased recruitment of primordial follicles. Nevertheless, these mice do not have proportionally more preovulatory follicles. Therefore, AMH null mice provide an interesting genetic model to study

  11. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency

    NARCIS (Netherlands)

    Kiezun, Adam; Pulit, Sara L.; Francioli, Laurent C.; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I.; van Duijn, Cornelia M.; Slagboom, P. Eline; van Ommen, G. J. B.; Wijmenga, Cisca; de Bakker, Paul I. W.; Sunyaev, Shamil R.

    Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral

  12. On Bäcklund transformation and vortex filament equation for null Cartan curve in Minkowski 3-space

    Energy Technology Data Exchange (ETDEWEB)

    Grbović, Milica, E-mail: milica.grbovic@kg.ac.rs; Nešović, Emilija, E-mail: nesovickg@sbb.rs [University of Kragujevac, Faculty of Science, Department of Mathematics and Informatics (Serbia)

    2016-12-15

    In this paper we introduce Bäcklund transformation of a null Cartan curve in Minkowski 3-space as a transformation which maps a null Cartan helix to another null Cartan helix, congruent to the given one. We also give the sufficient conditions for a transformation between two null Cartan curves in the Minkowski 3-space such that these curves have equal constant torsions. By using the Da Rios vortex filament equation, based on localized induction approximation, we derive the vortex filament equation for a null Cartan curve and obtain evolution equation for it’s torsion. As an application, we show that Cartan’s frame vectors generate new solutions of the Da Rios vortex filament equation.

  13. Humoral immune responses to a single allele PfAMA1 vaccine in healthy malaria-naïve adults.

    Directory of Open Access Journals (Sweden)

    Edmond J Remarque

    Full Text Available Plasmodium falciparum: apical membrane antigen 1 (AMA1 is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. The polymorphic nature of AMA1 may compromise vaccine induced protection. The humoral response induced by two dosages (10 and 50 µg of a single allele AMA1 antigen (FVO formulated with Alhydrogel, Montanide ISA 720 or AS02 was investigated in 47 malaria-naïve adult volunteers. Volunteers were vaccinated 3 times at 4 weekly intervals and serum samples obtained four weeks after the third immunization were analysed for (i Antibody responses to various allelic variants, (ii Domain specificity, (iii Avidity, (iv IgG subclass levels, by ELISA and (v functionality of antibody responses by Growth Inhibition Assay (GIA. About half of the antibodies induced by vaccination cross reacted with heterologous AMA1 alleles. The choice of adjuvant determined the magnitude of the antibody response, but had only a marginal influence on specificity, avidity, domain recognition or subclass responses. The highest antibody responses were observed for AMA1 formulated with AS02. The Growth Inhibition Assay activity of the antibodies was proportional to the amount of antigen specific IgG and the functional capacity of the antibodies was similar for heterologous AMA1-expressing laboratory strains.ClinicalTrials.gov NCT00730782.

  14. Inhibition of urethane-induced genotoxicity and cell proliferation in CYP2E1-null mice

    International Nuclear Information System (INIS)

    Hoffler, Undi; Dixon, Darlene; Peddada, Shyamal; Ghanayem, Burhan I.

    2005-01-01

    Urethane is a multi-site animal carcinogen and was classified as 'reasonably anticipated to be a human carcinogen.' Urethane is a fermentation by-product and found at appreciable levels in alcoholic beverages and foods such as bread and cheese. Recent work in this laboratory demonstrated for the first time that CYP2E1 is the principal enzyme responsible for urethane metabolism. The current studies were undertaken to assess the relationships between CYP2E1-mediated metabolism and urethane-induced genotoxicity and cell proliferation as determined by induction of micronucleated erythrocytes (MN) and expression of Ki-67, respectively, using CYP2E1-null and wild-type mice. Urethane was administered at 0 (vehicle), 1, 10, or 100 mg/kg/day (p.o.), 5 days/week for 6 weeks. A significant dose-dependent increase in MN was observed in wild-type mice; however, a slight increase was measured in the MN-polychromatic erythrocytes in CYP2E1-null mice treated with 100 mg/kg. A significant increase in the expression of Ki-67 was detected in the livers and the lungs (terminal bronchioles, alveoli, and bronchi) of wild-type mice administered 100 mg urethane/kg in comparison to controls. In contrast, CYP2E1-null mice administered this dose exhibited negligible alterations in Ki-67 expression in the livers and lungs compared to controls. Interestingly, while Ki-67 expression in the forestomach decreased in wild-type mice, it increased in CYP2E1-null mice. Subsequent comparative metabolism studies demonstrated that total urethane-derived radioactivity in the plasma, liver, and lung was significantly higher in CYP2E1-null versus wild-type mice and un-metabolized urethane constituted greater than 83% of the radioactivity in CYP2E1-null mice. Un-metabolized urethane was not detectable in the plasma, liver, and lung of wild-type mice. In conclusion, these data demonstrated that CYP2E1-mediated metabolism of urethane, presumably via epoxide formation, is necessary for the induction of

  15. Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S

    2012-09-01

    Full Text Available Abstract Background MSP1 is the major surface protein on merozoites and a prime candidate for a blood stage malaria vaccine. Preclinical and seroepidemiological studies have implicated antibodies to MSP1 in protection against blood stage parasitaemia and/or reduced parasite densities, respectively. Malaria endemic areas have multiple strains of Plasmodium falciparum circulating at any given time, giving rise to complex immune responses, an issue which is generally not addressed in clinical trials conducted in non-endemic areas. A lack of understanding of the effect of pre-existing immunity to heterologous parasite strains may significantly contribute to vaccine failure in the field. The purpose of this study was to model the effect of pre-existing immunity to MSP142 on the immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles. Methods Inbred and outbred mice were immunized with various recombinant P. falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20 (3D7 and Wellcome (K1, FVO. Humoral immune responses were analysed by ELISA and LuminexTM, and functional activity of induced MSP142-specific antibodies was assessed by growth inhibition assays. T-cell responses were characterized using ex vivo ELISpot assays. Results Analysis of the immune responses induced by various immunization regimens demonstrated a strong allele-specific response at the T cell level in both inbred and outbred mice. The success of heterologous regimens depended on the degree of homology of the N-terminal p33 portion of the MSP142, likely due to the fact that most T cell epitopes reside in this part of the molecule. Analysis of humoral immune responses revealed a marked cross-reactivity between the alleles. Functional analyses showed that some of the heterologous regimens induced antibodies with improved growth inhibitory activities. Conclusion The development of a more broadly efficacious MSP1 based vaccine may be

  16. Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

    Directory of Open Access Journals (Sweden)

    Gianni Liti

    2009-09-01

    Full Text Available In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp. Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE. Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80 resulting in very short telomeres.

  17. Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

    Science.gov (United States)

    Liti, Gianni; Haricharan, Svasti; Cubillos, Francisco A; Tierney, Anna L; Sharp, Sarah; Bertuch, Alison A; Parts, Leopold; Bailes, Elizabeth; Louis, Edward J

    2009-09-01

    In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (400 bp). Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE). Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs) were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resulting in very short telomeres.

  18. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots

    Czech Academy of Sciences Publication Activity Database

    Baker, C.L.; Petkova, P.; Walker, M.; Flachs, Petr; Mihola, Ondřej; Trachtulec, Zdeněk; Petkov, P.M.; Paigen, K.

    2015-01-01

    Roč. 11, č. 9 (2015), e1005512-e1005512 ISSN 1553-7390 R&D Projects: GA ČR GAP305/10/1931; GA ČR(CZ) GA14-20728S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : recombination * PRDM9 * allelic competition Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.528, year: 2014

  19. [Phenotypic effects of puroindoline gene alleles of bread wheat].

    Science.gov (United States)

    Chebotar, S V; Kurakina, K O; Khokhlov, O M; Chebotar, H O; Syvolap, Iu M

    2012-01-01

    85 winter bread wheat varieties and lines that have been developed mostly in Ukraine were analyzed with NIR for parameters of hardness and protein content. The hardness data were compared with the data of puroindoline gene alleles analysis done earlier and the published data. Significant variation of parameters of hardness was revealed when there was low polymorphism of puroindoline genes indicating the presence of additional genes that influence the hardness parameters.

  20. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  1. TRPV6 alleles do not influence prostate cancer progression

    OpenAIRE

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-01-01

    Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV...

  2. Mutant power: using mutant allele collections for yeast functional genomics.

    Science.gov (United States)

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  4. Null geodesics and wave front singularities in the Gödel space-time

    Science.gov (United States)

    Kling, Thomas P.; Roebuck, Kevin; Grotzke, Eric

    2018-01-01

    We explore wave fronts of null geodesics in the Gödel metric emitted from point sources both at, and away from, the origin. For constant time wave fronts emitted by sources away from the origin, we find cusp ridges as well as blue sky metamorphoses where spatially disconnected portions of the wave front appear, connect to the main wave front, and then later break free and vanish. These blue sky metamorphoses in the constant time wave fronts highlight the non-causal features of the Gödel metric. We introduce a concept of physical distance along the null geodesics, and show that for wave fronts of constant physical distance, the reorganization of the points making up the wave front leads to the removal of cusp ridges.

  5. Luxembourg in the Early Days of the EEC: Null Player or Not?

    Directory of Open Access Journals (Sweden)

    Alexander Mayer

    2018-05-01

    Full Text Available Voters whose yes-or-no decision never makes a difference to the outcome in a simple voting game are known as “null players”. Luxembourg’s role in the Council of Ministers during the first period of the European Economic Community (EEC is often cited as a real-world case. The paper contrasts the textbook claim that Luxembourg was a null player with a more comprehensive picture of Luxembourg’s role in EEC’s voting system. The assessment of Luxembourg’s voting power is sensitive to the role played by the European Commission in the decision-making procedure and the measurement concepts underlying power evaluations.

  6. Enhanced endotoxin sensitivity in fps/fes-null mice with minimal defects in hematopoietic homeostasis.

    Science.gov (United States)

    Zirngibl, Ralph A; Senis, Yotis; Greer, Peter A

    2002-04-01

    The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.

  7. Magnetic Nulls and Super-radial Expansion in the Solar Corona

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, Sarah E.; Dalmasse, Kevin; Tomczyk, Steven; Toma, Giuliana de; Burkepile, Joan; Galloy, Michael [National Center for Atmospheric Research, 3080 Center Green Drive, Boulder, CO 80301 (United States); Rachmeler, Laurel A. [NASA Marshall Space Flight Center, Huntsville, AL 35811 (United States); Rosa, Marc L. De, E-mail: sgibson@ucar.edu [Lockheed Martin Solar and Astrophysics Laboratory, 3251 Hanover Street B/252, Palo Alto, CA 94304 (United States)

    2017-05-10

    Magnetic fields in the Sun’s outer atmosphere—the corona—control both solar-wind acceleration and the dynamics of solar eruptions. We present the first clear observational evidence of coronal magnetic nulls in off-limb linearly polarized observations of pseudostreamers, taken by the Coronal Multichannel Polarimeter (CoMP) telescope. These nulls represent regions where magnetic reconnection is likely to act as a catalyst for solar activity. CoMP linear-polarization observations also provide an independent, coronal proxy for magnetic expansion into the solar wind, a quantity often used to parameterize and predict the solar wind speed at Earth. We introduce a new method for explicitly calculating expansion factors from CoMP coronal linear-polarization observations, which does not require photospheric extrapolations. We conclude that linearly polarized light is a powerful new diagnostic of critical coronal magnetic topologies and the expanding magnetic flux tubes that channel the solar wind.

  8. Local differential geometry of null curves in conformally flat space-time

    International Nuclear Information System (INIS)

    Urbantke, H.

    1989-01-01

    The conformally invariant differential geometry of null curves in conformally flat space-times is given, using the six-vector formalism which has generalizations to higher dimensions. This is then paralleled by a twistor description, with a twofold merit: firstly, sometimes the description is easier in twistor terms, sometimes in six-vector terms, which leads to a mutual enlightenment of both; and secondly, the case of null curves in timelike pseudospheres or 2+1 Minkowski space we were only able to treat twistorially, making use of an invariant differential found by Fubini and Cech. The result is the expected one: apart from stated exceptional cases there is a conformally invariant parameter and two conformally invariant curvatures which, when specified in terms of this parameter, serve to characterize the curve up to conformal transformations. 12 refs. (Author)

  9. Bursty, Broadband Electromagnetic Waves Associated with Three-Dimensional Nulls Observed in Turbulent Magnetosheath Reconnection

    Science.gov (United States)

    Adrian, Mark L.; Wendel, D. E.

    2012-01-01

    We investigate observations of intense bursts of electromagnetic wave energy in association with the thin current layers of turbulent magnetosheath reconnection. These observed emissions - typically detected in the layers immediately outside of the current layer proper - form two distinct types: (i) broadband emissions that extend continuously to lOs of Hertz; and (ii) structured bursts of emitted energy that occur above 80-Hz, often displaying features reminiscent of absorption bands and are observed near the local minima in the magnetic field. We present detailed analyses of these intense bursts of electromagnetic energy and quantify their proximity to X-IO-nulls and magnetic spine connected null pairs, as well as their correlation - if any - to the amount of magnetic energy converted by the process of magnetic reconnection.

  10. Vacuum solutions admitting a geodesic null congruence with shear proportional to expansion

    International Nuclear Information System (INIS)

    Kupeli, A.H.

    1988-01-01

    Algebraically general, nontwisting solutions for the vacuum to vacuum generalized Kerr--Schild (GKS) transformation are obtained. These solutions admit a geodesic null congruence with shear proportional to expansion. In the Newman--Penrose formalism, if l/sup μ/ is chosen to be the null vector of the GKS transformation, this property is stated as σ = arho and Da = 0. It is assumed that a is a constant, and the background is chosen as a pp-wave solution. For generic values of a, the GKS metrics consist of the Kasner solutions. For a = +- (1 +- (2)/sup 1/2/), there are solutions with less symmetries including special cases of the Kota--Perjes and Lukacs solutions

  11. Kinetic modeling of particle acceleration in a solar null point reconnection region

    DEFF Research Database (Denmark)

    Baumann, Gisela; Haugbølle, Troels; Nordlund, Åke

    2013-01-01

    The primary focus of this paper is on the particle acceleration mechanism in solar coronal 3D reconnection null-point regions. Starting from a potential field extrapolation of a SOHO magnetogram taken on 2002 November 16, we first performed MHD simulations with horizontal motions observed by SOHO...... particles and 3.5 billion grid cells of size 17.5\\,km --- these simulations offer a new opportunity to study particle acceleration in solar-like settings....... applied to the photospheric boundary of the computational box. After a build-up of electric current in the fan-plane of the null-point, a sub-section of the evolved MHD data was used as initial and boundary conditions for a kinetic particle-in-cell model of the plasma. We find that sub...

  12. The genetic structure of the Małopolski horses with special regard to the Przedświt strain

    OpenAIRE

    Mirosław Smugała; Ryszard Pikuła; Iva Jiskrová

    2006-01-01

    The present study covers immunogenetic characteristics of the Małopolski horses, involving 5 blood protein systems, with special regard to horses of the Przedświt strain. Basing on the obtained results it was found that high frequency of allele EsF is a characteristic feature of the examined Przedświt strain horses.

  13. The genetic structure of the Małopolski horses with special regard to the Przedświt strain

    Directory of Open Access Journals (Sweden)

    Mirosław Smugała

    2006-01-01

    Full Text Available The present study covers immunogenetic characteristics of the Małopolski horses, involving 5 blood protein systems, with special regard to horses of the Przedświt strain. Basing on the obtained results it was found that high frequency of allele EsF is a characteristic feature of the examined Przedświt strain horses.

  14. IMPROVING INTERFEROMETRIC NULL DEPTH MEASUREMENTS USING STATISTICAL DISTRIBUTIONS: THEORY AND FIRST RESULTS WITH THE PALOMAR FIBER NULLER

    International Nuclear Information System (INIS)

    Hanot, C.; Riaud, P.; Absil, O.; Mennesson, B.; Martin, S.; Liewer, K.; Loya, F.; Mawet, D.; Serabyn, E.

    2011-01-01

    A new 'self-calibrated' statistical analysis method has been developed for the reduction of nulling interferometry data. The idea is to use the statistical distributions of the fluctuating null depth and beam intensities to retrieve the astrophysical null depth (or equivalently the object's visibility) in the presence of fast atmospheric fluctuations. The approach yields an accuracy much better (about an order of magnitude) than is presently possible with standard data reduction methods, because the astrophysical null depth accuracy is no longer limited by the magnitude of the instrumental phase and intensity errors but by uncertainties on their probability distributions. This approach was tested on the sky with the two-aperture fiber nulling instrument mounted on the Palomar Hale telescope. Using our new data analysis approach alone-and no observations of calibrators-we find that error bars on the astrophysical null depth as low as a few 10 -4 can be obtained in the near-infrared, which means that null depths lower than 10 -3 can be reliably measured. This statistical analysis is not specific to our instrument and may be applicable to other interferometers.

  15. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

    Directory of Open Access Journals (Sweden)

    Timothy M. Adamo

    2009-09-01

    Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in complex Minkowski space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi’s integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum–conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  16. Potential of balloon payloads for in flight validation of direct and nulling interferometry concepts

    Science.gov (United States)

    Demangeon, Olivier; Ollivier, Marc; Le Duigou, Jean-Michel; Cassaing, Frédéric; Coudé du Foresto, Vincent; Mourard, Denis; Kern, Pierre; Lam Trong, Tien; Evrard, Jean; Absil, Olivier; Defrere, Denis; Lopez, Bruno

    2010-07-01

    While the question of low cost / low science precursors is raised to validate the concepts of direct and nulling interferometry space missions, balloon payloads offer a real opportunity thanks to their relatively low cost and reduced development plan. Taking into account the flight capabilities of various balloon types, we propose in this paper, several concepts of payloads associated to their flight plan. We also discuss the pros and cons of each concepts in terms of technological and science demonstration power.

  17. Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta

    Czech Academy of Sciences Publication Activity Database

    Zahradníček, Oldřich; Horáček, I.; Tucker, A. S.

    2012-01-01

    Roč. 221, č. 3 (2012), s. 195-208 ISSN 0021-8782 R&D Projects: GA ČR(CZ) GAP305/12/1766 Grant - others:GA AV ČR(CZ) KJB601110910 Program:KJ Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : cusps * gecko * null generation teeth Subject RIV: EA - Cell Biology Impact factor: 2.357, year: 2012

  18. Vascular Response to Intra-arterial Injury in the Thrombospondin-1 Null Mouse

    OpenAIRE

    Budhani, Faisal; Leonard, Katherine A.; Bergdahl, Andreas; Gao, Jimin; Lawler, Jack; Davis, Elaine C.

    2007-01-01

    Thrombospondin-1 (TSP-1) is a multifunctional, extracellular matrix protein that has been implicated in the regulation of smooth muscle cell proliferation, migration and differentiation during vascular development and injury. Vascular injury in wildtype and TSP-1 null mice was carried out by insertion of a straight spring guidewire into the femoral artery via a muscular arterial branch. Blood flow was restored after the muscular branch was ligated. The injury completely denuded the endotheliu...

  19. Null strings and complex Einstein-Maxwell fields with cosmological constant

    International Nuclear Information System (INIS)

    Garcia, A.; Plebanski, J.F.; Robinson, I.

    1977-01-01

    Previous results of Plebanski and Robinson (Phys. Rev. Lett.; 37:493 (1976)) concerning left-degenerate Einstein-flat complex space-times and preliminary results concerning the electromagnetic field, are here generalized and worked out in some detail for the system of Einstein-Maxwell equations with a cosmological constant. On the assumption that there exists a congruence of totally null surfaces, the system is reduced to a pair of equations for the two unknown functions. (author)

  20. The root infinitive stage in a null subject language: Romance in the Balkans

    Directory of Open Access Journals (Sweden)

    Larisa Avram

    2007-01-01

    Full Text Available The aim of the present paper is to determine which early non-finite verbal form is the Root Infinitive analogue in Romanian, an Inflection-licensed null subject language. In particular, we investigate whether the RI-analogue is the imperative, as predicted by Salustri and Hyams’s (2003 hypothesis, or whether it is a language specific underspecified form, overused during the early stages of acquisition, as predicted by Wexler et al. (2004.

  1. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation

    Directory of Open Access Journals (Sweden)

    Timothy M. Adamo

    2012-01-01

    Full Text Available A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, H-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss by (Bondi's integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum--conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  2. Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

    Directory of Open Access Journals (Sweden)

    Robert M Kaplan

    Full Text Available We explore whether the number of null results in large National Heart Lung, and Blood Institute (NHLBI funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease. Trials were included if direct costs >$500,000/year, participants were adult humans, and the primary outcome was cardiovascular risk, disease or death. The 55 trials meeting these criteria were coded for whether they were published prior to or after the year 2000, whether they registered in clinicaltrials.gov prior to publication, used active or placebo comparator, and whether or not the trial had industry co-sponsorship. We tabulated whether the study reported a positive, negative, or null result on the primary outcome variable and for total mortality.17 of 30 studies (57% published prior to 2000 showed a significant benefit of intervention on the primary outcome in comparison to only 2 among the 25 (8% trials published after 2000 (χ2=12.2,df= 1, p=0.0005. There has been no change in the proportion of trials that compared treatment to placebo versus active comparator. Industry co-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward null findings.The number NHLBI trials reporting positive results declined after the year 2000. Prospective declaration of outcomes in RCTs, and the adoption of transparent reporting standards, as required by clinicaltrials.gov, may have contributed to the trend toward null findings.

  3. Null Geodesic Congruences, Asymptotically-Flat Spacetimes and Their Physical Interpretation.

    Science.gov (United States)

    Adamo, Timothy M; Newman, Ezra T; Kozameh, Carlos

    2012-01-01

    A priori, there is nothing very special about shear-free or asymptotically shear-free null geodesic congruences. Surprisingly, however, they turn out to possess a large number of fascinating geometric properties and to be closely related, in the context of general relativity, to a variety of physically significant effects. It is the purpose of this paper to try to fully develop these issues. This work starts with a detailed exposition of the theory of shear-free and asymptotically shear-free null geodesic congruences, i.e., congruences with shear that vanishes at future conformal null infinity. A major portion of the exposition lies in the analysis of the space of regular shear-free and asymptotically shear-free null geodesic congruences. This analysis leads to the space of complex analytic curves in an auxiliary four-complex dimensional space, [Formula: see text]-space. They in turn play a dominant role in the applications. The applications center around the problem of extracting interior physical properties of an asymptotically-flat spacetime directly from the asymptotic gravitational (and Maxwell) field itself, in analogy with the determination of total charge by an integral over the Maxwell field at infinity or the identification of the interior mass (and its loss) by (Bondi's) integrals of the Weyl tensor, also at infinity. More specifically, we will see that the asymptotically shear-free congruences lead us to an asymptotic definition of the center-of-mass and its equations of motion. This includes a kinematic meaning, in terms of the center-of-mass motion, for the Bondi three-momentum. In addition, we obtain insights into intrinsic spin and, in general, angular momentum, including an angular-momentum-conservation law with well-defined flux terms. When a Maxwell field is present, the asymptotically shear-free congruences allow us to determine/define at infinity a center-of-charge world line and intrinsic magnetic dipole moment.

  4. Hypersensitivities for Acetaldehyde and Other Agents among Cancer Cells Null for Clinically Relevant Fanconi Anemia Genes

    OpenAIRE

    Ghosh, Soma; Sur, Surojit; Yerram, Sashidhar R.; Rago, Carlo; Bhunia, Anil K.; Hossain, M. Zulfiquer; Paun, Bogdan C.; Ren, Yunzhao R.; Iacobuzio-Donahue, Christine A.; Azad, Nilofer A.; Kern, Scott E.

    2014-01-01

    Large-magnitude numerical distinctions (>10-fold) among drug responses of genetically contrasting cancers were crucial for guiding the development of some targeted therapies. Similar strategies brought epidemiological clues and prevention goals for genetic diseases. Such numerical guides, however, were incomplete or low magnitude for Fanconi anemia pathway (FANC) gene mutations relevant to cancer in FANC-mutation carriers (heterozygotes). We generated a four-gene FANC-null cancer panel, inclu...

  5. Nav 1.8-null mice show stimulus-dependent deficits in spinal neuronal activity

    Directory of Open Access Journals (Sweden)

    Wood John N

    2006-02-01

    Full Text Available Abstract Background The voltage gated sodium channel Nav 1.8 has a highly restricted expression pattern to predominantly nociceptive peripheral sensory neurones. Behaviourally Nav 1.8-null mice show an increased acute pain threshold to noxious mechanical pressure and also deficits in inflammatory and visceral, but not neuropathic pain. Here we have made in vivo electrophysiology recordings of dorsal horn neurones in intact anaesthetised Nav 1.8-null mice, in response to a wide range of stimuli to further the understanding of the functional roles of Nav 1.8 in pain transmission from the periphery to the spinal cord. Results Nav 1.8-null mice showed marked deficits in the coding by dorsal horn neurones to mechanical, but not thermal, -evoked responses over the non-noxious and noxious range compared to littermate controls. Additionally, responses evoked to other stimulus modalities were also significantly reduced in Nav 1.8-null mice where the reduction observed to pinch > brush. The occurrence of ongoing spontaneous neuronal activity was significantly less in mice lacking Nav 1.8 compared to control. No difference was observed between groups in the evoked activity to electrical activity of the peripheral receptive field. Conclusion This study demonstrates that deletion of the sodium channel Nav 1.8 results in stimulus-dependent deficits in the dorsal horn neuronal coding to mechanical, but not thermal stimuli applied to the neuronal peripheral receptive field. This implies that Nav 1.8 is either responsible for, or associated with proteins involved in mechanosensation.

  6. Congruences of null strings in complex space-times and some Cauchy--Kovalevski-like problems

    International Nuclear Information System (INIS)

    Robinson, I.; Rozga, K.

    1984-01-01

    It is shown that a problem of construction of a local congruence of null strings is equivalent to a natural Cauchy--Kovalevski-like problem, related to an equation for a spinor field k/sub A/ defining the congruence. Initial data are specified on two-dimensional submanifolds. In left-conformally-flat spaces, the solution of that problem exists for arbitrary initial data

  7. Chronic Toxoplasma gondii in Nurr1-Null Heterozygous Mice Exacerbates Elevated Open Field Activity

    OpenAIRE

    Eells, Jeffrey B.; Varela-Stokes, Andrea; Guo-Ross, Shirley X.; Kummari, Evangel; Smith, Holly M.; Cox, Erin; Lindsay, David S.

    2015-01-01

    Latent infection with Toxoplasma gondii is common in humans (approximately 30% of the global population) and is a significant risk factor for schizophrenia. Since prevalence of T. gondii infection is far greater than prevalence of schizophrenia (0.5-1%), genetic risk factors are likely also necessary to contribute to schizophrenia. To test this concept in an animal model, Nurr1-null heterozygous (+/-) mice and wild-type (+/+) mice were evaluate using an emergence test, activity in an open fie...

  8. Internalizing Null Extraterrestrial "Signals": An Astrobiological App for a Technological Society

    OpenAIRE

    Chaisson, Eric J.

    2014-01-01

    One of the beneficial outcomes of searching for life in the Universe is that it grants greater awareness of our own problems here on Earth. Lack of contact with alien beings to date might actually comprise a null "signal" pointing humankind toward a viable future. Astrobiology has surprising practical applications to human society; within the larger cosmological context of cosmic evolution, astrobiology clarifies the energetic essence of complex systems throughout the Universe, including tech...

  9. On the dependence of energy confinement on elongation in Single Null divertor plasmas

    International Nuclear Information System (INIS)

    Weisen, H.; Martin, Y.; Moret, J. M.; Others

    2002-03-01

    An analysis of the effect of magnetic geometry on heat flux in a wide range of Single Null diverted discharge configurations with 1.5 κ ∼ 74, based on the configurations in the study. This is very close to dependences from the ITER database for discharge conditions, such as ELMy H-modes, obtained from a large number of experiments in various tokamak devices. (author)

  10. Bi-dimensional null model analysis of presence-absence binary matrices.

    Science.gov (United States)

    Strona, Giovanni; Ulrich, Werner; Gotelli, Nicholas J

    2018-01-01

    Comparing the structure of presence/absence (i.e., binary) matrices with those of randomized counterparts is a common practice in ecology. However, differences in the randomization procedures (null models) can affect the results of the comparisons, leading matrix structural patterns to appear either "random" or not. Subjectivity in the choice of one particular null model over another makes it often advisable to compare the results obtained using several different approaches. Yet, available algorithms to randomize binary matrices differ substantially in respect to the constraints they impose on the discrepancy between observed and randomized row and column marginal totals, which complicates the interpretation of contrasting patterns. This calls for new strategies both to explore intermediate scenarios of restrictiveness in-between extreme constraint assumptions, and to properly synthesize the resulting information. Here we introduce a new modeling framework based on a flexible matrix randomization algorithm (named the "Tuning Peg" algorithm) that addresses both issues. The algorithm consists of a modified swap procedure in which the discrepancy between the row and column marginal totals of the target matrix and those of its randomized counterpart can be "tuned" in a continuous way by two parameters (controlling, respectively, row and column discrepancy). We show how combining the Tuning Peg with a wise random walk procedure makes it possible to explore the complete null space embraced by existing algorithms. This exploration allows researchers to visualize matrix structural patterns in an innovative bi-dimensional landscape of significance/effect size. We demonstrate the rational and potential of our approach with a set of simulated and real matrices, showing how the simultaneous investigation of a comprehensive and continuous portion of the null space can be extremely informative, and possibly key to resolving longstanding debates in the analysis of ecological

  11. Null Geodesics and Strong Field Gravitational Lensing in a String Cloud Background

    International Nuclear Information System (INIS)

    Iftikhar, Sehrish; Sharif, M.

    2015-01-01

    This paper is devoted to studying two interesting issues of a black hole with string cloud background. Firstly, we investigate null geodesics and find unstable orbital motion of particles. Secondly, we calculate deflection angle in strong field limit. We then find positions, magnifications, and observables of relativistic images for supermassive black hole at the galactic center. We conclude that string parameter highly affects the lensing process and results turn out to be quite different from the Schwarzschild black hole

  12. TRPV6 alleles do not influence prostate cancer progression

    International Nuclear Information System (INIS)

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-01-01

    The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca 2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

  13. TRPV6 alleles do not influence prostate cancer progression.

    Science.gov (United States)

    Kessler, Thorsten; Wissenbach, Ulrich; Grobholz, Rainer; Flockerzi, Veit

    2009-10-26

    The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca(2+) selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Our results show that the frequencies of trpv6 alleles in healthy control individuals and prostate cancer patients

  14. TRPV6 alleles do not influence prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Flockerzi Veit

    2009-10-01

    Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

  15. On the Penrose inequality for dust null shells in the Minkowski spacetime of arbitrary dimension

    International Nuclear Information System (INIS)

    Mars, Marc; Soria, Alberto

    2012-01-01

    A particular, yet relevant, case of the Penrose inequality involves null shells propagating in the Minkowski spacetime. Despite previous claims in the literature, the validity of this inequality remains open. In this paper, we rewrite this inequality in terms of the geometry of the surface obtained by intersecting the past null cone of the original surface S with a constant time hyperplane and the 'time height' function of S over this hyperplane. We also specialize to the case when S lies in the past null cone of a point and show the validity of the corresponding inequality in any dimension (in four dimensions this inequality was proved by Tod (1985 Class. Quantum Grav. 2 L65-8). Exploiting properties of convex hypersurfaces in the Euclidean space, we write down the Penrose inequality in the Minkowski spacetime of an arbitrary dimension n + 2 as an inequality for two smooth functions on the sphere S n . We finally obtain a sufficient condition for the validity of the Penrose inequality in the four-dimensional Minkowski spacetime and show that this condition is satisfied by a large class of surfaces. (paper)

  16. A robust null hypothesis for the potential causes of megadrought in western North America

    Science.gov (United States)

    Ault, T.; St George, S.; Smerdon, J. E.; Coats, S.; Mankin, J. S.; Cruz, C. C.; Cook, B.; Stevenson, S.

    2017-12-01

    The western United States was affected by several megadroughts during the last 1200 years, most prominently during the Medieval Climate Anomaly (MCA: 800 to 1300 CE). A null hypothesis is developed to test the possibility that, given a sufficiently long period of time, these events are inevitable and occur purely as a consequence of internal climate variability. The null distribution of this hypothesis is populated by a linear inverse model (LIM) constructed from global sea-surface temperature anomalies and self-calibrated Palmer Drought Severity Index data for North America. Despite being trained only on seasonal data from the late 20th century, the LIM produces megadroughts that are comparable in their duration, spatial scale, and magnitude as the most severe events of the last 12 centuries. The null hypothesis therefore cannot be rejected with much confidence when considering these features of megadrought, meaning that similar events are possible today, even without any changes to boundary conditions. In contrast, the observed clustering of megadroughts in the MCA, as well as the change in mean hydroclimate between the MCA and the 1500-2000 period, are more likely to have been caused by either external forcing or by internal climate variability not well sampled during the latter half of the Twentieth Century. Finally, the results demonstrate the LIM is a viable tool for determining whether paleoclimate reconstructions events should be ascribed to external forcings, "out of sample" climate mechanisms, or if they are consistent with the variability observed during the recent period.

  17. Null-point titration measurements of free magnesium in stored erythrocytes

    International Nuclear Information System (INIS)

    Bock, J.L.; Yusuf, Y.; Puntillo, E.

    1987-01-01

    Free intracellular magnesium concentration (Mg/sub i/) was measured in stored human erythrocytes, using null-point titration with ionophore A23187. For cells stored 31 P NMR spectroscopy, which showed a decrease in Mg/sub i/ with storage. However, the NMR measurements are performed with no pretreatment of the cells, while the null-point method requires an initial washing step, which alters pH/sub i/ and may also alter Mg/sub i/. The titration-measured Mg/sub i/ values are still surprisingly low for long-stored cells, considering that depletion of ATP and 2,3-DPG should release bound Mg. Using the titration-measured Mg/sub i/ values along with measurements of total Mg, ATP, and 2,3-DPG, they estimate that an additional buffer contains about 47% of total Mg in cells stored 21 days. Mg/sub i/ determinations by both 31 P NMR and null-point titration thus indicate that erythrocyte Mg is largely bound to a high-capacity, low-affinity buffer whose relative importance increases during cell storage. Discrepancies between the methods require further investigation

  18. Asymptotic symmetries of Rindler space at the horizon and null infinity

    International Nuclear Information System (INIS)

    Chung, Hyeyoun

    2010-01-01

    We investigate the asymptotic symmetries of Rindler space at null infinity and at the event horizon using both systematic and ad hoc methods. We find that the approaches that yield infinite-dimensional asymptotic symmetry algebras in the case of anti-de Sitter and flat spaces only give a finite-dimensional algebra for Rindler space at null infinity. We calculate the charges corresponding to these symmetries and confirm that they are finite, conserved, and integrable, and that the algebra of charges gives a representation of the asymptotic symmetry algebra. We also use relaxed boundary conditions to find infinite-dimensional asymptotic symmetry algebras for Rindler space at null infinity and at the event horizon. We compute the charges corresponding to these symmetries and confirm that they are finite and integrable. We also determine sufficient conditions for the charges to be conserved on-shell, and for the charge algebra to give a representation of the asymptotic symmetry algebra. In all cases, we find that the central extension of the charge algebra is trivial.

  19. Identification of common bean alleles resistant to anthracnose using RAPD

    Directory of Open Access Journals (Sweden)

    Ana L.M. Castanheira

    1999-12-01

    Full Text Available RAPD markers were identified close to common bean alleles responsible for resistance to the fungus Colletotrichum lindemuthianum and may be useful in selecting plants resistant to this pathogen. DNA from F2 plants of the crosses Carioca 300V x P45, Carioca 300V x Ouro and P24 x Ouro was amplified by RAPD. Line P45 has the Co.4 allele for resistance, and the Ouro cultivar has the Co.5 allele. The primer OPC08 amplified a DNA fragment of about 1059 bp linked to the Co.4 allele. The recombination frequency was 0.133 (SE = 0.039; 95% CI = 0.056-0.211. Using the primer OPF10 a DNA fragment of about 912 bp was amplified and found to be associated with the Co.5 allele. The recombination frequency was 0.115 (SE = 0.038; 95% CI = 0.041-0.189. A second marker (1122 pb amplified by the OPR03 primer was identified in the population P24 x Ouro. The recombination frequency for this marker was 0.363 (SE = 0.081; 95% CI = 0.205-0.522. Both these markers flanked the Co.5 allele. The markers identified in this study may be useful in identifying lines with the Co.4 and Co.5 alleles.Marcadores RAPD foram identificados próximos de alelos do feijão responsáveis pela resistência ao Colletotrichum lindemuthianum, visando auxiliar na seleção de plantas resistentes ao patógeno. Empregou-se o método dos bulks segregantes de DNA extraídos de plantas F2 dos seguintes cruzamentos: Carioca 300V x P45, Carioca 300V x Ouro e P24 x Ouro. A linhagem P45 é portadora do alelo Co.4 de resistência e o cultivar Ouro é portador do alelo Co.5, os quais foram marcados. Procedeu-se à reação RAPD dos bulks e foi identificado o iniciador OPC08 que amplificou um fragmento de DNA com cerca de 1059 pb, ligado ao alelo Co.4. A freqüência de recombinação foi de 0,133 (erro padrão 0,039 e o intervalo de confiança foi 0,056 e 0,211, com 95% de probabilidade. Em relação ao alelo Co.5 foi identificado um fragmento de DNA amplificado pelo iniciador OPF10 com cerca de 912 pb, na

  20. A set of haploid strains available for genetic studies of Saccharomyces cerevisiae flor yeasts.

    Science.gov (United States)

    Coi, Anna Lisa; Legras, Jean-Luc; Zara, Giacomo; Dequin, Sylvie; Budroni, Marilena

    2016-09-01

    Flor yeasts of Saccharomyces cerevisiae have been extensively studied for biofilm formation, however the lack of specific haploid model strains has limited the application of genetic approaches such as gene knockout, allelic replacement and Quantitative Trait Locus mapping for the deciphering of the molecular basis of velum formation under biological ageing. The aim of this work was to construct a set of flor isogenic haploid strains easy to manipulate genetically. The analysis of the allelic variations at 12 minisatellite loci of 174 Saccharomyces cerevisiae strains allowed identifying three flor parental strains with different phylogenic positions. These strains were characterized for sporulation efficiency, growth on galactose, adherence to polystyrene, agar invasion, growth on wine and ability to develop a biofilm. Interestingly, the inability to grow on galactose was found associated with a frameshift in GAL4 gene that seems peculiar of flor strains. From these wild flor strains, isogenic haploid strains were constructed by deleting HO gene with a loxP-KanMX-loxP cassette followed by the removal of the kanamycin cassette. Haploid strains obtained were characterized for their phenotypic and genetic properties and compared with the parental strains. Preliminary results showed that the haploid strains represent new tools for genetic studies and breeding programs on biofilm formation. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.

    Science.gov (United States)

    Galmozzi, E; Facchetti, F; Degasperi, E; Aghemo, A; Lampertico, P

    2013-02-01

    Recently, genome-wide association studies (GWAS) in patients with chronic hepatitis C virus (HCV) infection have identified two functional single nucleotide polymorphisms (SNPs) in the inosine triphosphatase (ITPA) gene, that are associated strongly and independently with hemolytic anemia in patients exposed to pegylated-interferon (Peg-IFN) plus ribavirin (RBV) combined therapy. Here has been developed a simplified allele discrimination polymerase chain reaction (PCR) assay named allelic inhibition of displacement activity (AIDA) for evaluation of ITPA polymorphisms. AIDA system relies on three unlabeled primers only, two outer common primers and one inner primer with allele-specific 3' terminus mismatch. DNA samples from 192 patients with chronic HCV infection were used to validate the AIDA system and results were compared with the gold standard TaqMan(®) SNP genotyping assay. Concordant data were obtained for all samples, granting for high specificity of the method. In conclusion, AIDA is a practical one-tube method to reproducibly and to assess accurately rs7270101 and rs1127354 ITPA SNPs. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. HLA Dr beta 1 alleles in Pakistani patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Naqi, N.; Ahmed, T.A.; Bashir, M.M.

    2011-01-01

    Objective: To determine frequencies of HLA DR beta 1 alleles in rheumatoid arthritis in Pakistani patients. Study Design: Cross sectional / analytical study. Place and Duration of Study: Department of Immunology, Armed Forces Institute of Pathology, Rawalpindi in collaboration with Rheumatology departments of Military Hospital, Rawalpindi and Fauji Foundation Hospital, Rawalpindi, from January 2009 to January 2010. Methodology: HLA DR beta 1 genotyping of one hundred Pakistani patients, diagnosed as having RA as per American College of Rheumatology revised criteria 1987, was done. HLA DR beta 1 genotyping was carried out at allele group level (DR beta 1*01-DR beta 1*16) by sequence specific primers in RA patients. Comparison of HLA DR beta 1 allele frequencies between patients and control groups was made using Pearson's chi-square test to find possible association of HLA DR?1 alleles with RA in Pakistani rheumatoid patients. Results: HLA DR beta 1*04 was expressed with significantly increased frequency in patients with rheumatoid arthritis (p <0.05). HLA DR?1*11 was expressed statistically significantly more in control group as compared to rheumatoid patients indicating a possible protective effect. There was no statistically significant difference observed in frequencies of HLA DR beta 1 allele *01, DR beta 1 allele *03, DR beta 1 allele *07, DR beta 1 allele *08, DR beta 1 allele *09, DR beta 1 allele *10, DR beta 1 allele *12, DR beta 1 allele *13, DR beta 1 allele *14, DR?1 allele *15 and DR beta 1 allele *16 between patients and control groups. Conclusion: The identification of susceptible HLA DR beta 1 alleles in Pakistani RA patients may help physicians to make early decisions regarding initiation of early intensive therapy with disease modifying anti rheumatic medicines and biological agents decreasing disability in RA patients. (author)

  3. A high-throughput method for genotyping S-RNase alleles in apple

    DEFF Research Database (Denmark)

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles...

  4. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  5. Multi-Segment Radius Measurement Using an Absolute Distance Meter Through a Null Assembly

    Science.gov (United States)

    Merle, Cormic; Wick, Eric; Hayden, Joseph

    2011-01-01

    This system was one of the test methods considered for measuring the radius of curvature of one or more of the 18 segmented mirrors that form the 6.5 m diameter primary mirror (PM) of the James Webb Space Telescope (JWST). The assembled telescope will be tested at cryogenic temperatures in a 17-m diameter by 27-m high vacuum chamber at the Johnson Space Center. This system uses a Leica Absolute Distance Meter (ADM), at a wavelength of 780 nm, combined with beam-steering and beam-shaping optics to make a differential distance measurement between a ring mirror on the reflective null assembly and individual PM segments. The ADM is located inside the same Pressure-Tight Enclosure (PTE) that houses the test interferometer. The PTE maintains the ADM and interferometer at ambient temperature and pressure so that they are not directly exposed to the telescope s harsh cryogenic and vacuum environment. This system takes advantage of the existing achromatic objective and reflective null assembly used by the test interferometer to direct four ADM beamlets to four PM segments through an optical path that is coincident with the interferometer beam. A mask, positioned on a linear slide, contains an array of 1.25 mm diameter circular subapertures that map to each of the 18 PM segments as well as six positions around the ring mirror. A down-collimated 4 mm ADM beam simultaneously covers 4 adjacent PM segment beamlets and one ring mirror beamlet. The radius, or spacing, of all 18 segments can be measured with the addition of two orthogonally-oriented scanning pentaprisms used to steer the ADM beam to any one of six different sub-aperture configurations at the plane of the ring mirror. The interferometer beam, at a wavelength of 687 nm, and the ADM beamlets, at a wavelength of 780 nm, pass through the objective and null so that the rays are normally incident on the parabolic PM surface. After reflecting off the PM, both the ADM and interferometer beams return to their respective

  6. The Fourier-Kelvin Stellar Interferometer (FKSI) Nulling Testbed II: Closed-loop Path Length Metrology And Control Subsystem

    Science.gov (United States)

    Frey, B. J.; Barry, R. K.; Danchi, W. C.; Hyde, T. T.; Lee, K. Y.; Martino, A. J.; Zuray, M. S.

    2006-01-01

    The Fourier-Kelvin Stellar Interferometer (FKSI) is a mission concept for an imaging and nulling interferometer in the near to mid-infrared spectral region (3-8 microns), and will be a scientific and technological pathfinder for upcoming missions including TPF-I/DARWIN, SPECS, and SPIRIT. At NASA's Goddard Space Flight Center, we have constructed a symmetric Mach-Zehnder nulling testbed to demonstrate techniques and algorithms that can be used to establish and maintain the 10(exp 4) null depth that will be required for such a mission. Among the challenges inherent in such a system is the ability to acquire and track the null fringe to the desired depth for timescales on the order of hours in a laboratory environment. In addition, it is desirable to achieve this stability without using conventional dithering techniques. We describe recent testbed metrology and control system developments necessary to achieve these goals and present our preliminary results.

  7. Nickel reactivity and filaggrin null mutations--evaluation of the filaggrin bypass theory in a general population

    DEFF Research Database (Denmark)

    Ross-Hansen, Katrine; Menné, Torkil; Johansen, Jeanne D

    2011-01-01

    It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum....

  8. HLA-DR alleles among Pakistani patients of coeliac disease

    International Nuclear Information System (INIS)

    Saleem, N.; Ahmed, T.A.; Bashir, M.; Ali, S.; Iqbal, M.

    2013-01-01

    Objectives: To investigate whether certain DR alleles might also contribute to the genetic susceptibility among Coeliac disease patients in Pakistan. Methods: The case-control study was conducted at the Military Hospital, Rawalpindi, from October 2011 to January 2012, and analysed 25 children diagnosed to have coeliac disease as per the criteria set by the European Society of Paediatric Gastroenterology and Nutrition, which included histopathological alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of anti-endomyseal antibodies. Patients were compared with a group of 150 healthy subjects. Dioxyribonucleic acid was extracted from peripheral blood collected in ethylenediaminetetraacetic acid.K3. Human leukocyte antigen DRB1 typing was carried out on allele level (DRB1*01 - DRB1*16) using sequence specific primers. Human leukocyte antigen type was determined by agarose gel electrophoresis and results were recorded. Phenotype frequency of various alleles among the patient group and the control group was calculated by direct counting, and significance of their association was determined by Fisher Exact Test. Results: A total of 11 (44%) female paediatric coeliac patients in age range 1-9 (mean 7.2+-4.8 years) and 14 (56%) male paediatric patients in the age range 6-14 (mean 8.6+-5.1 years) were genotyped for HLA-DRB1 loci. A statistically significant positive association of the disease with HLA-DRB1*03 (n=23; 92% versus n=31; 21% in controls, p <0.01) was observed. Conclusion: HLA-DRB1*03 is associated with increased risk of developing coeliac disease. (author)

  9. Exploring new alleles for frost tolerance in winter rye.

    Science.gov (United States)

    Erath, Wiltrud; Bauer, Eva; Fowler, D Brian; Gordillo, Andres; Korzun, Viktor; Ponomareva, Mira; Schmidt, Malthe; Schmiedchen, Brigitta; Wilde, Peer; Schön, Chris-Carolin

    2017-10-01

    Rye genetic resources provide a valuable source of new alleles for the improvement of frost tolerance in rye breeding programs. Frost tolerance is a must-have trait for winter cereal production in northern and continental cropping areas. Genetic resources should harbor promising alleles for the improvement of frost tolerance of winter rye elite lines. For frost tolerance breeding, the identification of quantitative trait loci (QTL) and the choice of optimum genome-based selection methods are essential. We identified genomic regions involved in frost tolerance of winter rye by QTL mapping in a biparental population derived from a highly frost tolerant selection from the Canadian cultivar Puma and the European elite line Lo157. Lines per se and their testcrosses were phenotyped in a controlled freeze test and in multi-location field trials in Russia and Canada. Three QTL on chromosomes 4R, 5R, and 7R were consistently detected across environments. The QTL on 5R is congruent with the genomic region harboring the Frost resistance locus 2 (Fr-2) in Triticeae. The Puma allele at the Fr-R2 locus was found to significantly increase frost tolerance. A comparison of predictive ability obtained from the QTL-based model with different whole-genome prediction models revealed that besides a few large, also small QTL effects contribute to the genomic variance of frost tolerance in rye. Genomic prediction models assigning a high weight to the Fr-R2 locus allow increasing the selection intensity for frost tolerance by genome-based pre-selection of promising candidates.

  10. The Rh allele frequencies in Gaza city in Palestine

    Directory of Open Access Journals (Sweden)

    Skaik Younis

    2011-01-01

    Full Text Available Background: The Rh blood group system is the second most clinically significant blood group system. It includes 49 antigens, but only five (D, C, E, c and e are the most routinely identified due to their unique relation to hemolytic disease of the newborn (HDN and transfusion reactions. Frequency of the Rh alleles showed variation, with regard to race and ethnic. Objectives: The purpose of the study was to document the Rh alleles′ frequencies amongst males (M and females (F in Gaza city in Palestine. Materials and Methods: Two hundred and thirty-two blood samples (110 M and 122 F were tested against monoclonal IgM anti-C,anti-c, anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected Rh phenotypes were calculated using gene counting method. Results: The most frequent Rh antigen in the total sample was e, while the least frequent was E.The order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde > CdE > cDE > Cde > CDE. A significant difference was reported between M and F regarding the phenotypic frequencies (P < 0.05. However, no significance (P > 0.05 was reported with reference to the observed and expected Rh phenotypic frequencies in either M or F students. Conclusion: It was concluded that the Rh antigens, alleles and phenotypes in Gaza city have unique frequencies, which may be of importance to the Blood Transfusion Center in Gaza city and anthropology.

  11. Allele-sharing models: LOD scores and accurate linkage tests.

    Science.gov (United States)

    Kong, A; Cox, N J

    1997-11-01

    Starting with a test statistic for linkage analysis based on allele sharing, we propose an associated one-parameter model. Under general missing-data patterns, this model allows exact calculation of likelihood ratios and LOD scores and has been implemented by a simple modification of existing software. Most important, accurate linkage tests can be performed. Using an example, we show that some previously suggested approaches to handling less than perfectly informative data can be unacceptably conservative. Situations in which this model may not perform well are discussed, and an alternative model that requires additional computations is suggested.

  12. Allelic drop-out probabilities estimated by logistic regression

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic drop-out...... is occurring. With this discussion, we hope to improve the drop-out model, so that it can be used for practical forensic genetics and stimulate further discussions. We discuss how to estimate drop-out probabilities when using a varying number of PCR cycles and other experimental conditions....

  13. Haplotype Diversity at Sub1 Locus and Allelic Distribution Among Rice Varieties of Tide and Flood Prone Areas of South-East Asia

    Directory of Open Access Journals (Sweden)

    A.S.M. Masuduzzaman

    2017-07-01

    Full Text Available Single nucleotide polymorphisms and restriction digestion-based haplotype variations among 160 flood prone rice varieties were analyzed with enzymes Alu I and Cac8 I to generate polymorphisms at Sub1A and Sub1C loci (conferring submergence tolerance, respectively. Haplotype associated with phenotype was used to study the haplotype variations at Sub1A and Sub1C loci and to determine their functional influence on submergence tolerance and stem elongation. Three patterns at Sub1A locus, Sub1A0 (null allele, Sub1A1 (does not cut and Sub1A2 (one SNP, and four patterns at Sub1C locus, Sub1C1, Sub1C2, Sub1C3 and Sub1C4, were generated. Both tolerant Sub1A1 and intolerant Sub1A2 had the same length, but the difference was presence of a restriction site in the Sub1A2, but absent at the Sub1A1. Further, two types of polymorphism were detected at the Sub1C, one included major length polymorphisms (165, 170 and 175 bp and the other was a single restriction site at different position. Eight haplotypes (different combinations of the two loci, A1C1, A1C2, A1C4, A2C2, A2C4, A0C2, A0C3 and A0C4, were detected among 160 varieties. Haplotype A1C1 was comparatively more related to haplotypes A1C2 and A1C4, having the same Sub1A allele, and these haplotypes were found only in Bangladeshi, Sri Lankan and Indian varieties. Most tolerant varieties in A1C1 haplotype showed slow elongation, having tolerant specific Sub1A1 and Sub1C1 alleles. Further, the varieties Madabaru and Kottamali (A2C2 also showed moderate level of tolerance without Sub1A1 allele. These varieties were different with FR13A and also suspected to carry different novel tolerant genes at other loci. These materials could be used for hybridization with Sub1 varieties for pyramiding additional tolerant specific alleles into a single genotype for improving submergence tolerance in rice.

  14. Engineering of a novel Saccharomyces cerevisiae wine strain with a respiratory phenotype at high external glucose concentrations.

    Science.gov (United States)

    Henricsson, C; de Jesus Ferreira, M C; Hedfalk, K; Elbing, K; Larsson, C; Bill, R M; Norbeck, J; Hohmann, S; Gustafsson, L

    2005-10-01

    The recently described respiratory strain Saccharomyces cerevisiae KOY.TM6*P is, to our knowledge, the only reported strain of S. cerevisiae which completely redirects the flux of glucose from ethanol fermentation to respiration, even at high external glucose concentrations (27). In the KOY.TM6*P strain, portions of the genes encoding the predominant hexose transporter proteins, Hxt1 and Hxt7, were fused within the regions encoding transmembrane (TM) domain 6. The resulting chimeric gene, TM6*, encoded a chimera composed of the amino-terminal half of Hxt1 and the carboxy-terminal half of Hxt7. It was subsequently integrated into the genome of an hxt null strain. In this study, we have demonstrated the transferability of this respiratory phenotype to the V5 hxt1-7Delta strain, a derivative of a strain used in enology. We also show by using this mutant that it is not necessary to transform a complete hxt null strain with the TM6* construct to obtain a non-ethanol-producing phenotype. The resulting V5.TM6*P strain, obtained by transformation of the V5 hxt1-7Delta strain with the TM6* chimeric gene, produced only minor amounts of ethanol when cultured on external glucose concentrations as high as 5%. Despite the fact that glucose flux was reduced to 30% in the V5.TM6*P strain compared with that of its parental strain, the V5.TM6*P strain produced biomass at a specific rate as high as 85% that of the V5 wild-type strain. Even more relevant for the potential use of such a strain for the production of heterologous proteins and also of low-alcohol beverages is the observation that the biomass yield increased 50% with the mutant compared to its parental strain.

  15. Expression Profiling of Differentiating Emerin-Null Myogenic Progenitor Identifies Molecular Pathways Implicated in Their Impaired Differentiation

    Directory of Open Access Journals (Sweden)

    Ashvin Iyer

    2017-10-01

    Full Text Available Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD, a disorder causing progressive skeletal muscle wasting, irregular heart rhythms and contractures of major tendons. RNA sequencing was performed on differentiating wildtype and emerin-null myogenic progenitors to identify molecular pathways implicated in EDMD, 340 genes were uniquely differentially expressed during the transition from day 0 to day 1 in wildtype cells. 1605 genes were uniquely expressed in emerin-null cells; 1706 genes were shared among both wildtype and emerin-null cells. One thousand and forty-seven transcripts showed differential expression during the transition from day 1 to day 2. Four hundred and thirty-one transcripts showed altered expression in both wildtype and emerin-null cells. Two hundred and ninety-five transcripts were differentially expressed only in emerin-null cells and 321 transcripts were differentially expressed only in wildtype cells. DAVID, STRING and Ingenuity Pathway Analysis identified pathways implicated in impaired emerin-null differentiation, including cell signaling, cell cycle checkpoints, integrin signaling, YAP/TAZ signaling, stem cell differentiation, and multiple muscle development and myogenic differentiation pathways. Functional enrichment analysis showed biological functions associated with the growth of muscle tissue and myogenesis of skeletal muscle were inhibited. The large number of differentially expressed transcripts upon differentiation induction suggests emerin functions during transcriptional reprograming of progenitors to committed myoblasts.

  16. TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

    Science.gov (United States)

    Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

    2008-11-01

    The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

  17. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas

    2013-01-01

    Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...... no protective effect of the APOE ε2 allele on mortality compared with the APOE ε3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ε2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes....... We did not find a protective effect of the APOE ε2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ε4 carriers. The APOE ε2 allele may be protective on cognitive decline among the oldest old....

  18. Microsatellite polymorphism within pfcrt provides evidence of continuing evolution of chloroquine-resistant alleles in Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Sharma Yagya D

    2007-03-01

    Full Text Available Abstract Background Polymorphism in the pfcrt gene underlies Plasmodium falciparum chloroquine resistance (CQR, as sensitive strains consistently carry lysine (K, while CQR strains carry threonine (T at the codon 76. Previous studies have shown that microsatellite (MS haplotype variation can be used to study the evolution of CQR polymorphism and to characterize intra- and inter-population dispersal of CQR in Papua New Guinea (PNG. Methods Here, following identification of new polymorphic MS in introns 2 and 3 within the pfcrt gene (msint2 and msint3, respectively, locus-by-locus and haplotype heterozygosity (H analyses were performed to determine the distribution of this intronic polymorphism among pfcrt chloroquine-sensitive and CQR alleles. Results For MS flanking the pfcrt CQR allele, H ranged from 0.07 (B5M77, -18 kb to 0.094 (9B12, +2 kb suggesting that CQ selection pressure was responsible for strong homogenisation of this gene locus. In a survey of 206 pfcrt-SVMNT allele-containing field samples from malaria-endemic regions of PNG, H for msint2 was 0.201. This observation suggests that pfcrt msint2 exhibits a higher level of diversity than what is expected from the analyses of pfcrt flanking MS. Further analyses showed that one of the three haplotypes present in the early 1980's samples has become the predominant haplotype (frequency = 0.901 in CQR parasite populations collected after 1995 from three PNG sites, when CQR had spread throughout malaria-endemic regions of PNG. Apparent localized diversification of pfcrt haplotypes at each site was also observed among samples collected after 1995, where minor CQR-associated haplotypes were found to be unique to each site. Conclusion In this study, a higher level of diversity at MS loci within the pfcrt gene was observed when compared with the level of diversity at pfcrt flanking MS. While pfcrt (K76T and its immediate flanking region indicate homogenisation in PNG CQR parasite populations

  19. A matching-allele model explains host resistance to parasites.

    Science.gov (United States)

    Luijckx, Pepijn; Fienberg, Harris; Duneau, David; Ebert, Dieter

    2013-06-17

    The maintenance of genetic variation and sex despite its costs has long puzzled biologists. A popular idea, the Red Queen Theory, is that under rapid antagonistic coevolution between hosts and their parasites, the formation of new rare host genotypes through sex can be advantageous as it creates host genotypes to which the prevailing parasite is not adapted. For host-parasite coevolution to lead to an ongoing advantage for rare genotypes, parasites should infect specific host genotypes and hosts should resist specific parasite genotypes. The most prominent genetics capturing such specificity are matching-allele models (MAMs), which have the key feature that resistance for two parasite genotypes can reverse by switching one allele at one host locus. Despite the lack of empirical support, MAMs have played a central role in the theoretical development of antagonistic coevolution, local adaptation, speciation, and sexual selection. Using genetic crosses, we show that resistance of the crustacean Daphnia magna against the parasitic bacterium Pasteuria ramosa follows a MAM. Simulation results show that the observed genetics can explain the maintenance of genetic variation and contribute to the maintenance of sex in the facultatively sexual host as predicted by the Red Queen Theory. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Characterization of a Weak Allele of Zebrafish cloche Mutant

    Science.gov (United States)

    Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

    2011-01-01

    Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

  1. Seasonal Changes in Brain Serotonin Transporter Binding in Short Serotonin Transporter Linked Polymorphic Region-Allele Carriers but Not in Long-Allele Homozygotes

    DEFF Research Database (Denmark)

    Kalbitzer, Jan; Erritzoe, David; Holst, Klaus K

    2010-01-01

    of the short 5-HTTLPR allele but not in homozygote carriers of the long allele. Conclusions: Our findings are in line with S-carriers having an increased response in neural circuits involved in emotional processing to stressful environmental stimuli but here demonstrated as a endophenotype with dynamic changes...

  2. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele

  3. Numerical simulations of sheared magnetic lines at the solar null line

    Science.gov (United States)

    Kuźma, B.; Murawski, K.; Solov'ev, A.

    2015-05-01

    Aims: We perform numerical simulations of sheared magnetic lines at the magnetic null line configuration of two magnetic arcades that are settled in a gravitationally stratified and magnetically confined solar corona. Methods: We developed a general analytical model of a 2.5D solar atmospheric structure. As a particular application of this model, we adopted it for the curved magnetic field lines with an inverted Y shape that compose the null line above two magnetic arcades, which are embedded in the solar atmosphere that is specified by the realistic temperature distribution. The physical system is described by 2.5D magnetohydrodynamic equations that are numerically solved by the FLASH code. Results: The magnetic field line shearing, implemented about 200 km below the transition region, results in Alfvén and magnetoacoustic waves that are able to penetrate solar coronal regions above the magnetic null line. As a result of the coupling of these waves, partial reflection from the transition region and scattering from inhomogeneous regions the Alfvén waves experience fast attenuation on time scales comparable to their wave periods, and the physical system relaxes in time. The attenuation time grows with the large amplitude and characteristic growing time of the shearing. Conclusions: By having chosen a different magnetic flux function, the analytical model we devised can be adopted to derive equilibrium conditions for a diversity of 2.5D magnetic structures in the solar atmosphere. Movie associated to Fig. 5 is available in electronic form at http://www.aanda.org

  4. Gap junction mediated intercellular metabolite transfer in the cochlea is compromised in connexin30 null mice.

    Directory of Open Access Journals (Sweden)

    Qing Chang

    Full Text Available Connexin26 (Cx26 and connexin30 (Cx30 are two major protein subunits that co-assemble to form gap junctions (GJs in the cochlea. Mutations in either one of them are the major cause of non-syndromic prelingual deafness in humans. Because the mechanisms of cochlear pathogenesis caused by Cx mutations are unclear, we investigated effects of Cx30 null mutation on GJ-mediated ionic and metabolic coupling in the cochlea of mice. A novel flattened cochlear preparation was used to directly assess intercellular coupling in the sensory epithelium of the cochlea. Double-electrode patch clamp recordings revealed that the absence of Cx30 did not significantly change GJ conductance among the cochlear supporting cells. The preserved electrical coupling is consistent with immunolabeling data showing extensive Cx26 GJs in the cochlea of the mutant mice. In contrast, dye diffusion assays showed that the rate and extent of intercellular transfer of multiple fluorescent dyes (including a non-metabolizable D-glucose analogue, 2-NBDG among cochlear supporting cells were severely reduced in Cx30 null mice. Since the sensory epithelium in the cochlea is an avascular organ, GJ-facilitated intercellular transfer of nutrient and signaling molecules may play essential roles in cellular homeostasis. To test this possibility, NBDG was used as a tracer to study the contribution of GJs in transporting glucose into the cochlear sensory epithelium when delivered systemically. NBDG uptake in cochlear supporting cells was significantly reduced in Cx30 null mice. The decrease was also observed with GJ blockers or glucose competition, supporting the specificity of our tests. These data indicate that GJs facilitate efficient uptake of glucose in the supporting cells. This study provides the first direct experimental evidence showing that the transfer of metabolically-important molecules in cochlear supporting cells is dependent on the normal function of GJs, thereby suggesting a

  5. Null hypothesis significance tests. A mix-up of two different theories

    DEFF Research Database (Denmark)

    Schneider, Jesper Wiborg

    2015-01-01

    criticisms raised against NHST. As practiced, NHST has been characterized as a ‘null ritual’ that is overused and too often misapplied and misinterpreted. NHST is in fact a patchwork of two fundamentally different classical statistical testing models, often blended with some wishful quasi......-Bayesian interpretations. This is undoubtedly a major reason why NHST is very often misunderstood. But NHST also has intrinsic logical problems and the epistemic range of the information provided by such tests is much more limited than most researchers recognize. In this article we introduce to the scientometric community...

  6. Topology and Singularities in Cosmological Spacetimes Obeying the Null Energy Condition

    Science.gov (United States)

    Galloway, Gregory J.; Ling, Eric

    2018-06-01

    We consider globally hyperbolic spacetimes with compact Cauchy surfaces in a setting compatible with the presence of a positive cosmological constant. More specifically, for 3 + 1 dimensional spacetimes which satisfy the null energy condition and contain a future expanding compact Cauchy surface, we establish a precise connection between the topology of the Cauchy surfaces and the occurrence of past singularities. In addition to the Penrose singularity theorem, the proof makes use of some recent advances in the topology of 3-manifolds and of certain fundamental existence results for minimal surfaces.

  7. Null geodesics in black hole metrics with non-zero cosmological constant

    International Nuclear Information System (INIS)

    Stuchlik, Z.; Calvani, M.

    1990-02-01

    We study the radial motion along null geodesics in the Reissner-Nordstroem-de Sitter and Kerr-de Sitter space-times. We analyze the properties of the effective potential and we discuss circular orbits. We find that the radii of circular geodesics in the Reissner-Nordstroem-de Sitter space-time do not depend on the cosmological constant, and we explain this property using the optical reference geometry. In addition, we describe the unusual consequences of the interplay between rotation of the source and cosmological repulsion. (author). 16 refs, 8 figs

  8. Reply to "Comment on `Null weak values and the past of a quantum particle"'

    Science.gov (United States)

    Duprey, Q.; Matzkin, A.

    2018-04-01

    We discuss the preceding Comment [D. Sokolovski, preceding Comment, Phys. Rev. A 97, 046102 (2018), 10.1103/PhysRevA.97.046102] and conclude that the arguments given there against the relevance of null weak values as representing the absence of a system property are not compelling. We give an example in which the transition matrix elements that make the projector weak values vanish are the same ones that suppress detector clicks in strong measurements. Whether weak values are taken to account for the past of a quantum system or not depend on general interpretational commitments of the quantum formalism itself rather than on peculiarities of the weak measurements framework.

  9. Double null X-point operation in JET with NBI and ICRH heating

    International Nuclear Information System (INIS)

    Tubbing, B.; Bhatnagar, V.

    1989-01-01

    In this paper we report on a selection of experiments on H-modes, in 3 and 3.5MA discharges, in the double null X-point configuration. The first experiment, section 2, is an attempt to couple ICRH power to H-modes. Here we also report on a rather unique H-mode with a smaller than usual distance between plasma and limiter. The second experiment, section 3, is on H-modes in the low density, hot ion regime. (author) 5 refs., 4 figs

  10. The space-time outside a source of gravitational radiation: the axially symmetric null fluid

    Energy Technology Data Exchange (ETDEWEB)

    Herrera, L. [Universidad Central de Venezuela, Escuela de Fisica, Facultad de Ciencias, Caracas (Venezuela, Bolivarian Republic of); Universidad de Salamanca, Instituto Universitario de Fisica Fundamental y Matematicas, Salamanca (Spain); Di Prisco, A. [Universidad Central de Venezuela, Escuela de Fisica, Facultad de Ciencias, Caracas (Venezuela, Bolivarian Republic of); Ospino, J. [Universidad de Salamanca, Departamento de Matematica Aplicada and Instituto Universitario de Fisica Fundamental y Matematicas, Salamanca (Spain)

    2016-11-15

    We carry out a study of the exterior of an axially and reflection symmetric source of gravitational radiation. The exterior of such a source is filled with a null fluid produced by the dissipative processes inherent to the emission of gravitational radiation, thereby representing a generalization of the Vaidya metric for axially and reflection symmetric space-times. The role of the vorticity, and its relationship with the presence of gravitational radiation is put in evidence. The spherically symmetric case (Vaidya) is, asymptotically, recovered within the context of the 1 + 3 formalism. (orig.)

  11. Theory of synergistic effects: Hill-type response surfaces as 'null-interaction' models for mixtures.

    Science.gov (United States)

    Schindler, Michael

    2017-08-02

    The classification of effects caused by mixtures of agents as synergistic, antagonistic or additive depends critically on the reference model of 'null interaction'. Two main approaches are currently in use, the Additive Dose (ADM) or concentration addition (CA) and the Multiplicative Survival (MSM) or independent action (IA) models. We compare several response surface models to a newly developed Hill response surface, obtained by solving a logistic partial differential equation (PDE). Assuming that a mixture of chemicals with individual Hill-type dose-response curves can be described by an n-dimensional logistic function, Hill's differential equation for pure agents is replaced by a PDE for mixtures whose solution provides Hill surfaces as 'null-interaction' models and relies neither on Bliss independence or Loewe additivity nor uses Chou's unified general theory. An n-dimensional logistic PDE decribing the Hill-type response of n-component mixtures is solved. Appropriate boundary conditions ensure the correct asymptotic behaviour. Mathematica 11 (Wolfram, Mathematica Version 11.0, 2016) is used for the mathematics and graphics presented in this article. The Hill response surface ansatz can be applied to mixtures of compounds with arbitrary Hill parameters. Restrictions which are required when deriving analytical expressions for response surfaces from other principles, are unnecessary. Many approaches based on Loewe additivity turn out be special cases of the Hill approach whose increased flexibility permits a better description of 'null-effect' responses. Missing sham-compliance of Bliss IA, known as Colby's model in agrochemistry, leads to incompatibility with the Hill surface ansatz. Examples of binary and ternary mixtures illustrate the differences between the approaches. For Hill-slopes close to one and doses below the half-maximum effect doses MSM (Colby, Bliss, Finney, Abbott) predicts synergistic effects where the Hill model indicates 'null

  12. Comments on correlation functions of large spin operators and null polygonal Wilson loops

    Energy Technology Data Exchange (ETDEWEB)

    Cardona, Carlos A., E-mail: cargicar@iafe.uba.ar [Instituto de Astronomia y Fisica del Espacio (CONICET-UBA), C.C. 67 - Suc. 28, 1428 Buenos Aires (Argentina); Physics Department, University of Buenos Aires, CONICET, Ciudad Universitaria, 1428 Buenos Aires (Argentina)

    2013-02-11

    We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (ln{mu}{sup -2}){sup 2}, {mu} being a cut-off of the theory.

  13. The 10-D chiral null model and the relation to 4-D string solutions

    International Nuclear Information System (INIS)

    Behrndt, K.

    1994-12-01

    The chiral null model is a generalization of the fundamental string and gravitational wave background. It is an example of a conformally invariant model in all orders in α' and has unbroken supersymmetries. In a Kaluza-Klein approach we start in 10 dimensions and reduce the model down to 4 dimensions without making any restrictions. The 4-D field content is given by the metric, torsion, dilaton, a moduli field and 6 gauge fields. This model is self-dual and near the singularities asymptotically free. The relation to known IWP, Taub-NUT and rotating black hole solutions is discussed. (orig.)

  14. A critical discussion of null hypothesis significance testing and statistical power analysis within psychological research

    DEFF Research Database (Denmark)

    Jones, Allan; Sommerlund, Bo

    2007-01-01

    The uses of null hypothesis significance testing (NHST) and statistical power analysis within psychological research are critically discussed. The article looks at the problems of relying solely on NHST when dealing with small and large sample sizes. The use of power-analysis in estimating...... the potential error introduced by small and large samples is advocated. Power analysis is not recommended as a replacement to NHST but as an additional source of information about the phenomena under investigation. Moreover, the importance of conceptual analysis in relation to statistical analysis of hypothesis...

  15. Asymptotically shear-free and twist-free null geodesic congruences

    International Nuclear Information System (INIS)

    Kozameh, Carlos; Newman, Ezra T

    2007-01-01

    The Robinson-Trautman spacetime is a special case of asymptotically flat spacetimes that possess asymptotically shear-free and twist-free (surface forming) null geodesic congruences. In this paper we show that, although they are rare, a larger class of asymptotically flat spacetimes with this property does exist. In particular, we display the class of spacetimes that possess this dual property and demonstrate how these congruences can be found. In addition, we show that in each case the congruence is isolated in the sense that there are no other neighbouring congruences with this dual property

  16. High-contrast visible nulling coronagraph for segmented and arbitrary telescope apertures

    Science.gov (United States)

    Hicks, Brian A.; Lyon, Richard G.; Bolcar, Matthew R.; Clampin, Mark; Petrone, Peter

    2014-08-01

    Exoplanet coronagraphy will be driven by the telescope architectures available and thus the system designer must have available one or more suitable coronagraphic instrument choices that spans the set of telescope apertures, including filled (off-axis), obscured (e.g. with secondary mirror spiders and struts), segmented apertures, such as JWST, and interferometric apertures. In this work we present one such choice of coronagraph, known as the visible nulling coronagraph (VNC), that spans all four types of aperture and also employs differential sensing and control.

  17. Testing the null hypothesis of the nonexistence of a preseizure state

    International Nuclear Information System (INIS)

    Andrzejak, Ralph G.; Kraskov, Alexander; Mormann, Florian; Rieke, Christoph; Kreuz, Thomas; Elger, Christian E.; Lehnertz, Klaus

    2003-01-01

    A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit

  18. Testing the null hypothesis of the nonexistence of a preseizure state

    Energy Technology Data Exchange (ETDEWEB)

    Andrzejak, Ralph G; Kraskov, Alexander [John-von-Neumann Institute for Computing, Forschungszentrum Juelich, 52425 Juelich (Germany); Mormann, Florian; Rieke, Christoph [Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany); Helmholtz Institut fuer Strahlen- und Kernphysik, University of Bonn, Nussallee 14-16, 53115 Bonn (Germany); Kreuz, Thomas [John-von-Neumann Institute for Computing, Forschungszentrum Juelich, 52425 Juelich (Germany); Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany); Elger, Christian E; Lehnertz, Klaus [Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn (Germany)

    2003-01-01

    A rapidly growing number of studies deals with the prediction of epileptic seizures. For this purpose, various techniques derived from linear and nonlinear time series analysis have been applied to the electroencephalogram of epilepsy patients. In none of these works, however, the performance of the seizure prediction statistics is tested against a null hypothesis, an otherwise ubiquitous concept in science. In consequence, the evaluation of the reported performance values is problematic. Here, we propose the technique of seizure time surrogates based on a Monte Carlo simulation to remedy this deficit.

  19. Comments on correlation functions of large spin operators and null polygonal Wilson loops

    International Nuclear Information System (INIS)

    Cardona, Carlos A.

    2013-01-01

    We discuss the relation between correlation functions of twist-two large spin operators and expectation values of Wilson loops along light-like trajectories. After presenting some heuristic field theoretical arguments suggesting this relation, we compute the divergent part of the correlator in the limit of large 't Hooft coupling and large spins, using a semi-classical world-sheet which asymptotically looks like a GKP rotating string. We show this diverges as expected from the expectation value of a null Wilson loop, namely, as (lnμ −2 ) 2 , μ being a cut-off of the theory.

  20. Five-dimensional null-cone structure of big bang singularity

    International Nuclear Information System (INIS)

    Lauro, S.; Schucking, E.L.

    1985-01-01

    The Friedmann model PHI of positive space curvature, vanishing pressure and cosmological constant when isometrically imbedded as a hypersurface in five-dimensional Minkowski space M 5 is globally rigid: if F(PHI) and F'(PHI) are isometric embeddings in M 5 there is a motion π of M 5 such that F'=π 0 F. The big bang singularity is the vertex of a null half-cone in M 5 . Global rigidity leads to an invariant characterization of the singularity. The structure of matter at the singularity is governed by the de Sitter group. (author)