WorldWideScience

Sample records for transcript vector derived

  1. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    Although retroviral vector systems have been found to efficiently transduce a variety of cell types in vitro, the use of vectors based on murine leukemia virus in preclinical models of somatic gene therapy has led to the identification of transcriptional silencing in vivo as an important problem....... Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t...

  2. The core element of a CpG island protects avian sarcoma and leukosis virus-derived vectors from transcriptional silencing

    Czech Academy of Sciences Publication Activity Database

    Šenigl, Filip; Plachý, Jiří; Hejnar, Jiří

    2008-01-01

    Roč. 82, č. 16 (2008), s. 7818-7827 ISSN 0022-538X R&D Projects: GA ČR GA204/05/0939; GA ČR GA523/07/1171 Institutional research plan: CEZ:AV0Z50520514 Keywords : anti-methylation protection * retroviral vector * CpG island Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.308, year: 2008

  3. Coordinate enhancement of transgene transcription and translation in a lentiviral vector

    Directory of Open Access Journals (Sweden)

    Fernandez Soledad

    2006-02-01

    Full Text Available Abstract Background Coordinate enhancement of transgene transcription and translation would be a potent approach to significantly improve protein output in a broad array of viral vectors and nonviral expression systems. Many vector transgenes are complementary DNA (cDNA. The lack of splicing can significantly reduce the efficiency of their translation. Some retroviruses contain a 5' terminal post-transcriptional control element (PCE that facilitates translation of unspliced mRNA. Here we evaluated the potential for spleen necrosis virus PCE to stimulate protein production from HIV-1 based lentiviral vector by: 1 improving translation of the internal transgene transcript; and 2 functionally synergizing with a transcriptional enhancer to achieve coordinate increases in RNA synthesis and translation. Results Derivatives of HIV-1 SIN self-inactivating lentiviral vector were created that contain PCE and cytomegalovirus immediate early enhancer (CMV IE. Results from transfected cells and four different transduced cell types indicate that: 1 PCE enhanced transgene protein synthesis; 2 transcription from the internal promoter is enhanced by CMV IE; 3 PCE and CMV IE functioned synergistically to significantly increase transgene protein yield; 4 the magnitude of translation enhancement by PCE was similar in transfected and transduced cells; 5 differences were observed in steady state level of PCE vector RNA in transfected and transduced cells; 6 the lower steady state was not attributable to reduced RNA stability, but to lower cytoplasmic accumulation in transduced cells. Conclusion PCE is a useful tool to improve post-transcriptional expression of lentiviral vector transgene. Coordinate enhancement of transcription and translation is conferred by the combination of PCE with CMV IE transcriptional enhancer and increased protein yield up to 11 to 17-fold in transfected cells. The incorporation of the vector provirus into chromatin correlated with reduced

  4. Antigenic structures stably expressed by recombinant TGEV-derived vectors.

    Science.gov (United States)

    Becares, Martina; Sanchez, Carlos M; Sola, Isabel; Enjuanes, Luis; Zuñiga, Sonia

    2014-09-01

    Coronaviruses (CoVs) are positive-stranded RNA viruses with potential as immunization vectors, expressing high levels of heterologous genes and eliciting both secretory and systemic immune responses. Nevertheless, its high recombination rate may result in the loss of the full-length foreign gene, limiting their use as vectors. Transmissible gastroenteritis virus (TGEV) was engineered to express porcine reproductive and respiratory syndrome virus (PRRSV) small protein domains, as a strategy to improve heterologous gene stability. After serial passage in tissue cultures, stable expression of small PRRSV protein antigenic domains was achieved. Therefore, size reduction of the heterologous genes inserted in CoV-derived vectors led to the stable expression of antigenic domains. Immunization of piglets with these TGEV vectors led to partial protection against a challenge with a virulent PRRSV strain, as immunized animals showed reduced clinical signs and lung damage. Further improvement of TGEV-derived vectors will require the engineering of vectors with decreased recombination rate. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Thermosensitivity of the reverse transcription process as an inactivation mechanism of lentiviral vectors.

    Science.gov (United States)

    Carmo, M; Dias, J D; Panet, A; Coroadinha, A S; Carrondo, M J T; Alves, P M; Cruz, P E

    2009-10-01

    Lentiviral vectors are an important tool for gene transfer research and gene therapy purposes. However, the low stability of these vectors affects their production, storage, and efficacy in preclinical and clinical settings. In the present work the mechanism underlying the thermosensitivity of lentiviral vectors was evaluated. For lentiviral vectors pseudotyped with amphotropic and RDpro envelopes, the capacity to perform reverse transcription was lost rapidly at 37 degrees C, in high correlation with the loss of infectivity. The vector with RDpro envelope presented a higher level of stability than that with amphotropic envelope for both the reverse transcription process and viral infectivity. Reverse transcriptase enzyme inactivation and viral template RNA degradation were not implicated in the loss of the viral capacity to perform reverse transcription. Furthermore, early entry steps in the infection process do not determine the rate of viral inactivation, as the amount of viral RNA and p24 protein entering the cells decreased slowly for both vectors. Taken together, it can be concluded that the reverse transcription process is thermolabile and thus determines the rate of lentiviral inactivation. Strategies to stabilize the reverse transcription process should be pursued to improve the applicability of lentiviral vectors in gene therapy.

  6. Development of nitrilase promoter-derived inducible vectors for Streptomyces.

    Science.gov (United States)

    Matsumoto, Masako; Hashimoto, Yoshiteru; Saitoh, Yuki; Kumano, Takuto; Kobayashi, Michihiko

    2016-06-01

    An inducible expression vector, pSH19, which harbors regulatory expression system PnitA-NitR, for streptomycetes was constructed previously. Here, we have modified pSH19 to obtain shuttle vectors for Streptomyces-E. coli by introducing the replication origin of a plasmid for E. coli (ColE1) and an antibiotic-resistant gene. Six inducible shuttle vectors, pESH19cF, pESH19cR, pESH19kF, pESH19kR, pESH19aF, and pESH19aR, for Streptomyces-E. coli, were successfully developed. The stability of these vectors was examined in five different E. coli strains and Streptomyces lividans TK24. The stability test showed that the pSH19-derived shuttle vectors were stable in E. coli Stbl2 and S. lividans TK24. Heterologous expression experiments involving each of the catechol 2,3-dioxygenase, nitrilase, and N-substituted formamide deformylase genes as a reporter gene showed that pESH19cF, pESH19kF, and pESH19aF possess inducible expression ability in S. lividans TK24. Thus, these vectors were found to be useful expression tools for experiments on both Gram-negative and Gram-positive bacterial genes.

  7. RNA polymerase II mediated transcription from the polymerase III promoters in short hairpin RNA expression vector

    International Nuclear Information System (INIS)

    Rumi, Mohammad; Ishihara, Shunji; Aziz, Monowar; Kazumori, Hideaki; Ishimura, Norihisa; Yuki, Takafumi; Kadota, Chikara; Kadowaki, Yasunori; Kinoshita, Yoshikazu

    2006-01-01

    RNA polymerase III promoters of human ribonuclease P RNA component H1, human U6, and mouse U6 small nuclear RNA genes are commonly used in short hairpin RNA (shRNA) expression vectors due their precise initiation and termination sites. During transient transfection of shRNA vectors, we observed that H1 or U6 promoters also express longer transcripts enough to express several reporter genes including firefly luciferase, green fluorescent protein EGFP, and red fluorescent protein JRed. Expression of such longer transcripts was augmented by upstream RNA polymerase II enhancers and completely inhibited by downstream polyA signal sequences. Moreover, the transcription of firefly luciferase from human H1 promoter was sensitive to RNA polymerase II inhibitor α-amanitin. Our findings suggest that commonly used polymerase III promoters in shRNA vectors are also prone to RNA polymerase II mediated transcription, which may have negative impacts on their targeted use

  8. Frequent dual initiation of reverse transcription in murine leukemia virus-based vectors containing two primer-binding sites

    International Nuclear Information System (INIS)

    Voronin, Yegor A.; Pathak, Vinay K.

    2003-01-01

    Retroviruses package two copies of viral RNA into each virion. Although each RNA contains a primer-binding site for initiation of DNA synthesis, it is unknown whether reverse transcription is initiated on both RNAs. To determine whether a single virion is capable of initiating reverse transcription more than once, we constructed a murine leukemia virus-based vector containing a second primer-binding site (PBS) derived from spleen necrosis virus and inserted the green fluorescent protein gene (GFP) between the two PBSs. Initiation of reverse transcription at either PBS results in a provirus that expresses GFP. However, initiation at both PBSs can result in the deletion of GFP, which can be detected by flow cytometry and Southern blotting analysis. Approximately 22-29% of the proviruses formed deleted the GFP in a single replication cycle, indicating the minimum proportion of virions that initiated reverse transcription on both PBSs. These results show that a significant proportion of MLV-based vectors containing two PBSs have the capacity to initiate reverse transcription more than once

  9. Target-cell-derived tRNA-like primers for reverse transcription support retroviral infection at low efficiency

    DEFF Research Database (Denmark)

    Schmitz, Alexander; Lund, Anders H; Hansen, Anette C

    2002-01-01

    Reverse transcription of a retroviral genome takes place in the cytoplasm of an infected cell by a process primed by a producer-cell-derived tRNA annealed to an 18-nucleotide primer-binding site (PBS). By an assay involving primer complementation of PBS-mutated vectors we analyzed whether tRNA...... primers derived from the target cell can sustain reverse transcription during murine leukemia virus (MLV) infection. Transduction efficiencies were 4-5 orders of magnitude below those of comparable producer-cell complementations. However, successful usage of a target-cell-derived tRNA primer was proven...... by cases of correction of single mismatches between Akv-MLV vectors and complementary tRNA primers toward the primer sequence in the integrated vector. Thus, target-cell-derived tRNA-like primers are able to initiate first-strand cDNA synthesis and plus-strand transfer leading to a complete provirus...

  10. Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle

    Science.gov (United States)

    Schnepp, Bruce C.; Chulay, Jeffrey D.; Ye, Guo-Jie; Flotte, Terence R.; Trapnell, Bruce C.; Johnson, Philip R.

    2016-01-01

    Gene augmentation therapy as a strategy to treat alpha-1 antitrypsin (AAT) deficiency has reached phase 2 clinical testing in humans. Sustained serum levels of AAT have been observed beyond one year after intramuscular administration of a recombinant adeno-associated virus (rAAV) vector expressing the AAT gene. In this study, sequential muscle biopsies obtained at 3 and 12 months after vector injection were examined for the presence of rAAV vector genomes. Each biopsy sample contained readily detectable vector DNA, the majority of which existed as double-stranded supercoiled and open circular episomes. Episomes persisted through 12 months, although at slightly lower levels than observed at 3 months. There was a clear dose response when comparing the low- and mid-vector-dose groups to the high-dose group. The highest absolute copy numbers were found in a high-dose subject, and serum AAT levels at 12 months confirmed that the high-dose group also had the highest sustained serum AAT levels. Sequence analysis revealed that the vast majority of episomes contained double-D inverted terminal repeats ranging from fully intact to severely deleted. Molecular clones of vector genomes derived directly from the biopsies were transcriptionally active, potentially identifying them as the source of serum AAT in the trial subjects. PMID:26650966

  11. Development of a gene silencing DNA vector derived from a broad host range geminivirus

    Directory of Open Access Journals (Sweden)

    Hancock Leandria C

    2009-07-01

    Full Text Available Abstract Background Gene silencing is proving to be a powerful tool for genetic, developmental, and physiological analyses. The use of viral induced gene silencing (VIGS offers advantages to transgenic approaches as it can be potentially applied to non-model systems for which transgenic techniques are not readily available. However, many VIGS vectors are derived from Gemini viruses that have limited host ranges. We present a new, unipartite vector that is derived from a curtovirus that has a broad host range and will be amenable to use in many non-model systems. Results The construction of a gene silencing vector derived from the geminivirus Beet curly top virus (BCTV, named pWSRi, is reported. Two versions of the vector have been developed to allow application by biolistic techniques or by agro-infiltration. We demonstrate its ability to silence nuclear genes including ribulose bisphosphate carboxylase small subunit (rbcS, transketolase, the sulfur allele of magnesium chelatase (ChlI, and two homeotic transcription factors in spinach or tomato by generating gene-specific knock-down phenotypes. Onset of phenotypes occurred 3 to 12 weeks post-inoculation, depending on the target gene, in organs that developed after the application. The vector lacks movement genes and we found no evidence for significant spread from the site of inoculation. However, viral amplification in inoculated tissue was detected and is necessary for systemic silencing, suggesting that signals generated from active viral replicons are efficiently transported within the plant. Conclusion The unique properties of the pWSRi vector, the ability to silence genes in meristem tissue, the separation of virus and silencing phenotypes, and the broad natural host range of BCTV, suggest that it will have wide utility.

  12. Target-cell-derived tRNA-like primers for reverse transcription support retroviral infection at low efficiency

    DEFF Research Database (Denmark)

    Schmitz, Alexander; Lund, Anders H; Hansen, Anette C

    2002-01-01

    Reverse transcription of a retroviral genome takes place in the cytoplasm of an infected cell by a process primed by a producer-cell-derived tRNA annealed to an 18-nucleotide primer-binding site (PBS). By an assay involving primer complementation of PBS-mutated vectors we analyzed whether t......RNA primers derived from the target cell can sustain reverse transcription during murine leukemia virus (MLV) infection. Transduction efficiencies were 4-5 orders of magnitude below those of comparable producer-cell complementations. However, successful usage of a target-cell-derived tRNA primer was proven...

  13. Noncommutative vector bundles over fuzzy CPN and their covariant derivatives

    International Nuclear Information System (INIS)

    Dolan, Brian P.; Huet, Idrish; Murray, Sean; O'Connor, Denjoe

    2007-01-01

    We generalise the construction of fuzzy CP N in a manner that allows us to access all noncommutative equivariant complex vector bundles over this space. We give a simplified construction of polarization tensors on S 2 that generalizes to complex projective space, identify Laplacians and natural noncommutative covariant derivative operators that map between the modules that describe noncommuative sections. In the process we find a natural generalization of the Schwinger-Jordan construction to su(n) and identify composite oscillators that obey a Heisenberg algebra on an appropriate Fock space

  14. Derivative self-interactions for a massive vector field

    Energy Technology Data Exchange (ETDEWEB)

    Beltrán Jiménez, Jose, E-mail: jose.beltran@cpt.univ-mrs.fr [CPT, Aix Marseille Université, UMR 7332, 13288 Marseille (France); Heisenberg, Lavinia, E-mail: lavinia.heisenberg@eth-its.ethz.ch [Institute for Theoretical Studies, ETH Zurich, Clausiusstrasse 47, 8092 Zurich (Switzerland)

    2016-06-10

    In this work we revisit the construction of theories for a massive vector field with derivative self-interactions such that only the 3 desired polarizations corresponding to a Proca field propagate. We start from the decoupling limit by constructing healthy interactions containing second derivatives of the Stueckelberg field with itself and also with the transverse modes. The resulting interactions can then be straightforwardly generalized beyond the decoupling limit. We then proceed to a systematic construction of the interactions by using the Levi–Civita tensors. Both approaches lead to a finite family of allowed derivative self-interactions for the Proca field. This construction allows us to show that some higher order terms recently introduced as new interactions trivialize in 4 dimensions by virtue of the Cayley–Hamilton theorem. Moreover, we discuss how the resulting derivative interactions can be written in a compact determinantal form, which can also be regarded as a generalization of the Born-Infeld lagrangian for electromagnetism. Finally, we generalize our results for a curved background and give the necessary non-minimal couplings guaranteeing that no additional polarizations propagate even in the presence of gravity.

  15. Characterization of a Trichoplusia ni hexamerin-derived promoter in the AcMNPV baculovirus vector.

    Science.gov (United States)

    López-Vidal, Javier; Gómez-Sebastián, Silvia; Sánchez-Ramos, Ismael; Escribano, José M

    2013-06-10

    The promoter sequences of the encoding genes for the three most abundant hexamerins of the Lepidoptera Trichoplusia ni were isolated and cloned into the Autographa californica multiple nucleopolyhedrovirus (AcMNPV)-derived baculovirus expression vector. From the sequences analyzed, the DNA region driving the expression of the Basic juvenile hormone-suppressible protein 2 (BJHSP-2), denominated pB2, presented the highest promoter strength in the context of the baculovirus vector in Sf21 insect cells. This promoter activity occurred earlier in baculovirus-infected cells than that achieved by a conventional polyhedrin promoter (polh), but surprisingly stopped at 48h post-infection. A mapping of pB2 essential promoter elements determined that a region of about 400bp, denominated pB29, retained and even increased the transcriptional activity with respect to the parental full-length sequence. Finally, several chimeric combinations of the insect-derived pB2 with the virus-derived conventional polh or p10 promoters were constructed and incorporated into an AcMNPV baculovirus vector. The pB2-p10 combination showed increased recombinant protein expression at early times post-infection and similar expression levels at very late times post-infection in Sf21 cells with respect to conventional late promoters. To the best of our knowledge, pB2 is the first promoter isolated from the Lepidoptera T. ni, the natural host of AcMNPV, to be assayed in a baculovirus expression vector. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Gateway-compatible inducible vector set for the functional analysis of transcription factors in plants.

    Science.gov (United States)

    Guo, Zhaolai; Sun, Xudong; Xu, Huini

    2018-05-01

    The inducible vectors pER8-Gateway-3Flag and pER8-Gateway-3Flag-SRDX have been subjected to considerable research in terms of the function of transcription factors (TFs) via transcription activity and repression, respectively. Approximately 1500 TFs have been identified in Arabidopsis thaliana genome. To identify their functions, loss-of-function and gain-of-function mutants were generated to analyze the phenotype. However, many loss-of-function mutants did not show any evident phenotype because of the functional redundancy within the TF family. The constitutive misexpression of some TFs may result in lethality or sterility. To overcome these problems, we produced a Gateway-compatible inducible binary vector system that facilitates fast and reliable DNA cloning and biological function identification. The vector can be used for the inducible expression of protein fusions to a polypeptide protein tag named 3xFLAG tag. This vector system can also be used to generate an inducible transcription inhibition of protein fusion to an Ethylene-Responsive Factor-associated amphiphilic repression (EAR) motif. The EAR motif makes it possible to get rid of redundancy within a TF family, thereby facilitating studies on loss of function. With these Gateway vectors, conventional subcloning technology that depends on restriction digestion and ligation is avoided. Thus, these Gateway vectors should be useful not only for the rapid analysis of the functions of redundant plant TFs, but also for the manipulation of TF overexpression, resulting in plant lethality or sterility, via an inducible promoter.

  17. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Xiao [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Gang, Yi [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province (China); Wang, Honghong [No. 518 Hospital of Chinese People’s Liberation Army, Xi’an 710043, Shaanxi Province (China); Wang, Jiayin [The Genome Institute, Washington University in St. Louis, St. Louis, MO 63108 (United States); Zhao, Lina [Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Xu, Li, E-mail: lxuhelen@163.com [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China); Liu, Zhiguo, E-mail: liuzhiguo@fmmu.edu.cn [State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi Province (China)

    2015-02-06

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity.

  18. Double-stranded RNA transcribed from vector-based oligodeoxynucleotide acts as transcription factor decoy

    International Nuclear Information System (INIS)

    Xiao, Xiao; Gang, Yi; Wang, Honghong; Wang, Jiayin; Zhao, Lina; Xu, Li; Liu, Zhiguo

    2015-01-01

    Highlights: • A shRNA vector based transcription factor decoy, VB-ODN, was designed. • VB-ODN for NF-κB inhibited cell viability in HEK293 cells. • VB-ODN inhibited expression of downstream genes of target transcription factors. • VB-ODN may enhance nuclear entry ratio for its feasibility of virus production. - Abstract: In this study, we designed a short hairpin RNA vector-based oligodeoxynucleotide (VB-ODN) carrying transcription factor (TF) consensus sequence which could function as a decoy to block TF activity. Specifically, VB-ODN for Nuclear factor-κB (NF-κB) could inhibit cell viability and decrease downstream gene expression in HEK293 cells without affecting expression of NF-κB itself. The specific binding between VB-ODN produced double-stranded RNA and NF-κB was evidenced by electrophoretic mobility shift assay. Moreover, similar VB-ODNs designed for three other TFs also inhibit their downstream gene expression but not that of themselves. Our study provides a new design of decoy for blocking TF activity

  19. Estimating the accuracy of vectors derived from open data

    Science.gov (United States)

    Nikolakopoulos, Konstantinos G.; Dimitropoulos, George

    2017-10-01

    Many geological applications like mapping, open quarry monitoring or even the study of tectonic structures, require a high resolution and a very accurate representation of the surface in order to minimize errors. High resolution satellite images or airphotos can provide the necessary basemap for such applications. Nevertheless these kinds of images are quite expensive and hard to get access to. Google Earth is easily accessible to the public, but the question that arises is, if those images can be as reliable as the original satellite images and if they can be used in their place for geological applications. The purpose of this study was to investigate Google Earth images reliability, measure their accuracy and find out if they can provide valid results and finally if they can be used for mapping applications. The region that was investigated is Markopoulo quarry in Attiki Peninsula Greece. Images were taken using Google Earth, one for each direction (North, South, East, and West) from 2004 to 2015. All the images were of the same magnification and same image quality. Subsequently, those images were georeferenced with the use of ArcGIS software. The georeference procedure was executed again using Erdas Imagine software for comparison purposes. A quickbird satellite image over the same area was orthorectified in Leica Photogrammetry Suite. From the orthorectified Quickbird image and the Google Earth images the road network was digitized and the derived vectors were compared in ARCGIS. The comparison showed remarkably low deviation which leads us to the conclusion that Google Earth images can be used as alternative basemap in many applications.

  20. From retroviral vector production to gene transfer: spontaneous inactivation is caused by loss of reverse transcription capacity.

    Science.gov (United States)

    Carmo, M; Panet, A; Carrondo, M J T; Alves, P M; Cruz, P E

    2008-04-01

    The loss of gene transfer capacity in retroviral vectors constitutes a major disadvantage in the development of retroviral vectors for gene therapy applications. In the present work the loss of a vector's capacity to perform reverse transcription was studied as a possible explanation for the low stability of retroviral vectors from the production stage to the target cell gene transfer event. Inactivation studies were performed with murine leukemia virus vectors at 37 degrees C and several residual activities were tested, including viral infectivity, reverse transcription capacity, reverse transcriptase (RT) activities and viral RNA stability. The results indicate a high correlation between loss of infectivity and the capacity of the virus to perform the initial steps of reverse transcription. To further understand the thermosensitivity of the reverse transcription process, the two enzyme activities of RT were investigated. The results indicate that, although the inactivation rate of the DNA polymerase is faster than that of RNase H, the decline of these two enzyme activities is significantly slower than that of reverse transcription. Also, viral RNA stability is not implicated in the loss of the virus capacity to perform reverse transcription as the rate of viral RNA degradation was very slow. Furthermore, it was observed that the amount of viral RNA that entered the cells decreased slowly due to viral inactivation at 37 degrees C. The reverse transcription process is thermolabile and this sensitivity determines the rate of retroviral inactivation. Strategies targeting stabilization of the reverse transcription complex should be pursued to improve the applicability of retroviral vectors in gene therapy studies. (c) 2008 John Wiley & Sons, Ltd.

  1. Tanzanian Botanical Derivatives in the Control of Malaria Vectors ...

    African Journals Online (AJOL)

    Michael Horsfall

    children are mostly affected (Sachs, 2002). Tanzania ... estimated 32 million people (94 % of the population) living in areas ..... In: control of disease vector in the community. Curtis, C.F. (Ed.). Wolfe. Publishing Ltd., London, p 75-92. Dev, S; Koul, O (1997). Insecticides of Natural. Origin, Hartwood Academic Publishers, India.

  2. [Construction of RNAi vectors for SmNAC1 transcription factors of Salvia miltiorrhiza using Gateway cloning technology].

    Science.gov (United States)

    Zhao, Rong; Rong, Qi-Xian; Liu, Yu-Zhong; Shen, Ye; Huang, Lu-Qi

    2014-05-01

    NAC transcription factors involved in plant growth and development, as well as responses to biotic and abiotic stress. RNAi Vectors for SmNAC transcription factors of Salvia miltiorrhiza was constructed by using Gateway cloning technology, in order to further study the function of SmNAC1 transcription factor. According to Gateway cloning technology, the specific fragments of SmNAC1 containing attB adapter was amplified by PCR using ultra-fideling phusion polymerase of NEB. By the BP recombination reaction, the PCR product containing attB was transferred to an donor vector (pENTR/SD/D-TOPO). Finally, SmNACi specific gene was cloned into pK7GWIWG2D plant expression vectors by LR recombination reaction. Experimental results showed that Gateway cloning technology provide a rapid and highly efficient way to clone the interested gene.

  3. Extensions of vector-valued functions with preservation of derivatives

    Czech Academy of Sciences Publication Activity Database

    Koc, M.; Kolář, Jan

    2017-01-01

    Roč. 449, č. 1 (2017), s. 343-367 ISSN 0022-247X R&D Projects: GA ČR(CZ) GA14-07880S Institutional support: RVO:67985840 Keywords : vector -valued differentiable functions * extensions * strict differentiability * partitions of unity Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.064, year: 2016 http://www.sciencedirect.com/science/article/pii/S0022247X16307703

  4. Adenovirus Vector-Derived VA-RNA-Mediated Innate Immune Responses

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mizuguchi

    2011-07-01

    Full Text Available The major limitation of the clinical use of replication-incompetent adenovirus (Ad vectors is the interference by innate immune responses, including induction of inflammatory cytokines and interferons (IFN, following in vivo application of Ad vectors. Ad vector-induced production of inflammatory cytokines and IFNs also results in severe organ damage and efficient induction of acquired immune responses against Ad proteins and transgene products. Ad vector-induced innate immune responses are triggered by the recognition of Ad components by pattern recognition receptors (PRRs. In order to reduce the side effects by Ad vector-induced innate immune responses and to develop safer Ad vectors, it is crucial to clarify which PRRs and which Ad components are involved in Ad vector-induced innate immune responses. Our group previously demonstrated that myeloid differentiating factor 88 (MyD88 and toll-like receptor 9 (TLR9 play crucial roles in the Ad vector-induced inflammatory cytokine production in mouse bone marrow-derived dendritic cells. Furthermore, our group recently found that virus associated-RNAs (VA-RNAs, which are about 160 nucleotide-long non-coding small RNAs encoded in the Ad genome, are involved in IFN production through the IFN-β promoter stimulator-1 (IPS-1-mediated signaling pathway following Ad vector transduction. The aim of this review is to highlight the Ad vector-induced innate immune responses following transduction, especially VA-RNA-mediated innate immune responses. Our findings on the mechanism of Ad vector-induced innate immune responses should make an important contribution to the development of safer Ad vectors, such as an Ad vector lacking expression of VA-RNAs.

  5. Vectors

    DEFF Research Database (Denmark)

    Boeriis, Morten; van Leeuwen, Theo

    2017-01-01

    This article revisits the concept of vectors, which, in Kress and van Leeuwen’s Reading Images (2006), plays a crucial role in distinguishing between ‘narrative’, action-oriented processes and ‘conceptual’, state-oriented processes. The use of this concept in image analysis has usually focused...... on the most salient vectors, and this works well, but many images contain a plethora of vectors, which makes their structure quite different from the linguistic transitivity structures with which Kress and van Leeuwen have compared ‘narrative’ images. It can also be asked whether facial expression vectors...... should be taken into account in discussing ‘reactions’, which Kress and van Leeuwen link only to eyeline vectors. Finally, the question can be raised as to whether actions are always realized by vectors. Drawing on a re-reading of Rudolf Arnheim’s account of vectors, these issues are outlined...

  6. Transcriptional targeting of primary and metastatic tumor neovasculature by an adenoviral type 5 roundabout4 vector in mice.

    Directory of Open Access Journals (Sweden)

    Zhi Hong Lu

    Full Text Available New approaches targeting metastatic neovasculature are needed. Payload capacity, cellular transduction efficiency, and first-pass cellular uptake following systemic vector administration, motivates persistent interest in tumor vascular endothelial cell (EC adenoviral (Ad vector targeting. While EC transductional and transcriptional targeting has been accomplished, vector administration approaches of limited clinical utility, lack of tumor-wide EC expression quantification, and failure to address avid liver sequestration, challenged prior work. Here, we intravenously injected an Ad vector containing 3 kb of the human roundabout4 (ROBO4 enhancer/promoter transcriptionally regulating an enhanced green fluorescent protein (EGFP reporter into immunodeficient mice bearing 786-O renal cell carcinoma subcutaneous (SC xenografts and kidney orthotopic (KO tumors. Initial experiments performed in human coxsackie virus and adenovirus receptor (hCAR transgenic:Rag2 knockout mice revealed multiple ECs with high-level Ad5ROBO4-EGFP expression throughout KO and SC tumors. In contrast, Ad5CMV-EGFP was sporadically expressed in a few tumor vascular ECs and stromal cells. As the hCAR transgene also facilitated Ad5ROBO4 and control Ad5CMV vector EC expression in multiple host organs, follow-on experiments engaged warfarin-mediated liver vector detargeting in hCAR non-transgenic mice. Ad5ROBO4-mediated EC expression was undetectable in most host organs, while the frequencies of vector expressing intratumoral vessels and whole tumor EGFP protein levels remained elevated. In contrast, AdCMV vector expression was only detectable in one or two stromal cells throughout the whole tumor. The Ad5ROBO4 vector, in conjunction with liver detargeting, provides tractable genetic access for in-vivo EC genetic engineering in malignancies.

  7. Tanzanian Botanical Derivatives in the Control of Malaria Vectors ...

    African Journals Online (AJOL)

    This paper report on assessment of the chemicals derived from Tanzanian botanical resource as a viable source of safe, environmentally friendly and low cost mosquitocidal agents, but has yet to be developed into simple blends and formulations to be used in malaria control campaigns. Selection of bioactive plant species ...

  8. Vectors

    DEFF Research Database (Denmark)

    Boeriis, Morten; van Leeuwen, Theo

    2017-01-01

    This article revisits the concept of vectors, which, in Kress and van Leeuwen’s Reading Images (2006), plays a crucial role in distinguishing between ‘narrative’, action-oriented processes and ‘conceptual’, state-oriented processes. The use of this concept in image analysis has usually focused...... should be taken into account in discussing ‘reactions’, which Kress and van Leeuwen link only to eyeline vectors. Finally, the question can be raised as to whether actions are always realized by vectors. Drawing on a re-reading of Rudolf Arnheim’s account of vectors, these issues are outlined...

  9. Three results on the PageRank vector: eigenstructure, sensitivity, and the derivative

    OpenAIRE

    Gleich, David; Glynn, Peter; Golub, Gene; Greif, Chen

    2007-01-01

    The three results on the PageRank vector are preliminary but shed light on the eigenstructure of a PageRank modified Markov chain and what happens when changing the teleportation parameter in the PageRank model. Computations with the derivative of the PageRank vector with respect to the teleportation parameter show predictive ability and identify an interesting set of pages from Wikipedia.

  10. Transcriptional profiling of MEF2-regulated genes in human neural progenitor cells derived from embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Shing Fai Chan

    2015-03-01

    Full Text Available The myocyte enhancer factor 2 (MEF2 family of transcription factors is highly expressed in the brain and constitutes a key determinant of neuronal survival, differentiation, and synaptic plasticity. However, genome-wide transcriptional profiling of MEF2-regulated genes has not yet been fully elucidated, particularly at the neural stem cell stage. Here we report the results of microarray analysis comparing mRNAs isolated from human neural progenitor/stem cells (hNPCs derived from embryonic stem cells expressing a control vector versus progenitors expressing a constitutively-active form of MEF2 (MEF2CA, which increases MEF2 activity. Microarray experiments were performed using the Illumina Human HT-12 V4.0 expression beadchip (GEO#: GSE57184. By comparing vector-control cells to MEF2CA cells, microarray analysis identified 1880 unique genes that were differentially expressed. Among these genes, 1121 genes were up-regulated and 759 genes were down-regulated. Our results provide a valuable resource for identifying transcriptional targets of MEF2 in hNPCs.

  11. A direct derivation of the exact Fisther information matrix of Gaussian vector state space models

    NARCIS (Netherlands)

    Klein, A.A.B.; Neudecker, H.

    2000-01-01

    This paper deals with a direct derivation of Fisher's information matrix of vector state space models for the general case, by which is meant the establishment of the matrix as a whole and not element by element. The method to be used is matrix differentiation, see [4]. We assume the model to be

  12. [RelB silencing in mouse bone-marrow derived dendritic cells mediated by lentiviral vector].

    Science.gov (United States)

    Bao, Jie; Wang, Qian; Zheng, Lei; Qiu, Yu-rong; Zeng, Fang-yin; Yang, Chun-li; Huang, Xian-zhang

    2008-09-01

    To silence RelB gene in mouse bone-marrow derived dendritic cells (DC) utilizing lentiviral vector, a novel tolerogenic dendritic cell with a relatively low expression level RelB was constructed and a new way to treat and prevent autoimmune diseases was explored. Interferential targeting sequence R5 of RelB in mice was designed, synthesized and cloned into lentiviral vectors. Together with viral packaging materials were co-cultured in 293FT cell line to package lentiviral vector. Supernatant fluids were harvested, then virus titer detected. Mouse bone marrow derived DCs were infected by lentivirus particle. RelB gene expression level was detected by RT-PCR and immunofluorescence staining and analyzed by software of geo pro. There are three experiment control groups including immature DC, mature DC and DC infected by a negative independent control of T6. A similar RelB expression was detected by RT-PCR and immunofluorescence staining assay between DC infected virus R5 and immature DC, but was lower than that of mature DC. Significant difference in statistics P < 0.05. A similar RelB expression was detected by RT-PCR and immunofluorescence staining approaches between DC infected virus T6 and mature DC, but was higher than that of immature DC. Significant difference in statistics P < 0.05. RelB gene expressed by mouse bone marrow derived DC was silenced by Lentivirus vector effectively. The lentivirus vector with a low immunogenicity can be used to immunotherapy in vivo and overcome difficult transfection problem of primary DC. A new viral vector of DC immunotherapy can be obtained.

  13. Insertion of liver enriched transcription factor hepatocyte nuclear factor-4 (HNF-4) in a vector which contains simian virus (SV40) promoter

    International Nuclear Information System (INIS)

    Al-Nbaheen, M.; Pourzand, C.; Tyrrell, R.M.

    2006-01-01

    One way of targeting gene expression in vivo is to control transcription using a tissue-specific regulatory system. Tissue specific promoters or enhancers are in use in transgenic animals and could be utilized in medical for gene therapy. At present the usual method for selection of a tissue-specific promoter is to identify a gene, which is expressed at unusually high level in the target tissue, and then to use the promoter for this gene to drive expression of another therapeutic gene in the target tissue. This approach is logical but does not always lead to high levels of gene expression. A second approach is to investigate the scope for discovery of synthetic specific promoters using a target tissue. The objective of the work described in this paper was to use both approach to design plasmid DNA expression vectors that would carry liver-specific promoter/enhancer linked to reporter gene (i.e. luciferase). Then transfect these vectors to both liver-derived and non-liver cell lines. This is followed by evaluation of the liver-specificity of each construct by measuring the basal level expression of the reporter gene (i.e. luciferase activity) in both cell lines. Hepatocyte nuclear factor-4 (HNF-4) is liver-enriched transcription factor used to design new synthetic enhancers by inserting a tandem array of 1', 3' or 5' repeats of the HNF-4 binding site upstream of the SV40 promoter linked to the luciferase reporter gene within an Epstein-Barr virus (EBV)-based vector, p 706. The results of transfection revealed that unexpectedly the HNF-4 binding sites in these constructs act as a repressor rather than enhancer of the liver-specific expression of the luciferase gene. (author)

  14. Neighboring block based disparity vector derivation for multiview compatible 3D-AVC

    Science.gov (United States)

    Kang, Jewon; Chen, Ying; Zhang, Li; Zhao, Xin; Karczewicz, Marta

    2013-09-01

    3D-AVC being developed under Joint Collaborative Team on 3D Video Coding (JCT-3V) significantly outperforms the Multiview Video Coding plus Depth (MVC+D) which simultaneously encodes texture views and depth views with the multiview extension of H.264/AVC (MVC). However, when the 3D-AVC is configured to support multiview compatibility in which texture views are decoded without depth information, the coding performance becomes significantly degraded. The reason is that advanced coding tools incorporated into the 3D-AVC do not perform well due to the lack of a disparity vector converted from the depth information. In this paper, we propose a disparity vector derivation method utilizing only the information of texture views. Motion information of neighboring blocks is used to determine a disparity vector for a macroblock, so that the derived disparity vector is efficiently used for the coding tools in 3D-AVC. The proposed method significantly improves a coding gain of the 3D-AVC in the multiview compatible mode about 20% BD-rate saving in the coded views and 26% BD-rate saving in the synthesized views on average.

  15. In vivo production of recombinant proteins using occluded recombinant AcMNPV-derived baculovirus vectors.

    Science.gov (United States)

    Guijarro-Pardo, Eva; Gómez-Sebastián, Silvia; Escribano, José M

    2017-12-01

    Trichoplusia ni insect larvae infected with vectors derived from the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), are an excellent alternative to insect cells cultured in conventional bioreactors to produce recombinant proteins because productivity and cost-efficiency reasons. However, there is still a lot of work to do to reduce the manual procedures commonly required in this production platform that limit its scalability. To increase the scalability of this platform technology, a current bottleneck to be circumvented in the future is the need of injection for the inoculation of larvae with polyhedrin negative baculovirus vectors (Polh-) because of the lack of oral infectivity of these viruses, which are commonly used for production in insect cell cultures. In this work we have developed a straightforward alternative to obtain orally infective vectors derived from AcMNPV and expressing recombinant proteins that can be administered to the insect larvae (Trichoplusia ni) by feeding, formulated in the insect diet. The approach developed was based on the use of a recombinant polyhedrin protein expressed by a recombinant vector (Polh+), able to co-occlude any recombinant Polh- baculovirus vector expressing a recombinant protein. A second alternative was developed by the generation of a dual vector co-expressing the recombinant polyhedrin protein and the foreign gene of interest to obtain the occluded viruses. Additionally, by the incorporation of a reporter gene into the helper Polh+ vector, it was possible the follow-up visualization of the co-occluded viruses infection in insect larvae and will help to homogenize infection conditions. By using these methodologies, the production of recombinant proteins in per os infected larvae, without manual infection procedures, was very similar in yield to that obtained by manual injection of recombinant Polh- AcMNPV-based vectors expressing the same proteins. However, further analyses will be required for a

  16. Expression of rat oligodendrocyte transcription factor 2 in COS-7 cells following its eukaryotic expression vector construction.

    Science.gov (United States)

    Qu, D-W; Han, X-J; Wang, Y-L; Xu, H-S

    2014-08-01

    The basic HLH transcription factor Olig is a key regulator for differentiating the oligodendrocyte lineage cells during development. Oligodendrocyte transcription factor 2 (Olig2) plays a crucial role in differentiating the oligodendrocytes in the spinal cord. We aimed to construct and investigate the eukaryotic expression recombinant plasmid in the rat Olig2. The experiment was performed at the Laboratory of Neurobiology, Xuzhou Medical College from October 2011 to March 2012. The pEGFP-N1 vector was purchased from Invitrogen. JM101 competent cells and COS-7 cells were preserved at the Laboratory of Neurobiology, Xuzhou Medical College, China. The Olig2 cDNA fragment was cloned by RT-PCR with the total RNA from the neonatal rat spinal cord, and subsequently cloned into pGEM-T vector. The confirmed Olig2 fragment was then cloned into the pEGFP-N1 vector. The right recombinant was transfected into COS-7 cells by lipofectamine 2000. The expression of the Olig2 in COS-7 cells was detected by RT-PCR and immunoblot analysis. Enzyme digestion and sequencing of the recombinant plasmid; and expression of the Olig2 were analyzed by fluorescence microscope and western blot. The correct pEGFP-N1-Olig2 cloning was verified by restriction endonuclease digestion and sequencing. The western blot analysis indicated that the Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells at 72 h. The pEGFP-N1-Olig2 vector was constructed successfully. The Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells. This study lays the foundation for further research in gene therapy for central nervous system demyelinating diseases.

  17. Glycoprotein is enough for sindbis virus-derived DNA vector to express heterogenous genes

    Directory of Open Access Journals (Sweden)

    Fu Juanjuan

    2011-07-01

    Full Text Available Abstract To investigate the necessity and potential application of structural genes for expressing heterogenous genes from Sindbis virus-derived vector, the DNA-based expression vector pVaXJ was constructed by placing the recombinant genome of sindbis-like virus XJ-160 under the control of the human cytomegalovirus (CMV promoter of the plasmid pVAX1, in which viral structural genes were replaced by a polylinker cassette to allow for insertion of heterologous genes. The defect helper plasmids pVaE or pVaC were developed by cloning the gene of glycoprotein E3E26KE1 or capsid protein of XJ-160 virus into pVAX1, respectively. The report gene cassette pVaXJ-EGFP or pV-Gluc expressing enhanced green fluorescence protein (EGFP or Gaussia luciferase (G.luc were constructed by cloning EGFP or G.luc gene into pVaXJ. EGFP or G.luc was expressed in the BHK-21 cells co-transfected with report gene cassettes and pVaE at levels that were comparable to those produced by report gene cassettes, pVaC and pVaE and were much higher than the levels produced by report gene cassette and pVaC, suggesting that glycoprotein is enough for Sindbis virus-derived DNA vector to express heterogenous genes in host cells. The method of gene expression from Sindbis virus-based DNA vector only co-transfected with envelop E gene increase the conveniency and the utility of alphavirus-based vector systems in general.

  18. Landslide displacement vectors derived from multi-temporal topographic LiDAR data

    Science.gov (United States)

    Fey, Christine; Rutzinger, Martin; Bremer, Magnus; Prager, Christoph; Zangerl, Christian

    2014-05-01

    Information about slope geometry and kinematics of landslides is essential for hazard assessment, monitoring and planning of protection and mitigation measures. Especially for remote and inaccessible slopes, subsurface data (e.g. boreholes, tunnels, investigation adits) are often not available and thus the deformation characteristics must be derived from surface displacement data. In recent years, multi-temporal topographic LiDAR (Light Detection and Ranging) data became an increasingly improved tool for detecting topographic surface deformations. In this context, LiDAR-based change detection is commonly applied for quantifying surface elevation changes. Advanced change detection methods derive displacement vectors with direction and velocities of slope movements. To extract displacement vectors from LiDAR raster data (i) an approach based on feature tracking by image correlation and (ii) an approach based on feature tracking by vectors breaklines are investigated. The image correlation method is based on the IMCORR software (National Snow and Ice Data Center, University of Colorado, Boulder), implemented in a SAGA GIS module. The image correlation algorithm is based on a normalized cross-covariance method. The algorithm searches tie points in two feature rasters derived from a digital surface model acquired at different time stamps. The method assesses automatically the displacement rates and directions of distinct terrain features e.g. displaced mountain ridges or striking boulders. In contrast the vector-based breakline methods require manual selection of tie points. The breaklines are the product of vectorized curvature raster images and extracting the "upper terrain edges" (topographic ridges) and "lower terrain edges" (topographic depressions). Both methods were tested on simulated terrain with determined displacement rates in order to quantify i) the accuracy ii) the minimum detectable movement rates iii) the influence of terrain characteristics iv) the

  19. Analysis of salivary gland transcripts of the sand fly Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis

    Science.gov (United States)

    Kato, Hirotomo; Jochim, Ryan C.; Gomez, Eduardo A.; Uezato, Hiroshi; Mimori, Tatsuyuki; Korenaga, Masataka; Sakurai, Tatsuya; Katakura, Ken; Valenzuela, Jesus G.; Hashiguchi, Yoshihisa

    2013-01-01

    The saliva of blood sucking insects contains potent pharmacologically active components that assist them in counteracting the host hemostatic and inflammatory systems during blood feeding. In addition, sand fly salivary proteins affect host immunity and have the potential to be a vaccine against Leishmania infection. In the present study, the salivary gland transcripts of Lutzomyia ayacuchensis, a vector of cutaneous leishmaniasis in Ecuadorian and Peruvian Andes, were analyzed by sequencing randomly selected clones of the salivary gland cDNA library of this sand fly. This resulted in the identification of the most abundant transcripts coding for secreted proteins. These proteins were homologous to the salivary molecules present in other sand flies including the RGD-containing peptide, PpSP15/SL1 family protein, yellow-related protein, putative apyrase, antigen 5-related protein, D7 family protein, and 27 kDa salivary protein. Of note, homologues of maxadilan, an active vasodilator abundantly present in saliva of Lutzomyia longipalpis, were not identified. This analysis is the first description of salivary proteins from a sand fly of the subgenus Helcocyrtomyia and from vector of cutaneous leishmaniasis in the New World. The present analysis will provide further insights into the evolution of salivary components in blood sucking arthropods. PMID:23000112

  20. A Vector with a Single Promoter for In Vitro Transcription and Mammalian Cell Expression of CRISPR gRNAs.

    Directory of Open Access Journals (Sweden)

    Peter J Romanienko

    Full Text Available The genomes of more than 50 organisms have now been manipulated due to rapid advancement of gene editing technology. One way to perform gene editing in the mouse using the CRISPR/CAS system, guide RNA (gRNA and CAS9 mRNA transcribed in vitro are microinjected into fertilized eggs that are then allowed to develop to term. As a rule, gRNAs are tested first in tissue culture cells and the one with the highest locus-specific cleavage activity is chosen for microinjection. For cell transfections, gRNAs are typically expressed using the human U6 promoter (hU6. However, gRNAs for microinjection into zygotes are obtained by in vitro transcription from a T7 bacteriophage promoter in a separate plasmid vector. Here, we describe the design and construction of a combined U6T7 hybrid promoter from which the same gRNA sequence can be expressed. An expression vector containing such a hybrid promoter can now be used to generate gRNA for testing in mammalian cells as well as for microinjection purposes. The gRNAs expressed and transcribed from this vector are found to be functional in cells as well as in mice.

  1. Efficient Model Order Reduction for the Dynamics of Nonlinear Multilayer Sheet Structures with Trial Vector Derivatives

    Directory of Open Access Journals (Sweden)

    Wolfgang Witteveen

    2014-01-01

    Full Text Available The mechanical response of multilayer sheet structures, such as leaf springs or car bodies, is largely determined by the nonlinear contact and friction forces between the sheets involved. Conventional computational approaches based on classical reduction techniques or the direct finite element approach have an inefficient balance between computational time and accuracy. In the present contribution, the method of trial vector derivatives is applied and extended in order to obtain a-priori trial vectors for the model reduction which are suitable for determining the nonlinearities in the joints of the reduced system. Findings show that the result quality in terms of displacements and contact forces is comparable to the direct finite element method but the computational effort is extremely low due to the model order reduction. Two numerical studies are presented to underline the method’s accuracy and efficiency. In conclusion, this approach is discussed with respect to the existing body of literature.

  2. Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2012-01-31

    BACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.

  3. Design and application of cationic amphiphilic β-cyclodextrin derivatives as gene delivery vectors

    Science.gov (United States)

    Wan, Ning; Huan, Meng-Lei; Ma, Xi-Xi; Jing, Zi-Wei; Zhang, Ya-Xuan; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

    2017-11-01

    The nano self-assembly profiles of amphiphilic gene delivery vectors could improve the density of local cationic head groups to promote their DNA condensation capability and enhance the interaction between cell membrane and hydrophobic tails, thus increasing cellular uptake and gene transfection. In this paper, two series of cationic amphiphilic β-cyclodextrin (β-CD) derivatives were designed and synthesized by using 6-mono-OTs-β-CD (1) as the precursor to construct amphiphilic gene vectors with different building blocks in a selective and controlled manner. The effect of different type and degree of cationic head groups on transfection and the endocytic mechanism of β-CD derivatives/DNA nanocomplexes were also investigated. The results demonstrated that the designed β-cyclodextrin derivatives were able to compact DNA to form stable nanocomplexes and exhibited low cytotoxicity. Among them, PEI-1 with PEI head group showed enhanced transfection activity, significantly higher than commercially available agent PEI25000 especially in the presence of serum, showing potential application prospects in clinical trials. Moreover, the endocytic uptake mechanism involved in the gene transfection of PEI-1 was mainly through caveolae-mediated endocytosis, which could avoid the lysosomal degradation of loaded gene, and had great importance for improving gene transfection activity.

  4. Breaking the mold: transcription factors in the anucleate platelet and platelet-derived microparticles

    Directory of Open Access Journals (Sweden)

    Katie L Lannan

    2015-02-01

    Full Text Available Platelets are small anucleate blood cells derived from megakaryocytes. In addition to their pivotal roles in hemostasis, platelets are the smallest, yet most abundant, immune cell and regulate inflammation, immunity, and disease progression. Although platelets lack DNA, and thus no functional transcriptional activities, they are nonetheless rich sources of RNAs, possess an intact spliceosome, and are thus capable of synthesizing proteins. Previously, it was thought that platelet RNAs and translational machinery were remnants from the megakaryocyte. We now know that the initial description of platelets as cellular fragments is an antiquated notion, as mounting evidence suggests otherwise. Therefore, it is reasonable to hypothesize that platelet transcription factors are not vestigial remnants from megakaryoctes, but have important, if only partly understood functions. Proteins play multiple cellular roles to minimize energy expenditure for maximum cellular function; thus, the same can be expected for transcription factors. In fact, numerous transcription factors have non-genomic roles, both in platelets and in nucleated cells. Our lab and others have discovered the presence and nongenomic roles of transcription factors in platelets, such as the nuclear factor kappa β (NFκB family of proteins and peroxisome proliferator activated receptor gamma (PPARγ. In addition to numerous roles in regulating platelet activation, functional transcription factors can be transferred to vascular and immune cells through platelet microparticles. This method of transcellular delivery of key immune molecules may be a vital mechanism by which platelet transcription factors regulate inflammation and immunity. At the very least, platelets are an ideal model cell to dissect out the nongenomic roles of transcription factors in nucleated cells. There is abundant evidence to suggest that transcription factors in platelets play key roles in regulating inflammatory and

  5. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems.

    Directory of Open Access Journals (Sweden)

    Julia K Bialek

    Full Text Available CRISPR/Cas9 technology is currently considered the most advanced tool for targeted genome engineering. Its sequence-dependent specificity has been explored for locus-directed transcriptional modulation. Such modulation, in particular transcriptional activation, has been proposed as key approach to overcome silencing of dormant HIV provirus in latently infected cellular reservoirs. Currently available agents for provirus activation, so-called latency reversing agents (LRAs, act indirectly through cellular pathways to induce viral transcription. However, their clinical performance remains suboptimal, possibly because reservoirs have diverse cellular identities and/or proviral DNA is intractable to the induced pathways. We have explored two CRISPR/Cas9-derived activator systems as targeted approaches to induce dormant HIV-1 proviral DNA. These systems recruit multiple transcriptional activation domains to the HIV 5' long terminal repeat (LTR, for which we have identified an optimal target region within the LTR U3 sequence. Using this target region, we demonstrate transcriptional activation of proviral genomes via the synergistic activation mediator complex in various in culture model systems for HIV latency. Observed levels of induction are comparable or indeed higher than treatment with established LRAs. Importantly, activation is complete, leading to production of infective viral particles. Our data demonstrate that CRISPR/Cas9-derived technologies can be applied to counteract HIV latency and may therefore represent promising novel approaches in the quest for HIV elimination.

  6. Chapter five--The development of transcription-regulated adenoviral vectors with high cancer-selective imaging capabilities.

    Science.gov (United States)

    Jiang, Ziyue Karen; Sato, Makoto; Wu, Lily

    2012-01-01

    A clear benefit of molecular imaging is to enable noninvasive, repetitive monitoring of intrinsic signals within tumor cells as a means to identify the lesions as malignant or to assess the ability of treatment to perturb key pathways within the tumor cells. Due to the promising utility of molecular imaging in oncology, preclinical research to refine molecular imaging techniques in small animals is a blossoming field. We will first discuss the several imaging modalities such as fluorescent imaging, bioluminescence imaging, and positron emission tomography that are now commonly used in small animal settings. The indirect imaging approach, which can be adapted to a wide range of imaging reporter genes, is a useful platform to develop molecular imaging. In particular, reporter gene-based imaging is well suited for transcriptional-targeted imaging that can be delivered by recombinant adenoviral vectors. In this review, we will summarize transcription-regulated strategies used in adenoviral-mediated molecular imaging to visualize metastasis and monitor oncolytic therapy in preclinical models. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Regulation of anti-Plasmodium immunity by a LITAF-like transcription factor in the malaria vector Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Ryan C Smith

    Full Text Available The mosquito is the obligate vector for malaria transmission. To complete its development within the mosquito, the malaria parasite Plasmodium must overcome the protective action of the mosquito innate immune system. Here we report on the involvement of the Anopheles gambiae orthologue of a conserved component of the vertebrate immune system, LPS-induced TNFα transcription factor (LITAF, and its role in mosquito anti-Plasmodium immunity. An. gambiae LITAF-like 3 (LL3 expression is up-regulated in response to midgut invasion by both rodent and human malaria parasites. Silencing of LL3 expression greatly increases parasite survival, indicating that LL3 is part of an anti-Plasmodium defense mechanism. Electrophoretic mobility shift assays identified specific LL3 DNA-binding motifs within the promoter of SRPN6, a gene that also mediates mosquito defense against Plasmodium. Further experiments indicated that these motifs play a direct role in LL3 regulation of SRPN6 expression. We conclude that LL3 is a transcription factor capable of modulating SRPN6 expression as part of the mosquito anti-Plasmodium immune response.

  8. New method for numerical approximations of vector derivatives based on digital signal processing techniques

    Science.gov (United States)

    Brice, Henry; Ahmed, Mohammed Z.

    2012-05-01

    Accurate propagation models are required for predicting the propagation of electromagnetic waves within complex environments. This paper proposes the use of a new method to accurately compute the divergence and curl of electromagnetic fields. The computation of the derivatives of vector fields is normally approximated using numerical methods such as the Finite-Dierence Time-Domain Method (FDTD), the Finite Integration Technique and the Multi-Resolution Time-Domain Method. These methods are all limited in terms of their accuracy, resolution, computational efficiency and numerical stability. This paper introduces a new method for computing derivatives based on Two-Dimensional (2D) Digital Signal Processing (DSP) techniques. The method involves computing a numerical approximation of the derivative of a function by considering the frequency domain definition of the derivative and designing a 2Dfinite impulse response (FIR) filter that implements the differentiation. Appropriate windowing functions are used to ensure that the FIR response is as close to the ideal 2D differentiator response as possible. This paper provides an example where the curl of a vectorfield is determined using this method and accuracy within a few percent is achieved. The proposed innovative method can be extended to three dimensions and used to find numerical solutions of Maxwells Equations, thus allowing it to be applied to the design of accurate propagation models.

  9. Phenotyping of VIGS-mediated gene silencing in rice using a vector derived from a DNA virus.

    Science.gov (United States)

    Kant, Ravi; Dasgupta, Indranil

    2017-07-01

    Target genes in rice can be optimally silenced if inserted in antisense or hairpin orientation in the RTBV-derived VIGS vector and plants grown at 28 °C and 80% humidity after inoculation. Virus induced gene silencing (VIGS) is a method used to transiently silence genes in dicot as well as monocot plants. For the important monocot species rice, the Rice tungro bacilliform virus (RTBV)-derived VIGS system (RTBV-VIGS), which uses agroinoculation to initiate silencing, has not been standardized for optimal use. Here, using RTBV-VIGS, three sets of conditions were tested to achieve optimal silencing of the rice marker gene phytoene desaturase (pds). The effect of orientation of the insert in the RTBV-VIGS plasmid (sense, antisense and hairpin) on the silencing of the target gene was then evaluated using rice magnesium chelatase subunit H (chlH). Finally, the rice Xa21 gene, conferring resistance against bacterial leaf blight disease (BLB) was silenced using RTBV-VIGS system. In each case, real-time PCR-based assessment indicated approximately 40-80% fall in the accumulation levels of the transcripts of pds, chlH and Xa21. In the case of pds, the appearance of white streaks in the emerging leaves, and for chlH, chlorophyll levels and F v /F m ratio were assessed as phenotypes for silencing. For Xa21, the resistance levels to BLB were assessed by measuring the lesion length and the percent diseased areas of leaves, following challenge inoculation with Xanthomonas oryzae. In each case, the RTBV-MVIGS system gave rise to a discernible phenotype indicating the silencing of the respective target gene using condition III (temperature 28 °C, humidity 80% and 1 mM MES and 20 µM acetosyringone in secondary agrobacterium culture), which revealed the robustness of this gene silencing system for rice.

  10. An efficient nonviral gene-delivery vector based on hyperbranched cationic glycogen derivatives

    Directory of Open Access Journals (Sweden)

    Liang X

    2014-01-01

    Full Text Available Xuan Liang,1,* Xianyue Ren,2,* Zhenzhen Liu,1 Yingliang Liu,1 Jue Wang,2 Jingnan Wang,2 Li-Ming Zhang,1 David YB Deng,2 Daping Quan,1 Liqun Yang1 1Institute of Polymer Science, School of Chemistry and Chemical Engineering, Key Laboratory of Designed Synthesis and Application of Polymer Material, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-Sen University, Guangzhou, People's Republic of China; 2Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China *Both these authors contributed equally to this work Background: The purpose of this study was to synthesize and evaluate hyperbranched cationic glycogen derivatives as an efficient nonviral gene-delivery vector. Methods: A series of hyperbranched cationic glycogen derivatives conjugated with 3-(dimethylamino-1-propylamine (DMAPA-Glyp and 1-(2-aminoethyl piperazine (AEPZ-Glyp residues were synthesized and characterized by Fourier-transform infrared and hydrogen-1 nuclear magnetic resonance spectroscopy. Their buffer capacity was assessed by acid–base titration in aqueous NaCl solution. Plasmid deoxyribonucleic acid (pDNA condensation ability and protection against DNase I degradation of the glycogen derivatives were assessed using agarose gel electrophoresis. The zeta potentials and particle sizes of the glycogen derivative/pDNA complexes were measured, and the images of the complexes were observed using atomic force microscopy. Blood compatibility and cytotoxicity were evaluated by hemolysis assay and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, respectively. pDNA transfection efficiency mediated by the cationic glycogen derivatives was evaluated by flow cytometry and fluorescence microscopy in the 293T (human embryonic kidney and the CNE2 (human nasopharyngeal carcinoma cell lines. In vivo delivery of pDNA in model animals (Sprague Dawley

  11. miRNA-mediated post-transcriptional silencing of transgenes leads to increased adeno-associated viral vector yield and targeting specificity.

    Science.gov (United States)

    Reid, C A; Boye, S L; Hauswirth, W W; Lipinski, D M

    2017-08-01

    The production of high-titer recombinant adeno-associated virus (rAAV) vector is essential for treatment of genetic diseases affecting the retina and choroid, where anatomical constraints may limit injectable volumes. Problematically, cytotoxicity arising from overexpression of the transgene during vector production frequently leads to a reduction in vector yield. Herein, we evaluate the use of microRNA (miRNA)-mediated silencing to limit overexpression of cytotoxic transgenes during packaging as a method of increasing vector yield. We examined if post-transcriptional regulation of transgenes during packaging via miRNA technology would lead to increased rAAV yields. Our results demonstrate that silencing of cytotoxic transgenes during production resulted in up to a 22-fold increase in vector yield. The inclusion of organ-specific miRNA sequences improved biosafety by limiting off-target expression following systemic rAAV administration. The small size (22-23 bp) of the target site allows for the inclusion of multiple copies into the vector with minimal impact on coding capacity. Taken together, our results suggest that inclusion of miRNA target sites into the 3'-untranslated region of the AAV cassette allow for silencing of cytotoxic transgenes during vector production leading to improved vector yield, in addition to increasing targeting specificity without reliance on cell-specific promoters.

  12. Murine leukemia virus-derived retroviral vector has differential integration patterns in human cell lines used to produce recombinant factor VIII

    Directory of Open Access Journals (Sweden)

    Marcela Cristina Correa de Freitas

    2014-06-01

    Full Text Available OBJECTIVE: Nowadays recombinant factor VIII is produced in murine cells including in Chinese hamster ovary (CHO and baby hamster kidney cells (BHK. Previous studies, using the murine leukemia virus-derived retroviral vector pMFG-FVIII-P140K, modified two recombinant human cell lines, HepG2 and Hek293 to produce recombinant factor VIII. In order to characterize these cells, the present study aimed to analyze the integration pattern of retroviral vector pMFG-FVIII-P140K.METHODS: This study used ligation-mediated polymerase chain reaction to locate the site of viral vector integration by sequencing polymerase chain reaction products. The sequences were compared to genomic databases to characterize respective clones.RESULTS: The retroviral vector presented different and non-random profiles of integration between cells lines. A preference of integration for chromosomes 19, 17 and 11 was observed for HepG2FVIIIdB/P140K and chromosome 9 for Hek293FVIIIdB/P140K. In genomic regions such as CpG islands and transcription factor binding sites, there was no difference in the integration profiles for both cell lines. Integration in intronic regions of encoding protein genes (RefSeq genes was also observed in both cell lines. Twenty percent of integrations occurred at fragile sites in the genome of the HepG2 cell line and 17% in Hek293.CONCLUSION: The results suggest that the cell type can affect the profile of chromosomal integration of the retroviral vector used; these differences may interfere in the level of expression of recombinant proteins.

  13. Atomic force microscope observation of branching in single transcript molecules derived from human cardiac muscle

    Science.gov (United States)

    Reed, Jason; Hsueh, Carlin; Mishra, Bud; Gimzewski, James K.

    2008-09-01

    We have used an atomic force microscope to examine a clinically derived sample of single-molecule gene transcripts, in the form of double-stranded cDNA, (c: complementary) obtained from human cardiac muscle without the use of polymerase chain reaction (PCR) amplification. We observed a log-normal distribution of transcript sizes, with most molecules being in the range of 0.4-7.0 kilobase pairs (kb) or 130-2300 nm in contour length, in accordance with the expected distribution of mRNA (m: messenger) sizes in mammalian cells. We observed novel branching structures not previously known to exist in cDNA, and which could have profound negative effects on traditional analysis of cDNA samples through cloning, PCR and DNA sequencing.

  14. A new FACS approach isolates hESC derived endoderm using transcription factors.

    Directory of Open Access Journals (Sweden)

    Yuqiong Pan

    2011-03-01

    Full Text Available We show that high quality microarray gene expression profiles can be obtained following FACS sorting of cells using combinations of transcription factors. We use this transcription factor FACS (tfFACS methodology to perform a genomic analysis of hESC-derived endodermal lineages marked by combinations of SOX17, GATA4, and CXCR4, and find that triple positive cells have a much stronger definitive endoderm signature than other combinations of these markers. Additionally, SOX17(+ GATA4(+ cells can be obtained at a much earlier stage of differentiation, prior to expression of CXCR4(+ cells, providing an important new tool to isolate this earlier definitive endoderm subtype. Overall, tfFACS represents an advancement in FACS technology which broadly crosses multiple disciplines, most notably in regenerative medicine to redefine cellular populations.

  15. Transformation of Cowpea Vigna unguiculata Cells with an Antibiotic Resistance Gene Using a Ti-Plasmid-Derived Vector

    NARCIS (Netherlands)

    Hille, Jacques; Goldbach, Rob

    1986-01-01

    A chimaeric antibiotic resistance gene was transferred to cowpea (Vigna unguiculata), a member of the legume family. This transfer was established by inoculating cowpea leaf discs with an Agrobacterium tumefaciens strain harboring a Ti-plasmid-derived vector that contained two copies of a chimaeric

  16. A nuclear localization signal in the matrix of spleen necrosis virus (SNV) does not allow efficient gene transfer into quiescent cells with SNV-derived vectors.

    Science.gov (United States)

    Caron, Marie-Christine; Caruso, Manuel

    2005-08-01

    A major limitation in gene therapy for vectors derived from Moloney murine leukemia virus (MLV) is that they only deliver genes into dividing cells. In this study, a careful comparison of spleen necrosis virus (SNV)-derived vectors with MLV and human immunodeficiency virus (HIV)-1 retroviral vectors indicated that SNV vectors can deliver genes 4-fold more efficiently than MLV vectors into aphidicolin-arrested cells, although at a 25-fold lower efficiency than HIV-1-derived vectors. Furthermore, the addition of a NLS in the SNV matrix (MA) that mimics the one located in HIV-1 MA did not increase the ability of SNV vectors to transfer genes into arrested cells. Also, we found that the RD114 envelope was able to pseudotype SNV viral particles in a very efficient manner.

  17. Current strides in AAV-derived vectors and SIN channels further ...

    African Journals Online (AJOL)

    A.S. Odiba

    Vectors used in Gene Therapy Clinical Trials. Data Sourced from: The Journal of Gene. Medicine (www.wiley.co.uk/genmed/clinical) on 2nd June 2017. Vector. Gene Therapy. Clinical Trials. Number. %. Alphavirus (VEE) Replicon Vaccine. 1. 0. E. coli. 2. 0.1. Bifidobacterium longum. 1. 0. CRISPR-Cas9. 7. 0.3. Adenovirus + ...

  18. Can plastic bag derived-microplastics act as vectors for metal exposure in terrestrial invertebrates?

    Science.gov (United States)

    E Hodson, Mark; Duffus-Hodson, Calum A.; Prendergast-Miller, Miranda; Thorpe, Karen

    2017-04-01

    Microplastics are widely reported contaminants in marine and freshwater ecosystems and studies have shown that they can be ingested by aquatic organisms and lead to potential negative effects on health. The effects can arise from the physical effects of the plastics (e.g. food displacement and blockages of the digestive tract) and from their potential to adsorb contaminants, primarily organic compounds, resulting in an increased exposure of the organism to toxic contaminants. Studies are beginning to emerge that also show a high abundance of microplastics in the terrestrial environment but there remains a lack of data on the impacts of these terrestrial microplastics or their interaction with other terrestrial pollutants. We conducted Zn adsorption experiments using HDPE microplastics, derived from plastic bags. Zinc adsorption to microplastics was similar to that observed in soils, but in the presence of both soil and microplastics, preferential adsorption onto the soil was observed. In desorption experiments, desorption of Zn from microplastics and soils was minimal (earthworm guts desorption of 40 - 60% was observed for the microplastics compared to 2 - 15 % for the soils. In earthworm exposure experiments Lumbricus terrestris earthworms cultivated in soils containing 0.35% by mass of Zn-bearing plastic (236 - 4505 mg kg-1) ingested the microplastics with no evidence for either preferential feeding or avoidance. There was no evidence for an accumulation of the microplastics in the earthworm gut or for signs of toxicity. Our experiments demonstrate that earthworms will ingest microplastics and that microplastics can adsorb metals and act as vectors for metal exposure in soil invertebrates. However, for Zn, the risk associated with this exposure appears to be minimal.

  19. LANDSLIDES IDENTIFICATION USING AIRBORNE LASER SCANNING DATA DERIVED TOPOGRAPHIC TERRAIN ATTRIBUTES AND SUPPORT VECTOR MACHINE CLASSIFICATION

    Directory of Open Access Journals (Sweden)

    K. Pawłuszek

    2016-06-01

    Full Text Available Since the availability of high-resolution Airborne Laser Scanning (ALS data, substantial progress in geomorphological research, especially in landslide analysis, has been carried out. First and second order derivatives of Digital Terrain Model (DTM have become a popular and powerful tool in landslide inventory mapping. Nevertheless, an automatic landslide mapping based on sophisticated classifiers including Support Vector Machine (SVM, Artificial Neural Network or Random Forests is often computationally time consuming. The objective of this research is to deeply explore topographic information provided by ALS data and overcome computational time limitation. For this reason, an extended set of topographic features and the Principal Component Analysis (PCA were used to reduce redundant information. The proposed novel approach was tested on a susceptible area affected by more than 50 landslides located on Rożnów Lake in Carpathian Mountains, Poland. The initial seven PCA components with 90% of the total variability in the original topographic attributes were used for SVM classification. Comparing results with landslide inventory map, the average user’s accuracy (UA, producer’s accuracy (PA, and overall accuracy (OA were calculated for two models according to the classification results. Thereby, for the PCA-feature-reduced model UA, PA, and OA were found to be 72%, 76%, and 72%, respectively. Similarly, UA, PA, and OA in the non-reduced original topographic model, was 74%, 77% and 74%, respectively. Using the initial seven PCA components instead of the twenty original topographic attributes does not significantly change identification accuracy but reduce computational time.

  20. NOAA Composite Shoreline - Vectorized Shoreline Derived From NOAA-NOS Coastal Survey Maps and Aerial Photographs

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Composite Shoreline is primarily intended for high-resolution cartographic representation of the shoreline. It is a high-resolution vector shoreline based...

  1. Comparison of Potato and Asian Citrus Psyllid Adult and Nymph Transcriptomes Identified Vector Transcripts with Potential Involvement in Circulative, Propagative Liberibacter Transmission

    Directory of Open Access Journals (Sweden)

    Tonja W. Fisher

    2014-11-01

    Full Text Available The potato psyllid (PoP Bactericera cockerelli (Sulc and Asian citrus psyllid (ACP Diaphorina citri Kuwayama are the insect vectors of the fastidious plant pathogen, Candidatus Liberibacter solanacearum (CLso and Ca. L. asiaticus (CLas, respectively. CLso causes Zebra chip disease of potato and vein-greening in solanaceous species, whereas, CLas causes citrus greening disease. The reliance on insecticides for vector management to reduce pathogen transmission has increased interest in alternative approaches, including RNA interference to abate expression of genes essential for psyllid-mediated Ca. Liberibacter transmission. To identify genes with significantly altered expression at different life stages and conditions of CLso/CLas infection, cDNA libraries were constructed for CLso-infected and -uninfected PoP adults and nymphal instars. Illumina sequencing produced 199,081,451 reads that were assembled into 82,224 unique transcripts. PoP and the analogous transcripts from ACP adult and nymphs reported elsewhere were annotated, organized into functional gene groups using the Gene Ontology classification system, and analyzed for differential in silico expression. Expression profiles revealed vector life stage differences and differential gene expression associated with Liberibacter infection of the psyllid host, including invasion, immune system modulation, nutrition, and development.

  2. Novel endogenous retrovirus-derived transcript expressed in the bovine placenta is regulated by WNT signaling.

    Science.gov (United States)

    Sakurai, Toshihiro; Nakagawa, So; Bai, Hanako; Bai, Rulan; Kusama, Kazuya; Ideta, Atsushi; Aoyagi, Yoshito; Kaneko, Kazuyuki; Iga, Kosuke; Yasuda, Jiro; Miyazawa, Takayuki; Imakawa, Kazuhiko

    2017-10-10

    Endogenous retroviruses (ERVs) are involved in placentation; perhaps, the most well-known ERV s are the syncytins, actively transcribed env genes involved in cell-cell fusion and possible morphological variations. However, ERVs other than syncytins that play an important role in placental development have not been well characterized. To identify ERV genes expressed during the onset of placentation in the bovine species, we characterized the expression profiles of bovine conceptus transcripts during the peri-attachment period using RNA-seq analysis, and confirming some candidates through real-time PCR. Using in silico and PCR analyses, we identified a novel ERV proviral sequence derived from a gag region, designated bovine endogenous retroviruses (BERV)-K3, containing Gag _p10 and Gag _p24, zinc finger domain. Initial expression of this ERV in bovine conceptuses was on day 20 (day 0 = day of estrus), soon after conceptus attachment to the endometrial epithelium, and its high placental expression was maintained up to the middle of pregnancy. The BERV-K3 transcript was also found in the uterine luminal and glandular epithelia, liver, kidney, intestine, and skin. BERV-K3 is located on chromosome 7 and integrated within LOC100848658 , from which noncoding RNA could be transcribed. Furthermore, the expression of endogenous BERV-K3 in bovine trophoblast cell lines was induced by a WNT agonist, a signaling system common to genes expressed in placentas. These data support the argument that during the evolutionary process, mammals incorporated not only similar ERV sequences, but also ERV s unique to individual species. BERV-K3 is in the latter case, likely providing functions unique to ruminant gestation. © 2017 The Author(s).

  3. ROLES OF HUMAN AND VECTOR DERIVED PHENOTYPES OF DENV IN CAUSING HUMAN DISEASE- CAN MOSQUITO MEDIATION BE BYPASSED?

    Directory of Open Access Journals (Sweden)

    Rajan Joseph Payyappilly

    2017-03-01

    Full Text Available BACKGROUND Plasma membrane of midgut epithelial cells of the mosquito differs from that of human dendritic cells in composition with respect to protein and lipid content and posttranslational modifications, viz. glycosylation. Virus acquires its envelope from the host cell membrane. Expectedly therefore, such differences are reflected in the construction of its envelope, which may influence virulence. Lipid composition and glycosylation pattern of envelope protein E1 (with important roles in viral entry are different in the virus grown in insect cell lines and mammalian cells. As consequence, they have 'different modes' of cell entry each with role at different stages in disease course. Virions that initiate primary infection are mosquito derived; but then on, it is a phenotype of human cell origin that multiplies and spreads in the host. MATERIALS AND METHODS In a hospital-based yearlong prospective study conducted at our institute, we have tried to highlight (indirectly albeit, all important role of antibody mediated cell infection by DENV in the human host and how it modified disease process. RESULTS Mediation of the biological vector thus is required essential in ‘initiation’ of primary infection (emphasising the role of vector control as numero uno strategy for disease control; in the human tissues, thereafter, antibody mediated cell infection seems to take the lead role. CONCLUSION Mediation of the biological vector mosquito is required in natural cycle of transmission of DNV from man to man. Unique features of the envelope of 'mosquito derived' virions enabling them to enter human cells nonpermissive to human derived phenotype maybe capitalised and such mechanisms be targeted in designing vaccine or drugs against dengue and besides this emphasises the relative importance of vector control in dengue control.

  4. Differential transgene expression in brain cells in vivo and in vitro from AAV-2 vectors with small transcriptional control units

    International Nuclear Information System (INIS)

    Kuegler, S.; Lingor, P.; Schoell, U.; Zolotukhin, S.; Baehr, M.

    2003-01-01

    Adeno-associated- (AAV) based vectors are promising tools for gene therapy applications in several organs, including the brain, but are limited by their small genome size. Two short promoters, the human synapsin 1 gene promoter (hSYN) and the murine cytomegalovirus immediate early promoter (mCMV), were evaluated in bicistronic AAV-2 vectors for their expression profiles in cultured primary brain cells and in the rat brain. Whereas transgene expression from the hSYN promoter was exclusively neuronal, the murine CMV promoter targeted expression mainly to astrocytes in vitro and showed weak transgene expression in vivo in retinal and cortical neurons, but strong expression in thalamic neurons. We propose that neuron specific transgene expression in combination with enhanced transgene capacity will further substantially improve AAV based vector technology

  5. Comparison of random forests and support vector machine for real-time radar-derived rainfall forecasting

    Science.gov (United States)

    Yu, Pao-Shan; Yang, Tao-Chang; Chen, Szu-Yin; Kuo, Chen-Min; Tseng, Hung-Wei

    2017-09-01

    This study aims to compare two machine learning techniques, random forests (RF) and support vector machine (SVM), for real-time radar-derived rainfall forecasting. The real-time radar-derived rainfall forecasting models use the present grid-based radar-derived rainfall as the output variable and use antecedent grid-based radar-derived rainfall, grid position (longitude and latitude) and elevation as the input variables to forecast 1- to 3-h ahead rainfalls for all grids in a catchment. Grid-based radar-derived rainfalls of six typhoon events during 2012-2015 in three reservoir catchments of Taiwan are collected for model training and verifying. Two kinds of forecasting models are constructed and compared, which are single-mode forecasting model (SMFM) and multiple-mode forecasting model (MMFM) based on RF and SVM. The SMFM uses the same model for 1- to 3-h ahead rainfall forecasting; the MMFM uses three different models for 1- to 3-h ahead forecasting. According to forecasting performances, it reveals that the SMFMs give better performances than MMFMs and both SVM-based and RF-based SMFMs show satisfactory performances for 1-h ahead forecasting. However, for 2- and 3-h ahead forecasting, it is found that the RF-based SMFM underestimates the observed radar-derived rainfalls in most cases and the SVM-based SMFM can give better performances than RF-based SMFM.

  6. Gateway-compatible transposon vector to genetically modify human embryonic kidney and adipose-derived stromal cells.

    Science.gov (United States)

    Petrakis, Spyros; Raskó, Tamas; Mátés, Lajos; Ivics, Zoltan; Izsvák, Zsuzsanna; Kouzi-Koliakou, Kokkona; Koliakos, George

    2012-07-01

    The Gateway technology cloning system and transposon technology represent state-of-the-art laboratory techniques. Combination of these molecular tools allows rapid cloning of target genes into expression vectors. Here, we describe a novel Gateway technology-compatible transposon plasmid that combines the advantages of Gateway recombination cloning with the Sleeping Beauty (SB) transposon-mediated transgene integrations. In our system the transposition is catalyzed by the novel hyperactive SB100x transposase, and provides highly efficient and precise transgene integrations into the host genome. A Gateway-compatible transposon plasmid was generated in which the potential target gene can be fused with a yellow fluorescent protein (YFP) tag at the N-terminal. The vector utilizes the CAGGS promoter to control fusion protein expression. The transposon expression vector encoding the YFP-interferon-β protein (IFNB1) fusion protein together with the hyperactive SB100x transposase was used to generate stable cell lines in human embryonic kidney (HEK293) and rat adipose-derived stromal cells (ASC). ASCs and HEK293 cells stably expressed and secreted the human IFNB1 for up to 4 weeks after transfection. The generated Gateway-compatible transposon plasmid can be utilized for numerous experimental approaches, such as gene therapy or high-throughput screening methods in primary cells, representing a valuable molecular tool for laboratory applications. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Cloning vector

    Science.gov (United States)

    Guilfoyle, R.A.; Smith, L.M.

    1994-12-27

    A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site. 2 figures.

  8. Cloning vector

    Science.gov (United States)

    Guilfoyle, Richard A.; Smith, Lloyd M.

    1994-01-01

    A vector comprising a filamentous phage sequence containing a first copy of filamentous phage gene X and other sequences necessary for the phage to propagate is disclosed. The vector also contains a second copy of filamentous phage gene X downstream from a promoter capable of promoting transcription in a bacterial host. In a preferred form of the present invention, the filamentous phage is M13 and the vector additionally includes a restriction endonuclease site located in such a manner as to substantially inactivate the second gene X when a DNA sequence is inserted into the restriction site.

  9. Control of Transcriptional Fidelity by Active Center Tuning as Derived from RNA Polymerase Endonuclease Reaction*

    Science.gov (United States)

    Sosunova, Ekaterina; Sosunov, Vasily; Epshtein, Vitaly; Nikiforov, Vadim; Mustaev, Arkady

    2013-01-01

    Precise transcription by cellular RNA polymerase requires the efficient removal of noncognate nucleotide residues that are occasionally incorporated. Mis-incorporation causes the transcription elongation complex to backtrack, releasing a single strand 3′-RNA segment bearing a noncognate residue, which is hydrolyzed by the active center that carries two Mg2+ ions. However, in most x-ray structures only one Mg2+ is present. This Mg2+ is tightly bound to the active center aspartates, creating an inactive stable state. The first residue of the single strand RNA segment in the backtracked transcription elongation complex strongly promotes transcript hydrolytic cleavage by establishing a network of interactions that force a shift of stably bound Mg2+ to release some of its aspartate coordination valences for binding to the second Mg2+ thus enabling catalysis. Such a rearrangement that we call active center tuning (ACT) occurs when all recognition contacts of the active center-bound RNA segment are established and verified by tolerance to stress. Transcription factor Gre builds on the ACT mechanism in the same reaction by increasing the retention of the second Mg2+ and by activating the attacking water, causing 3000–4000-fold reaction acceleration and strongly reinforcing proofreading. The unified mechanism for RNA synthesis and degradation by RNA polymerase predicts that ACT also executes NTP selection thereby contributing to high transcription fidelity. PMID:23283976

  10. Control of transcriptional fidelity by active center tuning as derived from RNA polymerase endonuclease reaction.

    Science.gov (United States)

    Sosunova, Ekaterina; Sosunov, Vasily; Epshtein, Vitaly; Nikiforov, Vadim; Mustaev, Arkady

    2013-03-01

    Precise transcription by cellular RNA polymerase requires the efficient removal of noncognate nucleotide residues that are occasionally incorporated. Mis-incorporation causes the transcription elongation complex to backtrack, releasing a single strand 3'-RNA segment bearing a noncognate residue, which is hydrolyzed by the active center that carries two Mg(2+) ions. However, in most x-ray structures only one Mg(2+) is present. This Mg(2+) is tightly bound to the active center aspartates, creating an inactive stable state. The first residue of the single strand RNA segment in the backtracked transcription elongation complex strongly promotes transcript hydrolytic cleavage by establishing a network of interactions that force a shift of stably bound Mg(2+) to release some of its aspartate coordination valences for binding to the second Mg(2+) thus enabling catalysis. Such a rearrangement that we call active center tuning (ACT) occurs when all recognition contacts of the active center-bound RNA segment are established and verified by tolerance to stress. Transcription factor Gre builds on the ACT mechanism in the same reaction by increasing the retention of the second Mg(2+) and by activating the attacking water, causing 3000-4000-fold reaction acceleration and strongly reinforcing proofreading. The unified mechanism for RNA synthesis and degradation by RNA polymerase predicts that ACT also executes NTP selection thereby contributing to high transcription fidelity.

  11. Algorithms for Computing the Magnetic Field, Vector Potential, and Field Derivatives for Circular Current Loops in Cylindrical Coordinates

    Energy Technology Data Exchange (ETDEWEB)

    Walstrom, Peter Lowell [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-08-24

    A numerical algorithm for computing the field components Br and Bz and their r and z derivatives with open boundaries in cylindrical coordinates for circular current loops is described. An algorithm for computing the vector potential is also described. For the convenience of the reader, derivations of the final expressions from their defining integrals are given in detail, since their derivations (especially for the field derivatives) are not all easily found in textbooks. Numerical calculations are based on evaluation of complete elliptic integrals using the Bulirsch algorithm cel. Since cel can evaluate complete elliptic integrals of a fairly general type, in some cases the elliptic integrals can be evaluated without first reducing them to forms containing standard Legendre forms. The algorithms avoid the numerical difficulties that many of the textbook solutions have for points near the axis because of explicit factors of 1=r or 1=r2 in the some of the expressions.

  12. Algorithms for Computing the Magnetic Field, Vector Potential, and Field Derivatives for a Thin Solenoid with Uniform Current Density

    Energy Technology Data Exchange (ETDEWEB)

    Walstrom, Peter Lowell [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-08-07

    A numerical algorithm for computing the field components Br and Bz and their r and z derivatives with open boundaries in cylindrical coordinates for radially thin solenoids with uniform current density is described in this note. An algorithm for computing the vector potential Aθ is also described. For the convenience of the reader, derivations of the final expressions from their defining integrals are given in detail, since their derivations are not all easily found in textbooks. Numerical calculations are based on evaluation of complete elliptic integrals using the Bulirsch algorithm cel. The (apparently) new feature of the algorithms described in this note applies to cases where the field point is outside of the bore of the solenoid and the field-point radius approaches the solenoid radius. Since the elliptic integrals of the third kind normally used in computing Bz and Aθ become infinite in this region of parameter space, fields for points with the axial coordinate z outside of the ends of the solenoid and near the solenoid radius are treated by use of elliptic integrals of the third kind of modified argument, derived by use of an addition theorem. Also, the algorithms also avoid the numerical difficulties the textbook solutions have for points near the axis arising from explicit factors of 1/r or 1/r2 in the some of the expressions.

  13. Plastic Bag Derived-Microplastics as a Vector for Metal Exposure in Terrestrial Invertebrates.

    Science.gov (United States)

    Hodson, Mark E; Duffus-Hodson, Calum A; Clark, Andy; Prendergast-Miller, Miranda T; Thorpe, Karen L

    2017-04-18

    Microplastics are widespread contaminants in terrestrial environments but comparatively little is known about interactions between microplastics and common terrestrial contaminants such as zinc (Zn). In adsorption experiments fragmented HDPE bags c. one mm 2 in size showed similar sorption characteristics to soil. However, when present in combination with soil, concentrations of adsorbed Zn on a per mass basis were over an order of magnitude lower on microplastics. Desorption of the Zn was minimal from both microplastics and soil in synthetic soil solution (0.01 M CaCl 2 ), but in synthetic earthworm guts desorption was higher from microplastics (40-60%) than soil (2-15%), suggesting microplastics could increase Zn bioavailability. Individual Lumbricus terrestris earthworms exposed for 28 days in mesocosms of 260 g moist soil containing 0.35 wt % of Zn-bearing microplastic (236-4505 mg kg -1 ) ingested the microplastics, but there was no evidence of Zn accumulation, mortality, or weight change. Digestion of the earthworms showed that they did not retain microplastics in their gut. These findings indicate that microplastics could act as vectors to increase metal exposure in earthworms, but that the associated risk is unlikely to be significant for essential metals such as Zn that are well regulated by metabolic processes.

  14. Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Chen, Xiaoxu; Yang, Xiaoyu; Shen, Yu; Hou, Jin; Bao, Xiaoming

    2017-05-19

    Malonyl-CoA is a precursor of a variety of compounds such as polyketides and flavonoids. In Saccharomyces cerevisiae, malonyl-CoA concentration is tightly regulated and therefore maintained at a very low level, limiting the production of malonyl-CoA-derived chemicals. Here we manipulated the phospholipid synthesis transcriptional regulators to control the malonyl-CoA levels and increase the downstream product. Through manipulating different regulators including Ino2p, Ino4p, Opi1p, and a series of synthetic Ino2p variants, combining with studying the inositol and choline effect, the engineered strain achieved a 9-fold increase of the titer of malonyl-CoA-derived product 3-hydroxypropionic acid, which is among the highest improvement relative to previously reported strategies. Our study provides a new strategy to regulate malonyl-CoA availability and will contribute to the production of other highly valued malonyl-CoA-derived chemicals.

  15. Distinct malaria parasite sporozoites reveal transcriptional changes that cause differential tissue infection competence in the mosquito vector and mammalian host.

    Science.gov (United States)

    Mikolajczak, Sebastian A; Silva-Rivera, Hilda; Peng, Xinxia; Tarun, Alice S; Camargo, Nelly; Jacobs-Lorena, Vanessa; Daly, Thomas M; Bergman, Lawrence W; de la Vega, Patricia; Williams, Jack; Aly, Ahmed S I; Kappe, Stefan H I

    2008-10-01

    The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes).

  16. Distinct Malaria Parasite Sporozoites Reveal Transcriptional Changes That Cause Differential Tissue Infection Competence in the Mosquito Vector and Mammalian Host▿

    Science.gov (United States)

    Mikolajczak, Sebastian A.; Silva-Rivera, Hilda; Peng, Xinxia; Tarun, Alice S.; Camargo, Nelly; Jacobs-Lorena, Vanessa; Daly, Thomas M.; Bergman, Lawrence W.; de la Vega, Patricia; Williams, Jack; Aly, Ahmed S. I.; Kappe, Stefan H. I.

    2008-01-01

    The malaria parasite sporozoite transmission stage develops and differentiates within parasite oocysts on the Anopheles mosquito midgut. Successful inoculation of the parasite into a mammalian host is critically dependent on the sporozoite's ability to first infect the mosquito salivary glands. Remarkable changes in tissue infection competence are observed as the sporozoites transit from the midgut oocysts to the salivary glands. Our microarray analysis shows that compared to oocyst sporozoites, salivary gland sporozoites upregulate expression of at least 124 unique genes. Conversely, oocyst sporozoites show upregulation of at least 47 genes (upregulated in oocyst sporozoites [UOS genes]) before they infect the salivary glands. Targeted gene deletion of UOS3, encoding a putative transmembrane protein with a thrombospondin repeat that localizes to the sporozoite secretory organelles, rendered oocyst sporozoites unable to infect the mosquito salivary glands but maintained the parasites' liver infection competence. This phenotype demonstrates the significance of differential UOS expression. Thus, the UIS-UOS gene classification provides a framework to elucidate the infectivity and transmission success of Plasmodium sporozoites on a whole-genome scale. Genes identified herein might represent targets for vector-based transmission blocking strategies (UOS genes), as well as strategies that prevent mammalian host infection (UIS genes). PMID:18710954

  17. [Exosomes Derived from Mesenchymal Stem Cells--the Future Ideal Vector of Biological Therapy].

    Science.gov (United States)

    Zhang, Juan; Shi, Jing-Shu; Li, Jian

    2015-08-01

    MSC-exosomes are homogeneous menbrane vesicles with diameter 40-100 nm, derived from mesenchymal stem cells at physiological or pathology conditions. MSC-exosomes contain a great quantity and a wide variety of bioactive substances, such as proteins and miRNA. MSC-exosomes transfer bioactive substances to recipient cells to affect their functions through membrane fusion or endocytosis, which like the storage pools of signal vehicles for cell-to-cell comunication in vivo. MSC-exosomes can mimic the beneficial effect of MSC treatment, such as the promotion of tissue repair or the immune regulation. The biological property and functions of MSC-exosomes are reviwed in this article.

  18. Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative.

    Science.gov (United States)

    Kumarasamy, Vishnu Muthuraj; Sun, Daekyu

    2017-07-01

    Dominant-activating mutations in the RET (rearranged during transfection) proto-oncogene, which encodes a receptor tyrosine kinase, is often associated with the development of medullary thyroid carcinoma (MTC). The proximal promoter region of the RET gene consists of a guanine-rich sequence containing five runs of three consecutive guanine residues that serve as the binding site for transcriptional factors. As we have recently shown, this stretch of nucleotides in the promoter region is highly dynamic in nature and tend to form non-B DNA secondary structures called G-quadruplexes, which suppress the transcription of the RET gene. In the present study, ellipticine and its derivatives were identified as excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD) spectroscopic studies revealed that the incorporation of a piperidine ring in an ellipticine derivative, NSC311153 improves its binding with the G-quadruplex structure and the stability induced by this compound is more potent than ellipticine. Furthermore, this compound also interfered with the transcriptional mechanism of the RET gene in an MTC derived cell line, TT cells and significantly decreased the endogenous RET protein expression. We demonstrated the specificity of NSC311153 by using papillary thyroid carcinoma (PTC) cells, the TPC1 cell line which lacks the G-quadruplex forming sequence in the promoter region due to chromosomal rearrangement. The RET downregulation selectively suppresses cell proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways in the TT cells. In the present study, we also showed that the systemic administration of a water soluble NSC311153 analog in a mouse MTC xenograft model inhibited the tumor growth through RET downregulation.

  19. A fiber-modified adenoviral vector interacts with immunoevasion molecules of the B7 family at the surface of murine leukemia cells derived from dormant tumors

    Directory of Open Access Journals (Sweden)

    Rogée Sophie

    2011-08-01

    Full Text Available Abstract Tumor cells can escape the immune system by overexpressing molecules of the B7 family, e.g. B7-H1 (PD-L1 or CD86, which suppresses the anti-tumor T-cell responses through binding to the PD-1 receptor, and similarly for B7.1 (CD80, through binding to CTLA-4. Moreover, direct interactions between B7-H1 and B7.1 molecules are also likely to participate in the immunoevasion mechanism. In this study, we used a mouse model of tumor dormancy, DA1-3b leukemia cells. We previously showed that a minor population of DA1-3b cells persists in equilibrium with the immune system for long periods of time, and that the levels of surface expression of B7-H1 and B7.1 molecules correlates with the dormancy time. We found that leukemia cells DA1-3b/d365 cells, which derived from long-term dormant tumors and overexpressed B7-H1 and B7.1 molecules, were highly permissive to Ad5FB4, a human adenovirus serotype 5 (Ad5 vector pseudotyped with chimeric human-bovine fibers. Both B7-H1 and B7.1 were required for Ad5FB4-cell binding and entry, since (i siRNA silencing of one or the other B7 gene transcript resulted in a net decrease in the cell binding and Ad5FB4-mediated transduction of DA1-3b/d365; and (ii plasmid-directed expression of B7.1 and B7-H1 proteins conferred to Ad5FB4-refractory human cells a full permissiveness to this vector. Binding data and flow cytometry analysis suggested that B7.1 and B7-H1 molecules played different roles in Ad5FB4-mediated transduction of DA1-3b/d365, with B7.1 involved in cell attachment of Ad5FB4, and B7-H1 in Ad5FB4 internalization. BRET analysis showed that B7.1 and B7-H1 formed heterodimeric complexes at the cell surface, and that Ad5FB4 penton, the viral capsomere carrying the fiber projection, could negatively interfere with the formation of B7.1/B7-H1 heterodimers, or modify their conformation. As interactors of B7-H1/B7.1 molecules, Ad5FB4 particles and/or their penton capsomeres represent potential therapeutic agents

  20. Regulatory and Functional Connection of Microphthalmia-Associated Transcription Factor and Anti-Metastatic Pigment Epithelium Derived Factor in Melanoma

    Directory of Open Access Journals (Sweden)

    Asunción Fernández-Barral

    2014-06-01

    Full Text Available Pigment epithelium-derived factor (PEDF, a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

  1. RNA-Seq derived identification of differential transcription in the chrysanthemum leaf following inoculation with Alternaria tenuissima.

    Science.gov (United States)

    Li, Huiyun; Chen, Sumei; Song, Aiping; Wang, Haibin; Fang, Weimin; Guan, Zhiyong; Jiang, Jiafu; Chen, Fadi

    2014-01-04

    A major production constraint on the important ornamental species chrysanthemum is black spot which is caused by the necrotrophic fungus Alternaria tenuissima. The molecular basis of host resistance to A. tenuissima has not been studied as yet in any detail. Here, high throughput sequencing was taken to characterize the transcriptomic response of the chrysanthemum leaf to A. tenuissima inoculation. The transcriptomic data was acquired using RNA-Seq technology, based on the Illumina HiSeq™ 2000 platform. Four different libraries derived from two sets of leaves harvested from either inoculated or mock-inoculated plants were characterized. Over seven million clean reads were generated from each library, each corresponding to a coverage of >350,000 nt. About 70% of the reads could be mapped to a set of chrysanthemum unigenes. Read frequency was used as a measure of transcript abundance and therefore as an identifier of differential transcription in the four libraries. The differentially transcribed genes identified were involved in photosynthesis, pathogen recognition, reactive oxygen species generation, cell wall modification and phytohormone signalling; in addition, a number of varied transcription factors were identified. A selection of 23 of the genes was transcription-profiled using quantitative RT-PCR to validate the RNA-Seq output. A substantial body of chrysanthemum transcriptomic sequence was generated, which led to a number of insights into the molecular basis of the host response to A. tenuissima infection. Although most of the differentially transcribed genes were up-regulated by the presence of the pathogen, those involved in photosynthesis were down-regulated.

  2. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  3. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  4. Broad genomic and transcriptional analysis reveals a highly derived genome in dinoflagellate mitochondria

    Directory of Open Access Journals (Sweden)

    Keeling Patrick J

    2007-09-01

    Full Text Available Abstract Background Dinoflagellates comprise an ecologically significant and diverse eukaryotic phylum that is sister to the phylum containing apicomplexan endoparasites. The mitochondrial genome of apicomplexans is uniquely reduced in gene content and size, encoding only three proteins and two ribosomal RNAs (rRNAs within a highly compacted 6 kb DNA. Dinoflagellate mitochondrial genomes have been comparatively poorly studied: limited available data suggest some similarities with apicomplexan mitochondrial genomes but an even more radical type of genomic organization. Here, we investigate structure, content and expression of dinoflagellate mitochondrial genomes. Results From two dinoflagellates, Crypthecodinium cohnii and Karlodinium micrum, we generated over 42 kb of mitochondrial genomic data that indicate a reduced gene content paralleling that of mitochondrial genomes in apicomplexans, i.e., only three protein-encoding genes and at least eight conserved components of the highly fragmented large and small subunit rRNAs. Unlike in apicomplexans, dinoflagellate mitochondrial genes occur in multiple copies, often as gene fragments, and in numerous genomic contexts. Analysis of cDNAs suggests several novel aspects of dinoflagellate mitochondrial gene expression. Polycistronic transcripts were found, standard start codons are absent, and oligoadenylation occurs upstream of stop codons, resulting in the absence of termination codons. Transcripts of at least one gene, cox3, are apparently trans-spliced to generate full-length mRNAs. RNA substitutional editing, a process previously identified for mRNAs in dinoflagellate mitochondria, is also implicated in rRNA expression. Conclusion The dinoflagellate mitochondrial genome shares the same gene complement and fragmentation of rRNA genes with its apicomplexan counterpart. However, it also exhibits several unique characteristics. Most notable are the expansion of gene copy numbers and their arrangements

  5. A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.

    Directory of Open Access Journals (Sweden)

    Katherine James

    Full Text Available Fatigue is a debilitating condition with a significant impact on patients' quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren's Syndrome (pSS, a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms.Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren's Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA was used as a feature selection technique for input into a support vector machine (SVM classifier. Classification was assessed using area under curve (AUC of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W.Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W 0.002 and 0.525 (SE(W 0.006, respectively.Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

  6. A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren’s Syndrome

    Science.gov (United States)

    James, Katherine; Al-Ali, Shereen; Tarn, Jessica; Cockell, Simon J.; Gillespie, Colin S.; Hindmarsh, Victoria; Locke, James; Mitchell, Sheryl; Lendrem, Dennis; Bowman, Simon; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Hunter, John A.; Gupta, Monica; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Griffiths, Bridget; Wipat, Anil; Newton, Julia; Jones, David E.; Isaacs, John; Hallinan, Jennifer; Ng, Wan-Fai

    2015-01-01

    Background Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Methods Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren’s Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Results Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. Conclusions Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS. PMID:26694930

  7. Regulation of brain-derived neurotrophic factor exon IV transcription through calcium responsive elements in cortical neurons.

    Directory of Open Access Journals (Sweden)

    Fei Zheng

    Full Text Available Activity-dependent transcription of brain-derived neurotrophic factor (BDNF has been studied as an important model to elucidate the mechanisms underlying numerous aspects of neuroplasticity. It has been extensively emphasized that Ca(2+ influx through different routes may have significantly different effects on BDNF transcription. Here, we examined the regulatory property of the major calcium responsive elements (CaRE in BDNF promoter IV in cultured rat cortical neurons. BDNF promoter IV, as well as CaRE1 and CaRE3, was significantly activated by Ca(2+ influx through L-type voltage-gated calcium channel (L-VGCC or NMDA receptor (NMDAR. However, the L-VGCC- and NMDAR-mediated activation of CaRE was differentially regulated by different Ca(2+-stimulated protein kinases. Specifically, PKA, CaMKI, and CaMKIV activity were required for L-VGCC-, but not NMDAR-mediated CaRE1 activation. CaMKI activity was required for NMDAR- but not L-VGCC-mediated CaRE3 activation. Surprisingly, the activation of CaRF, a previously identified transcription factor for CaRE1, was stimulated via L-VGCC but not NMDAR, and required MEK, PI3K and CaMKII activity. These results suggest a new working model that activity-dependent BDNF IV up-regulation may be coordinately mediated by CaRE1 and CaRE3 activity, which show different responses to Ca(2+-stimulated kinases. Our data also explain how the individual cis-element in BDNF promoter is distinctively coupled to different Ca(2+ routes.

  8. Prostate-Derived Ets Transcription Factor Overexpression is Associated with Nodal Metastasis, Hormone Receptor Positivity in Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Simon Turcotte

    2007-10-01

    Full Text Available Prostate-derived Ets transcription factor (PDEF has recently been associated with invasive breast cancer, but no expression profile has been defined in clinical specimens. We undertook a comprehensive PDEF transcriptional expression study of 86 breast cancer clinical specimens, several cell lines, normal tissues. PDEF expression profile was analyzed according to standard clinicopathologic parameters, compared with hormonal receptor, HER-2/neu status, to the expression of the new tumor biomarker Dikkopf-1 (DKK1. Wide ranging PDEF overexpression was observed in 74% of tested tumors, at higher levels than the average expression found in normal breasts. High PDEF expression was associated with hormone receptor positivity (P < .001, moderate to good differentiation (less than grade III, P = .01, dissemination to axillary lymph nodes (P = .002. PDEF was an independent risk factor for nodal involvement (multivariate analysis, odds ratio 1.250, P = .002. It was expressed in a different subgroup compared to DKK1-expressing tumors (P < .001. Our data imply that PDEF mRNA expression could be useful in breast cancer molecular staging. Further insights into PDEF functions at the protein level, possible links with hormone receptors biology, bear great potential for new therapeutic avenues.

  9. Integration event induced changes in recombinant protein productivity in Pichia pastoris discovered by whole genome sequencing and derived vector optimization.

    Science.gov (United States)

    Schwarzhans, Jan-Philipp; Wibberg, Daniel; Winkler, Anika; Luttermann, Tobias; Kalinowski, Jörn; Friehs, Karl

    2016-05-20

    The classic AOX1 replacement approach is still one of the most often used techniques for expression of recombinant proteins in the methylotrophic yeast Pichia pastoris. Although this approach is largely successful, it frequently delivers clones with unpredicted production characteristics and a work-intense screening process is required to find the strain with desired productivity. In this project 845 P. pastoris clones, transformed with a GFP expression cassette, were analyzed for their methanol-utilization (Mut)-phenotypes, GFP gene expression levels and gene copy numbers. Several groups of strains with irregular features were identified. Such features include GFP expression that is markedly higher or lower than expected based on gene copy number as well as strains that grew under selective conditions but where the GFP gene cassette and its expression could not be detected. From these classes of strains 31 characteristic clones were selected and their genomes sequenced. By correlating the assembled genome data with the experimental phenotypes novel insights were obtained. These comprise a clear connection between productivity and cassette-to-cassette orientation in the genome, the occurrence of false-positive clones due to a secondary recombination event, and lower total productivity due to the presence of untransformed cells within the isolates were discovered. To cope with some of these problems, the original vector was optimized by replacing the AOX1 terminator, preventing the occurrence of false-positive clones due to the secondary recombination event. Standard methods for transformation of P. pastoris led to a multitude of unintended and sometimes detrimental integration events, lowering total productivity. By documenting the connections between productivity and integration event we obtained a deeper understanding of the genetics of mutation in P. pastoris. These findings and the derived improved mutagenesis and transformation procedures and tools will help

  10. Genome-Wide Transcription and Functional Analyses Reveal Heterogeneous Molecular Mechanisms Driving Pyrethroids Resistance in the Major Malaria Vector Anopheles funestus Across Africa.

    Science.gov (United States)

    Riveron, Jacob M; Ibrahim, Sulaiman S; Mulamba, Charles; Djouaka, Rousseau; Irving, Helen; Wondji, Murielle J; Ishak, Intan H; Wondji, Charles S

    2017-06-07

    Pyrethroid resistance in malaria vector, An. funestus is increasingly reported across Africa, threatening the sustainability of pyrethroid-based control interventions, including long lasting insecticidal nets (LLINs). Managing this problem requires understanding of the molecular basis of the resistance from different regions of the continent, to establish whether it is being driven by a single or independent selective events. Here, using a genome-wide transcription profiling of pyrethroid resistant populations from southern (Malawi), East (Uganda), and West Africa (Benin), we investigated the molecular basis of resistance, revealing strong differences between the different African regions. The duplicated cytochrome P450 genes ( CYP6P9a and CYP6P9b ) which were highly overexpressed in southern Africa are not the most upregulated in other regions, where other genes are more overexpressed, including GSTe2 in West (Benin) and CYP9K1 in East (Uganda). The lack of directional selection on both CYP6P9a and CYP6P9b in Uganda in contrast to southern Africa further supports the limited role of these genes outside southern Africa. However, other genes such as the P450 CYP9J11 are commonly overexpressed in all countries across Africa. Here, CYP9J11 is functionally characterized and shown to confer resistance to pyrethroids and moderate cross-resistance to carbamates (bendiocarb). The consistent overexpression of GSTe2 in Benin is coupled with a role of allelic variation at this gene as GAL4-UAS transgenic expression in Drosophila flies showed that the resistant 119F allele is highly efficient in conferring both DDT and permethrin resistance than the L119. The heterogeneity in the molecular basis of resistance and cross-resistance to insecticides in An. funestus populations throughout sub-Saharan African should be taken into account in designing resistance management strategies. Copyright © 2017 Riveron et al.

  11. Optimal construction and delivery of dual-functioning lentiviral vectors for type I collagen-suppressed chondrogenesis in synovium-derived mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Feng; Yao, Yongchang; Zhou, Ruijie; Su, Kai; Citra, Fudiman; Wang, Dong-An

    2011-06-01

    This study aims to deliver both transforming growth factor β3 (TGF-β3) and shRNA targeting type I collagen (Col I) by optimal construction and application of various dual-functioning lentiviral vectors to induce Col I-suppressed chondrogenesis in synovium-derived mesenchymal stem cells (SMSCs). We constructed four lentiviral vectors (LV-1, LV-2, LV-3 and LV-4) with various arrangements of the two expression cassettes in different positions and orientations. Col I inhibition efficiency and chondrogenic markers were assessed with qPCR, ELISA and staining techniques. Among the four vectors, LV-1 has two distant and reversely oriented cassettes, LV-2 has two distant and same-oriented cassettes, LV-3 has two proximal and reversely oriented cassettes, and LV-4 has two proximal and same-oriented cassettes. Col I and chondrogenic markers, including type II collagen (Col II), aggrecan and glycosaminoglycan (GAG), were examined in SMSCs cultured in 3-D alginate hydrogel. All of the four vectors showed distinct effects in Col I level as well as diverse inductive efficiencies in upregulation of the cartilaginous markers. Based on real-time PCR results, LV-1 was optimal towards Col I-suppressed chondrogenesis. LV-1 vector is competent to promote Col I-suppressed chondrogenesis in SMSCs.

  12. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex

    Directory of Open Access Journals (Sweden)

    Geller Alfred I

    2009-06-01

    Full Text Available Abstract Background Herpes Simplex Virus (HSV-1 gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (~99% of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase, or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days. These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. Results A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Conclusion Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve

  13. Improved long-term expression from helper virus-free HSV-1 vectors packaged using combinations of mutated HSV-1 proteins that include the UL13 protein kinase and specific components of the VP16 transcriptional complex.

    Science.gov (United States)

    Liu, Meng; Wang, Xiaodan; Geller, Alfred I

    2009-06-16

    Herpes Simplex Virus (HSV-1) gene expression is thought to shut off recombinant gene expression from HSV-1 vectors; however, in a helper virus-free HSV-1 vector system, a number of promoters support only short-term expression. These results raise the paradox that recombinant gene expression remains short-term even in the absence of almost all (approximately 99%) of the HSV-1 genome, HSV-1 genes, and HSV-1 gene expression. To resolve this paradox, we hypothesized that specific proteins in the HSV-1 virus particle shut off recombinant gene expression. In two earlier studies, we examined the effects on recombinant gene expression of packaging vectors using specific mutated HSV-1 proteins. We found that vectors packaged using mutated UL13 (a protein kinase), or VP16, or UL46 and/or UL47 (components of the VP16 transcriptional complex) supported improved long-term expression, and vectors packaged using mutated UL46 and/or UL47 also supported improved gene transfer (numbers of cells at 4 days). These results suggested the hypothesis that specific proteins in the HSV-1 particle act by multiple pathways to reduce recombinant gene expression. To test this hypothesis, we examined combinations of mutated proteins that included both UL13 and specific components of the VP16 transcriptional complex. A HSV-1 vector containing a neuronal-specific promoter was packaged using specific combinations of mutated proteins, and the resulting vector stocks were tested in the rat striatum. For supporting long-term expression, the preferred combination of mutated HSV-1 proteins was mutated UL13, UL46, and UL47. Vectors packaged using this combination of mutated proteins supported a higher efficiency of gene transfer and high levels expression for 3 months, the longest time examined. Vector particles containing this combination of mutated HSV-1 proteins improve recombinant gene expression. Implications of these results for strategies to further improve long-term expression are discussed

  14. In silico engineering and optimization of Transcription Activator-Like Effectors and their derivatives for improved DNA binding predictions.

    KAUST Repository

    Piatek, Marek J.

    2015-12-01

    Transcription Activator-Like Effectors (TALEs) can be used as adaptable DNAbinding modules to create site-specific chimeric nucleases or synthetic transcriptional regulators. The central repeat domain mediates specific DNA binding via hypervariable repeat di-residues (RVDs). This DNA-Binding Domain can be engineered to bind preferentially to any user-selected DNA sequence if engineered appropriately. Therefore, TALEs and their derivatives have become indispensable molecular tools in site-specific manipulation of genes and genomes. This thesis revolves around two problems: in silico design and improved binding site prediction of TALEs. In the first part, a study is shown where TALEs are successfully designed in silico and validated in laboratory to yield the anticipated effects on selected genes. Software is developed to accompany the process of designing and prediction of binding sites. I expanded the functionality of the software to be used as a more generic set of tools for the design, target and offtarget searching. Part two contributes a method and associated toolkit developed to allow users to design in silico optimized synthetic TALEs with user-defined specificities for various experimental purposes. This method is based on a mutual relationship of three consecutive tandem repeats in the DNA-binding domain. This approach revealed positional and compositional bias behind the binding of TALEs to DNA. In conclusion, I developed methods, approaches, and software to enhance the functionality of synthetic TALEs, which should improve understanding of TALEs biology and will further advance genome-engineering applications in various organisms and cell types.

  15. Statistics of the derivatives of complex signal derived from Riesz transform and its application to pseudo-Stokes vector correlation for speckle displacement measurement

    DEFF Research Database (Denmark)

    Zhang, Shun; Yang, Yi; Hanson, Steen Grüner

    2015-01-01

    As an improvement of the well-known intensity correlation used in conventional electronic speckle photography, we have proposed a new technique, to the best of our knowledge, for displacement measurement referred to as pseudo-Stokes vector correlation (PSVC). To provide a theoretical background f...

  16. An application of remotely derived climatological fields for risk assessment of vector-borne diseases : a spatial study of filariasis prevalence in the Nile Delta, Egypt.

    Energy Technology Data Exchange (ETDEWEB)

    Crombie, M. K.; Gillies, R. R.; Arvidson, R. E.; Brookmeyer, P.; Weil, G. J.; Sultan, M.; Harb, M.; Environmental Research; Washington Univ.; Utah State Univ.; Egyptian Ministry of Health

    1999-12-01

    This paper applies a relatively straightforward remote sensing method that is commonly used to derive climatological variables. Measurements of surface reflectance and surface radiant temperature derived from Landsat Thematic Mapper data were used to create maps of fractional vegetation and surface soil moisture availability for the southern Nile delta in Egypt. These climatological variables were subsequently used to investigate the spatial distribution of the vector borne disease Bancroftian filariasis in the Nile delta where it is focally endemic and a growing problem. Averaged surface soil moisture values, computed for a 5-km border area around affected villages, were compared to filariasis prevalence rates. Prevalence rates were found to be negligible below a critical soil moisture value of 0.2, presumably because of a lack of appropriate breeding sites for the Culex Pipiens mosquito species. With appropriate modifications to account for local conditions and vector species, this approach should be useful as a means to map, predict, and control insect vector-borne diseases that critically depend on wet areas for propagation. This type of analysis may help governments and health agencies that are involved in filariasis control to better focus limited resources to identifiable high-risk areas.

  17. Characterization of rice black-streaked dwarf virus- and rice stripe virus-derived siRNAs in singly and doubly infected insect vector Laodelphax striatellus.

    Directory of Open Access Journals (Sweden)

    Junmin Li

    Full Text Available Replication of RNA viruses in insect cells triggers an antiviral defense that is mediated by RNA interference (RNAi which generates viral-derived small interfering RNAs (siRNAs. However, it is not known whether an antiviral RNAi response is also induced in insects by reoviruses, whose double-stranded RNA genome replication is thought to occur within core particles. Deep sequencing of small RNAs showed that when the small brown planthopper (Laodelphax striatellus was infected by Rice black-streaked dwarf virus (RBSDV (Reoviridae; Fijivirus, more viral-derived siRNAs accumulated than when the vector insect was infected by Rice stripe virus (RSV, a negative single-stranded RNA virus. RBSDV siRNAs were predominantly 21 and 22 nucleotides long and there were almost equal numbers of positive and negative sense. RBSDV siRNAs were frequently generated from hotspots in the 5'- and 3'-terminal regions of viral genome segments but these hotspots were not associated with any predicted RNA secondary structures. Under laboratory condition, L. striatellus can be infected simultaneously with RBSDV and RSV. Double infection enhanced the accumulation of particular genome segments but not viral coat protein of RBSDV and correlated with an increase in the abundance of siRNAs derived from RBSDV. The results of this study suggest that reovirus replication in its insect vector potentially induces an RNAi-mediated antiviral response.

  18. Characterization of rice black-streaked dwarf virus- and rice stripe virus-derived siRNAs in singly and doubly infected insect vector Laodelphax striatellus.

    Science.gov (United States)

    Li, Junmin; Andika, Ida Bagus; Shen, Jiangfeng; Lv, Yuanda; Ji, Yongqiang; Sun, Liying; Chen, Jianping

    2013-01-01

    Replication of RNA viruses in insect cells triggers an antiviral defense that is mediated by RNA interference (RNAi) which generates viral-derived small interfering RNAs (siRNAs). However, it is not known whether an antiviral RNAi response is also induced in insects by reoviruses, whose double-stranded RNA genome replication is thought to occur within core particles. Deep sequencing of small RNAs showed that when the small brown planthopper (Laodelphax striatellus) was infected by Rice black-streaked dwarf virus (RBSDV) (Reoviridae; Fijivirus), more viral-derived siRNAs accumulated than when the vector insect was infected by Rice stripe virus (RSV), a negative single-stranded RNA virus. RBSDV siRNAs were predominantly 21 and 22 nucleotides long and there were almost equal numbers of positive and negative sense. RBSDV siRNAs were frequently generated from hotspots in the 5'- and 3'-terminal regions of viral genome segments but these hotspots were not associated with any predicted RNA secondary structures. Under laboratory condition, L. striatellus can be infected simultaneously with RBSDV and RSV. Double infection enhanced the accumulation of particular genome segments but not viral coat protein of RBSDV and correlated with an increase in the abundance of siRNAs derived from RBSDV. The results of this study suggest that reovirus replication in its insect vector potentially induces an RNAi-mediated antiviral response.

  19. New type of Sendai virus vector provides transgene-free iPS cells derived from chimpanzee blood.

    Directory of Open Access Journals (Sweden)

    Yasumitsu Fujie

    Full Text Available Induced pluripotent stem cells (iPSCs are potentially valuable cell sources for disease models and future therapeutic applications; however, inefficient generation and the presence of integrated transgenes remain as problems limiting their current use. Here, we developed a new Sendai virus vector, TS12KOS, which has improved efficiency, does not integrate into the cellular DNA, and can be easily eliminated. TS12KOS carries KLF4, OCT3/4, and SOX2 in a single vector and can easily generate iPSCs from human blood cells. Using TS12KOS, we established iPSC lines from chimpanzee blood, and used DNA array analysis to show that the global gene-expression pattern of chimpanzee iPSCs is similar to those of human embryonic stem cell and iPSC lines. These results demonstrated that our new vector is useful for generating iPSCs from the blood cells of both human and chimpanzee. In addition, the chimpanzee iPSCs are expected to facilitate unique studies into human physiology and disease.

  20. Vector regression introduced

    Directory of Open Access Journals (Sweden)

    Mok Tik

    2014-06-01

    Full Text Available This study formulates regression of vector data that will enable statistical analysis of various geodetic phenomena such as, polar motion, ocean currents, typhoon/hurricane tracking, crustal deformations, and precursory earthquake signals. The observed vector variable of an event (dependent vector variable is expressed as a function of a number of hypothesized phenomena realized also as vector variables (independent vector variables and/or scalar variables that are likely to impact the dependent vector variable. The proposed representation has the unique property of solving the coefficients of independent vector variables (explanatory variables also as vectors, hence it supersedes multivariate multiple regression models, in which the unknown coefficients are scalar quantities. For the solution, complex numbers are used to rep- resent vector information, and the method of least squares is deployed to estimate the vector model parameters after transforming the complex vector regression model into a real vector regression model through isomorphism. Various operational statistics for testing the predictive significance of the estimated vector parameter coefficients are also derived. A simple numerical example demonstrates the use of the proposed vector regression analysis in modeling typhoon paths.

  1. Derivation, Expansion, and Motor Neuron Differentiation of Human-Induced Pluripotent Stem Cells with Non-Integrating Episomal Vectors and a Defined Xenogeneic-free Culture System.

    Science.gov (United States)

    Hu, Wentao; He, Yongpei; Xiong, Yongjie; Lu, Hong; Chen, Hong; Hou, Limin; Qiu, Zhandong; Fang, Yu; Zhang, Suming

    2016-04-01

    Induced pluripotent stem cells (iPSCs) generated from patient-derived somatic cells provides the opportunity for model development in order to study patient-specific disease states with the potential for drug discovery. However, use of lentivirus and exposure of iPSCs to animal-derived products limit their therapeutic utility and affect lineage differentiation and subsequent downstream functionality of iPSC derivatives. Within the context of this study, we describe a simple and practical protocol enabling the efficient reprogramming of terminally differentiated adult fibroblasts into integration-free human iPSCs (hiPSCs) using a combination of episomal plasmids with small molecules (SMs). Using this approach, there was a 10-fold increase in reprogramming efficiency over single plasmid vector-based methods. We obtained approximately 100 iPSCs colonies from 1 × 10(5) human adult dermal fibroblasts (HADFs) and achieved approximately 0.1% reprogramming efficiencies. Concurrently, we developed a highly conducive culture system using xeno-free media and human vitronectin. The resulting hiPSCs were free of DNA integration and had completely lost episomal vectors, maintained long-term self-renewal, featured a normal karyotype, expressed pluripotent stem cell markers, and possessed the capability of differentiating into components of all three germ layers in vivo. Finally, we demonstrate that the integration-free hiPSCs could be differentiated into motor neurons under xeno-free culture conditions. This induction method will promote the derivation of patient-specific integration-free and xeno-free iPSCs and improve the strategy for motor neuron derivation. Our approach provides a useful tool for human disease models, drug screen, and clinical applications.

  2. Use of a vectored vaccine against infectious bursal disease of chickens in the face of high-titred maternally derived antibody.

    Science.gov (United States)

    Bublot, M; Pritchard, N; Le Gros, F-X; Goutebroze, S

    2007-07-01

    Interference by maternally derived antibody (MDA) is a major problem for the vaccination of young chickens against infectious bursal disease (IBD). The choice of the timing of vaccination and of the type (degree of attenuation) of modified-live vaccine (MLV) to use is often difficult. An IBD vectored vaccine (vHVT13), in which turkey herpesvirus (HVT) is used as the vector, was recently developed. This vaccine is administered once at the hatchery, either in ovo or by the subcutaneous route, to 1-day-old chicks at a time when MDA is maximal. In terms of safety, the vHVT13 vaccine had negligible impact on the bursa of Fabricius when compared with classical IBD MLV. Vaccination and challenge studies demonstrated that this vaccine is able to protect chickens against various IBD virus (IBDV) challenge strains including very virulent, classical, and USA variant IBDV, despite the presence of high-titred IBD MDA at the time of vaccination. These data show that the vector vaccine combines a safety and efficacy profile that cannot be achieved with classical IBD vaccines.

  3. Comment on ``Poynting vector, heating rate, and stored energy in structured materials: A first-principles derivation''

    Science.gov (United States)

    Richter, F.; Henneberger, K.; Florian, M.

    2010-07-01

    In Phys. Rev. B 80, 235120 (2009)10.1103/PhysRevB.80.235120, M. G. Silveirinha criticizes our work on Poynting’s theorem and energy conservation in systems with bounded media [EPL 81, 67005 (2008)10.1209/0295-5075/81/67005], especially with regard to our argumentation toward S=(1)/(μ0)(E×B) as a generally valid energy flux vector. We fully rebut the criticism, point out that it is based on undue comparison, clear up some misunderstandings and show that Silveirinha’s approach is rather a restricted than a general one.

  4. A novel hepatitis B virus-derived cis-acting sequence that enhances expression of transgenes delivered by plasmid vectors in eukaryote cell culture systems.

    Science.gov (United States)

    Lee, Seoung-Ae; Kim, Hong; Lee, So-Young; Kim, Bum-Joon

    2017-08-26

    We tested the effectiveness of a novel 13-bp hepatitis B virus (HBV)-derived cis-acting element (CAE) (ACCTCGACAAGGC), called the DT2 CAE, in augmenting transgene expression delivered by plasmid vectors in eukaryotic cells. The addition of the DT2 CAE just upstream of the start codon of several different target proteins (luciferase, EGFP, LHB, HBsAg, and MIF) in DNA plasmid constructs enhanced their translation in a posttranscriptional manner, irrespective of cell type (cell lines or primary cells) or promoter (CMV or HBV preS1 promoters), suggesting its feasibility for enhanced protein production in eukaryotic cell systems. In conclusion, a novel HBV-derived DT2 CAE could be used effectively for enhanced protein production in eukaryotic cell culture systems. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium.

    Science.gov (United States)

    Rojas, Anabel; Kong, Sek Won; Agarwal, Pooja; Gilliss, Brian; Pu, William T; Black, Brian L

    2008-09-01

    The anterior heart field (AHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract in mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the derivatives of the AHF. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the AHF and its derivatives. Gata4 AHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the AHF results in decreased myocyte proliferation in the right ventricle, and we identified numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that GATA4 is required for cyclin D2, cyclin A2, and Cdk4 expression in the right ventricle and that the Cyclin D2 and Cdk4 promoters are bound and activated by GATA4 via multiple consensus GATA binding sites in each gene's proximal promoter. These findings establish Cyclin D2 and Cdk4 as direct transcriptional targets of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes.

  6. Protolichesterinic acid derivatives: α-methylene-γ-lactones as potent dual activators of PPARγ and Nrf2 transcriptional factors.

    Science.gov (United States)

    Le Lamer, Anne-Cécile; Authier, Hélène; Rouaud, Isabelle; Coste, Agnès; Boustie, Joël; Pipy, Bernard; Gouault, Nicolas

    2014-08-15

    PPARγ and Nrf2 are important transcriptional factors involved in many signaling pathways, especially in the anti-infectious response of macrophages. Compounds bearing a Michael acceptor moiety are well known to activate such transcriptional factors, we thus evaluated the potency of α,β-unsaturated lactones synthesized using fluorous phase organic synthesis. Compounds were first screened for their cytotoxicity in order to select lactones for PPARγ and Nrf2 activation evaluation. Among them, two α-methylene-γ-lactones were identified as potent dual activators of PPARγ and Nrf2 in macrophages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Comparative Analysis of Major Mosquito Vectors Response to Seed-Derived Essential Oil and Seed Pod-Derived Extract from Acacia nilotica

    Directory of Open Access Journals (Sweden)

    Perumal Vivekanandhan

    2018-02-01

    Full Text Available Botanical metabolites are increasingly realized as potential replacements to chemical insecticides. In the present study, Acacia nilotica seed essential oil and seed pod solvent extracts were tested for bioefficacy against three important types of mosquitoes. Mortality was recorded 24 h post-treatment, while smoke toxicity of adult mosquitoes was recorded at 10 min intervals for 40 min. Seed pod powder was extracted with different solvents and hydrodistilled seed oil chemical constituents were determined by using Gas chromatography mass spectroscopy (GC-MS -. Larvicidal and adulticidal efficacy of seed hydrodistilled essential oil and solvent extracts were tested against larval and adult mosquitoes. The seed hydrodistilled oil provided strong larvicidal activity against Anopheles stephensi, (LC50 (lethal concentration that kills 50% of the exposed larvae = 5.239, LC90 (lethal concentration that kills 90% of the exposed larvae = 9.713 mg/L; Aedes aegypti, (LC50 = 3.174, LC90 = 11.739 mg/L; and Culex quinquefasciatus, (LC50 = 4.112, LC90 = 12.325 mg/L. Smoke toxicities were 82% in Cx. quinquefasciatus, 90% in Ae. aegypti, and 80% mortality in An. stephensi adults, whereas 100% mortality was recorded for commercial mosquito coil. The GC-MS profile of seed essential oil from A. nilotica showed the presence of hexadecane (18.440% and heptacosane (15.914%, which are the main and active compounds, and which may be involved in insecticidal activity. Overall findings suggest that the seed oil showed strong mosquitocidal activity against mosquito vectors and therefore may provide an ecofriendly replacement to chemical insecticides.

  8. Quantitative structure-activity relationship (QSAR) analysis of plant-derived compounds with larvicidal activity against Zika Aedes aegypti (Diptera: Culicidae) vector using freely available descriptors.

    Science.gov (United States)

    Saavedra, Laura M; Romanelli, Gustavo P; Duchowicz, Pablo R

    2018-01-04

    We have developed a quantitative structure-activity relationship (QSAR) model for predicting the larvicidal activity of 60 plant-derived molecules against Aedes aegypti L. (Diptera: Culicidae), a vector of several diseases such as dengue, yellow fever, chikungunya and Zika. The balanced subsets method (BSM) based on k-means cluster analysis (k-MCA) was employed to split the data set. The replacement method (RM) variable subset selection technique coupled with multivariable linear regression (MLR) proved to be successful for exploring 18 326 molecular descriptors and fingerprints calculated with PaDEL, Mold 2 and EPI Suite open-source softwares. A robust QSAR model (Rtrain2=0.84, S train  = 0.20 and Rtest2=0.92, S test  = 0.23) involving five non-conformational descriptors was established. The model was validated and tested through the use of an external test set of compounds, the leave-one-out (LOO) and leave-more-out (LMO) cross-validation methods, Y-randomization and applicability domain (AD) analysis. The QSAR model surpasses previously published models based on geometrical descriptors, thereby representing a suitable tool for predicting larvicidal activity against the vector A. aegypti using a conformation-independent approach. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  9. The quantitative structure-insecticidal activity relationships from plant derived compounds against chikungunya and zika Aedes aegypti (Diptera:Culicidae) vector.

    Science.gov (United States)

    Saavedra, Laura M; Romanelli, Gustavo P; Rozo, Ciro E; Duchowicz, Pablo R

    2018-01-01

    The insecticidal activity of a series of 62 plant derived molecules against the chikungunya, dengue and zika vector, the Aedes aegypti (Diptera:Culicidae) mosquito, is subjected to a Quantitative Structure-Activity Relationships (QSAR) analysis. The Replacement Method (RM) variable subset selection technique based on Multivariable Linear Regression (MLR) proves to be successful for exploring 4885 molecular descriptors calculated with Dragon 6. The predictive capability of the obtained models is confirmed through an external test set of compounds, Leave-One-Out (LOO) cross-validation and Y-Randomization. The present study constitutes a first necessary computational step for designing less toxic insecticides. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Boosted Regression Trees Outperforms Support Vector Machines in Predicting (Regional) Yields of Winter Wheat from Single and Cumulated Dekadal Spot-VGT Derived Normalized Difference Vegetation Indices

    Science.gov (United States)

    Stas, Michiel; Dong, Qinghan; Heremans, Stien; Zhang, Beier; Van Orshoven, Jos

    2016-08-01

    This paper compares two machine learning techniques to predict regional winter wheat yields. The models, based on Boosted Regression Trees (BRT) and Support Vector Machines (SVM), are constructed of Normalized Difference Vegetation Indices (NDVI) derived from low resolution SPOT VEGETATION satellite imagery. Three types of NDVI-related predictors were used: Single NDVI, Incremental NDVI and Targeted NDVI. BRT and SVM were first used to select features with high relevance for predicting the yield. Although the exact selections differed between the prefectures, certain periods with high influence scores for multiple prefectures could be identified. The same period of high influence stretching from March to June was detected by both machine learning methods. After feature selection, BRT and SVM models were applied to the subset of selected features for actual yield forecasting. Whereas both machine learning methods returned very low prediction errors, BRT seems to slightly but consistently outperform SVM.

  11. Inhibition of core gene of HCV 3a genotype using synthetic and vector derived siRNAs.

    Science.gov (United States)

    Khaliq, Saba; Jahan, Shah; Ijaz, Bushra; Ahmad, Waqar; Asad, Sultan; Pervaiz, Asim; Samreen, Baila; Khan, Mahwish; Hassan, Sajida

    2010-11-13

    Hepatitis C virus (HCV) is a major causative agent of liver associated diseases throughout the world, with genotype 3a responsible for most of the cases in Pakistan. Due to the limited efficiency of current therapy, RNA interference (RNAi) a novel regulatory and powerful silencing approach for molecular therapeutics through a sequence-specific RNA degradation process represents an alternative option. The current study was purposed to assess and explore the possibility of RNAi to silence the HCV-3a Core gene expression, which play complex role in regulation of cell growth and host genes expression essential for infectivity and disease progression. To identify the potent siRNA target sites, 5 small interfering RNAs (siRNAs) against Core gene were designed and in vitro transcribed after consensus sequence analysis of different HCV-3a isolates. Antiviral effects of siRNAs showed upto 80% inhibition of Core gene expression by different siRNAs into Huh-7 cells as compared with Mock transfected and control siRNAs treated cells. For long lasting effect of siRNAs, vector based short hairpin siRNAs (shRNAs) were designed and tested against HCV-3a Core which resulted in a similar pattern of inhibition on RNA and protein expression of HCV Core as synthetic siRNAs. Furthermore, the efficacy of cell culture tested siRNA and shRNA, were evaluated for inhibition of HCV replication in HCV infected serum inoculated Huh-7 cells and a significant decrease in HCV viral copy number was observed. Our results support the possibility of using consensus siRNA and shRNA-based molecular therapy as a promising strategy in effective inhibition of HCV-3a genotype.

  12. A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Xin; Pan Shirong; Wang Chi; Wen Yuting; Wu Hongmei; Wang Cuifeng; Wu Chuanbin; Feng Min [School of Pharmaceutical Sciences and the First Affiliated Hospital, Sun Yat-sen University, 80 Zhongshan Road II, Guangzhou 510080 (China); Li Jie, E-mail: gzpshr@163.com, E-mail: fengmin@mail.sysu.edu.cn [Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 80 Zhongshan Road II, Guangzhou 510080 (China)

    2011-09-16

    Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.

  13. A novel dendrimer based on poly (L-glutamic acid) derivatives as an efficient and biocompatible gene delivery vector

    International Nuclear Information System (INIS)

    Zeng Xin; Pan Shirong; Wang Chi; Wen Yuting; Wu Hongmei; Wang Cuifeng; Wu Chuanbin; Feng Min; Li Jie

    2011-01-01

    Non-viral gene delivery systems based on cationic polymers have faced limitations related to their relative low gene transfer efficiency, cytotoxicity and system instability in vivo. In this paper, a flexible and pompon-like dendrimer composed of poly (amidoamine) (PAMAM) G4.0 as the inner core and poly (L-glutamic acid) grafted low-molecular-weight polyethylenimine (PLGE) as the surrounding multiple arms was synthesized (MGI dendrimer). The novel MGI dendrimer was designed to combine the merits of size-controlled PAMAM G4.0 and the low toxicity and flexible chains of PLGE. In phosphate-buffered saline dispersions the well-defined DNA/MGI complex above a N/P ratio of 30 showed good stability with particle sizes of approximately 200 nm and a comparatively low polydispersity index. However, the particle size of the DNA/25 kDa polyethylenimine (DNA/PEI 25K) complex was larger than 700 nm under the same salt conditions. The shielding of the compact amino groups at the periphery of flexible PAMAM and biocompatible PLGE chains in MGI resulted in a dramatic decrease of the cytotoxicity compared to native PAMAM G4.0 dendrimer. The in vitro transfection efficiency of DNA/MGI dendrimer complex was higher than that of PAMAM G4.0 dendrimer. Importantly, in serum-containing medium, DNA/MGI complexes at their optimal N/P ratio maintained the same high levels of transfection efficiency as in serum-free medium, while the transfection efficiency of native PAMAM G4.0, PEI 25K and Lipofectamine 2000 were sharply decreased. In vivo gene delivery of pVEGF165/MGI complex into balloon-injured rabbit carotid arteries resulted in significant inhibition of restenosis by increasing VEGF165 expression in local vessels. Therefore, the pompon-like MGI dendrimer may be a promising vector candidate for efficient gene delivery in vivo.

  14. GATA4 Is a Direct Transcriptional Activator of Cyclin D2 and Cdk4 and Is Required for Cardiomyocyte Proliferation in Anterior Heart Field-Derived Myocardium▿

    Science.gov (United States)

    Rojas, Anabel; Kong, Sek Won; Agarwal, Pooja; Gilliss, Brian; Pu, William T.; Black, Brian L.

    2008-01-01

    The anterior heart field (AHF) comprises a population of mesodermal progenitor cells that are added to the nascent linear heart to give rise to the majority of the right ventricle, interventricular septum, and outflow tract in mammals and birds. The zinc finger transcription factor GATA4 functions as an integral member of the cardiac transcription factor network in the derivatives of the AHF. In addition to its role in cardiac differentiation, GATA4 is also required for cardiomyocyte replication, although the transcriptional targets of GATA4 required for proliferation have not been previously identified. In the present study, we disrupted Gata4 function exclusively in the AHF and its derivatives. Gata4 AHF knockout mice die by embryonic day 13.5 and exhibit hypoplasia of the right ventricular myocardium and interventricular septum and display profound ventricular septal defects. Loss of Gata4 function in the AHF results in decreased myocyte proliferation in the right ventricle, and we identified numerous cell cycle genes that are dependent on Gata4 by microarray analysis. We show that GATA4 is required for cyclin D2, cyclin A2, and Cdk4 expression in the right ventricle and that the Cyclin D2 and Cdk4 promoters are bound and activated by GATA4 via multiple consensus GATA binding sites in each gene's proximal promoter. These findings establish Cyclin D2 and Cdk4 as direct transcriptional targets of GATA4 and support a model in which GATA4 controls cardiomyocyte proliferation by coordinately regulating numerous cell cycle genes. PMID:18591257

  15. High-throughput sequencing as an effective approach in profiling small RNAs derived from a hairpin RNA expression vector in woody plants.

    Science.gov (United States)

    Zhao, Dongyan; Song, Guo-Qing

    2014-11-01

    Hairpin RNA (hpRNA)-mediated gene silencing has proved to be an efficient approach to develop virus-resistant transgenic plants. To characterize small RNA molecules (sRNAs) derived from an hpRNA expression vector in transgenic cherry rootstock plants, we conducted small RNA sequencing of (1) a transgenic rootstock containing an inverted repeat of the partial coat protein of Prunus necrotic ring spot virus (PNRSV-hpRNA); (2) a nontransgenic rootstock; and (3) a PNRSV-infected sweet cherry plant. Analysis of the PNRSV sRNA pools indicated that 24-nt (nucleotide) small interfering RNAs (siRNAs) were the most prevalent sRNAs in the transgenic rootstock whereas the most abundant sRNAs in the PNRSV-infected nontransgenic rootstock were 21-nt siRNAs. In addition, the 24-nt siRNAs of the PNRSV-hpRNA were more abundant on the sense strand than those on the antisense strand in the transgenic rootstock. In contrast, preference in generating PNRSV sRNAs, ranging from 19-nt to 30-nt for sense and antisense strands, was not distinct in the PNRSV-infected nontransgenic sweet cherry. Taken together, this is the first report on profiling hpRNA-derived sRNAs in woody plants using high-throughput sequencing technology, which is an efficient way to verify the presence/absence, the abundance, and the sequence features of certain sRNAs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Targeted suicide gene therapy for glioma using human embryonic stem cell-derived neural stem cells genetically modified by baculoviral vectors.

    Science.gov (United States)

    Zhao, Y; Lam, D H; Yang, J; Lin, J; Tham, C K; Ng, W H; Wang, S

    2012-02-01

    Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide gene into the cells and demonstrated that baculovirus-mediated transgene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted anticancer gene therapy.

  17. In vivo post-transcriptional gene silencing of alpha-1 antitrypsin by adeno-associated virus vectors expressing siRNA.

    Science.gov (United States)

    Cruz, Pedro E; Mueller, Christian; Cossette, Travis L; Golant, Alexandra; Tang, Qiushi; Beattie, Stuart G; Brantly, Mark; Campbell-Thompson, Martha; Blomenkamp, Keith S; Teckman, Jeffrey H; Flotte, Terence R

    2007-09-01

    alpha-1 Antitrypsin (AAT) deficiency is one of the most common genetic diseases in North America, with a carrier frequency of approximately 4% in the US population. Homozygosity for the most common mutation (Glu342Lys, PI(*)Z) leads to the synthesis of a mutant protein, which accumulates and polymerizes within hepatocytes rather than being efficiently secreted. This lack of secretion causes severe serum deficiency predisposing to chronic lung disease. Twelve to fifteen percent of patients with PI(*)ZZ also develop liver disease, which can be severe, even in infancy. This is thought to be due to toxic effects of the accumulated mutant Z-AAT within the hepatocyte. Thus, an approach to reduce AAT-deficient liver disease will likely require some mechanism to decrease the amount of Z-AAT within hepatocytes. In this report, we describe studies of small-interfering RNAs (siRNAs) designed to downregulate endogenous AAT within hepatocytes. Three different siRNA sequences were identified and cloned into a recombinant adeno-associated virus (rAAV) backbone, either singly or as a trifunctional (3X) construct. Each had activity independently, but the levels of AAT expression in cell culture models showed the greatest decrease with the 3X construct, resulting in levels that were five-fold lower than controls. The rAAV-3X-siRNA was then packaged into AAV8 capsids and used in vivo to transduce the livers of human Z-AAT overexpressing transgenic mice. Those studies showed a decrease in total human AAT, a clearing of Z-AAT accumulation by immunohistochemistry, and a decrease in monomer Z-AAT within the liver within 3 weeks after vector injection. The rAAV8-3X-siRNA vector may hold promise as a potential therapy for patients with AAT liver disease.

  18. PCB related effects thresholds as derived through gene transcript profiles in locally contaminated ringed seals (Pusa hispida).

    Science.gov (United States)

    Brown, Tanya M; Ross, Peter S; Reimer, Ken J; Veldhoen, Nik; Dangerfield, Neil J; Fisk, Aaron T; Helbing, Caren C

    2014-11-04

    Causal evidence linking toxic injury to polychlorinated biphenyl (PCB) exposure is typically confounded by the complexity of real-world contaminant mixtures to which aquatic wildlife are exposed. A local PCB "hotspot" on the Labrador coast provided a rare opportunity to evaluate the effects of PCBs on the health of a marine mammal as this chemical dominated their persistent organic pollutant (POP) burdens. The release of approximately 260 kg of PCBs by a military radar facility over a 30 year period (1970-2000) contaminated some local marine biota, including the ringed seal (Pusa hispida). The abundance profiles of eight health-related gene transcripts were evaluated in liver samples collected from 43 ringed seals in the affected area. The mRNA transcript levels of five gene targets, including aryl hydrocarbon receptor (Ahr), interleukin-1 β (Il1b), estrogen receptor α (Esr1), insulin like growth factor receptor 1 (Igf1), and glucocorticoid receptor α (Nr3c1) correlated with increasing levels of blubber PCBs. PCB threshold values calculated using best-fit hockey-stick regression models for these five genes averaged 1,680±206 ng/g lw, with the lowest, most conservative, being 1,370 ng/g lw for Il1b. Approximately 14% of the seals in the region exceeded this threshold. The dominance of PCBs in the seals studied enabled an assessment of the effects of this chemical on gene transcripts involved in regulating the health of a highly mobile predator, something that is rarely possible in the world of complex mixtures.

  19. Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

    Directory of Open Access Journals (Sweden)

    Jin Liu

    2018-03-01

    Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

  20. Cloning of fusion protein gene of Newcastle disease virus into a baculovirus derived bacmid shuttle vector, in order to express it in insect cell line

    Directory of Open Access Journals (Sweden)

    Hashemzadeh MS

    2015-05-01

    Full Text Available Abstract Background: Newcastle disease virus (NDV is one of the major pathogens in poultry and vaccination is intended to control the disease, as an effective solution, yet. Fusion protein (F on surface of NDV, has a fundamental role in virus pathogenicity and can induce protective immunity, alone. With this background, here our aim was to construct a baculovirus derived recombinant bacmid shuttle vector (encoding F-protein in order to express it in insect cell line. Materials and Methods: In this experimental study, at first complete F gene from avirulent strain La Sota of NDV was amplified by RT-PCR to produce F cDNA. The amplicon was cloned into T/A cloning vector and afterwards into pFastBac Dual donor plasmid. After the verification of cloning process by two methods, PCR and enzymatic digestion analysis, the accuracy of F gene sequence was confirmed by sequencing. Finally, F-containing recombinant bacmid was subsequently generated in DH10Bac cell and the construct production was confirmed by a special PCR panel, using F specific primers and M13 universal primers. Results: Analysis of confirmatory tests showed that the recombinant bacmid, expressing of F-protein gene in correct sequence and framework, has been constructed successfully. Conclusion: The product of this F-containing recombinant bacmid, in addition to its independent application in the induction of protective immunity, can be used with the other individual recombinant baculoviruses, expressing HN and NP genes to produce NDV-VLPs in insect cell line.

  1. Protective effects of 3-alkyl luteolin derivatives are mediated by Nrf2 transcriptional activity and decreased oxidative stress in Huntington's disease mouse striatal cells.

    Science.gov (United States)

    Oliveira, Ana M; Cardoso, Susana M; Ribeiro, Márcio; Seixas, Raquel S G R; Silva, Artur M S; Rego, A Cristina

    2015-12-01

    Huntington's disease (HD) is a polyglutamine-expansion neurodegenerative disorder caused by increased number of CAG repeats in the HTT gene, encoding for the huntingtin protein. The mutation is linked to several intracellular mechanisms, including oxidative stress. Flavones are compounds with a protective role in neurodegenerative pathologies. In the present study we analyzed the protective effect of luteolin (Lut, 3',4',5,7-tetrahydroxyflavone) and four luteolin derivatives bearing 3-alkyl chains of 1, 4, 6 and 10 carbons (Lut-C1, Lut-C4, Lut-C6, Lut-C10) in striatal cells derived from HD knock-in mice expressing mutant Htt (STHdh(Q111/Q111)) versus wild-type striatal cells (STHdh(Q7/Q7)). HD cells showed increased caspase-3-like activity and intracellular reactive oxygen species (ROS), which were significantly decreased following treatment with Lut-C4 and Lut-C6 under concentrations that enhanced cell viability. Interestingly, Lut-C4 and Lut-C6 rose the nuclear levels of phospho(Ser40)-nuclear factor (erythroid-derived-2)-like 2 (Nrf2) and Nrf2/ARE transcriptional activity. Concordantly with increased Nrf2/ARE transcription, Lut-C6 enhanced superoxide dismutase 1 (SOD1) mRNA and SOD activity and glutamate-cysteine ligase catalytic subunit (GCLc) mRNA and protein levels, while Lut-C4 induced mRNA levels of GCLc only in mutant striatal cells. Data suggest that Lut-C6 luteolin derivative (in particular) might be relevant for the development of antioxidant strategies in HD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Differential Effects of Resveratrol on the Expression of Brain-Derived Neurotrophic Factor Transcripts and Protein in the Hippocampus of Rat Brain

    Directory of Open Access Journals (Sweden)

    Shahla Shojaei

    2017-01-01

    Full Text Available Background: The induction of brain-derived neurotrophic factor (BDNF expression in the hippocampus has shown to play a role in the beneficial effects of resveratrol (RSV on the learning and memory. The BDNF gene has a complicated structure with eight 5’ noncoding exons (I-IXa, each of which can splice to a common coding exon (IX to form a functional transcript. Estrogens increase levels of BDNF transcripts in the hippocampus of rats. The aim of this study was to evaluate the effects of the phytoestrogen, RSV, on the splicing pattern of BDNF transcripts and on the pro-BDNF protein in the hippocampi of mother rats and their embryos. Methods: RSV (60 or 120 mg/kg BW/day was administered orally to pregnant rats from days 1 to 20 of gestation. Hippocampi of adults and embryos were dissected 24 h after the last administration of RSV. Extracts from hippocampi were subject to quantitative (q RT-PCR and Western blotting to assess splicing pattern of the BDNF transcripts and levels of pro-BDNF protein, respectively. Results: RSV (120 mg/kg BW/day caused a statistically significant increase in the expression levels of BDNF exons III, IV and IX, but not the exon I in the hippocampi of adult rats (P≤0.05. Levels of pro-BDNF protein remained unchanged in the hippocampal tissues from both adult and embryonic rats treated by RSV (60 or 120 mg/kg BW/day. Conclusion: Our results showed that RSV differentially activates promoters of the BDNF gene in the hippocampus of pregnant rats, but fails to affect the pro-BDNF level neither in adult nor in the embryonic hippocampal tissues.

  3. NANOG Plays a Hierarchical Role in the Transcription Network Regulating the Pluripotency and Plasticity of Adipose Tissue-Derived Stem Cells.

    Science.gov (United States)

    Pitrone, Maria; Pizzolanti, Giuseppe; Tomasello, Laura; Coppola, Antonina; Morini, Lorenzo; Pantuso, Gianni; Ficarella, Romina; Guarnotta, Valentina; Perrini, Sebastio; Giorgino, Francesco; Giordano, Carla

    2017-05-23

    The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self-renewal potential and differentiation capacity. Our aim was to study the different expression of the embryonic stem cell markers NANOG (homeobox protein NANOG), SOX2 (SRY (sex determining region Y)-box 2) and OCT4 (octamer-binding transcription factor 4) and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 ± 5 and 30 ± 5 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90, CD105, CD29, CD31, CD45 and CD146 were analyzed by flow cytometry, and the stem cell transcription factors NANOG, SOX2 and OCT4 were detected by immunoblotting and real-time PCR. NANOG , SOX2 and OCT4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT4. NANOG silencing induced a significant OCT4 (70 ± 0.05%) and SOX2 (75 ± 0.03%) downregulation, whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency.

  4. DensToolKit: A comprehensive open-source package for analyzing the electron density and its derivative scalar and vector fields

    Science.gov (United States)

    Solano-Altamirano, J. M.; Hernández-Pérez, Julio M.

    2015-11-01

    DensToolKit is a suite of cross-platform, optionally parallelized, programs for analyzing the molecular electron density (ρ) and several fields derived from it. Scalar and vector fields, such as the gradient of the electron density (∇ρ), electron localization function (ELF) and its gradient, localized orbital locator (LOL), region of slow electrons (RoSE), reduced density gradient, localized electrons detector (LED), information entropy, molecular electrostatic potential, kinetic energy densities K and G, among others, can be evaluated on zero, one, two, and three dimensional grids. The suite includes a program for searching critical points and bond paths of the electron density, under the framework of Quantum Theory of Atoms in Molecules. DensToolKit also evaluates the momentum space electron density on spatial grids, and the reduced density matrix of order one along lines joining two arbitrary atoms of a molecule. The source code is distributed under the GNU-GPLv3 license, and we release the code with the intent of establishing an open-source collaborative project. The style of DensToolKit's code follows some of the guidelines of an object-oriented program. This allows us to supply the user with a simple manner for easily implement new scalar or vector fields, provided they are derived from any of the fields already implemented in the code. In this paper, we present some of the most salient features of the programs contained in the suite, some examples of how to run them, and the mathematical definitions of the implemented fields along with hints of how we optimized their evaluation. We benchmarked our suite against both a freely-available program and a commercial package. Speed-ups of ˜2×, and up to 12× were obtained using a non-parallel compilation of DensToolKit for the evaluation of fields. DensToolKit takes similar times for finding critical points, compared to a commercial package. Finally, we present some perspectives for the future development and

  5. Vector analysis

    CERN Document Server

    Newell, Homer E

    2006-01-01

    When employed with skill and understanding, vector analysis can be a practical and powerful tool. This text develops the algebra and calculus of vectors in a manner useful to physicists and engineers. Numerous exercises (with answers) not only provide practice in manipulation but also help establish students' physical and geometric intuition in regard to vectors and vector concepts.Part I, the basic portion of the text, consists of a thorough treatment of vector algebra and the vector calculus. Part II presents the illustrative matter, demonstrating applications to kinematics, mechanics, and e

  6. About vectors

    CERN Document Server

    Hoffmann, Banesh

    1975-01-01

    From his unusual beginning in ""Defining a vector"" to his final comments on ""What then is a vector?"" author Banesh Hoffmann has written a book that is provocative and unconventional. In his emphasis on the unresolved issue of defining a vector, Hoffmann mixes pure and applied mathematics without using calculus. The result is a treatment that can serve as a supplement and corrective to textbooks, as well as collateral reading in all courses that deal with vectors. Major topics include vectors and the parallelogram law; algebraic notation and basic ideas; vector algebra; scalars and scalar p

  7. Vector-Vector Scattering on the Lattice

    Science.gov (United States)

    Romero-López, Fernando; Urbach, Carsten; Rusetsky, Akaki

    2018-03-01

    In this work we present an extension of the LüScher formalism to include the interaction of particles with spin, focusing on the scattering of two vector particles. The derived formalism will be applied to Scalar QED in the Higgs Phase, where the U(1) gauge boson acquires mass.

  8. Transcriptional analysis of Amorphotheca resinae ZN1 on biological degradation of furfural and 5-hydroxymethylfurfural derived from lignocellulose pretreatment.

    Science.gov (United States)

    Wang, Xia; Gao, Qiuqiang; Bao, Jie

    2015-01-01

    Furfural and 5-hydroxymethylfurfural (HMF) are the two major inhibitor compounds generated from lignocellulose pretreatment, especially for dilute acid, steam explosion, neutral hot water pretreatment methods. The two inhibitors severely inhibit the cell growth and metabolism of fermenting strains in the consequent bioconversion step. The biodetoxification strain Amorphotheca resinae ZN1 has demonstrated its extraordinary capacity of fast and complete degradation of furfural and HMF into corresponding alcohol and acid forms. The elucidation of degradation metabolism of A. resinae ZN1 at molecular level will facilitate the detoxification of the pretreated lignocellulose biomass and provide the metabolic pathway information for more powerful biodetoxification strain development. Amorphotheca resinae ZN1 was able to use furfural or HMF as the sole carbon source for cell growth. During the detoxification process, A. resinae ZN1 firstly reduced furfural or HMF into furfuryl alcohol or HMF alcohol, and then oxidized into furoic acid or HMF acid through furan aldehyde as the intermediate at low concentration level. The cell mass measurement suggested that furfural was more toxic to A. resinae ZN1 than HMF. In order to identify the degradation mechanism of A. resinae ZN1, transcription levels of 137 putative genes involved in the degradation of furfural and HMF in A. resinae ZN1 were investigated using the real-time quantitative PCR (qRT-PCR) method under the stress of furfural and HMF, as well as the stress of their secondary metabolites, furfuryl alcohol and HMF alcohol. Two Zn-dependent alcohol dehydrogenase genes and five AKR/ARI genes were found to be responsible for the furfural and HMF conversion to their corresponding alcohols. For the conversion of the two furan alcohols to the corresponding acids, three propanol-preferring alcohol dehydrogenase genes, one NAD(P)(+)-depending aldehyde dehydrogenase gene, or two oxidase genes with free oxygen as the substrate were

  9. Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.

    Science.gov (United States)

    Kawamoto, Taisuke; Ito, Yuichi; Morita, Osamu; Honda, Hiroshi

    2017-01-01

    Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.

  10. Endogenous siRNAs and piRNAs derived from transposable elements and genes in the malaria vector mosquito Anopheles gambiae.

    Science.gov (United States)

    Biryukova, Inna; Ye, Tao

    2015-04-10

    The siRNA and piRNA pathways have been shown in insects to be essential for regulation of gene expression and defence against exogenous and endogenous genetic elements (viruses and transposable elements). The vast majority of endogenous small RNAs produced by the siRNA and piRNA pathways originate from repetitive or transposable elements (TE). In D. melanogaster, TE-derived endogenous siRNAs and piRNAs are involved in genome surveillance and maintenance of genome integrity. In the medically relevant malaria mosquito Anopheles gambiae TEs constitute 12-16% of the genome size. Genetic variations induced by TE activities are known to shape the genome landscape and to alter the fitness in An. gambiae. Here, using bioinformatics approaches we analyzed the small RNA data sets from 6 libraries formally reported in a previous study and examined the expression of the mixed germline/somatic siRNAs and piRNAs produced in adult An. gambiae females. We characterized a large population of TE-derived endogenous siRNAs and piRNAs, which constitutes 56-60% of the total siRNA and piRNA reads in the analysed libraries. Moreover, we identified a number of protein coding genes producing gene-specific siRNAs and piRNAs that were generally expressed at much lower levels than the TE-associated small RNAs. Detailed sequence analysis revealed that An. gambiae piRNAs were produced by both "ping-pong" dependent (TE-associated piRNAs) and independent mechanisms (genic piRNAs). Similarly to D. melanogaster, more than 90% of the detected piRNAs were produced from TE-associated clusters in An. gambiae. We also found that biotic stress as blood feeding and infection with Plasmodium parasite, the etiological agent of malaria, modulated the expression levels of the endogenous siRNAs and piRNAs in An. gambiae. We identified a large and diverse set of the endogenously derived siRNAs and piRNAs that share common and distinct aspects of small RNA expression across insect species, and inferred their

  11. Natural derivatives of curcumin attenuate the Wnt/β-catenin pathway through down-regulation of the transcriptional coactivator p300

    International Nuclear Information System (INIS)

    Ryu, Min-Jung; Cho, Munju; Song, Jie-Young; Yun, Yeon-Sook; Choi, Il-Whan; Kim, Dong-Eun; Park, Byeoung-Soo; Oh, Sangtaek

    2008-01-01

    Curcumin, a component of turmeric (Curcuma longa), has been reported to suppress β-catenin response transcription (CRT), which is aberrantly activated in colorectal cancer. However, the effects of its natural analogs (demethoxycurcumin [DMC] and bisdemethoxycurcumin [BDMC]) and metabolite (tetrahydrocurcumin [THC]) on the Wnt/β-catenin pathway have not been investigated. Here, we show that DMC and BDMC suppressed CRT that was activated by Wnt3a conditioned-medium (Wnt3a-CM) without altering the level of intracellular β-catenin, and inhibited the growth of various colon cancer cells, with comparable potency to curcumin. Additionally, DMC and BDMC down-regulated p300, which is a positive regulator of the Wnt/β-catenin pathway. Notably, THC also inhibited CRT and cell proliferation, but to a much lesser degree than curcumin, DMC, or BDMC, indicating that the conjugated bonds in the central seven-carbon chain of curcuminoids are essential for the inhibition of Wnt/β-catenin pathway and the anti-proliferative activity of curcuminoids. Thus, our findings suggest that curcumin derivatives inhibit the Wnt/β-catenin pathway by decreasing the amount of the transcriptional coactivator p300.

  12. Elementary vectors

    CERN Document Server

    Wolstenholme, E Œ

    1978-01-01

    Elementary Vectors, Third Edition serves as an introductory course in vector analysis and is intended to present the theoretical and application aspects of vectors. The book covers topics that rigorously explain and provide definitions, principles, equations, and methods in vector analysis. Applications of vector methods to simple kinematical and dynamical problems; central forces and orbits; and solutions to geometrical problems are discussed as well. This edition of the text also provides an appendix, intended for students, which the author hopes to bridge the gap between theory and appl

  13. Transcriptional activation and production of tryptophan-derived secondary metabolites in arabidopsis roots contributes to the defense against the fungal vascular pathogen Verticillium longisporum.

    Science.gov (United States)

    Iven, Tim; König, Stefanie; Singh, Seema; Braus-Stromeyer, Susanna A; Bischoff, Matthias; Tietze, Lutz F; Braus, Gerhard H; Lipka, Volker; Feussner, Ivo; Dröge-Laser, Wolfgang

    2012-11-01

    The soil-borne fungal pathogen Verticillium longisporum causes vascular disease on Brassicaceae host plants such as oilseed rape. The fungus colonizes the root xylem and moves upwards to the foliage where disease symptoms become visible. Using Arabidopsis as a model for early gene induction, we performed root transcriptome analyses in response to hyphal growth immediately after spore germination and during penetration of the root cortex, respectively. Infected roots showed a rapid reprogramming of gene expression such as activation of transcription factors, stress-, and defense-related genes. Here, we focused on the highly coordinated gene induction resulting in the production of tryptophan-derived secondary metabolites. Previous studies in leaves showed that enzymes encoded by CYP81F2 and PEN2 (PENETRATION2) execute the formation of antifungal indole glucosinolate (IGS) metabolites. In Verticillium-infected roots, we found transcriptional activation of CYP81F2 and the PEN2 homolog PEL1 (PEN2-LIKE1), but no increase in antifungal IGS breakdown products. In contrast, indole-3-carboxylic acid (I3CA) and the phytoalexin camalexin accumulated in infected roots but only camalexin inhibited Verticillium growth in vitro. Whereas genetic disruption of the individual metabolic pathways leading to either camalexin or CYP81F2-dependent IGS metabolites did not alter Verticillium-induced disease symptoms, a cyp79b2 cyp79b3 mutant impaired in both branches resulted in significantly enhanced susceptibility. Hence, our data provide an insight into root-specific early defenses and suggest tryptophan-derived metabolites as active antifungal compounds against a vascular pathogen.

  14. ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth

    DEFF Research Database (Denmark)

    Markljung, Ellen; Jiang, Lin; Jaffe, Jacob D

    2009-01-01

    and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (Ch......A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor......IP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications...

  15. CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression

    Czech Academy of Sciences Publication Activity Database

    Hejnar, Jiří; Hájková, P.; Plachý, Jiří; Elleder, Daniel; Stepanets, Volodymyr; Svoboda, Jan

    2001-01-01

    Roč. 98, č. 2 (2001), s. 565-569 ISSN 0027-8424 R&D Projects: GA ČR GA312/97/P082; GA ČR GA312/98/0825; GA AV ČR IPP2052002 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.890, year: 2001

  16. CpG island protects Rous sarcoma virus-derived vectors integrated into nonpermissive cells from DNA methylation and transcriptional suppression

    Czech Academy of Sciences Publication Activity Database

    Hejnar, Jiří; Hájková, P.; Plachý, Jiří; Elleder, Daniel; Stepanets, Volodymyr; Svoboda, Jan

    2001-01-01

    Roč. 98, č. 2 (2001), s. 565-569 ISSN 0027-8424 R&D Projects: GA ČR GA312/97/P082; GA ČR GA312/98/0825 Keywords : CpG island * provirus silencing * DNA methylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.890, year: 2001

  17. HIV-1 reverse transcription.

    Science.gov (United States)

    Hu, Wei-Shau; Hughes, Stephen H

    2012-10-01

    Reverse transcription and integration are the defining features of the Retroviridae; the common name "retrovirus" derives from the fact that these viruses use a virally encoded enzyme, reverse transcriptase (RT), to convert their RNA genomes into DNA. Reverse transcription is an essential step in retroviral replication. This article presents an overview of reverse transcription, briefly describes the structure and function of RT, provides an introduction to some of the cellular and viral factors that can affect reverse transcription, and discusses fidelity and recombination, two processes in which reverse transcription plays an important role. In keeping with the theme of the collection, the emphasis is on HIV-1 and HIV-1 RT.

  18. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Directory of Open Access Journals (Sweden)

    Juan Roberto Rodriguez-Madoz

    Full Text Available The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272 improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  19. Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.

    Science.gov (United States)

    Rodriguez-Madoz, Juan Roberto; San Jose-Eneriz, Edurne; Rabal, Obdulia; Zapata-Linares, Natalia; Miranda, Estibaliz; Rodriguez, Saray; Porciuncula, Angelo; Vilas-Zornoza, Amaia; Garate, Leire; Segura, Victor; Guruceaga, Elizabeth; Agirre, Xabier; Oyarzabal, Julen; Prosper, Felipe

    2017-01-01

    The combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of iPSCs and could be used for disease modelling, high throughput screenings and/or regenerative medicine applications. In this study, we showed that a new first-in-class reversible dual G9a/DNMT1 inhibitor compound (CM272) improves the efficiency of human cell reprogramming and iPSC generation from primary cells of healthy donors and patient samples, using both integrative and non-integrative methods. Moreover, CM272 facilitates the generation of human iPSC with only two factors allowing the removal of the most potent oncogenic factor cMYC. Furthermore, we demonstrated that mechanistically, treatment with CM272 induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to OSKM refractory binding regions that are required for iPSC establishment, and enhances mesenchymal to epithelial transition during the early phase of cell reprogramming. Thus, the use of this new G9a/DNMT reversible dual inhibitor compound may represent an interesting alternative for improving cell reprogramming and human iPSC derivation for many different applications while providing interesting insights into reprogramming mechanisms.

  20. Vector analysis

    CERN Document Server

    Brand, Louis

    2006-01-01

    The use of vectors not only simplifies treatments of differential geometry, mechanics, hydrodynamics, and electrodynamics, but also makes mathematical and physical concepts more tangible and easy to grasp. This text for undergraduates was designed as a short introductory course to give students the tools of vector algebra and calculus, as well as a brief glimpse into these subjects' manifold applications. The applications are developed to the extent that the uses of the potential function, both scalar and vector, are fully illustrated. Moreover, the basic postulates of vector analysis are brou

  1. Low Molecular Weight Fraction of Commercial Human Serum Albumin Induces Morphologic and Transcriptional Changes of Bone Marrow-Derived Mesenchymal Stem Cells.

    Science.gov (United States)

    Bar-Or, David; Thomas, Gregory W; Rael, Leonard T; Gersch, Elizabeth D; Rubinstein, Pablo; Brody, Edward

    2015-08-01

    Osteoarthritis (OA) is the most common chronic disease of the joint; however, the therapeutic options for severe OA are limited. The low molecular weight fraction of commercial 5% human serum albumin (LMWF5A) has been shown to have anti-inflammatory properties that are mediated, in part, by a diketopiperazine that is present in the albumin preparation and that was demonstrated to be safe and effective in reducing pain and improving function when administered intra-articularly in a phase III clinical trial. In the present study, bone marrow-derived mesenchymal stem cells (BMMSCs) exposed to LMWF5A exhibited an elongated phenotype with diffuse intracellular F-actin, pronounced migratory leading edges, and filopodia-like projections. In addition, LMWF5A promoted chondrogenic condensation in "micromass" culture, concurrent with the upregulation of collagen 2α1 mRNA. Furthermore, the transcription of the CXCR4-CXCL12 axis was significantly regulated in a manner conducive to migration and homing. Several transcription factors involved in stem cell differentiation were also found to bind oligonucleotide response element probes following exposure to LMWF5A. Finally, a rapid increase in PRAS40 phosphorylation was observed following treatment, potentially resulting in the activation mTORC1. Proteomic analysis of synovial fluid taken from a preliminary set of patients indicated that at 12 weeks following administration of LMWF5A, a microenvironment exists in the knee conducive to stem cell infiltration, self-renewal, and differentiation, in addition to indications of remodeling with a reduction in inflammation. Taken together, these findings imply that LMWF5A treatment may prime stem cells for both mobilization and chondrogenic differentiation, potentially explaining some of the beneficial effects achieved in clinical trials. ©AlphaMed Press.

  2. HIV-1 Reverse Transcription

    OpenAIRE

    Hu, Wei-Shau; Hughes, Stephen H.

    2012-01-01

    Reverse transcription and integration are the defining features of the Retroviridae; the common name “retrovirus” derives from the fact that these viruses use a virally encoded enzyme, reverse transcriptase (RT), to convert their RNA genomes into DNA. Reverse transcription is an essential step in retroviral replication. This article presents an overview of reverse transcription, briefly describes the structure and function of RT, provides an introduction to some of the cellular and viral fact...

  3. Differential expression of brain-derived neurotrophic factor transcripts after pilocarpine-induced seizure-like activity is related to mode of Ca2+ entry

    DEFF Research Database (Denmark)

    Poulsen, F R; Lauterborn, J; Zimmer, J

    2004-01-01

    and on the individual sensitivity of BDNF transcripts to glutamate receptor and Ca2+ channel blockers were evaluated using hippocampal slice cultures and in situ hybridization of transcript-specific cRNA probes directed against mRNAs for the four 5' exons (I-IV) of the BDNF gene. mRNAs for nerve growth factor (NGF......M) was without detectable effect. Maximal NGF and trkB mRNA expression was induced by pilocarpine at 4 and 12 h, respectively. For the individual BDNF transcripts, APV blocked pilocarpine-induced increases in transcript II, whereas nifedipine blocked increases in transcripts I and III. Transcript IV levels were...... not altered by treatment. These results indicate that transcript II makes the greatest contribution to pilocarpine effects on total BDNF mRNA content in this model and provides evidence for regional and Ca2+ channel-specific differences in activity-dependent regulation of the different BDNF transcripts...

  4. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

    Energy Technology Data Exchange (ETDEWEB)

    Maroni, Paola [Istituto Ortopedico Galeazzi, Milano (Italy); Brini, Anna Teresa [Istituto Ortopedico Galeazzi, Milano (Italy); Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Arrigoni, Elena [Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Girolamo, Laura de [Istituto Ortopedico Galeazzi, Milano (Italy); Niada, Stefania [Istituto Ortopedico Galeazzi, Milano (Italy); Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Universita degli Studi di Milano, Milano (Italy); Matteucci, Emanuela; Bendinelli, Paola [Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Universita degli Studi di Milano, Milano (Italy); Desiderio, Maria Alfonsina, E-mail: a.desiderio@unimi.it [Dipartimento di Scienze Biomediche per la Salute, Molecular Pathology Laboratory, Universita degli Studi di Milano, Milano (Italy)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal

  5. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein codi...

  6. Vector velocimeter

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention relates to a compact, reliable and low-cost vector velocimeter for example for determining velocities of particles suspended in a gas or fluid flow, or for determining velocity, displacement, rotation, or vibration of a solid surface, the vector velocimeter comprising a laser...

  7. Prediction of overall in vitro microsomal stability of drug candidates based on molecular modeling and support vector machines. Case study of novel arylpiperazines derivatives.

    Directory of Open Access Journals (Sweden)

    Szymon Ulenberg

    Full Text Available Other than efficacy of interaction with the molecular target, metabolic stability is the primary factor responsible for the failure or success of a compound in the drug development pipeline. The ideal drug candidate should be stable enough to reach its therapeutic site of action. Despite many recent excellent achievements in the field of computational methods supporting drug metabolism studies, a well-recognized procedure to model and predict metabolic stability quantitatively is still lacking. This study proposes a workflow for developing quantitative metabolic stability-structure relationships, taking a set of 30 arylpiperazine derivatives as an example. The metabolic stability of the compounds was assessed in in vitro incubations in the presence of human liver microsomes and NADPH and subsequently quantified by liquid chromatography-mass spectrometry (LC-MS. Density functional theory (DFT calculations were used to obtain 30 models of the molecules, and Dragon software served as a source of structure-based molecular descriptors. For modeling structure-metabolic stability relationships, Support Vector Machines (SVM, a non-linear machine learning technique, were found to be more effective than a regression technique, based on the validation parameters obtained. Moreover, for the first time, general sites of metabolism for arylpiperazines bearing the 4-aryl-2H-pyrido[1,2-c]pyrimidine-1,3-dione system were defined by analysis of Q-TOF-MS/MS spectra. The results indicated that the application of one of the most advanced chemometric techniques combined with a simple and quick in vitro procedure and LC-MS analysis provides a novel and valuable tool for predicting metabolic half-life values. Given the reduced time and simplicity of analysis, together with the accuracy of the predictions obtained, this is a valid approach for predicting metabolic stability using structural data. The approach presented provides a novel, comprehensive and reliable tool

  8. Adenovirus vector-mediated ex vivo gene transfer of brain-derived neurotrophic factor (BDNF) tohuman umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) promotescrush-injured rat sciatic nerve regeneration.

    Science.gov (United States)

    Hei, Wei-Hong; Almansoori, Akram A; Sung, Mi-Ae; Ju, Kyung-Won; Seo, Nari; Lee, Sung-Ho; Kim, Bong-Ju; Kim, Soung-Min; Jahng, Jeong Won; He, Hong; Lee, Jong-Ho

    2017-03-16

    This study was designed toinvestigate the efficacy of adenovirus vector-mediated brain-derived neurotrophic factor (BDNF) ex vivo gene transfer to human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) in a rat sciatic nerve crush injury model. BDNF protein and mRNA expression after infection was checked through an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Male Sprague-Dawley rats (200-250g, 6 weeks old) were distributed into threegroups (n=20 each): the control group, UCB-MSC group, and BDNF-adenovirus infected UCB-MSC (BDNF-Ad+UCB-MSC) group. UCB-MSCs (1×10 6 cells/10μl/rat) or BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat)were transplantedinto the rats at the crush site immediately after sciatic nerve injury. Cell tracking was done with PKH26-labeled UCB-MSCs and BDNF-Ad+UCB-MSCs (1×10 6 cells/10μl/rat). The rats were monitored for 4 weeks post-surgery. Results showed that expression of BDNF at both the protein and mRNA levels was higher inthe BDNF-Ad+UCB-MSC group compared to theUCB-MSC group in vitro.Moreover, BDNF mRNA expression was higher in both UCB-MSC group and BDNF-Ad+ UCB-MSC group compared tothe control group, and BDNF mRNA expression in theBDNF-Ad+UCB-MSC group was higher than inboth other groups 5days after surgeryin vivo. Labeled neurons in the dorsal root ganglia (DRG), axon counts, axon density, and sciatic function index were significantly increased in the UCB-MSC and BDNF-Ad+ UCB-MSCgroupscompared to the controlgroup four weeksaftercell transplantation. Importantly,the BDNF-Ad+UCB-MSCgroup exhibited more peripheral nerve regeneration than the other two groups.Our results indicate thatboth UCB-MSCs and BDNF-Ad+UCB-MSCscan improve rat sciatic nerve regeneration, with BDNF-Ad+UCB-MSCsshowing a greater effectthan UCB-MSCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Development and Characterization of Transcription Factor Gene-Derived Microsatellite (TFGM) Markers in Medicago truncatula and Their Transferability in Leguminous and Non-Leguminous Species.

    Science.gov (United States)

    Liu, Wenxian; Jia, Xitao; Liu, Zhimin; Zhang, Zhengshe; Wang, Yanrong; Liu, Zhipeng; Xie, Wengang

    2015-05-15

    Transcription factors (TFs) are critical adaptor molecules that regulate many plant processes by controlling gene expression. The recent increase in the availability of TF data has made TFs a valuable resource for genic functional microsatellite marker development. In the present study, we developed TF gene-derived microsatellite (TFGM) markers for Medicago truncatula and assessed their cross-species transferability. A total of 203 SSRs were identified from 1467 M. truncatula TF coding sequences, 87.68% of which were trinucleotide repeats, followed by mono- (4.93%) and hexanucleotide repeats (1.48%). Further, 142 TFGM markers showed a high level of transferability to the leguminous (55.63%-85.21%) and non-leguminous (28.17%-50.00%) species. Polymorphisms of 27 TFGM markers were evaluated in 44 alfalfa accessions. The allele number per marker ranged from two to eight with an average of 4.41, and the PIC values ranged from 0.08 to 0.84 with an average of 0.60. Considering the high polymorphism, these TFGM markers developed in our study will be valuable for genetic relationship assessments, marker-assisted selection and comparative genomic studies in leguminous and non-leguminous species.

  10. The interplay between mosquitoes, entomopathogens and symbiotic microbes: A niche for the development of novel microbial-derived vector control strategies

    Science.gov (United States)

    The current outbreak of Zika virus in the Americas has highlighted the need for improved methods of control. This concern is exacerbated if we consider that all three major arboviruses (Zika, dengue, and chikungunya virus) are transmitted efficiently by two wide spread mosquito vectors: Aedes aegypt...

  11. Lentiviral Vector Design and Imaging Approaches to Visualize the Early Stages of Cellular Reprogramming

    OpenAIRE

    Warlich, Eva; Kuehle, Johannes; Cantz, Tobias; Brugman, Martijn H; Maetzig, Tobias; Galla, Melanie; Filipczyk, Adam A; Halle, Stephan; Klump, Hannes; Schöler, Hans R; Baum, Christopher; Schroeder, Timm; Schambach, Axel

    2011-01-01

    Induced pluripotent stem cells (iPSCs) can be derived from somatic cells by gene transfer of reprogramming transcription factors. Expression levels of these factors strongly influence the overall efficacy to form iPSC colonies, but additional contribution of stochastic cell-intrinsic factors has been proposed. Here, we present engineered color-coded lentiviral vectors in which codon-optimized reprogramming factors are co-expressed by a strong retroviral promoter that is rapidly silenced in iP...

  12. Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus.

    Directory of Open Access Journals (Sweden)

    Alessandra Vitelli

    Full Text Available Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP and matrix 1 (M1. We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.

  13. Complementation of a primer binding site-impaired murine leukemia virus-derived retroviral vector by a genetically engineered tRNA-like primer

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M; Lovmand, J

    1997-01-01

    , but not with a noncomplementary tRNA-like molecule. The engineered primer was shown to be involved in both the initiation of first-strand synthesis and second-strand transfer. These results provide an in vivo demonstration that the retroviral replication machinery may recognize sequence complementarity rather than actual primer...... binding site and 3' primer sequences. Use of mutated primer binding site vectors replicating via engineered primers may add additional control features to retroviral gene transfer technology....

  14. Vector geometry

    CERN Document Server

    Robinson, Gilbert de B

    2011-01-01

    This brief undergraduate-level text by a prominent Cambridge-educated mathematician explores the relationship between algebra and geometry. An elementary course in plane geometry is the sole requirement for Gilbert de B. Robinson's text, which is the result of several years of teaching and learning the most effective methods from discussions with students. Topics include lines and planes, determinants and linear equations, matrices, groups and linear transformations, and vectors and vector spaces. Additional subjects range from conics and quadrics to homogeneous coordinates and projective geom

  15. Calculus with vectors

    CERN Document Server

    Treiman, Jay S

    2014-01-01

    Calculus with Vectors grew out of a strong need for a beginning calculus textbook for undergraduates who intend to pursue careers in STEM. fields. The approach introduces vector-valued functions from the start, emphasizing the connections between one-variable and multi-variable calculus. The text includes early vectors and early transcendentals and includes a rigorous but informal approach to vectors. Examples and focused applications are well presented along with an abundance of motivating exercises. All three-dimensional graphs have rotatable versions included as extra source materials and may be freely downloaded and manipulated with Maple Player; a free Maple Player App is available for the iPad on iTunes. The approaches taken to topics such as the derivation of the derivatives of sine and cosine, the approach to limits, and the use of "tables" of integration have been modified from the standards seen in other textbooks in order to maximize the ease with which students may comprehend the material. Additio...

  16. VECTOR INTEGRATION

    NARCIS (Netherlands)

    Thomas, E. G. F.

    2012-01-01

    This paper deals with the theory of integration of scalar functions with respect to a measure with values in a, not necessarily locally convex, topological vector space. It focuses on the extension of such integrals from bounded measurable functions to the class of integrable functions, proving

  17. Mechanical Properties of Transcription

    Science.gov (United States)

    Sevier, Stuart A.; Levine, Herbert

    2017-06-01

    The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

  18. Derivation of simple rules for complex flow vector fields on the lower part of the human face for robot face design.

    Science.gov (United States)

    Ishihara, Hisashi; Ota, Nobuyuki; Asada, Minoru

    2017-09-26

    It is quite difficult for android robots to replicate the numerous and various types of human facial expressions owing to limitations in terms of space, mechanisms, and materials. This situation could be improved with greater knowledge regarding these expressions and their deformation rules, i.e., by using the biomimetic approach. In a previous study, we investigated 16 facial deformation patterns and found that each facial point moves almost only in its own principal direction and different deformation patterns are created with different combinations of moving lengths. However, the replication errors caused by moving each control point of a face in only their principal direction were not evaluated for each deformation pattern at that time. Therefore, we calculated the replication errors in this study using the second principal component scores of the 16 sets of flow vectors at each point on the face. More than 60% of the errors were within 1 mm, and approximately 90% of them were within 3 mm. The average error was 1.1 mm. These results indicate that robots can replicate the 16 investigated facial expressions with errors within 3 mm and 1 mm for about 90% and 60% of the vectors, respectively, even if each point on the robot face moves in only its own principal direction. This finding seems promising for the development of robots capable of showing various facial expressions because signifficantly fewer types of movements than previously predicted are necessary. Creative Commons Attribution license.

  19. Toward lattice fractional vector calculus

    Science.gov (United States)

    Tarasov, Vasily E.

    2014-09-01

    An analog of fractional vector calculus for physical lattice models is suggested. We use an approach based on the models of three-dimensional lattices with long-range inter-particle interactions. The lattice analogs of fractional partial derivatives are represented by kernels of lattice long-range interactions, where the Fourier series transformations of these kernels have a power-law form with respect to wave vector components. In the continuum limit, these lattice partial derivatives give derivatives of non-integer order with respect to coordinates. In the three-dimensional description of the non-local continuum, the fractional differential operators have the form of fractional partial derivatives of the Riesz type. As examples of the applications of the suggested lattice fractional vector calculus, we give lattice models with long-range interactions for the fractional Maxwell equations of non-local continuous media and for the fractional generalization of the Mindlin and Aifantis continuum models of gradient elasticity.

  20. Replication-competent human adenovirus 11p vectors can propagate in Vero cells

    Energy Technology Data Exchange (ETDEWEB)

    Gokumakulapalle, Madhuri; Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se

    2016-08-15

    The use of continuous cell lines derived from the African green monkey kidney (AGMK) has led to major advances in virus vaccine development. However, to date, these cells have not been used to facilitate the creation of human adenoviruses because most human adenoviruses undergo abortive infections in them. Here, we report the susceptibility of AGMK-derived cells to adenovirus 11p (Ad11p) infection. First, we showed that CD46 molecules, which act as receptors for Ad11p, are expressed in AGMK cells. We then monitored Ad11p replication by measuring GFP expression as an indicator of viral transcription. We found that AGMK-derived cells were as capable as carcinoma cells at propagating full-length replication-competent Ad11p (RCAd11p) DNA. Of the AGMK cell lines tested, Vero cells had the greatest capacity for adenovirus production. Thus, AGMK cells can be used to evaluate RCAd11p-mediated gene delivery, and Vero cells can be used for the production of RCAd11pGFP vectors at relatively high yields. - Highlights: • Africa green monkey cell lines were monitored for human adenovirus 11p GFP vector infection. • Human CD46 molecules were detectable in these monkey cell lines. • Adenovirus 11p GFP vector can be propagated in Vero cells increases the safety of Ad11p-based vectors for clinical trials. • To use Vero cells for preparation of Ad11p vector avoids the potential inclusion of oncogenes from tumor cells.

  1. Characterization of BRCA2 Transcriptional Regulation

    National Research Council Canada - National Science Library

    Couch, Fergus

    1998-01-01

    .... Initially, reagents for transcriptional studies were generated. The promoter was cloned into luciferase reporter vectors, and expression constructs of BRCA2, BRCA1, p53, p21, p27 and a number of other cell cycle regulating genes were generated...

  2. An introduction to vectors, vector operators and vector analysis

    CERN Document Server

    Joag, Pramod S

    2016-01-01

    Ideal for undergraduate and graduate students of science and engineering, this book covers fundamental concepts of vectors and their applications in a single volume. The first unit deals with basic formulation, both conceptual and theoretical. It discusses applications of algebraic operations, Levi-Civita notation, and curvilinear coordinate systems like spherical polar and parabolic systems and structures, and analytical geometry of curves and surfaces. The second unit delves into the algebra of operators and their types and also explains the equivalence between the algebra of vector operators and the algebra of matrices. Formulation of eigen vectors and eigen values of a linear vector operator are elaborated using vector algebra. The third unit deals with vector analysis, discussing vector valued functions of a scalar variable and functions of vector argument (both scalar valued and vector valued), thus covering both the scalar vector fields and vector integration.

  3. Insights into Protein Sequence and Structure-Derived Features Mediating 3D Domain Swapping Mechanism using Support Vector Machine Based Approach

    Directory of Open Access Journals (Sweden)

    Khader Shameer

    2010-06-01

    Full Text Available 3-dimensional domain swapping is a mechanism where two or more protein molecules form higher order oligomers by exchanging identical or similar subunits. Recently, this phenomenon has received much attention in the context of prions and neuro-degenerative diseases, due to its role in the functional regulation, formation of higher oligomers, protein misfolding, aggregation etc. While 3-dimensional domain swap mechanism can be detected from three-dimensional structures, it remains a formidable challenge to derive common sequence or structural patterns from proteins involved in swapping. We have developed a SVM-based classifier to predict domain swapping events using a set of features derived from sequence and structural data. The SVM classifier was trained on features derived from 150 proteins reported to be involved in 3D domain swapping and 150 proteins not known to be involved in swapped conformation or related to proteins involved in swapping phenomenon. The testing was performed using 63 proteins from the positive dataset and 63 proteins from the negative dataset. We obtained 76.33% accuracy from training and 73.81% accuracy from testing. Due to high diversity in the sequence, structure and functions of proteins involved in domain swapping, availability of such an algorithm to predict swapping events from sequence and structure-derived features will be an initial step towards identification of more putative proteins that may be involved in swapping or proteins involved in deposition disease. Further, the top features emerging in our feature selection method may be analysed further to understand their roles in the mechanism of domain swapping.

  4. Larvicidal, Repellent, and Irritant Potential of the Seed-Derived Essential oil of Apium graveolens Against Dengue Vector, Aedes aegypti L. (Diptera: Culicidae).

    Science.gov (United States)

    Kumar, Sarita; Mishra, Monika; Wahab, Naim; Warikoo, Radhika

    2014-01-01

    Aedes aegypti L. is one of the primary disease vectors spreading various dreadful diseases throughout the world, specifically over tropics and subtropics. Keeping in view the adverse effects of chemical insecticides-based intervention measures, the eco-friendly and bio-degradable essential oil extracted from the seeds of celery, Apium graveolens were investigated for its efficacy against Ae. aegypti. Larvicidal bioassay carried out with the seed oil against early fourth instars of Ae. aegypti caused an LC50 and LC90 values of 16.10 and 29.08 ppm, respectively, after an exposure to 24 h. The cidal effect of the celery seed oil augmented by 1.2-fold; after an exposure to 48 h; revealing an LC50 value of 13.22 ppm. Interestingly, the seed oil did not cause immediate larval mortality, suggesting a delayed toxicity against the larval stage. Present investigations also revealed remarkable effective repellency of the oil leading to 100% protection till 165 min as compared to control that did not result in any repellency against adult Ae. aegypti. Interestingly, only one bite was recorded in the 165th-min after which only two bites were scored until 180 min of exposure of the adult mosquitoes to the oil. An exciting observation was that the knocked-down effect in adults exposed to 10% oil-impregnated papers. The contact irritancy assays with paper impregnated with 1% celery seed oil caused first flight only after 4 s resulting in an average of 63.66 flights during 15 min of exposure revealing the relative irritability of 26.97. The qualitative phytochemical analysis of the seed oil showed the presence of flavonoids, lactones, and terpenoids as the major constituents suggesting their probable role in the toxicity. Our results confirmed that celery seed essential oil can be used as an efficient larvicide and repellent against Ae. aegypti. The identification of the bioactive components, their mode of action, and studying effects on non-target organisms and the

  5. Larvicidal, Repellent and Irritant Potential of the Seed-derived Essential oil of Apium graveolens against Dengue Vector, Aedes aegypti L. (Diptera: Culicidae

    Directory of Open Access Journals (Sweden)

    Sarita eKumar

    2014-09-01

    Full Text Available Aedes aegypti L., the primary carrier for viruses causing dengue, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. Keeping in view the adverse effects of chemical insecticides-based intervention measures; the eco-friendly, bio-degradable essential oil extracted from the seeds of celery, Apium graveolens; was investigated for anti-mosquito potential against Ae. aegypti. Evaluation of larvicidal potential of celery seed oil against early fourth instars of Ae. aegypti resulted in LC50 and LC90 values of 16.10 ppm and 29.08 ppm, respectively, after an exposure to 24 h; the toxic effect of the oil increasing by 1.2 fold with an LC50 value of 13.22 ppm after an exposure to 48h. Interestingly, the seed oil did not cause rapid mortality, suggesting a delayed type of larval killing effect. The remarkable finding of the present study was effective repellency of the essential oil leading to 100% protection till 165 min as compared to control that did not show any repellency against mosquitoes. Only 1 bite was recorded in the 165th minute after which only 2 bites were scored until 180 min of exposure of the oil to the adult mosquitoes. An exciting observation was the knocked-down of mosquitoes caused by the exposure to 10% oil-impregnated papers. The exposure to 1% oil resulted in first flight only after 4 sec and a total of 63.66 average flights during 15 min exposure revealing the relative irritability of 26.97.The qualitative phytochemical study of the oil showed the presence of terpenoids, lactones and flavonoids as the major constituents suggesting their possible role in the toxicity. Present investigations proved celery seed essential oil to be an efficient larvicide and repellent against dengue vector. Further studies are needed to identify the active principles involved, their mode of action, formulated preparations for enhancing potency and stability, toxicity and effects on non-target organisms and the

  6. Ultrasound Vector Flow Imaging: Part I: Sequential Systems

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Nikolov, Svetoslav Ivanov; Yu, Alfred C. H.

    2016-01-01

    The paper gives a review of the most important methods for blood velocity vector flow imaging (VFI) for conventional, sequential data acquisition. This includes multibeam methods, speckle tracking, transverse oscillation, color flow mapping derived vector flow imaging, directional beamforming...

  7. Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines

    OpenAIRE

    Yeo, Alan; Chennamadhavuni, Spandan; Whitty, Adrian; Porco, John; Gilmore, Thomas

    2015-01-01

    Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101) on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel) and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in ...

  8. A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance

    Directory of Open Access Journals (Sweden)

    Elizabeth M Everson

    2016-01-01

    Full Text Available Hematopoietic stem cell (HSC gene therapy using retroviral vectors has immense potential, but vector-mediated genotoxicity limits use in the clinic. Lentiviral vectors are less genotoxic than gammaretroviral vectors and have become the vector of choice in clinical trials. Foamy retroviral vectors have a promising integration profile and are less prone to read-through transcription than gammaretroviral or lentiviral vectors. Here, we directly compared the safety and efficacy of foamy vectors to lentiviral vectors in human CD34+ repopulating cells in immunodeficient mice. To increase their genotoxic potential, foamy and lentiviral vectors with identical transgene cassettes with a known genotoxic spleen focus forming virus promoter were used. Both vectors resulted in efficient marking in vivo and a total of 825 foamy and 460 lentiviral vector unique integration sites were recovered in repopulating cells 19 weeks after transplantation. Foamy vector proviruses were observed less often near RefSeq gene and proto-oncogene transcription start sites than lentiviral vectors. The foamy vector group were also more polyclonal with fewer dominant clones (two out of six mice than the lentiviral vector group (eight out of eight mice, and only lentiviral vectors had integrants near known proto-oncogenes in dominant clones. Our data further support the relative safety of foamy vectors for HSC gene therapy.

  9. Recombinant alphaviruses as vectors for anti-tumour and anti-microbial immunotherapy

    NARCIS (Netherlands)

    Riezebos-Brilman, A; de Mare, A; Bungener, L; Huckriede, A; Wischut, J; Daemen, T

    Background: Vectors derived from alphaviruses are gaining interest for their high transfection potency and strong immunogenicity. Objectives: After a brief introduction on alphaviruses and their vectors, an overview is given on current preclinical immunotherapy studies using vector systems based on

  10. Vector fields on nonorientable surfaces

    Directory of Open Access Journals (Sweden)

    Ilie Barza

    2003-01-01

    X, and the space of vector fields on X are proved by using a symmetrisation process. An example related to the normal derivative on the border of the Möbius strip supports the nontriviality of the concepts introduced in this paper.

  11. Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone.

    Science.gov (United States)

    Schmidt, Alexander C; Wenzke, Daniel R; McAuliffe, Josephine M; St Claire, Marisa; Elkins, William R; Murphy, Brian R; Collins, Peter L

    2002-02-01

    Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial virus (RSV) subgroups A and B. The backbone for each of the two components of this vaccine was the attenuated recombinant bovine/human PIV3 (rB/HPIV3), a recombinant BPIV3 in which the bovine HN and F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains the well-characterized host range attenuation phenotype of BPIV3, which appears to be appropriate for immunization of young infants. The open reading frames (ORFs) for the G and F major protective antigens of RSV subgroup A and B were each placed under the control of PIV3 transcription signals and inserted individually or in homologous pairs as supernumerary genes in the promoter proximal position of rB/HPIV3. The level of replication of rB/HPIV3-RSV chimeric viruses in the respiratory tract of rhesus monkeys was similar to that of their parent virus rB/HPIV3, and each of the chimeras induced a robust immune response to both RSV and HPIV3. RSV-neutralizing antibody titers induced by rB/HPIV3-RSV chimeric viruses were equivalent to those induced by infection with wild-type RSV, and HPIV3-specific antibody responses were similar to, or slightly less than, after infection with the rB/HPIV3 vector itself. This study describes a novel vaccine strategy against RSV in which vaccine viruses with a common attenuated backbone, specifically rB/HPIV3 derivatives expressing the G and/or F major protective antigens of RSV subgroup A and of RSV subgroup B, are used to immunize by the intranasal route against RSV and HPIV3, which are the first and second most important viral agents of pediatric respiratory tract disease worldwide.

  12. Application of Vectors to Relative Velocity

    Science.gov (United States)

    Tin-Lam, Toh

    2004-01-01

    The topic 'relative velocity' has recently been introduced into the Cambridge Ordinary Level Additional Mathematics syllabus under the application of Vectors. In this note, the results of relative velocity and the 'reduction to rest' technique of teaching relative velocity are derived mathematically from vector algebra, in the hope of providing…

  13. Transcript analyses of stromal cell derived factors (SDFs): SDF-2, SDF-4 and SDF-5 reveal a different pattern of expression and prognostic association in human breast cancer

    OpenAIRE

    Kang, H.; Escudero-Esparza, Astrid; Douglas-Jones, A.; Mansel, Robert Edward; Jiang, Wen G.

    2009-01-01

    Stromal derived factors, SDFs, are a loosely defined group of molecules that may be generated by stromal cells. Two of the stromal derived factors, SDF-1 and SDF-4 belong to the chemokine family. Other SDFs, such as SDF-2 and SDF-5 are not well defined and their biological functions are less known. Although SDF-1 and its receptor have been strongly indicated in the progression of various cancers including breast cancer, little is known with regard to the role of other SDFs in malignant condit...

  14. Molecular functions of the LIM-homeobox transcription factor Lhx2 in hematopoietic progenitor cells derived from mouse embryonic stem cells.

    Science.gov (United States)

    Kitajima, Kenji; Kawaguchi, Manami; Iacovino, Michelina; Kyba, Michael; Hara, Takahiko

    2013-12-01

    We previously demonstrated that hematopoietic stem cell (HSC)-like cells are robustly expanded from mouse embryonic stem cells (ESCs) by enforced expression of Lhx2, a LIM-homeobox domain (LIM-HD) transcription factor. In this study, we analyzed the functions of Lhx2 in that process using an ESC line harboring an inducible Lhx2 gene cassette. When ESCs are cultured on OP9 stromal cells, hematopoietic progenitor cells (HPCs) are differentiated and these HPCs are prone to undergo rapid differentiation into mature hematopoietic cells. Lhx2 inhibited differentiation of HPCs into mature hematopoietic cells and this effect would lead to accumulation of HSC-like cells. LIM-HD factors interact with LIM domain binding (Ldb) protein and this interaction abrogates binding of LIM-only (Lmo) protein to Ldb. We found that one of Lmo protein, Lmo2, was unstable due to dissociation of Lmo2 from Ldb1 in the presence of Lhx2. This effect of Lhx2 on the amount of Lmo2 contributed into accumulation of HSC-like cells, since enforced expression of Lmo2 into HSC-like cells inhibited their self-renewal. Expression of Gata3 and Tal1/Scl was increased in HSC-like cells and enforced expression of Lmo2 reduced expression of Gata3 but not Tal1/Scl. Enforced expression of Gata3 into HPCs inhibited mature hematopoietic cell differentiation, whereas Gata3-knockdown abrogated the Lhx2-mediated expansion of HPCs. We propose that multiple transcription factors/cofactors are involved in the Lhx2-mediated expansion of HSC-like cells from ESCs. Lhx2 appears to fine-tune the balance between self-renewal and differentiation of HSC-like cells. © AlphaMed Press.

  15. The Role of Transcription Factor PU.I in the Activity of the Intronic Enhancer of the Eosinophil-Derived Neurotoxin (RNS2) Gene

    NARCIS (Netherlands)

    Dijk, Thamar B. van; Caldenhoven, Eric; Raaijmakers, J.A.M.; Lammers, J.W.J.; Koenderman, L.; Groot, Rolf P. de

    1997-01-01

    Eosinophil-derived neurotoxin (EDN) found in the granules of human eosinophils is a cationic ribonuclease toxin. Expression of the EDN gene (RNS2) in eosinophils is dependent on proximal promoter sequences in combination with an enhancer located in the first intron. We further define here

  16. Altered regulation of platelet-derived growth factor receptor-alpha gene-transcription in vitro by spina bifida-associated mutant Pax1 proteins

    NARCIS (Netherlands)

    Joosten, P. H.; Hol, F. A.; van Beersum, S. E.; Peters, H.; Hamel, B. C.; Afink, G. B.; van Zoelen, E. J.; Mariman, E. C.

    1998-01-01

    Mouse models show that congenital neural tube defects (NTDs) can occur as a result of mutations in the platelet-derived growth factor receptor-alpha gene (PDGFRalpha). Mice heterozygous for the PDGFRalpha-mutation Patch, and at the same time homozygous for the undulated mutation in the Pax1 gene,

  17. On the radiative decays of light vector and axial-vector mesons

    International Nuclear Information System (INIS)

    Lutz, M.F.M.; Leupold, S.

    2008-01-01

    We study the light vector and axial-vector mesons. According to the hadrogenesis conjecture the nature of the two types of states is distinct. The axial-vector mesons are generated dynamically by coupled-channel interactions based on the chiral Lagrangian written down in terms of the Goldstone bosons and the light vector mesons. We propose a novel counting scheme that arises if the chiral Lagrangian is supplemented by constraints from large-N c QCD in the hadrogenesis conjecture. The counting scheme is successfully tested by a systematic study of the properties of vector mesons. The spectrum of light axial-vector mesons is derived relying on the leading order interaction of the Goldstone bosons with the vector mesons supplemented by phenomenological correction terms. The f 1 (1282), b 1 (1230), h 1 (1386), a 1 (1230) and K 1 (1272) mesons are recovered as molecular states. Based on those results the one-loop contributions to the electromagnetic decay amplitudes of axial-vector molecules into pseudo-scalar or vector mesons are evaluated systematically. In order to arrive at gauge invariant results in a transparent manner we choose to represent the vector particles by anti-symmetric tensor fields. At present we restrict ourselves to loops where a vector and a pseudo-scalar meson couple to the axial-vector molecule. We argue that final and predictive results require further computations involving intermediate states with two vector mesons. The relevance of the latter is predicted by our counting rules

  18. RNA viral vectors for improved Agrobacterium-mediated transient expression of heterologous proteins in Nicotiana benthamiana cell suspensions and hairy roots

    Directory of Open Access Journals (Sweden)

    Larsen Jeffrey S

    2012-05-01

    Full Text Available Abstract Background Plant cell suspensions and hairy root cultures represent scalable protein expression platforms. Low protein product titers have thus far limited the application of transient protein expression in these hosts. The objective of this work was to overcome this limitation by harnessing A. tumefaciens to deliver replicating and non-replicating RNA viral vectors in plant tissue co-cultures. Results Replicating vectors derived from Potato virus X (PVX and Tobacco rattle virus (TRV were modified to contain the reporter gene β-glucuronidase (GUS with a plant intron to prevent bacterial expression. In cell suspensions, a minimal PVX vector retaining only the viral RNA polymerase gene yielded 6.6-fold more GUS than an analogous full-length PVX vector. Transient co-expression of the minimal PVX vector with P19 of Tomato bushy stunt virus or HC-Pro of Tobacco etch virus to suppress post-transcriptional gene silencing increased GUS expression by 44 and 83%, respectively. A non-replicating vector containing a leader sequence from Cowpea mosaic virus (CPMV-HT modified for enhanced translation led to 70% higher transient GUS expression than a control treatment. In hairy roots, a TRV vector capable of systemic movement increased GUS accumulation by 150-fold relative to the analogous PVX vector. Histochemical staining for GUS in TRV-infected hairy roots revealed the capacity for achieving even higher productivity per unit biomass. Conclusions For the first time, replicating PVX vectors and a non-replicating CPMV-HT vector were successfully applied toward transient heterologous protein expression in cell suspensions. A replicating TRV vector achieved transient GUS expression levels in hairy roots more than an order of magnitude higher than the highest level previously reported with a viral vector delivered by A. tumefaciens.

  19. Reproductive stage physiological and transcriptional responses to salinity stress in reciprocal populations derived from tolerant (Horkuch) and susceptible (IR29) rice

    Science.gov (United States)

    Razzaque, Samsad; Haque, Taslima; Elias, Sabrina M.; Rahman, Md. Sazzadur; Biswas, Sudip; Schwartz, Scott; Ismail, Abdelbagi M.; Walia, Harkamal; Juenger, Thomas E.; Seraj, Zeba I.

    2017-04-01

    Global increase in salinity levels has made it imperative to identify novel sources of genetic variation for tolerance traits, especially in rice. The rice landrace Horkuch, endemic to the saline coastal area of Bangladesh, was used in this study as the source of tolerance in reciprocal crosses with the sensitive but high-yielding IR29 variety for discovering transcriptional variation associated with salt tolerance in the resulting populations. The cytoplasmic effect of the Horkuch background in leaves under stress showed functional enrichment for signal transduction, DNA-dependent regulation and transport activities. In roots the enrichment was for cell wall organization and macromolecule biosynthesis. In contrast, the cytoplasmic effect of IR29 showed upregulation of apoptosis and downregulation of phosphorylation across tissues relative to Horkuch. Differential gene expression in leaves of the sensitive population showed downregulation of GO processes like photosynthesis, ATP biosynthesis and ion transport. Roots of the tolerant plants conversely showed upregulation of GO terms like G-protein coupled receptor pathway, membrane potential and cation transport. Furthermore, genes involved in regulating membrane potentials were constitutively expressed only in the roots of tolerant individuals. Overall our work has developed genetic resources and elucidated the likely mechanisms associated with the tolerance response of the Horkuch genotype.

  20. Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes

    Directory of Open Access Journals (Sweden)

    Bihoreau Marie-Thérèse

    2009-02-01

    Full Text Available Abstract Background Microarray technologies are widely used to quantify the abundance of transcripts corresponding to thousands of genes. To maximise the robustness of transcriptome results, we have tested the performance and reproducibility of rat and mouse gene expression data obtained with Affymetrix, Illumina and Operon platforms. Results We present a thorough analysis of the degree of reproducibility provided by analysing the transcriptomic profile of the same animals of several experimental groups under different popular microarray technologies in different tissues. Concordant results from inter- and intra-platform comparisons were maximised by testing many popular computational methods for generating fold changes and significances and by only considering oligonucleotides giving high expression levels. The choice of Affymetrix signal extraction technique was shown to have the greatest effect on the concordance across platforms. In both species, when choosing optimal methods, the agreement between data generated on the Affymetrix and Illumina was excellent; this was verified using qRT-PCR on a selection of genes present on all platforms. Conclusion This study provides an extensive assessment of analytical methods best suited for processing data from different microarray technologies and can assist integration of technologically different gene expression datasets in biological systems.

  1. Identification of an IMPDH1 mutation in autosomal dominant retinitis pigmentosa (RP10) revealed following comparative microarray analysis of transcripts derived from retinas of wild-type and Rho(-/-) mice.

    Science.gov (United States)

    Kennan, Avril; Aherne, Aileen; Palfi, Arpad; Humphries, Marian; McKee, Alex; Stitt, Alan; Simpson, David A C; Demtroder, Karin; Orntoft, Torben; Ayuso, Carmen; Kenna, Paul F; Farrar, G Jane; Humphries, Pete

    2002-03-01

    Comparative analysis of the transcriptional profiles of approximately 6000 genes in the retinas of wild-type mice with those carrying a targeted disruption of the rhodopsin gene was undertaken by microarray analysis. This revealed a series of transcripts, of which some were derived from genes known to map at retinopathy loci, levels of which were reduced or elevated in the retinas of Rho(-/-) mice lacking functional photoreceptors. The human homologue of one of these genes, encoding inosine monophosphate dehydrogenase type 1 (IMPDH1), maps to the region of 7q to which an adRP gene (RP10) had previously been localized. Mutational screening of DNA from the Spanish adRP family, originally used to localize the RP10 gene, revealed an Arg224Pro substitution co-segregating with the disease phenotype. The amino acid at position 224 of the IMPDH1 protein is conserved among species and the substitution is not present in healthy, unrelated individuals of European origin. These data provide strong evidence that mutations within the IMPDH1 gene cause adRP, and validate approaches to mutation detection involving comparative analysis of global transcription profiles in normal and degenerating retinal tissues. Other genes showing significant alterations in expression include some with anti-apoptotic functions and many encoding components of the extracellular matrix or cytoskeleton, a possible reflection of a response by Muller cells to preserve the remaining outer nuclear layer of the retina. We suggest that those genes identified are prime candidates for etiological involvement in degenerative retinal disease.

  2. Inhibition of Oncogenic Transcription Factor REL by the Natural Product Derivative Calafianin Monomer 101 Induces Proliferation Arrest and Apoptosis in Human B-Lymphoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Alan T. Yeo

    2015-04-01

    Full Text Available Increased activity of transcription factor NF-κB has been implicated in many B-cell lymphomas. We investigated effects of synthetic compound calafianin monomer (CM101 on biochemical and biological properties of NF-κB. In human 293 cells, CM101 selectively inhibited DNA binding by overexpressed NF-κB subunits REL (human c-Rel and p65 as compared to NF-κB p50, and inhibition of REL and p65 DNA binding by CM101 required a conserved cysteine residue. CM101 also inhibited DNA binding by REL in human B-lymphoma cell lines, and the sensitivity of several B-lymphoma cell lines to CM101-induced proliferation arrest and apoptosis correlated with levels of cellular and nuclear REL. CM101 treatment induced both phosphorylation and decreased expression of anti-apoptotic protein Bcl-XL, a REL target gene product, in sensitive B-lymphoma cell lines. Ectopic expression of Bcl-XL protected SUDHL-2 B-lymphoma cells against CM101-induced apoptosis, and overexpression of a transforming mutant of REL decreased the sensitivity of BJAB B-lymphoma cells to CM101-induced apoptosis. Lipopolysaccharide-induced activation of NF-κB signaling upstream components occurred in RAW264.7 macrophages at CM101 concentrations that blocked NF-κB DNA binding. Direct inhibitors of REL may be useful for treating B-cell lymphomas in which REL is active, and may inhibit B-lymphoma cell growth at doses that do not affect some immune-related responses in normal cells.

  3. Conformal Vector Fields on Doubly Warped Product Manifolds and Applications

    Directory of Open Access Journals (Sweden)

    H. K. El-Sayied

    2016-01-01

    Full Text Available This article aimed to study and explore conformal vector fields on doubly warped product manifolds as well as on doubly warped spacetime. Then we derive sufficient conditions for matter and Ricci collineations on doubly warped product manifolds. A special attention is paid to concurrent vector fields. Finally, Ricci solitons on doubly warped product spacetime admitting conformal vector fields are considered.

  4. Topographic models for predicting malaria vector breeding habitats: potential tools for vector control managers

    OpenAIRE

    Nmor, Jephtha C; Sunahara, Toshihiko; Goto, Kensuke; Futami, Kyoko; Sonye, George; Akweywa, Peter; Dida, Gabriel; Minakawa, Noboru

    2013-01-01

    Background Identification of malaria vector breeding sites can enhance control activities. Although associations between malaria vector breeding sites and topography are well recognized, practical models that predict breeding sites from topographic information are lacking. We used topographic variables derived from remotely sensed Digital Elevation Models (DEMs) to model the breeding sites of malaria vectors. We further compared the predictive strength of two different DEMs and evaluated the ...

  5. Toward lattice fractional vector calculus

    International Nuclear Information System (INIS)

    Tarasov, Vasily E

    2014-01-01

    An analog of fractional vector calculus for physical lattice models is suggested. We use an approach based on the models of three-dimensional lattices with long-range inter-particle interactions. The lattice analogs of fractional partial derivatives are represented by kernels of lattice long-range interactions, where the Fourier series transformations of these kernels have a power-law form with respect to wave vector components. In the continuum limit, these lattice partial derivatives give derivatives of non-integer order with respect to coordinates. In the three-dimensional description of the non-local continuum, the fractional differential operators have the form of fractional partial derivatives of the Riesz type. As examples of the applications of the suggested lattice fractional vector calculus, we give lattice models with long-range interactions for the fractional Maxwell equations of non-local continuous media and for the fractional generalization of the Mindlin and Aifantis continuum models of gradient elasticity. (papers)

  6. Raster images vectorization system

    OpenAIRE

    Genytė, Jurgita

    2006-01-01

    The problem of raster images vectorization was analyzed and researched in this work. Existing vectorization systems are quite expensive, the results are inaccurate, and the manual vectorization of a large number of drafts is impossible. That‘s why our goal was to design and develop a new raster images vectorization system using our suggested automatic vectorization algorithm and the way to record results in a new universal vectorial file format. The work consists of these main parts: analysis...

  7. Different transcriptional profiles of human monocyte-derived dendritic cells infected with distinct strains of Mycobacterium tuberculosis and Mycobacterium bovis bacillus Calmette-Guérin.

    Science.gov (United States)

    Sanarico, Nunzia; Colone, Alessia; Grassi, Manuela; Speranza, Viviana; Giovannini, Daniela; Ciaramella, Antonio; Colizzi, Vittorio; Mariani, Francesca

    2011-01-01

    In order to analyze dendritic cells (DCs) activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulent Mycobacterium tuberculosis (MTB) laboratory strain, CMT97, a clinical MTB isolate, Mycobacterium bovis bacillus Calmette-Guérin (BCG), Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-α expression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

  8. Concerted transcription of auxin and carbohydrate homeostasis-related genes underlies improved adventitious rooting of microcuttings derived from far-red treated Eucalyptus globulus Labill mother plants.

    Science.gov (United States)

    Ruedell, Carolina Michels; de Almeida, Márcia Rodrigues; Fett-Neto, Arthur Germano

    2015-12-01

    Economically important plant species, such as Eucalyptus globulus, are often rooting recalcitrant. We have previously shown that far-red light enrichment applied to E. globulus donor-plants improved microcutting rooting competence and increased rooting zone/shoot carbohydrate ratio. To better understand this developmental response, the relative expression profiles of genes involved in auxin signaling (ARF6, ARF8, AGO1), biosynthesis (YUC3) and transport (AUX1, PIN1, PIN2); sucrose cleavage (SUS1, CWINV1), transport (SUC5), hexose phosphorylation (HXK1, FLN1) and starch biosynthesis (SS3) were quantified during adventitious rooting of E. globulus microcuttings derived from donor plants exposed to far-red or white light. Expression of auxin transport-related genes increased in the first days of root induction. Far-red enrichment of donor plants induced ARF6, ARF8 and AGO1 in microcuttings. The first two gene products could activate GH3 and other rooting related genes, whereas AGO1 deregulation of the repressor ARF17 may relief rooting inhibition. Increased sink strength at the basal stem with sucrose unloading in root tissue mediated by SUC and subsequent hydrolysis by SUS1 were also supported by gene expression profile. Fructose phosphorylation and starch biosynthesis could also contribute to proper carbon allocation at the site of rooting, as evidenced by increased expression of related genes. These data are in good agreement with increased contents of hexoses and starch at the cutting base severed from far-red exposed donor plants. To sum up, pathways integrating auxin and carbohydrate metabolism were activated in microcuttings derived from donor plants exposed to far red light enrichment, thereby improving rooting response in E. globulus. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Kochen-Specker vectors

    International Nuclear Information System (INIS)

    Pavicic, Mladen; Merlet, Jean-Pierre; McKay, Brendan; Megill, Norman D

    2005-01-01

    We give a constructive and exhaustive definition of Kochen-Specker (KS) vectors in a Hilbert space of any dimension as well as of all the remaining vectors of the space. KS vectors are elements of any set of orthonormal states, i.e., vectors in an n-dimensional Hilbert space, H n , n≥3, to which it is impossible to assign 1s and 0s in such a way that no two mutually orthogonal vectors from the set are both assigned 1 and that not all mutually orthogonal vectors are assigned 0. Our constructive definition of such KS vectors is based on algorithms that generate MMP diagrams corresponding to blocks of orthogonal vectors in R n , on algorithms that single out those diagrams on which algebraic (0)-(1) states cannot be defined, and on algorithms that solve nonlinear equations describing the orthogonalities of the vectors by means of statistically polynomially complex interval analysis and self-teaching programs. The algorithms are limited neither by the number of dimensions nor by the number of vectors. To demonstrate the power of the algorithms, all four-dimensional KS vector systems containing up to 24 vectors were generated and described, all three-dimensional vector systems containing up to 30 vectors were scanned, and several general properties of KS vectors were found

  10. CMV-beta-actin promoter directs higher expression from an adeno-associated viral vector in the liver than the cytomegalovirus or elongation factor 1 alpha promoter and results in therapeutic levels of human factor X in mice.

    Science.gov (United States)

    Xu, L; Daly, T; Gao, C; Flotte, T R; Song, S; Byrne, B J; Sands, M S; Parker Ponder, K

    2001-03-20

    Although AAV vectors show promise for hepatic gene therapy, the optimal transcriptional regulatory elements have not yet been identified. In this study, we show that an AAV vector with the CMV enhancer/chicken beta-actin promoter results in 9.5-fold higher expression after portal vein injection than an AAV vector with the EF1 alpha promoter, and 137-fold higher expression than an AAV vector with the CMV promoter/enhancer. Although induction of the acute-phase response with the administration of lipopolysaccharide (LPS) activated the CMV promoter/enhancer from the context of an adenoviral vector in a previous study, LPS resulted in only a modest induction of this promoter from an AAV vector in vivo. An AAV vector with the CMV-beta-actin promoter upstream of the coagulation protein human factor X (hFX) was injected intravenously into neonatal mice. This resulted in expression of hFX at 548 ng/ml (6.8% of normal) for up to 1.2 years, and 0.6 copies of AAV vector per diploid genome in the liver at the time of sacrifice. Neonatal intramuscular injection resulted in expression of hFX at 248 ng/ml (3.1% of normal), which derived from both liver and muscle. We conclude that neonatal gene therapy with an AAV vector with the CMV-beta-actin promoter might correct hemophilia due to hFX deficiency.

  11. Different Transcriptional Profiles of Human Monocyte-Derived Dendritic Cells Infected with Distinct Strains of Mycobacterium tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin

    Directory of Open Access Journals (Sweden)

    Nunzia Sanarico

    2011-01-01

    Full Text Available In order to analyze dendritic cells (DCs activation following infection with different mycobacterial strains, we studied the expression profiles of 165 genes of human monocyte-derived DCs infected with H37Rv, a virulent Mycobacterium tuberculosis (MTB laboratory strain, CMT97, a clinical MTB isolate, Mycobacterium bovis bacillus Calmette-Guérin (BCG, Aventis Pasteur, and BCG Japan, both employed as vaccine against tuberculosis. The analysis of the gene expression reveals that, despite a set of genes similarly modulated, DCs response resulted strain dependent. In particular, H37Rv significantly upregulated EBI3 expression compared with BCG Japan, while it was the only strain that failed to release a significant IL-10 amount. Of note, BCG Japan showed a marked increase in CCR7 and TNF-α expression regarding both MTB strains and it resulted the only strain failing in exponential intracellular growth. Our results suggest that DCs display the ability to elicit a tailored strain-specific immune response.

  12. Development of a new vector using Soybean yellow common mosaic virus for gene function study or heterologous protein expression in soybeans.

    Science.gov (United States)

    Lim, Seungmo; Nam, Moon; Kim, Kil Hyun; Lee, Su-Heon; Moon, Jung-Kyung; Lim, Hyoun-Sub; Choung, Myoung-Gun; Kim, Sang-Mok; Moon, Jae Sun

    2016-02-01

    A new vector using Soybean yellow common mosaic virus (SYCMV) was constructed for gene function study or heterologous protein expression in soybeans. The in vitro transcript with a 5' cap analog m7GpppG from an SYCMV full-length infectious vector driven by a T7 promoter infected soybeans (pSYCMVT7-full). The symptoms observed in the soybeans infected with either the sap from SYCMV-infected leaves or pSYCMVT7-full were indistinguishable, suggesting that the vector exhibits equivalent biological activity as the virus itself. To utilize the vector further, a DNA-based vector driven by the Cauliflower mosaic virus (CaMV) 35S promoter was constructed. The complete sequence of the SYCMV genome was inserted into a binary vector flanked by a CaMV 35S promoter at the 5' terminus of the SYCMV genome and a cis-cleaving ribozyme sequence followed by a nopaline synthase terminator at the 3' terminus of the SYCMV genome (pSYCMV-full). The SYCMV-derived vector was tested for use as a virus-induced gene silencing (VIGS) vector for the functional analysis of soybean genes. VIGS constructs containing either a fragment of the Phytoene desaturase (PDS) gene (pSYCMV-PDS1) or a fragment of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RbcS) gene (pSYCMV-RbcS2) were constructed. Plants infiltrated with each vector using the Agrobacterium-mediated inoculation method exhibited distinct symptoms, such as photo-bleaching in plants infiltrated with pSYCMV-PDS1 and yellow or pale green coloring in plants infiltrated with pSYCMV-RbcS2. In addition, down-regulation of the transcripts of the two target genes was confirmed via northern blot analysis. Particle bombardment and direct plasmid DNA rubbing were also confirmed as alternative inoculation methods. To determine if the SYCMV vector can be used for the expression of heterologous proteins in soybean plants, the vector encoding amino acids 135-160 of VP1 of Foot-and-mouth disease virus (FMDV) serotype O1 Campos (O1C

  13. Clifford Fourier transform on vector fields.

    Science.gov (United States)

    Ebling, Julia; Scheuermann, Gerik

    2005-01-01

    Image processing and computer vision have robust methods for feature extraction and the computation of derivatives of scalar fields. Furthermore, interpolation and the effects of applying a filter can be analyzed in detail and can be advantages when applying these methods to vector fields to obtain a solid theoretical basis for feature extraction. We recently introduced the Clifford convolution, which is an extension of the classical convolution on scalar fields and provides a unified notation for the convolution of scalar and vector fields. It has attractive geometric properties that allow pattern matching on vector fields. In image processing, the convolution and the Fourier transform operators are closely related by the convolution theorem and, in this paper, we extend the Fourier transform to include general elements of Clifford Algebra, called multivectors, including scalars and vectors. The resulting convolution and derivative theorems are extensions of those for convolution and the Fourier transform on scalar fields. The Clifford Fourier transform allows a frequency analysis of vector fields and the behavior of vector-valued filters. In frequency space, vectors are transformed into general multivectors of the Clifford Algebra. Many basic vector-valued patterns, such as source, sink, saddle points, and potential vortices, can be described by a few multivectors in frequency space.

  14. Transcriptional Analysis of Hair Follicle-Derived Keratinocytes from Donors with Atopic Dermatitis Reveals Enhanced Induction of IL32 Gene by IFN-γ

    Directory of Open Access Journals (Sweden)

    Yoshie Yoshikawa

    2013-02-01

    Full Text Available We cultured human hair follicle-derived keratinocytes (FDKs from plucked hairs. To gain insight into gene expression signatures that can distinguish atopic dermatitis from non-atopic controls without skin biopsies, we undertook a comparative study of gene expression in FDKs from adult donors with atopic dermatitis and non-atopic donors. FDK primary cultures (atopic dermatitis, n = 11; non-atopic controls, n = 7 before and after interferon gamma (IFN-γ treatment were used for microarray analysis and quantitative RT-PCR. Comparison of FDKs from atopic and non-atopic donors indicated that the former showed activated pathways with innate immunity and decreased pathways of cell growth, as indicated by increased NLRP2 expression and decreased DKK1 expression, respectively. Treatment with IFN-γ induced the enhanced expression of IL32, IL1B, IL8, and CXCL1 in the cells from atopic donors compared to that in cells from non-atopic donors at 24 h after treatment. IL1B expression in FDKs after IFN-γ treatment correlated with IL32 expression. We hypothesized that overexpression of IL32 in hair follicle keratinocytes of patients with atopic dermatitis would lead to the excessive production of pro-IL1β and that the activation of IL1β from pro-IL1β by inflammasome complex, in which NLRP2 protein might be involved, would be augmented. This is the first report to show enhanced induction of cytokine/chemokine genes by IFN-γ in atopic dermatitis using cultured FDKs.

  15. GAPS IN SUPPORT VECTOR OPTIMIZATION

    Energy Technology Data Exchange (ETDEWEB)

    STEINWART, INGO [Los Alamos National Laboratory; HUSH, DON [Los Alamos National Laboratory; SCOVEL, CLINT [Los Alamos National Laboratory; LIST, NICOLAS [Los Alamos National Laboratory

    2007-01-29

    We show that the stopping criteria used in many support vector machine (SVM) algorithms working on the dual can be interpreted as primal optimality bounds which in turn are known to be important for the statistical analysis of SVMs. To this end we revisit the duality theory underlying the derivation of the dual and show that in many interesting cases primal optimality bounds are the same as known dual optimality bounds.

  16. Light axial vector mesons

    Science.gov (United States)

    Chen, Kan; Pang, Cheng-Qun; Liu, Xiang; Matsuki, Takayuki

    2015-04-01

    Inspired by the abundant experimental observation of axial-vector states, we study whether the observed axial-vector states can be categorized into the conventional axial-vector meson family. In this paper we carry out an analysis based on the mass spectra and two-body Okubo-Zweig-Iizuka-allowed decays. Besides testing the possible axial-vector meson assignments, we also predict abundant information for their decays and the properties of some missing axial-vector mesons, which are valuable for further experimental exploration of the observed and predicted axial-vector mesons.

  17. Shutdown of HIV-1 Transcription in T Cells by Nullbasic, a Mutant Tat Protein

    OpenAIRE

    Jin, Hongping; Li, Dongsheng; Sivakumaran, Haran; Lor, Mary; Rustanti, Lina; Cloonan, Nicole; Wani, Shivangi; Harrich, David

    2016-01-01

    ABSTRACT Nullbasic is a derivative of the HIV-1 transactivator of transcription (Tat) protein that strongly inhibits HIV-1 replication in lymphocytes. Here we show that lentiviral vectors that constitutively express a Nullbasic-ZsGreen1 (NB-ZSG1) fusion protein by the eEF1? promoter led to robust long-term inhibition of HIV-1 replication in Jurkat cells. Although Jurkat-NB-ZSG1 cells were infected by HIV-1, no virus production could be detected and addition of phorbol ester 12-myristate 13-ac...

  18. Existence and Stability of Solutions for Implicit Multivalued Vector Equilibrium Problems

    Directory of Open Access Journals (Sweden)

    Li Qiuying

    2011-01-01

    Full Text Available A class of implicit multivalued vector equilibrium problems is studied. By using the generalized Fan-Browder fixed point theorem, some existence results of solutions for the implicit multivalued vector equilibrium problems are obtained under some suitable assumptions. Moreover, a stability result of solutions for the implicit multivalued vector equilibrium problems is derived. These results extend and unify some recent results for implicit vector equilibrium problems, multivalued vector variational inequality problems, and vector variational inequality problems.

  19. VectorBase

    Data.gov (United States)

    U.S. Department of Health & Human Services — VectorBase is a Bioinformatics Resource Center for invertebrate vectors. It is one of four Bioinformatics Resource Centers funded by NIAID to provide web-based...

  20. Custodial vector model

    DEFF Research Database (Denmark)

    Becciolini, Diego; Franzosi, Diogo Buarque; Foadi, Roshan

    2015-01-01

    We analyze the Large Hadron Collider (LHC) phenomenology of heavy vector resonances with a $SU(2)_L\\times SU(2)_R$ spectral global symmetry. This symmetry partially protects the electroweak S-parameter from large contributions of the vector resonances. The resulting custodial vector model spectrum...

  1. Maxwell's Multipole Vectors and the CMB

    OpenAIRE

    Weeks, Jeffrey R.

    2004-01-01

    The recently re-discovered multipole vector approach to understanding the harmonic decomposition of the cosmic microwave background traces its roots to Maxwell's Treatise on Electricity and Magnetism. Taking Maxwell's directional derivative approach as a starting point, the present article develops a fast algorithm for computing multipole vectors, with an exposition that is both simpler and better motivated than in the author's previous work. Tests show the resulting algorithm, coded up as a ...

  2. Euclidean fields: vector mesons and photons

    International Nuclear Information System (INIS)

    Loffelholz, J.

    1979-01-01

    Free transverse vector fields of mass >= 0 are studied. The model is related to the usual free vector meson and electromagnetic quantum field theories by extension of the field operators from transverse to arbitrary test functions. The one-particle states in transverse gauge and their localization are described. Reflexion positivity is proved and derived are free Feynman-Kac-Nelson formulas. An Euclidean approach to a photon field in a spherical world using dilatation covariance and inversions is given

  3. Vector extrapolation methods. Applications and numerical comparison

    Science.gov (United States)

    Jbilou, K.; Sadok, H.

    2000-10-01

    The present paper is a survey of the most popular vector extrapolation methods such as the reduced rank extrapolation (RRE), the minimal polynomial extrapolation (MPE), the modified minimal polynomial extrapolation (MMPE), the vector [var epsilon]-algorithm (VEA) and the topological [var epsilon]-algorithm (TEA). Using projectors, we derive a different interpretation of these methods and give some theoretical results. The second aim of this work is to give a numerical comparison of the vector extrapolation methods above when they are used for practical large problems such as linear and nonlinear systems of equations.

  4. Singular vectors for the WN algebras

    Science.gov (United States)

    Ridout, David; Siu, Steve; Wood, Simon

    2018-03-01

    In this paper, we use free field realisations of the A-type principal, or Casimir, WN algebras to derive explicit formulae for singular vectors in Fock modules. These singular vectors are constructed by applying screening operators to Fock module highest weight vectors. The action of the screening operators is then explicitly evaluated in terms of Jack symmetric functions and their skew analogues. The resulting formulae depend on sequences of pairs of integers that completely determine the Fock module as well as the Jack symmetric functions.

  5. Rotations with Rodrigues' vector

    International Nuclear Information System (INIS)

    Pina, E

    2011-01-01

    The rotational dynamics was studied from the point of view of Rodrigues' vector. This vector is defined here by its connection with other forms of parametrization of the rotation matrix. The rotation matrix was expressed in terms of this vector. The angular velocity was computed using the components of Rodrigues' vector as coordinates. It appears to be a fundamental matrix that is used to express the components of the angular velocity, the rotation matrix and the angular momentum vector. The Hamiltonian formalism of rotational dynamics in terms of this vector uses the same matrix. The quantization of the rotational dynamics is performed with simple rules if one uses Rodrigues' vector and similar formal expressions for the quantum operators that mimic the Hamiltonian classical dynamics.

  6. A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.

    Directory of Open Access Journals (Sweden)

    Kateřina Cetkovská

    Full Text Available Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification.

  7. Multi-task Vector Field Learning.

    Science.gov (United States)

    Lin, Binbin; Yang, Sen; Zhang, Chiyuan; Ye, Jieping; He, Xiaofei

    2012-01-01

    Multi-task learning (MTL) aims to improve generalization performance by learning multiple related tasks simultaneously and identifying the shared information among tasks. Most of existing MTL methods focus on learning linear models under the supervised setting. We propose a novel semi-supervised and nonlinear approach for MTL using vector fields. A vector field is a smooth mapping from the manifold to the tangent spaces which can be viewed as a directional derivative of functions on the manifold. We argue that vector fields provide a natural way to exploit the geometric structure of data as well as the shared differential structure of tasks, both of which are crucial for semi-supervised multi-task learning. In this paper, we develop multi-task vector field learning (MTVFL) which learns the predictor functions and the vector fields simultaneously. MTVFL has the following key properties. (1) The vector fields MTVFL learns are close to the gradient fields of the predictor functions. (2) Within each task, the vector field is required to be as parallel as possible which is expected to span a low dimensional subspace. (3) The vector fields from all tasks share a low dimensional subspace. We formalize our idea in a regularization framework and also provide a convex relaxation method to solve the original non-convex problem. The experimental results on synthetic and real data demonstrate the effectiveness of our proposed approach.

  8. Forced recombination of psi-modified murine leukaemia virus-based vectors with murine leukaemia-like and VL30 murine endogenous retroviruses

    DEFF Research Database (Denmark)

    Mikkelsen, J G; Lund, Anders Henrik; Duch, M

    1999-01-01

    -impaired Akv-MLV-derived vectors, we here examine putative genetic interactions between vector RNAs and copackaged endogenous retroviral RNAs of the murine leukaemia virus (MLV) and VL30 retroelement families. We show (i) that MLV recombination is not blocked by nonhomology within the 5' untranslated region....... We note that recombination-based rescue of primer binding site knock-out retroviral vectors may constitute a sensitive assay to register putative genetic interactions involving endogenous retroviral RNAs present in cells of various species.......Co-encapsidation of retroviral RNAs into virus particles allows for the generation of recombinant proviruses through events of template switching during reverse transcription. By use of a forced recombination system based on recombinational rescue of replication- defective primer binding site...

  9. Monitoring of gene expression in bacteria during infections using an adaptable set of bioluminescent, fluorescent and colorigenic fusion vectors.

    Directory of Open Access Journals (Sweden)

    Frank Uliczka

    Full Text Available A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ. The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective conditions. Transcriptional and translational fusions to the reporter genes gfp(mut3.1, amCyan, dsRed2, luxCDABE, phoA or lacZ can be constructed, and presence of identical multiple cloning sites in the vector system facilitates the interchange of promoters or reporter genes between the plasmids of the series. The promoter of the constitutively expressed gapA gene of Escherichia coli was included to obtain fluorescent and bioluminescent expression constructs. A combination of the plasmids allows simultaneous detection and gene expression analysis in individual bacteria, e.g. in bacterial communities or during mouse infections. To test our vector system, we analyzed and quantified expression of Yersinia pseudotuberculosis virulence genes under laboratory conditions, in association with cells and during the infection process.

  10. Monitoring of gene expression in bacteria during infections using an adaptable set of bioluminescent, fluorescent and colorigenic fusion vectors.

    Science.gov (United States)

    Uliczka, Frank; Pisano, Fabio; Kochut, Annika; Opitz, Wiebke; Herbst, Katharina; Stolz, Tatjana; Dersch, Petra

    2011-01-01

    A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ). The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective conditions. Transcriptional and translational fusions to the reporter genes gfp(mut3.1), amCyan, dsRed2, luxCDABE, phoA or lacZ can be constructed, and presence of identical multiple cloning sites in the vector system facilitates the interchange of promoters or reporter genes between the plasmids of the series. The promoter of the constitutively expressed gapA gene of Escherichia coli was included to obtain fluorescent and bioluminescent expression constructs. A combination of the plasmids allows simultaneous detection and gene expression analysis in individual bacteria, e.g. in bacterial communities or during mouse infections. To test our vector system, we analyzed and quantified expression of Yersinia pseudotuberculosis virulence genes under laboratory conditions, in association with cells and during the infection process.

  11. Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2 locus

    Directory of Open Access Journals (Sweden)

    Sakashita Kazuo

    2009-09-01

    Full Text Available Abstract Therapeutic retroviral vector integration near the oncogene LMO2 is thought to be a cause of leukemia in X-SCID gene therapy trials. However, no published studies have evaluated the frequency of vector integrations near exon 1 of the LMO2 locus. We identified a high incidence region (HIR of vector integration using PCR techniques in the upstream region close to the LMO2 transcription start site in the TPA-Mat T cell line. The integration frequency of the HIR was one per 4.46 × 104 cells. This HIR was also found in Jurkat T cells but was absent from HeLa cells. Furthermore, using human cord blood-derived CD34+ cells we identified a HIR in a similar region as the TPA-Mat T cell line. One of the X-linked severe combined immunodeficiency (X-SCID patients that developed leukemia after gene therapy had a vector integration site in this HIR. Therefore, the descriptions of the location and the integration frequency of the HIR presented here may help us to better understand vector-induced leukemogenesis.

  12. Rapid Identification of Dengue Virus by Reverse Transcription-Polymerase Chain Reaction Using Field-Deployable Instrumentation

    National Research Council Canada - National Science Library

    McAvin, James C; Escamilla, Elizabeth M; Blow, James A; Turell, Micahel J; Quintana, Miguel; Bowles, David E; Swaby, James A; Barnes, William J; Huff, William B; Lahman, Kenton L

    2005-01-01

    ...) reverse transcription-polymerase chain reaction assays were developed for screening and seroype identification of infected mosquito vectors and human sera using a field-deployable, fluorometric thermocycler...

  13. Supergravity inspired vector curvaton

    International Nuclear Information System (INIS)

    Dimopoulos, Konstantinos

    2007-01-01

    It is investigated whether a massive Abelian vector field, whose gauge kinetic function is growing during inflation, can be responsible for the generation of the curvature perturbation in the Universe. Particle production is studied and it is shown that the vector field can obtain a scale-invariant superhorizon spectrum of perturbations with a reasonable choice of kinetic function. After inflation the vector field begins coherent oscillations, during which it corresponds to pressureless isotropic matter. When the vector field dominates the Universe, its perturbations give rise to the observed curvature perturbation following the curvaton scenario. It is found that this is possible if, after the end of inflation, the mass of the vector field increases at a phase transition at temperature of order 1 TeV or lower. Inhomogeneous reheating, whereby the vector field modulates the decay rate of the inflaton, is also studied

  14. Deletion of the LTR enhancer/promoter has no impact on the integration profile of MLV vectors in human hematopoietic progenitors.

    Directory of Open Access Journals (Sweden)

    Arianna Moiani

    Full Text Available Moloney murine leukemia virus (MLV-derived gamma-retroviral vectors integrate preferentially near transcriptional regulatory regions in the human genome, and are associated with a significant risk of insertional gene deregulation. Self-inactivating (SIN vectors carry a deletion of the U3 enhancer and promoter in the long terminal repeat (LTR, and show reduced genotoxicity in pre-clinical assays. We report a high-definition analysis of the integration preferences of a SIN MLV vector compared to a wild-type-LTR MLV vector in the genome of CD34(+ human hematopoietic stem/progenitor cells (HSPCs. We sequenced 13,011 unique SIN-MLV integration sites and compared them to 32,574 previously generated MLV sites in human HSPCs. The SIN-MLV vector recapitulates the integration pattern observed for MLV, with the characteristic clustering of integrations around enhancer and promoter regions associated to H3K4me3 and H3K4me1 histone modifications, specialized chromatin configurations (presence of the H2A.Z histone variant and binding of RNA Pol II. SIN-MLV and MLV integration clusters and hot spots overlap in most cases and are generated at a comparable frequency, indicating that the reduced genotoxicity of SIN-MLV vectors in hematopoietic cells is not due to a modified integration profile.

  15. Orthogonalisation of Vectors

    Indian Academy of Sciences (India)

    The vectors aI, a2 are lin- early independent and each of them has norm 1. How- ever, they are not orthogonal to each other. The Gram-. Schmidt process applied to them gives the vectors ql == (1,0), q2 = (0,1). The distance between the pair {all a2} and the pair {q I' q2} is (t) ~. Can we find another pair of orthonormal vectors ...

  16. Vectors and their applications

    CERN Document Server

    Pettofrezzo, Anthony J

    2005-01-01

    Geared toward undergraduate students, this text illustrates the use of vectors as a mathematical tool in plane synthetic geometry, plane and spherical trigonometry, and analytic geometry of two- and three-dimensional space. Its rigorous development includes a complete treatment of the algebra of vectors in the first two chapters.Among the text's outstanding features are numbered definitions and theorems in the development of vector algebra, which appear in italics for easy reference. Most of the theorems include proofs, and coordinate position vectors receive an in-depth treatment. Key concept

  17. Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants.

    Science.gov (United States)

    Chen, Qiang; He, Junyun; Phoolcharoen, Waranyoo; Mason, Hugh S

    2011-03-01

    Expression of recombinant vaccine antigens and monoclonal antibodies using plant viral vectors has developed extensively during the past several years. The approach benefits from high yields of recombinant protein obtained within days after transient delivery of viral vectors to leaves of Nicotiana benthamiana, a tobacco relative. Modified viral genomes of both RNA and DNA viruses have been created. Geminiviruses such as bean yellow dwarf virus (BeYDV) have a small, single stranded DNA genome that replicates in the nucleus of an infected plant cell, using the cellular DNA synthesis apparatus and a virus-encoded replication initiator protein (Rep). BeYDV-derived expression vectors contain deletions of the viral genes encoding coat and movement proteins and insertion of an expression cassette for a protein of interest. Delivery of the geminiviral vector to leaf cells via Agrobacterium-mediated delivery produces very high levels of recombinant DNA that can act as a transcription template, yielding high levels of mRNA for the protein of interest. Several vaccine antigens, including Norwalk virus capsid protein and hepatitis B core antigen, were expressed using the BeYDV vector at levels up to 1 mg per g of leaf mass. BeYDV replicons can be stacked in the same vector molecule by linking them in tandem, which enables production of multi-subunit proteins like monoclonal antibody (mAb) heavy and light chains. The protective mAb 6D8 against Ebola virus was produced at 0.5 mg per g of leaf mass. Multi-replicon vectors could be conveniently used to produce protein complexes, e.g. virus-like particles that require two or more subunits.

  18. Vaccine protection of chickens against antigenically diverse H5 highly pathogenic avian influenza isolates with a live HVT vector vaccine expressing the influenza hemagglutinin gene derived from a clade 2.2 avian influenza virus.

    Science.gov (United States)

    Kapczynski, Darrell R; Esaki, Motoyuki; Dorsey, Kristi M; Jiang, Haijun; Jackwood, Mark; Moraes, Mauro; Gardin, Yannick

    2015-02-25

    Vaccination is an important tool in the protection of poultry against avian influenza (AI). For field use, the overwhelming majority of AI vaccines produced are inactivated whole virus formulated into an oil emulsion. However, recombinant vectored vaccines are gaining use for their ability to induce protection against heterologous isolates and ability to overcome maternal antibody interference. In these studies, we compared protection of chickens provided by a turkey herpesvirus (HVT) vector vaccine expressing the hemagglutinin (HA) gene from a clade 2.2 H5N1 strain (A/swan/Hungary/4999/2006) against homologous H5N1 as well as heterologous H5N1 and H5N2 highly pathogenic (HP) AI challenge. The results demonstrated all vaccinated birds were protected from clinical signs of disease and mortality following homologous challenge. In addition, oral and cloacal swabs taken from challenged birds demonstrated that vaccinated birds had lower incidence and titers of viral shedding compared to sham-vaccinated birds. Following heterologous H5N1 or H5N2 HPAI challenge, 80-95% of birds receiving the HVT vector AI vaccine at day of age survived challenge with fewer birds shedding virus after challenge than sham vaccinated birds. In vitro cytotoxicity analysis demonstrated that splenic T lymphocytes from HVT-vector-AI vaccinated chickens recognized MHC-matched target cells infected with H5, as well as H6, H7, or H9 AI virus. Taken together, these studies provide support for the use of HVT vector vaccines expressing HA to protect poultry against multiple lineages of HPAI, and that both humoral and cellular immunity induced by live vaccines likely contributes to protection. Published by Elsevier Ltd.

  19. Viral vector-based influenza vaccines

    Science.gov (United States)

    de Vries, Rory D.; Rimmelzwaan, Guus F.

    2016-01-01

    ABSTRACT Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors. PMID:27455345

  20. Viral vector-based influenza vaccines.

    Science.gov (United States)

    de Vries, Rory D; Rimmelzwaan, Guus F

    2016-11-01

    Antigenic drift of seasonal influenza viruses and the occasional introduction of influenza viruses of novel subtypes into the human population complicate the timely production of effective vaccines that antigenically match the virus strains that cause epidemic or pandemic outbreaks. The development of game-changing vaccines that induce broadly protective immunity against a wide variety of influenza viruses is an unmet need, in which recombinant viral vectors may provide. Use of viral vectors allows the delivery of any influenza virus antigen, or derivative thereof, to the immune system, resulting in the optimal induction of virus-specific B- and T-cell responses against this antigen of choice. This systematic review discusses results obtained with vectored influenza virus vaccines and advantages and disadvantages of the currently available viral vectors.

  1. A Hamilton-like vector for the special-relativistic Coulomb problem

    International Nuclear Information System (INIS)

    Munoz, Gerardo; Pavic, Ivana

    2006-01-01

    A relativistic point charge moving in a Coulomb potential does not admit a conserved Hamilton vector. Despite this fact, a Hamilton-like vector may be developed that proves useful in the derivation and analysis of the particle's orbit

  2. Effects of cranberry extracts and ursolic acid derivatives on P-fimbriated Escherichia coli, COX-2 activity, pro-inflammatory cytokine release and the NF-κβ transcriptional response in vitro

    Science.gov (United States)

    Huang, Yue; Nikolic, Dejan; Pendland, Susan; Doyle, Brian J.; Locklear, Tracie D.; Mahady, Gail B.

    2010-01-01

    Cranberry, the fresh or dried ripe fruit of Vaccinium macrocarpon Ait. (Ericaceae), is currently used as adjunct therapy for the prevention and symptomatic treatment of urinary tract infections. Data from clinical trials suggest that extracts of cranberry or cranberry juice reduce the bacterial load of E. coli and also suppress the inflammatory symptoms induced by E. coli infections. A methanol extract prepared from 10 kg of dehydrated cranberries did not directly inhibit the growth of E coli strains ATCC 700336 or ATCC 25922 in concentrations up to 256 μg/mL in vitro. However, the methanol extract (CR-ME) inhibited the activity of cyclooxygenase-2, with an IC50 of 12.8 μg/mL. Moreover, CR-ME also inhibited the NF-κβ transcriptional activation in human T lymphocytes with an IC50 of 19.4 μg/mL, and significantly (p < 0.01) inhibited the release of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α from E. coli lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells in vitro, at a concentration of 50 μg/mL. The extract had no effect on inducible nitric oxide synthase activity in the murine macrophage cell line RAW 264.7. The compounds responsible for this activity were identified using a novel LC-MS based assay as ursolic acid and ursolic acid derivatives. Taken together, these data suggest CR-ME and its constituent chemical compounds target specific pathways involved in E. coli-induced inflammation. PMID:20376297

  3. TPL2 (Therapeutic Targeting Tumor Progression Locus-2)/ATF4 (Activating Transcription Factor-4)/SDF1α (Chemokine Stromal Cell-Derived Factor-α) Axis Suppresses Diabetic Retinopathy.

    Science.gov (United States)

    Lai, De-Wei; Lin, Keng-Hung; Sheu, Wayne Huey-Herng; Lee, Maw-Rong; Chen, Chung-Yu; Lee, Wen-Jane; Hung, Yi-Wen; Shen, Chin-Chang; Chung, Tsung-Ju; Liu, Shing-Hwa; Sheu, Meei-Ling

    2017-09-01

    Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of N ε -(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Serum N ε -(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between N ε -(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell-derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). This study demonstrates that inhibiting the N ε -(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus-mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema. © 2017

  4. Enhanced gene expression from retroviral vectors

    Directory of Open Access Journals (Sweden)

    Micklem David R

    2008-02-01

    Full Text Available Abstract Background Retroviruses are widely used to transfer genes to mammalian cells efficiently and stably. However, genetic elements required for high-level gene expression are incompatible with standard systems. The retroviral RNA genome is produced by cellular transcription and post-transcriptional processing within packaging cells: Introns present in the retroviral genomic transcript are removed by splicing, while polyadenylation signals lead to the production of ineffective truncated genomes. Furthermore strong enhancer/promoters within the retroviral payload lead to detrimental competition with the retroviral enhancer/promoter. Results By exploiting a new method of producing the retroviral genome in vitro it is possible to produce infectious retroviral particles carrying a high-level expression cassette that completely prohibits production of infectious retroviral particles by conventional methods. We produced an expression cassette comprising a strong enhancer/promoter, an optimised intron, the GFP open reading frame and a strong polyadenylation signal. This cassette was cloned into both a conventional MMLV retroviral vector and a vector designed to allow in vitro transcription of the retroviral genome by T7 RNA polymerase. When the conventional retroviral vector was transfected into packaging cells, the expression cassette drove strong GFP expression, but no infectious retrovirus was produced. Introduction of the in vitro produced uncapped retroviral genomic transcript into the packaging cells did not lead to any detectable GFP expression. However, infectious retrovirus was easily recovered, and when used to infect target primary human cells led to very high GFP expression – up to 3.5 times greater than conventional retroviral LTR-driven expression. Conclusion Retroviral vectors carrying an optimized high-level expression cassette do not produce infectious virions when introduced into packaging cells by transfection of DNA

  5. De Vector wetenschappelijk bekeken

    NARCIS (Netherlands)

    Slot, D.E.; van der Weijden, F.

    2009-01-01

    In juni 2008 heeft de sectie Parodontologie van ACTA een systematische review gepubliceerd over het effect van de Vector®. De vraagstelling luidde: Wat is het effect van het gebruik van de Vector® op (menselijke) gebitselementen vergeleken met ultrasone apparatuur of handinstrumentarium op

  6. Brane vector phenomenology

    International Nuclear Information System (INIS)

    Clark, T.E.; Love, S.T.; Nitta, Muneto; Veldhuis, T. ter; Xiong, C.

    2009-01-01

    Local oscillations of the brane world are manifested as massive vector fields. Their coupling to the Standard Model can be obtained using the method of nonlinear realizations of the spontaneously broken higher-dimensional space-time symmetries, and to an extent, are model independent. Phenomenological limits on these vector field parameters are obtained using LEP collider data and dark matter constraints

  7. Advancing vector biology research

    NARCIS (Netherlands)

    Kohl, Alain; Pondeville, Emilie; Schnettler, Esther; Crisanti, Andrea; Supparo, Clelia; Christophides, George K.; Kersey, Paul J.; Maslen, Gareth L.; Takken, Willem; Koenraadt, Constantianus J.M.; Oliva, Clelia F.; Busquets, Núria; Abad, F.X.; Failloux, Anna Bella; Levashina, Elena A.; Wilson, Anthony J.; Veronesi, Eva; Pichard, Maëlle; Arnaud Marsh, Sarah; Simard, Frédéric; Vernick, Kenneth D.

    2016-01-01

    Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target

  8. Vector mesons in matter

    Indian Academy of Sciences (India)

    One consequence of the chiral restoration is the mixing of parity partners. We look for a possible signature of the mixing of vector and axial vector mesons in heavy-ion collisions. We suggest an experimental method for its observation. The dynamical evolution of the heavy-ion collision is described by a transport equation of ...

  9. Architecture and Vector Control

    DEFF Research Database (Denmark)

    von Seidlein, Lorenz; Knols, Bart GJ; Kirby, Matthew

    2012-01-01

    The character of buildings plays a major role in disease control. It is understood that water supply and sanitation are critical for the well-being of residents. Current vector control programs aim to prevent the access of vector to the human host. This can be achieved through screened windows, c...

  10. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    The two branches of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions...... or meromorphic (allowing poles as singularities) functions. There already exists a well-developed theory for iterative holomorphic dynamical systems, and successful relations found between iteration theory and flows of vector fields have been one of the main motivations for the recent interest in holomorphic...... vector fields. Since the class of complex polynomial vector fields in the plane is natural to consider, it is remarkable that its study has only begun very recently. There are numerous fundamental questions that are still open, both in the general classification of these vector fields, the decomposition...

  11. Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    vector fields. Since the class of complex polynomial vector fields in the plane is natural to consider, it is remarkable that its study has only begun very recently. There are numerous fundamental questions that are still open, both in the general classification of these vector fields, the decomposition...... of parameter spaces into structurally stable domains, and a description of the bifurcations. For this reason, the talk will focus on these questions for complex polynomial vector fields.......The two branches of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions...

  12. Optimal Hedging with the Vector Autoregressive Model

    NARCIS (Netherlands)

    L. Gatarek (Lukasz); S.G. Johansen (Soren)

    2014-01-01

    markdownabstract__Abstract__ We derive the optimal hedging ratios for a portfolio of assets driven by a Cointegrated Vector Autoregressive model with general cointegration rank. Our hedge is optimal in the sense of minimum variance portfolio. We consider a model that allows for the hedges to be

  13. Revisiting the vector and axial-vector vacuum susceptibilities

    International Nuclear Information System (INIS)

    Chang Lei; Liu Yuxin; Sun Weimin; Zong Hongshi

    2008-01-01

    We re-investigate the vector and axial-vector vacuum susceptibilities by taking advantage of the vector and axial-vector Ward-Takahashi identities. We show analytically that, in the chiral limit, the vector vacuum susceptibility is zero and the axial-vector vacuum susceptibility equals three fourths of the square of the pion decay constant. Besides, our analysis reproduces the Weinberg sum rule

  14. LandSat-Based Land Use-Land Cover (Vector)

    Data.gov (United States)

    Minnesota Department of Natural Resources — Vector-based land cover data set derived from classified 30 meter resolution Thematic Mapper satellite imagery. Classification is divided into 16 classes with source...

  15. Black holes in vector-tensor theories

    Energy Technology Data Exchange (ETDEWEB)

    Heisenberg, Lavinia [Institute for Theoretical Studies, ETH Zurich, Clausiusstrasse 47, 8092 Zurich (Switzerland); Kase, Ryotaro; Tsujikawa, Shinji [Department of Physics, Faculty of Science, Tokyo University of Science, 1-3, Kagurazaka, Shinjuku-ku, Tokyo 162-8601 (Japan); Minamitsuji, Masato, E-mail: lavinia.heisenberg@eth-its.ethz.ch, E-mail: r.kase@rs.tus.ac.jp, E-mail: masato.minamitsuji@tecnico.ulisboa.pt, E-mail: shinji@rs.kagu.tus.ac.jp [Centro Multidisciplinar de Astrofisica—CENTRA, Departamento de Fisica, Instituto Superior Tecnico—IST, Universidade de Lisboa—UL, Avenida Rovisco Pais 1, 1049-001 Lisboa (Portugal)

    2017-08-01

    We study static and spherically symmetric black hole (BH) solutions in second-order generalized Proca theories with nonminimal vector field derivative couplings to the Ricci scalar, the Einstein tensor, and the double dual Riemann tensor. We find concrete Lagrangians which give rise to exact BH solutions by imposing two conditions of the two identical metric components and the constant norm of the vector field. These exact solutions are described by either Reissner-Nordström (RN), stealth Schwarzschild, or extremal RN solutions with a non-trivial longitudinal mode of the vector field. We then numerically construct BH solutions without imposing these conditions. For cubic and quartic Lagrangians with power-law couplings which encompass vector Galileons as the specific cases, we show the existence of BH solutions with the difference between two non-trivial metric components. The quintic-order power-law couplings do not give rise to non-trivial BH solutions regular throughout the horizon exterior. The sixth-order and intrinsic vector-mode couplings can lead to BH solutions with a secondary hair. For all the solutions, the vector field is regular at least at the future or past horizon. The deviation from General Relativity induced by the Proca hair can be potentially tested by future measurements of gravitational waves in the nonlinear regime of gravity.

  16. How random is a random vector?

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2015-01-01

    Over 80 years ago Samuel Wilks proposed that the “generalized variance” of a random vector is the determinant of its covariance matrix. To date, the notion and use of the generalized variance is confined only to very specific niches in statistics. In this paper we establish that the “Wilks standard deviation” –the square root of the generalized variance–is indeed the standard deviation of a random vector. We further establish that the “uncorrelation index” –a derivative of the Wilks standard deviation–is a measure of the overall correlation between the components of a random vector. Both the Wilks standard deviation and the uncorrelation index are, respectively, special cases of two general notions that we introduce: “randomness measures” and “independence indices” of random vectors. In turn, these general notions give rise to “randomness diagrams”—tangible planar visualizations that answer the question: How random is a random vector? The notion of “independence indices” yields a novel measure of correlation for Lévy laws. In general, the concepts and results presented in this paper are applicable to any field of science and engineering with random-vectors empirical data.

  17. Noncausal Bayesian Vector Autoregression

    DEFF Research Database (Denmark)

    Lanne, Markku; Luoto, Jani

    We propose a Bayesian inferential procedure for the noncausal vector autoregressive (VAR) model that is capable of capturing nonlinearities and incorporating effects of missing variables. In particular, we devise a fast and reliable posterior simulator that yields the predictive distribution...

  18. Tagged Vector Contour (TVC)

    Data.gov (United States)

    Kansas Data Access and Support Center — The Kansas Tagged Vector Contour (TVC) dataset consists of digitized contours from the 7.5 minute topographic quadrangle maps. Coverage for the state is incomplete....

  19. Vector hysteresis models

    Czech Academy of Sciences Publication Activity Database

    Krejčí, Pavel

    1991-01-01

    Roč. 2, - (1991), s. 281-292 ISSN 0956-7925 Keywords : vector hysteresis operator * hysteresis potential * differential inequality Subject RIV: BA - General Mathematics http://www.math.cas.cz/~krejci/b15p.pdf

  20. Support vector machines applications

    CERN Document Server

    Guo, Guodong

    2014-01-01

    Support vector machines (SVM) have both a solid mathematical background and good performance in practical applications. This book focuses on the recent advances and applications of the SVM in different areas, such as image processing, medical practice, computer vision, pattern recognition, machine learning, applied statistics, business intelligence, and artificial intelligence. The aim of this book is to create a comprehensive source on support vector machine applications, especially some recent advances.

  1. Relativistic stars in vector-tensor theories

    Science.gov (United States)

    Kase, Ryotaro; Minamitsuji, Masato; Tsujikawa, Shinji

    2018-04-01

    We study relativistic star solutions in second-order generalized Proca theories characterized by a U (1 )-breaking vector field with derivative couplings. In the models with cubic and quartic derivative coupling, the mass and radius of stars become larger than those in general relativity for negative derivative coupling constants. This phenomenon is mostly attributed to the increase of star radius induced by a slower decrease of the matter pressure compared to general relativity. There is a tendency that the relativistic star with a smaller mass is not gravitationally bound for a low central density and hence is dynamically unstable, but that with a larger mass is gravitationally bound. On the other hand, we show that the intrinsic vector-mode couplings give rise to general relativistic solutions with a trivial field profile, so the mass and radius are not modified from those in general relativity.

  2. Vector financial rogue waves

    International Nuclear Information System (INIS)

    Yan, Zhenya

    2011-01-01

    The coupled nonlinear volatility and option pricing model presented recently by Ivancevic is investigated, which generates a leverage effect, i.e., stock volatility is (negatively) correlated to stock returns, and can be regarded as a coupled nonlinear wave alternative of the Black–Scholes option pricing model. In this Letter, we analytically propose vector financial rogue waves of the coupled nonlinear volatility and option pricing model without an embedded w-learning. Moreover, we exhibit their dynamical behaviors for chosen different parameters. The vector financial rogue wave (rogon) solutions may be used to describe the possible physical mechanisms for the rogue wave phenomena and to further excite the possibility of relative researches and potential applications of vector rogue waves in the financial markets and other related fields. -- Highlights: ► We investigate the coupled nonlinear volatility and option pricing model. ► We analytically present vector financial rogue waves. ► The vector financial rogue waves may be used to describe the extreme events in financial markets. ► This results may excite the relative researches and potential applications of vector rogue waves.

  3. Controlled Osteogenic Differentiation of Mouse Mesenchymal Stem Cells by Tetracycline-Controlled Transcriptional Activation of Amelogenin.

    Directory of Open Access Journals (Sweden)

    Fangfang Wang

    Full Text Available Regenerative dental therapies for bone tissues rely on efficient targeting of endogenous and transplanted mesenchymal stem cells (MSCs to guide bone formation. Amelogenin is the primary component of Emdogain, which is used to regenerate periodontal defects; however, the mechanisms underlying the therapeutic effects on alveolar bone remain unclear. The tetracycline (Tet-dependent transcriptional regulatory system is a good candidate to investigate distinct roles of genes of interest during stem cell differentiation. Here, we investigated amelogenin-dependent regulation of osteogenesis in MSCs by establishing a Tet-controlled transcriptional activation system. Clonal mouse bone marrow-derived MSCs were lentivirally transduced with the Tet repressor (TetR expression vector followed by drug selection to obtain MSCs constitutively expressing TetR (MSCs-TetR. Expression vectors that contained the Tet operator and amelogenin-coding (Amelx cDNA fragments were constructed using the Gateway system and lentivirally introduced into MSCs-TetR to generate a Tet regulation system in MSCs (MSCs-TetR/Amelx. MSCs-TetR/Amelx significantly overexpressed the Amelx gene and protein in the presence of the tetracycline derivative doxycycline. Concomitant expression of osterix, bone sialoprotein (BSP, osteopontin, and osteocalcin was modulated by addition or removal of doxycycline under osteogenic guidance. During osteogenic induction, MSCs-TetR/Amelx treated with doxycycline showed significantly increased gene expression of osterix, type I collagen, BSP, and osteocalcin in addition to increased alkaline phosphatase activity and mineralized nodule formation. Enhanced extracellular matrix calcification was observed when forced Amelx expression commenced at the early stage but not at the intermediate or late stages of osteogenesis. These results suggest that a Tet-controlled Amelx gene regulation system for mouse MSCs was successfully established, in which transcriptional

  4. Statistical Theory of the Vector Random Decrement Technique

    DEFF Research Database (Denmark)

    Asmussen, J. C.; Brincker, Rune; Ibrahim, S. R.

    1999-01-01

    decays. Due to the speed and/or accuracy of the Vector Random Decrement technique, it was introduced as an attractive alternative to the Random Decrement technique. In this paper, the theory of the Vector Random Decrement technique is extended by applying a statistical description of the stochastic...... processes describing the ambient measurements. The Vector Random Decrement functions are linked to the correlation functions of the stochastic processes provided they are stationary and Gaussian distributed. Furthermore, a new approach for quality assessment of the Vector Random Decrement functions is given...... on the basis of the derived results. The work presented in this paper makes the theory of the Vector Random Decrement technique equivalent to the theory of the Random Decrement technique. The theoretical derivations are illustrated by the analysis of the response of a 3DOF system loaded by white noise. ...

  5. Enhancing oligodendrocyte differentiation by transient transcription activation via DNA nanoparticle-mediated transfection.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Zamboni, Camila Gadens; Koliatsos, Vassilis E; Ming, Guo-Li; Green, Jordan J; Mao, Hai-Quan

    2017-05-01

    Current approaches to derive oligodendrocytes from human pluripotent stem cells (hPSCs) need extended exposure of hPSCs to growth factors and small molecules, which limits their clinical application because of the lengthy culture time required and low generation efficiency of myelinating oligodendrocytes. Compared to extrinsic growth factors and molecules, oligodendrocyte differentiation and maturation can be more effectively modulated by regulation of the cell transcription network. In the developing central nervous system (CNS), two basic helix-loop-helix transcription factors, Olig1 and Olig2, are decisive in oligodendrocyte differentiation and maturation. Olig2 plays a critical role in the specification of oligodendrocytes and Olig1 is crucial in promoting oligodendrocyte maturation. Recently viral vectors have been used to overexpress Olig2 and Olig1 in neural stem/progenitor cells (NSCs) to induce the maturation of oligodendrocytes and enhance the remyelination activity in vivo. Because of the safety issues with viral vectors, including the insertional mutagenesis and potential tumor formation, non-viral transfection methods are preferred for clinical translation. Here we report a poly(β-amino ester) (PBAE)-based nanoparticle transfection method to deliver Olig1 and Olig2 into human fetal tissue-derived NSCs and demonstrate efficient oligodendrocyte differentiation following transgene expression of Olig1 and Olig2. This approach is potentially translatable for engineering stem cells to treat injured or diseased CNS tissues. Current protocols to derive oligodendrocytes from human pluripotent stem cells (hPSCs) require lengthy culture time with low generation efficiencies of mature oligodendrocytes. We described a new approach to enhance oligodendrocyte differentiation through nanoparticle-mediated transcription modulation. We tested an effective transfection method using cell-compatible poly (β-amino ester) (PBAE)/DNA nanoparticles as gene carrier to deliver

  6. Redshift-space distortions from vector perturbations

    Science.gov (United States)

    Bonvin, Camille; Durrer, Ruth; Khosravi, Nima; Kunz, Martin; Sawicki, Ignacy

    2018-02-01

    We compute a general expression for the contribution of vector perturbations to the redshift space distortion of galaxy surveys. We show that they contribute to the same multipoles of the correlation function as scalar perturbations and should thus in principle be taken into account in data analysis. We derive constraints for next-generation surveys on the amplitude of two sources of vector perturbations, namely non-linear clustering and topological defects. While topological defects leave a very small imprint on redshift space distortions, we show that the multipoles of the correlation function are sensitive to vorticity induced by non-linear clustering. Therefore future redshift surveys such as DESI or the SKA should be capable of measuring such vector modes, especially with the hexadecapole which appears to be the most sensitive to the presence of vorticity.

  7. Vector-borne diseases: the basic reproduction number R0 and risk maps

    NARCIS (Netherlands)

    Hartemink, N.A.

    2009-01-01

    This thesis deals with the derivation of the basic reproduction number (R0) for vector-borne diseases, in the context of studying the effect of climate change on the risk of emergence diseases. Vector-borne diseases are transmitted from an infected individual to another individual by vectors,

  8. Enhancer RNAs: the new molecules of transcription.

    Science.gov (United States)

    Lai, Fan; Shiekhattar, Ramin

    2014-04-01

    In the past few years, technological advances in nucleotide sequencing have culminated in a greater understanding of the complexity of the human transcriptome. Notably, the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation. Here we review recent insights into the tissue-specific and temporal-specific gene regulation brought about by the discovery of eRNAs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Multithreading in vector processors

    Energy Technology Data Exchange (ETDEWEB)

    Evangelinos, Constantinos; Kim, Changhoan; Nair, Ravi

    2018-01-16

    In one embodiment, a system includes a processor having a vector processing mode and a multithreading mode. The processor is configured to operate on one thread per cycle in the multithreading mode. The processor includes a program counter register having a plurality of program counters, and the program counter register is vectorized. Each program counter in the program counter register represents a distinct corresponding thread of a plurality of threads. The processor is configured to execute the plurality of threads by activating the plurality of program counters in a round robin cycle.

  10. Twisting of paramodular vectors

    OpenAIRE

    Johnson-Leung, Jennifer; Roberts, Brooks

    2013-01-01

    Let $F$ be a non-archimedean local field of characteristic zero, let $(\\pi,V)$ be an irreducible, admissible representation of $\\GSp(4,F)$ with trivial central character, and let $\\chi$ be a quadratic character of $F^\\times$ with conductor $c(\\chi)>1$. We define a twisting operator $T_\\chi$ from paramodular vectors for $\\pi$ of level $n$ to paramodular vectors for $\\chi \\otimes \\pi$ of level $\\max(n+2c(\\chi),4c(\\chi))$, and prove that this operator has properties analogous to the well-known $...

  11. Matrix vector analysis

    CERN Document Server

    Eisenman, Richard L

    2005-01-01

    This outstanding text and reference applies matrix ideas to vector methods, using physical ideas to illustrate and motivate mathematical concepts but employing a mathematical continuity of development rather than a physical approach. The author, who taught at the U.S. Air Force Academy, dispenses with the artificial barrier between vectors and matrices--and more generally, between pure and applied mathematics.Motivated examples introduce each idea, with interpretations of physical, algebraic, and geometric contexts, in addition to generalizations to theorems that reflect the essential structur

  12. Sums and Gaussian vectors

    CERN Document Server

    Yurinsky, Vadim Vladimirovich

    1995-01-01

    Surveys the methods currently applied to study sums of infinite-dimensional independent random vectors in situations where their distributions resemble Gaussian laws. Covers probabilities of large deviations, Chebyshev-type inequalities for seminorms of sums, a method of constructing Edgeworth-type expansions, estimates of characteristic functions for random vectors obtained by smooth mappings of infinite-dimensional sums to Euclidean spaces. A self-contained exposition of the modern research apparatus around CLT, the book is accessible to new graduate students, and can be a useful reference for researchers and teachers of the subject.

  13. Perceptual vector quantization for video coding

    Science.gov (United States)

    Valin, Jean-Marc; Terriberry, Timothy B.

    2015-03-01

    This paper applies energy conservation principles to the Daala video codec using gain-shape vector quantization to encode a vector of AC coefficients as a length (gain) and direction (shape). The technique originates from the CELT mode of the Opus audio codec, where it is used to conserve the spectral envelope of an audio signal. Conserving energy in video has the potential to preserve textures rather than low-passing them. Explicitly quantizing a gain allows a simple contrast masking model with no signaling cost. Vector quantizing the shape keeps the number of degrees of freedom the same as scalar quantization, avoiding redundancy in the representation. We demonstrate how to predict the vector by transforming the space it is encoded in, rather than subtracting off the predictor, which would make energy conservation impossible. We also derive an encoding of the vector-quantized codewords that takes advantage of their non-uniform distribution. We show that the resulting technique outperforms scalar quantization by an average of 0.90 dB on still images, equivalent to a 24.8% reduction in bitrate at equal quality, while for videos, the improvement averages 0.83 dB, equivalent to a 13.7% reduction in bitrate.

  14. Two-host, two-vector basic reproduction ratio (R(0 for bluetongue.

    Directory of Open Access Journals (Sweden)

    Joanne Turner

    Full Text Available Mathematical formulations for the basic reproduction ratio (R(0 exist for several vector-borne diseases. Generally, these are based on models of one-host, one-vector systems or two-host, one-vector systems. For many vector borne diseases, however, two or more vector species often co-occur and, therefore, there is a need for more complex formulations. Here we derive a two-host, two-vector formulation for the R(0 of bluetongue, a vector-borne infection of ruminants that can have serious economic consequences; since 1998 for example, it has led to the deaths of well over 1 million sheep in Europe alone. We illustrate our results by considering the situation in South Africa, where there are two major hosts (sheep, cattle and two vector species with differing ecologies and competencies as vectors, for which good data exist. We investigate the effects on R(0 of differences in vector abundance, vector competence and vector host preference between vector species. Our results indicate that R(0 can be underestimated if we assume that there is only one vector transmitting the infection (when there are in fact two or more and/or vector host preferences are overlooked (unless the preferred host is less beneficial or more abundant. The two-host, one-vector formula provides a good approximation when the level of cross-infection between vector species is very small. As this approaches the level of intraspecies infection, a combination of the two-host, one-vector R(0 for each vector species becomes a better estimate. Otherwise, particularly when the level of cross-infection is high, the two-host, two-vector formula is required for accurate estimation of R(0. Our results are equally relevant to Europe, where at least two vector species, which co-occur in parts of the south, have been implicated in the recent epizootic of bluetongue.

  15. Nuclear medium effects via quasielastic (p vector, p vector') and (p vector, n vector) scattering

    International Nuclear Information System (INIS)

    Hillhouse, G.C.; Ventel, B.I.S. van der; Wyngaardt, S.M.; De Kock, P.R.

    1997-01-01

    For a 40 Ca target at a fixed momentum transfer of 1.97 fm -1 , and incident energies between 135 and 300 MeV, we quantitatively investigate the sensitivity of complete sets of quasielastic (p vector, p vector') and (p vector, n vector) spin observables to medium effects, pseudoscalar versus pseudovector forms of the πNN vertex, and exchange contributions to the NN amplitudes using a relativistic PWIA. The qualitative nature of previous studies failed to give an indication of the experimental statistical uncertainty required for distinguishing between the various model predictions. New Horowitz-Love-Franey relativistic NN amplitudes have been generated in order to yield improved and more quantitative spin observable values than before. This study indicates at which energies particular spin observables need to be measured in order to test current nuclear models. A comparison to the limited available data indicates that the relativistic parametrization of the NN scattering amplitudes in terms of only the five Fermi invariants (the SVPAT form) is questionable. (author)

  16. Orthogonalisation of Vectors

    Indian Academy of Sciences (India)

    converting these vectors to orthonormal ones demanded by the model. The process of finding the closest or- thonormal basis is called the Lowdin orthogonalisation after the Swedish chemist P 0 Lowdin who introduced it. This is related to one of the basic theorems in linear algebra as we will see. Matrix Approximation ...

  17. Estimation of vector velocity

    DEFF Research Database (Denmark)

    2000-01-01

    Using a pulsed ultrasound field, the two-dimensional velocity vector can be determined with the invention. The method uses a transversally modulated ultrasound field for probing the moving medium under investigation. A modified autocorrelation approach is used in the velocity estimation. The new...

  18. Sesquilinear uniform vector integral

    Indian Academy of Sciences (India)

    absolute integral which generalizes the Lebesgue integral and is more easy to manipulate. We speak so far about scalar integrals (scalar functions integrated with respect to positive measures-speaking approximately). The idea of integrating vector functions with respect to scalar measures came naturally on the scene of ...

  19. Vector-borne Infections

    Centers for Disease Control (CDC) Podcasts

    2011-04-18

    This podcast discusses emerging vector-borne pathogens, their role as prominent contributors to emerging infectious diseases, how they're spread, and the ineffectiveness of mosquito control methods.  Created: 4/18/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 4/27/2011.

  20. A novel Rieske-type protein derived from an apoptosis-inducing factor-like (AIFL) transcript with a retained intron 4 induces change in mitochondrial morphology and growth arrest

    Energy Technology Data Exchange (ETDEWEB)

    Murata, Yasuhiko, E-mail: 97318@ib.k.u-tokyo.ac.jp [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan); Furuyama, Isao; Oda, Shoji [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan); Mitani, Hiroshi, E-mail: mitani@k.u-tokyo.ac.jp [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8561 (Japan)

    2011-04-01

    Highlights: {yields} A novel major transcript, AIFL-I4, is found. {yields} Nuclear localization of AIFL-I4 induces mitochondrial morphology change and suppression of cell proliferation. {yields} AIFL-I4 mutant with a lesion in [2Fe-2S] cluster binding site does not induce these phenotypes. {yields} [2Fe-2S] cluster binding site is essential for these phenotypes. -- Abstract: Apoptosis-inducing factor-like (AIFL) protein contains a Rieske domain and pyridine nucleotide-disulfide oxidoreductase (Pyr{sub r}edox) domain that shows 35% homology to that of apoptosis-inducing factor (AIF) protein. We identified a novel major transcript of the medaka (Oryzias latipes) AIFL gene that retained intron 4 (AIFL-I4) in embryos and tissues from adult fish. The product of this transcript, AIFL-I4 protein, lacked the Pyr{sub r}edox domain because of a nonsense codon in intron 4. Both AIFL-I4 and full-length AIFL (fAIFL) transcripts were highly expressed in the brain and late embryos, and relative fAIFL and AIFL-I4 expression levels differed among tissues. Transient expression of AIFL-I4 and fAIFL tagged with GFP showed that AIFL-I4 localized in the nucleus, while fAIFL localized throughout the cytoplasm. We also found that overexpression of AIFL-I4 induced a change in mitochondrial morphology and suppression of cell proliferation. AIFL-I4 mutant with a lesion in [2Fe-2S] cluster binding site of the Rieske domain did not induce these phenotypes. This report is the first to demonstrate nuclear localization of a Rieske-type protein translated from the AIFL gene. Our data suggested that the [2Fe-2S] cluster binding site was essential for the nuclear localization and involved in mitochondrial morphology and suppression of cell proliferation.

  1. Current status of genome editing in vector mosquitoes: A review.

    Science.gov (United States)

    Reegan, Appadurai Daniel; Ceasar, Stanislaus Antony; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Al-Dhabi, Naif Abdullah

    2017-01-16

    Mosquitoes pose a major threat to human health as they spread many deadly diseases like malaria, dengue, chikungunya, filariasis, Japanese encephalitis and Zika. Identification and use of novel molecular tools are essential to combat the spread of vector borne diseases. Genome editing tools have been used for the precise alterations of the gene of interest for producing the desirable trait in mosquitoes. Deletion of functional genes or insertion of toxic genes in vector mosquitoes will produce either knock-out or knock-in mutants that will check the spread of vector-borne diseases. Presently, three types of genome editing tools viz., zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regulatory interspaced short palindromic repeats (CRISPR) and CRISPR associated protein 9 (Cas9) are widely used for the editing of the genomes of diverse organisms. These tools are also applied in vector mosquitoes to control the spread of vector-borne diseases. A few studies have been carried out on genome editing to control the diseases spread by vector mosquitoes and more studies need to be performed with the utilization of more recently invented tools like CRISPR/Cas9 to combat the spread of deadly diseases by vector mosquitoes. The high specificity and flexibility of CRISPR/Cas9 system may offer possibilities for novel genome editing for the control of important diseases spread by vector mosquitoes. In this review, we present the current status of genome editing research on vector mosquitoes and also discuss the future applications of vector mosquito genome editing to control the spread of vectorborne diseases.

  2. Modeling Chagas disease in Chile: From vector to congenital transmission.

    Science.gov (United States)

    Canals, Mauricio; Cáceres, Dante; Alvarado, Sergio; Canals, Andrea; Cattan, Pedro E

    Chagaś disease is a human health problem in Latin America. It is highly prevalent in northern Chile between the Arica-Parinacota and Coquimbo regions, with reported incidence of 3-11/100000 inhabitants and mortality of 0.3-0.4/100000. The interruption of vector transmission was reported in 1999 by means of the elimination of the primary vector, Triatoma infestans, from human dwellings, thus the epidemiologic dynamics of this disease should be modified. Here we model the dynamics of Chagaś disease based on previous models for vector and congenital transmission, propose a model that includes both transmission forms and perform simulations. We derive useful relationships for the reproductive number (R 0 ) showing that it may be expressed as the sum of the vector (R 0V ) and congenital (R 0C ) contributions. The vector contribution is larger than the congenital one; without the former Chagaś disease vanishes exponentially in two to three generations. Sensitivity analyses showed that the main parameters that intervene are the human bite rate, the density of vectors per human and the mortality rate of the insect vectors. Our model showed that the success of the eradication of Chagaś disease is based on the interruption of domestic transmission. Once this is obtained, the control strategies should focus on avoiding the domiciliation of wild vectors, re-colonization by the primary vector, and an adequate coverage of congenital case treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Generalized Proca action for an Abelian vector field

    International Nuclear Information System (INIS)

    Allys, Erwan; Peter, Patrick; Rodríguez, Yeinzon

    2016-01-01

    We revisit the most general theory for a massive vector field with derivative self-interactions, extending previous works on the subject to account for terms having trivial total derivative interactions for the longitudinal mode. In the flat spacetime (Minkowski) case, we obtain all the possible terms containing products of up to five first-order derivatives of the vector field, and provide a conjecture about higher-order terms. Rendering the metric dynamical, we covariantize the results and add all possible terms implying curvature

  4. Zinc finger protein 521 overexpression increased transcript levels of ...

    Indian Academy of Sciences (India)

    2016-02-12

    Feb 12, 2016 ... Zfp521 enhanced transcription levels of both EGFP and endogenous Fndc5. This result was confirmed by overexpression the aforementioned vectors in HEK cells and indicated that Zfp521 functions upstream of Fndc5 expression. It is most likely that Zfp521 may act through the binding to its response ...

  5. Vector-borne diseases

    DEFF Research Database (Denmark)

    More, Simon J.; Bicout, Dominique; Bøtner, Anette

    2017-01-01

    After a request from the Europea n Commission, EFSA’s Panel on Animal Health and Welfaresummarised the main characteristics of 36 vector-borne disease s (VBDs) in 36 web-based storymaps.The risk of introduction in the EU through movement of livestock or pets was assessed for eac h of the36 VBDs...... individually, using a semiquantitative Metho d to INTegrate all relevant RISK aspects(MINTRI SK model), which was further modified to a European scale into the EFSA-VBD-RISK-m odel .Only eight of the 36 VBD-agents had an overall rate of introduction in the EU (being the combinationof the rate of entry, vector...... transmission and establishment) which was estimated to be above 0.001introductions per year. These were Crimean-Congo haemorrhagic fever virus, bluetongue virus, WestNile virus, Schmallenberg virus, Hepatozoon canis, Leishmania infantum, Bunyamwera virus andHighlands J. virus. For these eight dise ases...

  6. Tensor Calculus: Unlearning Vector Calculus

    Science.gov (United States)

    Lee, Wha-Suck; Engelbrecht, Johann; Moller, Rita

    2018-01-01

    Tensor calculus is critical in the study of the vector calculus of the surface of a body. Indeed, tensor calculus is a natural step-up for vector calculus. This paper presents some pitfalls of a traditional course in vector calculus in transitioning to tensor calculus. We show how a deeper emphasis on traditional topics such as the Jacobian can…

  7. Propagating Gateway Vectors.

    Science.gov (United States)

    Reece-Hoyes, John S; Walhout, Albertha J M

    2018-01-02

    Generating stocks of Entry and Destination vectors for use in the Gateway recombinatorial cloning system requires transforming them into Escherichia coli strain DB3.1, where they can replicate because this strain is immune to the effects of the ccdB gene carried in the Gateway cassette. However, mutations in the ccdB gene can arise at low frequency, and these mutant plasmids will consequently allow growth of standard cloning strains of E. coli (e.g., DH5α). Therefore, after making new stocks of Gateway plasmids, their ability to grow in cloning strains of E. coli must be tested. This involves obtaining multiple stocks of vector, each arising from a single plasmid grown in a single DB3.1 bacterial colony, and transforming each stock into both DB3.1 and the preferred cloning strain of E. coli in a controlled fashion. Only vector stocks that effectively kill the standard cloning strain (i.e., no or few colonies are obtained after transformation) should be used in Gateway cloning reactions. The sequence can be performed in 3 d. © 2018 Cold Spring Harbor Laboratory Press.

  8. Vector polynomials for direct analysis of circular wavefront slope data.

    Science.gov (United States)

    Mahajan, Virendra N; Acosta, Eva

    2017-10-01

    In the aberration analysis of a circular wavefront, Zernike circle polynomials are used to obtain its wave aberration coefficients. To obtain these coefficients from the wavefront slope data, we need vector functions that are orthogonal to the gradients of the Zernike polynomials, and are irrotational so as to propagate minimum uncorrelated random noise from the data to the coefficients. In this paper, we derive such vector functions, which happen to be polynomials.

  9. Sp1 is an important transcriptional regulation factor for forkhead box ...

    Indian Academy of Sciences (India)

    DONG JIE ZHANG

    2018-02-08

    Feb 8, 2018 ... Abstract. The transcription factor forkhead box N1 (Foxn1) plays an important role in the development and function of thymic epithelial cells (TECs) in vertebrates. However, the transcriptional regulation of Foxn1 is still unknown. A series of dual luciferase report vectors were constructed and their relative ...

  10. Statistical Theory of the Vector Random Decrement Technique

    Science.gov (United States)

    ASMUSSEN, J. C.; BRINCKER, R.; IBRAHIM, S. R.

    1999-09-01

    The Vector Random Decrement technique has previously been introduced as an efficient method to transform ambient responses of linear structures into Vector Random Decrement functions which are equivalent to free decays of the current structure. The modal parameters can be extracted from the free decays. Due to the speed and/or accuracy of the Vector Random Decrement technique, it was introduced as an attractive alternative to the Random Decrement technique. In this paper, the theory of the Vector Random Decrement technique is extended by applying a statistical description of the stochastic processes describing the ambient measurements. The Vector Random Decrement functions are linked to the correlation functions of the stochastic processes provided they are stationary and Gaussian distributed. Furthermore, a new approach for quality assessment of the Vector Random Decrement functions is given on the basis of the derived results. The work presented in this paper makes the theory of the Vector Random Decrement technique equivalent to the theory of the Random Decrement technique. The theoretical derivations are illustrated by the analysis of the response of a 3DOF system loaded by white noise.

  11. Mechanism of reduction in titers from lentivirus vectors carrying large inserts in the 3'LTR.

    Science.gov (United States)

    Urbinati, Fabrizia; Arumugam, Paritha; Higashimoto, Tomoyasu; Perumbeti, Anil; Mitts, Kyle; Xia, Ping; Malik, Punam

    2009-09-01

    Self-inactivating (SIN) lentiviruses flanked by the 1.2-kb chicken hypersensitive site-4 (cHS4) insulator element provide consistent, improved expression of transgenes, but have significantly lower titers. The mechanism by which this occurs is unknown. Lengthening the lentiviral (LV) vector transgene cassette by an additional 1.2 kb by an internal cassette caused no further reduction in titers. However, when cHS4 sequences or inert DNA spacers of increasing size were placed in the 3'-long terminal repeat (LTR), infectious titers decreased proportional to the length of the insert. The stage of vector life cycle affected by vectors carrying the large cHS4 3'LTR insert was compared to a control vector: there was no increase in read-through transcription with insertion of the 1.2-kb cHS4 in the 3'LTR. Equal amount of full-length viral mRNA was produced in packaging cells and viral assembly/packaging was unaffected, resulting in comparable amounts of intact vector particles produced by either vectors. However, LV vectors carrying cHS4 in the 3'LTR were inefficiently processed following target-cell entry, with reduced reverse transcription and integration efficiency, and hence lower transduction titers. Therefore, vectors with large insertions in the 3'LTR are transcribed and packaged efficiently, but the LTR insert hinders viral-RNA (vRNA) processing and transduction of target cells. These studies have important implications in design of integrating vectors.

  12. Leishmaniasis vector behaviour in Kenya

    International Nuclear Information System (INIS)

    Mutinga, M.J.

    1980-01-01

    Leishmaniasis in Kenya exists in two forms: cutaneous and visceral. The vectors of visceral leishmaniasis have been the subject of investigation by various researchers since World War II, when the outbreak of the disease was first noticed. The vectors of cutaneous leishmaniasis were first worked on only a decade ago after the discovery of the disease focus in Mt. Elgon. The vector behaviour of these diseases, namely Phlebotomus pedifer, the vector of cutaneous leishmaniasis, and Phlebotomus martini, the vector of visceral leishmaniasis, are discussed in detail. P. pedifer has been found to breed and bite inside caves, whereas P. martini mainly bites inside houses. (author)

  13. Push-outs of derivations

    Indian Academy of Sciences (India)

    B containing A as an ideal, thereby exploiting (or establishing) hereditary properties. This is usually done using ... space X [Bl, G2], it is exploited that derivations can be extended to the Banach alge- bra B(X) of all ... A derivation is inner if it is of the form a ↦→ a.x − x.a for some x ∈ X. The vector space of all derivations D: A ...

  14. Transcriptional analysis of genes on human chromosome 21

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, P.W.; Van Kueren, M.L.; Kurnit, D.M. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others

    1994-09-01

    The polymerase chain reaction (PCR) was used to screen embryonic, fetal and adult human cDNA libraries for transcription on chromosome 21q22.1{yields}21q22.3. 73 pairs of oligonucleotide primers on chromosome 21 were applied to analyze 41 different cDNA libraries. Only phage eluate (and therefore no DNA isolation) was required for this sensitive screening. This technique was first used to demonstrate that huntingtin is expressed ubiquitiously throughout human life. 60 of the primers were positive with at least one library screening, indicating that the majority of primers derived from transcribed sequences. We examined embryonic (which we synthesized), fetal and adult human cDNA libraries. Even with our most complex human fetal brain library, we detected only ca. 50% of transcribed sequences, underscoring the need to screen multiple human cDNA libraries to determine if transcription occurred. Since only 2/73 clones were present in only one cDNA library, the vast majority of transcribed sequences are present in more than one tissue. Because this study involves random genes rather than genes selected because of their import, this demonstrates that only few anonymous genes are transcribed in a single tissue type. Expression of genes in different cDNA libraries aids in comparison between genotype and phenotype. Using combinations of gene-specific and vector-specific primers, we went on to develop a PCR-based technology that retrieves the largest sequences present in a cDNA library. This technology was used to isolate large genes on chromosome 21 that can be used in expression studies to examine the Down syndrome phenotype.

  15. pSiM24 is a novel versatile gene expression vector for transient assays as well as stable expression of foreign genes in plants.

    Directory of Open Access Journals (Sweden)

    Dipak Kumar Sahoo

    Full Text Available We have constructed a small and highly efficient binary Ti vector pSiM24 for plant transformation with maximum efficacy. In the pSiM24 vector, the size of the backbone of the early binary vector pKYLXM24 (GenBank Accession No. HM036220; a derivative of pKYLX71 was reduced from 12.8 kb to 7.1 kb. The binary vector pSiM24 is composed of the following genetic elements: left and right T-DNA borders, a modified full-length transcript promoter (M24 of Mirabilis mosaic virus with duplicated enhancer domains, three multiple cloning sites, a 3'rbcsE9 terminator, replication functions for Escherichia coli (ColE1 and Agrobacterium tumefaciens (pRK2-OriV and the replicase trfA gene, selectable marker genes for kanamycin resistance (nptII and ampicillin resistance (bla. The pSiM24 plasmid offers a wide selection of cloning sites, high copy numbers in E. coli and a high cloning capacity for easily manipulating different genetic elements. It has been fully tested in transferring transgenes such as green fluorescent protein (GFP and β-glucuronidase (GUS both transiently (agro-infiltration, protoplast electroporation and biolistic and stably in plant systems (Arabidopsis and tobacco using both agrobacterium-mediated transformation and biolistic procedures. Not only reporter genes, several other introduced genes were also effectively expressed using pSiM24 expression vector. Hence, the pSiM24 vector would be useful for various plant biotechnological applications. In addition, the pSiM24 plasmid can act as a platform for other applications, such as gene expression studies and different promoter expressional analyses.

  16. The Transcription Factor Encyclopedia

    NARCIS (Netherlands)

    Yusuf, Dimas; Butland, Stefanie L.; Swanson, Magdalena I.; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A.; Zhang, Xiao Yu Cindy; Dickman, Christopher T. D.; Fulton, Debra L.; Lim, Jonathan S.; Schnabl, Jake M.; Ramos, Oscar H. P.; Vasseur-Cognet, Mireille; de Leeuw, Charles N.; Simpson, Elizabeth M.; Ryffel, Gerhart U.; Lam, Eric W.-F.; Kist, Ralf; Wilson, Miranda S. C.; Marco-Ferreres, Raquel; Brosens, Jan J.; Beccari, Leonardo L.; Bovolenta, Paola; Benayoun, Bérénice A.; Monteiro, Lara J.; Schwenen, Helma D. C.; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A.; Chakravarthy, Harini; Hoodless, Pamela A.; Mancarelli, M. Michela; Torbett, Bruce E.; Banham, Alison H.; Reddy, Sekhar P.; Cullum, Rebecca L.; Liedtke, Michaela; Tschan, Mario P.; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J.; Eijkelenboom, Astrid; Brown, Philip J.; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L.; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H.; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J.; van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W. Z.; Breslin, Mary B.; Lan, Michael S.; Nanan, Kyster K.; Wegner, Michael; Hou, Juan; Mullen, Rachel D.; Colvin, Stephanie C.; Noy, Peter John; Webb, Carol F.; Witek, Matthew E.; Ferrell, Scott; Daniel, Juliet M.; Park, Jason; Waldman, Scott A.; Peet, Daniel J.; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J.; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M.; Woodcroft, Mark W.; Hough, Margaret R.; Chen, Edwin; Europe-Finner, G. Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; Lebrun, David P.; Biswal, Shyam; Harvey, Christopher J.; Debruyne, Jason P.; Hogenesch, John B.; Hevner, Robert F.; Héligon, Christophe; Luo, Xin M.; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S.; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M.; Bradley, Philip H.; Wasserman, Wyeth W.

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review

  17. The role of vector fields in modified gravity scenarios

    International Nuclear Information System (INIS)

    Tasinato, Gianmassimo; Koyama, Kazuya; Khosravi, Nima

    2013-01-01

    Gravitational vector degrees of freedom typically arise in many examples of modified gravity models. We start to systematically explore their role in these scenarios, studying the effects of coupling gravitational vector and scalar degrees of freedom. We focus on set-ups that enjoy a Galilean symmetry in the scalar sector and an Abelian gauge symmetry in the vector sector. These symmetries, together with the requirement that the equations of motion contain at most two space-time derivatives, only allow for a small number of operators in the Lagrangian for the gravitational fields. We investigate the role of gravitational vector fields for two broad classes of phenomena that characterize modified gravity scenarios. The first is self-acceleration: we analyze in general terms the behavior of vector fluctuations around self-accelerating solutions, and show that vanishing kinetic terms of vector fluctuations lead to instabilities on cosmological backgrounds. The second phenomenon is the screening of long range fifth forces by means of Vainshtein mechanism. We show that if gravitational vector fields are appropriately coupled to a spherically symmetric source, they can play an important role for defining the features of the background solution and the scale of the Vainshtein radius. Our general results can be applied to any concrete model of modified gravity, whose low-energy vector and scalar degrees of freedom satisfy the symmetry requirements that we impose

  18. Lentiviral vectors for treating and modeling human CNS disorders.

    Science.gov (United States)

    Azzouz, Mimoun; Kingsman, Susan M; Mazarakis, Nicholas D

    2004-09-01

    Vectors based on lentiviruses efficiently deliver genes into many different types of primary neurons from a broad range of species including man and the resulting gene expression is long term. These vectors are opening up new approaches for the treatment of neurological diseases such as Parkinson's disease (PD), Huntington's disease (HD), and motor neuron diseases (MNDs). Numerous animal studies have now been undertaken with these vectors and correction of disease models has been obtained. Lentiviral vectors also provide a new strategy for in vivo modeling of human diseases; for example, the lentiviral-mediated overexpression of mutated human alpha-synuclein or huntingtin genes in basal ganglia induces neuronal pathology in animals resembling PD and HD in man. These vectors have been refined to a very high level and can be produced safely for the clinic. This review will describe the general features of lentiviral vectors with particular emphasis on vectors derived from the non-primate lentivirus, equine infectious anemia virus (EIAV). It will then describe some key examples of genetic correction and generation of genetic animal models of neurological diseases. The prospects for clinical application of lentiviral vectors for the treatment of PD and MNDs will also be outlined. Copyright 2004 John Wiley & Sons, Ltd.

  19. On vector equilibrium problem

    Indian Academy of Sciences (India)

    Let X be a real topological vector space; K & X be a nonempty closed convex set; ЕYY PЖ be a real ordered ... induced by a solid pointed closed convex cone P, thus x P y@Ay └ x P P, VxY y P Y; f : X ┬ X└3Y with .... tone; VxY y P K, the function t P Й0Y 1К└3gЕty З Е1 └ tЖxY yЖ is continuous at 0З; g is a P-convex and ...

  20. Scalar and vector Galileons

    Science.gov (United States)

    Rodríguez, Yeinzon; Navarro, Andrés A.

    2017-03-01

    An alternative for the construction of fundamental theories is the introduction of Galileons. These are fields whose action leads to non higher than second-order equations of motion. As this is a necessary but not sufficient condition to make the Hamiltonian bounded from below, as long as the action is not degenerate, the Galileon construction is a way to avoid pathologies both at the classical and quantum levels. Galileon actions are, therefore, of great interest in many branches of physics, specially in high energy physics and cosmology. This proceedings contribution presents the generalities of the construction of both scalar and vector Galileons following two different but complimentary routes.

  1. Hybrid Lentivirus-transposon Vectors With a Random Integration Profile in Human Cells

    DEFF Research Database (Denmark)

    Staunstrup, Nicklas H; Moldt, Brian; Mátés, Lajos

    2009-01-01

    Sleeping Beauty (SB) transposon vectors have a significantly safer insertion profile, but efficient delivery into relevant cell/tissue types is a limitation. In an attempt to combine the favorable features of the two vector systems we established a novel hybrid vector technology based on SB transposase...... directs efficient transposon mobilization from DNA circles in vector-transduced cells. Both transfected plasmid DNA and transduced IDLVs can serve as the source of active transposase. Most important, we demonstrate that the SB transposase overrides the natural lentiviral integration pathway and directs...... vector integration less frequently toward transcriptional units, resulting in a random genomic integration profile. The novel hybrid vector system combines the attractive features of efficient gene delivery by viral transduction and a safer genomic integration profile by DNA transposition....

  2. Inhibition of Corneal Neovascularization with the Combination of Bevacizumab and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 (p-PEDF-SAINT-18 Vector in a Rat Corneal Experimental Angiogenesis Model

    Directory of Open Access Journals (Sweden)

    Ching-Hsein Chen

    2013-04-01

    Full Text Available Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups (Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μg of p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV. The bFGF and PEDF genes were successfully expressed as shown by western blot analysis, and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival.Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonalantibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeabilityproperties. In this study, we demonstrated that the combination of bevacizumaband plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18 has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and

  3. Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.

    Science.gov (United States)

    Kuo, Chien-Neng; Chen, Chung-Yi; Chen, San-Ni; Yang, Lin-Cheng; Lai, Li-Ju; Lai, Chien-Hsiung; Chen, Miao-Fen; Hung, Chia-Hui; Chen, Ching-Hsein

    2013-04-16

    Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.

  4. Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis.

    Science.gov (United States)

    Kuo, Chien-Neng; Yang, Lin-Cheng; Yang, Cheng-Ta; Lai, Chien-Hsiung; Chen, Miao-Fen; Chen, Chung-Yi; Chen, Chi-Hung; Wu, Pei-Chang; Kou, Hsi-Kung; Chen, Yung-Jen; Hung, Chia-Hui; Tsai, Chong-Bin

    2009-11-01

    The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.

  5. AAV VECTORS VACCINES AGAINST INFECTIOUS DISEASES

    Directory of Open Access Journals (Sweden)

    Karen eNieto

    2014-01-01

    Full Text Available Since their discovery as a tool for gene transfer, vectors derived from the Adeno-Associated Virus (AAV have been used for gene therapy applications and attracted scientist to this field for their exceptional properties of efficiency of in vivo gene transfer and the level and duration of transgene expression. For many years, AAVs have been considered as low immunogenic vectors due to their ability to induce long term expression of non-self-proteins in contrast to what has been observed with other viral vectors, such as adenovirus (Ad, for which strong immune responses against the same transgene products were documented. The perceived low immunogenicity likely explains why the use of AAV vectors for vaccination was not seriously considered before the early 2000s. Indeed, while analyses conducted using a variety of transgenes and animal species slowly changed the vision of the immunological properties of AAVs, an increasing number of studies were also performed in the field of vaccination. Even if the comparison with other modes of vaccination was not systemically performed, the analyses conducted so far in the field of active immunotherapy strongly suggest that AAVs possess some interesting features to be used as tools to produce an efficient and sustained antibody (Ab response. In addition, recent studies also highlighted the potential of AAVs for passive immunotherapy. This review summarizes the main studies conducted to evaluate the potential of AAV vectors for vaccination against infectious agents and discusses their advantages and drawbacks. Altogether, the variety of studies conducted in this field contributes to the understanding of the immunological properties of this versatile virus and to the definition of its possible future applications.

  6. Vertical vector face lift.

    Science.gov (United States)

    Somoano, Brian; Chan, Joanna; Morganroth, Greg

    2011-01-01

    Facial rejuvenation using local anesthesia has evolved in the past decade as a safer option for patients seeking fewer complications and minimal downtime. Mini- and short-scar face lifts using more conservative incision lengths and extent of undermining can be effective in the younger patient with lower face laxity and minimal loose, elastotic neck skin. By incorporating both an anterior and posterior approach and using an incision length between the mini and more traditional face lift, the Vertical Vector Face Lift can achieve longer-lasting and natural results with lesser cost and risk. Submentoplasty and liposuction of the neck and jawline, fundamental components of the vertical vector face lift, act synergistically with superficial musculoaponeurotic system plication to reestablish a more youthful, sculpted cervicomental angle, even in patients with prominent jowls. Dramatic results can be achieved in the right patient by combining with other procedures such as injectable fillers, chin implants, laser resurfacing, or upper and lower blepharoplasties. © 2011 Wiley Periodicals, Inc.

  7. Proofreading of misincorporated nucleotides in DNA transcription

    International Nuclear Information System (INIS)

    Voliotis, Margaritis; Liverpool, Tanniemola B; Cohen, Netta; Molina-París, Carmen

    2012-01-01

    The accuracy of DNA transcription is crucial for the proper functioning of the cell. Although RNA polymerases demonstrate selectivity for correct nucleotides, additional active mechanisms of transcriptional error correction are required to achieve observed levels of fidelity. Recent experimental findings have shed light on a particular mechanism of transcriptional error correction involving: (i) diffusive translocation of the RNA polymerase along the DNA (backtracking) and (ii) irreversible RNA cleavage. This mechanism achieves preferential cleavage of misincorporated nucleotides by biasing the local rates of translocation. Here, we study how misincorporated nucleotides affect backtracking dynamics and how this effect determines the level of transcriptional fidelity. We consider backtracking as a diffusive process in a periodic, one-dimensional energy landscape, which at a coarse-grained level gives rise to a hopping process between neighbouring local minima. We propose a model for how misincorporated nucleotides deform this energy landscape and hence affect the hopping rates. In particular, we show that this model can be used to derive both the theoretical limit on the fidelity (i.e. the minimum fraction of misincorporated nucleotides) and the actual fidelity relative to this optimum, achieved for specific combinations of the cleavage and polymerization rates. Finally, we study how external factors influencing backtracking dynamics affect transcriptional fidelity. We show that biologically relevant loads, similar to those exerted by nucleosomes or other transcriptional barriers, increase error correction. (paper)

  8. Optimality Conditions in Vector Optimization

    CERN Document Server

    Jiménez, Manuel Arana; Lizana, Antonio Rufián

    2011-01-01

    Vector optimization is continuously needed in several science fields, particularly in economy, business, engineering, physics and mathematics. The evolution of these fields depends, in part, on the improvements in vector optimization in mathematical programming. The aim of this Ebook is to present the latest developments in vector optimization. The contributions have been written by some of the most eminent researchers in this field of mathematical programming. The Ebook is considered essential for researchers and students in this field.

  9. Symmetric vectors and algebraic classification

    International Nuclear Information System (INIS)

    Leibowitz, E.

    1980-01-01

    The concept of symmetric vector field in Riemannian manifolds, which arises in the study of relativistic cosmological models, is analyzed. Symmetric vectors are tied up with the algebraic properties of the manifold curvature. A procedure for generating a congruence of symmetric fields out of a given pair is outlined. The case of a three-dimensional manifold of constant curvature (''isotropic universe'') is studied in detail, with all its symmetric vector fields being explicitly constructed

  10. Vector continued fractions using a generalized inverse

    International Nuclear Information System (INIS)

    Haydock, Roger; Nex, C M M; Wexler, Geoffrey

    2004-01-01

    A real vector space combined with an inverse (involution) for vectors is sufficient to define a vector continued fraction whose parameters consist of vector shifts and changes of scale. The choice of sign for different components of the vector inverse permits construction of vector analogues of the Jacobi continued fraction. These vector Jacobi fractions are related to vector and scalar-valued polynomial functions of the vectors, which satisfy recurrence relations similar to those of orthogonal polynomials. The vector Jacobi fraction has strong convergence properties which are demonstrated analytically, and illustrated numerically

  11. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    RNA); and ii) translation, in which the mRNA is translated into a protein. This thesis focus on the ¿rst of these steps, transcription, and speci¿cally the initiation of this. Simpli¿ed, initiation is preceded by the binding of several proteins, known as transcription factors (TFs), to DNA. This takes place...... published providing an unbiased overview of the transcription start site (TSS) usage in a tissue. We have paired this method with high-throughput sequencing technology to produce a library of unprecedented depth (DeepCAGE) for the mouse hippocampus. We investigated this in detail and focused particularly...... control spanning the range from completely muted to cranked up to maximum. The volume, in this case, is the production rate of proteins. This production is the result of a two step procedure: i) transcription, in which a small part of DNA from the genome (a gene) is transcribed into an RNA molecule (an m...

  12. Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing

    Directory of Open Access Journals (Sweden)

    Karine Cambon

    2017-06-01

    Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA, vectorized in an HIV-1-derived lentiviral vector (LV, that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL backbone and removing the original reporter genes. We demonstrate that this novel vector efficiently downregulated HTT expression in vitro in striatal neurons derived from induced pluripotent stem cells (iPSCs of HD patients. It reduced two major pathological HD hallmarks while triggering a minimal inflammatory response, up to 6 weeks after injection, when administered by stereotaxic surgery in the striatum of an in vivo rodent HD model. Further assessment of this shRNA vector in vitro showed proper processing by the endogenous silencing machinery, and we analyzed gene expression changes to identify potential off-targets. These preclinical data suggest that this new shRNA vector fulfills primary biosafety and efficiency requirements for further development in the clinic as a cure for HD.

  13. Covariant Lyapunov vectors

    International Nuclear Information System (INIS)

    Ginelli, Francesco; Politi, Antonio; Chaté, Hugues; Livi, Roberto

    2013-01-01

    Recent years have witnessed a growing interest in covariant Lyapunov vectors (CLVs) which span local intrinsic directions in the phase space of chaotic systems. Here, we review the basic results of ergodic theory, with a specific reference to the implications of Oseledets’ theorem for the properties of the CLVs. We then present a detailed description of a ‘dynamical’ algorithm to compute the CLVs and show that it generically converges exponentially in time. We also discuss its numerical performance and compare it with other algorithms presented in the literature. We finally illustrate how CLVs can be used to quantify deviations from hyperbolicity with reference to a dissipative system (a chain of Hénon maps) and a Hamiltonian model (a Fermi–Pasta–Ulam chain). This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Lyapunov analysis: from dynamical systems theory to applications’. (paper)

  14. Covariant Lyapunov vectors

    Science.gov (United States)

    Ginelli, Francesco; Chaté, Hugues; Livi, Roberto; Politi, Antonio

    2013-06-01

    Recent years have witnessed a growing interest in covariant Lyapunov vectors (CLVs) which span local intrinsic directions in the phase space of chaotic systems. Here, we review the basic results of ergodic theory, with a specific reference to the implications of Oseledets’ theorem for the properties of the CLVs. We then present a detailed description of a ‘dynamical’ algorithm to compute the CLVs and show that it generically converges exponentially in time. We also discuss its numerical performance and compare it with other algorithms presented in the literature. We finally illustrate how CLVs can be used to quantify deviations from hyperbolicity with reference to a dissipative system (a chain of Hénon maps) and a Hamiltonian model (a Fermi-Pasta-Ulam chain). This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to ‘Lyapunov analysis: from dynamical systems theory to applications’.

  15. Chameleon vector bosons

    International Nuclear Information System (INIS)

    Nelson, Ann E.; Walsh, Jonathan

    2008-01-01

    We show that for a force mediated by a vector particle coupled to a conserved U(1) charge, the apparent range and strength can depend on the size and density of the source, and the proximity to other sources. This chameleon effect is due to screening from a light charged scalar. Such screening can weaken astrophysical constraints on new gauge bosons. As an example we consider the constraints on chameleonic gauged B-L. We show that although Casimir measurements greatly constrain any B-L force much stronger than gravity with range longer than 0.1 μm, there remains an experimental window for a long-range chameleonic B-L force. Such a force could be much stronger than gravity, and long or infinite range in vacuum, but have an effective range near the surface of the earth which is less than a micron.

  16. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Science.gov (United States)

    Horino, Satoshi; Uchiyama, Toru; So, Takanori; Nagashima, Hiroyuki; Sun, Shu-Lan; Sato, Miki; Asao, Atsuko; Haji, Yoichi; Sasahara, Yoji; Candotti, Fabio; Tsuchiya, Shigeru; Kure, Shigeo; Sugamura, Kazuo; Ishii, Naoto

    2013-01-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV) vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  17. Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.

    Directory of Open Access Journals (Sweden)

    Satoshi Horino

    Full Text Available X-linked severe combined immunodeficiency (SCID-X1 is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc gene, and characterized by a complete defect of T and natural killer (NK cells. Gene therapy for SCID-X1 using conventional retroviral (RV vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. In this study, we established a gene therapy model of mouse SCID-X1 using a modified foamy virus (FV vector expressing human γc. Analysis of vector integration in a human T cell line demonstrated that the FV vector integration sites were significantly less likely to be located within or near transcriptional start sites than RV vector integration sites. To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.

  18. An Update on Canine Adenovirus Type 2 and Its Vectors

    Directory of Open Access Journals (Sweden)

    Eric J. Kremer

    2010-09-01

    Full Text Available Adenovirus vectors have significant potential for long- or short-term gene transfer. Preclinical and clinical studies using human derived adenoviruses (HAd have demonstrated the feasibility of flexible hybrid vector designs, robust expression and induction of protective immunity. However, clinical use of HAd vectors can, under some conditions, be limited by pre-existing vector immunity. Pre-existing humoral and cellular anti-capsid immunity limits the efficacy and duration of transgene expression and is poorly circumvented by injections of larger doses and immuno-suppressing drugs. This review updates canine adenovirus serotype 2 (CAV-2, also known as CAdV-2 biology and gives an overview of the generation of early region 1 (E1-deleted to helper-dependent (HD CAV-2 vectors. We also summarize the essential characteristics concerning their interaction with the anti-HAd memory immune responses in humans, the preferential transduction of neurons, and its high level of retrograde axonal transport in the central and peripheral nervous system. CAV-2 vectors are particularly interesting tools to study the pathophysiology and potential treatment of neurodegenerative diseases, as anti-tumoral and anti-viral vaccines, tracer of synaptic junctions, oncolytic virus and as a platform to generate chimeric vectors.

  19. Finding a Hadamard matrix by simulated annealing of spin vectors

    Science.gov (United States)

    Bayu Suksmono, Andriyan

    2017-05-01

    Reformulation of a combinatorial problem into optimization of a statistical-mechanics system enables finding a better solution using heuristics derived from a physical process, such as by the simulated annealing (SA). In this paper, we present a Hadamard matrix (H-matrix) searching method based on the SA on an Ising model. By equivalence, an H-matrix can be converted into a seminormalized Hadamard (SH) matrix, whose first column is unit vector and the rest ones are vectors with equal number of -1 and +1 called SH-vectors. We define SH spin vectors as representation of the SH vectors, which play a similar role as the spins on Ising model. The topology of the lattice is generalized into a graph, whose edges represent orthogonality relationship among the SH spin vectors. Starting from a randomly generated quasi H-matrix Q, which is a matrix similar to the SH-matrix without imposing orthogonality, we perform the SA. The transitions of Q are conducted by random exchange of {+, -} spin-pair within the SH-spin vectors that follow the Metropolis update rule. Upon transition toward zeroth energy, the Q-matrix is evolved following a Markov chain toward an orthogonal matrix, at which the H-matrix is said to be found. We demonstrate the capability of the proposed method to find some low-order H-matrices, including the ones that cannot trivially be constructed by the Sylvester method.

  20. Vector performance of a potential energy functional representation

    International Nuclear Information System (INIS)

    Lagana, A.; Ciccarelli, L.; Garcia, E.

    1987-01-01

    In computer codes based on classical mechanics treatments of the molecular dynamics the bottleneck to vectorization is the evaluation of the potential energy and of its derivatives. These calculations are usually confined inside ad hoc routines. Quite often these routines have a complex structure motivated by the complex form of the functional adopted for representing the molecular interaction. Typical examples of potential energy routines difficult to restructure for taking advantage of vector architectures are those concerned with interactions obtained by assembling different functional forms individually designed for describing accurately particular regions of the potential energy surface. A more favourable case are global representations of the potential energy. The authors' suggestion is to follow a multi-body expansion of the interaction. This representation of the potential energy of a triatomic system is not only quite accurate, but it is also easy to vectorize. Several ways of vectorizing related codes and their performances are discussed. Applications to chemical reactions are made

  1. Ricci collineation vectors in fluid space-times

    International Nuclear Information System (INIS)

    Tsamparlis, M.; Mason, D.P.

    1990-01-01

    The properties of fluid space-times that admit a Ricci collineation vector (RCV) parallel to the fluid unit four-velocity vector u a are briefly reviewed. These properties are expressed in terms of the kinematic quantities of the timelike congruence generated by u a . The cubic equation derived by Oliver and Davis [Ann. Inst. Henri Poincare 30, 339 (1979)] for the equation of state p=p(μ) of a perfect fluid space-time that admits an RCV, which does not degenerate to a Killing vector, is solved for physically realistic fluids. Necessary and sufficient conditions for a fluid space-time to admit a spacelike RCV parallel to a unit vector n a orthogonal to u a are derived in terms of the expansion, shear, and rotation of the spacelike congruence generated by n a . Perfect fluid space-times are studied in detail and analogues of the results for timelike RCVs parallel to u a are obtained. Properties of imperfect fluid space-times for which the energy flux vector q a vanishes and n a is a spacelike eigenvector of the anisotropic stress tensor π ab are derived. Fluid space-times with anisotropic pressure are discussed as a special case of imperfect fluid space-times for which n a is an eigenvector of π ab

  2. The Transcriptome of Leishmania major Developmental Stages in Their Natural Sand Fly Vector

    Directory of Open Access Journals (Sweden)

    Ehud Inbar

    2017-04-01

    Full Text Available The life cycle of the Leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. Based on transcriptome sequencing (RNA-Seq results, we describe the first high-resolution analysis of the transcriptome dynamics of four distinct stages of Leishmania major as they develop in a natural vector, Phlebotomus duboscqi. The early transformation from tissue amastigotes to procyclic promastigotes in the blood-fed midgut was accompanied by the greatest number of differentially expressed genes, including the downregulation of amastins, and upregulation of multiple cell surface proteins, sugar and amino acid transporters, and genes related to glucose metabolism and cell cycle progression. The global changes accompanying post-blood meal differentiation of procyclic promastigotes to the nectomonad and metacyclic stages were less extensive, though each displayed a unique signature. The transcriptome of nectomonads, which has not been studied previously, revealed changes consistent with cell cycle arrest and the upregulation of genes associated with starvation and stress, including autophagic pathways of protein recycling. Maturation to the infective, metacyclic stage was accompanied by changes suggesting preadaptation to the intracellular environment of the mammalian host, demonstrated by the amastigote-like profiles of surface proteins and metabolism-related genes. Finally, a direct comparison between sand fly-derived and culture-derived metacyclics revealed a reassuring similarity between the two forms, with the in vivo forms distinguished mainly by a stronger upregulation of transcripts associated with nutrient stress.

  3. Antisense transcription-dependent chromatin signature modulates sense transcript dynamics.

    Science.gov (United States)

    Brown, Thomas; Howe, Françoise S; Murray, Struan C; Wouters, Meredith; Lorenz, Philipp; Seward, Emily; Rata, Scott; Angel, Andrew; Mellor, Jane

    2018-02-12

    Antisense transcription is widespread in genomes. Despite large differences in gene size and architecture, we find that yeast and human genes share a unique, antisense transcription-associated chromatin signature. We asked whether this signature is related to a biological function for antisense transcription. Using quantitative RNA-FISH, we observed changes in sense transcript distributions in nuclei and cytoplasm as antisense transcript levels were altered. To determine the mechanistic differences underlying these distributions, we developed a mathematical framework describing transcription from initiation to transcript degradation. At GAL1 , high levels of antisense transcription alter sense transcription dynamics, reducing rates of transcript production and processing, while increasing transcript stability. This relationship with transcript stability is also observed as a genome-wide association. Establishing the antisense transcription-associated chromatin signature through disruption of the Set3C histone deacetylase activity is sufficient to similarly change these rates even in the absence of antisense transcription. Thus, antisense transcription alters sense transcription dynamics in a chromatin-dependent manner. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  4. Simplified Representation of Vector Fields

    NARCIS (Netherlands)

    Telea, Alexandru; Wijk, Jarke J. van

    1999-01-01

    Vector field visualization remains a difficult task. Although many local and global visualization methods for vector fields such as flow data exist, they usually require extensive user experience on setting the visualization parameters in order to produce images communicating the desired insight. We

  5. The Neural Support Vector Machine

    NARCIS (Netherlands)

    Wiering, Marco; van der Ree, Michiel; Embrechts, Mark; Stollenga, Marijn; Meijster, Arnold; Nolte, A; Schomaker, Lambertus

    2013-01-01

    This paper describes a new machine learning algorithm for regression and dimensionality reduction tasks. The Neural Support Vector Machine (NSVM) is a hybrid learning algorithm consisting of neural networks and support vector machines (SVMs). The output of the NSVM is given by SVMs that take a

  6. Estimation of Motion Vector Fields

    DEFF Research Database (Denmark)

    Larsen, Rasmus

    1993-01-01

    This paper presents an approach to the estimation of 2-D motion vector fields from time varying image sequences. We use a piecewise smooth model based on coupled vector/binary Markov random fields. We find the maximum a posteriori solution by simulated annealing. The algorithm generate sample...

  7. Disease Vector Ecology Profile: Peru

    Science.gov (United States)

    1998-12-01

    vector of urban plague in Peru is the Oriental rat flea, Xenopsylla cheopis. The human flea, Pulex irritans, although biologically an inefficient vector...TEL: (215) 688-4400 Peru - 10 Instituto Nacional de Hygiene Lima, Peru Peru – 11 Institutos Nacionales de Salud Departamento de Animales

  8. GPU Accelerated Vector Median Filter

    Science.gov (United States)

    Aras, Rifat; Shen, Yuzhong

    2011-01-01

    Noise reduction is an important step for most image processing tasks. For three channel color images, a widely used technique is vector median filter in which color values of pixels are treated as 3-component vectors. Vector median filters are computationally expensive; for a window size of n x n, each of the n(sup 2) vectors has to be compared with other n(sup 2) - 1 vectors in distances. General purpose computation on graphics processing units (GPUs) is the paradigm of utilizing high-performance many-core GPU architectures for computation tasks that are normally handled by CPUs. In this work. NVIDIA's Compute Unified Device Architecture (CUDA) paradigm is used to accelerate vector median filtering. which has to the best of our knowledge never been done before. The performance of GPU accelerated vector median filter is compared to that of the CPU and MPI-based versions for different image and window sizes, Initial findings of the study showed 100x improvement of performance of vector median filter implementation on GPUs over CPU implementations and further speed-up is expected after more extensive optimizations of the GPU algorithm .

  9. Archimedeanization of ordered vector spaces

    OpenAIRE

    Emelyanov, Eduard Yu.

    2014-01-01

    In the case of an ordered vector space with an order unit, the Archimedeanization method has been developed recently by V.I Paulsen and M. Tomforde. We present a general version of the Archimedeanization which covers arbitrary ordered vector spaces.

  10. Vector superconductivity in cosmic strings

    International Nuclear Information System (INIS)

    Dvali, G.R.; Mahajan, S.M.

    1992-03-01

    We argue that in most realistic cases, the usual Witten-type bosonic superconductivity of the cosmic string is automatically (independent of the existence of superconducting currents) accompanied by the condensation of charged gauge vector bosons in the core giving rise to a new vector type superconductivity. The value of the charged vector condensate is related with the charged scalar expectation value, and vanishes only if the latter goes to zero. The mechanism for the proposed vector superconductivity, differing fundamentally from those in the literature, is delineated using the simplest realistic example of the two Higgs doublet standard model interacting with the extra cosmic string. It is shown that for a wide range of parameters, for which the string becomes scalarly superconducting, W boson condensates (the sources of vector superconductivity) are necessarily excited. (author). 14 refs

  11. ESTIMATING ELECTRIC FIELDS FROM VECTOR MAGNETOGRAM SEQUENCES

    International Nuclear Information System (INIS)

    Fisher, G. H.; Welsch, B. T.; Abbett, W. P.; Bercik, D. J.

    2010-01-01

    Determining the electric field distribution on the Sun's photosphere is essential for quantitative studies of how energy flows from the Sun's photosphere, through the corona, and into the heliosphere. This electric field also provides valuable input for data-driven models of the solar atmosphere and the Sun-Earth system. We show how observed vector magnetogram time series can be used to estimate the photospheric electric field. Our method uses a 'poloidal-toroidal decomposition' (PTD) of the time derivative of the vector magnetic field. These solutions provide an electric field whose curl obeys all three components of Faraday's Law. The PTD solutions are not unique; the gradient of a scalar potential can be added to the PTD electric field without affecting consistency with Faraday's Law. We then present an iterative technique to determine a potential function consistent with ideal MHD evolution; but this field is also not a unique solution to Faraday's Law. Finally, we explore a variational approach that minimizes an energy functional to determine a unique electric field, a generalization of Longcope's 'Minimum Energy Fit'. The PTD technique, the iterative technique, and the variational technique are used to estimate electric fields from a pair of synthetic vector magnetograms taken from an MHD simulation; and these fields are compared with the simulation's known electric fields. The PTD and iteration techniques compare favorably to results from existing velocity inversion techniques. These three techniques are then applied to a pair of vector magnetograms of solar active region NOAA AR8210, to demonstrate the methods with real data. Careful examination of the results from all three methods indicates that evolution of the magnetic vector by itself does not provide enough information to determine the true electric field in the photosphere. Either more information from other measurements, or physical constraints other than those considered here are necessary to find

  12. Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, Naoki [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); College of Life and Health Sciences, Chubu University, Kasugai (Japan); Omori, Yukari [Department of Pathophysiological Laboratory Science, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kawamoto, Yoshiyuki; Sobue, Sayaka; Ichihara, Masatoshi [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Suzuki, Motoshi [Division of Molecular Carcinogenesis, Nagoya University Graduate School of Medicine, Nagoya (Japan); Kyogashima, Mamoru [Department of Microbiology and Molecular Biology, Nihon Pharmaceutical University, Saitama (Japan); Nakamura, Mitsuhiro [Department of Drug Information, Gifu Pharmaceutical University, Gifu (Japan); Tamiya-Koizumi, Keiko [College of Life and Health Sciences, Chubu University, Kasugai (Japan); Nozawa, Yoshinori [Tokai Gakuin University, Kakamigahara (Japan); Murate, Takashi, E-mail: murate@isc.chubu.ac.jp [College of Life and Health Sciences, Chubu University, Kasugai (Japan)

    2016-02-19

    Resveratrol (RSV) is a plant-derived phytoalexin present in plants, whose pleiotropic effects for health benefits have been previously reported. Its anti-cancer activity is among the current topics for novel cancer treatment. Here, effects of RSV on cell proliferation and the sphingolipid metabolism of K562, a human leukemia cell line, were analyzed. Some experiments were also performed in HCT116, a human colon cancer cell line. RSV inhibited cell proliferation of both cell lines. Increased cellular ceramide and decreased sphingomyelin and S1P by RSV were observed in RSV-treated K562 cells. Further analysis revealed that acid sphingomyelinase mRNA and enzyme activity levels were increased by RSV. Desipramine, a functional ASMase inhibitor, prevented RSV-induced ceramide increase. RSV increased ATF3, EGR1, EGR3 proteins and phosphorylated c-Jun and FOXO3. However, co-transfection using these transcription factor expression vectors and ASMase promoter reporter vector revealed positive effects of EGR1 and EGR3 but not others. Electrophoresis mobility shift assay (EMSA) and Chromatin immunoprecipitation (ChIP) assay demonstrated the direct binding of EGR1/3 transcription factors with ASMase 5′-promoter. These results indicate that increased EGR1/3 and ASMase expression play an important role in cellular ceramide increase by RSV treatment. - Highlights: • Resveratrol inhibited cell proliferation of K562 and HCT116 cells. • Resveratrol increased cellular ceramide and decreased sphingomyelin and S1P. • ASMase mRNA and activity were increased with resveratrol. • ASMase inhibition suppressed RSV-induced ceramide accumulation. • Increased ASMase transcription was at least partially due to EGR family proteins.

  13. Linearity and Misspecification Tests for Vector Smooth Transition Regression Models

    DEFF Research Database (Denmark)

    Teräsvirta, Timo; Yang, Yukai

    The purpose of the paper is to derive Lagrange multiplier and Lagrange multiplier type specification and misspecification tests for vector smooth transition regression models. We report results from simulation studies in which the size and power properties of the proposed asymptotic tests in small...

  14. Evaluation of vaccine competition using HVT vector vaccines

    Science.gov (United States)

    Turkey herpesvirus (HVT) has been widely used as a vaccine for Marek’s disease (MD) since the 1970s. Because HVT is a safe vaccine that is poorly sensitive to interference from maternally derived antibodies, it has seen rising use as a vector for vaccines developed for protection against other comm...

  15. Stability of Vector Functional Differential Equations: A Survey | Gil ...

    African Journals Online (AJOL)

    This paper is a survey of the recent results of the author on the stability of linear and nonlinear vector differential equations with delay. Explicit conditions for the exponential and absolute stabilities are derived. Moreover, solution estimates for the considered equations are established. They provide the bounds for the regions ...

  16. A human parvovirus, adeno-associated virus, as a eucaryotic vector: Transient expression and encapsidation of the procaryotic gene for chloramphenicol acetyltransferase

    Energy Technology Data Exchange (ETDEWEB)

    Tratschin, J.D.; West, M.H.P.; Sandbank, T.; Carter, B.J.

    1984-10-01

    The authors have used the defective human parvovirus adeno-associated virus (AAV) as a novel eurocaryotic vector (parvector) for the expression of a foreign gene in human cells. The recombinant, pAV2, contains the AAV genome in a pBR322-derived bacterial plasmid. When pAV2 is transfected into human cells together with helper adenovirus particles, the AAV genome is rescued from the recombinant plasmid and replicated to produce infectious AAV particles at high efficiency. To create a vector, we inserted a procaryotic sequence coding for chloramphenicol acetyltransferase (CAT) into derivatives of pAV2 following either of the AAV promoters p/sub 40/ (pAVHiCAT) and p/sub 19/ (pAVBcCAT). When transfected into human 293 cells or HeLa cells, pAVHiCAT expressed CAT activity in the absence of adenovirus. In the presence of adenovirus, this vector produced increased amounts of CAT activity and the recombinant AAV-CAT genome was replicated. In 293 cells, pAVBcCAT expressed a similar amount of CAT activity in the absence or presence of adenovirus and the recombinant AAV-CAT genome was not replicated. In HeLa cells, pAVBcCAT expressed low levels of CAT activity, but this level was elevated by coinfection with adenovirus particles or by cotransfection with a plasmid which expressed the adenovirus early region 1A (E1A) product. The E1A product is a transcriptional activator and is expressed in 293 cells. Thus, expression from two AAV promoters is differentially regulated: expression from p/sub 19/ is increased by E1A, whereas p/sub 40/ yields high levels of constitutive expression in the absence of E1A. Both AAV vectors were packaged into AAV particles by complementation with wild-type AAV and yielded CAT activity when subsequently infected into cells in the presence of adenovirus.

  17. Adenovirus-derived vectors for prostate cancer gene therapy

    Czech Academy of Sciences Publication Activity Database

    de Vrij, J.; Willemsen, R. A.; Lindholm, L.; Hoeben, R. C.; Bangma, Ch. H.; Barber, Ch.; Behr, J.-P.; Briggs, S.; Carlisle, R.; Cheng, W.-S.; Dautzenberg, I. J. C.; de Ridder, C.; Dzojic, H.; Erbacher, P.; Essand, M.; Fisher, K.; Frazier, A.; Georgopoulos, L. J.; Jennings, I.; Kochanek, S.; Koppers-Lalic, D.; Kraaij, R.; Kreppel, F.; Magnusson, M.; Maitland, N.; Neuberg, P.; Nugent, R.; Ogris, M.; Remy, J.-S.; Scaife, M.; Schenk, E.; Schooten, E.; Seymour, L.; Slade, M.; Szyjanowicz, P.; Totterman, T.; Uil, T. G.; Ulbrich, Karel; van der Weel, L.; van Weerden, W.; Wagner, E.; Zuber, G.

    2010-01-01

    Roč. 21, č. 7 (2010), s. 795-805 ISSN 1043-0342 EU Projects: European Commission(XE) 512087 - GIANT Keywords : adenovirus * gene delivery * prostate cancer Subject RIV: CD - Macromolecular Chemistry Impact factor: 4.829, year: 2010

  18. Vectorized Shoreline of Alamagan CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  19. Vectorized Shoreline of Anatahan CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  20. Vectorized Shoreline of Guguan CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  1. Vectorized Shoreline of Pagan CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  2. Vectorized Shoreline of Agrihan CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  3. Vectorized Shoreline of Asuncion CNMI 2001, Derived from IKONOS Imagery

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — IKONOS imagery was purchased to support the Pacific Islands Geographic Information System (GIS) project and the National Ocean Service's (NOS) coral mapping...

  4. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...... and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe....

  5. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  6. A host-vector system for gene cloning in the cyanobacterium Anacystis nidulans R2

    NARCIS (Netherlands)

    Kuhlemeier, C. J.; Thomas, A. A.; van der Ende, A.; van Leen, R. W.; Borrias, W. E.; van den Hondel, C. A.; van Arkel, G. A.

    1983-01-01

    We describe the construction of a series of vectors suitable for gene cloning in the cyanobacterium Anacystis nidulans R2. From the indigenous plasmid pUH24, derivatives were constructed with streptomycin as the selective marker; one of these plasmids was used to construct pUC303, a shuttle vector

  7. Characterization of infectivity of knob-modified adenoviral vectors in glioma

    NARCIS (Netherlands)

    C.P.L. Paul (C. P L); M. Everts (M.); J.N. Glasgow (J.); P. Dent (P.); P.B. Fisher (P.); I.V. Ulasov (I.); M.S. Lesniak (M.); M.A. Stoff-Khalili (M.); J.C. Roth (J.); M. Preuss (Michael); C.M.F. Dirven (Clemens); M.L.M. Lamfers (Martine); T. Siegal (Tali); Z.B. Zhu (Z.); R.E. Curiel (Rafael E.)

    2008-01-01

    textabstractMalignant glioma continues to be a major target for gene therapy and virotherapy due to its aggressive growth and the current lack of effective treatment. However, these approaches have been hampered by inefficient infection of glioma cells by viral vectors, particularly vectors derived

  8. Enhancing poxvirus vectors vaccine immunogenicity.

    Science.gov (United States)

    García-Arriaza, Juan; Esteban, Mariano

    2014-01-01

    Attenuated recombinant poxvirus vectors expressing heterologous antigens from pathogens are currently at various stages in clinical trials with the aim to establish their efficacy. This is because these vectors have shown excellent safety profiles, significant immunogenicity against foreign expressed antigens and are able to induce protective immune responses. In view of the limited efficacy triggered by some poxvirus strains used in clinical trials (i.e, ALVAC in the RV144 phase III clinical trial for HIV), and of the restrictive replication capacity of the highly attenuated vectors like MVA and NYVAC, there is a consensus that further improvements of these vectors should be pursuit. In this review we considered several strategies that are currently being implemented, as well as new approaches, to improve the immunogenicity of the poxvirus vectors. This includes heterologous prime/boost protocols, use of co-stimulatory molecules, deletion of viral immunomodulatory genes still present in the poxvirus genome, enhancing virus promoter strength, enhancing vector replication capacity, optimizing expression of foreign heterologous sequences, and the combined use of adjuvants. An optimized poxvirus vector triggering long-lasting immunity with a high protective efficacy against a selective disease should be sought.

  9. Chikungunya Virus–Vector Interactions

    Science.gov (United States)

    Coffey, Lark L.; Failloux, Anna-Bella; Weaver, Scott C.

    2014-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed. PMID:25421891

  10. Chikungunya Virus–Vector Interactions

    Directory of Open Access Journals (Sweden)

    Lark L. Coffey

    2014-11-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed.

  11. Violation of vector dominance in the vector manifestation

    International Nuclear Information System (INIS)

    Sasaki, Chihiro

    2003-01-01

    The vector manifestation (VM) is a new pattern for realizing the chiral symmetry in QCD. In the VM, the massless vector meson becomes the chiral partner of pion at the critical point, in contrast with the restoration based on the linear sigma model. Including the intrinsic temperature dependences of the parameters of the hidden local symmetry (HLS) Lagrangian determined from the underlying QCD through the Wilsonian matching together with the hadronic thermal corrections, we present a new prediction of the VM on the direct photon-π-π coupling which measures the validity of the vector dominance (VD) of the electromagnetic form factor of the pion. We find that the VD is largely violated at the critical temperature, which indicates that the assumption of the VD made in several analysis on the dilepton spectra in hot matter may need to be weakened for consistently including the effect of the dropping mass of the vector meson. (author)

  12. Vector calculation of particle code

    International Nuclear Information System (INIS)

    Nishiguchi, A.; Yabe, T.; Orii, S.

    1985-01-01

    The development of vector computer requires the modification of the algorithm into a suitable form for vector calculation. Among many algorithms, the particle code is a typical example which has suffered a damage in the calculation on supercomputer owing to its possibility of recurrent data access in collecting cell-wise quantities from particle's quartities. In this article, we report a new method to liberate the particle code from recurrent calculations. It should be noticed, however, that the method may depend on the architecture of supercomputer, and works well on FACOM VP-100 and VP-200: the indirect data accessing must be vectorized and its speed should be fast. (Mori, K.)

  13. On the Witt vector Frobenius

    DEFF Research Database (Denmark)

    Davis, Christopher James; Kedlaya, Kiran

    2014-01-01

    We study the kernel and cokernel of the Frobenius map on the p-typical Witt vectors of a commutative ring, not necessarily of characteristic p. We give many equivalent conditions to surjectivity of the Frobenius map on both finite and infinite length Witt vectors. In particular, surjectivity...... on finite Witt vectors turns out to be stable under certain integral extensions; this provides a clean formulation of a strong generalization of Faltings’s almost purity theorem from p-adic Hodge theory, incorporating recent improvements by Kedlaya–Liu and by Scholze....

  14. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Oddershede, Niels

    2008-01-01

    of the thesis considers a method for estimating the two-dimensional velocity vector within the image plane. This method, called synthetic aperture vector flow imaging, is first shortly reviewed. The main contribution of this work is partly an analysis of the method with respect to focusing effects, motion...... estimation. The method can be used for increasing the frame rate of color flow maps or alternatively for a new imaging modality entitled quadroplex imaging, featuring a color flow map and two independent spectrograms at a high frame rate. The second is an alternative method for ultrasonic vector velocity...

  15. Vector control of induction machines

    CERN Document Server

    Robyns, Benoit

    2012-01-01

    After a brief introduction to the main law of physics and fundamental concepts inherent in electromechanical conversion, ""Vector Control of Induction Machines"" introduces the standard mathematical models for induction machines - whichever rotor technology is used - as well as several squirrel-cage induction machine vector-control strategies. The use of causal ordering graphs allows systematization of the design stage, as well as standardization of the structure of control devices. ""Vector Control of Induction Machines"" suggests a unique approach aimed at reducing parameter sensitivity for

  16. Note onset detection for the transcription of polyphonic piano music

    OpenAIRE

    Boogaart, C. Gregor van den; Lienhart, Rainer (Prof. Dr.)

    2009-01-01

    Transcription of music is the process of generating a symbolic representation such as a score sheet or a MIDI file from an audio recording of a piece of music. A statistical machine learning approach for detecting note onsets in polyphonic piano music is presented. An area from the spectrogram of the sound is concatenated into one feature vector. A cascade of boosted classifiers is used for dimensionality reduction and classification in an one-versus-all manner. The presented system achieves ...

  17. Are Bred Vectors The Same As Lyapunov Vectors?

    Science.gov (United States)

    Kalnay, E.; Corazza, M.; Cai, M.

    Regional loss of predictability is an indication of the instability of the underlying flow, where small errors in the initial conditions (or imperfections in the model) grow to large amplitudes in finite times. The stability properties of evolving flows have been studied using Lyapunov vectors (e.g., Alligood et al, 1996, Ott, 1993, Kalnay, 2002), singular vectors (e.g., Lorenz, 1965, Farrell, 1988, Molteni and Palmer, 1993), and, more recently, with bred vectors (e.g., Szunyogh et al, 1997, Cai et al, 2001). Bred vectors (BVs) are, by construction, closely related to Lyapunov vectors (LVs). In fact, after an infinitely long breeding time, and with the use of infinitesimal ampli- tudes, bred vectors are identical to leading Lyapunov vectors. In practical applications, however, bred vectors are different from Lyapunov vectors in two important ways: a) bred vectors are never globally orthogonalized and are intrinsically local in space and time, and b) they are finite-amplitude, finite-time vectors. These two differences are very significant in a dynamical system whose size is very large. For example, the at- mosphere is large enough to have "room" for several synoptic scale instabilities (e.g., storms) to develop independently in different regions (say, North America and Aus- tralia), and it is complex enough to have several different possible types of instabilities (such as barotropic, baroclinic, convective, and even Brownian motion). Bred vectors share some of their properties with leading LVs (Corazza et al, 2001a, 2001b, Toth and Kalnay, 1993, 1997, Cai et al, 2001). For example, 1) Bred vectors are independent of the norm used to define the size of the perturba- tion. Corazza et al. (2001) showed that bred vectors obtained using a potential enstro- phy norm were indistinguishable from bred vectors obtained using a streamfunction squared norm, in contrast with singular vectors. 2) Bred vectors are independent of the length of the rescaling period as long as the

  18. Machine Dictation and Transcription.

    Science.gov (United States)

    Harvey, Evelyn; And Others

    This instructional package contains both an instructor's manual and a student's manual for a course in machine dictation and transcription. The instructor's manual contains an overview with tips on teaching the course, letters for dictation, and a key to the letters. The student's manual contains an overview of the course and of the skills needed…

  19. Automatic Music Transcription

    Science.gov (United States)

    Klapuri, Anssi; Virtanen, Tuomas

    Written musical notation describes music in a symbolic form that is suitable for performing a piece using the available musical instruments. Traditionally, musical notation indicates the pitch, target instrument, timing, and duration of each sound to be played. The aim of music transcription either by humans or by a machine is to infer these musical parameters, given only the acoustic recording of a performance.

  20. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any

  1. Spherical cap modelling of Orsted magnetic field vectors over southern Africa

    CSIR Research Space (South Africa)

    Kotze, PB

    2001-01-01

    Full Text Available Vector magnetic field observations by the Orsted satellite during geomagnetic quiet conditions around January 1, 2000, have been employed to derive a spherical cap harmonic model (Haines, 1985) over the southern African region between 10 degrees...

  2. Cyanobacterium sp. host cell and vector for production of chemical compounds in Cyanobacterial cultures

    Energy Technology Data Exchange (ETDEWEB)

    Piven, Irina; Friedrich, Alexandra; Duhring, Ulf; Uliczka, Frank; Baier, Kerstin; Inaba, Masami; Shi, Tuo; Wang, Kui; Enke, Heike; Kramer, Dan

    2016-04-19

    A cyanobacterial host cell, Cyanobacterium sp., that harbors at least one recombinant gene for the production of a chemical compounds is provided, as well as vectors derived from an endogenous plasmid isolated from the cell.

  3. Sum Capacity (Sub)optimality of Orthogonal Transmissions in Vector Gaussian Multiple Access Channels

    National Research Council Canada - National Science Library

    Shang, Xiaohu; Chen, Biao; Matyjas, John

    2007-01-01

    ...). Specifically, we derive the sufficient and necessary conditions, in terms of channel matrices and transmitter power constraints, for orthogonal transmission to achieve the sum capacity of a vector Gaussian MAC...

  4. Shifting suitability for malaria vectors across Africa with warming climates

    Directory of Open Access Journals (Sweden)

    Peterson A Townsend

    2009-05-01

    Full Text Available Abstract Background Climates are changing rapidly, producing warm climate conditions globally not previously observed in modern history. Malaria is of great concern as a cause of human mortality and morbidity, particularly across Africa, thanks in large part to the presence there of a particularly competent suite of mosquito vector species. Methods I derive spatially explicit estimates of human populations living in regions newly suitable climatically for populations of two key Anopheles gambiae vector complex species in Africa over the coming 50 years, based on ecological niche model projections over two global climate models, two scenarios of climate change, and detailed spatial summaries of human population distributions. Results For both species, under all scenarios, given the changing spatial distribution of appropriate conditions and the current population distribution, the models predict a reduction of 11.3–30.2% in the percentage of the overall population living in areas climatically suitable for these vector species in coming decades, but reductions and increases are focused in different regions: malaria vector suitability is likely to decrease in West Africa, but increase in eastern and southern Africa. Conclusion Climate change effects on African malaria vectors shift their distributional potential from west to east and south, which has implications for overall numbers of people exposed to these vector species. Although the total is reduced, malaria is likely to pose novel public health problems in areas where it has not previously been common.

  5. Shifting suitability for malaria vectors across Africa with warming climates.

    Science.gov (United States)

    Peterson, A Townsend

    2009-05-10

    Climates are changing rapidly, producing warm climate conditions globally not previously observed in modern history. Malaria is of great concern as a cause of human mortality and morbidity, particularly across Africa, thanks in large part to the presence there of a particularly competent suite of mosquito vector species. I derive spatially explicit estimates of human populations living in regions newly suitable climatically for populations of two key Anopheles gambiae vector complex species in Africa over the coming 50 years, based on ecological niche model projections over two global climate models, two scenarios of climate change, and detailed spatial summaries of human population distributions. For both species, under all scenarios, given the changing spatial distribution of appropriate conditions and the current population distribution, the models predict a reduction of 11.3-30.2% in the percentage of the overall population living in areas climatically suitable for these vector species in coming decades, but reductions and increases are focused in different regions: malaria vector suitability is likely to decrease in West Africa, but increase in eastern and southern Africa. Climate change effects on African malaria vectors shift their distributional potential from west to east and south, which has implications for overall numbers of people exposed to these vector species. Although the total is reduced, malaria is likely to pose novel public health problems in areas where it has not previously been common.

  6. Vectorization at the KENO-IV code

    International Nuclear Information System (INIS)

    Asai, K.; Higuchi, K.; Katakura, J.

    1986-01-01

    The multigroup criticality safety code KENO-IV has been vectorized and tested on the FACOM VP-100 vector processor. At first, the vectorized KENO-IV on a scalar processor was slower than the original one by a factor of 1.4 because of the overhead introduced by vectorization. Making modifications of algorithms and techniques for vectorization, the vectorized version has become faster than the original one by a factor of 1.4 on the vector processor. For further speedup of the code, some improvements on compiler and hardware, especially on addition of Monte Carlo pipelines to the vector processor, are discussed

  7. Introduction to matrices and vectors

    CERN Document Server

    Schwartz, Jacob T

    2001-01-01

    In this concise undergraduate text, the first three chapters present the basics of matrices - in later chapters the author shows how to use vectors and matrices to solve systems of linear equations. 1961 edition.

  8. Disease Vector Ecology Profile: Ecuador

    Science.gov (United States)

    1998-12-01

    biologically an inefficient vector, has an insatiable feeding preference for Rattus spp., Cavia porcellus (guinea pigs), domestic animals (swine...71 Peru – 11 Institutos Nacionales de Salud Departamento de Animales Venenosos Calle Capac Yupanqui 1400 Apartado 451 Lima, Peru TEL

  9. GRE Enzymes for Vector Analysis

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme data that were collected during the 2004-2006 EMAP-GRE program. These data were then used by Moorhead et al (2016) in their ecoenzyme vector...

  10. High Accuracy Vector Helium Magnetometer

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed HAVHM instrument is a laser-pumped helium magnetometer with both triaxial vector and omnidirectional scalar measurement capabilities in a single...

  11. Spectrum-generating SU(4) in particle physics. II. Electromagnetic decays of vector mesons

    International Nuclear Information System (INIS)

    Bohm, A.; Teese, R.B.

    1977-09-01

    The decay rates for the electromagnetic decays of vector mesons are derived within the spectrum-generating SU(4) approach. Radiative as well as leptonic decays of vector mesons can be derived from one theoretical assumption and given in terms of three reduced matrix elements. The implication of the experimental value GAMMA(rho → πγ) = (35 +- 10) keV for the form of the electromagnetic current operator is discussed

  12. The Transcriptome of Leishmania major Developmental Stages in Their Natural Sand Fly Vector.

    Science.gov (United States)

    Inbar, Ehud; Hughitt, V Keith; Dillon, Laura A L; Ghosh, Kashinath; El-Sayed, Najib M; Sacks, David L

    2017-04-04

    The life cycle of the Leishmania parasite in the sand fly vector involves differentiation into several distinctive forms, each thought to represent an adaptation to specific microenvironments in the midgut of the fly. Based on transcriptome sequencing (RNA-Seq) results, we describe the first high-resolution analysis of the transcriptome dynamics of four distinct stages of Leishmania major as they develop in a natural vector, Phlebotomus duboscqi The early transformation from tissue amastigotes to procyclic promastigotes in the blood-fed midgut was accompanied by the greatest number of differentially expressed genes, including the downregulation of amastins, and upregulation of multiple cell surface proteins, sugar and amino acid transporters, and genes related to glucose metabolism and cell cycle progression. The global changes accompanying post-blood meal differentiation of procyclic promastigotes to the nectomonad and metacyclic stages were less extensive, though each displayed a unique signature. The transcriptome of nectomonads, which has not been studied previously, revealed changes consistent with cell cycle arrest and the upregulation of genes associated with starvation and stress, including autophagic pathways of protein recycling. Maturation to the infective, metacyclic stage was accompanied by changes suggesting preadaptation to the intracellular environment of the mammalian host, demonstrated by the amastigote-like profiles of surface proteins and metabolism-related genes. Finally, a direct comparison between sand fly-derived and culture-derived metacyclics revealed a reassuring similarity between the two forms, with the in vivo forms distinguished mainly by a stronger upregulation of transcripts associated with nutrient stress. IMPORTANCE The life cycle of Leishmania parasites in the sand fly vector includes their growth and development as morphologically distinct forms of extracellular promastigotes found within the different microenvironments of the

  13. Propagation property of the non-paraxial vector Lissajous singularity beams in free space

    Science.gov (United States)

    Chen, Haitao; Gao, Zenghui

    2016-12-01

    The analytic expressions for the free-space propagation of paraxial and non-paraxial vector Lissajous singularity beams are derived, and used to compare the propagation property of a Lissajous singularity carried by paraxial and non-paraxial vector beams in free space. It is found that the creation of a single Lissajous singularity, the creation and annihilation of pairs Lissajous singularities may take place for the both cases. However, after the annihilation of a pair of singularities, no Lissajous singularities appear in the output field for non-paraxial vector Lissajous singularity beams, which is different from the paraxial vector Lissajous singularity beams.

  14. On the population dynamics of the malaria vector

    International Nuclear Information System (INIS)

    Ngwa, G.A.

    2005-10-01

    A deterministic differential equation model for the population dynamics of the human malaria vector is derived and studied. Conditions for the existence and stability of a non-zero steady state vector population density are derived. These reveal that a threshold parameter, the vectorial basic reproduction number, exist and the vector can establish itself in the community if and only if this parameter exceeds unity. When a non-zero steady state population density exists, it can be stable but it can also be driven to instability via a Hopf Bifurcation to periodic solutions, as a parameter is varied in parameter space. By considering a special case, an asymptotic perturbation analysis is used to derive the amplitude of the oscillating solutions for the full non-linear system. The present modelling exercise and results show that it is possible to study the population dynamics of disease vectors, and hence oscillatory behaviour as it is often observed in most indirectly transmitted infectious diseases of humans, without recourse to external seasonal forcing. (author)

  15. cAMP response element binding protein (CREB activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene

    Directory of Open Access Journals (Sweden)

    Stefano Luisa

    2005-01-01

    Full Text Available Abstract Background The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE. Results The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2, known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene. Conclusions Using a constitutively active CREB2

  16. A single-copy galK promoter cloning vector suitable for cloning strong promoters

    DEFF Research Database (Denmark)

    Dandanell, Gert; Court, Donald L.; Hammer, Karin

    1986-01-01

    We report the construction of lambda galK promoter cloning vectors for cloning and characterization of strong promoters. This phage, which contains a unique HindIII cloning site, was applied to the cloning and analysis of transcription initiations of the regulatory region of the deo-operon of...

  17. Building a bi-directional promoter binary vector from the intergenic ...

    African Journals Online (AJOL)

    ajl

    2013-03-13

    Mar 13, 2013 ... excision of the LOX-P Cre-cassette leaving only a single LOX-P site in MCS2 which is part of the '5 UTR of the GUS transcript. The sequence data of this bidirectional promoter transformation vector,. p2CABA have been submitted to the GenBank databases under accession number JQ965697 (Figure 1).

  18. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  19. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... them to participate in large interactomes, how they use only a few hydrophobic residues, short sequence motifs, prestructured motifs, and coupled folding and binding for their interactions with co-activators, and how their accessibility to post-translational modification affects their interactions...

  20. Spanish dialects: phonetic transcription

    OpenAIRE

    Moreno Bilbao, M. Asunción; Mariño Acebal, José Bernardo

    1998-01-01

    It is well known that canonical Spanish, the dialectal variant `central' of Spain, so called Castilian, can be transcribed by rules. This paper deals with the automatic grapheme to phoneme transcription rules in several Spanish dialects from Latin America. Spanish is a language spoken by more than 300 million people, has an important geographical dispersion compared among other languages and has been historically influenced by many native languages. In this paper authors expand the Castilian ...

  1. Characterization of human mesothelin transcripts in ovarian and pancreatic cancer

    International Nuclear Information System (INIS)

    Muminova, Zhanat E; Strong, Theresa V; Shaw, Denise R

    2004-01-01

    Mesothelin is an attractive target for cancer immunotherapy due to its restricted expression in normal tissues and high level expression in several tumor types including ovarian and pancreatic adenocarcinomas. Three mesothelin transcript variants have been reported, but their relative expression in normal tissues and tumors has been poorly characterized. The goal of the present study was to clarify which mesothelin transcript variants are commonly expressed in human tumors. Human genomic and EST nucleotide sequences in the public databases were used to evaluate sequences reported for the three mesothelin transcript variants in silico. Subsequently, RNA samples from normal ovary, ovarian and pancreatic carcinoma cell lines, and primary ovarian tumors were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and nucleotide sequencing to directly identify expressed transcripts. In silico comparisons of genomic DNA sequences with available EST sequences supported expression of mesothelin transcript variants 1 and 3, but there were no sequence matches for transcript variant 2. Newly-derived nucleotide sequences of RT-PCR products from tissues and cell lines corresponded to mesothelin transcript variant 1. Mesothelin transcript variant 2 was not detected. Transcript variant 3 was observed as a small percentage of total mesothelin amplification products from all studied cell lines and tissues. Fractionation of nuclear and cytoplasmic RNA indicated that variant 3 was present primarily in the nuclear fraction. Thus, mesothelin transcript variant 3 may represent incompletely processed hnRNA. Mesothelin transcript variant 1 represents the predominant mature mRNA species expressed by both normal and tumor cells. This conclusion should be important for future development of cancer immunotherapies, diagnostic tests, and gene microarray studies targeting mesothelin

  2. Analyzing the Genotoxicity of Retroviral Vectors in Hematopoietic Cell Gene Therapy

    Directory of Open Access Journals (Sweden)

    Luca Biasco

    2018-03-01

    Full Text Available Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face severe adverse events in the form of leukemias and myelodysplastic syndromes, related to the semi-random vector integration into the host cell genome that caused deregulation of neighboring proto-oncogenes. Although improvements in vector design clearly lowered the risk of this insertional mutagenesis, analysis of potential genotoxicity and the consequences of vector integration remain important parameters for basic and translational research and most importantly for the clinic. Here, we review current assays to analyze biodistribution and genotoxicity in the pre-clinical setting and describe tools to monitor vector integration sites in vector-treated patients as a biosafety readout.

  3. Ectopic expression of the erythrocyte band 3 anion exchange protein, using a new avian retrovirus vector

    DEFF Research Database (Denmark)

    Fuerstenberg, S; Beug, H; Introna, M

    1990-01-01

    -erbB sequences following the splice acceptor were replaced by a cloning linker allowing insertion of foreign genes. The vector has been tested in conjunction with several helper viruses for the transmission of G418 resistance, titer, stability, transcription, and the transduction and expression of foreign genes...... in both chicken embryo fibroblasts and the QT6 quail cell line. The results show that the vector is capable of producing high titers of Neor virus from stably integrated proviruses. These proviruses express a balanced ratio of genome length to spliced transcripts which are efficiently translated...... into protein. Using the Escherichia coli beta-galactosidase gene cloned into the vector as a test construct, expression of enzyme activity could be detected in 90 to 95% of transfected target cells and in 80 to 85% of subsequently infected cells. In addition, a cDNA encoding the avian erythrocyte band 3 anion...

  4. Decays of the vector glueball

    Science.gov (United States)

    Giacosa, Francesco; Sammet, Julia; Janowski, Stanislaus

    2017-06-01

    We calculate two- and three-body decays of the (lightest) vector glueball into (pseudo)scalar, (axial-)vector, as well as pseudovector and excited vector mesons in the framework of a model of QCD. While absolute values of widths cannot be predicted because the corresponding coupling constants are unknown, some interesting branching ratios can be evaluated by setting the mass of the yet hypothetical vector glueball to 3.8 GeV as predicted by quenched lattice QCD. We find that the decay mode ω π π should be one of the largest (both through the decay chain O →b1π →ω π π and through the direct coupling O →ω π π ). Similarly, the (direct and indirect) decay into π K K*(892 ) is sizable. Moreover, the decays into ρ π and K*(892 )K are, although subleading, possible and could play a role in explaining the ρ π puzzle of the charmonium state ψ (2 S ) thanks to a (small) mixing with the vector glueball. The vector glueball can be directly formed at the ongoing BESIII experiment as well as at the future PANDA experiment at the FAIR facility. If the width is sufficiently small (≲100 MeV ) it should not escape future detection. It should be stressed that the employed model is based on some inputs and simplifying assumptions: the value of glueball mass (at present, the quenched lattice value is used), the lack of mixing of the glueball with other quarkonium states, and the use of few interaction terms. It then represents a first step toward the identification of the main decay channels of the vector glueball, but shall be improved when corresponding experimental candidates and/or new lattice results will be available.

  5. RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti

    Directory of Open Access Journals (Sweden)

    Olson Ken E

    2011-01-01

    Full Text Available Abstract Background Hematophagy is a common trait of insect vectors of disease. Extensive genome-wide transcriptional changes occur in mosquitoes after blood meals, and these are related to digestive and reproductive processes, among others. Studies of these changes are expected to reveal molecular targets for novel vector control and pathogen transmission-blocking strategies. The mosquito Aedes aegypti (Diptera, Culicidae, a vector of Dengue viruses, Yellow Fever Virus (YFV and Chikungunya virus (CV, is the subject of this study to look at genome-wide changes in gene expression following a blood meal. Results Transcriptional changes that follow a blood meal in Ae. aegypti females were explored using RNA-seq technology. Over 30% of more than 18,000 investigated transcripts accumulate differentially in mosquitoes at five hours after a blood meal when compared to those fed only on sugar. Forty transcripts accumulate only in blood-fed mosquitoes. The list of regulated transcripts correlates with an enhancement of digestive activity and a suppression of environmental stimuli perception and innate immunity. The alignment of more than 65 million high-quality short reads to the Ae. aegypti reference genome permitted the refinement of the current annotation of transcript boundaries, as well as the discovery of novel transcripts, exons and splicing variants. Cis-regulatory elements (CRE and cis-regulatory modules (CRM enriched significantly at the 5'end flanking sequences of blood meal-regulated genes were identified. Conclusions This study provides the first global view of the changes in transcript accumulation elicited by a blood meal in Ae. aegypti females. This information permitted the identification of classes of potentially co-regulated genes and a description of biochemical and physiological events that occur immediately after blood feeding. The data presented here serve as a basis for novel vector control and pathogen transmission

  6. Local Patch Vectors Encoded by Fisher Vectors for Image Classification

    Directory of Open Access Journals (Sweden)

    Shuangshuang Chen

    2018-02-01

    Full Text Available The objective of this work is image classification, whose purpose is to group images into corresponding semantic categories. Four contributions are made as follows: (i For computational simplicity and efficiency, we directly adopt raw image patch vectors as local descriptors encoded by Fisher vector (FV subsequently; (ii For obtaining representative local features within the FV encoding framework, we compare and analyze three typical sampling strategies: random sampling, saliency-based sampling and dense sampling; (iii In order to embed both global and local spatial information into local features, we construct an improved spatial geometry structure which shows good performance; (iv For reducing the storage and CPU costs of high dimensional vectors, we adopt a new feature selection method based on supervised mutual information (MI, which chooses features by an importance sorting algorithm. We report experimental results on dataset STL-10. It shows very promising performance with this simple and efficient framework compared to conventional methods.

  7. Learning with LOGO: Logo and Vectors.

    Science.gov (United States)

    Lough, Tom; Tipps, Steve

    1986-01-01

    This is the first of a two-part series on the general concept of vector space. Provides tool procedures to allow investigation of vector properties, vector addition and subtraction, and X and Y components. Lists several sources of additional vector ideas. (JM)

  8. Hexons from adenovirus serotypes 5 and 48 differentially protect adenovirus vectors from neutralization by mouse and human serum

    Science.gov (United States)

    Harmon, Andrew W.; Moitra, Rituparna; Xu, Zhili

    2018-01-01

    Adenovirus vectors are widely used in gene therapy clinical trials, and preclinical studies with these vectors are often conducted in mice. It is therefore critical to understand whether mouse studies adequately predict the behavior of adenovirus vectors in humans. The most commonly-used adenovirus vectors are derived from adenovirus serotype 5 (Ad5). The Ad5 hexon protein can bind coagulation factor X (FX), and binding of FX has a major impact on vector interactions with other blood proteins. In mouse serum, FX protects Ad5 vectors from neutralization by natural antibodies and complement. In the current study, we similarly find that human FX inhibits neutralization of Ad5 vectors by human serum, and this finding is consistent among individual human sera. We show that human IgM and human IgG can each induce complement-mediated neutralization when Ad5 vectors are not protected by FX. Although mouse and human serum had similar effects on Ad5 vectors, we found that this was not true for a chimeric Ad5 vector that incorporated hexon regions from adenovirus serotype 48. Interestingly, this hexon-chimeric vector was neutralized by human serum, but not by mouse serum. These findings indicate that studies in mouse serum accurately predict the behavior of Ad5 vectors in human serum, but mouse serum is not an accurate model system for all adenovirus vectors. PMID:29401488

  9. Hexons from adenovirus serotypes 5 and 48 differentially protect adenovirus vectors from neutralization by mouse and human serum.

    Science.gov (United States)

    Harmon, Andrew W; Moitra, Rituparna; Xu, Zhili; Byrnes, Andrew P

    2018-01-01

    Adenovirus vectors are widely used in gene therapy clinical trials, and preclinical studies with these vectors are often conducted in mice. It is therefore critical to understand whether mouse studies adequately predict the behavior of adenovirus vectors in humans. The most commonly-used adenovirus vectors are derived from adenovirus serotype 5 (Ad5). The Ad5 hexon protein can bind coagulation factor X (FX), and binding of FX has a major impact on vector interactions with other blood proteins. In mouse serum, FX protects Ad5 vectors from neutralization by natural antibodies and complement. In the current study, we similarly find that human FX inhibits neutralization of Ad5 vectors by human serum, and this finding is consistent among individual human sera. We show that human IgM and human IgG can each induce complement-mediated neutralization when Ad5 vectors are not protected by FX. Although mouse and human serum had similar effects on Ad5 vectors, we found that this was not true for a chimeric Ad5 vector that incorporated hexon regions from adenovirus serotype 48. Interestingly, this hexon-chimeric vector was neutralized by human serum, but not by mouse serum. These findings indicate that studies in mouse serum accurately predict the behavior of Ad5 vectors in human serum, but mouse serum is not an accurate model system for all adenovirus vectors.

  10. Principal-vector-directed fringe-tracking technique.

    Science.gov (United States)

    Zhang, Zhihui; Guo, Hongwei

    2014-11-01

    Fringe tracking is one of the most straightforward techniques for analyzing a single fringe pattern. This work presents a principal-vector-directed fringe-tracking technique. It uses Gaussian derivatives for estimating fringe gradients and uses hysteresis thresholding for segmenting singular points, thus improving the principal component analysis method. Using it allows us to estimate the principal vectors of fringes from a pattern with high noise. The fringe-tracking procedure is directed by these principal vectors, so that erroneous results induced by noise and other error-inducing factors are avoided. At the same time, the singular point regions of the fringe pattern are identified automatically. Using them allows us to determine paths through which the "seed" point for each fringe skeleton is easy to find, thus alleviating the computational burden in processing the fringe pattern. The results of a numerical simulation and experiment demonstrate this method to be valid.

  11. Quantifying and resolving multiple vector transformants in S. cerevisiae plasmid libraries

    Directory of Open Access Journals (Sweden)

    Gray Elizabeth C

    2009-11-01

    Full Text Available Abstract Background In addition to providing the molecular machinery for transcription and translation, recombinant microbial expression hosts maintain the critical genotype-phenotype link that is essential for high throughput screening and recovery of proteins encoded by plasmid libraries. It is known that Escherichia coli cells can be simultaneously transformed with multiple unique plasmids and thusly complicate recombinant library screening experiments. As a result of their potential to yield misleading results, bacterial multiple vector transformants have been thoroughly characterized in previous model studies. In contrast to bacterial systems, there is little quantitative information available regarding multiple vector transformants in yeast. Saccharomyces cerevisiae is the most widely used eukaryotic platform for cell surface display, combinatorial protein engineering, and other recombinant library screens. In order to characterize the extent and nature of multiple vector transformants in this important host, plasmid-born gene libraries constructed by yeast homologous recombination were analyzed by DNA sequencing. Results It was found that up to 90% of clones in yeast homologous recombination libraries may be multiple vector transformants, that on average these clones bear four or more unique mutant genes, and that these multiple vector cells persist as a significant proportion of library populations for greater than 24 hours during liquid outgrowth. Both vector concentration and vector to insert ratio influenced the library proportion of multiple vector transformants, but their population frequency was independent of transformation efficiency. Interestingly, the average number of plasmids born by multiple vector transformants did not vary with their library population proportion. Conclusion These results highlight the potential for multiple vector transformants to dominate yeast libraries constructed by homologous recombination. The

  12. Gauge Theories of Vector Particles

    Science.gov (United States)

    Glashow, S. L.; Gell-Mann, M.

    1961-04-24

    The possibility of generalizing the Yang-Mills trick is examined. Thus we seek theories of vector bosons invariant under continuous groups of coordinate-dependent linear transformations. All such theories may be expressed as superpositions of certain "simple" theories; we show that each "simple theory is associated with a simple Lie algebra. We may introduce mass terms for the vector bosons at the price of destroying the gauge-invariance for coordinate-dependent gauge functions. The theories corresponding to three particular simple Lie algebras - those which admit precisely two commuting quantum numbers - are examined in some detail as examples. One of them might play a role in the physics of the strong interactions if there is an underlying super-symmetry, transcending charge independence, that is badly broken. The intermediate vector boson theory of weak interactions is discussed also. The so-called "schizon" model cannot be made to conform to the requirements of partial gauge-invariance.

  13. Introduction to vector velocity imaging

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt; Udesen, Jesper; Hansen, Kristoffer Lindskov

    it virtually impossible to compensate for the factor and obtain correct velocity estimates for either CFM or spectral velocity estimation. This talk will describe methods for finding the correct velocity by estimating both the axial and lateral component of the velocity vector. The transverse oscillation...... method introduces an ultrasound field that oscillation not only along the ultrasound beam both also transverse to it to estimate both the lateral and axial velocity for the full velocity vector. The correct velocity magnitude can be found from this as well as the instantaneous angle. This can be obtained...... over the full region of interest and a real time image at a frame rate of 20 Hz can be displayed. Real time videos have been obtained from both our research systems and from commercial BK Medical scanners. The vector velocity images reveal the full complexity of the human blood flow. It is easy to see...

  14. 3D vector flow imaging

    DEFF Research Database (Denmark)

    Pihl, Michael Johannes

    The main purpose of this PhD project is to develop an ultrasonic method for 3D vector flow imaging. The motivation is to advance the field of velocity estimation in ultrasound, which plays an important role in the clinic. The velocity of blood has components in all three spatial dimensions, yet...... conventional methods can estimate only the axial component. Several approaches for 3D vector velocity estimation have been suggested, but none of these methods have so far produced convincing in vivo results nor have they been adopted by commercial manufacturers. The basis for this project is the Transverse...... on the TO fields are suggested. They can be used to optimize the TO method. In the third part, a TO method for 3D vector velocity estimation is proposed. It employs a 2D phased array transducer and decouples the velocity estimation into three velocity components, which are estimated simultaneously based on 5...

  15. Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy.

    Science.gov (United States)

    Vink, Conrad A; Counsell, John R; Perocheau, Dany P; Karda, Rajvinder; Buckley, Suzanne M K; Brugman, Martijn H; Galla, Melanie; Schambach, Axel; McKay, Tristan R; Waddington, Simon N; Howe, Steven J

    2017-08-02

    Lentiviral vector genomic RNA requires sequences that partially overlap wild-type HIV-1 gag and env genes for packaging into vector particles. These HIV-1 packaging sequences constitute 19.6% of the wild-type HIV-1 genome and contain functional cis elements that potentially compromise clinical safety. Here, we describe the development of a novel lentiviral vector (LTR1) with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wild-type genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. We show that LTR1 vectors offer improved safety in their resistance to remobilization in HIV-1 particles and reduced frequency of splicing into human genes. Following intravenous luciferase vector administration to neonatal mice, LTR1 sustained a higher level of liver transgene expression than an equivalent dose of a standard lentivirus. LTR1 vectors produce reverse-transcription products earlier and start to express transgenes significantly quicker than standard lentiviruses after transduction. Finally, we show that LTR1 is an effective lentiviral gene therapy vector as demonstrated by correction of a mouse hemophilia B model. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression.

    Science.gov (United States)

    Jiang, Xiaoou; Yu, Han; Teo, Cui Rong; Tan, Genim Siu Xian; Goh, Sok Chin; Patel, Parasvi; Chua, Yiqiang Kevin; Hameed, Nasirah Banu Sahul; Bertoletti, Antonio; Patzel, Volker

    2016-09-01

    Dumbbell-shaped DNA minimal vectors lacking nontherapeutic genes and bacterial sequences are considered a stable, safe alternative to viral, nonviral, and naked plasmid-based gene-transfer systems. We investigated novel molecular features of dumbbell vector/span>s aiming to reduce vector size and to improve the expression of noncoding or coding RNA. We minimized small hairpin RNA (shRNA) or microRNA (miRNA) expressing dumbbell vector/span>s in size down to 130 bp generating the smallest genetic expression vectors reported. This was achieved by using a minimal H1 promoter with integrated transcriptional terminator transcribing the RNA hairpin structure around the dumbbell loop. Such vectors were generated with high conversion yields using a novel protocol. Minimized shRNA-expressing dumbbells showed accelerated kinetics of delivery and transcription leading to enhanced gene silencing in human tissue culture cells. In primary human T cells, minimized miRNA-expressing dumbbells revealed higher stability and triggered stronger target gene suppression as compared with plasmids and miRNA mimics. Dumbbell-driven gene expression was enhanced up to 56- or 160-fold by implementation of an intron and the SV40 enhancer compared with control dumbbells or plasmids. Advanced dumbbell vector/span>s may represent one option to close the gap between durable expression that is achievable with integrating viral vectors and short-term effects triggered by naked RNA.

  17. Advanced Design of Dumbbell-shaped Genetic Minimal Vectors Improves Non-coding and Coding RNA Expression

    Science.gov (United States)

    Jiang, Xiaoou; Yu, Han; Teo, Cui Rong; Tan, Genim Siu Xian; Goh, Sok Chin; Patel, Parasvi; Chua, Yiqiang Kevin; Hameed, Nasirah Banu Sahul; Bertoletti, Antonio; Patzel, Volker

    2016-01-01

    Dumbbell-shaped DNA minimal vectors lacking nontherapeutic genes and bacterial sequences are considered a stable, safe alternative to viral, nonviral, and naked plasmid-based gene-transfer systems. We investigated novel molecular features of dumbbell vectors aiming to reduce vector size and to improve the expression of noncoding or coding RNA. We minimized small hairpin RNA (shRNA) or microRNA (miRNA) expressing dumbbell vectors in size down to 130 bp generating the smallest genetic expression vectors reported. This was achieved by using a minimal H1 promoter with integrated transcriptional terminator transcribing the RNA hairpin structure around the dumbbell loop. Such vectors were generated with high conversion yields using a novel protocol. Minimized shRNA-expressing dumbbells showed accelerated kinetics of delivery and transcription leading to enhanced gene silencing in human tissue culture cells. In primary human T cells, minimized miRNA-expressing dumbbells revealed higher stability and triggered stronger target gene suppression as compared with plasmids and miRNA mimics. Dumbbell-driven gene expression was enhanced up to 56- or 160-fold by implementation of an intron and the SV40 enhancer compared with control dumbbells or plasmids. Advanced dumbbell vectors may represent one option to close the gap between durable expression that is achievable with integrating viral vectors and short-term effects triggered by naked RNA. PMID:27357627

  18. Engineered zinc-finger transcription factors inhibit the replication and transcription of HBV in vitro and in vivo.

    Science.gov (United States)

    Luo, Wei; Wang, Junxia; Xu, Dengfeng; Bai, Huili; Zhang, Yangli; Zhang, Yuhong; Li, Xiaosong

    2018-04-01

    In the present study, an artificial zinc-finger transcription factor eukaryotic expression vector specifically recognizing and binding to the hepatitis B virus (HBV) enhancer (Enh) was constructed, which inhibited the replication and expression of HBV DNA. The HBV EnhI‑specific pcDNA3.1‑artificial transcription factor (ATF) vector was successfully constructed, and then transformed or injected into HepG2.2.15 cells and HBV transgenic mice, respectively. The results demonstrated that the HBV EnhI (1,070‑1,234 bp)‑specific ATF significantly inhibited the replication and transcription of HBV DNA in vivo and in vitro. The HBV EnhI‑specific ATF may be a meritorious component of progressive combination therapies for eliminating HBV DNA in infected patients. A radical cure for chronic HBV infection may become feasible by using this bioengineering technology.

  19. Hemoglobin derivatives

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003371.htm Hemoglobin derivatives To use the sharing features on this page, please enable JavaScript. Hemoglobin derivatives are altered forms of hemoglobin . Hemoglobin is ...

  20. Antisymmetric tensor generalizations of affine vector fields.

    Science.gov (United States)

    Houri, Tsuyoshi; Morisawa, Yoshiyuki; Tomoda, Kentaro

    2016-02-01

    Tensor generalizations of affine vector fields called symmetric and antisymmetric affine tensor fields are discussed as symmetry of spacetimes. We review the properties of the symmetric ones, which have been studied in earlier works, and investigate the properties of the antisymmetric ones, which are the main theme in this paper. It is shown that antisymmetric affine tensor fields are closely related to one-lower-rank antisymmetric tensor fields which are parallelly transported along geodesics. It is also shown that the number of linear independent rank- p antisymmetric affine tensor fields in n -dimensions is bounded by ( n + 1)!/ p !( n - p )!. We also derive the integrability conditions for antisymmetric affine tensor fields. Using the integrability conditions, we discuss the existence of antisymmetric affine tensor fields on various spacetimes.

  1. Topological vector spaces and distributions

    CERN Document Server

    Horvath, John

    2012-01-01

    ""The most readable introduction to the theory of vector spaces available in English and possibly any other language.""-J. L. B. Cooper, MathSciNet ReviewMathematically rigorous but user-friendly, this classic treatise discusses major modern contributions to the field of topological vector spaces. The self-contained treatment includes complete proofs for all necessary results from algebra and topology. Suitable for undergraduate mathematics majors with a background in advanced calculus, this volume will also assist professional mathematicians, physicists, and engineers.The precise exposition o

  2. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Villagómez Hoyos, Carlos Armando

    The main objective of this project was to continue the development of a synthetic aperture vector flow estimator. This type of estimator is capable of overcoming two of the major limitations in conventional ultrasound systems: 1) the inability to scan large region of interest with high temporal......, this thesis showed that novel information can be obtained with vector velocity methods providing quantitative estimates of blood flow and insight into the complexity of the hemodynamics dynamics. This could give the clinician a new tool in assessment and treatment of a broad range of diseases....

  3. Generation of arbitrary vector beams

    Science.gov (United States)

    Perez-Garcia, Benjamin; López-Mariscal, Carlos; Hernandez-Aranda, Raul I.; Gutiérrez-Vega, Julio C.

    2017-08-01

    Optical vector beams arise from point to point spatial variations of the electric component of an electromagnetic field over the transverse plane. In this work, we present a novel experimental technique to generate arbitrary vec- tor beams, and provide sufficient evidence to validate their state of polarization. This technique takes advantage of the capability of a Spatial Light Modulator to simultaneously generate two components of an electromagnetic field by halving the screen of the device and subsequently recombining them in a Sagnac interferometer. Our experimental results show the versatility and robustness of this technique for the generation of vector beams.

  4. Learning with Support Vector Machines

    CERN Document Server

    Campbell, Colin

    2010-01-01

    Support Vectors Machines have become a well established tool within machine learning. They work well in practice and have now been used across a wide range of applications from recognizing hand-written digits, to face identification, text categorisation, bioinformatics, and database marketing. In this book we give an introductory overview of this subject. We start with a simple Support Vector Machine for performing binary classification before considering multi-class classification and learning in the presence of noise. We show that this framework can be extended to many other scenarios such a

  5. Bearing estimation with acoustic vector-sensor arrays

    International Nuclear Information System (INIS)

    Hawkes, M.; Nehorai, A.

    1996-01-01

    We consider direction-of-arrival (DOA) estimation using arrays of acoustic vector sensors in free space, and derive expressions for the Cramacute er-Rao bound on the DOA parameters when there is a single source. The vector-sensor array is seen to have improved performance over the traditional scalar-sensor (pressure-sensor) array for two distinct reasons: its elements have an inherent directional sensitivity and the array makes a greater number of measurements. The improvement is greatest for small array apertures and low signal-to-noise ratios. Examination of the conventional beamforming and Capon DOA estimators shows that vector-sensor arrays can completely resolve the bearing, even with a linear array, and can remove the ambiguities associated with spatial undersampling. We also propose and analyze a diversely-oriented array of velocity sensors that possesses some of the advantages of the vector-sensor array without the increase in hardware and computation. In addition, in certain scenarios it can avoid problems with spatially correlated noise that the vector-sensor array may suffer. copyright 1996 American Institute of Physics

  6. Λ and Σ resonances coupled to vector and pseudoscalar mesons

    Energy Technology Data Exchange (ETDEWEB)

    Khemchandani, K.P., E-mail: kanchan@if.usp.br [Instituto de Física, Universidade de São Paulo, C.P 66318, 05314-970 São Paulo, SP (Brazil); Martínez Torres, A. [Instituto de Física, Universidade de São Paulo, C.P 66318, 05314-970 São Paulo, SP (Brazil); Nagahiro, H. [Research Center for Nuclear Physics (RCNP), Mihogaoka 10-1, Ibaraki 567-0047 (Japan); Department of Physics, Nara Women' s University, Nara 630-8506 (Japan); Hosaka, A. [Research Center for Nuclear Physics (RCNP), Mihogaoka 10-1, Ibaraki 567-0047 (Japan)

    2013-09-20

    The vector and pseudoscalar meson–baryon systems have been studied in a coupled channel formalism recently, which has lead to findings of some important results. The formalism consists of obtaining a detailed vector meson–baryon interaction originating from the s-, t-, u-channel diagrams and a contact interaction, all derived from the Lagrangian invariant under the gauge of the hidden local symmetry (HLS). We find the contributions from all the diagrams (except s-channel) to be important, contrary to the systems involving light Goldstone bosons where Weinberg–Tomozawa interaction gives the dominant contribution. Further, the transitions between the pseudoscalar meson–baryon (PB) and vector meson–baryon (VB) channels is obtained consistently by extending the Kroll–Ruderman theorem by replacing the photon by a vector meson, assuming the vector meson dominance. We find that the low-lying resonances couple strongly to VB channels. This information can be very useful in studying processes like photoproduction of low-lying resonances. Further, we find dynamical generation of new states in PB–VB coupled systems which can be related to the known resonances: Λ(2000), Σ(1750), Σ(1940) and Σ(2000)

  7. Use of a mixture statistical model in studying malaria vectors density.

    Science.gov (United States)

    Boussari, Olayidé; Moiroux, Nicolas; Iwaz, Jean; Djènontin, Armel; Bio-Bangana, Sahabi; Corbel, Vincent; Fonton, Noël; Ecochard, René

    2012-01-01

    Vector control is a major step in the process of malaria control and elimination. This requires vector counts and appropriate statistical analyses of these counts. However, vector counts are often overdispersed. A non-parametric mixture of Poisson model (NPMP) is proposed to allow for overdispersion and better describe vector distribution. Mosquito collections using the Human Landing Catches as well as collection of environmental and climatic data were carried out from January to December 2009 in 28 villages in Southern Benin. A NPMP regression model with "village" as random effect is used to test statistical correlations between malaria vectors density and environmental and climatic factors. Furthermore, the villages were ranked using the latent classes derived from the NPMP model. Based on this classification of the villages, the impacts of four vector control strategies implemented in the villages were compared. Vector counts were highly variable and overdispersed with important proportion of zeros (75%). The NPMP model had a good aptitude to predict the observed values and showed that: i) proximity to freshwater body, market gardening, and high levels of rain were associated with high vector density; ii) water conveyance, cattle breeding, vegetation index were associated with low vector density. The 28 villages could then be ranked according to the mean vector number as estimated by the random part of the model after adjustment on all covariates. The NPMP model made it possible to describe the distribution of the vector across the study area. The villages were ranked according to the mean vector density after taking into account the most important covariates. This study demonstrates the necessity and possibility of adapting methods of vector counting and sampling to each setting.

  8. Use of a mixture statistical model in studying malaria vectors density.

    Directory of Open Access Journals (Sweden)

    Olayidé Boussari

    Full Text Available Vector control is a major step in the process of malaria control and elimination. This requires vector counts and appropriate statistical analyses of these counts. However, vector counts are often overdispersed. A non-parametric mixture of Poisson model (NPMP is proposed to allow for overdispersion and better describe vector distribution. Mosquito collections using the Human Landing Catches as well as collection of environmental and climatic data were carried out from January to December 2009 in 28 villages in Southern Benin. A NPMP regression model with "village" as random effect is used to test statistical correlations between malaria vectors density and environmental and climatic factors. Furthermore, the villages were ranked using the latent classes derived from the NPMP model. Based on this classification of the villages, the impacts of four vector control strategies implemented in the villages were compared. Vector counts were highly variable and overdispersed with important proportion of zeros (75%. The NPMP model had a good aptitude to predict the observed values and showed that: i proximity to freshwater body, market gardening, and high levels of rain were associated with high vector density; ii water conveyance, cattle breeding, vegetation index were associated with low vector density. The 28 villages could then be ranked according to the mean vector number as estimated by the random part of the model after adjustment on all covariates. The NPMP model made it possible to describe the distribution of the vector across the study area. The villages were ranked according to the mean vector density after taking into account the most important covariates. This study demonstrates the necessity and possibility of adapting methods of vector counting and sampling to each setting.

  9. Enhancer RNAs and regulated transcriptional programs.

    Science.gov (United States)

    Lam, Michael T Y; Li, Wenbo; Rosenfeld, Michael G; Glass, Christopher K

    2014-04-01

    A large portion of the human genome is transcribed into RNAs without known protein-coding functions, far outnumbering coding transcription units. Extensive studies of long noncoding RNAs (lncRNAs) have clearly demonstrated that they can play critical roles in regulating gene expression, development, and diseases, acting both as transcriptional activators and repressors. More recently, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs. Here, we review emerging evidence suggesting that at least some eRNAs contribute to enhancer function. We discuss these findings with respect to potential mechanisms of action of eRNAs and other ncRNAs in regulated gene expression. Copyright © 2014. Published by Elsevier Ltd.

  10. Transcriptional repressor DREAM regulates trigeminal noxious perception.

    Science.gov (United States)

    Benedet, Tomaso; Gonzalez, Paz; Oliveros, Juan C; Dopazo, Jose M; Ghimire, Kedar; Palczewska, Malgorzata; Mellstrom, Britt; Naranjo, Jose R

    2017-05-01

    Expression of the downstream regulatory element antagonist modulator (DREAM) protein in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons, high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that transgenic mice expressing a dominant active mutant of DREAM in trigeminal neurons show increased responses following orofacial sensory stimulation, which correlates with a decreased expression of prodynorphin and brain-derived neurotrophic factor in trigeminal ganglia. Genome-wide analysis of trigeminal neurons in daDREAM transgenic mice identified cathepsin L and the monoglyceride lipase as two new DREAM transcriptional targets related to pain. Our results suggest a role for DREAM in the regulation of trigeminal nociception. This article is part of the special article series "Pain". © 2016 International Society for Neurochemistry.

  11. How effective is integrated vector management against malaria and lymphatic filariasis where the diseases are transmitted by the same vector?

    Directory of Open Access Journals (Sweden)

    Christopher M Stone

    2014-12-01

    Full Text Available The opportunity to integrate vector management across multiple vector-borne diseases is particularly plausible for malaria and lymphatic filariasis (LF control where both diseases are transmitted by the same vector. To date most examples of integrated control targeting these diseases have been unanticipated consequences of malaria vector control, rather than planned strategies that aim to maximize the efficacy and take the complex ecological and biological interactions between the two diseases into account.We developed a general model of malaria and LF transmission and derived expressions for the basic reproductive number (R0 for each disease. Transmission of both diseases was most sensitive to vector mortality and biting rate. Simulating different levels of coverage of long lasting-insecticidal nets (LLINs and larval control confirms the effectiveness of these interventions for the control of both diseases. When LF was maintained near the critical density of mosquitoes, minor levels of vector control (8% coverage of LLINs or treatment of 20% of larval sites were sufficient to eliminate the disease. Malaria had a far greater R0 and required a 90% population coverage of LLINs in order to eliminate it. When the mosquito density was doubled, 36% and 58% coverage of LLINs and larval control, respectively, were required for LF elimination; and malaria elimination was possible with a combined coverage of 78% of LLINs and larval control.Despite the low level of vector control required to eliminate LF, simulations suggest that prevalence of LF will decrease at a slower rate than malaria, even at high levels of coverage. If representative of field situations, integrated management should take into account not only how malaria control can facilitate filariasis elimination, but strike a balance between the high levels of coverage of (multiple interventions required for malaria with the long duration predicted to be required for filariasis elimination.

  12. Surveillance of arthropod vector-borne infectious diseases using remote sensing techniques: a review.

    Directory of Open Access Journals (Sweden)

    Satya Kalluri

    2007-10-01

    Full Text Available Epidemiologists are adopting new remote sensing techniques to study a variety of vector-borne diseases. Associations between satellite-derived environmental variables such as temperature, humidity, and land cover type and vector density are used to identify and characterize vector habitats. The convergence of factors such as the availability of multi-temporal satellite data and georeferenced epidemiological data, collaboration between remote sensing scientists and biologists, and the availability of sophisticated, statistical geographic information system and image processing algorithms in a desktop environment creates a fertile research environment. The use of remote sensing techniques to map vector-borne diseases has evolved significantly over the past 25 years. In this paper, we review the status of remote sensing studies of arthropod vector-borne diseases due to mosquitoes, ticks, blackflies, tsetse flies, and sandflies, which are responsible for the majority of vector-borne diseases in the world. Examples of simple image classification techniques that associate land use and land cover types with vector habitats, as well as complex statistical models that link satellite-derived multi-temporal meteorological observations with vector biology and abundance, are discussed here. Future improvements in remote sensing applications in epidemiology are also discussed.

  13. Enhancers Are Major Targets for Murine Leukemia Virus Vector Integration

    Science.gov (United States)

    De Ravin, Suk See; Su, Ling; Theobald, Narda; Choi, Uimook; Macpherson, Janet L.; Poidinger, Michael; Symonds, Geoff; Pond, Susan M.; Ferris, Andrea L.; Hughes, Stephen H.

    2014-01-01

    ABSTRACT Retroviral vectors have been used in successful gene therapies. However, in some patients, insertional mutagenesis led to leukemia or myelodysplasia. Both the strong promoter/enhancer elements in the long terminal repeats (LTRs) of murine leukemia virus (MLV)-based vectors and the vector-specific integration site preferences played an important role in these adverse clinical events. MLV integration is known to prefer regions in or near transcription start sites (TSS). Recently, BET family proteins were shown to be the major cellular proteins responsible for targeting MLV integration. Although MLV integration sites are significantly enriched at TSS, only a small fraction of the MLV integration sites (integration map of more than one million integration sites from CD34+ hematopoietic stem cells transduced with a clinically relevant MLV-based vector. The integration sites form ∼60,000 tight clusters. These clusters comprise ∼1.9% of the genome. The vast majority (87%) of the integration sites are located within histone H3K4me1 islands, a hallmark of enhancers. The majority of these clusters also have H3K27ac histone modifications, which mark active enhancers. The enhancers of some oncogenes, including LMO2, are highly preferred targets for integration without in vivo selection. IMPORTANCE We show that active enhancer regions are the major targets for MLV integration; this means that MLV preferentially integrates in regions that are favorable for viral gene expression in a variety of cell types. The results provide insights for MLV integration target site selection and also explain the high risk of insertional mutagenesis that is associated with gene therapy trials using MLV vectors. PMID:24501411

  14. Selection-free gene repair after adenoviral vector transduction of designer nucleases: rescue of dystrophin synthesis in DMD muscle cell populations.

    Science.gov (United States)

    Maggio, Ignazio; Stefanucci, Luca; Janssen, Josephine M; Liu, Jin; Chen, Xiaoyu; Mouly, Vincent; Gonçalves, Manuel A F V

    2016-02-18

    Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle-wasting disorder caused by mutations in the 2.4 Mb dystrophin-encoding DMD gene. The integration of gene delivery and gene editing technologies based on viral vectors and sequence-specific designer nucleases, respectively, constitutes a potential therapeutic modality for permanently repairing defective DMD alleles in patient-derived myogenic cells. Therefore, we sought to investigate the feasibility of combining adenoviral vectors (AdVs) with CRISPR/Cas9 RNA-guided nucleases (RGNs) alone or together with transcriptional activator-like effector nucleases (TALENs), for endogenous DMD repair through non-homologous end-joining (NHEJ). The strategies tested involved; incorporating small insertions or deletions at out-of-frame sequences for reading frame resetting, splice acceptor knockout for DNA-level exon skipping, and RGN-RGN or RGN-TALEN multiplexing for targeted exon(s) removal. We demonstrate that genome editing based on the activation and recruitment of the NHEJ DNA repair pathway after AdV delivery of designer nuclease genes, is a versatile and robust approach for repairing DMD mutations in bulk populations of patient-derived muscle progenitor cells (up to 37% of corrected DMD templates). These results open up a DNA-level genetic medicine strategy in which viral vector-mediated transient designer nuclease expression leads to permanent and regulated dystrophin synthesis from corrected native DMD alleles. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Transcriptomics of differential vector competence: West Nile virus infection in two populations of Culex pipiens quinquefasciatus linked to ovary development.

    Science.gov (United States)

    Shin, Dongyoung; Civana, Ayse; Acevedo, Carolina; Smartt, Chelsea T

    2014-06-22

    Understanding mechanisms that contribute to viral dissemination in mosquito vectors will contribute to our ability to interfere with the transmission of viral pathogens that impact public health. The expression of genes in two Culex pipiens quinquefasciatus populations from Florida with known differences in vector competence to West Nile virus (WNV) were compared using high throughput sequencing. A total of 15,176 transcripts were combined for comparison of expression differences between the two populations and 118 transcripts were differentially expressed (p Culex populations in Florida. Both populations control energy allocations to reproduction as a response to WNV. This result provides novel insight into the defense mechanism used by Culex spp. mosquitoes against WNV.

  16. The consequences of poor vectorization

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    This talk briefly discusses the vectorization problem and how it impacts scientific and engineering systems. A simple cost model of designing such system in context of different phases of software lifetime is considered. Finally a concept for scalable solution is presented.

  17. Parallel Sparse Matrix - Vector Product

    DEFF Research Database (Denmark)

    Alexandersen, Joe; Lazarov, Boyan Stefanov; Dammann, Bernd

    This technical report contains a case study of a sparse matrix-vector product routine, implemented for parallel execution on a compute cluster with both pure MPI and hybrid MPI-OpenMP solutions. C++ classes for sparse data types were developed and the report shows how these class can be used...

  18. Phlebotomine Vectors of Human Disease.

    Science.gov (United States)

    1983-12-30

    different. We refrain from naming this specimen until more material becomes available. 12. Lutzomyia olmeca bicolor Fairchild and Theodor 1971...Castillo (1958) and Arzube (1960). Lutzomyia olmeca bicolor is the suspected vector of Leishmania mexicana aristedesi among rodents and marsupials in

  19. Scalar Calibration of Vector Magnetometers

    DEFF Research Database (Denmark)

    Merayo, José M.G.; Brauer, Peter; Primdahl, Fritz

    2000-01-01

    The calibration parameters of a vector magnetometer are estimated only by the use of a scalar reference magnetometer. The method presented in this paper differs from those previously reported in its linearized parametrization. This allows the determination of three offsets or signals in the absence...

  20. Vector-meson dominance revisited

    Directory of Open Access Journals (Sweden)

    Terschlüsen Carla

    2012-12-01

    Full Text Available The interaction of mesons with electromagnetism is often well described by the concept of vector-meson dominance (VMD. However, there are also examples where VMD fails. A simple chiral Lagrangian for pions, rho and omega mesons is presented which can account for the respective agreement and disagreement between VMD and phenomenology in the sector of light mesons.

  1. Portfolio Analysis for Vector Calculus

    Science.gov (United States)

    Kaplan, Samuel R.

    2015-01-01

    Classic stock portfolio analysis provides an applied context for Lagrange multipliers that undergraduate students appreciate. Although modern methods of portfolio analysis are beyond the scope of vector calculus, classic methods reinforce the utility of this material. This paper discusses how to introduce classic stock portfolio analysis in a…

  2. Vector ecology of equine piroplasmosis

    Science.gov (United States)

    Equine piroplasmosis (EP) is a disease of equidae including horses, donkeys, mules and zebras caused by either of two protozoan parasites, Theileria equi or Babesia caballi. These parasites are biologically transmitted between hosts via tick-vectors and although they have inherent differences, they ...

  3. Vector potential and metric perturbations of a rotating black hole

    International Nuclear Information System (INIS)

    Chrzanowski, P.L.

    1975-01-01

    The assumption of factorized Green's functions together with the inhomogeneous Teukolsky equations are used to derive analytic expressions for homogeneous metric (and vector potential) perturbations of a Kerr black hole. These homogeneous solutions are used to construct solutions to the perturbation equations when sources are present. What one finds are particularly simple formulas for the energy and angular momentum flux in the asymptotic regions r* → plus-or-minusinfinity

  4. Identification of active transcriptional regulatory elements with GRO-seq

    Science.gov (United States)

    Danko, Charles G.; Hyland, Stephanie L.; Core, Leighton J.; Martins, Andre L.; Waters, Colin T; Lee, Hyung Won; Cheung, Vivian G.; Kraus, W. Lee; Lis, John T.; Siepel, Adam

    2015-01-01

    Transcriptional regulatory elements (TREs), including enhancers and promoters, determine the transcription levels of associated genes. We have recently shown that global run-on and sequencing (GRO-seq) with enrichment for 5'-capped RNAs reveals active TREs with high accuracy. Here, we demonstrate that active TREs can be identified by applying sensitive machine-learning methods to standard GRO-seq data. This approach allows TREs to be assayed together with gene expression levels and other transcriptional features in a single experiment. Our prediction method, called discriminative Regulatory Element detection from GRO-seq (dREG), summarizes GRO-seq read counts at multiple scales and uses support vector regression to identify active TREs. The predicted TREs are more strongly enriched for several marks of transcriptional activation, including eQTL, GWAS-associated SNPs, H3K27ac, and transcription factor binding than those identified by alternative functional assays. Using dREG, we survey TREs in eight human cell types and provide new insights into global patterns of TRE function. PMID:25799441

  5. Compositional Model Based Fisher Vector Coding for Image Classification.

    Science.gov (United States)

    Liu, Lingqiao; Wang, Peng; Shen, Chunhua; Wang, Lei; Hengel, Anton van den; Wang, Chao; Shen, Heng Tao

    2017-12-01

    Deriving from the gradient vector of a generative model of local features, Fisher vector coding (FVC) has been identified as an effective coding method for image classification. Most, if not all, FVC implementations employ the Gaussian mixture model (GMM) as the generative model for local features. However, the representative power of a GMM can be limited because it essentially assumes that local features can be characterized by a fixed number of feature prototypes, and the number of prototypes is usually small in FVC. To alleviate this limitation, in this work, we break the convention which assumes that a local feature is drawn from one of a few Gaussian distributions. Instead, we adopt a compositional mechanism which assumes that a local feature is drawn from a Gaussian distribution whose mean vector is composed as a linear combination of multiple key components, and the combination weight is a latent random variable. In doing so we greatly enhance the representative power of the generative model underlying FVC. To implement our idea, we design two particular generative models following this compositional approach. In our first model, the mean vector is sampled from the subspace spanned by a set of bases and the combination weight is drawn from a Laplace distribution. In our second model, we further assume that a local feature is composed of a discriminative part and a residual part. As a result, a local feature is generated by the linear combination of discriminative part bases and residual part bases. The decomposition of the discriminative and residual parts is achieved via the guidance of a pre-trained supervised coding method. By calculating the gradient vector of the proposed models, we derive two new Fisher vector coding strategies. The first is termed Sparse Coding-based Fisher Vector Coding (SCFVC) and can be used as the substitute of traditional GMM based FVC. The second is termed Hybrid Sparse Coding-based Fisher vector coding (HSCFVC) since it

  6. Monitoring of Gene Expression in Bacteria during Infections Using an Adaptable Set of Bioluminescent, Fluorescent and Colorigenic Fusion Vectors

    OpenAIRE

    Uliczka, Frank; Pisano, Fabio; Kochut, Annika; Opitz, Wiebke; Herbst, Katharina; Stolz, Tatjana; Dersch, Petra

    2011-01-01

    A family of versatile promoter-probe plasmids for gene expression analysis was developed based on a modular expression plasmid system (pZ). The vectors contain different replicons with exchangeable antibiotic cassettes to allow compatibility and expression analysis on a low-, midi- and high-copy number basis. Suicide vector variants also permit chromosomal integration of the reporter fusion and stable vector derivatives can be used for in vivo or in situ expression studies under non-selective...

  7. The role of remote sensing and GIS for spatial prediction of vector-borne diseases transmission: a systematic review.

    Science.gov (United States)

    Palaniyandi, M

    2012-12-01

    There have been several attempts made to the appreciation of remote sensing and GIS for the study of vectors, biodiversity, vector presence, vector abundance and the vector-borne diseases with respect to space and time. This study was made for reviewing and appraising the potential use of remote sensing and GIS applications for spatial prediction of vector-borne diseases transmission. The nature of the presence and the abundance of vectors and vector-borne diseases, disease infection and the disease transmission are not ubiquitous and are confined with geographical, environmental and climatic factors, and are localized. The presence of vectors and vector-borne diseases is most complex in nature, however, it is confined and fueled by the geographical, climatic and environmental factors including man-made factors. The usefulness of the present day availability of the information derived from the satellite data including vegetation indices of canopy cover and its density, soil types, soil moisture, soil texture, soil depth, etc. is integrating the information in the expert GIS engine for the spatial analysis of other geoclimatic and geoenvironmental variables. The present study gives the detailed information on the classical studies of the past and present, and the future role of remote sensing and GIS for the vector-borne diseases control. The ecological modeling directly gives us the relevant information to understand the spatial variation of the vector biodiversity, vector presence, vector abundance and the vector-borne diseases in association with geoclimatic and the environmental variables. The probability map of the geographical distribution and seasonal variations of horizontal and vertical distribution of vector abundance and its association with vector -borne diseases can be obtained with low cost remote sensing and GIS tool with reliable data and speed.

  8. A novel binary T-vector with the GFP reporter gene for promoter characterization.

    Directory of Open Access Journals (Sweden)

    Shu-Ye Jiang

    Full Text Available Several strategies have been developed to clone PCR fragments into desired vectors. However, most of commercially available T-vectors are not binary vectors and cannot be directly used for Agrobacterium-mediated plant genetic transformation. In this study, a novel binary T-vector was constructed by integrating two AhdI restriction sites into the backbone vector pCAMBIA 1300. The T-vector also contains a GFP reporter gene and thus, can be used to analyze promoter activity by monitoring the reporter gene. On the other hand, identification and characterization of various promoters not only benefit the functional annotation of their genes but also provide alternative candidates to be used to drive interesting genes for plant genetic improvement by transgenesis. More than 1,000 putative pollen-specific rice genes have been identified in a genome-wide level. Among them, 67 highly expressed genes were further characterized. One of the pollen-specific genes LOC_Os10g35930 was further surveyed in its expression patterns with more details by quantitative real-time reverse-transcription PCR (qRT-PCR analysis. Finally, its promoter activity was further investigated by analyzing transgenic rice plants carrying the promoter::GFP cassette, which was constructed from the newly developed T-vector. The reporter GFP gene expression in these transgenic plants showed that the promoter was active only in mature but not in germinated pollens.

  9. Lentiviral vectors can be used for full-length dystrophin gene therapy.

    Science.gov (United States)

    Counsell, John R; Asgarian, Zeinab; Meng, Jinhong; Ferrer, Veronica; Vink, Conrad A; Howe, Steven J; Waddington, Simon N; Thrasher, Adrian J; Muntoni, Francesco; Morgan, Jennifer E; Danos, Olivier

    2017-03-06

    Duchenne Muscular Dystrophy (DMD) is caused by a lack of dystrophin expression in patient muscle fibres. Current DMD gene therapy strategies rely on the expression of internally deleted forms of dystrophin, missing important functional domains. Viral gene transfer of full-length dystrophin could restore wild-type functionality, although this approach is restricted by the limited capacity of recombinant viral vectors. Lentiviral vectors can package larger transgenes than adeno-associated viruses, yet lentiviral vectors remain largely unexplored for full-length dystrophin delivery. In our work, we have demonstrated that lentiviral vectors can package and deliver inserts of a similar size to dystrophin. We report a novel approach for delivering large transgenes in lentiviruses, in which we demonstrate proof-of-concept for a 'template-switching' lentiviral vector that harnesses recombination events during reverse-transcription. During this work, we discovered that a standard, unmodified lentiviral vector was efficient in delivering full-length dystrophin to target cells, within a total genomic load of more than 15,000 base pairs. We have demonstrated gene therapy with this vector by restoring dystrophin expression in DMD myoblasts, where dystrophin was expressed at the sarcolemma of myotubes after myogenic differentiation. Ultimately, our work demonstrates proof-of-concept that lentiviruses can be used for permanent full-length dystrophin gene therapy, which presents a significant advancement in developing an effective treatment for DMD.

  10. Transcriptional Regulation in Haematopoiesis:

    DEFF Research Database (Denmark)

    Lauridsen, Felicia K B

    Haematopoietic stem cells (HSCs) are responsible for the formation of all of the distinct mature cell types found in the blood. HSCs can – as the only cells of the haematopoietic system – regenerate all of the blood cells when transplanted into a irradiated host, because they are endowed...... of distinct lineage affiliated genes in the otherwise highly purified HSCs. Taken together, these studies demonstrate the use of our model as a tool for isolating superior HSCs, and show that low-level expression of mature lineage markers is inherent in the highly purified stem cell compartment. In the second...... in transplantation studies. Consistent with this, transcriptome profiling revealed very low expression of cell cycle genes in these reporter-dim HSCs. Sequencing of >1200 single HSCs confirmed that the main source of transcriptional heterogeneity was the cell cycle. It also revealed a low-level expression...

  11. Vector variational inequalities and their relations with vector optimization

    Directory of Open Access Journals (Sweden)

    Surjeet Kaur Suneja

    2014-01-01

    Full Text Available In this paper, K- quasiconvex, K- pseudoconvex and other related functions have been introduced in terms of their Clarke subdifferentials, where is an arbitrary closed convex, pointed cone with nonempty interior. The (strict, weakly -pseudomonotonicity, (strict K- naturally quasimonotonicity and K- quasimonotonicity of Clarke subdifferential maps have also been defined. Further, we introduce Minty weak (MVVIP and Stampacchia weak (SVVIP vector variational inequalities over arbitrary cones. Under regularity assumption, we have proved that a weak minimum solution of vector optimization problem (VOP is a solution of (SVVIP and under the condition of K- pseudoconvexity we have obtained the converse for MVVIP (SVVIP. In the end we study the interrelations between these with the help of strict K-naturally quasimonotonicity of Clarke subdifferential map.

  12. Euglena Transcript Processing.

    Science.gov (United States)

    McWatters, David C; Russell, Anthony G

    2017-01-01

    RNA transcript processing is an important stage in the gene expression pathway of all organisms and is subject to various mechanisms of control that influence the final levels of gene products. RNA processing involves events such as nuclease-mediated cleavage, removal of intervening sequences referred to as introns and modifications to RNA structure (nucleoside modification and editing). In Euglena, RNA transcript processing was initially examined in chloroplasts because of historical interest in the secondary endosymbiotic origin of this organelle in this organism. More recent efforts to examine mitochondrial genome structure and RNA maturation have been stimulated by the discovery of unusual processing pathways in other Euglenozoans such as kinetoplastids and diplonemids. Eukaryotes containing large genomes are now known to typically contain large collections of introns and regulatory RNAs involved in RNA processing events, and Euglena gracilis in particular has a relatively large genome for a protist. Studies examining the structure of nuclear genes and the mechanisms involved in nuclear RNA processing have revealed that indeed Euglena contains large numbers of introns in the limited set of genes so far examined and also possesses large numbers of specific classes of regulatory and processing RNAs, such as small nucleolar RNAs (snoRNAs). Most interestingly, these studies have also revealed that Euglena possesses novel processing pathways generating highly fragmented cytosolic ribosomal RNAs and subunits and non-conventional intron classes removed by unknown splicing mechanisms. This unexpected diversity in RNA processing pathways emphasizes the importance of identifying the components involved in these processing mechanisms and their evolutionary emergence in Euglena species.

  13. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  14. Potential Role of Activating Transcription Factor 5 during Osteogenesis.

    Science.gov (United States)

    Vicari, Luisa; Calabrese, Giovanna; Forte, Stefano; Giuffrida, Raffaella; Colarossi, Cristina; Parrinello, Nunziatina Laura; Memeo, Lorenzo

    2016-01-01

    Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB) family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2), encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  15. Financial derivatives

    OpenAIRE

    Koutný, Ondřej

    2012-01-01

    1 Abstract/ Financial derivatives The purpose of this thesis is to provide an introduction to financial derivatives which has been, from the legal perspective, described in a not satisfactory manner as quite little literature that can be found about this topic. The main objectives of this thesis are to define the term "financial derivatives" and its particular types and to analyse legal nature of these financial instruments. The last objective is to try to draft future law regulation of finan...

  16. Nonseparable closed vector subspaces of separable topological vector spaces

    Czech Academy of Sciences Publication Activity Database

    Kąkol, Jerzy; Leiderman, A. G.; Morris, S. A.

    2017-01-01

    Roč. 182, č. 1 (2017), s. 39-47 ISSN 0026-9255 R&D Projects: GA ČR GF16-34860L Institutional support: RVO:67985840 Keywords : locally convex topological vector space * separable topological space Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.716, year: 2016 https://link.springer.com/article/10.1007%2Fs00605-016-0876-2

  17. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded and inheren......Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...

  18. Initiation of HIV Reverse Transcription

    Directory of Open Access Journals (Sweden)

    Roland Marquet

    2010-01-01

    Full Text Available Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of reverse transcription and its importance for viral infectivity further points toward reverse transcription and potentially its initiation step as an important drug target.

  19. Octamer and heat shock elements regulate transcription from the AcMNPV polyhedrin gene promoter.

    Science.gov (United States)

    Kumar, M Senthil; Ramachandran, Aruna; Hasnain, Seyed E; Bashyam, Murali Dharan

    2009-01-01

    The baculovirus expression vector system exploits the polyhedrin (polh) promoter for high expression of foreign proteins in insect cells. The mechanism of basal and hyperactivated transcription from this promoter, however, remains poorly understood. We have analyzed the 4-kb upstream region of the polh promoter; deletion of two separate parts of the 4-kb upstream region, harboring the Oct binding site and the heat shock element, respectively, resulted in significant reduction of reporter gene expression regulated by the polh promoter. Insect cell host factors could bind to these elements in vitro. Moreover, these elements could activate polh transcription during viral infection when present upstream of a minimal polh promoter in transient expression reporter assays. Our results suggest the possible existence of transcription factors belonging to the POU and heat shock transcription factor family in Spodoptera frugiperda cells and support the hypothesis that host proteins may play a major role in activating transcription from the polh promoter.

  20. Single-dose protection against Plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron A.

    Science.gov (United States)

    Sridhar, S; Reyes-Sandoval, A; Draper, S J; Moore, A C; Gilbert, S C; Gao, G P; Wilson, J M; Hill, A V S

    2008-04-01

    Human adenovirus serotype 5 (AdH5) vector vaccines elicit strong immune responses to the encoded antigen and have been used in various disease models. We designed AdH5 vectors expressing antigen under the control of a human cytomegalovirus (HCMV) immediate-early promoter containing its intron A sequence. The transcriptional levels of antigen and immune responses to antigen for vectors with the HCMV promoter with the intron A sequence (LP) were greater than those for AdH5 vectors using the HCMV promoter sequence without intron A (SP). We compared an E1E3-deleted AdH5 adenoviral vector, which affords more space for insertion of foreign sequences, and showed it to be as immunogenic as an E1-deleted AdH5 vector. Neutralizing antibodies to AdH5 limit the efficacy of vaccines based on the AdH5 serotype, and simian adenoviral vectors offer an attractive option to overcome this problem. We constructed E1E3-deleted human and simian adenoviral vectors encoding the pre-erythrocytic-stage malarial antigen Plasmodium berghei circumsporozoite protein. We compared the immunogenicity and efficacy of AdC6, a recombinant simian adenovirus serotype 6 vector, in a murine malaria model to those of AdH5 and the poxviral vectors MVA and FP9. AdC6 induced sterile protection from a single dose in 90% of mice, in contrast to AdH5 (25%) and poxviral vectors MVA and FP9 (0%). Adenoviral vectors maintained potent CD8(+) T-cell responses for a longer period after immunization than did poxviral vectors and mainly induced an effector memory phenotype of cells. Significantly, AdC6 was able to maintain protection in the presence of preexisting immunity to AdH5.

  1. A modular cloning toolbox for the generation of chloroplast transformation vectors.

    Directory of Open Access Journals (Sweden)

    Yavar Vafaee

    Full Text Available Plastid transformation is a powerful tool for basic research, but also for the generation of stable genetically engineered plants producing recombinant proteins at high levels or for metabolic engineering purposes. However, due to the genetic makeup of plastids and the distinct features of the transformation process, vector design, and the use of specific genetic elements, a large set of basic transformation vectors is required, making cloning a tedious and time-consuming effort. Here, we describe the adoption of standardized modular cloning (GoldenBraid to the design and assembly of the full spectrum of plastid transformation vectors. The modular design of genetic elements allows straightforward and time-efficient build-up of transcriptional units as well as construction of vectors targeting any homologous recombination site of choice. In a three-level assembly process, we established a vector fostering gene expression and formation of griffithsin, a potential viral entry inhibitor and HIV prophylactic, in the plastids of tobacco. Successful transformation as well as transcript and protein production could be shown. In concert with the aforesaid endeavor, a set of modules facilitating plastid transformation was generated, thus augmenting the GoldenBraid toolbox. In short, the work presented in this study enables efficient application of synthetic biology methods to plastid transformation in plants.

  2. Linearized vector radiative transfer model MCC++ for a spherical atmosphere

    International Nuclear Information System (INIS)

    Postylyakov, O.V.

    2004-01-01

    Application of radiative transfer models has shown that optical remote sensing requires extra characteristics of radiance field in addition to the radiance intensity itself. Simulation of spectral measurements, analysis of retrieval errors and development of retrieval algorithms are in need of derivatives of radiance with respect to atmospheric constituents under investigation. The presented vector spherical radiative transfer model MCC++ was linearized, which allows the calculation of derivatives of all elements of the Stokes vector with respect to the volume absorption coefficient simultaneously with radiance calculation. The model MCC++ employs Monte Carlo algorithm for radiative transfer simulation and takes into account aerosol and molecular scattering, gas and aerosol absorption, and Lambertian surface albedo. The model treats a spherically symmetrical atmosphere. Relation of the estimated derivatives with other forms of radiance derivatives: the weighting functions used in gas retrieval and the air mass factors used in the DOAS retrieval algorithms, is obtained. Validation of the model against other radiative models is overviewed. The computing time of the intensity for the MCC++ model is about that for radiative models treating sphericity of the atmosphere approximately and is significantly shorter than that for the full spherical models used in the comparisons. The simultaneous calculation of all derivatives (i.e. with respect to absorption in all model atmosphere layers) and the intensity is only 1.2-2 times longer than the calculation of the intensity only

  3. Transversals of Complex Polynomial Vector Fields

    DEFF Research Database (Denmark)

    Dias, Kealey

    Vector fields in the complex plane are defined by assigning the vector determined by the value P(z) to each point z in the complex plane, where P is a polynomial of one complex variable. We consider special families of so-called rotated vector fields that are determined by a polynomial multiplied...... by rotational constants. Transversals are a certain class of curves for such a family of vector fields that represent the bifurcation states for this family of vector fields. More specifically, transversals are curves that coincide with a homoclinic separatrix for some rotation of the vector field. Given...... a concrete polynomial, it seems to take quite a bit of work to prove that it is generic, i.e. structurally stable. This has been done for a special class of degree d polynomial vector fields having simple equilibrium points at the d roots of unity, d odd. In proving that such vector fields are generic...

  4. Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity

    NARCIS (Netherlands)

    Thorner, Anna R.; Lemckert, Angelique A. C.; Goudsmit, Jaap; Lynch, Diana M.; Ewald, Bonnie A.; Denholtz, Matthew; Havenga, Menzo J. E.; Barouch, Dan H.

    2006-01-01

    The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations has led to the development of recombinant adenovirus (rAd) vectors derived from rare Ad serotypes as vaccine candidates for human immunodeficiency virus type 1 and other pathogens. Vaccine vectors have

  5. Construction of stably maintained non-mobilizable derivatives of RSF1010 lacking all known elements essential for mobilization

    Directory of Open Access Journals (Sweden)

    Tokmakova Irina L

    2007-11-01

    Full Text Available Abstract Background RSF1010 is a well-studied broad-host-range plasmid able to be mobilized to different bacteria and plants. RSF1010-derived plasmid vectors are widely used in both basic research and industrial applications. In the latter case, exploiting of mobilizable plasmids or even the plasmids possessing negligible mobilization frequency, but containing DNA fragments that could promote conjugal transfer, is undesirable because of biosafety considerations. Previously, several mutations significantly decreasing efficiency of RSF1010 mobilization have been selected. Nevertheless, construction of the RSF1010 derivative lacking all known loci involved in the conjugal transfer has not been reported yet. Results Novel non-mobilizable derivatives of RSF1010 lacking all known DNA sequences involved in the mobilization process have been obtained due to the exploiting of λRed-driven recombination between the plasmid and a constructed in vitro linear DNA fragment. To provide auto-regulated transcription of the essential replication gene, repB, the plasmid loci oriT, mobC and mobA were substituted by the DNA fragment containing PlacUV5→lacI. Mobilization of the obtained RSFmob plasmid was not detected in standard tests. The derivative of RSFmob with increased copy number has been obtained after lacI elimination. High stability of both constructed plasmids has been demonstrated in Escherichia coli and Pantoea ananatis. Design of RSFmob allows easy substitution of PlacUV5 by any desirable promoter for construction of novel derivatives with changed copy number or host range. Conclusion Novel non-mobilizable derivatives of RSF1010 lacking all known DNA sequences involved in the mobilization process and stably maintained at least in E. coli and P. ananatis have been constructed. The obtained plasmids became the progenitors of new cloning vectors answering all biosafety requirements of genetically modified organisms used in scale-up production.

  6. Vector field statistical analysis of kinematic and force trajectories.

    Science.gov (United States)

    Pataky, Todd C; Robinson, Mark A; Vanrenterghem, Jos

    2013-09-27

    When investigating the dynamics of three-dimensional multi-body biomechanical systems it is often difficult to derive spatiotemporally directed predictions regarding experimentally induced effects. A paradigm of 'non-directed' hypothesis testing has emerged in the literature as a result. Non-directed analyses typically consist of ad hoc scalar extraction, an approach which substantially simplifies the original, highly multivariate datasets (many time points, many vector components). This paper describes a commensurately multivariate method as an alternative to scalar extraction. The method, called 'statistical parametric mapping' (SPM), uses random field theory to objectively identify field regions which co-vary significantly with the experimental design. We compared SPM to scalar extraction by re-analyzing three publicly available datasets: 3D knee kinematics, a ten-muscle force system, and 3D ground reaction forces. Scalar extraction was found to bias the analyses of all three datasets by failing to consider sufficient portions of the dataset, and/or by failing to consider covariance amongst vector components. SPM overcame both problems by conducting hypothesis testing at the (massively multivariate) vector trajectory level, with random field corrections simultaneously accounting for temporal correlation and vector covariance. While SPM has been widely demonstrated to be effective for analyzing 3D scalar fields, the current results are the first to demonstrate its effectiveness for 1D vector field analysis. It was concluded that SPM offers a generalized, statistically comprehensive solution to scalar extraction's over-simplification of vector trajectories, thereby making it useful for objectively guiding analyses of complex biomechanical systems. © 2013 Published by Elsevier Ltd. All rights reserved.

  7. Development of all-in-one multicistronic Tet-On lentiviral vectors for inducible co-expression of two transgenes.

    Science.gov (United States)

    Huang, Yide; Zhen, Ruonan; Jiang, Meiqin; Yang, Jie; Yang, Yun; Huang, Zhen; Lin, Yao

    2015-01-01

    Inducible co-expression of multiple genes is often needed in research. Here we describe a single-vector-based Tet-On inducible system for co-expression of two transgenes. The two transgenes (DsRed1 and eGFP as model genes) and reverse tetracycline-controlled transactivator were separated by internal ribosomal entry sites and 2A sequences, and their transcription was controlled by the same tetracycline responsive element. Two novel vectors with different internal ribosomal entry sites and 2A positions on the vectors were constructed. The DsRed1 and eGFP in cells transduced with both vectors are undetectable in the absence of doxycycline and can be efficiently induced in the presence of doxycycline in vitro and in vivo. These two vectors can be useful tools when regulated co-expression of two ecotopic genes is needed. © 2014 International Union of Biochemistry and Molecular Biology, Inc.

  8. Vespucci: a system for building annotated databases of nascent transcripts.

    Science.gov (United States)

    Allison, Karmel A; Kaikkonen, Minna U; Gaasterland, Terry; Glass, Christopher K

    2014-02-01

    Global run-on sequencing (GRO-seq) is a recent addition to the series of high-throughput sequencing methods that enables new insights into transcriptional dynamics within a cell. However, GRO-sequencing presents new algorithmic challenges, as existing analysis platforms for ChIP-seq and RNA-seq do not address the unique problem of identifying transcriptional units de novo from short reads located all across the genome. Here, we present a novel algorithm for de novo transcript identification from GRO-sequencing data, along with a system that determines transcript regions, stores them in a relational database and associates them with known reference annotations. We use this method to analyze GRO-sequencing data from primary mouse macrophages and derive novel quantitative insights into the extent and characteristics of non-coding transcription in mammalian cells. In doing so, we demonstrate that Vespucci expands existing annotations for mRNAs and lincRNAs by defining the primary transcript beyond the polyadenylation site. In addition, Vespucci generates assemblies for un-annotated non-coding RNAs such as those transcribed from enhancer-like elements. Vespucci thereby provides a robust system for defining, storing and analyzing diverse classes of primary RNA transcripts that are of increasing biological interest.

  9. Problems of vector Lagrangians in field theories

    International Nuclear Information System (INIS)

    Krivsky, I.Yu.; Simulik, V.M.

    1997-01-01

    A vector Lagrange approach to the Dirac spinor field and the relationship between the vector Lagrangians for the spinor and electromagnetic fields are considered. A vector Lagrange approach for the system of interacting electromagnetic B=(B μ υ)=(E-bar,H-bar) and spinor Ψ fields is constructed. New Lagrangians (scalar and vector) for electromagnetic field in terms of field strengths are found. The foundations of two new QED models are formulated

  10. Active set support vector regression.

    Science.gov (United States)

    Musicant, David R; Feinberg, Alexander

    2004-03-01

    This paper presents active set support vector regression (ASVR), a new active set strategy to solve a straightforward reformulation of the standard support vector regression problem. This new algorithm is based on the successful ASVM algorithm for classification problems, and consists of solving a finite number of linear equations with a typically large dimensionality equal to the number of points to be approximated. However, by making use of the Sherman-Morrison-Woodbury formula, a much smaller matrix of the order of the original input space is inverted at each step. The algorithm requires no specialized quadratic or linear programming code, but merely a linear equation solver which is publicly available. ASVR is extremely fast, produces comparable generalization error to other popular algorithms, and is available on the web for download.

  11. 3-D Vector Flow Imaging

    DEFF Research Database (Denmark)

    Holbek, Simon

    ultrasonic vector flow estimation and bring it a step closer to a clinical application. A method for high frame rate 3-D vector flow estimation in a plane using the transverse oscillation method combined with a 1024 channel 2-D matrix array is presented. The proposed method is validated both through phantom...... studies and in vivo. Phantom measurements are compared with their corresponding reference value, whereas the in vivo measurement is validated against the current golden standard for non-invasive blood velocity estimates, based on magnetic resonance imaging (MRI). The study concludes, that a high precision...... are introduced with the array. The major disadvantage with an RC transducer, is the limited field-of-view, which is restricted to the forward looking array. It is discussed, that this drawback may be solved with a diverging lens, providing a larger field-of-view, due the the dispersion of the energy. Based...

  12. Lentiviral vectors in cancer immunotherapy.

    Science.gov (United States)

    Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

    2015-01-01

    Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

  13. Vector fields on singular varieties

    CERN Document Server

    Brasselet, Jean-Paul; Suwa, Tatsuo

    2009-01-01

    Vector fields on manifolds play a major role in mathematics and other sciences. In particular, the Poincaré-Hopf index theorem gives rise to the theory of Chern classes, key manifold-invariants in geometry and topology. It is natural to ask what is the ‘good’ notion of the index of a vector field, and of Chern classes, if the underlying space becomes singular. The question has been explored by several authors resulting in various answers, starting with the pioneering work of M.-H. Schwartz and R. MacPherson. We present these notions in the framework of the obstruction theory and the Chern-Weil theory. The interplay between these two methods is one of the main features of the monograph.

  14. Thermodynamics-based models of transcriptional regulation with gene sequence.

    Science.gov (United States)

    Wang, Shuqiang; Shen, Yanyan; Hu, Jinxing

    2015-12-01

    Quantitative models of gene regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled or heuristic approximations of the underlying regulatory mechanisms. In this work, we have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence. The proposed model relies on a continuous time, differential equation description of transcriptional dynamics. The sequence features of the promoter are exploited to derive the binding affinity which is derived based on statistical molecular thermodynamics. Experimental results show that the proposed model can effectively identify the activity levels of transcription factors and the regulatory parameters. Comparing with the previous models, the proposed model can reveal more biological sense.

  15. Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter

    Directory of Open Access Journals (Sweden)

    Hiu Man Grisch-Chan

    2017-06-01

    Full Text Available Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH by delivery of naked DNA/minicircle (MC-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU. Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of 95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters.

  16. Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter.

    Science.gov (United States)

    Grisch-Chan, Hiu Man; Schlegel, Andrea; Scherer, Tanja; Allegri, Gabriella; Heidelberger, Raphael; Tsikrika, Panagiota; Schmeer, Marco; Schleef, Martin; Harding, Cary O; Häberle, Johannes; Thöny, Beat

    2017-06-16

    Limited duration of transgene expression, insertional mutagenesis, and size limitations for transgene cassettes pose challenges and risk factors for many gene therapy vectors. Here, we report on physiological expression of liver phenylalanine hydroxylase (PAH) by delivery of naked DNA/minicircle (MC)-based vectors for correction of homozygous enu2 mice, a model of human phenylketonuria (PKU). Because MC vectors lack a defined size limit, we constructed a MC vector expressing a codon-optimized murine Pah cDNA that includes a truncated intron and is under the transcriptional control of a 3.6-kb native Pah promoter/enhancer sequence. This vector, delivered via hydrodynamic injection, yielded therapeutic liver PAH activity and sustained correction of blood phenylalanine comparable to viral or synthetic liver promoters. Therapeutic efficacy was seen with vector copy numbers of 95% loss of vector genomes and PAH activity in liver, demonstrating that MC vectors had not integrated into the liver genome. In conclusion, MC vectors, which do not have a defined size-limitation, offer a favorable safety profile for hepatic gene therapy due to their non-integration in combination with native promoters. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Arthropods: Vectors of Disease Agents

    Science.gov (United States)

    1994-07-01

    African trypanosomiasis (sleep- Relationships between pathogens and a cycle of development or multipli- ing sickness) and American try- their vectors are...introduced cases of arthropods directly affect human of malaria. This is just a small per- this and other exotic diseases con- health. This article...diseases that are occasionally education credits, earned by complet- transmitted to humans . Tick-borne ing the Laboratory Medicine CE From the

  18. Disease Vector Ecology Profile: Colombia

    Science.gov (United States)

    1998-12-01

    collected in human dwellings using a mouth or powered aspirator and aided by a flashlight. Collections from whatever source are suitable for...Ecuadorian lowland provinces of Sucumbios and Napo bordering the Colombian departments of Putumayo and eastern Amazonas . Otherwise, little is known about...in Appendix A.4. 4. Vector Surveillance and Suppression. Surveillance of triatomines is best conducted with the aid of a flashlight during

  19. A ocean bottom vector magnetometer

    Science.gov (United States)

    Wang, Xiaomei; Teng, Yuntian; Wang, Chen; Ma, Jiemei

    2017-04-01

    The new development instrument with a compact spherical coil system and Overhauser magnetometer for measuring the total strength of the magnetic field and the vectors of strength, Delta inclination - Delta declination, meanwhile we also use a triaxial fluxgate instrument of the traditional instrument for geomagnetic vector filed measurement. The advantages of this method are be calibrated by each other and get good performances with automatic operation, good stability and high resolution. Firstly, a brief description of the instrument measurement principles and the key technologies are given. The instrument used a spherical coil system with 34 coils to product the homogeneous volume inside the coils which is large enough to accommodate the sensor of Overhauser total field sensor; the rest of the footlocker-sized ocean-bottom vector magnetometer consists of equipment to run the sensors and records its data (batteries and a data logger), weight to sink it to the sea floor, a remote-controlled acoustic release and flotation to bring the instrument back to the surface. Finally, the accuracy of the instrument was tested in the Geomagnetic station, and the measurement accuracies of total strength and components were better than 0.2nT and 1nT respectively. The figure 1 shows the development instrument structure. it includes six thick glass spheres which protect the sensor, data logger and batteries from the pressures of the deep sea, meanwhile they also provide recycling positive buoyancy; To cushion the glass, the spheres then go inside yellow plastic "hardhats". The triaxial fluxgate is inside No.1 glass spheres, data logger and batteries are inside No.2 glass spheres, the new vector sensor is inside No.3 glass spheres, acoustic communication unit is inside No.4 glass spheres, No.5 and No.6 glass spheres are empty which only provide recycling positive buoyancy. The figure 2 shows the development instrument Physical photo.

  20. Vector Fields and Flows on Differentiable Stacks

    DEFF Research Database (Denmark)

    A. Hepworth, Richard

    2009-01-01

    This paper introduces the notions of vector field and flow on a general differentiable stack. Our main theorem states that the flow of a vector field on a compact proper differentiable stack exists and is unique up to a uniquely determined 2-cell. This extends the usual result on the existence...... of vector fields....

  1. Construction of expression vectors carrying mouse peroxisomal ...

    African Journals Online (AJOL)

    The aim of this study was to construct expression vectors carrying mouse peroxisomal protein gene (PEP-cDNA) in prokaryotic and mammalian expression vectors in ... pGEX6p2-PEP and pUcD3-FLAG-PEP constructed vectors were transformed into the one shot TOP10 and JM105 bacterial competent cells, respectively.

  2. SOLIS vector spectromagnetograph: status and science

    NARCIS (Netherlands)

    Henney, C.J.; Keller, C.U.; Harvey, J.W.; Georgoulis, M.K.; Hadder, N.L.; Norton, A.A.; Raouafi, N.-E.; Toussaint, R.M.

    2007-01-01

    The Vector Spectromagnetograph (VSM) instrument has recorded photospheric and chromospheric magnetograms daily since August 2003. Fulldisk photospheric vector magnetograms are observed at least weekly and, since November 2006, area-scans of active regions daily. Quick-look vector magnetic images,

  3. Vector and tensor analysis with applications

    CERN Document Server

    Borisenko, A I; Silverman, Richard A

    1979-01-01

    Concise and readable, this text ranges from definition of vectors and discussion of algebraic operations on vectors to the concept of tensor and algebraic operations on tensors. It also includes a systematic study of the differential and integral calculus of vector and tensor functions of space and time. Worked-out problems and solutions. 1968 edition.

  4. Vector fields and gravity on the lattice

    International Nuclear Information System (INIS)

    Khatsymovsky, V.M.

    1988-01-01

    The problem of discretization of vector field on Regge lattice is considered. Our approach is based on geometrical interpretation of the vector field as the field of infinitesimal coordinate transformation. A discrete version of the vector field action is obtained as a particular case of the continuum action, and it is shown to have the true continuum limit

  5. Extremal vectors and rectifiability | Enflo | Quaestiones Mathematicae

    African Journals Online (AJOL)

    Extremal vectors and rectifiability. ... The concept of extremal vectors of a linear operator with a dense range but not onto on a Hilbert space was introduced by P. Enflo in 1996 as a new approach to study invariant subspaces ... We show that in general curves that map numbers to backward minimal vectors are not rectifiable.

  6. Identification of germline transcriptional regulatory elements in Aedes aegypti

    Science.gov (United States)

    Akbari, Omar S.; Papathanos, Philippos A.; Sandler, Jeremy E.; Kennedy, Katie; Hay, Bruce A.

    2014-02-01

    The mosquito Aedes aegypti is the principal vector for the yellow fever and dengue viruses, and is also responsible for recent outbreaks of the alphavirus chikungunya. Vector control strategies utilizing engineered gene drive systems are being developed as a means of replacing wild, pathogen transmitting mosquitoes with individuals refractory to disease transmission, or bringing about population suppression. Several of these systems, including Medea, UDMEL, and site-specific nucleases, which can be used to drive genes into populations or bring about population suppression, utilize transcriptional regulatory elements that drive germline-specific expression. Here we report the identification of multiple regulatory elements able to drive gene expression specifically in the female germline, or in the male and female germline, in the mosquito Aedes aegypti. These elements can also be used as tools with which to probe the roles of specific genes in germline function and in the early embryo, through overexpression or RNA interference.

  7. Consciousness disintegrates without conscious vectors.

    Science.gov (United States)

    Bodovitz, Steven

    2008-01-01

    Consciousness is discontinuous. The transition from the raw output of parallel, distributed processors into the unified, serial content of consciousness is not instantaneous. Consciousness is divided into discrete cycles, yet appears to be continuous. The continuity requires temporal integration. The simplest mechanism is the calculation of the direction and magnitude of change from one conscious cycle to the next and then the fusion of these conscious vectors with the content of subsequent cycles. This mechanism, while putative, has supporting evidence. It is based on the same mechanism as motion vision, in which motion vectors are calculated in MT/V5 and then fused with discrete images. Moreover, it is based on the known separation of cognitive timing in the brain, in which temporal integrity is maintained in the prefrontal cortex (PFC) and the rest of the content of consciousness is maintained in the rest of the cortex. In fact, limited activity of the PFC matches the predicted effects of the absence of conscious vectors: thoughts strobe and consciousness disintegrates into a series of discrete cycles. The PFC, for example, is one of the primary brain regions deactivated during dreaming, when thoughts shift without any awareness of the transitions. In addition, the PFC is immature in infants, when there is no memory of the experience of consciousness because there is no temporal integrity to assemble the discrete cycles into a coherent experience. Without temporal integration, the human brain is an advanced biological computer, but is not sentient.

  8. Nuclear Dynamics of BRCA1-Dependent Transcription Regulation

    National Research Council Canada - National Science Library

    Sharp, Zelton D

    2005-01-01

    ...) Construction of fluorescent GAL4-DBD and ZBRK1 fusion protein has been achieved, and BRCA1 derivatives are in progress. When operational, this system will document real time nuclear dynamics of ZBRK1/BRCA1-dependent chromatin modification systems, as cells mount transcriptional responses to genotoxins.

  9. Accelerating anisotropic cosmologies in Brans-Dicke gravity coupled to a mass-varying vector field

    OpenAIRE

    Akarsu, Ozgur; Dereli, Tekin; Oflaz, Neslihan

    2013-01-01

    The field equations of Brans-Dicke gravity coupled to a mass-varying vector field are derived. Anisotropic cosmological solutions with a locally rotationally symmetric Bianchi type I metric and time-dependent scalar and electric vector fields are studied. A particular class of exact solutions for which all the variable parameters have a power-law time dependence is given. The universe expands with a constant expansion anisotropy within this class of solutions. We show that the accelerating ex...

  10. Principal fiber bundle description of number scaling for scalars and vectors: application to gauge theory

    Energy Technology Data Exchange (ETDEWEB)

    Donkor, Eric; Pirich, Andrew R.; Hayduk, Michael; Benioff, Paul

    2015-05-21

    The purpose of this paper is to put the description of number scaling and its effects on physics and geometry on a firmer foundation, and to make it more understandable. A main point is that two different concepts, number and number value are combined in the usual representations of number structures. This is valid as long as one structure of each number type is being considered. It is not valid when different structures of each number type are being considered. Elements of base sets of number structures, considered by themselves, have no meaning. They acquire meaning or value as elements of a number structure. Fiber bundles over a space or space time manifold, M, are described. The fiber consists of a collection of many real or complex scaling factor, s. A vector space at a fiber level, s, has as scalars, real or complex number structures at the same level. Connections are described that relate scalar and vector space structures at both neighbor M locations and at neighbor scaling levels. Scalar and vector structure valued fields are described and covariant derivatives of these fields are obtained. Two complex vector fields, each with one real and one imaginary field, appear, with one complex field associated with positions in M and the other with position dependent scaling factors. A derivation of the covariant derivative for scalar and vector values fields gives the same vector fields. The derivation shoes that complex vector field associated with scaling fiber levels is the gradient of a complex scalar field. Use of these results in gauge theory shows that the imaginary part of the vector field associated with M positions acts like the electromagnetic field. The physical relevance of the other three fields, if any, is not known.

  11. Geometric quantization of vector bundles and the correspondence with deformation quantization

    International Nuclear Information System (INIS)

    Hawkins, E.

    2000-01-01

    I repeat my definition for quantization of a vector bundle. For the cases of the Toeplitz and geometric quantizations of a compact Kaehler manifold, I give a construction for quantizing any smooth vector bundle, which depends functorially on a choice of connection on the bundle. Using this, the classification of formal deformation quantizations, and the formal, algebraic index theorem, I give a simple proof as to which formal deformation quantization (modulo isomorphism) is derived from a given geometric quantization. (orig.)

  12. Inactivation of PITX2 transcription factor induced apoptosis of gonadotroph tumoral cells.

    Science.gov (United States)

    Acunzo, Julie; Roche, Catherine; Defilles, Celine; Thirion, Sylvie; Quentien, Marie-Helene; Figarella-Branger, Dominique; Graillon, Thomas; Dufour, Henry; Brue, Thierry; Pellegrini, Isabelle; Enjalbert, Alain; Barlier, Anne

    2011-10-01

    Nonfunctioning pituitary adenomas (NFPA; gonadotroph derived), even not inducing hormonal hypersecretion, cause significant morbidity by compression neighboring structures. No effective and specific medical methods are available so far for treating these tumors. The pituitary homeobox 2 (PITX2) gene is a member of the bicoid-like homeobox transcription factor family, which is involved in the Wnt/Dvl/β-catenin pathway. PITX2 is overexpressed in NFPA. PITX2 mutations are known to be responsible for Axenfield Rieger syndrome, a genetic disorder in which pituitary abnormalities have been detected. The R91P mutant identified in Axenfeld Rieger syndrome is a dominant-negative factor, which is able to block the expression of several pituitary genes activated by PITX2. To better understand the role of Pitx2 on gonadotroph tumorigenesis and to explore new approach for inhibiting tumoral growth, the R91P mutant was transferred via a lentiviral vector in tumoral gonadotroph cells of two kinds: the αT3-1 cell line and human adenoma cells. R91P mutant and small interfering RNA directed against Pitx2 both decreased the viability of αT3-1 cells via an apoptotic mechanism involving the activation of executioner caspase. Similar effects of the R91P mutant were observed on human gonadotroph cells in primary culture. Therefore, Pitx2 overexpression may play an antiapoptotic role during NFPA tumorigenesis.

  13. Mitotic bookmarking by transcription factors.

    Science.gov (United States)

    Kadauke, Stephan; Blobel, Gerd A

    2013-04-02

    Mitosis is accompanied by dramatic changes in chromatin organization and nuclear architecture. Transcription halts globally and most sequence-specific transcription factors and co-factors are ejected from mitotic chromatin. How then does the cell maintain its transcriptional identity throughout the cell division cycle? It has become clear that not all traces of active transcription and gene repression are erased within mitotic chromatin. Many histone modifications are stable or only partially diminished throughout mitosis. In addition, some sequence-specific DNA binding factors have emerged that remain bound to select sites within mitotic chromatin, raising the possibility that they function to transmit regulatory information through the transcriptionally silent mitotic phase, a concept that has been termed "mitotic bookmarking." Here we review recent approaches to studying potential bookmarking factors with regards to their mitotic partitioning, and summarize emerging ideas concerning the in vivo functions of mitotically bound nuclear factors.

  14. Black holes in vector-tensor theories and their thermodynamics

    Science.gov (United States)

    Fan, Zhong-Ying

    2018-01-01

    In this paper, we study Einstein gravity either minimally or non-minimally coupled to a vector field which breaks the gauge symmetry explicitly in general dimensions. We first consider a minimal theory which is simply the Einstein-Proca theory extended with a quartic self-interaction term for the vector field. We obtain its general static maximally symmetric black hole solution and study the thermodynamics using Wald formalism. The aspects of the solution are much like a Reissner-Nordstrøm black hole in spite of that a global charge cannot be defined for the vector. For non-minimal theories, we obtain a lot of exact black hole solutions, depending on the parameters of the theories. In particular, many of the solutions are general static and have maximal symmetry. However, there are some subtleties and ambiguities in the derivation of the first laws because the existence of an algebraic degree of freedom of the vector in general invalids the Wald entropy formula. The thermodynamics of these solutions deserves further studies.

  15. Problems and worked solutions in vector analysis

    CERN Document Server

    Shorter, LR

    2014-01-01

    ""A handy book like this,"" noted The Mathematical Gazette, ""will fill a great want."" Devoted to fully worked out examples, this unique text constitutes a self-contained introductory course in vector analysis for undergraduate and graduate students of applied mathematics.Opening chapters define vector addition and subtraction, show how to resolve and determine the direction of two or more vectors, and explain systems of coordinates, vector equations of a plane and straight line, relative velocity and acceleration, and infinitely small vectors. The following chapters deal with scalar and vect

  16. Stokes vector and its relationship to Discrete Wigner Functions of multiqubit states

    International Nuclear Information System (INIS)

    Srinivasan, K.; Raghavan, G.

    2016-01-01

    A Stokes vectors and Discrete Wigner Functions (DWF) provide two alternate ways of representing the state of multiqubit systems. A general relationship between the Stokes vector and the DWF is derived for arbitrary n-qubit states for all possible choices of quantum nets. The Stokes vector and the DWF are shown to be related through a Hadamard Matrix. Using these results, a relationship between the Stokes vector of a spin-flipped state and the DWF is derived. Finally, we also present a method to express the Minkowskian squared norm of the Stokes vector, corresponding to n-concurrence in terms of the DWF. - Highlights: • Relationship between Stokes vector (SV) and discrete Wigner function (DWF) for arbitrary multiqubit states is presented. • It is shown that SV and DWF are related to one another through Hadamard matrices. • We show that the Hadamard matrices depend on the choice of the quantum net. • Relationship between SV of the spin flipped state and the DWF is derived. • Expression to compute n-concurrence of the pure n-qubit systems purely in terms of DWF is given.

  17. Large-scale Clinical-grade Retroviral Vector Production in a Fixed-Bed Bioreactor

    Science.gov (United States)

    Wang, Xiuyan; Olszewska, Malgorzata; Qu, Jinrong; Wasielewska, Teresa; Bartido, Shirley; Hermetet, Gregory; Sadelain, Michel

    2015-01-01

    The successful genetic engineering of patient T cells with γ-retroviral vectors expressing chimeric antigen receptors or T-cell receptors for phase II clinical trials and beyond requires the large-scale manufacture of high-titer vector stocks. The production of retroviral vectors from stable packaging cell lines using roller bottles or 10- to 40-layer cell factories is limited by a narrow harvest window, labor intensity, open-system operations, and the requirement for significant incubator space. To circumvent these shortcomings, we optimized the production of vector stocks in a disposable fixed-bed bioreactor using good manufacturing practice–grade packaging cell lines. High-titer vector stocks were harvested over 10 days, representing a much broader harvest window than the 3-day harvest afforded by cell factories. For PG13 and 293Vec packaging cells, the average vector titer and the vector stocks’ yield in the bioreactor were higher by 3.2- to 7.3-fold, and 5.6- to 13.1-fold, respectively, than those obtained in cell factories. The vector production was 10.4 and 18.6 times more efficient than in cell factories for PG13 and 293Vec cells, respectively. Furthermore, the vectors produced from the fixed-bed bioreactors passed the release test assays for clinical applications. Therefore, a single vector lot derived from 293Vec is suitable to transduce up to 500 patients cell doses in the context of large clinical trials using chimeric antigen receptors or T-cell receptors. These findings demonstrate for the first time that a robust fixed-bed bioreactor process can be used to produce γ-retroviral vector stocks scalable up to the commercialization phase. PMID:25751502

  18. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    ." - Steen Parsholt, Chairman and CEO, Aon Nordic Region. "Andersen has done a wonderful job of developing a comprehensive text that deals with risk management in global markets. I would recommend this book to any student or businessman who has a need to better understand the risks and risk management......""In Global Derivatives: A Strategic Risk Management Perspective", Torben Juul Andersen has succeeded to gather in one book a complete and thorough summary and an easy-to-read explanation of all types of derivative instruments and their background, and their use in modern management of risk...... approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk...

  19. Multiscale vector fields for image pattern recognition

    Science.gov (United States)

    Low, Kah-Chan; Coggins, James M.

    1990-01-01

    A uniform processing framework for low-level vision computing in which a bank of spatial filters maps the image intensity structure at each pixel into an abstract feature space is proposed. Some properties of the filters and the feature space are described. Local orientation is measured by a vector sum in the feature space as follows: each filter's preferred orientation along with the strength of the filter's output determine the orientation and the length of a vector in the feature space; the vectors for all filters are summed to yield a resultant vector for a particular pixel and scale. The orientation of the resultant vector indicates the local orientation, and the magnitude of the vector indicates the strength of the local orientation preference. Limitations of the vector sum method are discussed. Investigations show that the processing framework provides a useful, redundant representation of image structure across orientation and scale.

  20. Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication.

    Science.gov (United States)

    Taylor, Jason A; Vojtech, Lucia; Bahner, Ingrid; Kohn, Donald B; Laer, Dorothee Von; Russell, David W; Richard, Robert E

    2008-01-01

    Gene therapy has the potential to control human immunodeficiency virus (HIV) in patients who do not respond to traditional antiviral therapy. In this study, we tested foamy virus (FV) vectors expressing three anti-HIV transgenes, both individually and in a combination vector. The transgenes tested in this study are RevM10, a dominant negative version of the viral rev protein, Sh1, a short hairpin RNA directed against a conserved overlapping sequence of tat and rev, and membrane-associated C46 (maC46), a membrane-attached peptide that blocks HIV cell entry. FV vectors efficiently transduce hematopoietic stem cells and, unlike lentivirus (LV) vectors, do not share viral proteins with HIV. The titers of the FV vectors described in this study were not affected by anti-HIV transgenes. On a direct comparison of FV vectors expressing the individual transgenes, entry inhibition using the maC46 transgene was found to be the most effective at blocking HIV replication. A clinically relevant FV vector expressing three anti-HIV transgenes effectively blocked HIV infection in primary macrophages derived from transduced, peripheral blood CD34-selected cells and in a cell line used for propagating HIV, CEMx174. These results suggest that there are potential benefits of using FV vectors in HIV gene therapy.

  1. 21 CFR 12.98 - Official transcript.

    Science.gov (United States)

    2010-04-01

    ..., participants, and counsel have 30 days from the time the transcript becomes available to propose corrections in the transcript of oral testimony. Corrections are permitted only for transcription errors. The... a verbatim stenographic transcript of oral testimony and for necessary copies of the transcript. (b...

  2. Hepatitis virus protein X-Phenylalanine Hydroxylase fusion proteins identified in PKU mice treated with AAV-WPRE vectors

    Science.gov (United States)

    Utilizing the Pahenu2 mouse model for phenylketonuria (PKU), we developed an improved expression vector containing the Woodchuck Hepatitis Virus post-transcriptional regulatory element inserted into a rAAV-mPAH construct (rAAV-mPAH-WPRE) for treatment of PKU. Following portal vein delivery of these ...

  3. Effects of insertion sites in a Newcastle disease virus vector on foreign gene expression through an internal ribosomal entry site

    Science.gov (United States)

    Newcastle disease virus (NDV), avian paramyxovirus type 1, has been developed as a vector to express foreign genes for vaccine and gene therapy purposes. The foreign genes are usually inserted into a non-coding region of the NDV genome as an independent transcription unit (ITU), which potentially a...

  4. Development of a Newcastle disease virus vector expressing a foreign gene through an internal ribosomal entry site

    Science.gov (United States)

    Newcastle disease virus (NDV) has been developed as a vector to express foreign genes for vaccine and gene therapy purposes. The foreign genes are usually inserted into a non-coding region of the NDV genome as an independent transcription unit (ITU). Based on the well-accepted “stop-start” transcr...

  5. Determination of key parameters of vector multifractal vector fields

    Science.gov (United States)

    Schertzer, D. J. M.; Tchiguirinskaia, I.

    2017-12-01

    For too long time, multifractal analyses and simulations have been restricted to scalar-valued fields (Schertzer and Tchiguirinskaia, 2017a,b). For instance, the wind velocity multifractality has been mostly analysed in terms of scalar structure functions and with the scalar energy flux. This restriction has had the unfortunate consequences that multifractals were applicable to their full extent in geophysics, whereas it has inspired them. Indeed a key question in geophysics is the complexity of the interactions between various fields or they components. Nevertheless, sophisticated methods have been developed to determine the key parameters of scalar valued fields. In this communication, we first present the vector extensions of the universal multifractal analysis techniques to multifractals whose generator belong to a Levy-Clifford algebra (Schertzer and Tchiguirinskaia, 2015). We point out further extensions noting the increased complexity. For instance, the (scalar) index of multifractality becomes a matrice. Schertzer, D. and Tchiguirinskaia, I. (2015) `Multifractal vector fields and stochastic Clifford algebra', Chaos: An Interdisciplinary Journal of Nonlinear Science, 25(12), p. 123127. doi: 10.1063/1.4937364. Schertzer, D. and Tchiguirinskaia, I. (2017) `An Introduction to Multifractals and Scale Symmetry Groups', in Ghanbarian, B. and Hunt, A. (eds) Fractals: Concepts and Applications in Geosciences. CRC Press, p. (in press). Schertzer, D. and Tchiguirinskaia, I. (2017b) `Pandora Box of Multifractals: Barely Open ?', in Tsonis, A. A. (ed.) 30 Years of Nonlinear Dynamics in Geophysics. Berlin: Springer, p. (in press).

  6. On Weighted Support Vector Regression

    DEFF Research Database (Denmark)

    Han, Xixuan; Clemmensen, Line Katrine Harder

    2014-01-01

    We propose a new type of weighted support vector regression (SVR), motivated by modeling local dependencies in time and space in prediction of house prices. The classic weights of the weighted SVR are added to the slack variables in the objective function (OF‐weights). This procedure directly...... the differences and similarities of the two types of weights by demonstrating the connection between the Least Absolute Shrinkage and Selection Operator (LASSO) and the SVR. We show that an SVR problem can be transformed to a LASSO problem plus a linear constraint and a box constraint. We demonstrate...

  7. [Pluripotency candidate signaling network and transcription factors in domesticated ungulates: a review].

    Science.gov (United States)

    Zhao, Yuncheng; Chen, Bo; Zhou, Chuan; Zhang, Xiuhua; Huang, Juncheng

    2010-12-01

    Domesticated ungulates embryonic stem (ES) cells have great significances in biology and wide application prospects. This review compared the key signaling pathways related with pluripotency between mouse and human ES cells, and the difference of transcription factors in mouse, human and domesticated ungulates ES cells were elaborated. Finally the pluripotency candidate signaling network and transcription factors related in the derivation of domesticated ungulates ES cell were discussed combined with practical experience of ovine embryonic stem cell derivation in our laboratory.

  8. Estimation of pure autoregressive vector models for revenue series ...

    African Journals Online (AJOL)

    This paper aims at applying multivariate approach to Box and Jenkins univariate time series modeling to three vector series. General Autoregressive Vector Models with time varying coefficients are estimated. The first vector is a response vector, while others are predictor vectors. By matrix expansion each vector, whether ...

  9. A new estimator for vector velocity estimation [medical ultrasonics

    DEFF Research Database (Denmark)

    Jensen, Jørgen Arendt

    2001-01-01

    A new estimator for determining the two-dimensional velocity vector using a pulsed ultrasound field is derived. The estimator uses a transversely modulated ultrasound field for probing the moving medium under investigation. A modified autocorrelation approach is used in the velocity estimation....... The new estimator automatically compensates for the axial velocity when determining the transverse velocity. The estimation is optimized by using a lag different from one in the estimation process, and noise artifacts are reduced by averaging RF samples. Further, compensation for the axial velocity can...... be introduced, and the velocity estimation is done at a fixed depth in tissue to reduce the influence of a spatial velocity spread. Examples for different velocity vectors and field conditions are shown using both simple and more complex field simulations. A relative accuracy of 10.1% is obtained...

  10. Optimal hedging with the cointegrated vector autoregressive model

    DEFF Research Database (Denmark)

    Gatarek, Lukasz; Johansen, Søren

    We derive the optimal hedging ratios for a portfolio of assets driven by a Coin- tegrated Vector Autoregressive model (CVAR) with general cointegration rank. Our hedge is optimal in the sense of minimum variance portfolio. We consider a model that allows for the hedges to be cointegrated...... with the hedged asset and among themselves. We nd that the minimum variance hedge for assets driven by the CVAR, depends strongly on the portfolio holding period. The hedge is dened as a function of correlation and cointegration parameters. For short holding periods the correlation impact is predominant. For long...... horizons, the hedge ratio should overweight the cointegration parameters rather then short-run correlation information. In the innite horizon, the hedge ratios shall be equal to the cointegrating vector. The hedge ratios for any intermediate portfolio holding period should be based on the weighted average...

  11. Vector-tensor and vector-vector decay amplitude analysis of B0-->phiK*0.

    Science.gov (United States)

    Aubert, B; Bona, M; Boutigny, D; Couderc, F; Karyotakis, Y; Lees, J P; Poireau, V; Tisserand, V; Zghiche, A; Grauges, E; Palano, A; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Ofte, I; Stugu, B; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Charles, E; Gill, M S; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Pegna, D Lopes; Lynch, G; Mir, L M; Orimoto, T J; Pripstein, M; Roe, N A; Ronan, M T; Wenzel, W A; Sanchez, P del Amo; Barrett, M; Ford, K E; Harrison, T J; Hart, A J; Hawkes, C M; Watson, A T; Held, T; Koch, H; Lewandowski, B; Pelizaeus, M; Peters, K; Schroeder, T; Steinke, M; Boyd, J T; Burke, J P; Cottingham, W N; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Knecht, N S; Mattison, T S; McKenna, J A; Khan, A; Kyberd, P; Saleem, M; Sherwood, D J; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Best, D S; Bondioli, M; Bruinsma, M; Chao, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Roethel, W; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Long, O; Shen, B C; Wang, K; Zhang, L; Hadavand, H K; Hill, E J; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Nesom, G; Schalk, T; Schumm, B A; Seiden, A; Spradlin, P; Williams, D C; Wilson, M G; Albert, J; Chen, E; Cheng, C H; Dvoretskii, A; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Ruddick, W O; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Chen, A; Eckhart, E A; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Zeng, Q; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Brandt, T; Klose, V; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cibinetto, G; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Vetere, M Lo; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Brandenburg, G; Chaisanguanthum, K S; Lee, C L; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Bhimji, W; Bowerman, D A; Dauncey, P D; Egede, U; Flack, R L; Nash, J A; Nikolich, M B; Vazquez, W Panduro; Behera, P K; Chai, X; Charles, M J; Mallik, U; Meyer, N T; Ziegler, V; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y; Gritsan, A V; Guo, Z J; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Diberder, F Le; Lutz, A M; Oyanguren, A; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Chavez, C A; Forster, I J; Fry, J R; Gabathuler, E; Gamet, R; George, K A; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; Clarke, C K; Lodovico, F Di; Menges, W; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Jackson, P S; McMahon, T R; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; Naisbit, M T; Williams, J C; Yi, J I; Chen, C; Hulsbergen, W D; Jawahery, A; Lae, C K; Roberts, D A; Simi, G; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Saremi, S; Staengle, H; Cowan, R; Sciolla, G; Sekula, S J; Spitznagel, M; Taylor, F; Yamamoto, R K; Kim, H; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; Cavallo, N; Nardo, G De; Fabozzi, F; Gatto, C; Lista, L; Monorchio, D; Paolucci, P; Piccolo, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Losecco, J M; Benelli, G; Corwin, L A; Gan, K K; Honscheid, K; Hufnagel, D; Jackson, P D; Kagan, H; Kass, R; Rahimi, A M; Regensburger, J J; Ter-Antonyan, R; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Potter, C T; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C

    2007-02-02

    We perform an amplitude analysis of the decays B(0)-->phiK*(2)(1430)(0), phiK*(892)(0), and phi(Kpi)(0)(S-wave) with a sample of about 384x10(6) BB[over ] pairs recorded with the BABAR detector. The fractions of longitudinal polarization f(L) of the vector-tensor and vector-vector decay modes are measured to be 0.853(-0.069+0.061)+/-0.036 and 0.506+/-0.040+/-0.015, respectively. Overall, twelve parameters are measured for the vector-vector decay and seven parameters for the vector-tensor decay, including the branching fractions and parameters sensitive to CP violation.

  12. Transcriptional Auto-Regulation of RUNX1 P1 Promoter

    Science.gov (United States)

    Martinez, Milka; Hinojosa, Marcela; Trombly, Daniel; Morin, Violeta; Stein, Janet; Stein, Gary; Javed, Amjad; Gutierrez, Soraya E.

    2016-01-01

    RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5’UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription. PMID:26901859

  13. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  14. Derivative chameleons

    International Nuclear Information System (INIS)

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  15. Dengue Vectors and their Spatial Distribution.

    Science.gov (United States)

    Higa, Yukiko

    2011-12-01

    The distribution of dengue vectors, Ae. aegypti and Ae. albopictus, is affected by climatic factors. In addition, since their life cycles are well adapted to the human environment, environmental changes resulting from human activity such as urbanization exert a great impact on vector distribution. The different responses of Ae. aegypti and Ae albopictus to various environments result in a difference in spatial distribution along north-south and urban-rural gradients, and between the indoors and outdoors. In the north-south gradient, climate associated with survival is an important factor in spatial distribution. In the urban-rural gradient, different distribution reflects a difference in adult niches and is modified by geographic and human factors. The direct response of the two species to the environment around houses is related to different spatial distribution indoors and outdoors. Dengue viruses circulate mainly between human and vector mosquitoes, and the vector presence is a limiting factor of transmission. Therefore, spatial distribution of dengue vectors is a significant concern in the epidemiology of the disease.Current technologies such as GIS, satellite imagery and statistical models allow researchers to predict the spatial distribution of vectors in the changing environment. Although it is difficult to confirm the actual effect of environmental and climate changes on vector abundance and vector-borne diseases, environmental changes caused by humans and human behavioral changes due to climate change can be expected to exert an impact on dengue vectors. Longitudinal monitoring of dengue vectors and viruses is therefore necessary.

  16. Chromosomal contact permits transcription between coregulated genes

    CSIR Research Space (South Africa)

    Fanucchi, Stephanie

    2013-10-01

    Full Text Available Transcription of coregulated genes occurs in the context of long-range chromosomal contacts that form multigene complexes. Such contacts and transcription are lost in knockout studies of transcription factors and structural chromatin proteins...

  17. Use of Lanczos vectors in fluid/structure interaction problems

    International Nuclear Information System (INIS)

    Jeans, R.; Mathews, I.C.

    1992-01-01

    The goals of any numerical computational technique used for the solution of structural acoustics problems in the exterior infinite domain should be of accuracy with rapid convergence, robustness, and computational efficiency. A computer program has been developed to achieve each of these three goals. Accuracy and robustness in the numerical representation of the integral equations used to represent the infinite fluid was attained through the use of boundary element implementations of the surface Helmholtz integral equations. The computational efficiency was resolved through the use of Lanczos vectors to model the deformation characteristics of the structure. The authors have developed collocation and variational techniques to overcome the difficulties previously encountered in the numerical implementation of the hypersingular integral operator. The Cauchy singularity present in the integral formulation is made numerically amenable through the use of tangential derivatives in both the collocation and variational techniques. The variational approach has the advantage that the resulting added fluid mass term is symmetric and combines efficiently with a finite element approximation of the structural elastic response. Several different strategies making use of the Lanczos vectors have been investigated. The first involved the use of Lanczos vectors solely to characterize the structural response. This reduced form of the structural dynamical matrix was then substituted back into a Burton and Miller formulation of the acoustic problem. The second strategy investigated involved forming the complex Lanzcos vectors of the dynamical matrix formed from the addition of a symmetrical added fluid matrix to the structural mass matrix. The size of resultant matrix equation set solved at each frequency for this strategy is determined by the number of Lanczos vectors used. 19 refs., 10 figs., 2 tabs

  18. Transcriptional control of megakaryocyte development.

    Science.gov (United States)

    Goldfarb, A N

    2007-10-15

    Megakaryocytes are highly specialized cells that arise from a bipotent megakaryocytic-erythroid progenitor (MEP). This developmental leap requires coordinated activation of megakaryocyte-specific genes, radical changes in cell cycle properties, and active prevention of erythroid differentiation. These programs result from upregulation of megakaryocyte-selective transcription factors, downregulation of erythroid-selective transcription factors and ongoing mediation of common erythro-megakaryocytic transcription factors. Unlike most developmental programs, no single lineage-unique family of master regulators exerts executive control over the megakaryocytic plan. Rather, an assemblage of non-unique factors and signals converge to determine lineage and differentiation. In human megakaryopoiesis, hereditary disorders of platelet production have confirmed contributions from three distinct transcription factor families. Murine models have extended this repertoire to include multiple additional factors. At a mechanistic level, the means by which these non-unique factors collaborate in the establishment of a perfectly unique cell type remains a central question.

  19. RNA-guided transcriptional regulation

    Science.gov (United States)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  20. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    , postgraduate qualification or MBA programme. This book also caters for practicing managers and executives who need to understand current developments in global derivatives markets and require cutting-edge insight on strategic risk management issues. Dr Torben Juul Andersen is currently Associate Professor...... approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk...... management practice. Of particular note is the global and integrated approach chosen in this book which should be of special interest to aspiring managers active in global and international markets." - Dr Jean-Pierre Zigrand, Lecturer in Finance, London School of Economics, UK. More than 90 per cent...

  1. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  2. Ectopic expression of the erythrocyte band 3 anion exchange protein, using a new avian retrovirus vector

    DEFF Research Database (Denmark)

    Fuerstenberg, S; Beug, H; Introna, M

    1990-01-01

    A retrovirus vector was constructed from the genome of avian erythroblastosis virus ES4. The v-erbA sequences of avian erythroblastosis virus were replaced by those coding for neomycin phosphotransferase, creating a gag-neo fusion protein which provides G418 resistance as a selectable marker. The v...... into protein. Using the Escherichia coli beta-galactosidase gene cloned into the vector as a test construct, expression of enzyme activity could be detected in 90 to 95% of transfected target cells and in 80 to 85% of subsequently infected cells. In addition, a cDNA encoding the avian erythrocyte band 3 anion......-erbB sequences following the splice acceptor were replaced by a cloning linker allowing insertion of foreign genes. The vector has been tested in conjunction with several helper viruses for the transmission of G418 resistance, titer, stability, transcription, and the transduction and expression of foreign genes...

  3. Initiation of HIV Reverse Transcription

    OpenAIRE

    Isel, Catherine; Ehresmann, Chantal; Marquet, Roland

    2010-01-01

    Reverse transcription of retroviral genomes into double stranded DNA is a key event for viral replication. The very first stage of HIV reverse transcription, the initiation step, involves viral and cellular partners that are selectively packaged into the viral particle, leading to an RNA/protein complex with very specific structural and functional features, some of which being, in the case of HIV-1, linked to particular isolates. Recent understanding of the tight spatio-temporal regulation of...

  4. Hybrid lentivirus-phiC31-int-NLS vector allows site-specific recombination in murine and human cells but induces DNA damage.

    Directory of Open Access Journals (Sweden)

    Nicolas Grandchamp

    Full Text Available Gene transfer allows transient or permanent genetic modifications of cells for experimental or therapeutic purposes. Gene delivery by HIV-derived lentiviral vector (LV is highly effective but the risk of insertional mutagenesis is important and the random/uncontrollable integration of the DNA vector can deregulate the cell transcriptional activity. Non Integrative Lentiviral Vectors (NILVs solve this issue in non-dividing cells, but they do not allow long term expression in dividing cells. In this context, obtaining stable expression while avoiding the problems inherent to unpredictable DNA vector integration requires the ability to control the integration site. One possibility is to use the integrase of phage phiC31 (phiC31-int which catalyzes efficient site-specific recombination between the attP site in the phage genome and the chromosomal attB site of its Streptomyces host. Previous studies showed that phiC31-int is active in many eukaryotic cells, such as murine or human cells, and directs the integration of a DNA substrate into pseudo attP sites (pattP which are homologous to the native attP site. In this study, we combined the efficiency of NILV for gene delivery and the specificity of phiC31-int for DNA substrate integration to engineer a hybrid tool for gene transfer with the aim of allowing long term expression in dividing and non-dividing cells preventing genotoxicity. We demonstrated the feasibility to target NILV integration in human and murine pattP sites with a dual NILV vectors system: one which delivers phiC31-int, the other which constitute the substrate containing an attB site in its DNA sequence. These promising results are however alleviated by the occurrence of significant DNA damages. Further improvements are thus required to prevent chromosomal rearrangements for a therapeutic use of the system. However, its use as a tool for experimental applications such as transgenesis is already applicable.

  5. Cloning and characterization of a putative transcription factor ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-12-15

    Dec 15, 2009 ... with SpeI and KpnI, fused to the pMDC85-derived GFP-expression vector, then transiently expressed in onion epidermal cells (Scott et al., 1999) using a biolistic PDS-1000/HeTM particle gun (Bio-Rad). After incubation for 18 - 24 h, fluorescence emission of GFP was observed under a confocal microscope ...

  6. Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle.

    Science.gov (United States)

    Allera-Moreau, Camille; Delluc-Clavières, Aurélie; Castano, Caroline; Van den Berghe, Loïc; Golzio, Muriel; Moreau, Marc; Teissié, Justin; Arnal, Jean-François; Prats, Anne-Catherine

    2007-10-28

    Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs) allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV) IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the FGF-1 IRES. The use of a cellular IRES over one of viral

  7. Long term expression of bicistronic vector driven by the FGF-1 IRES in mouse muscle

    Directory of Open Access Journals (Sweden)

    Van den Berghe Loïc

    2007-10-01

    Full Text Available Abstract Background Electrotransfer of plasmid DNA into skeletal muscle is a promising strategy for the delivery of therapeutic molecules targeting various muscular diseases, cancer and lower-limb ischemia. Internal Ribosome Entry Sites (IRESs allow co-expression of proteins of interest from a single transcriptional unit. IRESs are RNA elements that have been found in viral RNAs as well as a variety of cellular mRNAs with long 5' untranslated regions. While the encephalomyocarditis virus (EMCV IRES is often used in expression vectors, we have shown that the FGF-1 IRES is equally active to drive short term transgene expression in mouse muscle. To compare the ability of the FGF-1 IRES to drive long term expression against the EMCV and FGF-2 IRESs, we performed analyses of expression kinetics using bicistronic vectors that express the bioluminescent renilla and firefly luciferase reporter genes. Long term expression of bicistronic vectors was also compared to that of monocistronic vectors. Bioluminescence was quantified ex vivo using a luminometer and in vivo using a CCD camera that monitors luminescence within live animals. Results Our data demonstrate that the efficiency of the FGF-1 IRES is comparable to that of the EMCV IRES for long term expression of bicistronic transgenes in mouse muscle, whereas the FGF-2 IRES has a very poor activity. Interestingly, we show that despite the global decrease of vector expression over time, the ratio of firefly to renilla luciferase remains stable with bicistronic vectors containing the FGF-1 or FGF-2 IRES and is slightly affected with the EMCV IRES, whereas it is clearly unstable for mixed monocistronic vectors. In addition, long term expression more drastically decreases with monocistronic vectors, and is different for single or mixed vector injection. Conclusion These data validate the use of bicistronic vectors rather than mixed monocistronic vectors for long term expression, and support the use of the

  8. Global embedding via coordinate basis vectors

    Science.gov (United States)

    Goedecke, G. H.

    2011-03-01

    Following the work reported in an earlier paper (G.H. Goedecke, J. Math. Phys. 15, 789 (1974)), the coordinate basis vector approach to tensor calculus is exploited fully to obtain additional and stronger results, including: i) any curved Riemannian space must be a subspace of a larger flat host space; ii) a free test particle moves uniformly on a geodesic in the host space, but experiences gravity and other pseudoforces as viewed in four-dimensional (4D) spacetime; iii) the 4D Riemann-Christoffel curvature tensor is identically equal to a geometrical tensor associated with the complementary subspace of the host space; iv) Einstein's field equations are automatically geometrized, with the stress-energy tensor expressed in terms of the contracted complementary tensor; v) there cannot be a conventional cosmological term in these field equations, except as an approximation; vi) other geometrical field equations involving the complementary subspace metric fields exist and should be physical equations; vii) the long-range two-body time-independent central forces due to all metric fields that have localized sources are inverse square or generalized Yukawa forces. Some of the relationships between this theory and Kaluza-Klein (KK) and string theories are noted; for example, some of the results derived herein must be postulated in KK theories.

  9. Recursive support vector machines for dimensionality reduction.

    Science.gov (United States)

    Tao, Qing; Chu, Dejun; Wang, Jue

    2008-01-01

    The usual dimensionality reduction technique in supervised learning is mainly based on linear discriminant analysis (LDA), but it suffers from singularity or undersampled problems. On the other hand, a regular support vector machine (SVM) separates the data only in terms of one single direction of maximum margin, and the classification accuracy may be not good enough. In this letter, a recursive SVM (RSVM) is presented, in which several orthogonal directions that best separate the data with the maximum margin are obtained. Theoretical analysis shows that a completely orthogonal basis can be derived in feature subspace spanned by the training samples and the margin is decreasing along the recursive components in linearly separable cases. As a result, a new dimensionality reduction technique based on multilevel maximum margin components and then a classifier with high accuracy are achieved. Experiments in synthetic and several real data sets show that RSVM using multilevel maximum margin features can do efficient dimensionality reduction and outperform regular SVM in binary classification problems.

  10. Vectorization of phase space Monte Carlo code in FACOM vector processor VP-200

    International Nuclear Information System (INIS)

    Miura, Kenichi

    1986-01-01

    This paper describes the vectorization techniques for Monte Carlo codes in Fujitsu's Vector Processor System. The phase space Monte Carlo code FOWL is selected as a benchmark, and scalar and vector performances are compared. The vectorized kernel Monte Carlo routine which contains heavily nested IF tests runs up to 7.9 times faster in vector mode than in scalar mode. The overall performance improvement of the vectorized FOWL code over the original scalar code reaches 3.3. The results of this study strongly indicate that supercomputer can be a powerful tool for Monte Carlo simulations in high energy physics. (Auth.)

  11. National Capital Planning Commission Meeting Transcripts

    Data.gov (United States)

    National Capital Planning Commission — Transcripts of the monthly (with the exception of August) National Capital Planning Commission meeting transcripts are provided for research to confirm actions taken...

  12. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca)

    Science.gov (United States)

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra; McBain, James; Dold, Christopher; Stott, Jeffrey L.

    2016-01-01

    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify “insults” and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The

  13. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca).

    Science.gov (United States)

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra T; McBain, James; Dold, Christopher; Stott, Jeffrey L

    2016-07-01

    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic

  14. Vector assembly of colloids on monolayer substrates

    Science.gov (United States)

    Jiang, Lingxiang; Yang, Shenyu; Tsang, Boyce; Tu, Mei; Granick, Steve

    2017-06-01

    The key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize `vector assembly' by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers.

  15. Electricity derivatives

    OpenAIRE

    Barone-Adesi, Giovanni; Gigli, Andrea

    2006-01-01

    In this paper we propose an algorithm for pricing derivatives written on electricity in an incomplete market setting. A discrete time model for price dynamics which embodies the main features of electricity price revealed by simple time series analysis is considered. We use jointly Binomial and Monte Carlo methods for pricing under a risk-neutral measure of which we prove the existence.

  16. dione derivatives

    Indian Academy of Sciences (India)

    dione derivatives via de-Boc and cyclization reaction in modest yield. Spectroscopic (1H, 13C NMR, and Mass) and analytical techniques have been used to identify and confirm the structure of the products. Keywords. Triflic anhydride; Boc anhydride; Negishi coupling; acid-amine coupling; cyclization reaction; cytotoxicity ...

  17. [Spatial vector electrocardiography: technique, perspectives of use].

    Science.gov (United States)

    Bakutskiĭ, V N; Volobuev, A N; Kriukov, N N; Romanchuk, P I

    2003-01-01

    Potentials of the use of computer synthesis of integral electrical vector of the heart D0 are described. Calculation of spatial angular vector velocity and linear velocity of its movement along trajectory can be carried out in a framework of biophysical dipole model. Spatial presentation of vector is realized and its behavior in accordance with established pathologies discussed. Possible diagnostic value of obtained results and utility of their introduction into clinical practice are stressed.

  18. [Research progress on malaria vector control].

    Science.gov (United States)

    Zhu, Guo-Ding; Cao, Jun; Zhou, Hua-Yun; Gao, Qi

    2013-06-01

    Vector control plays a crucial role in the stages of malaria control and elimination. Currently, it mainly relies on the chemical control methods for adult mosquitoes in malaria endemic areas, however, it is undergoing the serious threat by insecticide resistance. In recent years, the transgenic technologies of malaria vectors have made a great progress in the laboratory. This paper reviews the challenges of the traditional methods and the rapid developed genetic modified technology in the application of vector control.

  19. Quark spin content of vector mesons

    International Nuclear Information System (INIS)

    Bander, M.

    1991-01-01

    η' dominance of form factors of the topological QCD current leads to an expression for the portion of the spin of the light vector mesons that is due to quarks. Vector dominance of the radiative decays of the η' is used to estimate the couplings of this meson to the vector ones. This results in the conclusion that only around 30% of the spin of these particles is due to quarks. Possible interpretations of this result are presented

  20. Integrated vector management for malaria control

    OpenAIRE

    Impoinvil Daniel E; Macdonald Michael B; Githure John I; Keating Joseph; Beier John C; Novak Robert J

    2008-01-01

    Abstract Integrated vector management (IVM) is defined as "a rational decision-making process for the optimal use of resources for vector control" and includes five key elements: 1) evidence-based decision-making, 2) integrated approaches 3), collaboration within the health sector and with other sectors, 4) advocacy, social mobilization, and legislation, and 5) capacity-building. In 2004, the WHO adopted IVM globally for the control of all vector-borne diseases. Important recent progress has ...