Sample records for synthetic lethality analysis

  1. Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

    National Research Council Canada - National Science Library

    Bellows, David S


    I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

  2. Anti-Cancer Drug Discovery Using Synthetic Lethal Chemogenetic (SLC) Analysis

    National Research Council Canada - National Science Library

    Bellows, David S


    I am developing a novel cell-based small-molecule screening approach that can identify inhibitors of any non-essential protein function through a surrogate synthetic lethal phenotype in the baker's...

  3. Annotating novel genes by integrating synthetic lethals and genomic information

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou


    Full Text Available Abstract Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process.

  4. Suicide Lethality: A Concept Analysis. (United States)

    DeBastiani, Summer; De Santis, Joseph P


    Suicide is a significant health problem internationally. Those who complete suicide may have different behaviors and risk factors than those who attempt a non-fatal suicide. The purpose of this article is to analyze the concept of suicide lethality and propose a clear definition of the concept through the identification of antecedents, attributes, and consequences. A literature search for articles published in the English language between 1970 and 2016 was conducted using MEDLINE, the Cochrane Library, Pubmed, Psychlit, Ovid, PsycINFO, and Proquest. The bibliographies of all included studies were also reviewed to identify additional relevant citations. A concept analysis was conducted on the literature findings using six stages of Walker and Avant's method. The concept analysis differentiated between suicide, lethality, suicidal behavior, and suicide lethality. Presence of a suicide plan or a written suicide note was not found to be associated with the majority of completed suicides included in the definition of suicide lethality. There are a few scales that measure the lethality of a suicide attempt, but none that attempt to measure the concept of suicide lethality as described in this analysis. Clarifying the concept of suicide lethality encourages awareness of the possibility of different suicidal behaviors associated with different suicide outcomes and will inform the development of future nursing interventions. A clearer definition of the concept of suicide lethality will guide clinical practice, research, and policy development aimed at suicide prevention.

  5. Synthetically lethal nanoparticles for treatment of endometrial cancer (United States)

    Ebeid, Kareem; Meng, Xiangbing; Thiel, Kristina W.; Do, Anh-Vu; Geary, Sean M.; Morris, Angie S.; Pham, Erica L.; Wongrakpanich, Amaraporn; Chhonker, Yashpal S.; Murry, Daryl J.; Leslie, Kimberly K.; Salem, Aliasger K.


    Uterine serous carcinoma, one of the most aggressive types of endometrial cancer, is characterized by poor outcomes and mutations in the tumour suppressor p53. Our objective was to engender synthetic lethality to paclitaxel (PTX), the frontline treatment for endometrial cancer, in tumours with mutant p53 and enhance the therapeutic efficacy using polymeric nanoparticles (NPs). First, we identified the optimal NP formulation through comprehensive analyses of release profiles and cellular-uptake and cell viability studies. Not only were PTX-loaded NPs superior to PTX in solution, but the combination of PTX-loaded NPs with the antiangiogenic molecular inhibitor BIBF 1120 (BIBF) promoted synthetic lethality specifically in cells with the loss-of-function (LOF) p53 mutation. In a xenograft model of endometrial cancer, this combinatorial therapy resulted in a marked inhibition of tumour progression and extended survival. Together, our data provide compelling evidence for future studies of BIBF- and PTX-loaded NPs as a therapeutic opportunity for LOF p53 cancers.

  6. Antiangiogenic Resistance and Cancer Metabolism: Opportunities for Synthetic Lethality. (United States)

    Lord, Simon; Funes, Juan M; Harris, Adrian L; Quintela-Fandino, Miguel


    Antiangiogenic resistance is a major problem in cancer therapeutics. Preclinical research has identified several compensatory proangiogenic pathways that arise upon vascular endothelial growth factor inhibition, several of which have led to the development of novel drugs. However, the combination of two or more targeted agents in the angiogenesis system is hampered by toxicity, as the system is involved in normal physiology. We propose a different approach for improving the efficacy of this drug class, which takes advantage of aberrant cancer metabolism. Several features distinguish cancer metabolism from that of normal cells, including increased glycolysis, glutaminolysis, and pentose-phosphate shunt, as well as an anaplerotic shift of the Krebs cycle. In addition, these aberrations are driven by most of the common mutations that can be targeted by drugs. Antiangiogenics may hamper the ability of cancer to sustain aberrant metabolism due to their impacts on nutrient and oxygen supplies, and thus they may induce some metabolic pathways to become essential for tumor survival (induced essentiality or contextual lethality, a type of synthetic lethality). Thus, some metabolic and signaling pathways that are otherwise nonessential may induce synthetic lethality when inhibited in combination with antiangiogenics. The key problems, however, are interpatient and intratumor heterogeneity, as not all patients with the same tumor type show the same metabolic traits and the same metabolic reprogramming in response to antiangiogenics. With each cancer there are heterogeneous hypoxic areas. Integrating dynamic tracking of metabolism may allow us to tailor our choices of companion drugs with antiangiogenics, taking advantage of window-of-opportunity designs.

  7. Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.

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    Andrei Zinovyev


    Full Text Available Systematic analysis of synthetic lethality (SL constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.

  8. Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors. (United States)

    Falchi, Federico; Giacomini, Elisa; Masini, Tiziana; Boutard, Nicolas; Di Ianni, Lorenza; Manerba, Marcella; Farabegoli, Fulvia; Rossini, Lara; Robertson, Janet; Minucci, Saverio; Pallavicini, Isabella; Di Stefano, Giuseppina; Roberti, Marinella; Pellicciari, Roberto; Cavalli, Andrea


    In BRCA2-defective cells, poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors can trigger synthetic lethality, as two independent DNA-repairing mechanisms are simultaneously impaired. Here, we have pharmacologically induced synthetic lethality, which was triggered by combining two different small organic molecules. When administered with a BRCA2-Rad51 disruptor in nonmutant cells, Olaparib showed anticancer activity comparable to that shown when administered alone in BRCA2-defective cells. This strategy could represent an innovative approach to anticancer drug discovery and could be extended to other synthetic lethality pathways.

  9. Malignancy of Cancers and Synthetic Lethal Interactions Associated With Mutations of Cancer Driver Genes. (United States)

    Wang, Xiaosheng; Zhang, Yue; Han, Ze-Guang; He, Kun-Yan


    The mutation status of cancer driver genes may correlate with different degrees of malignancy of cancers. The doubling time and multidrug resistance are 2 phenotypes that reflect the degree of malignancy of cancer cells. Because most of cancer driver genes are hard to target, identification of their synthetic lethal partners might be a viable approach to treatment of the cancers with the relevant mutations.The genome-wide screening for synthetic lethal partners is costly and labor intensive. Thus, a computational approach facilitating identification of candidate genes for a focus synthetic lethal RNAi screening will accelerate novel anticancer drug discovery.We used several publicly available cancer cell lines and tumor tissue genomic data in this study.We compared the doubling time and multidrug resistance between the NCI-60 cell lines with mutations in some cancer driver genes and those without the mutations. We identified some candidate synthetic lethal genes to the cancer driver genes APC, KRAS, BRAF, PIK3CA, and TP53 by comparison of their gene phenotype values in cancer cell lines with the relevant mutations and wild-type background. Further, we experimentally validated some of the synthetic lethal relationships we predicted.We reported that mutations in some cancer driver genes mutations in some cancer driver genes such as APC, KRAS, or PIK3CA might correlate with cancer proliferation or drug resistance. We identified 40, 21, 5, 43, and 18 potential synthetic lethal genes to APC, KRAS, BRAF, PIK3CA, and TP53, respectively. We found that some of the potential synthetic lethal genes show significantly higher expression in the cancers with mutations of their synthetic lethal partners and the wild-type counterparts. Further, our experiments confirmed several synthetic lethal relationships that are novel findings by our methods.We experimentally validated a part of the synthetic lethal relationships we predicted. We plan to perform further experiments to validate

  10. Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality

    NARCIS (Netherlands)

    van Haaften, Gijs; Vastenhouw, Nadine L; Nollen, Ellen A A; Plasterk, Ronald H A; Tijsterman, Marcel


    Here, we describe a systematic search for synthetic gene interactions in a multicellular organism, the nematode Caenorhabditis elegans. We established a high-throughput method to determine synthetic gene interactions by genome-wide RNA interference and identified genes that are required to protect

  11. A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments (United States)

    Mohni, Kareem N.; Thompson, Petria S.; Luzwick, Jessica W.; Glick, Gloria G.; Pendleton, Christopher S.; Lehmann, Brian D.; Pietenpol, Jennifer A.; Cortez, David


    The DNA damage response kinase ATR may be a useful cancer therapeutic target. ATR inhibition synergizes with loss of ERCC1, ATM, XRCC1 and DNA damaging chemotherapy agents. Clinical trials have begun using ATR inhibitors in combination with cisplatin. Here we report the first synthetic lethality screen with a combination treatment of an ATR inhibitor (ATRi) and cisplatin. Combination treatment with ATRi/cisplatin is synthetically lethal with loss of the TLS polymerase ζ and 53BP1. Other DNA repair pathways including homologous recombination and mismatch repair do not exhibit synthetic lethal interactions with ATRi/cisplatin, even though loss of some of these repair pathways sensitizes cells to cisplatin as a single-agent. We also report that ATRi strongly synergizes with PARP inhibition, even in homologous recombination-proficient backgrounds. Lastly, ATR inhibitors were able to resensitize cisplatin-resistant cell lines to cisplatin. These data provide a comprehensive analysis of DNA repair pathways that exhibit synthetic lethality with ATR inhibitors when combined with cisplatin chemotherapy, and will help guide patient selection strategies as ATR inhibitors progress into the cancer clinic. PMID:25965342

  12. The population genetics of X-autosome synthetic lethals and steriles. (United States)

    Lachance, Joseph; Johnson, Norman A; True, John R


    Epistatic interactions are widespread, and many of these interactions involve combinations of alleles at different loci that are deleterious when present in the same individual. The average genetic environment of sex-linked genes differs from that of autosomal genes, suggesting that the population genetics of interacting X-linked and autosomal alleles may be complex. Using both analytical theory and computer simulations, we analyzed the evolutionary trajectories and mutation-selection balance conditions for X-autosome synthetic lethals and steriles. Allele frequencies follow a set of fundamental trajectories, and incompatible alleles are able to segregate at much higher frequencies than single-locus expectations. Equilibria exist, and they can involve fixation of either autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic alleles are dominant or recessive and whether fitness effects are seen in males, females, or both sexes. When single-locus fitness effects and synthetic incompatibilities are both present, population dynamics depend on the dominance of alleles and historical contingency (i.e., whether X-linked or autosomal mutations occur first). Recessive synthetic lethality can result in high-frequency X-linked alleles, and dominant synthetic lethality can result in high-frequency autosomal alleles. Many X-autosome incompatibilities in natural populations may be cryptic, appearing to be single-locus effects because one locus is fixed. We also discuss the implications of these findings with respect to standing genetic variation and the origins of Haldane's rule.

  13. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer (United States)


    Next, lithium acetylide addition to 3 provides 4, which was subsequently reduced to the E-olefin 5 in excellent yield. Manganese dioxide oxidation Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of...therapy for patients with metastatic soft tissue or bone sarcoma who have stable disease or better after four or more cycles of chemotherapy. The

  14. Improving the iMM904 S. cerevisiae metabolic model using essentiality and synthetic lethality data

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    Maranas Costas D


    Full Text Available Abstract Background Saccharomyces cerevisiae is the first eukaryotic organism for which a multi-compartment genome-scale metabolic model was constructed. Since then a sequence of improved metabolic reconstructions for yeast has been introduced. These metabolic models have been extensively used to elucidate the organizational principles of yeast metabolism and drive yeast strain engineering strategies for targeted overproductions. They have also served as a starting point and a benchmark for the reconstruction of genome-scale metabolic models for other eukaryotic organisms. In spite of the successive improvements in the details of the described metabolic processes, even the recent yeast model (i.e., iMM904 remains significantly less predictive than the latest E. coli model (i.e., iAF1260. This is manifested by its significantly lower specificity in predicting the outcome of grow/no grow experiments in comparison to the E. coli model. Results In this paper we make use of the automated GrowMatch procedure for restoring consistency with single gene deletion experiments in yeast and extend the procedure to make use of synthetic lethality data using the genome-scale model iMM904 as a basis. We identified and vetted using literature sources 120 distinct model modifications including various regulatory constraints for minimal and YP media. The incorporation of the suggested modifications led to a substantial increase in the fraction of correctly predicted lethal knockouts (i.e., specificity from 38.84% (87 out of 224 to 53.57% (120 out of 224 for the minimal medium and from 24.73% (45 out of 182 to 40.11% (73 out of 182 for the YP medium. Synthetic lethality predictions improved from 12.03% (16 out of 133 to 23.31% (31 out of 133 for the minimal medium and from 6.96% (8 out of 115 to 13.04% (15 out of 115 for the YP medium. Conclusions Overall, this study provides a roadmap for the computationally driven correction of multi-compartment genome

  15. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. (United States)

    Scholl, Claudia; Fröhling, Stefan; Dunn, Ian F; Schinzel, Anna C; Barbie, David A; Kim, So Young; Silver, Serena J; Tamayo, Pablo; Wadlow, Raymond C; Ramaswamy, Sridhar; Döhner, Konstanze; Bullinger, Lars; Sandy, Peter; Boehm, Jesse S; Root, David E; Jacks, Tyler; Hahn, William C; Gilliland, D Gary


    An alternative to therapeutic targeting of oncogenes is to perform "synthetic lethality" screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with "undruggable" genetic alterations.

  16. A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis. (United States)

    Hartin, Samantha N; Hudson, Martin L; Yingling, Curtis; Ackley, Brian D


    The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens.

  17. Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma (United States)

    Yang, Yibin; Shaffer, Arthur L.; Emre, N.C. Tolga; Ceribelli, Michele; Zhang, Meili; Wright, George; Xiao, Wenming; Powell, John; Platig, John; Kohlhammer, Holger; Young, Ryan M.; Zhao, Hong; Yang, Yandan; Xu, Weihong; Buggy, Joseph J.; Balasubramanian, Sriram; Mathews, Lesley A.; Shinn, Paul; Guha, Rajarshi; Ferrer, Marc; Thomas, Craig; Waldmann, Thomas A.; Staudt, Louis M.


    Summary Knowledge of oncogenic mutations can inspire therapeutic strategies that are synthetically lethal, affecting cancer cells while sparing normal cells. Lenalidomide is an active agent in the activated B-cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), but its mechanism of action is unknown. Lenalidomide kills ABC DLBCL cells by augmenting interferon β (IFNβ) production, owing to the oncogenic MYD88 mutations in these lymphomas. In a cereblon-dependent fashion, lenalidomide downregulates IRF4 and SPIB, transcription factors that together prevent IFNβ production by repressing IRF7 and also amplify pro-survival NF-κB signaling by transactivating CARD11. Blockade of B cell receptor (BCR) signaling using the BTK inhibitor ibrutinib also downregulates IRF4 and consequently synergizes with lenalidomide in killing ABC DLBCLs, suggesting attractive therapeutic strategies. PMID:22698399

  18. Synthetic lethal interaction between the tumour suppressor STAG2 and its paralog STAG1. (United States)

    Benedetti, Lorena; Cereda, Matteo; Monteverde, LeeAnn; Desai, Nikita; Ciccarelli, Francesca D


    Cohesin is a multi-protein complex that tethers sister chromatids during mitosis and mediates DNA repair, genome compartmentalisation and regulation of gene expression. Cohesin subunits frequently acquire cancer loss-of-function alterations and act as tumour suppressors in several tumour types. This has led to increased interest in cohesin as potential target in anti-cancer therapy. Here we show that the loss-of-function of STAG2, a core component of cohesin and an emerging tumour suppressor, leads to synthetic dependency of mutated cancer cells on its paralog STAG1. STAG1 and STAG2 share high sequence identity, encode mutually exclusive cohesin subunits and retain partially overlapping functions. We inhibited STAG1 and STAG2 in several cancer cell lines where the two genes have variable mutation and copy number status. In all cases, we observed that the simultaneous blocking of STAG1 and STAG2 significantly reduces cell proliferation. We further confirmed the synthetic lethal interaction developing a vector-free CRISPR system to induce STAG1/STAG2 double gene knockout. We provide strong evidence that STAG1 is a promising therapeutic target in cancers with inactivating alterations of STAG2.

  19. Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

    International Nuclear Information System (INIS)

    Tsang, Patricia S; Cheuk, Adam T; Chen, Qing-Rong; Song, Young K; Badgett, Thomas C; Wei, Jun S; Khan, Javed


    Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma. We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by in vitro and in vivo studies. We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity in vitro. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments. Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma

  20. Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

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    Tsang Patricia S


    Full Text Available Abstract Background Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma. Methods We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by in vitro and in vivo studies. Results We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib significantly reduced cell growth and induced caspase 3 activity in vitro. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments. Conclusions Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.

  1. CSNK1E/CTNNB1 Are Synthetic Lethal To TP53 in Colorectal Cancer and Are Markers for Prognosis

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    Khong-Loon Tiong


    Full Text Available Two genes are called synthetic lethal (SL if their simultaneous mutations lead to cell death, but each individual mutation does not. Targeting SL partners of mutated cancer genes can kill cancer cells specifically, but leave normal cells intact. We present an integrated approach to uncovering SL pairs in colorectal cancer (CRC. Screening verified SL pairs using microarray gene expression data of cancerous and normal tissues, we first identified potential functionally relevant (simultaneously differentially expressed gene pairs. From the top-ranked pairs, ~20 genes were chosen for immunohistochemistry (IHC staining in 171 CRC patients. To find novel SL pairs, all 169 combined pairs from the individual IHC were synergistically correlated to five clinicopathological features, e.g. overall survival. Of the 11 predicted SL pairs, MSH2-POLB and CSNK1E-MYC were consistent with literature, and we validated the top two pairs, CSNK1E-TP53 and CTNNB1-TP53 using RNAi knockdown and small molecule inhibitors of CSNK1E in isogenic HCT-116 and RKO cells. Furthermore, synthetic lethality of CSNK1E and TP53 was verified in mouse model. Importantly, multivariate analysis revealed that CSNK1E-P53, CTNNB1-P53, MSH2-RB1, and BRCA1-WNT5A were independent prognosis markers from stage, with CSNK1E-P53 applicable to early-stage and the remaining three throughout all stages. Our findings suggest that CSNK1E is a promising target for TP53-mutant CRC patients which constitute ~40% to 50% of patients, while to date safety regarding inhibition of TP53 is controversial. Thus the integrated approach is useful in finding novel SL pairs for cancer therapeutics, and it is readily accessible and applicable to other cancers.

  2. Roles of PARP inhibitor in synthetic lethality and as a sensitizer in cancer therapy

    International Nuclear Information System (INIS)

    Hirai, Takahisa; Masutani, Mitsuko; Sasai, Keisuke


    In a search for novel chemotherapeutic targets for cancer, recent interest has focused on DNA repair pathways. Poly (ADP-ribose) polymerase (PARP)-1 is an important protein for base excision repair and inhibitors of this pathway show anti-cancer effects when used as a mono-therapy for BRCA-deficient cancers in clinical trials. The results of such studies proved the concept of ''synthetic lethality'' by targeting DNA repair pathways. Considering the action of the PARP inhibitor (PARPi) in DNA repair pathways, PARPi is also predicted to act as a sensitizer for DNA damaging agents, such as certain chemotherapeutic drugs and radiation. A number of clinical trials using PARPi in combination with existing therapies are underway. We investigated the use of PARPi as a radiosensitizer for high LET (linear energy transfer) radiation. PARPi showed the radiosensitization effect of carbon-ion radiation, and the radiosensitization effect of PARPi was attributed to a delay in the DNA damage response and double strand break processing. Via its effects on DNA repair, the PARP inhibitor might be applicable as a radiosensitizer for a wide range of therapeutic LET radiation. This study suggests that development of research into DNA repair pathways could yield still further targets for cancer therapy. (author)

  3. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. (United States)

    Asim, Mohammad; Tarish, Firas; Zecchini, Heather I; Sanjiv, Kumar; Gelali, Eleni; Massie, Charles E; Baridi, Ajoeb; Warren, Anne Y; Zhao, Wanfeng; Ogris, Christoph; McDuffus, Leigh-Anne; Mascalchi, Patrice; Shaw, Greg; Dev, Harveer; Wadhwa, Karan; Wijnhoven, Paul; Forment, Josep V; Lyons, Scott R; Lynch, Andy G; O'Neill, Cormac; Zecchini, Vincent R; Rennie, Paul S; Baniahmad, Aria; Tavaré, Simon; Mills, Ian G; Galanty, Yaron; Crosetto, Nicola; Schultz, Niklas; Neal, David; Helleday, Thomas


    Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.Tumours with homologous recombination (HR) defects become sensitive to PARPi. Here, the authors show that androgen receptor (AR) regulates HR and AR inhibition activates the PARP pathway in vivo, thus inhibition of both AR and PARP is required for effective treatment of high risk prostate cancer.

  4. Targeting Synthetic Lethal Interactions between Myc and the eIF4F Complex Impedes Tumorigenesis

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    Chen-Ju Lin


    Full Text Available The energetically demanding process of translation is linked to multiple signaling events through mTOR-mediated regulation of eukaryotic initiation factor (eIF4F complex assembly. Disrupting mTOR constraints on eIF4F activity can be oncogenic and alter chemotherapy response, making eIF4F an attractive antineoplastic target. Here, we combine a newly developed inducible RNAi platform and pharmacological targeting of eIF4F activity to define a critical role for endogenous eIF4F in Myc-dependent tumor initiation. We find elevated Myc levels are associated with deregulated eIF4F activity in the prelymphomatous stage of the Eμ-Myc lymphoma model. Inhibition of eIF4F is synthetic lethal with elevated Myc in premalignant pre-B/B cells resulting in reduced numbers of cycling pre-B/B cells and delayed tumor onset. At the organismal level, eIF4F suppression affected a subset of normal regenerating cells, but this was well tolerated and rapidly and completely reversible. Therefore, eIF4F is a key Myc client that represents a tumor-specific vulnerability.

  5. Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma

    DEFF Research Database (Denmark)

    Wittig-Blaich, Stephanie; Wittig, Rainer; Schmidt, Steffen


    Next-generation sequencing has dramatically increased genome-wide profiling options and conceptually initiates the possibility for personalized cancer therapy. State-of-the-art sequencing studies yield large candidate gene sets comprising dozens or hundreds of mutated genes. However, few technolo...... to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression....

  6. ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin. (United States)

    Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu


    PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Analysis of time of death of prenatally lethal Steeloid mutations

    International Nuclear Information System (INIS)

    Rinchik, E.M.; Cummings, C.C.; Bangham, J.W.; Hunsicker, P.R.; Phipps, E.L.; Stelzner, K.F.


    Deletion mutations have been extremely useful in initiating the functional and molecular dissections of regions of the mouse genome. For the d-se and c regions, for example, it was observed that radiation mutations carrying lethal factors separable, by complementation analysis, from the primary d, se, or c mutation itself, could often be associated at both the genetic and molecular levels with multilocus chromosomal deletions. Since many of the Oak Ridge Sld mutations arose in radiation mutagenesis experiments, a substantial number may carry chromosomal deletions that involve the Sl locus in chromosome 10. Because of the great value of deletion mutations for the genetic and molecular analysis of chromosomal regions and complex genetic loci, they have initiated a series of experiments designed to test whether radiation-induced Sld mutations carry other lethal factors, in addition to the lethality caused by severe alleles of the Sl locus itself, as one prescreen for identifying Sld's that are caused by deletions

  8. Systems biology-guided identification of synthetic lethal gene pairs and its potential use to discover antibiotic combinations

    DEFF Research Database (Denmark)

    Aziz, Ramy K.; Monk, Jonathan M.; Lewis, R. M.


    be found that inhibit the growth of Gram-negative bacteria. One set of molecules was identified that, depending on the concentrations, inhibits E. coli and S. enterica serovar Typhimurium in an additive or antagonistic manner. These findings pinpoint specific ways in which to improve the predictive ability...... and phenotype, but their ability to accurately simulate gene-gene interactions has not been investigated extensively. Here we assess how accurately a metabolic model for Escherichia coli computes one particular type of gene-gene interaction, synthetic lethality, and find that the accuracy rate is between 25...

  9. Shape analysis of synthetic diamond

    CERN Document Server

    Mullan, C


    Two-dimensional images of synthetic industrial diamond particles were obtained using a camera, framegrabber and PC-based image analysis software. Various methods for shape quantification were applied, including two-dimensional shape factors, Fourier series expansion of radius as a function of angle, boundary fractal analysis, polygonal harmonics, and comer counting methods. The shape parameter found to be the most relevant was axis ratio, defined as the ratio of the minor axis to the major axis of the ellipse with the same second moments of area as the particle. Axis ratio was used in an analysis of the sorting of synthetic diamonds on a vibrating table. A model was derived based on the probability that a particle of a given axis ratio would travel to a certain bin. The model described the sorting of bulk material accurately but it was found not to be applicable if the shape mix of the feed material changed dramatically. This was attributed to the fact that the particle-particle interference was not taken int...

  10. Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival. (United States)

    Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A


    Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

  11. Analysis of the Synthetic Jet

    Czech Academy of Sciences Publication Activity Database

    Dančová, Petra; Vít, Tomáš


    Roč. 2, č. 1 (2009), s. 11-17 ISSN 1803-0203 R&D Projects: GA AV ČR(CZ) IAA200760801 Institutional research plan: CEZ:AV0Z20760514 Keywords : synthetic jet * actuator * nominal frequency Subject RIV: BJ - Thermodynamics

  12. MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth.

    Directory of Open Access Journals (Sweden)

    Ivan D Schlatter

    Full Text Available The novel protein Memo (Mediator of ErbB2 driven cell motility was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a similarity of >50%. In the present study we used the model organism S. cerevisiae to characterize the Memo-homologue Mho1 (Yjr008wp and to investigate its function in yeast. In a synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of human Memo into the memoΔplc1Δ strain rescued the synthetic lethal phenotype suggesting that yeast and human proteins have similar functions. Mho1 is present in the cytoplasm and the nucleus of yeast cells; the same distribution of Memo was found in mammalian cells. None of the Memo homologues have a characteristic nuclear localization sequence, however, a conserved nuclear export sequence is found in all. In mammalian cells, blocking nuclear export with Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively exported from the nucleus. In yeast MHO1 expression is induced by stress conditions. Since invasive growth in S. cerevisiea is also stress-induced, we tested Mho1's role in this response. MHO1 deletion had no effect on invasion induced by nutrient deprivation, however, Mho1 overexpression blocked the invasive ability of yeast cells, suggesting that Mho1 might be acting in a dominant negative manner. Taken together, our results show that MHO1 is a novel synthetic lethal interactor with PLC1, and that both gene products are required for proliferation. Moreover, a role for Memo in cell motility/invasion appears to be conserved across species.

  13. Synthetic aperture interferometry: error analysis

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Amiya; Coupland, Jeremy


    Synthetic aperture interferometry (SAI) is a novel way of testing aspherics and has a potential for in-process measurement of aspherics [Appl. Opt.42, 701 (2003)].APOPAI0003-693510.1364/AO.42.000701 A method to measure steep aspherics using the SAI technique has been previously reported [Appl. Opt.47, 1705 (2008)].APOPAI0003-693510.1364/AO.47.001705 Here we investigate the computation of surface form using the SAI technique in different configurations and discuss the computational errors. A two-pass measurement strategy is proposed to reduce the computational errors, and a detailed investigation is carried out to determine the effect of alignment errors on the measurement process.

  14. Synthetic aperture interferometry: error analysis

    International Nuclear Information System (INIS)

    Biswas, Amiya; Coupland, Jeremy


    Synthetic aperture interferometry (SAI) is a novel way of testing aspherics and has a potential for in-process measurement of aspherics [Appl. Opt.42, 701 (2003)].APOPAI0003-693510.1364/AO.42.000701 A method to measure steep aspherics using the SAI technique has been previously reported [Appl. Opt.47, 1705 (2008)].APOPAI0003-693510.1364/AO.47.001705 Here we investigate the computation of surface form using the SAI technique in different configurations and discuss the computational errors. A two-pass measurement strategy is proposed to reduce the computational errors, and a detailed investigation is carried out to determine the effect of alignment errors on the measurement process.

  15. Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target. (United States)

    McLellan, Jessica; O'Neil, Nigel; Tarailo, Sanja; Stoepel, Jan; Bryan, Jennifer; Rose, Ann; Hieter, Philip


    Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFC(CTF18) complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.

  16. Model-driven discovery of synergistic inhibitors against E. coli and S. enterica serovar Typhimurium targeting a novel synthetic lethal pair, aldA and prpC

    Directory of Open Access Journals (Sweden)

    Ramy Karam Aziz


    Full Text Available Mathematical models of biochemical networks form a cornerstone of bacterial systems biology. Inconsistencies between simulation output and experimental data point to gaps in knowledge about the fundamental biology of the organism. One such inconsistency centers on the gene aldA in Escherichia coli: it is essential in a computational model of E. coli metabolism, but experimentally it is not. Here we reconcile this disparity by providing evidence that aldA and prpC form a synthetic lethal pair, as the double knockout could only be created through complementation with a plasmid-borne copy of aldA. Moreover, virtual and biological screening against the two proteins led to a set of compounds that inhibited the growth of E. coli and Salmonella enterica serovar Typhimurium synergistically at 100 – 200 μM individual concentrations. These results highlight the power of metabolic models to drive basic biological discovery and their potential use to discover new combination antibiotics.

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

    International Nuclear Information System (INIS)

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


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

  18. Efficient analysis methods in synthetic biology. (United States)

    Madsen, Curtis; Myers, Chris; Roehner, Nicholas; Winstead, Chris; Zhang, Zhen


    This chapter describes new analysis and verification techniques for synthetic genetic circuits. In particular, it applies stochastic model checking techniques to models of genetic circuits in order to ensure that they behave correctly and are as robust as possible for a variety of different inputs and parameter settings. In addition to stochastic model checking, this chapter proposes new variants to the incremental stochastic simulation algorithm (iSSA) that are capable of presenting a researcher with a simulation trace of the typical behavior of the system. Before the development of this algorithm, discerning this information was extremely error-prone as it involved performing many simulations and attempting to wade through the massive amounts of data. This algorithm greatly aids researchers in designing genetic circuits as it efficiently shows the researcher the most likely behavior of the circuit. Both the iSSA and stochastic model checking can be used in concert to give a researcher the likelihood that the system exhibits its most typical behavior, as well as, non-typical behaviors. This methodology is applied to several genetic circuits leading to new understanding of the effects of various parameters on the behavior of these circuits.

  19. A Synthetic Lethality Screen Using a Focused siRNA Library to Identify Sensitizers to Dasatinib Therapy for the Treatment of Epithelial Ovarian Cancer.

    Directory of Open Access Journals (Sweden)

    Harsh B Pathak

    Full Text Available Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC. The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK and in preclinical studies shown to have substantial activity in EOC. However, when evaluated in a phase 2 clinical trial for patients with recurrent or persistent EOC, it was found to have minimal activity. We hypothesized that synthetic lethality screens performed using a cogently designed siRNA library would identify second-site molecular targets that could synergize with SFK inhibition and improve dasatinib efficacy. Using a systematic approach, we performed primary siRNA screening using a library focused on 638 genes corresponding to a network centered on EGFR, HER2, and the SFK-scaffolding proteins BCAR1, NEDD9, and EFS to screen EOC cells in combination with dasatinib. We followed up with validation studies including deconvolution screening, quantitative PCR to confirm effective gene silencing, correlation of gene expression with dasatinib sensitivity, and assessment of the clinical relevance of hits using TCGA ovarian cancer data. A refined list of five candidates (CSNK2A1, DAG1, GRB2, PRKCE, and VAV1 was identified as showing the greatest potential for improving sensitivity to dasatinib in EOC. Of these, CSNK2A1, which codes for the catalytic alpha subunit of protein kinase CK2, was selected for additional evaluation. Synergistic activity of the clinically relevant inhibitor of CK2, CX-4945, with dasatinib in reducing cell proliferation and increasing apoptosis was observed across multiple EOC cell lines. This overall approach to improving drug efficacy can be applied to other

  20. Spectral analysis of a synthetic jet

    Czech Academy of Sciences Publication Activity Database

    Tesař, Václav; Kordík, Jozef


    Roč. 167, č. 2 (2011), s. 213-225 ISSN 0924-4247 R&D Projects: GA ČR GA101/07/1499; GA AV ČR IAA200760705 Institutional research plan: CEZ:AV0Z20760514 Keywords : jet * synthetic jet * frequency spectrum Subject RIV: BK - Fluid Dynamics Impact factor: 1.802, year: 2011

  1. Stability analysis of artificial synthetic overweight elements

    International Nuclear Information System (INIS)

    Zhou Jian


    Stability of artificial synthetic overweight elements has been analysed theoretically using a diagram of nuclear stability. It is indicated that overweight nucleus can be synthesized only when a certain amount of neutrons participate simultaneously in the synthesis. The maximum number of protons in overweight elements is 1002. The proton number of 'extreme overweight' elements of which the neutron star is possibly composed is in the range from 326 to 1002. It is expected that the mass number of the stable overweight elements with proton number 114 is in the range from 299 to 315

  2. Synthetic

    Directory of Open Access Journals (Sweden)

    Anna Maria Manferdini


    Full Text Available Traditionally materials have been associated with a series of physical properties that can be used as inputs to production and manufacturing. Recently we witnessed an interest in materials considered not only as ‘true matter’, but also as new breeds where geometry, texture, tooling and finish are able to provoke new sensations when they are applied to a substance. These artificial materials can be described as synthetic because they are the outcome of various qualities that are not necessarily true to the original matter, but they are the combination of two or more parts, whether by design or by natural processes. The aim of this paper is to investigate the potential of architectural surfaces to produce effects through the invention of new breeds of artificial matter, using micro-scale details derived from Nature as an inspiration.

  3. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)

    The present study was conducted to assess the genetic diversity of Elite-II synthetic hexaploid (SH) wheat by genome DNA fingerprinting as revealed by random amplified polymorphic DNA (RAPD) analysis. Ten decamer RAPD primers (OPG-1, OPG-2, OPG-3, OPG-4, OPG-5, OPA-3, OPA-4, OPA-5, OPA-8, and OPA-15) ...

  4. Molecular analysis of genetic diversity in elite II synthetic hexaploid ...

    African Journals Online (AJOL)



    Jul 20, 2009 ... Full Length Research Paper. Molecular analysis of genetic diversity in elite II synthetic hexaploid wheat screened against Barley yellow dwarf virus. Huma Saffdar1 ... The history of cultiva- ted wheat and human .... and viewed under the UV light chamber using the computer pro- gram UVIPhotoMW.

  5. Time–frequency analysis of submerged synthetic jet (United States)

    Kumar, Abhay; Saha, Arun K.; Panigrahi, P. K.


    The coherent structures transport the finite body of fluid mass through rolling which plays an important role in heat transfer, boundary layer control, mixing, cooling, propulsion and other engineering applications. A synthetic jet in the form of a train of vortex rings having coherent structures of different length scales is expected to be useful in these applications. The propagation and sustainability of these coherent structures (vortex rings) in downstream direction characterize the performance of synthetic jet. In the present study, the velocity signal acquired using the S-type hot-film probe along the synthetic jet centerline has been taken for the spectral analysis. One circular and three rectangular orifices of aspect ratio 1, 2 and 4 actuating at 1, 6 and 18 Hz frequency have been used for creating different synthetic jets. The laser induced fluorescence images are used to study the flow structures qualitatively and help in explaining the velocity signal for detection of coherent structures. The study depicts four regions as vortex rollup and suction region (X/D h ≤ 3), steadily translating region (X/D h ≤ 3–8), vortex breakup region (X/Dh ≤ 4–8) and dissipation of small-scale vortices (X/D h ≤ 8–15). The presence of coherent structures localized in physical and temporal domain is analyzed for the characterization of synthetic jet. Due to pulsatile nature of synthetic jet, analysis of velocity time trace or signal in time, frequency and combined time–frequency domain assist in characterizing the signatures of coherent structures. It has been observed that the maximum energy is in the first harmonic of actuation frequency, which decreases slowly in downstream direction at 6 Hz compared to 1 and 18 Hz of actuation.

  6. Fine Mapping and Transcriptome Analysis Reveal Candidate Genes Associated with Hybrid Lethality in Cabbage (Brassica Oleracea). (United States)

    Xiao, Zhiliang; Hu, Yang; Zhang, Xiaoli; Xue, Yuqian; Fang, Zhiyuan; Yang, Limei; Zhang, Yangyong; Liu, Yumei; Li, Zhansheng; Liu, Xing; Liu, Zezhou; Lv, Honghao; Zhuang, Mu


    Hybrid lethality is a deleterious phenotype that is vital to species evolution. We previously reported hybrid lethality in cabbage ( Brassica oleracea ) and performed preliminary mapping of related genes. In the present study, the fine mapping of hybrid lethal genes revealed that BoHL1 was located on chromosome C1 between BoHLTO124 and BoHLTO130, with an interval of 101 kb. BoHL2 was confirmed to be between insertion-deletion (InDels) markers HL234 and HL235 on C4, with a marker interval of 70 kb. Twenty-eight and nine annotated genes were found within the two intervals of BoHL1 and BoHL2 , respectively. We also applied RNA-Seq to analyze hybrid lethality in cabbage. In the region of BoHL1 , seven differentially expressed genes (DEGs) and five resistance (R)-related genes (two in common, i.e., Bo1g153320 and Bo1g153380 ) were found, whereas in the region of BoHL2 , two DEGs and four R-related genes (two in common, i.e., Bo4g173780 and Bo4g173810 ) were found. Along with studies in which R genes were frequently involved in hybrid lethality in other plants, these interesting R-DEGs may be good candidates associated with hybrid lethality. We also used SNP/InDel analyses and quantitative real-time PCR to confirm the results. This work provides new insight into the mechanisms of hybrid lethality in cabbage.

  7. Analysis of turbulent synthetic jet by dynamic mode decomposition

    Directory of Open Access Journals (Sweden)

    Hyhlík Tomáš


    Full Text Available The article deals with the analysis of CFD results of the turbulent synthetic jet. The numerical simulation of Large Eddy Simulation (LES using commercial solver ANSYS CFX has been performed. The unsteady flow field is studied from the point of view of identification of the moving vortex ring, which has been identified both on the snapshots of flow field using swirling-strength criterion and using the Dynamic Mode Decomposition (DMD of five periods. It is shown that travelling vortex ring vanishes due to interaction with vortex structures in the synthesised turbulent jet. DMD modes with multiple of the basic frequency of synthetic jet, which are connected with travelling vortex structure, have largest DMD amplitudes.

  8. Analysis of new aphid lethal paralysis virus (ALPV) isolates suggests evolution of two ALPV species. (United States)

    Liu, Sijun; Vijayendran, Diveena; Carrillo-Tripp, Jimena; Miller, W Allen; Bonning, Bryony C


    Aphid lethal paralysis virus (ALPV; family Dicistroviridae) was first isolated from the bird cherry-oat aphid, Rhopalosiphum padi. ALPV-like virus sequences have been reported from many insects and insect predators. We identified a new isolate of ALPV (ALPV-AP) from the pea aphid, Acyrthosiphon pisum, and a new isolate (ALPV-DvV) from western corn rootworm, Diabrotica virgifera virgifera. ALPV-AP has an ssRNA genome of 9940 nt. Based on phylogenetic analysis, ALPV-AP was closely related to ALPV-AM, an ALPV isolate from honeybees, Apis mellifera, in Spain and Brookings, SD, USA. The distinct evolutionary branches suggested the existence of two lineages of the ALPV virus. One consisted of ALPV-AP and ALPV-AM, whilst all other isolates of ALPV grouped into the other lineage. The similarity of ALPV-AP and ALPV-AM was up to 88 % at the RNA level, compared with 78-79 % between ALPV-AP and other ALPV isolates. The sequence identity of proteins between ALPV-AP and ALPV-AM was 98-99 % for both ORF1 and ORF2, whilst only 85-87 % for ORF1 and 91-92 % for ORF2 between ALPV-AP and other ALPV isolates. Sequencing of RACE (rapid amplification of cDNA ends) products and cDNA clones of the virus genome revealed sequence variation in the 5' UTRs and in ORF1, indicating that ALPV may be under strong selection pressure, which could have important biological implications for ALPV host range and infectivity. Our results indicated that ALPV-like viruses infect insects in the order Coleoptera, in addition to the orders Hemiptera and Hymenoptera, and we propose that ALPV isolates be classified as two separate viral species. © 2014 The Authors.

  9. Lethal Epistaxis. (United States)

    Byard, Roger W


    Epistaxis or nosebleed refers to bleeding from the nostrils, nasal cavity, or nasopharynx. Occasional cases may present with torrential lethal hemorrhage. Three cases are reported to demonstrate particular features: Case 1: A 51-year-old woman with lethal epistaxis with no obvious bleeding source; Case 2: A 77-year-old man with treated nasopharyngeal carcinoma who died from epistaxis arising from a markedly neovascularized tumor bed; Case 3: A 2-year-old boy with hemophilia B who died from epistaxis with airway obstruction in addition to gastrointestinal bleeding. Epistaxis may be associated with trauma, tumors, vascular malformations, bleeding diatheses, infections, pregnancy, endometriosis, and a variety of different drugs. Careful dissection of the nasal cavity is required to locate the site of hemorrhage and to identify any predisposing conditions. This may be guided by postmortem computerized tomographic angiography (PCTA). Despite careful dissection, however, a source of bleeding may never be identified. © 2016 American Academy of Forensic Sciences.

  10. Protection Against Lethal Sendai Virus Infection by in vivo Priming of Virus-Specific Cytotoxic T Lymphocytes with a Free Synthetic Peptide (United States)

    Kast, W. Martin; Roux, Laurent; Curren, Joseph; Blom, Hendrika J. J.; Voordouw, Arie C.; Meloen, Rob H.; Kolakofsky, Daniel; Melief, Cornelis J. M.


    The only peptide of Sendai virus that is recognized by cytotoxic T lymphocytes (CTL) in B6 mice was found with (i) the use of recombinant vaccinia virus constructs containing separate genes of Sendai virus and (ii) a set of overlapping peptides completely spanning the identified nucleoprotein (NP) gene product. This immunodominant NP peptide is recognized by Sendai virus-specific CTL that are known to have therapeutic effects in vivo. By subcutaneous immunization, this peptide induced Sendai virus and NP peptide-specific CTL memory responses in vivo. Most importantly, mice that had been immunized with this peptide were protected against a lethal virus dose, indicating that viral peptides can be used as antiviral T-cell vaccines. The induction of T-cell memory by free peptide immunization potentially has wide applicability in biology and medicine, including protection against infectious disease.

  11. Analysis of dominant and recessive sex-linked lethal mutations induced by low radiation doses in genetically different strains of Drosophila melanogaster w and MS

    International Nuclear Information System (INIS)

    Aslanyan, M.M.; Kim, A.I.; Magomedova, M.A.; Fatkulbayanova, N.L.


    Frequencies of induced recessive sex-linked lethal mutations (RSLLM) and dominant lethal mutations (DLM) were analyzed in genetically different Drosophila melanogaster strains w and MS after their exposure to radiation on radioactive soil in laboratory conditions. The RSLLM test applied to males after their 14-day radiation exposure yielded controversial results. An analysis of induced and spontaneous DLM demonstrated an increase in the frequency of early embryonic lethal mutations in the experiment (radiation exposure) in comparison with the control (spontaneous mutation rate) in both strains examined

  12. The pkaB Gene Encoding the Secondary Protein Kinase A Catalytic Subunit Has a Synthetic Lethal Interaction with pkaA and Plays Overlapping and Opposite Roles in Aspergillus nidulans (United States)

    Ni, Min; Rierson, Sara; Seo, Jeong-Ah; Yu, Jae-Hyuk


    Filamentous fungal genomes contain two distantly related cyclic AMP-dependent protein kinase A catalytic subunits (PKAs), but only one PKA is found to play a principal role. In Aspergillus nidulans, PkaA is the primary PKA that positively functions in vegetative growth and spore germination but negatively controls asexual sporulation and production of the mycotoxin sterigmatocystin. In this report, we present the identification and characterization of pkaB, encoding the secondary PKA in A. nidulans. Although deletion of pkaB alone does not cause any apparent phenotypic changes, the absence of both pkaB and pkaA is lethal, indicating that PkaB and PkaA are essential for viability of A. nidulans. Overexpression of pkaB enhances hyphal proliferation and rescues the growth defects caused by ΔpkaA, indicating that PkaB plays a role in vegetative growth signaling. However, unlike ΔpkaA, deletion of pkaB does not suppress the fluffy-autolytic phenotype resulting from ΔflbA. While upregulation of pkaB rescues the defects of spore germination resulting from ΔpkaA in the presence of glucose, overexpression of pkaB delays spore germination. Furthermore, upregulation of pkaB completely abolishes spore germination on medium lacking a carbon source. In addition, upregulation of pkaB enhances the level of submerged sporulation caused by ΔpkaA and reduces hyphal tolerance to oxidative stress. In conclusion, PkaB is the secondary PKA that has a synthetic lethal interaction with PkaA, and it plays an overlapping role in vegetative growth and spore germination in the presence of glucose but an opposite role in regulating asexual sporulation, germination in the absence of a carbon source, and oxidative stress responses in A. nidulans. PMID:16087751

  13. Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yanyan; Verbiest, Tom; Devery, Aoife M.; Bokobza, Sivan M.; Weber, Anika M.; Leszczynska, Katarzyna B.; Hammond, Ester M.; Ryan, Anderson J., E-mail:


    olaparib by contextual synthetic killing, and that tumor hypoxia may be a potential biomarker for selecting patients who may get the greatest benefit from the addition of olaparib to radiation therapy.

  14. Biophysical analysis of a lethal laminin alpha-1 mutation reveals altered self-interaction

    KAUST Repository

    Patel, Trushar R.


    Laminins are key basement membrane molecules that influence several biological activities and are linked to a number of diseases. They are secreted as heterotrimeric proteins consisting of one α, one β, and one γ chain, followed by their assembly into a polymer-like sheet at the basement membrane. Using sedimentation velocity, dynamic light scattering, and surface plasmon resonance experiments, we studied self-association of three laminin (LM) N-terminal fragments α-1 (hLM α-1 N), α-5 (hLM α-5 N) and β-3 (hLM β-3 N) originating from the short arms of the human laminin αβγ heterotrimer. Corresponding studies of the hLM α-1 N C49S mutant, equivalent to the larval lethal C56S mutant in zebrafish, have shown that this mutation causes enhanced self-association behavior, an observation that provides a plausible explanation for the inability of laminin bearing this mutation to fulfill functional roles in vivo, and hence for the deleterious pathological consequences of the mutation on lens function.

  15. Analysis of lethal and sublethal impacts of environmental disasters on sperm whales using stochastic modeling. (United States)

    Ackleh, Azmy S; Chiquet, Ross A; Ma, Baoling; Tang, Tingting; Caswell, Hal; Veprauskas, Amy; Sidorovskaia, Natalia


    Mathematical models are essential for combining data from multiple sources to quantify population endpoints. This is especially true for species, such as marine mammals, for which data on vital rates are difficult to obtain. Since the effects of an environmental disaster are not fixed, we develop time-varying (nonautonomous) matrix population models that account for the eventual recovery of the environment to the pre-disaster state. We use these models to investigate how lethal and sublethal impacts (in the form of reductions in the survival and fecundity, respectively) affect the population's recovery process. We explore two scenarios of the environmental recovery process and include the effect of demographic stochasticity. Our results provide insights into the relationship between the magnitude of the disaster, the duration of the disaster, and the probability that the population recovers to pre-disaster levels or a biologically relevant threshold level. To illustrate this modeling methodology, we provide an application to a sperm whale population. This application was motivated by the 2010 Deepwater Horizon oil rig explosion in the Gulf of Mexico that has impacted a wide variety of species populations including oysters, fish, corals, and whales.

  16. Lack of Constitutively Active DNA Repair Sensitizes Glioblastomas to Akt Inhibition and Induces Synthetic Lethality with Radiation Treatment in a p53-Dependent Manner. (United States)

    Palanichamy, Kamalakannan; Patel, Disha; Jacob, John R; Litzenberg, Kevin T; Gordon, Nicolaus; Acus, Kirstin; Noda, Shin-Ei; Chakravarti, Arnab


    Treatment refractory glioblastoma (GBM) remains a major clinical problem globally, and targeted therapies in GBM have not been promising to date. The Cancer Genome Atlas integrative analysis of GBM reported the striking finding of genetic alterations in the p53 and PI3K pathways in more than 80% of GBMs. Given the role of these pathways in making cell-fate decisions and responding to genotoxic stress, we investigated the reliance of these two pathways in mediating radiation resistance. We selected a panel of GBM cell lines and glioma stem cells (GSC) with wild-type TP53 (p53-wt) and mutant TP53 , mutations known to interfere with p53 functionality (p53-mt). Cell lines were treated with a brain permeable inhibitor of P-Akt (ser473), phosphatidylinositol ether lipid analogue (PIA), with and without radiation treatment. Sensitivity to treatment was measured using Annexin-V/PI flow cytometry and Western blot analysis for the markers of apoptotic signaling, alkaline COMET assay. All results were verified in p53 isogenic cell lines. p53-mt cell lines were selectively radiosensitized by PIA. This radiosensitization effect corresponded with an increase in DNA damage and a decrease in DNA-PKcs levels. TP53 silencing in p53-wt cells showed a similar response as the p53-mt cells. In addition, the radiosensitization effects of Akt inhibition were not observed in normal human astrocytes, suggesting that this treatment strategy could have limited off-target effects. We demonstrate that the inhibition of the PI3K/Akt pathway by PIA radiosensitizes p53-mt cells by antagonizing DNA repair. In principle, this strategy could provide a large therapeutic window for the treatment of TP53 -mutant tumors. Mol Cancer Ther; 17(2); 336-46. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

  17. CRTAP mutations in lethal and severe osteogenesis imperfecta: the importance of combining biochemical and molecular genetic analysis.

    NARCIS (Netherlands)

    Dijk, F.S. Van; Nesbitt, I.M.; Nikkels, P.G.J.; Dalton, A.; Bongers, E.M.H.F.; Kamp, J.M. van de; Hilhorst-Hofstee, Y.; Hollander, N.S. den; Lachmeijer, A.M.; Marcelis, C.L.M.; Tan-Sindhunata, G.M.; Rijn, R.R. van; Meijers-Heijboer, H.; Cobben, J.M.; Pals, G.


    Autosomal recessive lethal and severe osteogenesis imperfecta (OI) is caused by the deficiency of cartilage-associated protein (CRTAP) and prolyl-3-hydroxylase 1 (P3H1) because of CRTAP and LEPRE1 mutations. We analyzed five families in which 10 individuals had a clinical diagnosis of lethal and

  18. Protease Addiction and Synthetic Lethality in Cancer

    International Nuclear Information System (INIS)

    Freije, José M. P.; Fraile, Julia M.; López-Otín, Carlos


    The “oncogene addiction” concept refers to the dependence of cancer cells on the function of the oncogenes responsible for their transformed phenotype, while the term “non-oncogene addiction” has been introduced to define the exacerbated necessity of the normal function of non-mutated genes. In this Perspective, we focus on the importance of proteolytic enzymes to maintain the viability of cancer cells and hypothesize that most, if not all, tumors present “addiction” to a number of proteolytic activities, which in turn may represent valuable targets of anti-cancer therapies, even without being mutated or over-expressed by the malignant cells.

  19. What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries.

    Directory of Open Access Journals (Sweden)

    Roland Mergl

    Full Text Available In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in lethality can be explained by factors such as choice of more lethal methods or lethality differences within the same suicide method or age. In addition, we explored gender differences in the intentionality of suicide attempts.Methods. Design: Epidemiological study using a combination of self-report and official data. Setting: Mental health care services in four European countries: Germany, Hungary, Ireland, and Portugal. Data basis: Completed suicides derived from official statistics for each country (767 acts, 74.4% male and assessed suicide attempts excluding habitual intentional self-harm (8,175 acts, 43.2% male. Main Outcome Measures and Data Analysis. We collected data on suicidal acts in eight regions of four European countries participating in the EU-funded "OSPI-Europe"-project ( We calculated method-specific lethality using the number of completed suicides per method * 100 / (number of completed suicides per method + number of attempted suicides per method. We tested gender differences in the distribution of suicidal acts for significance by using the χ2-test for two-by-two tables. We assessed the effect sizes with phi coefficients (φ. We identified predictors of lethality with a binary logistic regression analysis. Poisson regression analysis examined the contribution of choice of methods and method-specific lethality to gender differences in the lethality of suicidal acts.Suicidal acts (fatal and non-fatal were 3.4 times more lethal in men than in women (lethality 13.91% (regarding 4106 suicidal acts versus 4.05% (regarding 4836 suicidal acts, the difference being significant for the methods hanging, jumping, moving objects, sharp

  20. From Cognitive Task Analysis to Simulation: Developing a Synthetic Team Task for AWACS Weapons Directors

    National Research Council Canada - National Science Library

    Hess, Stephen M; MacMillan, Jean; Serfaty, Daniel; Elliott, Linda


    ... while maintaining others. This paper reports the results of a successful effort to create a synthetic task environment that captures key elements of a team task based on Cognitive Task Analysis of the important features...

  1. Biocompatible synthetic and semi-synthetic polymers - A patent preliminary analysis. (United States)

    Ranganathan, Balu; Miller, Charles; Sinskey, Anthony


    Bioengineering has come of ages by setting up spare parts manufacturing units to be used in human body such as invasive implants and interventional controlled drug delivery in vivo systems. As a matter of fact patients on basis of their fiscal strength have the option of undergoing prophylactic tactical manoeuvre for longevity. In this sphere of invasive implants, biocompatible polymer implants are a state of the art cutting edge technology with outstanding innovations leading to number of very successful start-up companies with a plethora of patent portfolios. From 2000 onwards, around fifteen years on patent filings and grants for biocompatible polymers are expanding. Pair Bulk Data (PBD) portal was used to mine patent portfolios. In this patent preliminary analysis report, patents from 2000 to 2015 were evaluated using 317(c) filings, grants and classifications data for poly(vinyl alcohol) (PVA), poly(glycolic acid) (PGA), poly(hydroxyalkanoates) (PHAs) and poly(lactic acid) (PLA). Patent portfolio of Commercial giant Thepa Inc. was analysed for Cooperative Patent Classification (CPC) sections. This patent portfolio preliminary analysis embarks into patent analysis for New Product Development (NPD) for corporate R&D investment managerial decisions and on government advocacy for federal funding which is decisive for developmental advances. An in-depth patent portfolio investigation with return of investment (RoI) is in the pipeline. Copyright© Bentham Science Publishers; For any queries, please email at



    KAYA, Ertuğrul


    Deaths from mushroom poisoning, due to the ingestionofmushrooms containing amatoxins, seem to be increasingboth in Turkey andworldwide. The amatoxinsfound in Amanita phalloides (also called thedeath capmushroom) are most toxic agents, and they are responsible for more than 95% ofthe cases of deadlymushroom poisoning. Alpha amanitin is best known toxin ofthis group. Alpha amanitin analysis can be carried out with special methodssuch as chromatography and ELISA. ELISA method is suitable in orde...

  3. Shape analysis of isoseismals based on empirical and synthetic data

    International Nuclear Information System (INIS)

    Molchan, G.; Panza, G.F.


    We present an attempt to compare modeled ground motion acceleration fields with macroseismic observations. Two techniques for the representation of the observed intensities by isoseismals, a smoothing technique and one which visualizes the local uncertainty of an isoseismal, are tested with synthetic and observed data. We show how noise in the data and irregularities in the distribution of observation sites affect the resolution of the isoseismal's shape. In addition to ''standard'' elongated shapes, we identify cross-like patterns in the macroseismic observations for two Italian earthquakes of strike-slip type; similar patterns are displayed by the theoretical peak acceleration fields calculated assuming the point source models given in the literature. (author)

  4. Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis

    Energy Technology Data Exchange (ETDEWEB)

    Brenna, Elisabetta [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail:; Fronza, Giovanni [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Instituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)], E-mail:; Fuganti, Claudio [Dipartimento di Chimica, Materiali e di Ingegneria Chimica del Politecnico di Milano (Italy) and Istituto CNR per la Chimica del Riconoscimento Molecolare, Via Mancinelli 7, Milan I-20131 (Italy)


    Samples of fluoxetine of different origin were submitted to natural abundance {sup 2}H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known. These preliminary results give an idea of the potential of site-specific isotope ratio analysis in the fight against patent infringement and drug counterfeiting.

  5. Seamless Synthetic Aperture Radar Archive for Interferometry Analysis (United States)

    Baker, S.; Baru, C.; Bryson, G.; Buechler, B.; Crosby, C.; Fielding, E.; Meertens, C.; Nicoll, J.; Youn, C.


    The NASA Advancing Collaborative Connections for Earth System Science (ACCESS) seamless synthetic aperture radar (SAR) archive (SSARA) project is a collaboration between UNAVCO, the Alaska Satellite Facility (ASF), the Jet Propulsion Laboratory (JPL), and OpenTopography at the San Diego Supercomputer Center (SDSC) to design and implement a seamless distributed access system for SAR data and derived interferometric SAR (InSAR) data products. A unified application programming interface (API) has been created to search the SAR archives at ASF and UNAVCO, 30 and 90-m SRTM DEM data available through OpenTopography, and tropospheric data from the NASA OSCAR project at JPL. The federated query service provides users a single access point to search for SAR granules, InSAR pairs, and corresponding DEM and tropospheric data products from the four archives, as well as the ability to search and download pre-processed InSAR products from ASF and UNAVCO.

  6. Synthetic Plant Defense Elicitors

    Directory of Open Access Journals (Sweden)

    Yasemin eBektas


    Full Text Available To defend themselves against invading pathogens plants utilize a complex regulatory network that coordinates extensive transcriptional and metabolic reprogramming. Although many of the key players of this immunity-associated network are known, the details of its topology and dynamics are still poorly understood. As an alternative to forward and reverse genetic studies, chemical genetics-related approaches based on bioactive small molecules have gained substantial popularity in the analysis of biological pathways and networks. Use of such molecular probes can allow researchers to access biological space that was previously inaccessible to genetic analyses due to gene redundancy or lethality of mutations. Synthetic elicitors are small drug like molecules that induce plant defense responses, but are distinct from known natural elicitors of plant immunity. While the discovery of the some synthetic elicitors had already been reported in the 1970s, recent breakthroughs in combinatorial chemical synthesis now allow for inexpensive high-throughput screens for bioactive plant defense-inducing compounds. Along with powerful reverse genetics tools and resources available for model plants and crop systems, comprehensive collections of new synthetic elicitors will likely allow plant scientists to study the intricacies of plant defense signaling pathways and networks in an unparalleled fashion. As synthetic elicitors can protect crops from diseases, without the need to be directly toxic for pathogenic organisms, they may also serve as promising alternatives to conventional biocidal pesticides, which often are harmful for the environment, farmers and consumers. Here we are discussing various types of synthetic elicitors that have been used for studies on the plant immune system, their modes-of-action as well as their application in crop protection.

  7. Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS. (United States)

    Choi, Hyeyoung; Heo, Sewoong; Choe, Sanggil; Yang, Wonkyung; Park, Yuran; Kim, Eunmi; Chung, Heesun; Lee, Jaesin


    A rapid and simple gas chromatography-mass spectrometry (GC-MS) method was developed and validated to identify and quantify synthetic cannabinoids in the materials seized during drug trafficking. Accuracy and reproducibility of the method were improved by using deuterated JWH-018 and JWH-073 as internal standards. Validation results of the GC-MS method showed that it was suitable for simultaneous qualitative and quantitative analyses of synthetic cannabinoids, and we analyzed synthetic cannabinoids in seized materials using the validated GC-MS method. As a result of the analysis, ten species of synthetic cannabinoids were identified in dried leaves (n = 40), bulk powders (n = 6), and tablets (n = 14) seized in Korea during 2009-2012, as a single ingredient or as a mixture with other active co-ingredients. JWH-018 and JWH-073 were the most frequently identified compounds in the seized materials. Synthetic cannabinoids in the dried leaves showed broad concentration ranges, which may cause unexpected toxicity to abusers. The bulk powders were considered as raw materials used to prepare legal highs, and they contained single ingredient of JWH-073, JWH-019, or JWH-250 with the purity over 70 %. In contrast, JWH-018 and JWH-073 contents in the tablets were 7.1-13.8 and 3.0-10.2 mg/g, respectively. Relatively low contents in the tablets suggest that the synthetic cannabinoids may have been added to the tablets as supplements to other active co-ingredients.

  8. Integrated In Silico Analysis of Pathway Designs for Synthetic Photo-Electro-Autotrophy.

    Directory of Open Access Journals (Sweden)

    Michael Volpers

    Full Text Available The strong advances in synthetic biology enable the engineering of novel functions and complex biological features in unprecedented ways, such as implementing synthetic autotrophic metabolism into heterotrophic hosts. A key challenge for the sustainable production of fuels and chemicals entails the engineering of synthetic autotrophic organisms that can effectively and efficiently fix carbon dioxide by using sustainable energy sources. This challenge involves the integration of carbon fixation and energy uptake systems. A variety of carbon fixation pathways and several types of photosystems and other energy uptake systems can be chosen and, potentially, modularly combined to design synthetic autotrophic metabolism. Prior to implementation, these designs can be evaluated by the combination of several computational pathway analysis techniques. Here we present a systematic, integrated in silico analysis of photo-electro-autotrophic pathway designs, consisting of natural and synthetic carbon fixation pathways, a proton-pumping rhodopsin photosystem for ATP regeneration and an electron uptake pathway. We integrated Flux Balance Analysis of the heterotrophic chassis Escherichia coli with kinetic pathway analysis and thermodynamic pathway analysis (Max-min Driving Force. The photo-electro-autotrophic designs are predicted to have a limited potential for anaerobic, autotrophic growth of E. coli, given the relatively low ATP regenerating capacity of the proton pumping rhodopsin photosystems and the high ATP maintenance of E. coli. If these factors can be tackled, our analysis indicates the highest growth potential for the natural reductive tricarboxylic acid cycle and the synthetic pyruvate synthase-pyruvate carboxylate -glyoxylate bicycle. Both carbon fixation cycles are very ATP efficient, while maintaining fast kinetics, which also results in relatively low estimated protein costs for these pathways. Furthermore, the synthetic bicycles are highly

  9. Assessing the Relevance of Anomie Theory for Explaining Spatial Variation in Lethal Criminal Violence: An Aggregate-Level Analysis of Homicide within the United States

    Directory of Open Access Journals (Sweden)

    Eric P. Baumer


    Full Text Available One of the most influential statements in the anomie theory tradition has been Merton’s argument that the volume of instrumental property crime should be higher where there is a greater imbalance between the degree of commitment to monetary success goals and the degree of commitment to legitimate means of pursuing such goals. Contemporary anomie theories stimulated by Merton’s perspective, most notably Messner and Rosenfeld’s institutional anomie theory, have expanded the scope conditions by emphasizing lethal criminal violence as an outcome to which anomie theory is highly relevant, and virtually all contemporary empirical studies have focused on applying the perspective to explaining spatial variation in homicide rates. In the present paper, we argue that current explications of Merton’s theory and IAT have not adequately conveyed the relevance of the core features of the anomie perspective to lethal violence. We propose an expanded anomie model in which an unbalanced pecuniary value system – the core causal variable in Merton’s theory and IAT – translates into higher levels of homicide primarily in indirect ways by increasing levels of firearm prevalence, drug market activity, and property crime, and by enhancing the degree to which these factors stimulate lethal outcomes. Using aggregate-level data collected during the mid-to-late 1970s for a sample of relatively large social aggregates within the U.S., we find a significant effect on homicide rates of an interaction term reflecting high levels of commitment to monetary success goals and low levels of commitment to legitimate means. Virtually all of this effect is accounted for by higher levels of property crime and drug market activity that occur in areas with an unbalanced pecuniary value system. Our analysis also reveals that property crime is more apt to lead to homicide under conditions of high levels of structural disadvantage. These and other findings underscore the

  10. 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

    Directory of Open Access Journals (Sweden)

    Myrna J. Simpson


    Full Text Available 1H NMR-based metabolomics was used to measure the response of Eisenia fetida earthworms after exposure to sub-lethal concentrations of perfluorooctane sulfonate (PFOS in soil. Earthworms were exposed to a range of PFOS concentrations (five, 10, 25, 50, 100 or 150 mg/kg for two, seven and fourteen days. Earthworm tissues were extracted and analyzed by 1H NMR. Multivariate statistical analysis of the metabolic response of E. fetida to PFOS exposure identified time-dependent responses that were comprised of two separate modes of action: a non-polar narcosis type mechanism after two days of exposure and increased fatty acid oxidation after seven and fourteen days of exposure. Univariate statistical analysis revealed that 2-hexyl-5-ethyl-3-furansulfonate (HEFS, betaine, leucine, arginine, glutamate, maltose and ATP are potential indicators of PFOS exposure, as the concentrations of these metabolites fluctuated significantly. Overall, NMR-based metabolomic analysis suggests elevated fatty acid oxidation, disruption in energy metabolism and biological membrane structure and a possible interruption of ATP synthesis. These conclusions obtained from analysis of the metabolic profile in response to sub-lethal PFOS exposure indicates that NMR-based metabolomics is an excellent discovery tool when the mode of action (MOA of contaminants is not clearly defined.

  11. Proteomic analysis of vascular smooth muscle cells in physiological condition and in pulmonary arterial hypertension: Toward contractile versus synthetic phenotypes. (United States)

    Régent, Alexis; Ly, Kim Heang; Lofek, Sébastien; Clary, Guilhem; Tamby, Mathieu; Tamas, Nicolas; Federici, Christian; Broussard, Cédric; Chafey, Philippe; Liaudet-Coopman, Emmanuelle; Humbert, Marc; Perros, Frédéric; Mouthon, Luc


    Vascular smooth muscle cells (VSMCs) are highly specialized cells that regulate vascular tone and participate in vessel remodeling in physiological and pathological conditions. It is unclear why certain vascular pathologies involve one type of vessel and spare others. Our objective was to compare the proteomes of normal human VSMC from aorta (human aortic smooth muscle cells, HAoSMC), umbilical artery (human umbilical artery smooth muscle cells, HUASMC), pulmonary artery (HPASMC), or pulmonary artery VSMC from patients with pulmonary arterial hypertension (PAH-SMC). Proteomes of VSMC were compared by 2D DIGE and MS. Only 19 proteins were differentially expressed between HAoSMC and HPASMC while 132 and 124 were differentially expressed between HUASMC and HAoSMC or HPASMC, respectively (fold change 1.5≤ or -1.5≥, p < 0.05). As much as 336 proteins were differentially expressed between HPASMC and PAH-SMC (fold change 1.5≤ or -1.5≥, p < 0.05). HUASMC expressed increased amount of α-smooth muscle actin compared to either HPASMC or HAoSMC (although not statistically significant). In addition, PAH-SMC expressed decreased amount of smooth muscle myosin heavy chain and proliferation rate was increased compared to HPASMC thus supporting that PAH-SMC have a more synthetic phenotype. Analysis with Ingenuity identified paxillin and (embryonic lethal, abnormal vision, drosophila) like 1 (ELAVL1) as molecules linked with a lot of proteins differentially expressed between HPASMC and PAH-SMC. There was a trend toward reduced proliferation of PAH-SMC with paxillin-si-RNA and increased proliferation with ELAVL1-siRNA. Thus, VSMCs have very diverse protein content depending on their origin and this is in link with phenotypic differentiation. Paxillin targeting may be a promising treatment of PAH. ELAVL1 also participate in the regulation of PAH-SMC proliferation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Texture Based Quality Analysis of Simulated Synthetic Ultrasound Images Using Local Binary Patterns †

    Directory of Open Access Journals (Sweden)

    Prerna Singh


    Full Text Available Speckle noise reduction is an important area of research in the field of ultrasound image processing. Several algorithms for speckle noise characterization and analysis have been recently proposed in the area. Synthetic ultrasound images can play a key role in noise evaluation methods as they can be used to generate a variety of speckle noise models under different interpolation and sampling schemes, and can also provide valuable ground truth data for estimating the accuracy of the chosen methods. However, not much work has been done in the area of modeling synthetic ultrasound images, and in simulating speckle noise generation to get images that are as close as possible to real ultrasound images. An important aspect of simulated synthetic ultrasound images is the requirement for extensive quality assessment for ensuring that they have the texture characteristics and gray-tone features of real images. This paper presents texture feature analysis of synthetic ultrasound images using local binary patterns (LBP and demonstrates the usefulness of a set of LBP features for image quality assessment. Experimental results presented in the paper clearly show how these features could provide an accurate quality metric that correlates very well with subjective evaluations performed by clinical experts.

  13. Comparison of LC-ESI-MS and GC-MS for the Analysis of a Synthetic Tabun Sample

    National Research Council Canada - National Science Library

    D'Agostino, Paul


    Packed capillary LC-ESI-MS and capillary column GC-MS were compared for the analysis of a synthetic tabun sample as each method has advantages for the analysis of samples containing chemical warfare...

  14. Biologic mesh versus synthetic mesh in open inguinal hernia repair: system review and meta-analysis. (United States)

    Fang, Zhixue; Ren, Feng; Zhou, Jianping; Tian, Jiao


    Biologic meshes are mostly used for abdominal wall reinforcement in infected fields, but no consensus has been reached on its use for inguinal hernia repairing. The purpose of this study was to compare biologic mesh with synthetic mesh in open inguinal herniorrhaphy. A systematic literature review and meta-analysis was undertaken to identify studies comparing the outcomes of biologic mesh and synthetic mesh in open inguinal hernia repair. Published studies were identified by the databases PubMed, EMBASE and the Cochrane Library. A total of 382 patients in five randomized controlled trials were reviewed (179 patients in biologic mesh group; 203 patients in synthetic mesh group). The two groups did not significantly differ in chronic groin pain (P = 0.06) or recurrence (P = 0.38). The incidence of seroma trended higher in biologic mesh group (P = 0.03). Operating time was significantly longer with biologic mesh (P = 0.03). There was no significant difference in hematomas (P = 0.23) between the two groups. From the data of this study, biologic mesh had no superiority to synthetic mesh in open inguinal hernia repair with similar recurrence rates and incidence of chronic groin pain, but higher rate of seroma and longer operating time. However, this mesh still needs to be assessed in a large, multicentre, well-designed randomized controlled trial. © 2015 Royal Australasian College of Surgeons.

  15. Multiscale analysis of enantioselectivity in enzyme-catalysed ‘lethal synthesis’ using projector-based embedding (United States)

    Bennie, Simon J.; van der Kamp, Marc W.; Manby, Frederick R.; Mulholland, Adrian J.


    The action of fluoroacetate as a broad-spectrum mammalian pesticide depends on the ‘lethal synthesis’ of fluorocitrate by citrate synthase, through a subtle enantioselective enolization of fluoroacetyl-coenzyme A. In this work, we demonstrate how a projection-based embedding method can be applied to calculate coupled cluster (CCSD(T)) reaction profiles from quantum mechanics/molecular mechanics optimized pathways for this enzyme reaction. Comparison of pro-R and pro-S proton abstraction in citrate synthase at the CCSD(T)-in-DFT//MM level yields the correct enantioselectivity. We thus demonstrate the potential of projection-based embedding for determining stereoselectivity in enzymatic systems. We further show that the method is simple to apply, eliminates variability due to the choice of density functional theory functional and allows the efficient calculation of CCSD(T) quality enzyme reaction barriers. PMID:29515856

  16. 3D-QSAR Investigation of Synthetic Antioxidant Chromone Derivatives by Molecular Field Analysis

    Directory of Open Access Journals (Sweden)

    Jiraporn Ungwitayatorn


    Full Text Available A series of 7-hydroxy, 8-hydroxy and 7,8-dihydroxy synthetic chromone derivatives was evaluated for their DPPH free radical scavenging activities. A training set of 30 synthetic chromone derivatives was subject to three-dimensional quantitative structure-activity relationship (3D-QSAR studies using molecular field analysis (MFA. The substitutional requirements for favorable antioxidant activity were investigated and a predictive model that could be used for the design of novel antioxidants was derived. Regression analysis was carried out using genetic partial least squares (G/PLS method. A highly predictive and statistically significant model was generated. The predictive ability of the developed model was assessed using a test set of 5 compounds (r2pred = 0.924. The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and crossvalidated coefficient r2cv value of 0.771.

  17. Application of the 'GammaGen' Computer Code for NORM Synthetic Spectra Analysis

    International Nuclear Information System (INIS)

    Sarusi, B.; Levinson, S.; German, U.; Antropov, S.; Kovler, K.


    'GammaGen' (GG) is a computer software developed to simulate gamma ray spectra obtained from NaI(Tl) or Ge detectors. The detector efficiency, resolution and peak to Compton ratios are used to generate synthetic pulse height spectra for specific detector and geometrical configurations. GG was used in the past for several applications, as to predict the detector response to different radio-nuclides mixtures, to predict the pulse height spectra near a nuclear spent fuel site as a function of the shielding thickness and cooling time and for homeland security purposes. An updated version of the GG program was developed, and the application presented in the present work consists of building a library and simulating the detection and analysis of synthetic spectra to check the performance of a commercial spectrometry system based on a NaI(Tl) detector intended for NORM analysis, which was developed by Amplituda/Russia

  18. The preparation of synthetic standards for use in instrumental neutron-activation analysis

    International Nuclear Information System (INIS)

    Eddy, B.T.; Watterson, J.I.W.; Erasmus, C.S.


    An account is given of the formulation and preparation of synthetic standards suitable for the routine analysis of minerals, ores, and ore concentrates by instrumental neutron activation. Fifteen standards were prepared, each containing from one to seven elements. The standards contain forty-four elements that produce isotopes with half-lives longer than 12 hours. An evaluation of the accuracy and precision of the method of preparation is given

  19. Rapid in vivo analysis of synthetic promoters for plant pathogen phytosensing

    Directory of Open Access Journals (Sweden)

    Liu Wusheng


    Full Text Available Abstract Background We aimed to engineer transgenic plants for the purpose of early detection of plant pathogen infection, which was accomplished by employing synthetic pathogen inducible promoters fused to reporter genes for altered phenotypes in response to the pathogen infection. Toward this end, a number of synthetic promoters consisting of inducible regulatory elements fused to a red fluorescent protein (RFP reporter were constructed for use in phytosensing. Results For rapid analysis, an Agrobacterium-mediated transient expression assay was evaluated, then utilized to assess the inducibility of each synthetic promoter construct in vivo. Tobacco (Nicotiana tabacum cv. Xanthi leaves were infiltrated with Agrobacterium harboring the individual synthetic promoter-reporter constructs. The infiltrated tobacco leaves were re-infiltrated with biotic (bacterial pathogens or abiotic (plant defense signal molecules salicylic acid, ethylene and methyl jasmonate agents 24 and 48 hours after initial agroinfiltration, followed by RFP measurements at relevant time points after treatment. These analyses indicated that the synthetic promoter constructs were capable of conferring the inducibility of the RFP reporter in response to appropriate phytohormones and bacterial pathogens, accordingly. Conclusions These observations demonstrate that the Agrobacterium-mediated transient expression is an efficient method for in vivo assays of promoter constructs in less than one week. Our results provide the opportunity to gain further insights into the versatility of the expression system as a potential tool for high-throughput in planta expression screening prior to generating stably transgenic plants for pathogen phytosensing. This system could also be utilized for temporary phytosensing; e.g., not requiring stably transgenic plants.

  20. High-content analysis screening for cell cycle regulators using arrayed synthetic crRNA libraries. (United States)

    Strezoska, Žaklina; Perkett, Matthew R; Chou, Eldon T; Maksimova, Elena; Anderson, Emily M; McClelland, Shawn; Kelley, Melissa L; Vermeulen, Annaleen; Smith, Anja van Brabant


    The CRISPR-Cas9 system has been utilized for large-scale, loss-of-function screens mainly using lentiviral pooled formats and cell-survival phenotypic assays. Screening in an arrayed format expands the types of phenotypic readouts that can be used to now include high-content, morphology-based assays, and with the recent availability of synthetic crRNA libraries, new studies are emerging. Here, we use a cell cycle reporter cell line to perform an arrayed, synthetic crRNA:tracrRNA screen targeting 169 genes (>600 crRNAs) and used high content analysis (HCA) to identify genes that regulate the cell cycle. Seven parameters were used to classify cells into cell cycle categories and multiple parameters were combined using a new analysis technique to identify hits. Comprehensive hit follow-up experiments included target gene expression analysis, confirmation of DNA insertions/deletions, and validation with orthogonal reagents. Our results show that most hits had three or more independent crRNAs per gene that demonstrated a phenotype with consistent individual parameters, indicating that our screen produced high-confidence hits with low off-target effects and allowed us to identify hits with more subtle phenotypes. The results of our screen demonstrate the power of using arrayed, synthetic crRNAs for functional phenotypic screening using multiparameter HCA assays. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  1. Synthetic fuels and the environment: an environmental and regulatory impacts analysis

    Energy Technology Data Exchange (ETDEWEB)



    Since July 1979 when DOE/EV-0044 report Environmental Analysis of Synthetic Liquid fuels was published the synthetic fuels program proposals of the Administration have undergone significant modifications. The program year for which the development goal of 1.5 million barrels per day is to be reached has been changed from 1990 to 1995. The program plan is now proposed to have two stages to ensure, among other things, better environmental protection: an initial stage emphasizing applied research and development (R and D), including environmental research, followed by a second stage that would accelerate deployment of those synthetic fuel technologies then judged most ready for rapid deployment and economic operation within the environmental protection requirements. These program changes have significantly expanded the scope of technologies to be considered in this environmental analysis and have increased the likelihood that accelerated environmental R and D efforts will be successful in solving principal environmental and worker safety concerns for most technologies prior to the initiation of the second stage of the accelerated deployment plan. Information is presented under the following section headings: summary; study description; the technologies and their environmental concerns (including, coal liquefaction and gasification, oil shale production, biomass and urban waste conversion); regulatory and institutional analyses; and environmental impacts analysis (including air and water quaility analyses, impacts of carbon dioxide and acid rain, water availability, solid and hazardous wastes, coal mining environmental impacts, transportation issues, community growth and change, and regional impacts). Additional information is presented in seventeen appendixes. (JGB)

  2. Accuracy of imaging parameters in the prediction of lethal pulmonary hypoplasia secondary to mid-trimester prelabor rupture of fetal membranes: a systematic review and meta-analysis. (United States)

    van Teeffelen, A S P; Van Der Heijden, J; Oei, S G; Porath, M M; Willekes, C; Opmeer, B; Mol, B W J


    In women who have suffered mid-trimester prelabor rupture of membranes (PPROM), prediction of pulmonary hypoplasia is important for optimal management. We performed a systematic review to assess the capacity of imaging parameters to predict pulmonary hypoplasia. We searched for published articles that reported on biometric parameters and allowed the construction of a 2 × 2 table, comparing at least one of these parameters with the occurrence of pulmonary hypoplasia. The selected studies were scored on methodological quality and we calculated sensitivity and specificity of the tests in the prediction of pulmonary hypoplasia and lethal pulmonary hypoplasia. Overall performance was assessed by summary receiver-operating characteristics (sROC) analyses that were performed with bivariate meta-analysis. We detected 13 studies that reported on the prediction of lethal pulmonary hypoplasia. The quality of the included studies was poor to mediocre. The estimated sROC curves for the chest circumference/abdominal circumference ratio and other parameters showed limited accuracy in the prediction of pulmonary hypoplasia. In women with mid-trimester PPROM, the available evidence indicates limited accuracy of biometric parameters in the prediction of pulmonary hypoplasia. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

  3. Thermodynamic analysis of synthetic hydrocarbon fuel production in pressurized solid oxide electrolysis cells

    DEFF Research Database (Denmark)

    Sun, Xiufu; Chen, Ming; Jensen, Søren Højgaard


    improved system efficiency, potentially lowering the fuel production cost significantly. In this paper, we present a thermodynamic analysis of synthetic methane and dimethyl ether (DME) production using pressurized SOECs, in order to determine feasible operating conditions for producing the desired......A promising way to store wind and solar electricity is by electrolysis of H2O and CO2 using solid oxide electrolysis cells (SOECs) to produce synthetic hydrocarbon fuels that can be used in existing fuel infrastructure. Pressurized operation decreases the cell internal resistance and enables...... hydrocarbon fuel and avoiding damage to the cells. The main parameters of cell operating temperature, pressure, inlet gas composition and reactant utilization are varied to examine how they influence cell thermoneutral and reversible potentials, in situ formation of methane and carbon at the Ni–YSZ electrode...

  4. Analysis and optimization of a synthetic milkweed floral attractant for mosquitoes. (United States)

    Otienoburu, Philip E; Ebrahimi, Babak; Phelan, P Larry; Foster, Woodbridge A


    A pentane extract of flowers of common milkweed, Asclepias syriaca (Asclepiadaceae), elicited significant orientation from both male and female Culex pipiens in a dual-port flight olfactometer. Analysis of the extract by gas chromatography-mass spectrometry revealed six major constituents in order of relative abundance: benzaldehyde, (E)-β-ocimene, phenylacetaldehyde, benzyl alcohol, nonanal, and (E)-2-nonenal. Although not all were collected from the headspace profile of live flowers, a synthetic blend of these six compounds, when presented to mosquitoes in the same levels and proportions that occur in the extract, elicited a response comparable to the extract. Subtractive behavioral bioassays demonstrated that a three-component blend consisting of benzaldehyde, phenylacetaldehyde, and (E)-2-nonenal was as attractive as the full blend. These findings suggest the potential use of synthetic floral-odor blends for monitoring or control of both male and female disease-vectoring mosquitoes.

  5. Immunoinformatic Analysis of Crimean Congo Hemorrhagic Fever Virus Glycoproteins and Epitope Prediction for Synthetic Peptide Vaccine. (United States)

    Tipu, Hamid Nawaz


    To determine the Crimean Congo Hemorrhagic Fever (CCHF) virus M segement glycoprotein's immunoinformatic parameters, and identify Human Leukocyte Antigen (HLA) class I binders as candidates for synthetic peptide vaccines. Cross-sectional study. Combined Military Hospital, Khuzdar Cantt, in May 2015. Data acquisition, antigenicity prediction, secondary and tertiary structure prediction, residue analysis were done using immunoinformatics tools. HLAclass I binders in glycoprotein's sequence were identified at nanomer length using NetMHC 3.4 and mapped onto tertiary structure. Docking was done for strongest binder against its corresponding allele with CABS-dock. HLAA*0101, 0201, 0301, 2402, 2601 and B*0702, 0801, 2705, 3901, 4001, 5801, 1501 were analyzed against two glycoprotein components of the virus. Atotal of 35 nanomers from GP1, and 3 from GP2 were identified. HLAB*0702 bound maximum number of peptides (6), while HLAB*4001 showed strongest binding affinity. HLAspecific glycoproteins epitope prediction can help identify synthetic peptide vaccine candidates.

  6. Synthetic environments (United States)

    Lukes, George E.; Cain, Joel M.


    The Advanced Distributed Simulation (ADS) Synthetic Environments Program seeks to create robust virtual worlds from operational terrain and environmental data sources of sufficient fidelity and currency to interact with the real world. While some applications can be met by direct exploitation of standard digital terrain data, more demanding applications -- particularly those support operations 'close to the ground' -- are well-served by emerging capabilities for 'value-adding' by the user working with controlled imagery. For users to rigorously refine and exploit controlled imagery within functionally different workstations they must have a shared framework to allow interoperability within and between these environments in terms of passing image and object coordinates and other information using a variety of validated sensor models. The Synthetic Environments Program is now being expanded to address rapid construction of virtual worlds with research initiatives in digital mapping, softcopy workstations, and cartographic image understanding. The Synthetic Environments Program is also participating in a joint initiative for a sensor model applications programer's interface (API) to ensure that a common controlled imagery exploitation framework is available to all researchers, developers and users. This presentation provides an introduction to ADS and the associated requirements for synthetic environments to support synthetic theaters of war. It provides a technical rationale for exploring applications of image understanding technology to automated cartography in support of ADS and related programs benefitting from automated analysis of mapping, earth resources and reconnaissance imagery. And it provides an overview and status of the joint initiative for a sensor model API.

  7. Complex Wishart distribution based analysis of polarimetric synthetic aperture radar data

    DEFF Research Database (Denmark)

    Nielsen, Allan Aasbjerg; Skriver, Henning; Conradsen, Knut


    Multi-look, polarimetric synthetic aperture radar (SAR) data are often worked with in the so-called covariance matrix representation. For each pixel this representation gives a 3x3 Hermitian, positive definite matrix which follows a complex Wishart distribution. Based on this distribution a test ...... covering agricultural fields near Foulum, Denmark, are used. Soon the Japanese ALOS, the German TerraSAR-X and the Canadian RADARSAT-2 will acquire space-borne, polarimetric data making analysis based on these methods important....

  8. Synthetic wind speed scenarios generation for probabilistic analysis of hybrid energy systems

    International Nuclear Information System (INIS)

    Chen, Jun; Rabiti, Cristian


    Hybrid energy systems consisting of multiple energy inputs and multiple energy outputs have been proposed to be an effective element to enable ever increasing penetration of clean energy. In order to better understand the dynamic and probabilistic behavior of hybrid energy systems, this paper proposes a model combining Fourier series and autoregressive moving average (ARMA) to characterize historical weather measurements and to generate synthetic weather (e.g., wind speed) data. In particular, Fourier series is used to characterize the seasonal trend in historical data, while ARMA is applied to capture the autocorrelation in residue time series (e.g., measurements with seasonal trends subtracted). The generated synthetic wind speed data is then utilized to perform probabilistic analysis of a particular hybrid energy system configuration, which consists of nuclear power plant, wind farm, battery storage, natural gas boiler, and chemical plant. Requirements on component ramping rate, economic and environmental impacts of hybrid energy systems, and the effects of deploying different sizes of batteries in smoothing renewable variability, are all investigated. - Highlights: • Computational model to synthesize artificial wind speed data with consistent characteristics with database. • Fourier series to capture seasonal trends in the database. • Monte Carlo simulation and probabilistic analysis of hybrid energy systems. • Investigation of the effect of battery in smoothing variability of wind power generation.

  9. Synthetic spider silk sustainability verification by techno-economic and life cycle analysis (United States)

    Edlund, Alan

    Major ampullate spider silk represents a promising biomaterial with diverse commercial potential ranging from textiles to medical devices due to the excellent physical and thermal properties from the protein structure. Recent advancements in synthetic biology have facilitated the development of recombinant spider silk proteins from Escherichia coli (E. coli), alfalfa, and goats. This study specifically investigates the economic feasibility and environmental impact of synthetic spider silk manufacturing. Pilot scale data was used to validate an engineering process model that includes all of the required sub-processing steps for synthetic fiber manufacture: production, harvesting, purification, drying, and spinning. Modeling was constructed modularly to support assessment of alternative protein production methods (alfalfa and goats) as well as alternative down-stream processing technologies. The techno-economic analysis indicates a minimum sale price from pioneer and optimized E. coli plants at 761 kg-1 and 23 kg-1 with greenhouse gas emissions of 572 kg CO2-eq. kg-1 and 55 kg CO2-eq. kg-1, respectively. Spider silk sale price estimates from goat pioneer and optimized results are 730 kg-1 and 54 kg-1, respectively, with pioneer and optimized alfalfa plants are 207 kg-1 and 9.22 kg-1 respectively. Elevated costs and emissions from the pioneer plant can be directly tied to the high material consumption and low protein yield. Decreased production costs associated with the optimized plants include improved protein yield, process optimization, and an Nth plant assumption. Discussion focuses on the commercial potential of spider silk, the production performance requirements for commercialization, and impact of alternative technologies on the sustainability of the system.

  10. Quantitative wake analysis of a freely swimming fish using 3D synthetic aperture PIV (United States)

    Mendelson, Leah; Techet, Alexandra H.


    Synthetic aperture PIV (SAPIV) is used to quantitatively analyze the wake behind a giant danio ( Danio aequipinnatus) swimming freely in a seeded quiescent tank. The experiment is designed with minimal constraints on animal behavior to ensure that natural swimming occurs. The fish exhibits forward swimming and turning behaviors at speeds between 0.9 and 1.5 body lengths/second. Results show clearly isolated and linked vortex rings in the wake structure, as well as the thrust jet coming off of a visual hull reconstruction of the fish body. As a benchmark for quantitative analysis of volumetric PIV data, the vortex circulation and impulse are computed using methods consistent with those applied to planar PIV data. Volumetric momentum analysis frameworks are discussed for linked and asymmetric vortex structures, laying a foundation for further volumetric studies of swimming hydrodynamics with SAPIV. Additionally, a novel weighted refocusing method is presented as an improvement to SAPIV reconstruction.

  11. Performance evaluation of phage-displayed synthetic human single-domain antibody libraries: A retrospective analysis. (United States)

    Henry, Kevin A; Tanha, Jamshid


    Fully human synthetic single-domain antibodies (sdAbs) are desirable therapeutic molecules but their development is a considerable challenge. Here, using a retrospective analysis of in-house historical data, we examined the parameters that impact the outcome of screening phage-displayed synthetic human sdAb libraries to discover antigen-specific binders. We found no evidence for a differential effect of domain type (V H or V L ), library randomization strategy, incorporation of a stabilizing disulfide linkage or sdAb display format (monovalent vs. multivalent) on the probability of obtaining any antigen-binding human sdAbs, instead finding that the success of library screens was primarily related to properties of target antigens, especially molecular mass. The solubility and binding affinity of sdAbs isolated from successful screens depended both on properties of the sdAb libraries (primarily domain type) and the target antigens. Taking attrition of sdAbs with major manufacturability concerns (aggregation; low expression) and sdAbs that do not recognize native cell-surface antigens as independent probabilities, we calculate the overall likelihood of obtaining ≥1 antigen-binding human sdAb from a single library-target screen as ~24%. Successful library-target screens should be expected to yield ~1.3 human sdAbs on average, each with average binding affinity of ~2 μM. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Immunoinformatic Analysis of Crimean Congo Hemorrhagic Fever Virus Glycoproteins and Epitope Prediction for Synthetic Peptide Vaccine

    International Nuclear Information System (INIS)

    Tipu, H. N.


    Objective: To determine the Crimean Congo Hemorrhagic Fever (CCHF) virus M segement glycoprotein's immunoinformatic parameters, and identify Human Leukocyte Antigen (HLA) class I binders as candidates for synthetic peptide vaccines. Study Design: Cross-sectional study. Place and Duration of Study: Combined Military Hospital, Khuzdar Cantt, in May 2015. Methodology: Data acquisition, antigenicity prediction, secondary and tertiary structure prediction, residue analysis were done using immunoinformatics tools. HLA class I binders in glycoprotein's sequence were identified at nanomer length using NetMHC 3.4 and mapped onto tertiary structure. Docking was done for strongest binder against its corresponding allele with CABS-dock. Results: HLA A*0101, 0201, 0301, 2402, 2601 and B*0702, 0801, 2705, 3901, 4001, 5801, 1501 were analyzed against two glycoprotein components of the virus. A total of 35 nanomers from GP1, and 3 from GP2 were identified. HLA B*0702 bound maximum number of peptides (6), while HLA B*4001 showed strongest binding affinity. Conclusion: HLA specific glycoproteins epitope prediction can help identify synthetic peptide vaccine candidates. (author)

  13. Proteomic analysis of differentiating neuroblastoma cells treated with sub-lethal neurite inhibitory concentrations of diazinon: Identification of novel biomarkers of effect

    International Nuclear Information System (INIS)

    Harris, W.; Sachana, M.; Flaskos, J.; Hargreaves, A.J.


    In previous work we showed that sub-lethal levels of diazinon inhibited neurite outgrowth in differentiating N2a neuroblastoma cells. Western blotting analysis targeted at proteins involved in axon growth and stress responses, revealed that such exposure led to a reduction in the levels of neurofilament heavy chain, microtubule associated protein 1 B (MAP 1B) and HSP-70. The aim of this study was to apply the approach of 2 dimensional polyacrylamide gel electrophoresis and mass spectrometry to identify novel biomarkers of effect. A number of proteins were found to be up-regulated compared to the control on silver-stained gels. These were classified in to 3 main groups of proteins: cytosolic factors, chaperones and the actin-binding protein cofilin, all of which are involved in cell differentiation, survival or metabolism. The changes observed for cofilin were further confirmed by quantitative Western blotting analysis with anti-actin and anti-cofilin antibodies. Indirect immunofluorescence staining with the same antibodies indicated that the microfilament network was disrupted in diazinon-treated cells. Our data suggest that microfilament organisation is disrupted by diazinon exposure, which may be related to increased cofilin expression.

  14. Feasibility analysis of high resolution tissue image registration using 3-D synthetic data

    Directory of Open Access Journals (Sweden)

    Yachna Sharma


    Full Text Available Background: Registration of high-resolution tissue images is a critical step in the 3D analysis of protein expression. Because the distance between images (~4-5μm thickness of a tissue section is nearly the size of the objects of interest (~10-20μm cancer cell nucleus, a given object is often not present in both of two adjacent images. Without consistent correspondence of objects between images, registration becomes a difficult task. This work assesses the feasibility of current registration techniques for such images. Methods: We generated high resolution synthetic 3-D image data sets emulating the constraints in real data. We applied multiple registration methods to the synthetic image data sets and assessed the registration performance of three techniques (i.e., mutual information (MI, kernel density estimate (KDE method [1], and principal component analysis (PCA at various slice thicknesses (with increments of 1μm in order to quantify the limitations of each method. Results: Our analysis shows that PCA, when combined with the KDE method based on nuclei centers, aligns images corresponding to 5μm thick sections with acceptable accuracy. We also note that registration error increases rapidly with increasing distance between images, and that the choice of feature points which are conserved between slices improves performance. Conclusions: We used simulation to help select appropriate features and methods for image registration by estimating best-case-scenario errors for given data constraints in histological images. The results of this study suggest that much of the difficulty of stained tissue registration can be reduced to the problem of accurately identifying feature points, such as the center of nuclei.

  15. Genomewide Clonal Analysis of Lethal Mutations in the Drosophila melanogaster Eye: Comparison of the X Chromosome and Autosomes


    Call, Gerald B.; Olson, John M.; Chen, Jiong; Villarasa, Nikki; Ngo, Kathy T.; Yabroff, Allison M.; Cokus, Shawn; Pellegrini, Matteo; Bibikova, Elena; Bui, Chris; Cespedes, Albert; Chan, Cheryl; Chan, Stacy; Cheema, Amrita K.; Chhabra, Akanksha


    Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved ...

  16. Analysis of binding centers in nicotinic receptors with the aid of synthetic peptides. (United States)

    Kasheverov, I E; Kryukova, E V; Kudryavtsev, D S; Ivanov, I A; Egorova, N V; Zhmak, M N; Spirova, E N; Shelukhina, I V; Odinokov, A V; Alfimov, M V; Tsetlin, V I


    We studies the receptor-binding specificity of the synthetic peptide HAP (High Affinity Peptide) and its analogues, which are regarded as a model of the orthosteric site nicotinic acetylcholine receptors (nAChR). Using radioligand analysis, electrophysiology tests, and calcium imaging, we assessed the ability of HAP to interact with nAChR antagonists: long α-neurotoxins and α-conotoxins. A high affinity of HAP for α-bungarotoxin and the absence of its interaction with α-cobratoxin and α-conotoxins was found. The synthesized analogues of HAP in general retained the properties of the original peptide. Thus, HAP cannot be a model of a ligand-binding site.

  17. Synthetic graph generation for data-intensive HPC benchmarking: Scalability, analysis and real-world application

    Energy Technology Data Exchange (ETDEWEB)

    Powers, Sarah S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lothian, Joshua [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)


    The benchmarking effort within the Extreme Scale Systems Center at Oak Ridge National Laboratory seeks to provide High Performance Computing benchmarks and test suites of interest to the DoD sponsor. The work described in this report is a part of the effort focusing on graph generation. A previously developed benchmark, SystemBurn, allows the emulation of a broad spectrum of application behavior profiles within a single framework. To complement this effort, similar capabilities are desired for graph-centric problems. This report described the in-depth analysis of the generated synthetic graphs' properties at a variety of scales using different generator implementations and examines their applicability to replicating real world datasets.

  18. Genomewide clonal analysis of lethal mutations in the Drosophila melanogaster eye: comparison of the X chromosome and autosomes. (United States)

    Call, Gerald B; Olson, John M; Chen, Jiong; Villarasa, Nikki; Ngo, Kathy T; Yabroff, Allison M; Cokus, Shawn; Pellegrini, Matteo; Bibikova, Elena; Bui, Chris; Cespedes, Albert; Chan, Cheryl; Chan, Stacy; Cheema, Amrita K; Chhabra, Akanksha; Chitsazzadeh, Vida; Do, Minh-Tu; Fang, Q Angela; Folick, Andrew; Goodstein, Gelsey L; Huang, Cheng R; Hung, Tony; Kim, Eunha; Kim, William; Kim, Yulee; Kohan, Emil; Kuoy, Edward; Kwak, Robert; Lee, Eric; Lee, JiEun; Lin, Henry; Liu, H-C Angela; Moroz, Tatiana; Prasad, Tharani; Prashad, Sacha L; Patananan, Alexander N; Rangel, Alma; Rosselli, Desiree; Sidhu, Sohrab; Sitz, Daniel; Taber, Chelsea E; Tan, Jingwen; Topp, Kasey; Tran, PhuongThao; Tran, Quynh-Minh; Unkovic, Mary; Wells, Maggie; Wickland, Jessica; Yackle, Kevin; Yavari, Amir; Zaretsky, Jesse M; Allen, Christopher M; Alli, Latifat; An, Ju; Anwar, Abbas; Arevalo, Sonia; Ayoub, Danny; Badal, Shawn S; Baghdanian, Armonde; Baghdanian, Arthur H; Baumann, Sara A; Becerra, Vivian N; Chan, Hei J; Chang, Aileen E; Cheng, Xibin A; Chin, Mabel; Chong, Fleurette; Crisostomo, Carlyn; Datta, Sanjit; Delosreyes, Angela; Diep, Francie; Ekanayake, Preethika; Engeln, Mark; Evers, Elizabeth; Farshidi, Farzin; Fischer, Katrina; Formanes, Arlene J; Gong, Jun; Gupta, Riju; Haas, Blake E; Hahm, Vicky; Hsieh, Michael; Hui, James Z; Iao, Mei L; Jin, Sophia D; Kim, Angela Y; Kim, Lydia S-H; King, Megan; Knudsen-Robbins, Chloe; Kohanchi, David; Kovshilovskaya, Bogdana; Ku, Amy; Kung, Raymond W; Landig, Mark E L; Latterman, Stephanie S; Lauw, Stephanie S; Lee, Daniel S; Lee, Joann S; Lei, Kai C; Leung, Lesley L; Lerner, Renata; Lin, Jian-ya; Lin, Kathleen; Lim, Bryon C; Lui, Crystal P Y; Liu, Tiffany Q; Luong, Vincent; Makshanoff, Jacob; Mei, An-Chi; Meza, Miguel; Mikhaeil, Yara A; Moarefi, Majid; Nguyen, Long H; Pai, Shekhar S; Pandya, Manish; Patel, Aadit R; Picard, Paul D; Safaee, Michael M; Salame, Carol; Sanchez, Christian; Sanchez, Nina; Seifert, Christina C; Shah, Abhishek; Shilgevorkyan, Oganes H; Singh, Inderroop; Soma, Vanessa; Song, Junia J; Srivastava, Neetika; StaAna, Jennifer L; Sun, Christie; Tan, Diane; Teruya, Alison S; Tikia, Robyn; Tran, Trinh; Travis, Emily G; Trinh, Jennifer D; Vo, Diane; Walsh, Thomas; Wong, Regan S; Wu, Katherine; Wu, Ya-Whey; Yang, Nkau X V; Yeranosian, Michael; Yu, James S; Zhou, Jennifer J; Zhu, Ran X; Abrams, Anna; Abramson, Amanda; Amado, Latiffe; Anderson, Jenny; Bashour, Keenan; Beyer, Elsa; Bookatz, Allen; Brewer, Sarah; Buu, Natalie; Calvillo, Stephanie; Cao, Joseph; Chan, Amy; Chan, Jenny; Chang, Aileen; Chang, Daniel; Chang, Yuli; Chen, YiBing; Choi, Joo; Chou, Jeyling; Dang, Peter; Datta, Sumit; Davarifar, Ardy; Deravanesian, Artemis; Desai, Poonam; Fabrikant, Jordan; Farnad, Shahbaz; Fu, Katherine; Garcia, Eddie; Garrone, Nick; Gasparyan, Srpouhi; Gayda, Phyllis; Go, Sherrylene; Goffstein, Chad; Gonzalez, Courtney; Guirguis, Mariam; Hassid, Ryan; Hermogeno, Brenda; Hong, Julie; Hong, Aria; Hovestreydt, Lindsay; Hu, Charles; Huff, Devon; Jamshidian, Farid; Jen, James; Kahen, Katrin; Kao, Linda; Kelley, Melissa; Kho, Thomas; Kim, Yein; Kim, Sarah; Kirkpatrick, Brian; Langenbacher, Adam; Laxamana, Santino; Lee, Janet; Lee, Chris; Lee, So-Youn; Lee, ToHang S; Lee, Toni; Lewis, Gemma; Lezcano, Sheila; Lin, Peter; Luu, Thanh; Luu, Julie; Marrs, Will; Marsh, Erin; Marshall, Jamie; Min, Sarah; Minasian, Tanya; Minye, Helena; Misra, Amit; Morimoto, Miles; Moshfegh, Yasaman; Murray, Jessica; Nguyen, Kha; Nguyen, Cynthia; Nodado, Ernesto; O'Donahue, Amanda; Onugha, Ndidi; Orjiakor, Nneka; Padhiar, Bhavin; Paul, Eric; Pavel-Dinu, Mara; Pavlenko, Alex; Paz, Edwin; Phaklides, Sarah; Pham, Lephong; Poulose, Preethi; Powell, Russell; Pusic, Aya; Ramola, Divi; Regalia, Kirsten; Ribbens, Meghann; Rifai, Bassel; Saakyan, Manyak; Saarikoski, Pamela; Segura, Miriam; Shadpour, Farnaz; Shemmassian, Aram; Singh, Ramnik; Singh, Vivek; Skinner, Emily; Solomin, Daniel; Soneji, Kosha; Spivey, Kristin; Stageberg, Erika; Stavchanskiy, Marina; Tekchandani, Leena; Thai, Leo; Thiyanaratnam, Jayantha; Tong, Maurine; Toor, Aneet; Tovar, Steve; Trangsrud, Kelly; Tsang, Wah-Yung; Uemura, Marc; Vollmer, Emily; Weiss, Emily; Wood, Damien; Wu, Joy; Wu, Sophia; Wu, Winston; Xu, Qing; Yamauchi, Yuki; Yarosh, Will; Yee, Laura; Yen, George; Banerjee, Utpal


    Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes.

  19. Co-lethality studied as an asset against viral drug escape: the HIV protease case

    Directory of Open Access Journals (Sweden)

    Ollivier Emmanuelle


    Full Text Available Abstract Background Co-lethality, or synthetic lethality is the documented genetic situation where two, separately non-lethal mutations, become lethal when combined in one genome. Each mutation is called a "synthetic lethal" (SL or a co-lethal. Like invariant positions, SL sets (SL linked couples are choice targets for drug design against fast-escaping RNA viruses: mutational viral escape by loss of affinity to the drug may induce (synthetic lethality. Results From an amino acid sequence alignment of the HIV protease, we detected the potential SL couples, potential SL sets, and invariant positions. From the 3D structure of the same protein we focused on the ones that were close to each other and accessible on the protein surface, to possibly bind putative drugs. We aligned 24,155 HIV protease amino acid sequences and identified 290 potential SL couples and 25 invariant positions. After applying the distance and accessibility filter, three candidate drug design targets of respectively 7 (under the flap, 4 (in the cantilever and 5 (in the fulcrum amino acid positions were found. Conclusions These three replication-critical targets, located outside of the active site, are key to our anti-escape strategy. Indeed, biological evidence shows that 2/3 of those target positions perform essential biological functions. Their mutational variations to escape antiviral medication could be lethal, thus limiting the apparition of drug-resistant strains. Reviewers This article was reviewed by Arcady Mushegian, Shamil Sunyaev and Claus Wilke.

  20. Genetic analysis of Enterobius vermicularis isolated from a chimpanzee with lethal hemorrhagic colitis and pathology of the associated lesions. (United States)

    Yaguchi, Yuji; Okabayashi, Sachi; Abe, Niichiro; Masatou, Haruhisa; Iida, Shinya; Teramoto, Isao; Matsubayashi, Makoto; Shibahara, Tomoyuki


    Human pinworms, Enterobius vermicularis, are normally recognized as minor pathogens. However, a fatal case of human pinworm infection has been reported in a nonhuman primate, a zoo reared chimpanzee. Here, we histopathologically examined the lesions in tissues from the deceased chimpanzee and genetically characterized the isolated worms to investigate the pathogenicity and determine the phylogeny. We identified ulcers deep in the submucosa where many parasites were found to have invaded the lamina propria mucosa or submucous tissue. An inflammatory reaction consisting mainly of neutrophils and lymphocytes but not eosinophils was observed around the parasites, and intense hemorrhage in the lamina propria was confirmed. The parasites were morphologically similar to E. vermicularis based on the shape of the copulatory spicules. Mitochondrial cytochrome c oxidase subunit 1 gene products were amplified from worm DNA by PCR and were genetically identified as E. vermicularis based on >98.7% similarity of partial sequences. Phylogenetic analysis revealed that the sequences clustered together with other chimpanzee E. vermicularis isolates in a group which has been referred to as type C and which differs from human isolates (type A). The samples were negative for bacterial pathogens and Entamoeba histolytica indicating that E. vermicularis could be pathogenic in chimpanzees. Phylogenetic clustering of the isolates indicated that the parasite may be host specific.

  1. Histopathological effects of lethal and sub-lethal concentrations of ...

    African Journals Online (AJOL)

    The histopathological effects of lethal and sub-lethal concentrations of glyphosate on African catfish Clarias gariepinus were investigated. C. gariepinus juveniles were assessed in a static renewal bioassay for 96 hours (acute toxicity) and 28 days (chronic toxicity) using varying concentrations (0.0 mg/l 20.0 mg/l, 30.0 mg/l, ...

  2. Information Theory Analysis of Cascading Process in a Synthetic Model of Fluid Turbulence

    Directory of Open Access Journals (Sweden)

    Massimo Materassi


    Full Text Available The use of transfer entropy has proven to be helpful in detecting which is the verse of dynamical driving in the interaction of two processes, X and Y . In this paper, we present a different normalization for the transfer entropy, which is capable of better detecting the information transfer direction. This new normalized transfer entropy is applied to the detection of the verse of energy flux transfer in a synthetic model of fluid turbulence, namely the Gledzer–Ohkitana–Yamada shell model. Indeed, this is a fully well-known model able to model the fully developed turbulence in the Fourier space, which is characterized by an energy cascade towards the small scales (large wavenumbers k, so that the application of the information-theory analysis to its outcome tests the reliability of the analysis tool rather than exploring the model physics. As a result, the presence of a direct cascade along the scales in the shell model and the locality of the interactions in the space of wavenumbers come out as expected, indicating the validity of this data analysis tool. In this context, the use of a normalized version of transfer entropy, able to account for the difference of the intrinsic randomness of the interacting processes, appears to perform better, being able to discriminate the wrong conclusions to which the “traditional” transfer entropy would drive.

  3. Comparative analysis of biologic versus synthetic mesh outcomes in contaminated hernia repairs. (United States)

    Majumder, Arnab; Winder, Joshua S; Wen, Yuxiang; Pauli, Eric M; Belyansky, Igor; Novitsky, Yuri W


    Contaminated operative fields pose significant challenges for surgeons performing ventral hernia repair. Although biologic meshes have been utilized increasingly in these fields, recent evidence suggests that synthetic meshes represent a viable option. We analyzed the outcomes of biologic and synthetic mesh utilized in patients undergoing major ventral hernia repair in clean-contaminated/contaminated fields. We conducted a multicenter, retrospective review of patients undergoing open ventral hernia repair in clean-contaminated/contaminated fields using biologic or synthetic mesh. Patient and hernia details were characterized. Primary outcomes included 90-day surgical site event, surgical site infection, and hernia recurrence. A total of 126 patients undergoing major ventral hernia repair in clean-contaminated/contaminated fields (69 biologic and 57 synthetic meshes) were analyzed. Groups were similar in both patient and hernia characteristics. There were 13 (22.8%) surgical site events in the synthetic cohort compared to 29 (42.0%) in the biologic cohort, P = .024. Similarly, surgical site infections were less frequent in the synthetic group, with 7 (12.3%) vs 22 (31.9%), P = .01. With a mean follow-up of 20 months, there were more recurrences in the biologic group: 15 (26.3%) vs 4 (8.9%) in the synthetic group, P = .039. The choice of mesh for clean-contaminated/contaminated ventral hernia repair remains debatable. We demonstrated that using synthetic sublay mesh resulted in a significantly lower wound morbidity and more durable outcomes versus a similar cohort of biologic repairs. This is likely secondary to improved bacterial clearance and faster integration of macroporous synthetics. Overall, our findings not only support suitability of synthetic mesh in contaminated settings but also challenge the purported advantage of biologics in clean-contaminated/contaminated ventral hernia repairs. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Exergy analysis of synthetic biofuel production via fast pyrolysis and hydroupgrading

    International Nuclear Information System (INIS)

    Peters, Jens F.; Petrakopoulou, Fontina; Dufour, Javier


    This paper presents the first assessment of the exergetic performance of a biorefinery process based on catalytic hydroupgrading of bio-oil from fast pyrolysis. Lignocellulosic biomass is converted into bio-oil through fast pyrolysis, which is then upgraded to synthetic fuels in a catalytic hydrotreating process. The biorefinery process is simulated numerically using commercial software and analyzed using exergetic analysis. Exergy balances are defined for each component of the plant and the exergetic efficiencies and exergy destruction rates are calculated at the component, section and plant level, identifying thermodynamic inefficiencies and revealing the potential for further improvement of the process. The overall biofuel process results in an exergetic efficiency of 60.1%, while the exergetic efficiency of the upgrading process in the biorefinery alone is 77.7%. Within the biorefinery, the steam reforming reactor is the main source of inefficiencies, followed by the two hydrotreating reactors. In spite of the high operating pressures in the hydrotreating section, the compressors have little impact on the total exergy destruction. Compared to competing lignocellulosic biofuel processes, like gasification with Fischer–Tropsch synthesis or lignocellulosic ethanol processes, the examined system achieves a significantly higher exergetic efficiency. - Highlights: • Exergetic analysis of a biorefinery for bio-oil hydroupgrading. • Detailed simulation model using 83 model compounds. • Exergy destruction quantified in each component of the plant. • Exergetic efficiency and potential for improvement determined on component level. • Highest exergy destruction in the pyrolysis plant and the steam reformer


    Directory of Open Access Journals (Sweden)

    Livia Oltean


    Full Text Available Having an increased complexity, the internationalization process of small and medium- sized enterprises (SMEs becomes, in the context of globalization and of the freedom of circulation of goods, services, and capital, a decisive factor of both the evolution of the company and the economic force distribution report on the market. The evolution of the world economic system opened a wide action field for small and medium sized companies, who had to adapt to new rules. The internationalization of SMEs is no longer an option, but it becomes a condition of their existence. A high importance in this process belongs to the way decisions are made, both regarding the target market and the entry option, the way entry barriers are overcome and the promotional techniques in this extended business environment. A synthetic analysis of the decisional factors and process is needed in order to fully and correctly understand the internationalization strategies adopted by SMEs. This paper is built around three major objectives, with the scope of determining the SMEs’ internationalization decisions, as well s the impediments met in the process. The paper contributes to the literature in the field of the internationalization of SMEs through the analysis and interpretation of the results acquired during the study regarding their behavior towards the activity expansion on international markets.

  6. Fourier analysis of a new P1 synthetic acceleration for Sn transport equations

    International Nuclear Information System (INIS)

    Turcksin, B.; Ragusa, J. C.


    In this work, is derived a new P1 synthetic acceleration scheme (P1SA) for the S N transport equation and analyze its convergence properties through the means of a Fourier analysis. The Fourier analysis is carried out for both continuous (i.e., not spatially discretized) S N equations and linear discontinuous Fem discretization. We show, thanks to the continuous analysis, that the scheme is unstable when the anisotropy is important (μ - >0.5). However, the discrete analysis shows that when cells are large in comparison to the mean free path, the spectral radius decreases and the acceleration scheme becomes effective, even for highly anisotropic scattering. In charged particles transport, scattering is highly anisotropic and mean free paths are very small and, thus, this scheme could be of interest. To use the P1SA when cells are small and anisotropy is important, the scheme is modified by altering the update of the accelerated flux or by using either K transport sweeps before the application of P1SA. The update scheme performs well as long as μ - - ≥0.9, the modified update scheme is unstable. The multiple transport sweeps scheme is convergent with an arbitrary μ - but the spectral radius increases when scattering is isotropic. When anisotropic increases, the frequency of use of the acceleration scheme needs to be decreased. Even if the P1SA is used less often, the spectral radius is significantly smaller when compared with a method that does not use it for high anisotropy (μ - ≥0.5). It is interesting to notice that using P1SA every two iterations gives the same spectral radius than the update method when μ - ≥0.5 but it is much less efficient when μ - <0.5. (Author)

  7. What Are Reasons for the Large Gender Differences in the Lethality of Suicidal Acts? An Epidemiological Analysis in Four European Countries

    NARCIS (Netherlands)

    Mergl, Roland; Koburger, Nicole; Heinrichs, Katherina; Szekely, Andras; Toth, Monika Ditta; Coyne, James; Quintao, Sonia; Arensman, Ella; Coffey, Claire; Maxwell, Margaret; Vaernik, Airi; van Audenhove, Chantal; McDaid, David; Sarchiapone, Marco; Schmidtke, Armin; Genz, Axel; Gusmao, Ricardo; Hegerl, Ulrich


    Background In Europe, men have lower rates of attempted suicide compared to women and at the same time a higher rate of completed suicides, indicating major gender differences in lethality of suicidal behaviour. The aim of this study was to analyse the extent to which these gender differences in

  8. Virtual analysis of structurally diverse synthetic analogs as inhibitors of snake venom secretory phospholipase A2. (United States)

    Sivaramakrishnan, V; Ilamathi, M; Ghosh, K S; Sathish, S; Gowda, T V; Vishwanath, B S; Rangappa, K S; Dhananjaya, B L


    Due to the toxic pathophysiological role of snake venom phospholipase A2 (PLA2 ), its compelling limitations to anti-venom therapy in humans and the need for alternative therapy foster considerable pharmacological interest towards search of PLA2 specific inhibitors. In this study, an integrated approach involving homology modeling, molecular dynamics and molecular docking studies on VRV-PL-V (Vipera russellii venom phospholipase A2 fraction-V) belonging to Group II-B secretory PLA2 from Daboia russelli pulchella is carried out in order to study the structure-based inhibitor design. The accuracy of the model was validated using multiple computational approaches. The molecular docking study of this protein was undertaken using different classes of experimentally proven, structurally diverse synthetic inhibitors of secretory PLA2 whose selection is based on IC50 value that ranges from 25 μM to 100 μM. Estimation of protein-ligand contacts by docking analysis sheds light on the importance of His 47 and Asp 48 within the VRV-PL-V binding pocket as key residue for hydrogen bond interaction with ligands. Our virtual analysis revealed that compounds with different scaffold binds to the same active site region. ADME analysis was also further performed to filter and identify the best potential specific inhibitor against VRV-PL-V. Additionally, the e-pharmacophore was generated for the best potential specific inhibitor against VRV-PL-V and reported here. The present study should therefore play a guiding role in the experimental design of VRV-PL-V inhibitors that may provide better therapeutic molecular models for PLA2 recognition and anti-ophidian activity. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Rare earth element concentrations in geological and synthetic samples using synchrotron X-ray fluorescence analysis (United States)

    Chen, J.R.; Chao, E.C.T.; Back, J.M.; Minkin, J.A.; Rivers, M.L.; Sutton, S.R.; Cygan, G.L.; Grossman, J.N.; Reed, M.J.


    The concentrations of rare earth elements (REEs) in specific mineral grains from the Bayan Obo ore deposit and synthetic high-silica glass samples have been measured by synchrotron X-ray fluorescence (SXRF) analysis using excitation of the REE K lines between 33 and 63 keV. Because SXRF, a nondestructive analytical technique, has much lower minimum detection limits (MDLs) for REEs, it is an important device that extends the in situ analytical capability of electron probe microanalysis (EPMA). The distribution of trace amounts of REEs in common rock-forming minerals, as well as in REE minerals and minerals having minor quantities of REEs, can be analyzed with SXRF. Synchrotron radiation from a bending magnet and a wiggler source at the National Synchrotron Light Source, Brookhaven National Laboratory, was used to excite the REEs. MDLs of 6 ppm (La) to 26 ppm (Lu) for 3600 s in 60-??m-thick standard samples were obtained with a 25-??m diameter wiggler beam. The MDLs for the light REEs were a factor of 10-20 lower than the MDLs obtained with a bending magnet beam. The SXRF REE concentrations in mineral grains greater than 25 ??m compared favorably with measurements using EPMA. Because EPMA offered REE MDLs as low as several hundred ppm, the comparison was limited to the abundant light REEs (La, Ce, Pr, Nd). For trace values of medium and heavy REEs, the SXRF concentrations were in good agreement with measurements using instrumental neutron activation analysis (INAA), a bulk analysis technique. ?? 1993.

  10. The effect of crustal anisotropy on SKS splitting analysis - synthetic models and real data observations (United States)

    Latifi, Koorosh; Kaviani, Ayoub; Rümpker, Georg; Mahmoodabadi, Meysam; Ghassemi, Mohammad R.; Sadidkhouy, Ahmad


    The contribution of crustal anisotropy to the observation of SKS splitting parameters is often assumed to be negligible. Based on synthetic models we show that the impact of crustal anisotropy on the SKS splitting parameters can be significant even in the case of moderate to weak anisotropy within the crust. In addition, real-data examples reveal that significant azimuthal variations in SKS splitting parameters can be caused by crustal anisotropy. Ps-splitting analysis of receiver functions can be used to infer the anisotropic parameters of the crust. These crustal splitting parameters may then be used to constrain the inversion of SKS apparent splitting parameters to infer the anisotropy of the mantle. The observation of SKS splitting for different azimuths is indispensable to verify the presence or absence of multiple layers of anisotropy beneath a seismic station. By combining SKS and RF observations in different azimuths at a station, we are able to uniquely decipher the anisotropic parameters of crust and upper mantle.

  11. Synthetic oligomer analysis using atmospheric pressure photoionization mass spectrometry at different photon energies

    Energy Technology Data Exchange (ETDEWEB)

    Desmazières, Bernard [Global Bioenergies, 5 rue Henri Desbruyeres, 91030 Evry (France); Legros, Véronique [CNRS, UMR8587, Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry (France); Giuliani, Alexandre [Synchrotron SOLEIL, L’Orme des Merisiers, Saint-Aubin, 91192 Gif-sur-Yvette (France); UAR1008, CEPIA, INRA, Rue de la Geraudiere, F-44316 Nantes (France); Buchmann, William, E-mail: [CNRS, UMR8587, Université d’Evry-Val-d’Essonne, Laboratoire Analyse et Modélisation pour la Biologie et l’Environnement, F-91025 Evry (France)


    Graphical abstract: Atmospheric pressure photoIonization mass spectra of synthetic oligomers were recorded in the negative mode by varying the photon energy using synchrotron radiation. Photon energy required for an efficient ionization of the polymer was correlated to ionization potential of the solvent (for example 9.4 eV for tetrahydrofuran). -- Highlights: •Atmospheric pressure photoionization was performed using synchrotron radiation. •Photoionization of oligomers in THF with 10% CH{sub 2}Cl{sub 2} produces intact [M + Cl]{sup −} ions. •The photon energy required corresponds to ionization potential of the solvent. •Polymer distributions depend on source parameters such T °C and applied voltages. •Liquid chromatography was coupled to MS using an APPI interface for polymer analysis. -- Abstract: Atmospheric pressure photoionization (APPI) followed by mass spectrometric detection was used to ionize a variety of polymers: polyethylene glycol, polymethyl methacrylate, polystyrene, and polysiloxane. In most cases, whatever the polymer or the solvent used (dichloromethane, tetrahydrofuran, hexane, acetone or toluene), only negative ion mode produced intact ions such as chlorinated adducts, with no or few fragmentations, in contrast to the positive ion mode that frequently led to important in-source fragmentations. In addition, it was shown that optimal detection of polymer distributions require a fine tuning of other source parameters such as temperature and ion transfer voltage. Series of mass spectra were recorded in the negative mode, in various solvents (dichloromethane, tetrahydrofuran, hexane, toluene, and acetone), by varying the photon energy from 8 eV up to 10.6 eV using synchrotron radiation. To these solvents, addition of a classical APPI dopant (toluene or acetone) was not necessary. Courtesy of the synchrotron radiation, it was demonstrated that the photon energy required for an efficient ionization of the polymer was correlated to the

  12. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer (United States)


    6. Varma DR, Sareen KN, Roy AK, & Gural ML. Oral contraceptive . Part IV. Hormonal and antihormonal effects of rottlerin. Indian J Physiol...Pharmacol. 3:246-54 (1959). 7. Varma DR, Sareen KN, Roy AK, & Gural ML. Oral contraceptive . Part III. Further observations on the antifertility effect...Prostate Cancer PRINCIPAL INVESTIGATOR: Douglas V. Faller, Ph.D., M.D. CONTRACTING

  13. Synthetic antigens, radiolabelled derivatives thereof, and methods of analysis using such derivatives

    International Nuclear Information System (INIS)

    Eisenhardt, W.A. Jr.; Hedaya, E.; Theodoropulos, S.


    This patent claim on behalf of Union Carbide Corporation, relates to a method of carrying out a competitive binding radioassay of a compound of interest in a clinical sample, using isocyanates labelled with radioiodine as synthetic antigens. (U.K.)

  14. A kinematic analysis of the spine during rugby scrummaging on natural and synthetic turfs. (United States)

    Swaminathan, Ramesh; Williams, Jonathan M; Jones, Michael D; Theobald, Peter S


    Artificial surfaces are now an established alternative to grass (natural) surfaces in rugby union. Little is known, however, about their potential to reduce injury. This study characterises the spinal kinematics of rugby union hookers during scrummaging on third-generation synthetic (3G) and natural pitches. The spine was sectioned into five segments, with inertial sensors providing three-dimensional kinematic data sampled at 40 Hz/sensor. Twenty-two adult, male community club and university-level hookers were recruited. An equal number were analysed whilst scrummaging on natural or synthetic turf. Players scrummaging on synthetic turf demonstrated less angular velocity in the lower thoracic spine for right and left lateral bending and right rotation. The general reduction in the range of motion and velocities, extrapolated over a prolonged playing career, may mean that the synthetic turf could result in fewer degenerative injuries. It should be noted, however, that this conclusion considers only the scrummaging scenario.

  15. Atomic force microscopy analysis of synthetic membranes applied in release studies

    International Nuclear Information System (INIS)

    Olejnik, Anna; Nowak, Izabela


    Graphical abstract: - Highlights: • We compare eight synthetic membranes by atomic force microscopy. • We predict the behavior of membranes in the release experiments. • The polymeric synthetic membranes varied in shape and size. • We detect substructures in pores of cellulose esters and nylon membranes. • Substructures limit the release rate of active compound. - Abstract: Synthetic membranes are commonly used in drug release studies and are applied mostly in quality control. They contain pores through which the drug can be diffused directly into the receptor fluid. Investigation of synthetic membranes permits determination of their structure and characterization of their properties. We suggest that the preliminary characterization of the membranes can be relevant to the interpretation of the release results. The aim of this study was to compare eight synthetic membranes by using atomic force microscopy in order to predict and understand their behavior in the release experiments. The results proved that polytetrafluoroethylene membrane was not suitable for the release study of tetrapeptide due to its hydrophobic nature, thickness and the specific structure with high trapezoid shaped blocks. The additional substructures in pores of mixed cellulose esters and nylon membranes detected by AFM influenced the diffusion rate of the active compound. These findings indicate that the selection of the membrane for the release studies should be performed cautiously by taking into consideration the membrane properties and by analyzing them prior the experiment.

  16. Synthetic Aperture Radar Interferometry Analysis of Ground Deformation within the Coso Geothermal Site, California (United States)

    Brawner, Erik

    Earth's surface movement may cause as a potential hazard to infrastructure and people. Associated earthquake hazards pose a potential side effect of geothermal activity. Modern remote sensing techniques known as Interferometric Synthetic Aperture Radar (InSAR) can measure surface change with a high degree of precision to mm scale movements. Previous work has identified a deformation anomaly within the Coso Geothermal site in eastern California. Surface changes have not been analyzed since the 1990s, allowing a decade of geothermal production impact to occur since previously assessed. In this study, InSAR data was acquired and analyzed between the years 2005 and 2010. Acquired by the ENVISAT satellite from both ascending and descending modes. This provides an independent dataset from previous work. Incorporating data generated from a new sensor covering a more modern temporal study period. Analysis of this time period revealed a subsidence anomaly in correlation with the extents of the geothermal production area under current operation. Maximum subsidence rates in the region reached approximately 3.8 cm/yr. A similar rate assessed from previous work throughout the 1990s. The correlation of subsidence patterns suggests a linear source of deformation from measurements spanning multiple decades. Regions of subsidence branch out from the main anomaly to the North-Northeast and to the South where additional significant peaks of subsidence occurring. The extents of the deformation anomaly directly correlate with the dispersal of geothermal production well site locations. Depressurization within the geothermal system provides a leading cause to surface subsidence from excessive extraction of hydrothermal fluids. As a result of minimal reinjection of production fluids.

  17. Quantum synthetic aperture radar (United States)

    Lanzagorta, Marco; Jitrik, Oliverio; Uhlmann, Jeffrey; Venegas-Andraca, Salvador E.


    Synthetic aperture radar (SAR) uses sensor motion to generate finer spatial resolution of a given target area. In this paper we explore the theoretical potential of quantum synthetic aperture quantum radar (QSAR). We provide theoretical analysis and simulation results which suggest that QSAR can provide improved detection performance over classical SAR in the high-noise low-brightness regime.

  18. Energy System Analysis of Solid Oxide Electrolysis cells for Synthetic Fuel Production

    DEFF Research Database (Denmark)

    Ridjan, Iva; Mathiesen, Brian Vad; Connolly, David


    system by balancing and storing excess electricity is essential. One of the possible solutions is the use of electrolysers for the production of synthetic fuels based on carbon sources and hydrogen, providing a way to store electricity in the form of fuel that can be either used in other energy sectors...... that require high energy density fuels or reused for power generation. The purpose of this paper is to provide an overview of fuel production cost for two types of synthetic fuels – methanol and methane, and comparable costs of biodiesel, bioethanol and biogas....

  19. The Bioethicist Who Cried "Synthetic Biology":An Analysis of the Function of Bioterrorism Predictions in Bioethics


    Holm, Søren


    This article analyzes a specter that has haunted bioethics almost since its inception, namely the specter of the misuse of biotechnology by maleficent agents bent on mass destruction, or the complete eradication of human kind and life as we know it. The article provides a general account of why bioethicists cry "catastrophic bioterrorism potential" when new biotechnologies emerge, and an analysis of the arguments that flow from the prediction, especially in relation to synthetic biology.

  20. Synthetic Brainbows

    KAUST Repository

    Wan, Y.


    Brainbow is a genetic engineering technique that randomly colorizes cells. Biological samples processed with this technique and imaged with confocal microscopy have distinctive colors for individual cells. Complex cellular structures can then be easily visualized. However, the complexity of the Brainbow technique limits its applications. In practice, most confocal microscopy scans use different florescence staining with typically at most three distinct cellular structures. These structures are often packed and obscure each other in rendered images making analysis difficult. In this paper, we leverage a process known as GPU framebuffer feedback loops to synthesize Brainbow-like images. In addition, we incorporate ID shuffing and Monte-Carlo sampling into our technique, so that it can be applied to single-channel confocal microscopy data. The synthesized Brainbow images are presented to domain experts with positive feedback. A user survey demonstrates that our synthetic Brainbow technique improves visualizations of volume data with complex structures for biologists.

  1. Hair analysis as a tool to evaluate the prevalence of synthetic cannabinoids in different populations of drug consumers. (United States)

    Salomone, A; Luciano, C; Di Corcia, D; Gerace, E; Vincenti, M


    Among the new psychoactive products, herbal mixtures containing synthetic cannabimimetics are likely the most abused worldwide. In this study, a specific ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the detection of 23 synthetic cannabinoids in hair samples was developed in order to (1) expand the number of screened compounds, coherent with new substances emerging in the European territory, (2) evaluate their consumption on a large period of examination, and (3) evaluate the diffusion of cannabimimetics among different populations of drug consumers. The method employs digestion of hair sample with NaOH followed by extraction with n-hexane/ethylacetate, and injection into the UHPLC-MS/MS system. After validation, the method was applied to the analysis of 344 hair samples previously tested in our laboratory for the most common drugs. Overall, 15 samples were found positive for at least one synthetic cannabinoid. Coherent with previously published results, the present data show that young males, former or still active Cannabis consumers, represent the population most often involved in synthetic cannabimimetics consumption. Several cases of poly-abuse were also determined. The drug most frequently detected was JWH-073 (11 samples) generally at low concentration (mean 7.69 ± 14.4 pg/mg, median 1.9 pg/mg, range 1.6-50.5 pg/mg), followed by JWH-122 (8 samples, mean concentration: 544 ± 968 pg/mg, median 28.4 pg/mg, range 7.4-2800 pg/mg). Other detected drugs included JWH-250, JWH-081, JWH-018, JWH-210, JWH-019, and AM-1220. For several positive samples, the synthetic cannabinoid concentration was lower than 50 pg/mg, underlining the need for established cut-off values for discrimination between chronic consumption and occasional use (or external contamination). Copyright © 2013 John Wiley & Sons, Ltd.

  2. Analysis of the synthetic house-tree-person drawing test for developmental disorder. (United States)

    Fujii, Chikako; Okada, Ayumi; Akagi, Tomoko; Shigeyasu, Yoshie; Shimauchi, Aya; Hosogi, Mizuho; Munemori, Eriko; Ocho, Keiko; Morishima, Tsuneo


    Some patients cannot draw three subjects on the same page during the synthetic house-tree-person drawing test (S-HTP). We call this phenomenon "no synthetic sign". The aim of this study was to clarify the pathological meaning of no synthetic sign and investigate its use for the early detection of developmental disorders at a pediatric primary care center. We administered the S-HTP to 283 people who consulted the child psychosomatic medical clinic of Okayama University Hospital in 2007-2012. We diagnosed developmental disability based on DSM-IV-TR criteria and compared findings between the different diagnostic groups. A total of 241 patients completed the S-HTP (S-HTP group) and 22 patients were not able to complete the S-HTP, but did complete the HTP (an original version of the S-HTP) or tree test (HTP group). Significantly more people in the HTP group had autism spectrum disorder (ASD) compared with the S-HTP group. Full-scale intelligence quotient was significantly lower in the HTP group compared with the S-HTP group. There were two types of patients with no synthetic sign. The first involved patients with a suspected mental age younger than 5 years 11 months. The second type consisted of patients with ASD. Although drawing ability reflects multiple domains, it may help in early identification of children with developmental problems and facilitate earlier initiation of interventions. © 2015 Japan Pediatric Society.

  3. Chemical and Physical Analysis Methods for Characterizing Tire Crumb Rubber Used in Synthetic Turf Fields (United States)

    Tire crumb rubber from recycled tires is widely used as infill material in synthetic turf fields in the United States. Recycled crumb rubber is a complex and potentially variable matrix with many metal, VOC, and SVOC constituents, presenting challenges for characterization and ex...

  4. Functional analysis of synthetic insectatachykinin analogs on recombinant neurokinin receptor expressing cell lines

    NARCIS (Netherlands)

    Torfs, H.; Akerman, K.E.; Nachman, R.J.; Oonk, H.B.; Detheux, M.; Poels, J.; Loy, van T.; Loof, A.; Meloen, R.H.; Vassart, G.; Parmentier, M.; Broeck, van den J.


    The activity of a series of synthetic tachykinin-like peptide analogs was studied by means of microscopic calcium imaging on recombinant neurokinin receptor expressing cell lines. A C-terminal pentapeptide (FTGMRa) is sufficient for activation of the stomoxytachykinin receptor (STKR) expressed in

  5. Synthetic methods in phase equilibria: A new apparatus and error analysis of the method

    DEFF Research Database (Denmark)

    Fonseca, José; von Solms, Nicolas


    A new apparatus for the study of high-pressure phase equilibria using a synthetic method is described. The apparatus was especially developed for the study of solubilities of gases in condensed phases, at temperatures ranging from 243 K to 353 K and pressures up to 20 MPa. The quality of the equi...

  6. Molecular analysis of genetic fidelity in Cannabis sativa L. plants grown from synthetic (encapsulated) seeds following in vitro storage. (United States)

    Lata, Hemant; Chandra, Suman; Techen, Natascha; Khan, Ikhlas A; ElSohly, Mahmoud A


    The increasing utilization of synthetic (encapsulated) seeds for germplasm conservation and propagation necessitates the assessment of genetic stability of conserved propagules following their plantlet conversion. We have assessed the genetic stability of synthetic seeds of Cannabis sativa L. during in vitro multiplication and storage for 6 months at different growth conditions using inter simple sequence repeat (ISSR) DNA fingerprinting. Molecular analysis of randomly selected plants from each batch was conducted using 14 ISSR markers. Of the 14 primers tested, nine produced 40 distinct and reproducible bands. All the ISSR profiles from in vitro stored plants were monomorphic and comparable to the mother plant which confirms the genetic stability among the clones. GC analysis of six major cannabinoids [Δ(9)-tetrahydrocannabinol, tetrahydrocannabivarin, cannabidiol, cannabichromene, cannabigerol and cannabinol] showed homogeneity in the re-grown clones and the mother plant with insignificant differences in cannabinoids content, thereby confirming the stability of plants derived from synthetic seeds following 6 months storage. © Springer Science+Business Media B.V. 2011

  7. Genome-wide association for grain morphology in synthetic hexaploid wheats using digital imaging analysis (United States)


    Background Grain size and shape greatly influence grain weight which ultimately enhances grain yield in wheat. Digital imaging (DI) based phenomic characterization can capture the three dimensional variation in grain size and shape than has hitherto been possible. In this study, we report the results from using digital imaging of grain size and shape to understand the relationship among different components of this trait, their contribution to enhance grain weight, and to identify genomic regions (QTLs) controlling grain morphology using genome wide association mapping with high density diversity array technology (DArT) and allele-specific markers. Results Significant positive correlations were observed between grain weight and grain size measurements such as grain length (r = 0.43), width, thickness (r = 0.64) and factor from density (FFD) (r = 0.69). A total of 231 synthetic hexaploid wheats (SHWs) were grouped into five different sub-clusters by Bayesian structure analysis using unlinked DArT markers. Linkage disequilibrium (LD) decay was observed among DArT loci > 10 cM distance and approximately 28% marker pairs were in significant LD. In total, 197 loci over 60 chromosomal regions and 79 loci over 31 chromosomal regions were associated with grain morphology by genome wide analysis using general linear model (GLM) and mixed linear model (MLM) approaches, respectively. They were mainly distributed on homoeologous group 2, 3, 6 and 7 chromosomes. Twenty eight marker-trait associations (MTAs) on the D genome chromosomes 2D, 3D and 6D may carry novel alleles with potential to enhance grain weight due to the use of untapped wild accessions of Aegilops tauschii. Statistical simulations showed that favorable alleles for thousand kernel weight (TKW), grain length, width and thickness have additive genetic effects. Allelic variations for known genes controlling grain size and weight, viz. TaCwi-2A, TaSus-2B, TaCKX6-3D and TaGw2-6A, were also associated

  8. Assessing the experience of using synthetic cannabinoids by means of interpretative phenomenological analysis. (United States)

    Kassai, Szilvia; Pintér, Judit Nóra; Rácz, József; Böröndi, Brigitta; Tóth-Karikó, Tamás; Kerekes, Kitti; Gyarmathy, V Anna


    New psychoactive substances (NPS) have been increasingly consumed by people who use drugs in recent years, which pose a new challenge for treatment services. One of the largest groups of NPS is synthetic cannabinoids (SCs), which are intended as a replacement to cannabis. While there is an increasing body of research on the motivation and the effects associated with SC use, little is known about the subjective interpretation of SC use by the people who use drugs themselves. The aim of this study was to examine the experiences and personal interpretations of SC use of users who were heavily dependent on SC and are in treatment. A qualitative research method was applied in order to explore unknown and personal aspects of SC use. Semi-structured interviews were conducted with six participants who had problematic SC use and entered treatment. The research was conducted in Hungary in 2015. We analyzed data using interpretative phenomenological analysis (IPA). Participants perceived SCs to be unpredictable: their initial positive experiences quickly turned negative. They also reported that SCs took over their lives both interpersonally and intrapersonally: the drug took their old friends away, and while initially it gave them new ones, in the end it not only made them asocial but the drug became their only friend, it hijacked their personalities and made them addicted. Participants experienced rapid development of effects and they had difficulties interpreting or integrating these experiences. The rapid alteration of effects and experiences may explain the severe psychopathological symptoms, which may be important information for harm reduction and treatment services. Since, these experiences are mostly unknown and unpredictable for people who use SCs, a forum where they could share their experiences could have a harm reducing role. For a harm reduction point of view of SCs, which are underrepresented in literature, it is important to emphasize the impossibility of

  9. Synthetic Methods for Ester Bond Formation and Conformational Analysis of Ester-Containing Carbohydrates (United States)

    Hackbusch, Sven

    This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general. Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity dependent on the presence or absence of an achiral amine catalyst. In particular, this work establishes a structure-activity relationship with regard to the trans-2-substituent and its role as a chiral auxiliary in the reversal of diastereoselectivity. In the second part, the synthesis of various ester-linked carbohydrate derivatives, and their conformational analysis is presented. Using multidimensional NMR experiments and computational methods, the compounds' solution-phase structures were established and the effect of the ester functional group on the molecules' flexibility and three-dimensional (3D) structure was investigated and compared to ether or glycosidic linkages. To aid in this, a novel Karplus equation for the C(sp2)OCH angle in ester-linked carbohydrates was developed on the basis of a model ester-linked carbohydrate. This equation describes the sinusoidal relationship between the C(sp2)OCH dihedral angle and the corresponding 3JCH coupling constant that can be determined from a J-HMBC NMR experiment. The insights from this research will be useful in describing the 3D structure of naturally occurring and lab-made ester-linked derivatives of carbohydrates, as well as guiding the de novo-design of

  10. A method for the analysis of natural and synthetic folate in foods. (United States)

    Doherty, Robert F; Beecher, Gary R


    The essentiality of dietary folates for human beings has been known for many years. Over the shorter term, biological activities associated with several human maladies and the attenuation of biomarkers for several chronic diseases also have been assigned to folates. In the United States, these observations have led to the addition of folic acid to several foods and food ingredients (food fortification) and to dietary recommendations that assign biological activity to each of the forms of folate in the food supply. There currently is unavailable a robust, instrumental procedure that will distinguish between naturally occurring food folates and synthetic folic acid as part of the routine analysis of foods. The procedure proposed in this publication is unique in that it uses "off-the-shelf" supplies and instrumentation, to the extent possible, and was developed with "normal" corporate work schedules in mind. This method takes advantage of the tri-enzyme food digestion and folate deconjugation steps but was optimized with a commercially available rat plasma as the source of conjugase. A high-capacity styrene-divinylbenzene-based solid-phase extraction column was identified, and conditions were developed for quantitative recovery of 5-methyltetrahydrofolate and folic acid (FA) with it. The various forms of food folates are separated on a C-18 high-performance liquid chromatography (HPLC) column which is resistant to degradation at low pH. As a result, the mobile phase was simplified to a gradient of low-pH phosphate buffer (pH 2.2) and acetonitrile. Although FA does not exhibit fluorescence, a UV-induced photolysis system was added, which is controlled by the HPLC system, so that an appropriate segment of the HPLC column effluent is subjected to photolytic conditions and, thereby, FA can be measured as a fluorescent product. The application of the system was verified by analyzing several certified reference materials and foods and comparing results with certified values

  11. Beyond Cost-Benefit Analysis in the Governance of Synthetic Biology. (United States)

    Wallach, Wendell; Saner, Marc; Marchant, Gary


    For many innovations, oversight fits nicely within existing governance mechanisms; nevertheless, others pose unique public health, environmental, and ethical challenges. Synthetic artemisinin, for example, has many precursors in laboratory-developed drugs that emulate natural forms of the same drug. The policy challenges posed by synthetic artemisinin do not differ significantly in kind from other laboratory-formulated drugs. Synthetic biofuels and gene drives, however, fit less clearly into existing governance structures. How many of the new categories of products require new forms of regulatory oversight, or at least extensive forms of testing, remains unclear. Any effort to improve the governance of synthetic biology should start with a rich understanding of the different possible science-policy interfaces that could help to inform governance. CBA falls into a subset of the overall range of possibilities, and which interface is appropriate may turn out to depend on context, on the demands of the decision at hand. In what follows, we lay out a typology of interfaces. After that, we turn to the question of how to draw upon the range of possible interfaces and effectively address the factual and moral complexities of emerging technologies. We propose a governance model built around structures that we call "governance coordinating committees." GCCs are intended to be mechanisms for accommodating the complexities of innovations that have far-ranging societal impacts. The production of biofuels, for example, could contaminate water supplies and have a destructive environmental impact if not managed correctly. The introduction of a gene drive could have economic and environmental impacts that are not restricted to one nation. Forging appropriate means for determining and evaluating those societal impacts, to the best of a corporation's, industry's, or government's ability, is central to responsible research and innovation. Public policy must be shaped in a manner that

  12. Quantitative wake analysis of a freely swimming fish using 3D synthetic aperture PIV


    Mendelson, Leah Rose; Techet, Alexandra H.


    Synthetic aperture PIV (SAPIV) is used to quantitatively analyze the wake behind a giant danio (Danio aequipinnatus) swimming freely in a seeded quiescent tank. The experiment is designed with minimal constraints on animal behavior to ensure that natural swimming occurs. The fish exhibits forward swimming and turning behaviors at speeds between 0.9 and 1.5 body lengths/second. Results show clearly isolated and linked vortex rings in the wake structure, as well as the thrust jet coming off of ...

  13. Oral Fluid vs. Urine Analysis to Monitor Synthetic Cannabinoids and Classic Drugs Recent Exposure. (United States)

    Blandino, Vincent; Wetzel, Jillian; Kim, Jiyoung; Haxhi, Petrit; Curtis, Richard; Concheiro, Marta


    Urine is a common biological sample to monitor recent drug exposure, and oral fluid is an alternative matrix of increasing interest in clinical and forensic toxicology. Limited data are available about oral fluid vs. urine drug disposition, especially for synthetic cannabinoids. To compare urine and oral fluid as biological matrices to monitor recent drug exposure among HIV-infected homeless individuals. Seventy matched urine and oral fluid samples were collected from 13 participants. Cannabis, amphetamines, benzodiazepines, cocaine and opiates were analyzed in urine by the enzyme-multipliedimmunoassay- technique and in oral fluid by liquid chromatography tandem mass spectrometry (LCMSMS). Eleven synthetic cannabinoids were analyzed in urine and in oral fluid by LC-MSMS. Five oral fluid samples were positive for AB-FUBINACA. In urine, 4 samples tested positive for synthetic cannabinoids PB-22, 5-Fluoro-PB-22, AB-FUBINACA, and metabolites UR-144 5-pentanoic acid and UR-144 4-hydroxypentyl. In only one case, oral fluid and urine results matched, both specimens being AB-FUBINACA positive. For cannabis, 40 samples tested positive in urine and 30 in oral fluid (85.7% match). For cocaine, 37 urine and 52 oral fluid samples were positive (75.7% match). Twenty-four urine samples were positive for opiates, and 25 in oral fluid (81.4% match). For benzodiazepines, 23 samples were positive in urine and 25 in oral fluid (85.7% match). These results offer new information about drugs disposition between urine and oral fluid. Oral fluid is a good alternative matrix to urine for monitoring cannabis, cocaine, opiates and benzodiazepines recent use; however, synthetic cannabinoids showed mixed results. Copyright© Bentham Science Publishers; For any queries, please email at

  14. Atomic force microscopy analysis of synthetic membranes applied in release studies (United States)

    Olejnik, Anna; Nowak, Izabela


    Synthetic membranes are commonly used in drug release studies and are applied mostly in quality control. They contain pores through which the drug can be diffused directly into the receptor fluid. Investigation of synthetic membranes permits determination of their structure and characterization of their properties. We suggest that the preliminary characterization of the membranes can be relevant to the interpretation of the release results. The aim of this study was to compare eight synthetic membranes by using atomic force microscopy in order to predict and understand their behavior in the release experiments. The results proved that polytetrafluoroethylene membrane was not suitable for the release study of tetrapeptide due to its hydrophobic nature, thickness and the specific structure with high trapezoid shaped blocks. The additional substructures in pores of mixed cellulose esters and nylon membranes detected by AFM influenced the diffusion rate of the active compound. These findings indicate that the selection of the membrane for the release studies should be performed cautiously by taking into consideration the membrane properties and by analyzing them prior the experiment.

  15. Coherent Performance Analysis of the HJ-1-C Synthetic Aperture Radar

    Directory of Open Access Journals (Sweden)

    Li Hai-ying


    Full Text Available Synthetic Aperture Radar (SAR is a coherent imaging radar. Hence, coherence is critical in SAR imaging. In a coherent system, several sources can degrade performance. Based on the HJ-1-C SAR system implementation and sensor characteristics, this study evaluates the effect of frequency stability and pulse-to-pulse timing jitter on the SAR coherent performance. A stable crystal oscillator with short-term stability of 10×1.0−10 / 5 ms is used to generate the reference frequency by using a direct multiplier and divider. Azimuth ISLR degradation owing to the crystal oscillator phase noise is negligible. The standard deviation of the pulse-to-pulse timing jitter of HJ-1-C SAR is lower than 2ns (rms and the azimuth random phase error in the synthetic aperture time slightly degrades the side lobe of the azimuth impulse response. The mathematical expressions and simulation results are presented and suggest that the coherent performance of the HJ-1-C SAR system meets the requirements of synthetic aperture radar imaging.

  16. Synthetic Cannabinoids

    Directory of Open Access Journals (Sweden)

    Aslihan Okan Ibiloglu


    Full Text Available Synthetic cannabinoids which is a subgroup of cannabinoids are commonly used for recreational drug use throughout the whole world. Although both marijuana and synthetic cannabinoids stimulate the same receptors, cannabinoid receptor 1 (CB1 and cannabinoid receptor 2 (CB2, studies have shown that synthetic cannabinoids are much more potent than marijuana. The longer use of synthetic cannabinoids can cause severe physical and psychological symptoms that might even result in death, similar to many known illicit drugs. Main treatment options mostly involve symptom management and supportive care. The aim of this article is to discuss clinical and pharmacological properties of the increasingly used synthetic cannabinoids. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2017; 9(3.000: 317-328

  17. Volcanic Ash and SO2 retrievals using synthetic MODIS TIR data: comparison between inversion procedures and sensitivity analysis

    Directory of Open Access Journals (Sweden)

    Stefano Corradini


    Full Text Available In this work the volcanic ash and SO2 retrievals obtained by applying three different procedures (LUT - Look Up Table, NN - Neural Network and VPR - Volcanic Plume Removal on MODIS Thermal InfraRed (TIR synthetic measurements have been compared. The synthetic measurements are generated using MODTRAN Radiative Transfer Model (RTM for defined volcanic cloud configurations. The results, presented as the percentage difference between the retrieved ash and SO2 total masses and the true values used for the synthetic data generation, indicate maximum differences of +/- 15% and +/- 10% for all the procedures and for ash and SO2 retrievals respectively. A sensitivity analysis has been also realized to investigate the influence of volcanic cloud altitude and water vapour profile on SO2 retrievals at 7.3 and 8.6 μm. Results confirm the high sensitivity of the 7.3 μm retrieval to the volcanic cloud altitude and show that the SO2 total masses estimated at 7.3 and 8.6 μm separately can be used to improve the information on the plume height. Finally, the water vapour profile is used to compute the minimum altitude over which the 7.3 μm retrieval is effective. 


    African Journals Online (AJOL)


    East African Medical Journal Vol. 80. No. 7 July 2003. MIDLINE LETHAL GRANULOMA COMPLICATING PREGNANCY: CASE REPORT. B.D.O. Saheeb, BDS, FWACS, FICS, FDS, RCS (Edin) Senior Lecturer/Consultant, and M.A. Ojo, BDS, MMed Sc, Dip Maxfac Rad, Associate Professor/Consultant. Department of oral ...

  19. [The "lethal white foal" syndrome]. (United States)

    Blendinger, C; Müller, G; Bostedt, H


    The lethal white foal syndrome (congenital intestinal aganglionosis) was diagnosed by history, clinical signs and pathological findings in a female foal, born in March 1992, that was an offspring of two overo-spotted paint horses. The syndrome is a congenital innervation defect of the gastrointestinal tract. A literature review of this condition, relatively unknown in Germany, is given.

  20. [From synthetic biology to synthetic humankind]. (United States)

    Nouvel, Pascal


    In this paper, we propose an historical survey of the expression "synthetic biology" in order to identify its main philosophical components. The result of the analysis is then used to investigate the meaning of the notion of "synthetic man". It is shown that both notions share a common philosophical background that can be summed up by the short but meaningful assertion: "biology is technology". The analysis allows us to distinguish two notions that are often confused in transhumanist literature: the notion of synthetic man and the notion of renewed man. The consequences of this crucial distinction are discussed. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  1. Phosphoethanolamine Synthetic: Analysis of a Judicialization of Controversial Case Drug Supply without Proof Scientific

    Directory of Open Access Journals (Sweden)

    Tiago Antonio Paulosso Anibal


    Full Text Available The object of this work is to verify the possibility of the judiciary receive a request for supply of synthetic phosphoethanolamine substance. Through a bibliographical and jurisprudential review, notes that the legalization of public policy has been peaceful when it comes to grant requests for medications, except in the event of lack of therapeutic efficacy of accreditation and patient safety , with its Agency registration national Health Surveillance . It is concluded by no host application providing phosphoethanolamine by the courts due to the lack of legal and scientific support, and should the courts decide legal criteria, not political.

  2. In-situ study of ferric iron distribution in synthetic spinels by electron microprobe analysis (United States)

    Goncharov, Alexey; Olga, Sinelshikova; Rustam, Lukmanov


    The iron oxidation state in mantle minerals is a key value in oxygen fugacity calculation and the most widely used analytical approach for Fe3+/ΣFe determination is Mössbauer spectroscopy, which is a bulk method and there is a lack of information on Fe3+/ΣFe zonation in individual mineral grains and Fe3+/ΣFe in inclusions. Here we present application of the flank method using the electron microprobe by analysing the FeLα and FeLβ X-ray emission spectra to a suite of 20 synthetic MgAl2O2-Cr2O3-Fe2O3(FeO) spinels. Materials were done with 5 - 25 FeO wt.%, and 2-70 Cr2O3 wt.% and Fe3+/ΣFe = 0.10 to 0.80, where Fe3+/ΣFe was determined independently using Mössbauer spectroscopy on the same grains used for the flank method measurements. Synthesis of the samples produced using a pyrolysis method of organic salt compositions in MgAl2O2-Cr2O3-Fe2O3(FeO) system with following heating in corundum crucibles at 1300 ° C for 5 -10 hours under controlled oxygen fugacity. All synthetic materials were investigated by X-ray and Mössbauer spectroscopy to examine a phase and iron oxidation state features. In terms of chemical composition and Fe3+/ΣFe resulting synthetic material covers a whole range of spinels derived in mantle peridotites and pyroxenites. These synthetic products were used as a standard sample to investigate co-variations of ratios of intensities measured on the flanks of FeLα and Lβ peaks and Fe3+/ΣFe, FeO content and Cr#. The obtained correlations can be used to perform in-situ studies of ferric iron distribution in natural mantle spinels. The presented approach will allow investigating the difference in mantle spinel Fe3+/ΣFe at a microscale from core to rim in individual grain, inclusion, melting pocket and in intergrows with other mantle mineral assemblage. The reported study was funded by RFBR according to the research project № 16-35-60076 mol_a_dk.

  3. Deuterium, carbon and nitrogen isotopic analysis of natural and synthetic caffeines. Authentication of coffees and coffee extracts

    International Nuclear Information System (INIS)

    Danho, D.; Naulet, N.; Martin, G.J.


    Isotope ratio mass spectrometry (IRMS) was used to determine the δ( 13 C) and δ( 15 N) values of a series of caffeine samples extracted from coffee beans or obtained by synthesis, 2 H NMR spectra were recorded in order to compute the site-specific isotope ratios of caffeine. The set of the five isotope ratios measured for the 26 different samples was studied by multi-variate analysis (principal component and discriminant analyse) and it is shown that the synthetic samples are clearly distinguishable from the natural caffeines which in turn can be classified with complete accuracy as of either American or African origin

  4. Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

    International Nuclear Information System (INIS)

    Almaraz, R.


    The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

  5. In vivo analysis of biocompatibility and vascularization of the synthetic bone grafting substitute NanoBone. (United States)

    Abshagen, K; Schrodi, I; Gerber, T; Vollmar, B


    One of the major challenges in the application of bone substitutes is adequate vascularization and biocompatibility of the implant. Thus, the temporal course of neovascularization and the microvascular inflammatory response of implants of NanoBone (fully synthetic nanocrystalline bone grafting material) were studied in vivo by using the mouse dorsal skinfold chamber model. Angiogenesis, microhemodynamics, and leukocyte-endothelial cell interaction were analyzed repetitively after implantation in the center and in the border zone of the implant up to 15 days. Both NanoBone granules and plates exhibited high biocompatibility comparable to that of cancellous bone, as indicated by a lack of venular leukocyte activation after implantation. In both synthetic NanoBone groups, signs of angiogenesis could be observed even at day 5 after implantation, whereas granules showed higher functional vessel density compared with NanoBone plates. The angiogenic response of the cancellous bone was markedly accelerated in the center of the implant tissue. Histologically, implant tissue showed an ingrowth of vascularized fibrous tissue into the material combined with an increased number of foreign-body giant cells. In conclusion, NanoBone, particularly in granular form, showed high biocompatibility and high angiogenic response, thus improving the healing of bone defects. Our results underline that, beside the composition and nanostructure, the macrostructure is also of importance for the incorporation of the biomaterial by the host tissue. (c) 2008 Wiley Periodicals, Inc.

  6. Metabolism and toxicological analysis of synthetic cannabinoids in biological fluids and tissues. (United States)

    Presley, B C; Gurney, S M R; Scott, K S; Kacinko, S L; Logan, B K


    Synthetic cannabinoids, which began proliferating in the United States in 2009, have gone through numerous iterations of modification to their chemical structures. More recent generations of compounds have been associated with significant adverse outcomes following use, including cognitive and psychomotor impairment, seizures, psychosis, tissue injury and death. These effects increase the urgency for forensic and public health laboratories to develop methods for the detection and identification of novel substances, and apply these to the determination of their metabolism and disposition in biological samples. This comprehensive review describes the history of the appearance of the drugs in the United States, discusses the naming conventions emerging to designate new structures, and describes the most prominent new compounds linked to the adverse effects now associated with their use. We review in depth the metabolic pathways that have been elucidated for the major members of each of the prevalent synthetic cannabinoid drug subclasses, the enzyme systems responsible for their metabolism, and the use of in silico approaches to assist in predicting and identifying the metabolites of novel compounds and drug subclasses that will continue to appear. Finally, we review and critique analytical methods applied to the detection of the drugs and their metabolites, including immunoassay screening, and liquid chromatography mass spectrometry confirmatory techniques applied to urine, serum, whole blood, oral fluid, hair, and tissues. Copyright © 2016 Central Police University.

  7. Synthetic oils (United States)

    Hatton, R. E.


    Synthetic lubricants are discussed by chemical class and their general strengths and weaknesses in terms of lubrication properties are analyzed. Comparative ratings are given for 14 chemical classes and are used as a guide for lubricant selection. The effects of chemical structure on the properties of the lubricant are described with special emphasis on thermal stability. The diversity of synthetic lubricants which is provided by the wide range of properties permits many applications, some of which are reported.

  8. Synthetic Genetic Arrays: Automation of Yeast Genetics. (United States)

    Kuzmin, Elena; Costanzo, Michael; Andrews, Brenda; Boone, Charles


    Genome-sequencing efforts have led to great strides in the annotation of protein-coding genes and other genomic elements. The current challenge is to understand the functional role of each gene and how genes work together to modulate cellular processes. Genetic interactions define phenotypic relationships between genes and reveal the functional organization of a cell. Synthetic genetic array (SGA) methodology automates yeast genetics and enables large-scale and systematic mapping of genetic interaction networks in the budding yeast,Saccharomyces cerevisiae SGA facilitates construction of an output array of double mutants from an input array of single mutants through a series of replica pinning steps. Subsequent analysis of genetic interactions from SGA-derived mutants relies on accurate quantification of colony size, which serves as a proxy for fitness. Since its development, SGA has given rise to a variety of other experimental approaches for functional profiling of the yeast genome and has been applied in a multitude of other contexts, such as genome-wide screens for synthetic dosage lethality and integration with high-content screening for systematic assessment of morphology defects. SGA-like strategies can also be implemented similarly in a number of other cell types and organisms, includingSchizosaccharomyces pombe,Escherichia coli, Caenorhabditis elegans, and human cancer cell lines. The genetic networks emerging from these studies not only generate functional wiring diagrams but may also play a key role in our understanding of the complex relationship between genotype and phenotype. © 2016 Cold Spring Harbor Laboratory Press.

  9. Development of synthetic velocity - depth damage curves using a Weighted Monte Carlo method and Logistic Regression analysis (United States)

    Vozinaki, Anthi Eirini K.; Karatzas, George P.; Sibetheros, Ioannis A.; Varouchakis, Emmanouil A.


    Damage curves are the most significant component of the flood loss estimation models. Their development is quite complex. Two types of damage curves exist, historical and synthetic curves. Historical curves are developed from historical loss data from actual flood events. However, due to the scarcity of historical data, synthetic damage curves can be alternatively developed. Synthetic curves rely on the analysis of expected damage under certain hypothetical flooding conditions. A synthetic approach was developed and presented in this work for the development of damage curves, which are subsequently used as the basic input to a flood loss estimation model. A questionnaire-based survey took place among practicing and research agronomists, in order to generate rural loss data based on the responders' loss estimates, for several flood condition scenarios. In addition, a similar questionnaire-based survey took place among building experts, i.e. civil engineers and architects, in order to generate loss data for the urban sector. By answering the questionnaire, the experts were in essence expressing their opinion on how damage to various crop types or building types is related to a range of values of flood inundation parameters, such as floodwater depth and velocity. However, the loss data compiled from the completed questionnaires were not sufficient for the construction of workable damage curves; to overcome this problem, a Weighted Monte Carlo method was implemented, in order to generate extra synthetic datasets with statistical properties identical to those of the questionnaire-based data. The data generated by the Weighted Monte Carlo method were processed via Logistic Regression techniques in order to develop accurate logistic damage curves for the rural and the urban sectors. A Python-based code was developed, which combines the Weighted Monte Carlo method and the Logistic Regression analysis into a single code (WMCLR Python code). Each WMCLR code execution

  10. Analysis of Natural Graphite, Synthetic Graphite, and Thermosetting Resin Candidates for Use in Fuel Compact Matrix

    Energy Technology Data Exchange (ETDEWEB)

    Trammell, Michael P [ORNL; Pappano, Peter J [ORNL


    The AGR-1 and AGR-2 compacting process involved overcoating TRISO particles and compacting them in a steel die. The overcoating step is the process of applying matrix to the OPyC layer of TRISO particles in a rotating drum in order to build up an overcoat layer of desired thickness. The matrix used in overcoating is a mixture of natural graphite, synthetic graphite, and thermosetting resin in the ratio, by weight, of 64:16:20. A wet mixing process was used for AGR-1 and AGR-2, in that the graphites and resin were mixed in the presence of ethyl alcohol. The goal of the wet mixing process was to 'resinate' the graphite particles, or coat each individual graphite particle with a thin layer of resin. This matrix production process was similar to the German, Chinese, Japanese, and South African methods, which also use various amount of solvent during mixing. See Appendix 1 for information on these countries matrix production techniques. The resin used for AGR-1 and AGR-2 was provided by Hexion, specifically Hexion grade Durite SC1008. Durite SC1008 is a solvated (liquid) resole phenolic resin. A resole resin does not typically have a hardening agent added. The major constituent of SC1008 is phenol, with minor amounts of formaldehyde. Durite SC1008 is high viscosity, so additional ethyl alcohol was added during matrix production in order to reduce its viscosity and enhance graphite particle resination. The current compacting scale up plan departs from a wet mixing process. The matrix production method specified in the scale up plan is a co-grinding jet mill process where powdered phenolic resin and graphite are all fed into a jet mill at the same time. Because of the change in matrix production style, SC1008 cannot be used in the jet milling process because it is a liquid. The jet milling/mixing process requires that a suite of solid or powdered resins be investigated. The synthetic graphite used in AGR-1 and AGR-2 was provided by SGL Carbon, grade KRB2000. KRB

  11. Coastal Flooding in Florida's Big Bend Region with Application to Sea Level Rise Based on Synthetic Storms Analysis

    Directory of Open Access Journals (Sweden)

    Scott C. Hagen Peter Bacopoulos


    Full Text Available Flooding is examined by comparing maximum envelopes of water against the 0.2% (= 1-in-500-year return-period flooding surface generated as part of revising the Federal Emergency Management Agency¡¦s flood insurance rate maps for Franklin, Wakulla, and Jefferson counties in Florida¡¦s Big Bend Region. The analysis condenses the number of storms to a small fraction of the original 159 used in production. The analysis is performed by assessing which synthetic storms contributed to inundation extent (the extent of inundation into the floodplain, coverage (the overall surface area of the inundated floodplain and the spatially variable 0.2% flooding surface. The results are interpreted in terms of storm attributes (pressure deficit, radius to maximum winds, translation speed, storm heading, and landfall location and the physical processes occurring within the natural system (storms surge and waves; both are contextualized against existing and new hurricane scales. The approach identifies what types of storms and storm attributes lead to what types of inundation, as measured in terms of extent and coverage, in Florida¡¦s Big Bend Region and provides a basis in the identification of a select subset of synthetic storms for studying the impact of sea level rise. The sea level rise application provides a clear contrast between a dynamic approach versus that of a static approach.

  12. Synthetic Analysis about Single-Criterion and Multi-Criterion Financial Assets Portfolio

    Directory of Open Access Journals (Sweden)

    Leonardo Badea


    Full Text Available This paper as a synthetic analyzis based on the Markowitz and Sharpe models deals with the problem of portfolio trying to determine both the optimum proportion of titles and the influence of a considered macroeconomic factor over their level of efficiency and risk. The improvement of these models was made through the introduction of a new model, the APT model (Arbitrage Price Theory, as a development of the uni-factorial CAPM model, in other words, the above-mentioned model only constitutes a particular form of the APT model trying to establish a relationship between the individual efficiency of a title from the portfolio and several macroeconomic factors. Also, this model involves the identification of macroeconomic factors influencing the profitability of the titles and the determination of the influence of these factors individually, through the application of the APT model.

  13. Analysis of early synthetic dyes with HPLC-DAD-MS: an important database for analysis of colorants used in cultural heritage


    Souto, Cátia Susana da Costa Nogueira


    Presented thesis at Faculdade de Ciências e Tecnologias, Universidade de Lisboa, to obtain the Master Degree in Conservation and Restoration of Textiles The analysis of 62 early synthetic dyes from the Smithsonian‟s Helmut Schweppe Collection with High Performance Liquid Chromatography – Diode Array Detection – Mass Spectrometry (HPLC-DAD-MSn) was performed. Several chromatographic and mass parameters were optimized in order to characterize the 62 dyes. This approach was also applied to se...

  14. Macrocyclic glycopeptide chiral selectors bonded to core-shell particles enables enantiopurity analysis of the entire verubecestat synthetic route. (United States)

    Barhate, Chandan L; Lopez, Diego A; Makarov, Alexey A; Bu, Xiaodong; Morris, William J; Lekhal, Azzeddine; Hartman, Robert; Armstrong, Daniel W; Regalado, Erik L


    Verubecestat is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease. Synthetic route development involves diastereoselective transformations with a need for enantiomeric excess (ee) determination of each intermediate and final active pharmaceutical ingredient (API). The analytical technical package of validated methods relies on enantioselective SFC and RPLC separations using multiple 3 and 5 μm coated polysaccharide-based chiral stationary phases (CSPs) and mobile phases combinations. Evaluation of recently developed chiral columns revealed a single chiral selector (Teicoplanin) bonded to 2.7 μm core-shell particles using H 3 PO 4 in H 2 O/ACN and triethylammonium acetate: methanol based eluents at different isocratic compositions allowed good enatioseparation of all verubecestat intermediates. EE determination of verubecestat is easily performed on NicoShell, another macrocyclic glycopeptide chiral selector bonded to 2.7 μm superficially porous particles. This approach enables fast and reliable enantiopurity analysis of the entire verubecestat synthetic route using only two chiral columns and mobile phases on a conventional HPLC system, simplifying technical package preparation, method validation and transfer to manufacturing facilities. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Synthetic hardware performance analysis in virtualized cloud environment for healthcare organization. (United States)

    Tan, Chee-Heng; Teh, Ying-Wah


    The main obstacles in mass adoption of cloud computing for database operations in healthcare organization are the data security and privacy issues. In this paper, it is shown that IT services particularly in hardware performance evaluation in virtual machine can be accomplished effectively without IT personnel gaining access to actual data for diagnostic and remediation purposes. The proposed mechanisms utilized the hypothetical data from TPC-H benchmark, to achieve 2 objectives. First, the underlying hardware performance and consistency is monitored via a control system, which is constructed using TPC-H queries. Second, the mechanism to construct stress-testing scenario is envisaged in the host, using a single or combination of TPC-H queries, so that the resource threshold point can be verified, if the virtual machine is still capable of serving critical transactions at this constraining juncture. This threshold point uses server run queue size as input parameter, and it serves 2 purposes: It provides the boundary threshold to the control system, so that periodic learning of the synthetic data sets for performance evaluation does not reach the host's constraint level. Secondly, when the host undergoes hardware change, stress-testing scenarios are simulated in the host by loading up to this resource threshold level, for subsequent response time verification from real and critical transactions.

  16. Conformational analysis of a synthetic fish kisspeptin 1 peptide in membrane mimicking environments. (United States)

    Thakuria, Dimpal; Shahi, Neetu; Singh, Atul Kumar; Khangembam, Victoria Chanu; Singh, Arvind Kumar; Kumar, Satish


    Kisspeptin 1 is a neuropeptide hormone of the RFamide family, which act as an upstream regulator of brain-pituitary-gonad (BPG) axis in most vertebrates including teleosts. In the present study, a 16 amino acid long putative mature bioactive peptide (kiss 1) from preprokisspeptin 1 of golden mahseer, Tor putitora (Hamilton, 1822), was synthesized and characterized using an integrated (experimental and in silico) approach. The far-UV circular dichroism (CD) spectrum of this peptide was evaluated both in aqueous and membrane mimicking solvents (TFE, HFIP and Dioxane). The results indicate that kiss 1 peptide adopted helical, turn and β conformations in membrane like environments. The near-UV CD spectroscopy was also carried out to examine the tertiary packing around aromatic residues of kiss 1 peptide and the peptide-membrane complex. The kiss 1 peptide exhibited little signal in water, but a prominent negative band was observed at around 275 nm when membrane mimetic solution was added. The observed ordered conformations of kiss 1 peptide in the different solvents indicated its potential biological activity which could enhance the secretion of gonadotropin-releasing hormone (GnRH) at BPG axis. The conformational information generated from the present study reinforces the application prospects of bioactive synthetic peptide analogs of kisspeptin 1 in improving the reproductive performances of important cultivable fish species.

  17. Functional analysis of synthetic DELLA domain peptides and bioactive gibberellin assay using surface plasmon resonance technology. (United States)

    Zhao, Zhuoya; Xing, Zenan; Zhou, Min; Chen, Yi; Li, Chenzhong; Wang, Ruozhong; Xu, Wenzhong; Ma, Mi


    DELLA proteins and phytohormone gibberellin act together to control convergence point of plant development. A gibberellin-bound nuclear receptor that interacts with the N-terminal domain of DELLA proteins is required for gibberellin induced degradation of DELLA proteins. N-terminal DELLA domain includes two conserved motifs: DELLA and VHYNP. However, their respective functions remain unclear. Meanwhile, the identification and detection of several bioactive gibberellins from the more than 100 gibberellin metabolites are overwhelmingly difficult for their similar structures. Using in vitro biochemical approach, our work demonstrates for the first time that the synthetic GAI N-terminal DELLA domain peptides have similar bioactive function as the expressed protein to interact with AtGID1a receptor. Furthermore, our results reveal that DELLA motif is vitally important region and DELLA segment is essentially required region to recognize AtGID1a receptor. Finally, based on bioactive GA-dependent of the interaction between AtGID1a and DELLA protein, we generated a new method that could identify and detect bioactive GAs accurately and rapidly with surface plasmon resonance assays. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Antimicrobial activity predictors benchmarking analysis using shuffled and designed synthetic peptides. (United States)

    Porto, William F; Pires, Állan S; Franco, Octavio L


    The antimicrobial activity prediction tools aim to help the novel antimicrobial peptides (AMP) sequences discovery, utilizing machine learning methods. Such approaches have gained increasing importance in the generation of novel synthetic peptides by means of rational design techniques. This study focused on predictive ability of such approaches to determine the antimicrobial sequence activities, which were previously characterized at the protein level by in vitro studies. Using four web servers and one standalone software, we evaluated 78 sequences generated by the so-called linguistic model, being 40 designed and 38 shuffled sequences, with ∼60 and ∼25% of identity to AMPs, respectively. The ab initio molecular modelling of such sequences indicated that the structure does not affect the predictions, as both sets present similar structures. Overall, the systems failed on predicting shuffled versions of designed peptides, as they are identical in AMPs composition, which implies in accuracies below 30%. The prediction accuracy is negatively affected by the low specificity of all systems here evaluated, as they, on the other hand, reached 100% of sensitivity. Our results suggest that complementary approaches with high specificity, not necessarily high accuracy, should be developed to be used together with the current systems, overcoming their limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Lethal means access and assessment among suicidal emergency department patients (United States)

    Betz, Marian E.; Miller, Matthew; Barber, Catherine; Beaty, Brenda; Miller, Ivan; Camargo, Carlos A.; Boudreaux, Edwin D.


    Background Reducing access to lethal means (especially firearms) might prevent suicide, but counseling of at-risk individuals about this strategy may not be routine. Among emergency department (ED) patients with suicidal ideation or attempts (SI/SA), we sought to describe home firearm access and examine ED provider assessment of access to lethal means. Methods This secondary analysis used data from the Emergency Department Safety Assessment and Follow-up Evaluation, a 3-phase, 8-center study of adult ED patients with SI/SA (2010-2013). Research staff surveyed participants about suicide-related factors (including home firearms) and later reviewed the ED chart (including documented assessment of lethal means access). Results Among 1358 patients with SI/SA, 11% (95%CI 10-13%) reported ≥1 firearm at home; rates varied across sites (range: 6% to 26%) but not over time. On chart review, 50% (95%CI 47-52%) of patients had documentation of lethal means access assessment. Frequency of documented assessment increased over study phases (40% to 60%, pfirearm ownership rates. Among the 337 (25%, 95%CI 23-27%) patients discharged to home, 55% (95%CI 49-60%) had no documentation of lethal means assessment; of these, 13% (95%CI 8-19; n=24) actually had ≥1 firearm at home. Among all those reporting ≥1 home firearm to study staff, only half (50%, 95%CI 42-59) had provider documentation of assessment of lethal means access. Conclusions Among these ED patients with SI/SA, many did not have documented assessment of home access to lethal means, including patients who were discharged home and had ≥1 firearm at home. PMID:26989850

  20. Synthetic Rutile

    International Nuclear Information System (INIS)

    Burastero, J.


    This work is about the laboratory scale investigation of the conditions in the rutile synthetic production from one me nita in Aguas Dulces reservoir. The iron mineral is chlorinated and volatilized selectively leaving a residue enriched in titanium dioxide which can be used as a substitute of rutile mineral

  1. The Benefits of Using Time-Frequency Analysis with Synthetic Aperture Focusing Technique

    Energy Technology Data Exchange (ETDEWEB)

    Albright, Austin P [ORNL; Clayton, Dwight A [ORNL


    Improvements in detection and resolution are always desired and needed. There are various instruments available for the inspection of concrete structures that can be used with confidence for detecting different defects. However, more often than not that confidence is heavily dependent on the experience of the operator rather than the clear, objective discernibility of the output of the instrument. The challenge of objective discernment is amplified when the concrete structures contain multiple layers of reinforcement, are of significant thickness, or both, such as concrete structures in nuclear power plants. We seek to improve and extend the usefulness of results produced using the synthetic aperture focusing technique (SAFT) on data collected from thick, complex concrete structures. A secondary goal is to improve existing SAFT results, with regards to repeatedly and objectively identifying defects and/or internal structure of concrete structures. Towards these goals, we are applying the time-frequency technique of wavelet packet decomposition and reconstruction using a mother wavelet that possesses the exact reconstruction property. However, instead of analyzing the coefficients of each decomposition node, we select and reconstruct specific nodes based on the frequency band it contains to produce a frequency band specific time-series representation. SAFT is then applied to these frequency specific reconstructions allowing SAFT to be used to visualize the reflectivity of a frequency band and that band s interaction with the contents of the concrete structure. We apply our technique to data sets collected using a commercial, ultrasonic linear array (MIRA) from two 1.5m x 2m x 25cm concrete test specimens. One specimen contains multiple layers of rebar. The other contains honeycomb, crack, and rebar bonding defect analogs. This approach opens up a multitude of possibilities for improved detection, readability, and overall improved objectivity. We will focus on

  2. The benefits of using time-frequency analysis with synthetic aperture focusing technique

    Energy Technology Data Exchange (ETDEWEB)

    Albright, Austin, E-mail:, E-mail:; Clayton, Dwight, E-mail:, E-mail: [Oak Ridge National Laboratory, One Bethel Valley Road, Oak Ridge, TN 37831 (United States)


    Improvements in detection and resolution are always desired and needed. There are various instruments available for the inspection of concrete structures that can be used with confidence for detecting different defects. However, more often than not that confidence is heavily dependent on the experience of the operator rather than the clear, objective discernibility of the output of the instrument. The challenge of objective discernment is amplified when the concrete structures contain multiple layers of reinforcement, are of significant thickness, or both, such as concrete structures in nuclear power plants. We seek to improve and extend the usefulness of results produced using the synthetic aperture focusing technique (SAFT) on data collected from thick, complex concrete structures. A secondary goal is to improve existing SAFT results, with regards to repeatedly and objectively identifying defects and/or internal structure of concrete structures. Towards these goals, we are applying the time-frequency technique of wavelet packet decomposition and reconstruction using a mother wavelet that possesses the exact reconstruction property. However, instead of analyzing the coefficients of each decomposition node, we select and reconstruct specific nodes based on the frequency band it contains to produce a frequency band specific time-series representation. SAFT is then applied to these frequency specific reconstructions allowing SAFT to be used to visualize the reflectivity of a frequency band and that band's interaction with the contents of the concrete structure. We apply our technique to data sets collected using a commercial, ultrasonic linear array (MIRA) from two 1.5m × 2m × 25cm concrete test specimens. One specimen contains multiple layers of rebar. The other contains honeycomb, crack, and rebar bonding defect analogs. This approach opens up a multitude of possibilities for improved detection, readability, and overall improved objectivity. We will focus on

  3. The benefits of using time-frequency analysis with synthetic aperture focusing technique (United States)

    Albright, Austin; Clayton, Dwight


    Improvements in detection and resolution are always desired and needed. There are various instruments available for the inspection of concrete structures that can be used with confidence for detecting different defects. However, more often than not that confidence is heavily dependent on the experience of the operator rather than the clear, objective discernibility of the output of the instrument. The challenge of objective discernment is amplified when the concrete structures contain multiple layers of reinforcement, are of significant thickness, or both, such as concrete structures in nuclear power plants. We seek to improve and extend the usefulness of results produced using the synthetic aperture focusing technique (SAFT) on data collected from thick, complex concrete structures. A secondary goal is to improve existing SAFT results, with regards to repeatedly and objectively identifying defects and/or internal structure of concrete structures. Towards these goals, we are applying the time-frequency technique of wavelet packet decomposition and reconstruction using a mother wavelet that possesses the exact reconstruction property. However, instead of analyzing the coefficients of each decomposition node, we select and reconstruct specific nodes based on the frequency band it contains to produce a frequency band specific time-series representation. SAFT is then applied to these frequency specific reconstructions allowing SAFT to be used to visualize the reflectivity of a frequency band and that band's interaction with the contents of the concrete structure. We apply our technique to data sets collected using a commercial, ultrasonic linear array (MIRA) from two 1.5m × 2m × 25cm concrete test specimens. One specimen contains multiple layers of rebar. The other contains honeycomb, crack, and rebar bonding defect analogs. This approach opens up a multitude of possibilities for improved detection, readability, and overall improved objectivity. We will focus on

  4. Imaging and size analysis of stress corrosion cracks in austenitic components using the synthetic aperture focus technique

    International Nuclear Information System (INIS)

    Spies, Martin; Rieder, Hans; Dillhoefer, Alexander; Dugan, Sandra


    Riss formation and growth by intercrystalline stress corrosion cracking occurs especially in nickel alloys in case of mixed steels and also in the heat-affected zone in some austenitic Cr-Ni steels. In view of the strong branching of these cracks, amplitude-based ultrasonic methods of measurement may fail. The contribution describes the detection and size analysis of stress corrosion cracks. The synthetic aperture focus technique (SAFT) was used to improve the signal-noise ratio of the ultrasonic inspection data, especially for crack tip identification. several test bodies with intercrystalline stress corrosion cracks with depths ranging from 2.5 mm to 16 mm were analyzed successfully by a combination of conventional techniques for acquisition of B-scan data, followed by SAFT processing.

  5. Fourier analysis of parallel block-Jacobi splitting with transport synthetic acceleration in two-dimensional geometry

    International Nuclear Information System (INIS)

    Rosa, M.; Warsa, J. S.; Chang, J. H.


    A Fourier analysis is conducted in two-dimensional (2D) Cartesian geometry for the discrete-ordinates (SN) approximation of the neutron transport problem solved with Richardson iteration (Source Iteration) and Richardson iteration preconditioned with Transport Synthetic Acceleration (TSA), using the Parallel Block-Jacobi (PBJ) algorithm. The results for the un-accelerated algorithm show that convergence of PBJ can degrade, leading in particular to stagnation of GMRES(m) in problems containing optically thin sub-domains. The results for the accelerated algorithm indicate that TSA can be used to efficiently precondition an iterative method in the optically thin case when implemented in the 'modified' version MTSA, in which only the scattering in the low order equations is reduced by some non-negative factor β<1. (authors)

  6. Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control. (United States)

    Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H Annika; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha


    Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

  7. Electroshock weapons can be lethal! (United States)

    Lundquist, Marjorie


    Electroshock weapons (EWs)-stun guns, tasers, riot shields-are electroconductive devices designed to safely incapacitate healthy men neuromuscularly, so they are called nonlethal or less-lethal. EW firms seeking large nonmilitary markets targeted law enforcement and corrections personnel, who began using EWs in prisons/jails and on public patrol in 1980 in the USA. This shifted the EW-shocked population from healthy soldiers to a heterogeneous mix of both sexes, ages 6-92, in a wide variety of health conditions! An EW operates by disrupting normal physiological processes, producing transient effects in healthy people. But if a person's health is sufficiently compromised, the margin of safety can be lost, resulting in death or permanent health problems. 325 people have died after EW shock since 1980. Did the EW cause these deaths? Evidence indicates that EWs do play a causal role in most such deaths. EWs can be lethal for people in diabetic shock^1 (hypoglycemia), which may be why Robert Dziekanski-a Polish immigrant to Canada-died so quickly after he was tasered at Vancouver Airport: not having eaten for over 10 hours, he likely was severely hypoglycemic. The EW death rate in North America is 30 times higher than need be, because EW users have not been properly trained to use EWs on a heterogeneous population safely! ^1J. Clinical Engineering 30(3):111(2005).

  8. Two-stream Instabilities within the Front of Supercritical Quasi-perpendicular Shocks: a Synthetic Analysis (United States)

    Muschietti, L.; Lembege, B.


    toward upstream for the oblique whistlers, as expected. We present a synthetic view of wave emissions of two-stream origin and connect our results with the low-frequency whistlers of Hellinger and Mangeney [JGR 102, 1997], the MTSI-1 and 2 of Matsukyio and Scholer [JGR 111, 2006], and the Bernstein waves of Muschietti and Lembege [JGR 118, 2013].

  9. pBAM1: an all-synthetic genetic tool for analysis and construction of complex bacterial phenotypes

    Directory of Open Access Journals (Sweden)

    Arévalo-Rodríguez Miguel


    Full Text Available Abstract Background Since publication in 1977 of plasmid pBR322, many breakthroughs in Biology have depended on increasingly sophisticated vector platforms for analysis and engineering of given bacterial strains. Although restriction sites impose a certain format in the procedures for assembling cloned genes, every attempt thus far to standardize vector architecture and nomenclature has ended up in failure. While this state of affairs may still be tolerable for traditional one-at-a-time studies of single genes, the onset of systems and synthetic biology calls for a simplification -along with an optimization- of the currently unwieldy pool of genetic tools. Results The functional DNA sequences present in the natural bacterial transposon Tn5 have been methodically edited and refactored for the production of a multi-purpose genetic tool named pBAM1, which allows a range of manipulations in the genome of Gram-negative bacteria. This all-synthetic construct enhances the power of mini-transposon vectors for either de-construction or re-construction of phenotypes á la carte by incorporating features inspired in systems engineering: modularity, re-usability, minimization, and compatibility with other genetic tools. pBAM1 bears an streamlined, restriction site-freed and narrow-host range replication frame bearing the sequences of R6K oriV, oriT and an ampicillin resistance marker. These go along with a business module that contains a host-independent and hyperactive transposition platform for in vivo or in vitro insertion of desired DNA into the genome of the target bacterium. All functional sequences were standardized for a straightforward replacement by equivalent counterparts, if required. pBAM1 can be delivered into recipient cells by either mating or electroporation, producing transposon insertion frequencies of 1.8 × 10-3 and 1.02 × 10-7, respectively in the soil bacterium Pseudomonas putida. Analyses of the resulting clones revealed a 100% of

  10. Examining the Impact of Psychiatric Diagnosis and Comorbidity on the Medical Lethality of Adolescent "Suicide Attempts" (United States)

    Mc Manama O'Brien, Kimberly H.; Berzin, Stephanie C.


    Specific psychiatric diagnoses and comorbidity patterns were examined to determine if they were related to the medical lethality of "suicide attempts" among adolescents presenting to an urban general hospital (N = 375). Bivariate analysis showed that attempters with substance abuse disorders had higher levels of lethality than attempters without…

  11. The Danger Assessment: Validation of a Lethality Risk Assessment Instrument for Intimate Partner Femicide (United States)

    Campbell, Jacquelyn C.; Webster, Daniel W.; Glass, Nancy


    The Danger Assessment (DA) is an instrument designed to assess the likelihood of lethality or near lethality occurring in a case of intimate partner violence. This article describes the development, psychometric validation, and suggestions for use of the DA. An 11-city study of intimate partner femicide used multivariate analysis to test the…

  12. Improving the Analysis Capabilities of the Synthetic Theater Operations Research Model (STORM) (United States)


    through multiple MySQL queries, which identify those metrics and dump them into an Excel file for analysis. MySQL is an open source SQL (Structured Query...Language) database server. MySQL allows a program or user to store, manipulate, and retrieve data in table structures. This server was chosen

  13. Synthetic Genetic Targeting of Genome Instability in Cancer

    International Nuclear Information System (INIS)

    Sajesh, Babu V.; Guppy, Brent J.; McManus, Kirk J.


    Cancer is a leading cause of death throughout the World. A limitation of many current chemotherapeutic approaches is that their cytotoxic effects are not restricted to cancer cells, and adverse side effects can occur within normal tissues. Consequently, novel strategies are urgently needed to better target cancer cells. As we approach the era of personalized medicine, targeting the specific molecular defect(s) within a given patient’s tumor will become a more effective treatment strategy than traditional approaches that often target a given cancer type or sub-type. Synthetic genetic interactions are now being examined for their therapeutic potential and are designed to target the specific genetic and epigenetic phenomena associated with tumor formation, and thus are predicted to be highly selective. In general, two complementary approaches have been employed, including synthetic lethality and synthetic dosage lethality, to target aberrant expression and/or function associated with tumor suppressor genes and oncogenes, respectively. Here we discuss the concepts of synthetic lethality and synthetic dosage lethality, and explain three general experimental approaches designed to identify novel genetic interactors. We present examples and discuss the merits and caveats of each approach. Finally, we provide insight into the subsequent pre-clinical work required to validate novel candidate drug targets



    Hassani, Abdessalem; Aifaoui, Nizar; Benamara, Abdelmajid; Samper, Serge


    International audience; The tolerancing step has a great importance in the design process. It characterises the relationship between the different sectors of the product life cycle: Design, Manufacturing and Control. We can distinguish several methods to assist the tolerancing process in the design. Based on arithmetic and statistical method, this paper presents a new approach of analysis and verification of tolerances. The chosen approach is based on the Worst Case Method as an arithmetic me...

  15. Synthetic analysis of associations between IL-10 polymorphisms and skin cancer risk. (United States)

    Zhao, Hongbo; Yang, Jiaoli; Yu, Zhenzhen; Shen, Hui; Huang, Xinlin; Zhang, Mi; Long, Teng; Cailing, A; Wang, Wenhui


    The current study was designed to quantitatively summarize the evidence for the strength of the associations between common IL-10 functional polymorphisms and skin cancer risk. Relevant publications concerning the associations between common IL-10 functional polymorphisms(-1082G>A, -819C>T and -592C>A) and skin cancer were retrieved by a comprehensive electronic literature search in PubMed, Web of Science, EBSCO, Embase, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database (CBM). The odds ratio (OR) and 95% confidence interval (CI) were utilized to assess the strength of the relationship. A total of 26 studies including 4090 cases and 4133 controls (-1082G>A, 10 studies with 1809 cases and 1830 controls; -819C>T, 7 studies with 862 cases and 957 controls; -592C>A, 9 studies with 1419 cases and 1346 controls) were enrolled in the meta-analysis. Overall, the results revealed a borderline decreased risk of skin cancer in heterozygote model (OR = 0.82, 95CI = 0.67-1.00, p = 0.05). The subgroup analysis also presented similar association for non-melanoma skin cancer in heterozygote model (OR = 0.67, 95CI = 0.50-0.91, p = 0.01). Moreover, the further analysis based on the histological type of non-melanoma skin cancer indicated a significantly decreased risk of BCC in allele model (OR = 0.67, 95% CI = 0.50-0.91, p = 0.02) and dominant model (OR = 0.68, 95% CI = 0.48-0.98, p = 0.04). However, neither overall analysis nor subgroup analysis based on cancer subtype revealed a significant association of -1082G>A or -592C>A polymorphisms with skin cancer. The present study suggested a potential association between IL-10 -819C>T polymorphism and decreased risk of skin cancer, but a lack of association for -1082G>A and -592C>A polymorphisms. Further invalidation is urgently needed.

  16. Characterization of Synthetic Peptides by Mass Spectrometry. (United States)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter; Hansen, Paul R


    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS and LC-MS of synthetic peptides.

  17. Effect of lethal and sub-lethal concentrations of tobacco (Nicotiana ...

    African Journals Online (AJOL)

    Lethal and sub-lethal bioassays on Clarias gariepinus were conducted to evaluate the toxicity of tobacco (Nicotiana tobaccum) leaf dust on weight gain and haematological indices of Clarias gariepinus (mean weight 10.5±0.70g) in glass aquaria with aeration system. The concentrations used during the lethal exposure are: ...

  18. Analysis of Metrics for Human Detection behind Walls Using Experimental 3-D Synthetic Aperture Radar Imagery (United States)


    analysis. Significance to defence and security This study of metrics for discriminating human targets from other sources behind walls will allow the...ainsi obtenues. Le rapport présente les données RSO 3D d’une étude approfondie menée sur les caractéristiques des signatures de cibles humaines ...derrière trois structures murales différentes. Il comporte également l’analyse d’une signature de cible humaine selon différentes positions, derrière une

  19. Targeted analysis with benchtop quadrupole–orbitrap hybrid mass spectrometer: Application to determination of synthetic hormones in animal urine

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Praveen [Departament de Química Analítica, Universitat de Barcelona, Barcelona (Spain); Rúbies, Antoni; Centrich, Francesc [Laboratori Agència Salut Pública de Barcelona, Barcelona (Spain); CIBER of Epidemiology and Public Health (CIBERESP), Madrid (Spain); Granados, Mercè [Departament de Química Analítica, Universitat de Barcelona, Barcelona (Spain); Cortés-Francisco, Nuria; Caixach, Josep [Mass Spectrometry Laboratory-Organic Pollutants, IDAEA-CSIC, Barcelona (Spain); Companyó, Ramon, E-mail: [Departament de Química Analítica, Universitat de Barcelona, Barcelona (Spain)


    Graphical abstract: -- Highlights: •The quadrupole in Q Exactive acts as a powerful filter to reduce ion suppression. •Reducing mass range using quadrupole in targeted modes increases the S/N ratio. •Targeted SIM data dependent scan modes are the most suitable for residue analysis. •A HRMS confirmatory method for synthetic hormones in urine has been developed. •The Q Exactive provides similar sensitivity and enhanced selectivity compared to QqQ. -- Abstract: Sensitive and unequivocal determination of analytes/contaminants in complex matrices is a challenge in the field of food safety control. In this study, various acquisition modes (Full MS/AIF, Full MS + tMS/MS, Full MS/dd MS/MS and tSIM/ddMS/MS) and parameters of a quadrupole–orbitrap hybrid mass spectrometer (Q Exactive) were studied in detail. One of the main conclusions has been that, reducing the scan range for Full MS (using the quadrupole) and targeted modes give higher signal-to-noise (S/N) ratios and thereby better detection limits for analytes in matrix. The use of Q Exactive in a complex case, for the confirmatory analysis of hormones in animal urine is presented. A targeted SIM data dependent MS/MS (tSIM/ddMS/MS) acquisition method for determination of eight synthetic hormones (trenbolone, 17α ethinylestradiol, zeranol, stanozolol, dienestrol, diethylstilbestrol, hexestrol, taleranol) and a naturally occurring hormone (zearalenone) in animal urine were optimized to have sensitive precursors from targeted SIM mode and trigger MS/MS scans over the entire chromatograph peak. The method was validated according to EC/657/2002. CCα (decision limit) for the analytes ranged between 0.11 μg L{sup −1} and 0.69 μg L{sup −1} and CCβ (detection capability) ranged between 0.29 μg L{sup −1} and 0.90 μg L{sup −1}.

  20. accessions resistants to lethal yellowing disease

    African Journals Online (AJOL)



    Feb 19, 2007 ... One of the problems faced in coconut cultivation is the lethal yellowing disease. Experimental trials, conducted in endemic region, showed that the Vanuatu Tall and Sri-Lanka Green Dwarf genotypes were tolerant while the West African Tall appeared susceptible to the lethal yellowing disease. Genetic.

  1. Synthetic Cannabinoids. (United States)

    Mills, Brooke; Yepes, Andres; Nugent, Kenneth


    Synthetic cannabinoids (SCBs), also known under the brand names of "Spice," "K2," "herbal incense," "Cloud 9," "Mojo" and many others, are becoming a large public health concern due not only to their increasing use but also to their unpredictable toxicity and abuse potential. There are many types of SCBs, each having a unique binding affinity for cannabinoid receptors. Although both Δ-tetrahydrocannabinol (THC) and SCBs stimulate the same receptors, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), studies have shown that SCBs are associated with higher rates of toxicity and hospital admissions than is natural cannabis. This is likely due to SCBs being direct agonists of the cannabinoid receptors, whereas THC is a partial agonist. Furthermore, the different chemical structures of SCBs found in Spice or K2 may interact in unpredictable ways to elicit previously unknown, and the commercial products may have unknown contaminants. The largest group of users is men in their 20s who participate in polydrug use. The most common reported toxicities with SCB use based on studies using Texas Poison Control records are tachycardia, agitation and irritability, drowsiness, hallucinations, delusions, hypertension, nausea, confusion, dizziness, vertigo and chest pain. Acute kidney injury has also been strongly associated with SCB use. Treatment mostly involves symptom management and supportive care. More research is needed to identify which contaminants are typically found in synthetic marijuana and to understand the interactions between different SBCs to better predict adverse health outcomes.

  2. Synthetical Analysis for Morphology, biological Species, and stable Isotopes (SAMSI) of single-cell planktonic foraminifer (United States)

    Ujiie, Y.; Kimoto, K.; Ishimura, T.


    Planktonic foraminifers are widely used in the studies of paleontology and paleoceanography, because the morphology of their calcareous shells is enough highly variable to identify the morphospecies and the chemical composition of the shells reflect ambient seawater condition. Although the morphospecies were believed to represent environments associating with latitudinal temperature range of the world ocean, molecular phylogeographic studies have unveiled the presence of multiple biological species in a single morphospecies and their species-specific distributions. This implicates the actual complexity of planktonic foraminiferal ecology. Conversely, these biological species have a high potential for providing novel ecological and environmental information to us. In order to reassess the morphological and geochemical characters of biological species, the DNA extraction method with the guanidium isothiocyanate buffer was developed to preserve the calcareous shells. The present study carefully tested the physical and chemical damages of the DNA extraction process to the shells, by our novel approaches with geochemical analysis of the shells after non-destructive analysis for morphometrics on a same specimen. First, we checked the changes of the shell densities between pre- and post-DNA extraction by using the micro-focus X-ray CT (MXCT) scanning. Based on the simultaneous measurement of a sample and the standard material, we confirmed no significant changes to the shell densities through the DNA extraction process. As a next step, we compared stable oxygen and carbon isotopes among individuals of three sample sets: (1) no chemical and incubation as control, (2) incubation in the DNA extraction buffer at 65-70°C for 40 minutes as standard way, and (3) incubation in the DNA extraction buffer at 65-70°C for 120 minutes, by using the microscale isotopic analytical system (MICAL3c). Consequently, there were no significant differences among the three sample sets. These

  3. Synthetic analysis of the Neuropterids - their interest for the decipherment of Carboniferous palaeogeography

    Energy Technology Data Exchange (ETDEWEB)

    Laveine, J.P. [Universitaire de Science et Technologie de Lille, Villeneuve d`Ascq (France). Lab. Paleobotanique


    `Neuropterids` are of the dominant groups of Carboniferous fossil-plants. The original definition of Nevropteris, initially given as a section of the genus Filicites, was based only on the shape, the mode of attachment to the rachis, and the venation of the pinnules. Subsequent information has shown that the originally defined taxon, in fact, comprises many genera belonging to several distinct families of Pteridosperms, which are distinguished on various features of frond architecture, male and female reproductive organs and apparatuses, anatom, and morphology and venation of the pinnules. Unfortunately, these characteristics are not equally known within each group, even at a general level, and are not always available through usual palaeobotanical collecting. However, it is essential to reach the most precise, `natural` level of taxonomy for the decipherment of the many interrelated problems raised by palaeobotanical studies, i.e. evolution, biostratigraphy, palaeobiogeography, palaeoecology and, as a feedback consequence, systematics. Despite restricting the analysis mainly to the external morphological characters, the `Neuropterids` provide a fine example of such interrelated fundamental questions.

  4. Lethality of patients with rheumatoid arthritis depending on adalimumab administration: imitation modeling

    Directory of Open Access Journals (Sweden)

    D V Goryachev


    Full Text Available Lethality of pts with rheumatoid arthritis (RA exceeds mortality values in general population. Possibility of disease modifying anti-rheumatic drugs (DMARD influence on RA pts lethality has been widely discussed lately in scientific works. Objective. To determine possible lethality diminishment in Russian population of RA pts with one of biological drugs TNFα antagonist adalimumab. Material and methods. Model construction is based on the fact of lethality dependence on pt functional state assessed by HAQ. Model simulating progression of functional disability in pts with RA visiting medical institutions of Russia was made (RAISER study. 3 model variants for imitation of consecutive change of DMARDs including adalimumab were done. First consecution assessed DMARD change in the next chain: adalimumab-methotrexate-sulfasalazine-leflunomide-azathioprine-cyclosporine-palliative therapy. Second consecution: adalimumab administration after failure of first 3 DMARDs. Third consecution considered only change of synthetic DMARDs without adalimumab inclusion. Model imitated participation of 3000 pts in every consecution. Prognosis horizon was 12 years. Age of pts and initial HAQ distribution were get from results of epidemiological RAISER study. Calculation was done on the base of elevation of standardized lethality level (SLL in population of RA pts in average from 135% to 300%. SLL values from 80 to 320% were used depending on functional disability degree with converting to Russian values of age-specific lethality coefficient for 1999. Results. Lethality in treatment consecutions including adalimumab was significantly lower. To the end of 12th year in group not using adalimumab, using it at once and using it after 376 DMARDs respectively 65,1%, 71,6% and 71,1% of pts were still alive. Conclusion. Significant decrease of lethality with adalimumab inclusion in consecution of DMARD change during treatment of RA pts was demonstrated with imitation modeling

  5. Analysis of triacetone triperoxide (TATP) and TATP synthetic intermediates by electrospray ionization mass spectrometry. (United States)

    Sigman, Michael E; Clark, C Douglas; Caiano, Tara; Mullen, Rebecca


    The explosive triacetone triperoxide (TATP) has been analyzed by electrospray ionization mass spectrometry (ESI-MS) on a linear quadrupole instrument, giving a 62.5 ng limit of detection in full scan positive ion mode. In the ESI interface with no applied fragmentor voltage the m/z 245 [TATP + Na](+) ion was observed along with m/z 215 [TATP + Na - C(2)H(6)](+) and 81 [(CH(3))(2)CO + Na](+). When TATP was ionized by ESI with an applied fragmentor voltage of 75 V, ions at m/z 141 [C(4)H(6)O(4) + Na](+) and 172 [C(5)H(9)O(5) + Na](+) were also observed. When the precipitates formed in the synthesis of TATP were analyzed before the reaction was complete, a new series of ions was observed in which the ions were separated by 74 m/z units, with ions occurring at m/z 205, 279, 353, 427, 501, 575, 649 and 723. The series of evenly spaced ions is accounted for as oligomeric acetone carbonyl oxides terminated as hydroperoxides, [HOOC(CH(3))(2){OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1, 2 ... 8). The ESI-MS spectra for this homologous series of oligoperoxides have previously been observed from the ozonolysis of tetramethylethylene at low temperatures. Precipitates from the incomplete reaction mixture, under an applied fragmentor voltage of 100 V in ESI, produced an additional ion observed at m/z 99 [C(2)H(4)O(3) + Na](+), and a set of ions separated by 74 m/z units occurring at m/z 173, 247, 321, 395, 469 and 543, proposed to correspond to [CH(3)CO{OOC(CH(3))(2)}(n)OOH + Na](+) (n = 1,2 ... 5). Support for the assigned structures was obtained through the analysis of both protiated and perdeuterated TATP samples. Copyright (c) 2007 John Wiley & Sons, Ltd.

  6. Simultaneous kinetic spectrophotometric analysis of five synthetic food colorants with the aid of chemometrics. (United States)

    Ni, Yongnian; Wang, Yong; Kokot, Serge


    This paper describes a simple and sensitive kinetic spectrophotometric method for the simultaneous determination of Amaranth, Ponceau 4R, Sunset Yellow, Tartrazine and Brilliant Blue in mixtures with the aid of chemometrics. The method involved two coupled reactions, viz. the reduction of iron(III) by the analytes to iron(II) in sodium acetate/hydrochloric acid solution (pH 1.71) and the chromogenic reaction between iron(II) and hexacyanoferrate(III) ions to yield a Prussian blue peak at 760 nm. The spectral data were recorded over the 500-1000 nm wavelength range every 2s for 600 s. The kinetic data were collected at 760 nm and 600 s, and linear calibration models were satisfactorily constructed for each of the dyes with detection limits in the range of 0.04-0.50 mg L(-1). Multivariate calibration models for kinetic data were established and verified for methods such as the Iterative target transform factor analysis (ITTFA), principal component regression (PCR), partial least squares (PLS), and principal component-radial basis function-artificial neural network (PC-RBF-ANN) with and without wavelet packet transform (WPT) pre-treatment. The PC-RBF-ANN with WPT calibration performed somewhat better than others on the basis of the %RPE(T) (approximately 9) and %Recovery parameters (approximately 108), although the effect of the WPT pre-treatment was marginal (approximately 0.5% RPE(T)). The proposed method was applied for the simultaneous determination of the five colorants in foodstuff samples, and the results were comparable with those from a reference HPLC method.

  7. A simplified analysis of granule behavior in ASBR and UASB reactors treating low-strength synthetic wastewater

    Directory of Open Access Journals (Sweden)

    R. G. Veronez


    Full Text Available This work presents an analysis of the changes observed in granule characteristics of sludge in the treatment of synthetic wastewater at a concentration of about 500 mgCOD/L in batch, fed-batch (ASBR and continuous (UASB bench-scale reactors under similar experimental conditions. Physical and microbiological properties of the granules were characterized as average particle size and sedimentation time and by optical and epifluorescence microscopy. Several samples were analyzed in order to identify the morphologies. Granules from sequencing batch and fed-batch reactors, either with or without mechanical mixing, did not undergo any physical or microbiological changes. However, during the experiment granules from the UASB reactor agglomerated due to the formation and accumulation of a viscous material, probably of microbial origin, when operated at low superficial velocities (0.072, 0.10 and 0.19 m/h. When the superficial velocity was increased to 8.0-10.0 m/h by means of liquid-phase recirculation, the granules from the UASB reactor underwent flocculation and the microbiological characteristics changed in such a way that the equilibrium of microbial diversity in the inoculum was not maintained. As a result, the only reactor that maintained efficiency and good solids retention during the assays was the ASBR, showing that there is a correlation between maintenance of microbial diversity and operating mode in the case of anaerobic treatment of low-strength wastewaters.

  8. Time-series analysis of surface deformation at Brady Hot Springs geothermal field (Nevada) using interferometric synthetic aperture radar

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S. T. [Univ. of Wisconsin, Madison, WI (United States); Akerley, J. [Ormat Technologies Inc., Reno, NV (United States); Baluyut, E. C. [Univ. of Wisconsin, Madison, WI (United States); Cardiff, M. [Univ. of Wisconsin, Madison, WI (United States); Davatzes, N. C. [Temple Univ., Philadelphia, PA (United States). Dept. of Earth and Environmental Science; Feigl, K. L. [Univ. of Wisconsin, Madison, WI (United States); Foxall, W. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fratta, D. [Univ. of Wisconsin, Madison, WI (United States); Mellors, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Spielman, P. [Ormat Technologies Inc., Reno, NV (United States); Wang, H. F. [Univ. of Wisconsin, Madison, WI (United States); Zemach, E. [Ormat Technologies Inc., Reno, NV (United States)


    We analyze interferometric synthetic aperture radar (InSAR) data acquired between 2004 and 2014, by the ERS-2, Envisat, ALOS and TerraSAR-X/TanDEM-X satellite missions to measure and characterize time-dependent deformation at the Brady Hot Springs geothermal field in western Nevada due to extraction of fluids. The long axis of the ~4 km by ~1.5 km elliptical subsiding area coincides with the strike of the dominant normal fault system at Brady. Within this bowl of subsidence, the interference pattern shows several smaller features with length scales of the order of ~1 km. This signature occurs consistently in all of the well-correlated interferometric pairs spanning several months. Results from inverse modeling suggest that the deformation is a result of volumetric contraction in shallow units, no deeper than 600 m, likely associated with damaged regions where fault segments mechanically interact. Such damaged zones are expected to extend downward along steeply dipping fault planes, providing a high permeability conduit to the production wells. Using time series analysis, we test the hypothesis that geothermal production drives the observed deformation. We find a good correlation between the observed deformation rate and the rate of production in the shallow wells. We also explore mechanisms that could potentially cause the observed deformation, including thermal contraction of rock, decline in pore pressure and dissolution of minerals over time.

  9. System architecture and operational analysis of medium displacement unmanned surface vehicle sea hunter as a surface warfare component of distributed lethality (United States)


    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release. Distribution is unlimited. SYSTEM ARCHITECTURE ...TITLE AND SUBTITLE SYSTEM ARCHITECTURE AND OPERATIONAL ANALYSIS OF MEDIUM DISPLACEMENT UNMANNED SURFACE VEHICLE SEA HUNTER AS A SURFACE WARFARE...traceability, requirements and capabilities while determining the architecture framework in accordance with the Department of Defense Architectural

  10. Traveltime and waveform tomography analysis of synthetic borehole seismic data based on the CO2SINK project site, Germany (United States)

    Yang, Can; Fan, Wenfang; Juhlin, Christopher


    Time lapse analysis of seismic data is very important for CO2 storage projects. Therefore, we have tested traveltime and waveform tomography methods to detect velocity changes in a CO2 injection reservoir using synthetic time lapse data. The structural model tested is based on the CO2SINK injection site at Ketzin, Germany where CO2 is being injected at about 630-650 m into a saline aquifer. First, we created synthetic time lapse moving source profiling (MSP) data, also known as walkaway profiling. The velocity model used for modeling was based on well logging and lithological information in the injection borehole. Gassmann fluid substitution was used to calculate the reservoir velocity after injection. In this substitution, we assumed a saturation of CO2 of 30%. The model velocity of the reservoir changed from 2750 m/s (before injection) to 2150 m/s (after injection). A 2D finite difference code available in Seismic Unix ( was used. 60 source points were distributed along a surface line. The distance from the injection well was between 150m and 858m, with an interval of 12m. We recorded 21 channels at receiver depths from 470m to 670m, with an interval of 10m. The injection layer was assumed to be between 629m and 650m depth. The wavelet used for the synthetic data was a Gaussian derivative with an average frequency of 60Hz. Then first arrivals were picked on both data sets and used as input data for traveltime tomography. For traveltime tomography, the PS_tomo program was used. Since no data were recorded above 470m, the initial velocity model used above this depth was the true velocity model. Below 470m, the initial velocity model increases linearly from 3000m/s to 3250m/s. After inversion, the reservoir velocity and an anhydrite layer (high velocity layer) can be seen clearly in the final inverted velocity models. Using these velocity models as starting models, we performed waveform tomography in the frequency domain using a program supplied by

  11. Synthetic Botany. (United States)

    Boehm, Christian R; Pollak, Bernardo; Purswani, Nuri; Patron, Nicola; Haseloff, Jim


    Plants are attractive platforms for synthetic biology and metabolic engineering. Plants' modular and plastic body plans, capacity for photosynthesis, extensive secondary metabolism, and agronomic systems for large-scale production make them ideal targets for genetic reprogramming. However, efforts in this area have been constrained by slow growth, long life cycles, the requirement for specialized facilities, a paucity of efficient tools for genetic manipulation, and the complexity of multicellularity. There is a need for better experimental and theoretical frameworks to understand the way genetic networks, cellular populations, and tissue-wide physical processes interact at different scales. We highlight new approaches to the DNA-based manipulation of plants and the use of advanced quantitative imaging techniques in simple plant models such as Marchantia polymorpha. These offer the prospects of improved understanding of plant dynamics and new approaches to rational engineering of plant traits. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. Habitat mapping of the Brazilian Pantanal using synthetic aperture radar imagery and object based image analysis (United States)

    Evans, Teresa Lynne

    for both fine and medium resolution classifications related to issues of 1) scale of habitats, for instance, capoes, cordilheiras, and lakes, in relation to spatial resolution of the imagery, and 2) issues relating to variable flooding patterns in the subregion, and 3) arbitrary class membership rules. The 50 m spatial resolution classification of the entire Pantanal wetland resulted in an overall accuracy of 80%, and defined ten land cover classes. Given the analysis of the comparison of fine and relatively medium spatial resolution classifications of the Lower Nhecolândia subregion, I conclude that significant improvements in accuracy can be achieved with the finer spatial resolution dataset, particularly in subregions with high spatial heterogeneity in land cover. The produced habitat spatial distribution maps will provide vital information for determining refuge zones for terrestrial species, connectivity of aquatic habitats during the dry season, and crucial baseline data to aid in monitoring changes in the region, as well as to help define conservation strategies for habitat in this critically important wetland.

  13. Comprehensive Proteomic Analysis of Spider Dragline Silk from Black Widows: A Recipe to Build Synthetic Silk Fibers. (United States)

    Larracas, Camille; Hekman, Ryan; Dyrness, Simmone; Arata, Alisa; Williams, Caroline; Crawford, Taylor; Vierra, Craig A


    The outstanding material properties of spider dragline silk fibers have been attributed to two spidroins, major ampullate spidroins 1 and 2 (MaSp1 and MaSp2). Although dragline silk fibers have been treated with different chemical solvents to elucidate the relationship between protein structure and fiber mechanics, there has not been a comprehensive proteomic analysis of the major ampullate (MA) gland, its spinning dope, and dragline silk using a wide range of chaotropic agents, inorganic salts, and fluorinated alcohols to elucidate their complete molecular constituents. In these studies, we perform in-solution tryptic digestions of solubilized MA glands, spinning dope and dragline silk fibers using five different solvents, followed by nano liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis with an Orbitrap Fusion™ Tribrid™. To improve protein identification, we employed three different tryptic peptide fragmentation modes, which included collision-induced dissociation (CID), electron transfer dissociation (ETD), and high energy collision dissociation (HCD) to discover proteins involved in the silk assembly pathway and silk fiber. In addition to MaSp1 and MaSp2, we confirmed the presence of a third spidroin, aciniform spidroin 1 (AcSp1), widely recognized as the major constituent of wrapping silk, as a product of dragline silk. Our findings also reveal that MA glands, spinning dope, and dragline silk contain at least seven common proteins: three members of the Cysteine-Rich Protein Family (CRP1, CRP2 and CRP4), cysteine-rich secretory protein 3 (CRISP3), fasciclin and two uncharacterized proteins. In summary, this study provides a proteomic blueprint to construct synthetic silk fibers that most closely mimic natural fibers.

  14. Comprehensive Proteomic Analysis of Spider Dragline Silk from Black Widows: A Recipe to Build Synthetic Silk Fibers

    Directory of Open Access Journals (Sweden)

    Camille Larracas


    Full Text Available The outstanding material properties of spider dragline silk fibers have been attributed to two spidroins, major ampullate spidroins 1 and 2 (MaSp1 and MaSp2. Although dragline silk fibers have been treated with different chemical solvents to elucidate the relationship between protein structure and fiber mechanics, there has not been a comprehensive proteomic analysis of the major ampullate (MA gland, its spinning dope, and dragline silk using a wide range of chaotropic agents, inorganic salts, and fluorinated alcohols to elucidate their complete molecular constituents. In these studies, we perform in-solution tryptic digestions of solubilized MA glands, spinning dope and dragline silk fibers using five different solvents, followed by nano liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS analysis with an Orbitrap Fusion™ Tribrid™. To improve protein identification, we employed three different tryptic peptide fragmentation modes, which included collision-induced dissociation (CID, electron transfer dissociation (ETD, and high energy collision dissociation (HCD to discover proteins involved in the silk assembly pathway and silk fiber. In addition to MaSp1 and MaSp2, we confirmed the presence of a third spidroin, aciniform spidroin 1 (AcSp1, widely recognized as the major constituent of wrapping silk, as a product of dragline silk. Our findings also reveal that MA glands, spinning dope, and dragline silk contain at least seven common proteins: three members of the Cysteine-Rich Protein Family (CRP1, CRP2 and CRP4, cysteine-rich secretory protein 3 (CRISP3, fasciclin and two uncharacterized proteins. In summary, this study provides a proteomic blueprint to construct synthetic silk fibers that most closely mimic natural fibers.

  15. Factors influencing circadian rhythms in acetaminophen lethality. (United States)

    Schnell, R C; Bozigian, H P; Davies, M H; Merrick, B A; Park, K S; McMillan, D A


    Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00-18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00-06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

  16. Examining the impact of psychiatric diagnosis and comorbidity on the medical lethality of adolescent suicide attempts. (United States)

    McManama O'Brien, Kimberly H; Berzin, Stephanie C


    Specific psychiatric diagnoses and comorbidity patterns were examined to determine if they were related to the medical lethality of suicide attempts among adolescents presenting to an urban general hospital (N=375). Bivariate analysis showed that attempters with substance abuse disorders had higher levels of lethality than attempters without substance abuse. Regression results indicated having depression comorbid with any other diagnosis was not associated with medical lethality. However, having a substance abuse disorder was associated with higher suicide attempt lethality, highlighting the importance of substance abuse as a risk factor for lethal suicide attempts in adolescents. This finding stimulates critical thinking around the understanding of suicidal behavior in youth and the development and implementation of treatment strategies for suicidal adolescents with substance abuse disorders. © 2012 The American Association of Suicidology.

  17. Costs analysis of surgical treatment of stress urinary incontinence in a brazilian public hospital, comparing burch and synthetic sling techniques. (United States)

    Limberger, Leo Francisco; Faria, Fernanda Pacheco; Campos, Luciana Silveira; Anzolch, Karin Marise Jaeger; Fornari, Alexandre


    Surgical treatment of urinary incontinence progressed significantly with the introduction of synthetic slings. However, in some public Brazilian hospitals, the costs of these materials prevent their routine use. To compare the costs of ambulatory synthetic sling surgery with an historical series of patients submitted to Burch surgery in a Brazilian public hospital. Twenty nine incontinent patients were selected to synthetic sling surgery. Demographic data were prospectively collected and also the costs of the procedure, including drugs and materials, use of surgical and recovery wards, medical staff and hospitalization. These data were compared to the costs of 29 Burch surgeries performed before the introduction of synthetic slings. Demographic data were similar, although median age was lower in the group submitted to Burch surgery (46.3±8.6 versus 56.2±11.3 (pCost was significantly lower in patients submitted to sling in all items, except for time spent in recovery ward. Total value of 29 Burch surgeries was R$ 217.766.12, and of R$ 68.049.92 of 29 patients submitted to sling surgery (pcost of the synthetic sling was considered. Copyright® by the International Brazilian Journal of Urology.

  18. Targeted analysis with benchtop quadrupole-orbitrap hybrid mass spectrometer: application to determination of synthetic hormones in animal urine. (United States)

    Kumar, Praveen; Rúbies, Antoni; Centrich, Francesc; Granados, Mercè; Cortés-Francisco, Nuria; Caixach, Josep; Companyó, Ramon


    Sensitive and unequivocal determination of analytes/contaminants in complex matrices is a challenge in the field of food safety control. In this study, various acquisition modes (Full MS/AIF, Full MS+tMS/MS, Full MS/dd MS/MS and tSIM/ddMS/MS) and parameters of a quadrupole-orbitrap hybrid mass spectrometer (Q Exactive) were studied in detail. One of the main conclusions has been that, reducing the scan range for Full MS (using the quadrupole) and targeted modes give higher signal-to-noise (S/N) ratios and thereby better detection limits for analytes in matrix. The use of Q Exactive in a complex case, for the confirmatory analysis of hormones in animal urine is presented. A targeted SIM data dependent MS/MS (tSIM/ddMS/MS) acquisition method for determination of eight synthetic hormones (trenbolone, 17α ethinylestradiol, zeranol, stanozolol, dienestrol, diethylstilbestrol, hexestrol, taleranol) and a naturally occurring hormone (zearalenone) in animal urine were optimized to have sensitive precursors from targeted SIM mode and trigger MS/MS scans over the entire chromatograph peak. The method was validated according to EC/657/2002. CCα (decision limit) for the analytes ranged between 0.11 μg L(-1) and 0.69 μg L(-1) and CCβ (detection capability) ranged between 0.29 μg L(-1) and 0.90 μg L(-1). Copyright © 2013 Elsevier B.V. All rights reserved.

  19. The nitrogen acceptor in 2H-Polytype synthetic MoS2. Frequency and temperature dependent ESR analysis

    International Nuclear Information System (INIS)

    Schoenaers, Ben; Stesmans, Andre; Afanas'ev, Valery V.


    In extending on recent electron spin resonance (ESR) work which has revealed the N acceptor (N substituting for S site) in 2H-polytype bulk synthetic MoS 2 , the dopant is extensively analyzed in terms of its frequency, temperature (T), and magnetic field B angular dependent ESR spectral characteristics. For B parallel c-axis, the multi-frequency analysis confirms the ESR spectrum as being composed of a 14 N hyperfine (hf) triplet with hf splitting constant A parallel = 14.7 ± 0.2 G (B parallel c-axis) and making up ∼74% of the total spectrum intensity, superimposed on a central line centered at about equal g-value [g parallel = 2.032(2)]. The presence of the latter signal, points to some non-uniformity in dopant distribution, that is, clustering, with about ∼26% of the total N response not originating from N incorporated in the preferred ''isolated'' dopant configuration. Angular dependent measurements reveal distinct anisotropy of the hf matrix, whereas ESR probing over a wide T-range exposes drastic signal broadening with increasing T above ∼150 K. Detailed study of the N acceptor signal intensity versus T at Q-band reveals an activation energy E a = 50 ± 10 meV, herewith consolidating the value reported initially. Besides unveiling the S-site substitutional N impurity as an appropriate p-type dopant for MoS 2 , the total of the ESR work establishes a basic frame of the N acceptor ESR characteristics, giving way for further in-depth theoretical perusal. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  20. Command and Control for Distributed Lethality (United States)


    communications over vast distances, and the need for near-real-time coordination means that stakeholders for the distributed lethality concept can encompass a...and methods of effective communication systems. 14. SUBJECT TERMS command and control (C2) distributed lethality system of systems (SOS) model...refinement through simulations of the C2 structure and further research into technologies and methods of effective communication systems. vi THIS PAGE

  1. Experiences in therapy for lethal midline granuloma

    Energy Technology Data Exchange (ETDEWEB)

    Tosaka, K.; Ishikawa, T. (Kumamoto Univ. (Japan). School of Medicine)


    Four cases of the lethal midline granuloma or malignant granuloma of the nose were treated by irradiation and chemotherapy, which are generally prescribed for malignant lymphomas. Clinical, histological and laboratory examination indicated that they were the lethal midline granuloma and clearly differentiated from Wegener's granulomatosis or malignant lymphoma. All of the cases exhibited primary remission. The four cases were observed up to 38, 22, 14, and 10 months since the beginning of the therapy, showing no local or general recurrence.

  2. Optical and Scanning electron Microscopy as advanced analysis methods to determine the condition of synthetic geo membranes

    International Nuclear Information System (INIS)

    Soriano Carrillo, J.; Blanco Fernandez, M.; Garcia Calleja, M. A.; Leiro Lopez, A.; Mateo Sanz, B.; Aguilar Gonzalez, E.; Rubin de Celix, M.


    Microscopic techniques have been widely used for years in the study of inorganic materials however their use in organic materials and specifically, in synthetic geo membranes, is very limited. In this study, this innovative technology has been used with the different geo synthetic polymeric barriers with which this research team is experienced: plasticized polyvinyl chloride, polyethylenes, rubbers such as ethenyltriphenyl-diene monomer terpolymer and butyl, polyolefins, ethylene-vinyl acetate copolymer, chlorosulfonated polyethylene and polypropylene. the influence of the extraction area and the time since their application is tested. (Author)

  3. Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis

    NARCIS (Netherlands)

    Wildt, William de; Kooijman, Huub; Funke, Carel; Üstün, Bülent; Leika, Afranina; Lunenburg, Maarten; Kaspersen, Frans; Kellenbach, Edwin


    Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra(®). The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming

  4. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala K; Mirza, Osman; Højrup, Peter


    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an......Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI...

  5. Analysis and confirmation of synthetic anorexics in adulterated traditional Chinese medicines by high-performance capillary electrophoresis. (United States)

    Ku, Y R; Chang, Y S; Wen, K C; Ho, L K


    Six synthetic anorexics, clobenzorex, diethylpropion, fenfluramine, methamphetamine, phenylpropanolamine and phentermine, which can be found as adulterants in traditional Chinese medicines were assayed simultaneously by high-performance capillary electrophoresis. The electrolyte was a buffer solution containing 120 mM phosphate buffer (NaH2PO4/H3PO4, pH 2.0) and 15% acetonitrile. Applied voltage was 16 kV and temperature was 30 degrees C. Fluoren-2,7-diammonium chloride was used as an internal standard and detector set at 200 nm. The recoveries of the synthetic anorexic adulterants in traditional Chinese medicinal formula using C8-SCX mixed solid-phase extraction were studied. Several traditional Chinese medicinal powders obtained from clinics were also studied by the above HPCE method and confirmed by GC-MS. Clobenzorex, diethylpropion and fenfluramine were found and determine in these samples.

  6. Lethality Index 2008-2014: Less shootings, same lethality, more opacity

    Directory of Open Access Journals (Sweden)

    Carlos Silva Forné


    Full Text Available This article evaluates the use of lethal force by Mexican federal security forces during shootings with presumed members of organized crime from 2008-2014. The authors use official data and press reports on deaths and wounded in shootings to construct indicators such as the number of dead civilians over the number of dead officials from the federal security forces and the number of dead civilians over the number of wounded civilians. In a context where certain factors that contribute to an excessive use of force become more common, the results of the study show a growing use of lethal force. This raises questions over the possible excessive use of lethal force as a normal or systematic practice. The study also shows a growing context of opacity in the information available to evaluate the use of lethal force and the general lack of a legal framework to regulate the use of lethal force in Mexico.

  7. Molecular cloning, expression and in vitro analysis of soluble cationic synthetic antimicrobial peptide from salt-inducible Escherichia coli GJ1158

    Directory of Open Access Journals (Sweden)

    Jawahar Babu Peravali


    Full Text Available Antimicrobial peptides are the upcoming therapeutic molecules as alternative drugs to the existing antibiotics owing to their potent action against pathogenic microorganisms. In this study, to obtain an antimicrobial peptide with a broad range of activity, the synthetic cationic antimicrobial peptide was designed by using in silico tools viz., antimicrobial peptide database, protparam, hierarchical neural network. Later, the peptide was translated back into a core nucleotide sequence and the gene for the peptide was constructed by overlapping PCR. The amplified gene was cloned into pRSET–A vector and transformed into salt inducible expression host E. coli GJ1158. The expression results show high yields of soluble recombinant fusion peptide (0.52 g/L from salt-inducible E. coli. The recombinant peptide was purified by the IMAC purification system and cleaved by enterokinase. The digested product was further purified and 0.12 g/L of biologically active recombinant cationic antimicrobial peptide was obtained. In vitro analysis of the purified peptide demonstrated high antimicrobial activity against both Gram positive and Gram negative bacteria devoid of hemolytic activity. Therefore, this synthetic cationic antimicrobial peptide could serves as an promising agent over chemical antibiotics. In this study, a synthetic cationic antimicrobial peptide was designed, cloned and expressed from salt-inducible E. coli GJ1158 using cost effective media in the large scale production of antimicrobial peptide and its biological activity was analysed against different Gram positive and negative organisms.

  8. Lethal and Sub-lethal Effects of Four Insecticides on the Aphidophagous Coccinellid Adalia bipunctata (Coleoptera: Coccinellidae). (United States)

    Depalo, Laura; Lanzoni, Alberto; Masetti, Antonio; Pasqualini, Edison; Burgio, Giovanni


    Conventional insecticide assays, which measure the effects of insecticide exposure on short-term mortality, overlook important traits, including persistence of toxicity or sub-lethal effects. Therefore, such approaches are especially inadequate for prediction of the overall impact of insecticides on beneficial arthropods. In this study, the side effects of four modern insecticides (chlorantraniliprole, emamectin benzoate, spinosad, and spirotetramat) on Adalia bipunctata (L.) (Coleoptera: Coccinellidae) were evaluated under laboratory conditions by exposition on treated potted plants. In addition to investigation of acute toxicity and persistence of harmful activity in both larvae and adults of A. bipunctata, demographic parameters were evaluated, to provide a comprehensive picture of the nontarget effects of these products. Field doses of the four insecticides caused detrimental effects to A. bipunctata; but in different ways. Overall, spinosad showed the best toxicological profile among the products tested. Emamectin benzoate could be considered a low-risk insecticide, but had high persistence. Chlorantraniliprole exhibited lethal effects on early instar larvae and adults, along with a long-lasting activity, instead spirotetramat showed a low impact on larval and adult mortality and can be considered a short-lived insecticide. However, demographic analysis demonstrated that chlorantraniliprole and spirotetramat caused sub-lethal effects. Our findings highlight that sole assessment of mortality can lead to underestimation of the full impact of pesticides on nontarget insects. Demographic analysis was demonstrated to be a sensitive method for detection of the sub-lethal effects of insecticides on A. bipunctata, and this approach should be considered for evaluation of insecticide selectivity. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail:

  9. Suitability of Synthetic Driving Profiles from Traffic Micro-Simulation for Real-World Energy Analysis: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Hou, Yunfei; Wood, Eric; Burton, Evan; Gonder, Jeffrey


    A shift towards increased levels of driving automation is generally expected to result in improved safety and traffic congestion outcomes. However, little empirical data exists to estimate the impact that automated driving could have on energy consumption and greenhouse gas emissions. In the absence of empirical data on differences between drive cycles from present day vehicles (primarily operated by humans) and future vehicles (partially or fully operated by computers) one approach is to model both situations over identical traffic conditions. Such an exercise requires traffic micro-simulation to not only accurately model vehicle operation under high levels of automation, but also (and potentially more challenging) vehicle operation under present day human drivers. This work seeks to quantify the ability of a commercial traffic micro-simulation program to accurately model real-world drive cycles in vehicles operated primarily by humans in terms of driving speed, acceleration, and simulated fuel economy. Synthetic profiles from models of freeway and arterial facilities near Atlanta, Georgia, are compared to empirical data collected from real-world drivers on the same facilities. Empirical and synthetic drive cycles are then simulated in a powertrain efficiency model to enable comparison on the basis of fuel economy. Synthetic profiles from traffic micro-simulation were found to exhibit low levels of transient behavior relative to the empirical data. Even with these differences, the synthetic and empirical data in this study agree well in terms of driving speed and simulated fuel economy. The differences in transient behavior between simulated and empirical data suggest that larger stochastic contributions in traffic micro-simulation (relative to those present in the traffic micro-simulation tool used in this study) are required to fully capture the arbitrary elements of human driving. Interestingly, the lack of stochastic contributions from models of human drivers

  10. Critical analysis of the maximum non inhibitory concentration (MNIC) method in quantifying sub-lethal injury in Saccharomyces cerevisiae cells exposed to either thermal or pulsed electric field treatments. (United States)

    Kethireddy, V; Oey, I; Jowett, Tim; Bremer, P


    Sub-lethal injury within a microbial population, due to processing treatments or environmental stress, is often assessed as the difference in the number of cells recovered on non-selective media compared to numbers recovered on a "selective media" containing a predetermined maximum non-inhibitory concentration (MNIC) of a selective agent. However, as knowledge of cell metabolic response to injury, population diversity and dynamics increased, the rationale behind the conventional approach of quantifying sub-lethal injury must be scrutinized further. This study reassessed the methodology used to quantify sub-lethal injury for Saccharomyces cerevisiae cells (≈ 4.75 Log CFU/mL) exposed to either a mild thermal (45°C for 0, 10 and 20min) or a mild pulsed electric field treatment (field strengths of 8.0-9.0kV/cm and energy levels of 8, 14 and 21kJ/kg). Treated cells were plated onto either Yeast Malt agar (YM) or YM containing NaCl, as a selective agent at 5-15% in 1% increments. The impact of sub-lethal stress due to initial processing, the stress due to selective agents in the plating media, and the subsequent variation of inhibition following the treatments was assessed based on the CFU count (cell numbers). ANOVA and a generalised least squares model indicated significant effects of media, treatments, and their interaction effects (P<0.05) on cell numbers. It was shown that the concentration of the selective agent used dictated the extent of sub-lethal injury recorded owing to the interaction effects of the selective component (NaCl) in the recovery media. Our findings highlight a potential common misunderstanding on how culture conditions impact on sub-lethal injury. Interestingly for S. cerevisiae cells the number of cells recovered at different NaCl concentrations in the media appears to provide valuable information about the mode of injury, the comparative efficacy of different processing regimes and the inherent degree of resistance within a population. This

  11. Synthetic cannabinoids revealing adrenoleukodystrophy. (United States)

    Fellner, Avi; Benninger, Felix; Djaldetti, Ruth


    We report a 41-year-old man who presented with a first generalized tonic-clonic seizure after recent consumption of a synthetic cannabinoid. MRI showed extensive bilateral, mainly frontal, white matter lesions. Blood analysis for very long chain fatty acids was compatible with adrenoleukodystrophy, and a missense mutation in the ABCD1 gene confirmed the diagnosis. We hypothesize that cannabinoid use might have contributed to metabolic decompensation with subacute worsening of the underlying condition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Lethal effects of Helianthemum lippii (L.) on Acanthamoeba castellanii cysts in vitro. (United States)

    Badria, F A; Hetta, M H; Sarhan, Rania M; Ezz El-Din, M H


    Acanthamoeba spp. commonly cause Acanthamoeba keratitis which is typically associated with the wear of contact lenses. Therefore, finding an economic, efficient, and safe therapy of natural origin is of outmost importance. This study examined the in vitro lethal potential of ethyl acetate and methanol extracts of Helianthemum lippii (L.) (sun roses) against Acanthamoeba castellanii cysts isolated from patients with amoebic keratitis. Both extracts proved to be potent as regard to their lethal effects on A. castellanii cysts with comparable results to chlorhexidine. The ethyl acetate was more promising with cumulative lethality. It showed a highly significant lethal percentage along the duration of treatment. The analysis of the more potent ethyl acetate extract revealed the presence of 2.96 mg/100 g of total phenolics, 0.289 mg/100 ml of total flavonoids and 37 mg/100 mg of total tannins which highlighted their phytomedicinal role.

  13. A new approach to the determination of the synthetic or natural origin of red pigments through spectroscopic analysis (United States)

    Franquelo, Maria Luisa; Perez-Rodriguez, Jose Luis


    This work suggests a way of differentiation between the natural or synthetic origin of inorganic materials that were historically used in the Cultural Heritage field. An exhaustive review of different reported procedures of synthesis of pigments was conducted, as well as a review of the accompanying minerals in case of natural pigments. The natural or synthetic origin of the pigments studied in this work was performed through the characterization of the accompanying minerals, in the case of the natural pigments, or the trace elements that are present as part of synthesis by-products or washing/purifying reagents and/or reactants that have only been partly removed in the final steps of these processes. This work characterized red pigments due to their wide variety, complexity and possibility of use in different mixtures. The following pigments were studied: cinnabar-vermilion, red lead and iron pigments. Also mixtures of these pigments between them and with red lake were also studied. Natural cinnabar was accompanied by silicon oxide (opal, chalcedony or quartz), calcite, clay minerals and, sometimes, pyrite. K together with S indicated a synthetic pigment (vermilion) obtained through the wet method. Nevertheless, K has not been found in layers containing only vermilion in our samples. The presence of Sn in some cases indicated vermilion that came from the dry process. K from the synthesis always appeared in the red lead pigment. The red natural ochre was confirmed by presence of clay minerals and iron. It should be said that Ca and S, and sometimes Al and K, were usually found in Mars red pigment. The presence of Al and Ca allowed the identification of carmine lake.

  14. Micromagnetic analysis of current-induced domain wall motion in a bilayer nanowire with synthetic antiferromagnetic coupling

    Energy Technology Data Exchange (ETDEWEB)

    Komine, Takashi, E-mail:; Aono, Tomosuke [Faculty of Engineering, Ibaraki University 4-12-1, Nakanarusawa, Hitachi, Ibaraki, 316-8511 (Japan)


    We demonstrate current-induced domain wall motion in bilayer nanowire with synthetic antiferromagnetic (SAF) coupling by modeling two body problems for motion equations of domain wall. The influence of interlayer exchange coupling and magnetostatic interactions on current-induced domain wall motion in SAF nanowires was also investigated. By assuming the rigid wall model for translational motion, the interlayer exchange coupling and the magnetostatic interaction between walls and domains in SAF nanowires enhances domain wall speed without any spin-orbit-torque. The enhancement of domain wall speed was discussed by energy distribution as a function of wall angle configuration in bilayer nanowires.

  15. Digital Beamforming Synthetic Aperture Radar (DBSAR): Performance Analysis During the Eco-3D 2011 and Summer 2012 Flight Campaigns (United States)

    Rincon, Rafael F.; Fatoyinbo, Temilola; Carter, Lynn; Ranson, K. Jon; Vega, Manuel; Osmanoglu, Batuhan; Lee, SeungKuk; Sun, Guoqing


    The Digital Beamforming Synthetic Aperture radar (DBSAR) is a state-of-the-art airborne radar developed at NASA/Goddard for the implementation, and testing of digital beamforming techniques applicable to Earth and planetary sciences. The DBSAR measurements have been employed to study: The estimation of vegetation biomass and structure - critical parameters in the study of the carbon cycle; The measurement of geological features - to explore its applicability to planetary science by measuring planetary analogue targets. The instrument flew two test campaigns over the East coast of the United States in 2011, and 2012. During the campaigns the instrument operated in full polarimetric mode collecting data from vegetation and topography features.

  16. On the shape and albedo variegation of asteroids - Results from Fourier analysis of synthetic and observed asteroid lightcurves (United States)

    Barucci, M. Antonietta; Capria, M. Teresa; Harris, Alan W.; Fulchignoni, Marcello


    Fourier analyses have been conducted of those asteroids in the Lagerkvist et al. (1987) lightcurves with substantially complete phase coverage and point density, and for which a unique period has been identified. Fourier coefficients are thereby obtained for 188 lightcurves of 91 asteroids, as well as for 868 synthetic lightcurves from a set of models different in shape and albedo markings; by comparing model and asteroid lightcurve coefficients, the possible shape and albedo variations for 18 asteroids are derived. An attempt is made to define the general distribution of shapes of all asteroid samples analyzed.

  17. Analysis of recessive sex-linked lethal mutations in genetically different strains of Drosophila melanogaster ms and w irradiated in the five-kilometer zone of the Chernobyl meltdown

    International Nuclear Information System (INIS)

    Aslanyan, M.M.; Kim, A.I.; Magomedova, M.A.; Fatkulbayanova, N.L.


    The frequency of induced and spontaneous recessive sex-linked lethal mutations (RSLLM) in Drosophila melanogaster strains w and ms was estimated after their chronic irradiation in the five-kilometer zone of the Chernobyl' meltdown. The mutagenic effect of relatively low radiation doses was analyzed. In an experiment conducted in 1990, a significant increase in the RSLLM frequency was recorded, while, in 1991, no significant difference between the experiment and control was found

  18. Identification of a cryptic lethal mutation in the mouse t(w73) haplotype. (United States)

    Howell, Gareth R; Bergstrom, Rebecca A; Munroe, Robert J; Masse, Jessica; Schimenti, John C


    t haplotypes are naturally occurring, variant forms of the t complex on mouse chromosome 17, characterized by the presence of four inversions with respect to wild-type. They harbour mutations causing male sterility, male transmission ratio distortion (TRD) and embryonic lethality. Mice carrying t haplotypes have been found throughout the world, and genetic studies of the lethal mutations have identified at least 16 complementation groups. The embryonic lethal phenotypes of many t haplotypes have been characterized in detail, and are thought to be the consequence of homozygosity for single gene mutations. However, the existence of additional mutations in genes that function at later stages of development would be obscured. Here we investigated the possibility of multiple mutations in t haplotypes by screening the t(w73) haplotype for the presence of novel mutations. Since genetic analysis of t haplotype mutations is hindered by recombination suppression due to the inversions, deletion complexes covering the proximal two-thirds of the t complex were used to uncover the presence of any new lethal alleles. This analysis revealed a novel mutation between D17Jcs41 and D17Mit100, causing mice carrying both t(w73) and selected deletions to die at birth, prior to feeding. The finding of a new, cryptic lethal mutation in t haplotypes is an indication that these recombinationally isolated chromosomes, which already contain at least one lethal mutation that prevents homozygosity, may serve as sinks for the accumulation of additional recessive mutations.

  19. Guidebook for non-lethal experimentation

    NARCIS (Netherlands)

    Paulissen, J.J.M.; Rahimi, R.


    In the 2009-2011 timeframe, NATO conducts a capability based assessment of Non-Lethal Weapon (NLW) systems. The work, performed by the RTO study team SAS-078, involves the development of NLW requirement descriptions, which are put against a set of NLW systems. Gaps are likely to occur, indicating

  20. Genetics Home Reference: Amish lethal microcephaly (United States)

    ... 1 in 500 newborns in the Old Order Amish population of Pennsylvania. It has not been found outside this population. Related Information What information about a genetic condition can statistics provide? Why are some genetic ... gene cause Amish lethal microcephaly . The SLC25A19 gene provides instructions for ...

  1. A new lethal sclerosing bone dysplasia

    International Nuclear Information System (INIS)

    Kingston, H.M.; Freeman, J.S.; Hall, C.M.


    A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology. (orig.)

  2. Plant synthetic biology. (United States)

    Liu, Wusheng; Stewart, C Neal


    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Lethal and sub-lethal effects of copper to the african catfish ( clarias ...

    African Journals Online (AJOL)

    Lethal and sub-lethal effects of copper on Clarias gariepinus were studied using a 96-hour static bioassay. Copper (as copper chloride, CuCl2 . H2O) was used to prepare the stock solution from which five standard concentrations 0.0, 1.8, 3.2, 5.6, and 10.0 mg/L were prepared (coded A – E). 15 juvenile C. gariepinus fish ...

  4. Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of 'legal high' packages containing synthetic cathinones. (United States)

    Araújo, Ana Margarida; Valente, Maria João; Carvalho, Márcia; Dias da Silva, Diana; Gaspar, Helena; Carvalho, Félix; de Lourdes Bastos, Maria; Guedes de Pinho, Paula


    The world's status quo on recreational drugs has dramatically changed in recent years due to the rapid emergence of new psychoactive substances (NPS), represented by new narcotic or psychotropic drugs, in pure form or in preparation, which are not controlled by international conventions, but that may pose a public health threat comparable with that posed by substances listed in these conventions. These NPS, also known as 'legal highs' or 'smart drugs', are typically sold via Internet or 'smartshops' as legal alternatives to controlled substances, being announced as 'bath salts' and 'plant feeders' and is often sought after for consumption especially among young people. Although NPS have the biased reputation of being safe, the vast majority has hitherto not been tested and several fatal cases have been reported, namely for synthetic cathinones, with pathological patterns comparable with amphetamines. Additionally, the unprecedented speed of appearance and distribution of the NPS worldwide brings technical difficulties in the development of analytical procedures and risk assessment in real time. In this study, 27 products commercialized as 'plant feeders' were chemically characterized by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. It was also evaluated, for the first time, the in vitro hepatotoxic effects of individual synthetic cathinones, namely methylone, pentedrone, 4-methylethcathinone (4-MEC) and 3,4-methylenedioxypyrovalerone (MDPV). Two commercial mixtures ('Bloom' and 'Blow') containing mainly cathinone derivatives were also tested, and 3,4-methylenedioxymethamphetamine (MDMA) was used as the reference drug. The study allowed the identification of 19 compounds, showing that synthetic cathinones are the main active compounds present in these products. Qualitative and quantitative variability was found in products sold with the same trade name in matching or different 'smartshops'. In the toxicity studies performed in

  5. Microfluidic Technologies for Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Sung Kuk Lee


    Full Text Available Microfluidic technologies have shown powerful abilities for reducing cost, time, and labor, and at the same time, for increasing accuracy, throughput, and performance in the analysis of biological and biochemical samples compared with the conventional, macroscale instruments. Synthetic biology is an emerging field of biology and has drawn much attraction due to its potential to create novel, functional biological parts and systems for special purposes. Since it is believed that the development of synthetic biology can be accelerated through the use of microfluidic technology, in this review work we focus our discussion on the latest microfluidic technologies that can provide unprecedented means in synthetic biology for dynamic profiling of gene expression/regulation with high resolution, highly sensitive on-chip and off-chip detection of metabolites, and whole-cell analysis.

  6. Synthetic antifreeze peptide



    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  7. Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C. (United States)

    Sánchez-Martín, Maria Jesús; Hristova, Kalina; Pujol, Montserrat; Gómara, Maria J; Haro, Isabel; Alsina, M Asunción; Busquets, M Antònia


    The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS. Copyright © 2011 Elsevier Inc. All rights reserved.


    Sergeyev, O V; Barinsky, I F


    An update on the development and trials of synthetic peptide vaccines is reviewed. The review considers the successful examples of specific protection as a result of immunization with synthetic peptides using various protocols. The importance of conformation for the immunogenicity of the peptide is pointed out. An alternative strategy of the protection of the organism against the infection using synthetic peptides is suggested.

  9. Transionospheric synthetic aperture imaging

    CERN Document Server

    Gilman, Mikhail; Tsynkov, Semyon


    This landmark monograph presents the most recent mathematical developments in the analysis of ionospheric distortions of SAR images and offers innovative new strategies for their mitigation. As a prerequisite to addressing these topics, the book also discusses the radar ambiguity theory as it applies to synthetic aperture imaging and the propagation of radio waves through the ionospheric plasma, including the anisotropic and turbulent cases. In addition, it covers a host of related subjects, such as the mathematical modeling of extended radar targets (as opposed to point-wise targets) and the scattering of radio waves off those targets, as well as the theoretical analysis of the start-stop approximation, which is used routinely in SAR signal processing but often without proper justification. The mathematics in this volume is clean and rigorous – no assumptions are hidden or ambiguously stated. The resulting work is truly interdisciplinary, providing both a comprehensive and thorough exposition of the field,...

  10. Lethal neonatal short-limbed dwarfism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Hwa; Yim, Chung Ik; Bahk, Yong Whee [Catholic Medical College, Seoul (Korea, Republic of)


    We have detailed our experiences on 6 cases of neonatal lethal short-limbed dwarfism and reviewed the articles. They include, achondrogenesis, thanatophoric dysplasia, asphyxiating thoracic dysplasia, osteogenesis imperfect a congenita, and hypophosphatasia lethals. Five babies were born alive but died soon after birth and one was a stillbirth. The main cause of failure to thrive was respiratory insufficiency. Each case was having quite characteristic radiologic findings, even if the general appearances were similar to the achondroplasts clinically. Precise diagnosis is very important for genetic counselling of the parents and alarm to them the possibility of bone dysplasias to the next offsprings. For this purpose, the radiologists play major role for the correct diagnosis. We stress that when the baby is born with short-limbed dwarfism, whole body radiogram should be taken including lateral view and postmortem radiogram is also very precious.

  11. Lethal Interpersonal Violence in the Middle Pleistocene


    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-P?rez, Ana; Pablos, Adri?n; Mart?nez, Ignacio; Quam, Rolf M.; G?mez-Olivencia, Asier; Berm?dez de Castro, Jos? Mar?a; Carbonell, Eudald


    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force ...

  12. Lethal midline granuloma syndrome: a diagnostic dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Bruno Niemeyer de Freitas; Bahia, Paulo Roberto Valle [Radiology, Hospital Universitario Clementino Fraga Filho - Universidade Federal do Rio de Janeiro (HUCFF-UFRJ), Rio de Janeiro, RJ (Brazil); Oliveira, Ana Luiza Vianna Sobral de Magalhaes [Resident of Medical Practice, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil); Marchon Junior, Joao Luiz [Unit of Computed Tomography, Hospital Federal da Lagoa, Rio de Janeiro, RJ (Brazil)


    The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis. (author)

  13. Non-Lethal Weapons (NLW) Reference Book (United States)


    exist regarding the use of a Optical Distractors (e.g., Dazzling Lasers )? ANSWER: Strict laws, SECDEF guidance, and ROE exist to control the use of...National Guard Bureau (NGB) 1 Domestic Operations Kits (DOK) Joint Non-Lethal Warning Munitions (JNLWM) 2 Green Lasers 2...Chemical Weapons and on their Destruction. Paris, 13 January 1993. 16. UNCCW Protocol on Blinding Laser Weapons (Protocol IV to the 1980

  14. Analysis of U-47700, a Novel Synthetic Opioid, in Human Urine by LC-MS-MS and LC-QToF. (United States)

    Fleming, Steven W; Cooley, Justin C; Johnson, Leonard; Frazee, C Clinton; Domanski, Kristina; Kleinschmidt, Kurt; Garg, Uttam


    The illicit drug market has rapidly evolved from synthetic cannabinoids to cathinone derivatives and now a new emerging threat of synthetic opioids. These compounds were mostly developed by pharmaceutical companies during drug discovery. The new psychoactive substances are not routinely covered in drug screening and may go undetected. Recently fentanyl analogous, AH-7921, MT-45 and now U-47700 have been encountered in clinical and forensic casework. U-47700 is gaining popularity on drug user forms as a legal alternative to heroin. It is a µ-receptor agonist that is part of the trans-1-2-diamine opioid analgesic drug class developed by The Upjohn Company in an attempt to develop a non-addicting analgesic. A LC-MS-MS method was developed and validated to detect and quantify U-47700. Additional analysis was conducted with an LC-QToF to identify the presence of the parent drug and metabolites. A total of four cases have been evaluated by the LC-MS-MS methodology which has an analytical range of 1-1,250 ng/mL and limit of detection of 1 ng/mL. The concentration of U-47700 in urine specimens ranged from below the limit of quantification to 224 ng/mL. The ToF analysis detected the presence of suspected phase I demethylated metabolites that may assist future analysis of this compound. The prevalence of designer opioids in casework highlights the importance of analysis for new psychoactive substances. Traditional opiates/opioids were not detected in the presented cases, but the available case histories revealed an opioid toxidrome. These findings suggest that U-47700 drug may cause significant morbidity and mortality within the United States as an emerging drug threat. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email:

  15. Lethal interpersonal violence in the Middle Pleistocene.

    Directory of Open Access Journals (Sweden)

    Nohemi Sala

    Full Text Available Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  16. Lethal interpersonal violence in the Middle Pleistocene. (United States)

    Sala, Nohemi; Arsuaga, Juan Luis; Pantoja-Pérez, Ana; Pablos, Adrián; Martínez, Ignacio; Quam, Rolf M; Gómez-Olivencia, Asier; Bermúdez de Castro, José María; Carbonell, Eudald


    Evidence of interpersonal violence has been documented previously in Pleistocene members of the genus Homo, but only very rarely has this been posited as the possible manner of death. Here we report the earliest evidence of lethal interpersonal violence in the hominin fossil record. Cranium 17 recovered from the Sima de los Huesos Middle Pleistocene site shows two clear perimortem depression fractures on the frontal bone, interpreted as being produced by two episodes of localized blunt force trauma. The type of injuries, their location, the strong similarity of the fractures in shape and size, and the different orientations and implied trajectories of the two fractures suggest they were produced with the same object in face-to-face interpersonal conflict. Given that either of the two traumatic events was likely lethal, the presence of multiple blows implies an intention to kill. This finding shows that the lethal interpersonal violence is an ancient human behavior and has important implications for the accumulation of bodies at the site, supporting an anthropic origin.

  17. Synthetic biology and its promises

    Directory of Open Access Journals (Sweden)

    José Manuel De Cózar Escalante


    Full Text Available Synthetic biology is a new science and emerging technology, or rather a technoscience, which converges with others such as nanotechnology, information technology, robotics, artificial intelligence and neuroscience. All have common features that could have highly concerning social and environmental impacts. With its ambitious goals of controlling complexity, redesigning and creating new living entities, synthetic biology perfectly exemplifies the new bioeconomic reality. This requires expanding the focus of the discussion beyond the limited comparative analysis of risks and benefits, to address uncertainties, reassign responsibilities and initiate a thorough social assessment of what is at stake.

  18. Control theory meets synthetic biology. (United States)

    Del Vecchio, Domitilla; Dy, Aaron J; Qian, Yili


    The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology. © 2016 The Author(s).

  19. Analysis of the synthetic pyrethroids, permethrin and 1(R)-phenothrin, in grain using a monoclonal antibody-based test

    Energy Technology Data Exchange (ETDEWEB)

    Skerritt, J.H.; Hill, A.S. (CSIRO Division of Plant Industry, North Ryde (Australia)); McAdam, D.P. (CSIRO Division of Plant Industry, Canberra (Australia)); Stanker, L.H. (University of California, Livermore (United States))


    A monoclonal antibody generated to the synthetic pyrethroid-related hapten, (3-phenoxybenzyl)-2,2-dimethylcyclopropane-1, 3-dicarboxylate-protein conjugate, was used to develop assays for determinations of permethrin and 1(R)-phenothrin in wheat grain and flour milling fractions. The earlier 3-h assay was simplified using two approaches. The antibody was directly conjugated to the enzyme horseradish peroxidase (HRP), which removes a separate incubation and washing step from the assay. Also, an assay has been developed using microwell-bound monoclonal antibody and a HRP-labeled 3-phenoxybenzoic acid derivative. These assay formats have advantages in increased sensitivity and, in the case of the latter assay, accuracy with grain and flour samples. The most sensitive assay format could detect 1.5 ng/mL permethrin; 50% inhibition of antibody binding occurred at 10 ng/mL. These values corresponded to 75 and 500 ppb, respectively, in the original wheat sample. Methanol was the most effective pyrethroid extractant. Use of a simple cleanup procedure for ground grain extracts improved ELISA accuracy but could by omitted for screening purposes.

  20. Error in Radar-Derived Soil Moisture due to Roughness Parameterization: An Analysis Based on Synthetical Surface Profiles

    Directory of Open Access Journals (Sweden)

    Bernard De Baets


    Full Text Available In the past decades, many studies on soil moisture retrieval from SAR demonstrated a poor correlation between the top layer soil moisture content and observed backscatter coefficients, which mainly has been attributed to difficulties involved in the parameterization of surface roughness. The present paper describes a theoretical study, performed on synthetical surface profiles, which investigates how errors on roughness parameters are introduced by standard measurement techniques, and how they will propagate through the commonly used Integral Equation Model (IEM into a corresponding soil moisture retrieval error for some of the currently most used SAR configurations. Key aspects influencing the error on the roughness parameterization and consequently on soil moisture retrieval are: the length of the surface profile, the number of profile measurements, the horizontal and vertical accuracy of profile measurements and the removal of trends along profiles. Moreover, it is found that soil moisture retrieval with C-band configuration generally is less sensitive to inaccuracies in roughness parameterization than retrieval with L-band configuration.

  1. Brief Analysis on the Development and Application of Multi-Input Multi-Output Synthetic Aperture Radar

    Directory of Open Access Journals (Sweden)

    Zhou Wei


    Full Text Available Recently, a novel conception of Synthetic Aperture Radar (SAR based on Multi-Input Multi-Output (MIMO technology draws much attention for its potential advantages. MIMO-SAR could obtain much more equivalent channels than the number of the physical array elements by simultaneously utilizing multiple antennas at transmission and reception. These additional channels are demonstrated to be useful for the application of High-Resolution Wide-Swath (HRWS imaging and slowly moving target indication. In this paper, a detailed discussion on the conception and connotation of MIMO-SAR is made firstly, and then the investigation states of MIMO-SAR, such as high range resolution SAR imaging, three-dimensional down-looking SAR imaging, HRWS imaging and Ground Moving Target Indication (GMTI, are discussed. Base on the discussion mentioned above, the advantages and disadvantages of MIMO-SAR system are analyzed, and the key technical issues in MIMO-SAR are summarized. At last, the prospects of MIMO-SAR application are pointed out.

  2. Analysis of synthetic profile of CZTS as photovoltaic material obtained with variations of titanium and TiN (United States)

    Muñoz, M.; Vera, E.; Gómez, J.; Pineda, Y.


    Semiconductor type Cu2ZnTiS4 (CZTiS) and Cu2ZnSnS4 (CZTS),were synthetized starting from a hydrothermal route from precursor powders such as copper, zinc, tin, titanium isopropoxide and tiocarbammide metal nitrates dissolved in deionized water in concentrations of 1molL-1. Dosed and placed in a steel autoclave equipped with a Teflon jacket under magnetic stirring (150rpm) and at a temperature of 300°C for 24 hours in order to promote the formation of the respective ceramic phases. Segregates have been repeatedly washed with ethanol at all times until obtaining crystalline-looking solids. Subsequently, in order to promote the production of pure crystalline phases, the materials were subjected to a second reaction stage in a tubular furnace at 400°C in flow (50mLmin-1) for the purpose of Reduce the concentration of secondary phases of sulphides. The characterization of the CZTiS and CZTS materials was performed by X-ray Diffraction (XRD) and Raman spectroscopy where the presence of Kesterite type crystalline structures was confirmed in the two materials revealing that the effect of titanium with a higher ionic radius than tin produces a distortion in the cell of the CZTiS material compared to the report for the CZTS system. The results of Scanning Electron Microscopy (SEM), confirm the regular aggregates obtained with composition consistent with the proposal theoretically and validated by Energy-Dispersion X-ray Spectroscopy (EDX) techniques and comparison between secondary emission spectra and Retro-dispersed.

  3. HPLC analysis of 4',5'-monoadduct formation in calf thymus DNA and synthetic polynucleotides treated with UVA and 8-methoxypsoralen

    International Nuclear Information System (INIS)

    Gasparro, F.P.; Bagel, J.; Edelson, R.L.


    8-methoxypsoralen monoadduct formation in calf thymus DNA irradiated with subbands of ultraviolet A light has been quantitated by HPLC analysis of the enzymatic hydrolysates of the DNA. Normalization of the yield of monoadducts for the variation in source output and the absorptivity of 8-MOP at each of the irradiating wavelengths showed that the 4',5'-furan monoadduct was the principal photoproduct and the efficiency of its formation was independent of irradiating wavelength. Synthetic polynucleotides irradiated with ultraviolet A light demonstrated a base composition and sequence dependence for 8-MOP photoreactivity: (poly(dAdT.dAdT)>poly(dA.dT)>poly(dGdC.dGdC) in both the B and Z forms>poly(dT). (author)

  4. Synthetic Biomaterials to Rival Nature's Complexity-a Path Forward with Combinatorics, High-Throughput Discovery, and High-Content Analysis. (United States)

    Zhang, Douglas; Lee, Junmin; Kilian, Kristopher A


    Cells in tissue receive a host of soluble and insoluble signals in a context-dependent fashion, where integration of these cues through a complex network of signal transduction cascades will define a particular outcome. Biomaterials scientists and engineers are tasked with designing materials that can at least partially recreate this complex signaling milieu towards new materials for biomedical applications. In this progress report, recent advances in high throughput techniques and high content imaging approaches that are facilitating the discovery of efficacious biomaterials are described. From microarrays of synthetic polymers, peptides and full-length proteins, to designer cell culture systems that present multiple biophysical and biochemical cues in tandem, it is discussed how the integration of combinatorics with high content imaging and analysis is essential to extracting biologically meaningful information from large scale cellular screens to inform the design of next generation biomaterials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Regiospecific analysis of neutral ether lipids by liquid chromatography/electrospray ionization/single quadrupole mass spectrometry: validation with synthetic compounds

    DEFF Research Database (Denmark)

    Hartvigsen, Karsten; Ravandi, A.; Bukhave, Klaus


    A reversed-phase high-performance liquid chromatography (HPLC) method with on-line electrospray ionization/collision-induced dissociation/mass spectrometry (ESI/CID/MS) is presented for the regiospecific analysis of synthetic reference compounds of neutral ether lipids. The reference compounds were....... The diagnostic ions of directly analyzed 1-O-alkyl-2,3-diacyl-sn- glycerols were the [M - alkyl](+), [M - sn-2-acyl](+) and [M - sn-3-acyl](+) ions. Regiospecific characterization of the fatty acid identity and position was evident from the relative ion intensities, as fragmentation of the sn-2 fatty acids...... for each neutral ether lipid class. The present study demonstrates that reversed-phase HPLC and positive ion ESI/CID/MS provide direct and unambiguous information about the configuration and identity of molecular species in neutral 1-O-alkyl-sn-glycerol classes....

  6. Synthetic Cathinones ("Bath Salts") (United States)

    ... cathinones? Behavioral therapy can be used to treat addiction to synthetic cathinones. Examples include: cognitive-behavioral therapy contingency management, or motivational incentives—providing rewards to ...

  7. Comparative analysis of the effects of synthetic derivatives of batrachotoxin on sodium currents in frog node of Ranvier. (United States)

    Khodorov, B I; Yelin, E A; Zaborovskaya, L D; Maksudov, M Z; Tikhomirova, O B; Leonov, V N


    1. In voltage-clamp experiments on frog myelinated nerve fibers, the effects of nine synthetic derivatives of batrachotoxin (BTX) obtained from 7,8-dihydrobatrachotoxinin A (DBTX-A) on Na+ currents (INa) have been investigated. 2. Both of 20 alpha-esters of DBTX-A with 2,4,5-trimethylpyrrol-3-carboxylic acid (DBTX-P) and benzoic acid (DBTX) at a 10(-5) M concentration caused modification of INa qualitatively similar to that induced by BTX. 3. The quaternary derivative of DBTX (QDBTX) produced such changes in INa only at a 5.10(-4) M concentration, apparently due to its much lower lipid solubility. 4. Replacement of a -CH2- by a -C = O. group in the homomorpholine ring near the tertiary nitrogen atom abolished the DBTX activity, strongly suggesting the necessity of tertiary nitrogen protonation for the toxin interaction with the channel receptor. 5. Transfer of an 11-hydroxygroup from the alpha- to the beta-position in the DBTX molecule did not decrease its activity in spite of the fact that in the beta-position this group is sterically very hindered. The activity of 11 beta-DBTX is at variance with the prediction of Codding's (1983) "oxygen triad" hypothesis. 6. DBTX-A and compounds obtained from DBTX by oxidation of the 11 alpha-hydroxygroup (K-DBTX), acetylation (Ac-DBTX), or reduction of the hemiketal moiety (H2DBTX) even at a concentration as high as 10(-3) M were able to modify only a very small fraction of the Na channels. However, a clear-cut reversible blocking action on both normal and modified Na channels was observed. 7. These results led us to conclude that BTX modifies the Na channels only in the charged form and hemiketal and 20 alpha-ester moieties provide adequate disposition of toxin on the receptor surface. The inability of H2DBTX, DBTX-A, and K-DBTX and Ac-DBTX to modify most of the Na channels can be explained by a low "probability of correct disposition" of these ligands on the receptor surface.

  8. SU-D-207A-01: Female Pelvic Synthetic CT Generation Based On Joint Shape and Intensity Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, L; Jolly, S; Cao, Y; Vineberg, K; Fessler, J; Balter, J [University Michigan, Ann Arbor, MI (United States)


    Purpose: To develop a method for generating female pelvic synthetic CT (MRCT) images from a single MR scan and evaluate its utility in radiotherapy. Methods: Under IRB-approval, an imaging sequence (T1-VIBE-Dixon) was acquired for 10 patients. This sequence yields 3 useful image volumes of different contrast (“in-phase” T1-weighted, fat and water). A previously published pelvic bone shape model was used to generate a rough bone mask for each patient. A modified fuzzy c-means classification was performed on the multi spectral MR data, with a regularization term that utilizes the prior knowledge provided by the bone mask and addresses the intensity overlap between different tissue types. A weighted sum of classification probabilities with attenuation values yielded MRCT volumes. The mean absolute error (MAE) between MRCT and real CT on various regions was calculated following deformable alignment (Velocity). Intensity modulated Treatment plans based on actual CT and MRCT were made and compared. Results: The average/standard deviation of MAE across 10 patients was 10.1/6.7 HU for muscle, 6.7/4.6 HU for fat, 136.9/53.5 HU for bony tissues under 850 HU (97% of total bone volume), 188.9/119.3 HU for bony tissues above 850 HU and 17.3/13.3 HU for intrapelvic soft tissues. Calculated doses were comparable for plans generated on CT and calculated using MRCT densities or vice versa, with differences in PTV D99% (mean/σ) of (–0.1/0.2 Gy) and (0.3/0.2 Gy), PTV D0.5cc of (–0.3/0.2 Gy) and (–0.4/1.7 Gy). OAR differences were similarly small for comparable structures, with differences in bowel V50Gy of (–0.3/0.2%) and (0.0/0.2%), femur V30Gy of (0.7/1.2%) and (0.2/1.2%), sacrum V20GY of (0.0/0.1%) and (–0.1/1.1%) and mean pelvic V20Gy of (0.0/0.1%) and (0.6/1.8%). Conclusion: MRCT based on a single imaging sequence in the female pelvis is feasible, with acceptably small variations in attenuation estimates and calculated doses to target and critical organs. Work

  9. Brave New Warfare: Autonomy in Lethal UAVs (United States)


    Executions,” United Nations General Assembly, May 28, 2010, bodies /hrcouncil/docs/14session/A.HRC.14.24.Add6.pdf. 34 Rique...capability 40 The Army’s Future Combat Sytems (FCS) program was canceled in May 2009 as part of... bodies /hrcouncil/docs/14session/A.HRC.14.24.Ad d6.pdf. Arkin, Ronald. Governing Lethal Behavior in Autonomous Robots. Boca Raton: CRC Press, 2009. doi

  10. Killing Range: Explaining Lethality Variance within a Terrorist Organization. (United States)

    Asal, Victor; Gill, Paul; Rethemeyer, R Karl; Horgan, John


    This paper presents an analysis of the Provisional Irish Republican Army's (PIRA) brigade level behavior during the Northern Ireland Conflict (1970-1998) and identifies the organizational factors that impact a brigade's lethality as measured via terrorist attacks. Key independent variables include levels of technical expertise, cadre age, counter-terrorism policies experienced, brigade size, and IED components and delivery methods. We find that technical expertise within a brigade allows for careful IED usage, which significantly minimizes civilian casualties (a specific strategic goal of PIRA) while increasing the ability to kill more high value targets with IEDs. Lethal counter-terrorism events also significantly affect a brigade's likelihood of killing both civilians and high-value targets but in different ways. Killing PIRA members significantly decreases IED fatalities but also significantly decreases the possibility of zero civilian IED-related deaths in a given year. Killing innocent Catholics in a Brigade's county significantly increases total and civilian IED fatalities. Together the results suggest the necessity to analyze dynamic situational variables that impact terrorist group behavior at the sub-unit level.

  11. Issues surrounding lethal injection as a means of capital punishment. (United States)

    Romanelli, Frank; Whisman, Tyler; Fink, Joseph L


    Lethal injection as a method of state-sanctioned capital punishment was initially proposed in the United States in 1977 and used for the first time in 1982. Most lethal injection protocols use a sequential drug combination of sodium thiopental, pancuronium bromide, and potassium chloride. Lethal injection was originally introduced as a more humane form of execution compared with existing mechanical methods such as electrocution, toxic gassing, hanging, or firing squad. Lethal injection has not, however, been without controversy. Several states are considering whether lethal injection meets constitutional scrutiny forbidding cruel and unusual punishment. Recently in the case of Ralph Baze and Thomas C. Bowling, Petitioners, v John D. Rees, Commissioner, Kentucky Department of Corrections et al, the United States Supreme Court upheld the constitutionality of the lethal injection protocol as carried out in the Commonwealth of Kentucky. Most of the debate has surrounded the dosing and procedures used in lethal injection and whether the drug combinations and measures for administering the drugs truly produce a timely, pain-free, and fail-safe death. Many have also raised issues regarding the "medicalization" of execution and the ethics of health care professionals' participation in any part of the lethal injection process. As a result of all these issues, the future of lethal injection as a means of execution in the United States is under significant scrutiny. Outcomes of ongoing legislative and judicial reviews might result in cessation of lethal injection in totality or in alterations involving specific drug combinations or administration procedures.

  12. A novel poxvirus lethal to red squirrels (Sciurus vulgaris). (United States)

    Thomas, Kathryn; Tompkins, Daniel M; Sainsbury, Anthony W; Wood, Ann R; Dalziel, Robert; Nettleton, Peter F; McInnes, Colin J


    A parapoxvirus has been implicated in the decline of the red squirrel in the United Kingdom. Virus was isolated from an outbreak of lethal disease in red squirrels in the north-east of England. Experimental infection of captive-bred red squirrels confirmed that this virus was the cause of the severe skin lesions observed. Electron microscopic examination of the virus showed that it had a morphology typical of parapoxviruses whilst preliminary sequence data suggested a genomic G+C composition of approximately 66 %, again similar to that found in other parapoxviruses. However Southern hybridization analysis failed to detect three known parapoxvirus genes, two of which have been found so far only in the genus parapoxvirus. Comparative sequence analysis of two other genes, conserved across the eight recognized chordopoxvirus genera, suggests that the squirrel virus represents a previously unrecognized genus of the chordopoxvirus.

  13. Characterization of desmoglein-3 epitope region peptides as synthetic antigens: analysis of their in vitro T cell stimulating efficacy, cytotoxicity, stability, and their conformational features. (United States)

    Szabados, Hajnalka; Uray, Katalin; Majer, Zsuzsa; Silló, Pálma; Kárpáti, Sarolta; Hudecz, Ferenc; Bősze, Szilvia


    Desmoglein-3 (Dsg3) adhesion protein is the main target of autoantibodies and autoreactive T cells in Pemphigus vulgaris (PV) autoimmune skin disorder. Several mapping studies of Dsg3 T cell epitope regions were performed, and based on those data, we designed and synthesized four peptide series corresponding to Dsg3 T cell epitope regions. Each peptide series consists of a 17mer full-length peptide (Dsg3/189-205, Dsg3/206-222, Dsg3/342-358, and Dsg3/761-777) and its N-terminally truncated derivatives, resulting in 15 peptides altogether. The peptides were prepared on solid phase and were chemically characterized. In order to establish a structure-activity relationship, the solution conformation of the synthetic peptides has been investigated using electronic circular dichroism spectroscopy. The in vitro T cell stimulating efficacy of the peptides has been determined on peripheral blood mononuclear cells isolated from whole blood of PV patients and also from healthy donors. After 20 h of stimulation, the interferon (IFN)-γ content of the supernatants was measured by enzyme-linked immunosorbent assay. In the in vitro conditions, peptides were stable and non-cytotoxic. The in vitro IFN-γ production profile of healthy donors and PV patients, induced by peptides as synthetic antigens, was markedly different. The most unambiguous differences were observed after stimulation with 17mer peptide Dsg3/342-358, and three truncated derivatives from two other peptide series, namely, peptides Dsg3/192-205, Dsg3/763-777, and Dsg3/764-777. Comparative analysis of in vitro activity and the capability of oligopeptides to form ordered or unordered secondary structure showed that peptides bearing high solvent sensibility and backbone flexibility were the most capable to distinguish between healthy and PV donors. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  14. Does trade liberalization reduce child mortality in low- and middle-income countries? A synthetic control analysis of 36 policy experiments, 1963-2005. (United States)

    Barlow, Pepita


    Scholars have long argued that trade liberalization leads to lower rates of child mortality in developing countries. Yet current scholarship precludes definitive conclusions about the magnitude and direction of this relationship. Here I analyze the impact of trade liberalization on child mortality in 36 low- and middle-income countries, 1963-2005, using the synthetic control method. I test the hypothesis that trade liberalization leads to lower rates of child mortality, examine whether this association varies between countries and over time, and explore the potentially modifying role of democratic politics, historical context, and geographic location on the magnitude and direction of this relationship. My analysis shows that, on average, trade liberalization had no impact on child mortality in low- and middle-income countries between 1963 and 2005 (Average effect (AE): -0.15%; 95% CI: -2.04%-2.18%). Yet the scale, direction and statistical significance of this association varied markedly, ranging from a ∼20% reduction in child mortality in Uruguay to a ∼20% increase in the Philippines compared with synthetic controls. Trade liberalization was also followed by the largest declines in child mortality in democracies (AE 10-years post reform (AE 10 ): -3.28%), in Latin America (AE 10 : -4.15%) and in the 1970s (AE 10 : -6.85%). My findings show that trade liberalization can create an opportunity for reducing rates of child mortality, but its effects cannot be guaranteed. Inclusive and pro-growth contextual factors appear to influence whether trade liberalization actually yields beneficial consequences in developing societies. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  15. The organisational structure of protein networks: revisiting the centrality-lethality hypothesis. (United States)

    Raman, Karthik; Damaraju, Nandita; Joshi, Govind Krishna


    Protein networks, describing physical interactions as well as functional associations between proteins, have been unravelled for many organisms in the recent past. Databases such as the STRING provide excellent resources for the analysis of such networks. In this contribution, we revisit the organisation of protein networks, particularly the centrality-lethality hypothesis, which hypothesises that nodes with higher centrality in a network are more likely to produce lethal phenotypes on removal, compared to nodes with lower centrality. We consider the protein networks of a diverse set of 20 organisms, with essentiality information available in the Database of Essential Genes and assess the relationship between centrality measures and lethality. For each of these organisms, we obtained networks of high-confidence interactions from the STRING database, and computed network parameters such as degree, betweenness centrality, closeness centrality and pairwise disconnectivity indices. We observe that the networks considered here are predominantly disassortative. Further, we observe that essential nodes in a network have a significantly higher average degree and betweenness centrality, compared to the network average. Most previous studies have evaluated the centrality-lethality hypothesis for Saccharomyces cerevisiae and Escherichia coli; we here observe that the centrality-lethality hypothesis hold goods for a large number of organisms, with certain limitations. Betweenness centrality may also be a useful measure to identify essential nodes, but measures like closeness centrality and pairwise disconnectivity are not significantly higher for essential nodes.

  16. Potential Clinical Uses of CDK Inhibitors: Lessons from Synthetic Lethality Screens

    Czech Academy of Sciences Publication Activity Database

    Vymětalová, Ladislava; Kryštof, Vladimír


    Roč. 35, č. 6 (2015), s. 1156-1174 ISSN 0198-6325 R&D Projects: GA MŠk(CZ) LO1204; GA ČR(CZ) GA15-15264S Institutional support: RVO:61389030 Keywords : cyclin-dependent kinase * inhibitor * cancer Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 9.135, year: 2015

  17. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer.


    Asim, Mohammad; Tarish, Firas; Zecchini, Heather I; Sanjiv, Kumar; Gelali, Eleni; Massie, Charles Edward; Baridi, Ajoeb; Warren, Anne Y; Zhao, Wanfeng; Ogris, Christoph; McDuffus, Leigh-Anne; Mascalchi, Patrice; Shaw, Greg; Dev, Harveer; Wadhwa, Karan


    Emerging data demonstrate homologous recombination (HR) defects in castration resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here, we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival...

  18. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer


    Asim, Mohammad; Tarish, Firas; Zecchini, Heather I.; Sanjiv, Kumar; Gelali, Eleni; Massie, Charles E.; Baridi, Ajoeb; Warren, Anne Y.; Zhao, Wanfeng; Ogris, Christoph; McDuffus, Leigh-Anne; Mascalchi, Patrice; Shaw, Greg; Dev, Harveer; Wadhwa, Karan


    This study was supported by the National Cancer Research Institute (National Institute of Health Research (NIHR) Collaborative Study: ‘Prostate Cancer: Mechanisms of Progression and Treatment (PROMPT)” (grant G0500966/75466). This work was funded by a Cancer Research UK program grant (D.N.), the Swedish Research Council (T.H.), AFA insurance (T.H.), Swedish Cancer Society (T.H.), the Swedish Pain Relief Foundation (T.H.), the Torsten and Ragnar Söderberg Foundation (T.H.), AstraZeneca (T.H.) ...

  19. Genomewide Screen for Synthetic Lethal Interactions with Mutant KRAS in Lung Cancer (United States)


    platform is based on negative selection, i.e., gRNA clones of our interest are lost after selection, we have to address the technical...fragments and then these two fragments were ligated together. Finally, we cloned left arm and right arm of AAVS1 into this vector sequentially...DhCas9TRE3G BlastCAG TRE3G hCas9TRE3G BlastCAG hCas9 hCas9TRE3G 1st PCR 2nd PCR Fig. 1, Construction of inducible human codon optimized Cas9 (hCas9) through 2

  20. Synthetic Lethal Therapeutic Approaches for ARID1A-Mutated Ovarian Cancer (United States)


    Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be an official Department of the Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form

  1. Lethal congenital contracture syndrome (LCCS) and other lethal arthrogryposes in Finland--an epidemiological study. (United States)

    Pakkasjärvi, Niklas; Ritvanen, Annukka; Herva, Riitta; Peltonen, Leena; Kestilä, Marjo; Ignatius, Jaakko


    Arthrogryposis multiplex congenita is a heterogeneous group of disorders characterized by multiple contractures with an estimated frequency of 1 in 3,000 births. With improving diagnostic methods, increasing numbers of fetuses with arthrogryposis are found. The pathogenetic mechanisms are relatively well known but the epidemiology and genetics of the prenatally lethal forms of arthrogryposis are less well known. In this study we collected all cases of a multiple contractures diagnosed in Finland during 1987-2002 including live born infants, stillbirths, and terminated pregnancies. Ninety-two cases of 214 suffered intrauterine demise (68 selective pregnancy terminations and 24 stillbirths) and 58 died in infancy. In 141 out of these cases the diagnosis could be included within lethal arthrogryposes, with a prevalence of 1 in 6,985 (1.43/10,000) births. Of these, 59 had spinal cord pathology at autopsy and thus were of neurogenic origin. Thirty-nine cases had lethal congenital contracture syndrome (LCCS) clinically characterized by total immobility of the fetus at all ultrasound examinations (12 weeks or later), multiple joint contractures in both upper and lower limbs, hydrops, and fetal death before the 32nd week of pregnancy. LCCS is noted as a unique Finnish disorder with a prevalence of 1 in 25,250 (0.40/10,000) births and is a major cause of lethal arthrogryposis in Finland.

  2. Designing synthetic biology. (United States)

    Agapakis, Christina M


    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology.

  3. Methods for preparing synthetic freshwaters. (United States)

    Smith, E J; Davison, W; Hamilton-Taylor, J


    Synthetic solutions that emulate the major ion compositions of natural waters are useful in experiments aimed at understanding biogeochemical processes. Standard recipes exist for preparing synthetic analogues of seawater, with its relatively constant composition, but, due to the diversity of freshwaters, a range of compositions and recipes is required. Generic protocols are developed for preparing synthetic freshwaters of any desired composition. The major problems encountered in preparing hard and soft waters include dissolving sparingly soluble calcium carbonate, ensuring that the ionic components of each concentrated stock solution cannot form an insoluble salt and dealing with the supersaturation of calcium carbonate in many hard waters. For acidic waters the poor solubility of aluminium salts requires attention. These problems are overcome by preparing concentrated stock solutions according to carefully designed reaction paths that were tested using a combination of experiment and equilibrium modeling. These stock solutions must then be added in a prescribed order to prepare a final solution that is brought into equilibrium with the atmosphere. The example calculations for preparing hard, soft and acidic freshwater surrogates with major ion compositions the same as published analyses, are presented in a generalized fashion that should allow preparation of any synthetic freshwater according to its known analysis.

  4. QTL mapping of inbreeding-related cold sensitivity and conditional lethality in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker


    of inbreeding-related and conditionally expressed lethality in Drosophila melanogaster. The lethal effect was triggered by exposure to a cold shock. We used a North Carolina crossing Design 3 to establish the mapping population, as well as to estimate the average dominance ratio and heritability. We found two......Inbreeding depression is a central theme within genetics, and is of specific interest for researchers within evolutionary and conservation genetics and animal and plant breeding. Inbreeding effects are thought to be caused by the joint expression of conditional and unconditional deleterious alleles....... Whenever the expression of deleterious alleles is conditional, this can result in extreme environmental sensitivity in certain inbred lineages. Analysis of conditional lethal effects can reveal some of the loci that are sensitive to inbreeding. We performed a QTL (quantitative trait locus) mapping study...

  5. Performance analysis of a continuous serpentine flow reactor for electrochemical oxidation of synthetic and real textile wastewater: Energy consumption, mass transfer coefficient and economic analysis. (United States)

    Pillai, Indu M Sasidharan; Gupta, Ashok K


    A continuous flow electrochemical reactor was developed, and its application was tested for the treatment of textile wastewater. A parallel plate configuration with serpentine flow was chosen for the continuous flow reactor. Uniparameter optimization was carried out for electrochemical oxidation of synthetic and real textile wastewater (collected from the inlet of the effluent treatment plant). Chemical Oxygen Demand (COD) removal efficiency of 90% was achieved for synthetic textile wastewater (initial COD - 780 mg L -1 ) at a flow rate of 500 mL h -1 (retention time of 6 h) and a current density of 1.15 mA cm -2 and the energy consumption for the degradation was 9.2 kWh (kg COD) -1 . The complete degradation of real textile wastewater (initial COD of 368 mg L -1 ) was obtained at a current density of 1.15 mA cm -2 , NaCl concentration of 1 g L -1 and retention time of 6 h. Energy consumption and mass transfer coefficient of the reactions were calculated. The continuous flow reactor performed better than batch reactor with reference to energy consumption and economy. The overall treatment cost for complete COD removal of real textile wastewater was 5.83 USD m -3 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy. (United States)

    Kandadi, Machender R; Yu, Xuejun; Frankel, Arthur E; Ren, Jun


    Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Wild type (WT) and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.)). Cardiomyocyte contractile and intracellular Ca(2+) properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca(2+) handling), the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, possibly through regulation of autophagy and mitochondrial function.

  7. Cardiac-specific catalase overexpression rescues anthrax lethal toxin-induced cardiac contractile dysfunction: role of oxidative stress and autophagy

    Directory of Open Access Journals (Sweden)

    Kandadi Machender R


    Full Text Available Abstract Background Lethal and edema toxins secreted by Bacillus anthracis during anthrax infection were found to incite serious cardiovascular complications. However, the underlying mechanisms in anthrax lethal toxin-induced cardiac anomalies remain unknown. This study was designed to evaluate the impact of antioxidant enzyme catalase in anthrax lethal toxin-induced cardiomyocyte contractile dysfunction. Methods Wild type (WT and cardiac-specific catalase overexpression mice were challenged with lethal toxin (2 μg/g, intraperotineally (i.p.. Cardiomyocyte contractile and intracellular Ca2+ properties were assessed 18 h later using an IonOptix edge-detection system. Proteasome function was assessed using chymotrypsin-like and caspase-like activities. GFP-LC3 puncta and Western blot analysis were used to evaluate autophagy and protein ubiquitination. Results Lethal toxin exposure suppressed cardiomyocyte contractile function (suppressed peak shortening, maximal velocity of shortening/re-lengthening, prolonged duration of shortening/re-lengthening, and impaired intracellular Ca2+ handling, the effects of which were alleviated by catalase. In addition, lethal toxin triggered autophagy, mitochondrial and ubiquitin-proteasome defects, the effects of which were mitigated by catalase. Pretreatment of cardiomyocytes from catalase mice with the autophagy inducer rapamycin significantly attenuated or ablated catalase-offered protection against lethal toxin-induced cardiomyocyte dysfunction. On the other hand, the autophagy inhibitor 3-MA ablated or significantly attenuated lethal toxin-induced cardiomyocyte contractile anomalies. Conclusions Our results suggest that catalase is protective against anthrax lethal toxin-induced cardiomyocyte contractile and intracellular Ca2+ anomalies, possibly through regulation of autophagy and mitochondrial function.

  8. Testing of candidate non-lethal sampling methods for detection of Renibacterium salmoninarum in juvenile Chinook salmon Oncorhynchus tshawytscha (United States)

    Elliott, Diane G.; McKibben, Constance L.; Conway, Carla M.; Purcell, Maureen K.; Chase, Dorothy M.; Applegate, Lynn M.


    Non-lethal pathogen testing can be a useful tool for fish disease research and management. Our research objectives were to determine if (1) fin clips, gill snips, surface mucus scrapings, blood draws, or kidney biopsies could be obtained non-lethally from 3 to 15 g Chinook salmon Oncorhynchus tshawytscha, (2) non-lethal samples could accurately discriminate between fish exposed to the bacterial kidney disease agent Renibacterium salmoninarum and non-exposed fish, and (3) non-lethal samples could serve as proxies for lethal kidney samples to assess infection intensity. Blood draws and kidney biopsies caused ≥5% post-sampling mortality (Objective 1) and may be appropriate only for larger fish, but the other sample types were non-lethal. Sampling was performed over 21 wk following R. salmoninarum immersion challenge of fish from 2 stocks (Objectives 2 and 3), and nested PCR (nPCR) and real-time quantitative PCR (qPCR) results from candidate non-lethal samples were compared with kidney tissue analysis by nPCR, qPCR, bacteriological culture, enzyme-linked immunosorbent assay (ELISA), fluorescent antibody test (FAT) and histopathology/immunohistochemistry. R. salmoninarum was detected by PCR in >50% of fin, gill, and mucus samples from challenged fish. Mucus qPCR was the only non-lethal assay exhibiting both diagnostic sensitivity and specificity estimates >90% for distinguishing between R. salmoninarum-exposed and non-exposed fish and was the best candidate for use as an alternative to lethal kidney sample testing. Mucus qPCR R. salmoninarum quantity estimates reflected changes in kidney bacterial load estimates, as evidenced by significant positive correlations with kidney R. salmoninaruminfection intensity scores at all sample times and in both fish stocks, and were not significantly impacted by environmentalR. salmoninarum concentrations.

  9. Lead preconcentration in synthetic samples with triton x-114 in the cloud point extraction and analysis by atomic absorption (EAAF)

    International Nuclear Information System (INIS)

    Zegarra Pisconti, Marixa; Cjuno Huanca, Jesus


    A methodology was developed about lead preconcentration in water samples that were added dithizone as complexing agent, previously dissolved in the nonionic surfactant Triton X-114, until the formation of the critical micelle concentration and the cloud point temperature. The centrifuged system gave a precipitate with high concentrations of Pb (II) that was measured by atomic absorption spectroscopy with flame (EAAF). The method has proved feasible to be implemented as a method of preconcentration and analysis of Pb in aqueous samples with concentrations less than 1 ppm. Several parameters were evaluated to obtain a percentage recovery of 89.8%. (author)

  10. Lethal photosensitization of biofilm-grown bacteria (United States)

    Wilson, Michael


    Antibacterial agents are increasingly being used for the prophylaxis and treatment of oral diseases. As these agents can be rendered ineffective by resistance development in the target organisms there is a need to develop alternative antimicrobial approaches. Light-activated antimicrobial agents release singlet oxygen and free radicals which can kill adjacent bacteria and a wide range of cariogenic and periodontopathogenic bacteria has been shown to be susceptible to such agents. In the oral cavity these organisms are present as biofilms (dental plaques) which are less susceptible to traditional antimicrobial agents than bacterial suspensions. The results of these studies have shown that biofilm-grown oral bacteria are also susceptible to lethal photosensitization although the light energy doses required are grater than those needed to kill the organisms when they are grown as aqueous suspensions.

  11. Lethal fish hook attachment - An unusual occurrence. (United States)

    Byard, Roger W


    A 39-year-old fisherman is reported who was dragged into the water from a boat after he became entangled in fishing line. His death was attributed to salt water drowning. At autopsy the cause of death was confirmed and the mechanism of the lethal event elucidated. Specifically, a large fish hook attached to line was embedded in his right wrist. The hook had passed beneath flexor tendons and had firmly attached him to fishing line that was being dropped from the vessel. There were no other significant injuries or underlying diseases present. This case demonstrates another rare situation in the commercial fishing industry that may result in a victim being dragged from a boat and drowned. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  12. Parental response to severe or lethal prenatal diagnosis

    DEFF Research Database (Denmark)

    Lou, Stina; Jensen, Lotte Groth; Petersen, Olav Bjørn


    . Prospective parents who continued the pregnancy wished to be acknowledged as parents, and engaged in planning to obtain a sense of meaning and control. Selective disclosure and concerns about negative responses were issues both for the parents who terminated and those who continued a pregnancy. Conclusion......Objective A severe or lethal prenatal diagnosis places great demands on prospective parents, who face choices of far-reaching consequences, such as continuing or terminating the pregnancy. How best to support these parents is a clinical challenge. This systematic review aimed to identify...... and synthesize the qualitative evidence regarding prospective parents’ responses to such prenatal diagnoses. Methods Following PRISMA guidelines, four databases were systematically searched and 28 studies met the inclusion criteria. Thematic analysis guided data extraction and synthesis of findings. The CERQual...

  13. Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome. (United States)

    Byard, Roger W


    A case of intracerebral hemorrhage in Turner syndrome is reported with an analysis of possible causes of cerebrovascular accidents in this condition. A 42-year-old woman with known Turner syndrome died soon after hospital admission having been found unconscious at her home address. At autopsy, she showed typical features of Turner syndrome with short stature, webbing of the neck, underdeveloped breasts, and an increased carrying angle of the arm. Death was due to a large left-sided intracerebral hemorrhage extending from the left basal ganglia into the white matter of the frontal lobe and lateral ventricle. Cases of unexpected death in Turner syndrome may arise from occult cerebrovascular accidents which may be hemorrhagic or nonhemorrhagic. Associated features include hypertension, vascular malformations, accelerated atherogenesis, cystic medial necrosis, and moyamoya syndrome. The possibility of Turner syndrome should be considered in cases where there has been a lethal cerebrovascular event in a younger woman. © 2016 American Academy of Forensic Sciences.

  14. Immunopathologic responses to non-lethal sepsis. (United States)

    Ebong, S J; Call, D R; Bolgos, G; Newcomb, D E; Granger, J I; O'Reilly, M; Remick, D G


    Although sepsis causes significant morbidity and mortality, its basic pathology is still not well understood. We investigated the inflammatory and physiologic alterations of non-lethal sepsis using cecal ligation and puncture (CLP), a model that induces peritonitis due to mixed intestinal flora, reproducing the complex immunology of sepsis. Groups of mice were subjected to CLP (25G needle) or sham surgery, had minimitters implanted to continuously monitor temperature and activity, and were sacrificed daily for 6 days. There was significant hypothermia (6-13 hrs post-surgery), and decreases in activity (to day 4) and weight (to day 3) but no mortality in the CLP group. Blood analyses of the CLP-treated mice showed reduced hemoglobin, platelets, lymphocytes, monocytes, and neutrophils, compared to sham animals. Both groups had nearly equivalent neutrophil influx into the peritoneum. Plasma and peritoneal G-CSF, IL-6, as well as the murine chemokines KC and MIP2-alpha were significantly higher in the CLP-treated mice at day 1. Plasma and peritoneal TNF were low (<70 pg/mL). While there was elevated IL-1beta in the peritoneum of the CLP-treated mice, this cytokine was not detected in the plasma in either treatment group. Cytokines were not detected in the pulmonary airspace of the CLP-treated mice and PMNs were not recruited to this site. Our data shows altered immunopathology in non-lethal sepsis with significant blood and cytokine alterations. Since there was 100% survival, the inflammatory response was appropriate and probably even protective.

  15. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M


    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  16. Synthetic Base Fluids (United States)

    Brown, M.; Fotheringham, J. D.; Hoyes, T. J.; Mortier, R. M.; Orszulik, S. T.; Randles, S. J.; Stroud, P. M.

    The chemical nature and technology of the main synthetic lubricant base fluids is described, covering polyalphaolefins, alkylated aromatics, gas-to-liquid (GTL) base fluids, polybutenes, aliphatic diesters, polyolesters, polyalkylene glycols or PAGs and phosphate esters.Other synthetic lubricant base oils such as the silicones, borate esters, perfluoroethers and polyphenylene ethers are considered to have restricted applications due to either high cost or performance limitations and are not considered here.Each of the main synthetic base fluids is described for their chemical and physical properties, manufacture and production, their chemistry, key properties, applications and their implications when used in the environment.

  17. Microwave-accelerated derivatization for the simultaneous gas chromatographic-mass spectrometric analysis of natural and synthetic estrogenic steroids. (United States)

    Zuo, Yuegang; Zhang, Kai; Lin, Yuejuan


    A rapid microwave-accelerated derivatization process for the GC-MS analysis of steroid estrogens, estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethynylestradiol (EE2) and mestranol (MeEE2), was developed. Under microwave irradiation, the five estrogenic hormones studied were simultaneously derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA)+trimethylchlorosilane (TMCS) in pyridine solution. Effects of irradiation time (15-120 s) and power level (240-800 W) on the yield of the derivatization were investigated. The derivatization under the irradiation of 800 W microwave for 60s produced comparable results when compared with the conventional heating process in a sand bath for 30 min at 80 degrees C in terms of derivatization yield, linearity and precision for all steroid hormones tested. The calibration curves are linear between 3.00 and 3.00 x 10(2) microg mL(-1). The square of the regression coefficients (R(2)) range from 0.979 to 1.000. The applicability of the method was evaluated on spiked river and distilled water samples at two concentrations, 25.0 and 2.00 x 10(2) ng mL(-1). The recoveries obtained by using microwave heating (60s, 800 W) were similar to those by conventional heating. When combined solid-phase extraction (SPE) with the application of the microwave-accelerated derivatization proposed here, the detection limits of 0.02-0.1 ng L(-1) for the steroid hormones have been achieved. The results demonstrated that microwave-accelerated derivatization is an efficient and suitable sample preparation method for the GC-MS analysis of estrogenic steroids.

  18. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta


    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.

  19. Synthetic Biological Membrane (SBM) (United States)

    National Aeronautics and Space Administration — The ultimate goal of the Synthetic Biological Membrane project is to develop a new type of membrane that will enable the wastewater treatment system required on...

  20. Design response spectra-compliant real and synthetic GMS for seismic analysis of seismically isolated nuclear reactor containment building

    Energy Technology Data Exchange (ETDEWEB)

    Ali, Ahmer [ENVICO Consultants Co. Ltd., Seoul (Korea, Republic of); Abu-Hayah, Nadin; Kim, Doo Kie [Civil and Environmental Engineering, Kunsan National University, Gunsan (Korea, Republic of); Cho, Sung Gook [Innose Tech Co., Ltd., Incheon (Korea, Republic of)


    Due to the severe impacts of recent earthquakes, the use of seismic isolation is paramount for the safety of nuclear structures. The diversity observed in seismic events demands ongoing research to analyze the devastating attributes involved, and hence to enhance the sustainability of base-isolated nuclear power plants. This study reports the seismic performance of a seismically-isolated nuclear reactor containment building (NRCB) under strong short-period ground motions (SPGMs) and long-period ground motions (LPGMs). The United States Nuclear Regulatory Commission-based design response spectrum for the seismic design of nuclear power plants is stipulated as the reference spectrum for ground motion selection. Within the period range(s) of interest, the spectral matching of selected records with the target spectrum is ensured using the spectral-compatibility approach. NRC-compliant SPGMs and LPGMs from the mega-thrust Tohoku earthquake are used to obtain the structural response of the base-isolated NRCB. To account for the lack of earthquakes in low-to-moderate seismicity zones and the gap in the artificial synthesis of long-period records, wavelet-decomposition based autoregressive moving average modeling for artificial generation of real ground motions is performed. Based on analysis results from real and simulated SPGMs versus LPGMs, the performance of NRCBs is discussed with suggestions for future research and seismic provisions.

  1. Hybridization with synthetic oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

    Szostak, J.W.; Stiles, J.I.; Tye, B.K.; Sherman, F.; Wu, R.


    Procedures are described for the use of synthetic oligonucleotides for Southern blot experiments and gene bank screening, and the effect of various mismatches on the efficiency of hybridization is demonstrated. The following topics are discussed: sensitivity vs. specificity, hybridization of a 12-mer to the lambda endolysin gene; hybridization of oligonucleotide probes to the E. coli lac operator; hybridization of synthetic probes to the CYC1 gene of yeast; and cloning eucaryotic genes. (HLW)

  2. Mammalian Synthetic Biology


    Martella, Andrea; Pollard, Steven M; Dai, Junbiao; Cai, Yizhi


    The enabling technologies of synthetic biology are opening up new opportunities for engineering and enhancement of mammalian cells. This will stimulate diverse applications in many life science sectors such as regenerative medicine, development of biosensing cell lines, therapeutic protein production, and generation of new synthetic genetic regulatory circuits. Harnessing the full potential of these new engineering-based approaches requires the design and assembly of large DNA constructs-pote...

  3. Fast analysis of synthetic antioxidants in edible vegetable oil using trilinear component modeling of liquid chromatography-diode array detection data. (United States)

    Wang, Jian-Yao; Wu, Hai-Long; Chen, Yao; Sun, Yan-Mei; Yu, Yong-Jie; Zhang, Xiao-Hua; Yu, Ru-Qin


    A new chromatographic methodology is presented for fast quantitative analysis of ten synthetic phenolic antioxidants in five kinds of oil samples: propyl gallate (PG), 2,4,5-trihydroxybutyrophenone (THBP), tert-butylhydroquinone (TBHQ), nordihydroguaiaretic acid (NDGA), ethoxyquin (EQ), 3-tert-butyl-4- hydroxyanisole (BHA), octyl gallate (OG), 2,6-di-tert-butyl-4-hydroxymethyphenol (Ionox-100), dodecyl gallate (DG), 3,5-di-tert-butyl-4-hydroxytoluene (BHT). The second-order calibration, with second-order advantage, based on the alternating penalty trilinear decomposition (APTLD) algorithm has shown to be an excellent tool for modeling the three-way data, where overlapping peaks, uncalibrated inteferences, and baseline drift existed, making the fast determination and resolution of the phenolic antioxidants in oils possible. Such extraction procedure in which the antioxidants of interest would be seperated is unnecessary and the ten antioxidants can be eluted within 6 mins. For the validation of the method, linearity, root-mean-square error of prediction (RMSEP) and limit of detection (LOD) have been performed. The average recovery of antioxidants ranges from 94.9 to 106.1% and the ten analytes can be adequately determined with limits of detection of 0.18-5.72 μgm l(-1). Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Absolute probability estimates of lethal vessel strikes to North Atlantic right whales in Roseway Basin, Scotian Shelf. (United States)

    van der Hoop, Julie M; Vanderlaan, Angelia S M; Taggart, Christopher T


    Vessel strikes are the primary source of known mortality for the endangered North Atlantic right whale (Eubalaena glacialis). Multi-institutional efforts to reduce mortality associated with vessel strikes include vessel-routing amendments such as the International Maritime Organization voluntary "area to be avoided" (ATBA) in the Roseway Basin right whale feeding habitat on the southwestern Scotian Shelf. Though relative probabilities of lethal vessel strikes have been estimated and published, absolute probabilities remain unknown. We used a modeling approach to determine the regional effect of the ATBA, by estimating reductions in the expected number of lethal vessel strikes. This analysis differs from others in that it explicitly includes a spatiotemporal analysis of real-time transits of vessels through a population of simulated, swimming right whales. Combining automatic identification system (AIS) vessel navigation data and an observationally based whale movement model allowed us to determine the spatial and temporal intersection of vessels and whales, from which various probability estimates of lethal vessel strikes are derived. We estimate one lethal vessel strike every 0.775-2.07 years prior to ATBA implementation, consistent with and more constrained than previous estimates of every 2-16 years. Following implementation, a lethal vessel strike is expected every 41 years. When whale abundance is held constant across years, we estimate that voluntary vessel compliance with the ATBA results in an 82% reduction in the per capita rate of lethal strikes; very similar to a previously published estimate of 82% reduction in the relative risk of a lethal vessel strike. The models we developed can inform decision-making and policy design, based on their ability to provide absolute, population-corrected, time-varying estimates of lethal vessel strikes, and they are easily transported to other regions and situations.

  5. Lethal and sublethal effects of pesticides in the management of Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae) on Capsicum annuum L. (United States)

    Breda, Mariana O; Oliveira, José V; Esteves Filho, Alberto B; Barbosa, Douglas Rs; Santos, Andrezo A


    The evaluation of lethal and sublethal effects is of great importance for a complete assessment of the total impact of chemical compounds upon pest populations and the development of management strategies. In this study, we evaluated the lethal and sublethal effects of different synthetic and botanical products on the broad mite Polyphagotarsonemus latus (Banks), a major pest of Capsicum annuum L. and other crops. Abamectin had the highest lethal effect on P. latus, followed by spiromesifen, azadirachtin, neem oil and nitrogen fertiliser + citric acid. The sublethal effects of the products were indicated by the influence on mite population growth, affecting the numbers of females, males, larvae, pupae and eggs. Furthermore, a negative instantaneous rate of increase in P. latus and repellent effects were observed. The lethal and sublethal effects of abamectin, spiromesifen, azadirachtin and neem oil significantly affect P. latus population growth, as well as causing repellence to this mite on C. annuum, and they should be considered in the integrated pest management of this mite. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  6. Perinatal-lethal Gaucher disease presenting as hydrops fetalis ...

    African Journals Online (AJOL)

    Perinatal-lethal Gaucher disease is very rare and is considered a variant of type 2 Gaucher disease that occurs in the neonatal period. The most distinct features of perinatal-lethal Gaucher disease are non-immune hydrops fetalis. Less common signs of the disease are hepatosplenomegaly, ichthyosis and arthrogryposis.

  7. The lethal injection quandary: how medicine has dismantled the death penalty. (United States)

    Denno, Deborah W


    On February 20, 2006, Michael Morales was hours away from execution in California when two anesthesiologists declined to participate in his lethal injection procedure, thereby halting all state executions. The events brought to the surface the long-running schism between law and medicine, raising the question of whether any beneficial connection between the professions ever existed in the execution context. History shows it seldom did. Decades of botched executions prove it. This Article examines how states ended up with such constitutionally vulnerable lethal injection procedures, suggesting that physician participation in executions, though looked upon with disdain, is more prevalent--and perhaps more necessary--than many would like to believe. The Article also reports the results of this author's unique nationwide study of lethal injection protocols and medical participation. The study demonstrates that states have continued to produce grossly inadequate protocols that severely restrict sufficient understanding of how executions are performed and heighten the likelihood of unconstitutionality. The analysis emphasizes in particular the utter lack of medical or scientific testing of lethal injection despite the early and continuous involvement of doctors but ongoing detachment of medical societies. Lastly, the Article discusses the legal developments that led up to the current rush of lethal injection lawsuits as well as the strong and rapid reverberations that followed, particularly with respect to medical involvement. This Article concludes with two recommendations. First, much like what occurred in this country when the first state switched to electrocution, there should be a nationwide study of proper lethal injection protocols. An independent commission consisting of a diverse group of qualified individuals, including medical personnel, should conduct a thorough assessment of lethal injection, especially the extent of physician participation. Second, this

  8. A Synthetic Teammate for UAV Applications: A Prospective Look

    National Research Council Canada - National Science Library

    Gluck, Kevin A; Ball, Jerry T; Gunzelmann, Glenn; Krusmark, Michael A; Lyon, Don R; Cooke, Nancy J


    ..., computational cognitive process modeling of aircraft maneuvering and reconnaissance missions, verbal interaction between human operators and synthetic entities, and the formal analysis of team skill...

  9. Toward Synthetic Biology Strategies for Adipic Acid Production: An in Silico Tool for Combined Thermodynamics and Stoichiometric Analysis of Metabolic Networks. (United States)

    Averesch, Nils J H; Martínez, Verónica S; Nielsen, Lars K; Krömer, Jens O


    Adipic acid, a nylon-6,6 precursor, has recently gained popularity in synthetic biology. Here, 16 different production routes to adipic acid were evaluated using a novel tool for network-embedded thermodynamic analysis of elementary flux modes. The tool distinguishes between thermodynamically feasible and infeasible modes under determined metabolite concentrations, allowing the thermodynamic feasibility of theoretical yields to be assessed. Further, patterns that always caused infeasible flux distributions were identified, which will aid the development of tailored strain design. A review of cellular efflux mechanisms revealed that significant accumulation of extracellular product is only possible if coupled with ATP hydrolysis. A stoichiometric analysis demonstrated that the maximum theoretical product carbon yield heavily depends on the metabolic route, ranging from 32 to 99% on glucose and/or palmitate in Escherichia coli and Saccharomyces cerevisiae metabolic models. Equally important, metabolite concentrations appeared to be thermodynamically restricted in several pathways. Consequently, the number of thermodynamically feasible flux distributions was reduced, in some cases even rendering whole pathways infeasible, highlighting the importance of pathway choice. Only routes based on the shikimate pathway were thermodynamically favorable over a large concentration and pH range. The low pH capability of S. cerevisiae shifted the thermodynamic equilibrium of some pathways toward product formation. One identified infeasible-pattern revealed that the reversibility of the mitochondrial malate dehydrogenase contradicted the current state of knowledge, which imposes a major restriction on the metabolism of S. cerevisiae. Finally, the evaluation of industrially relevant constraints revealed that two shikimate pathway-based routes in E. coli were the most robust.

  10. Lethal and sub-lethal effects of five pesticides used in rice farming on the earthworm Eisenia fetida

    NARCIS (Netherlands)

    Rico, Andreu; Sabater, Consuelo; Castillo, María Ángeles


    The toxicity of five pesticides typically used in rice farming (trichlorfon, dimethoate, carbendazim, tebuconazole and prochloraz) was evaluated on different lethal and sub-lethal endpoints of the earthworm Eisenia fetida. The evaluated endpoints included: avoidance behaviour after an exposure

  11. [Lethality and outcome in multiple injured patients after severe abdominal and pelvic trauma. Influence of preclinical volume replacement - an analysis of 604 patients from the trauma registry of the DGU]. (United States)

    Hussmann, B; Taeger, G; Lefering, R; Waydhas, C; Nast-Kolb, D; Ruchholtz, S; Lendemans, S


    Uncontrollable hemorrhaging after blunt trauma and the resulting hemorrhagic shock is still one of the main causes of death in trauma patients. Starting volume replacement before admission to hospital is one of the main pillars of immediate treatment. The statements concerning the quantity of the preclinically administered fluid are still controversial and have a low level of evidence in the literature. Massive abdominal trauma and unstable pelvic fractures belong to the most relevant causes of hemorrhagic shock. The aim of this study was to analyze the influence of the quantity of the preclinically administered fluid on the posttraumatic course of patients with massive abdominal and pelvic injuries. All patients of the trauma registry of the DGU (German Society for Trauma Surgery) who met the following criteria were included: injury severity score ≥16 points, primary admission to hospital, age ≥16 years, initial blood pressure 3000 ml). Of the 375 patients with abdominal trauma and 229 patients with pelvic trauma were consistent with the inclusion criteria. In both groups an increasing volume replacement was associated with an increased need for transfusion and a reduction of the coagulation ability (Quick 61% in the case of 3000 ml). The rescue time had a relevant influence on the quantity of preclinically infused volume (62 min for 3000 ml). On admission to hospital the blood pressure values were on average the same in all patients (~ 95 mmHg). With an increasing volume a slight elevation of lethality was found as well as a significant increase of the transfused erythrocyte concentrates, a significant deterioration of coagulation and an increase of patients with mass transfusions. In the case of a preclinical relevant bleeding after blunt pelvic or abdominal trauma moderate volume replacement (<1000 ml) results in an enhancement of the initial coagulation situation and in a reduction in the need for transfusion. The results of this study support the

  12. Tumor clone dynamics in lethal prostate cancer. (United States)

    Carreira, Suzanne; Romanel, Alessandro; Goodall, Jane; Grist, Emily; Ferraldeschi, Roberta; Miranda, Susana; Prandi, Davide; Lorente, David; Frenel, Jean-Sebastien; Pezaro, Carmel; Omlin, Aurelius; Rodrigues, Daniel Nava; Flohr, Penelope; Tunariu, Nina; S de Bono, Johann; Demichelis, Francesca; Attard, Gerhardt


    It is unclear whether a single clone metastasizes and remains dominant over the course of lethal prostate cancer. We describe the clonal architectural heterogeneity at different stages of disease progression by sequencing serial plasma and tumor samples from 16 ERG-positive patients. By characterizing the clonality of commonly occurring deletions at 21q22, 8p21, and 10q23, we identified multiple independent clones in metastatic disease that are differentially represented in tissue and circulation. To exemplify the clinical utility of our studies, we then showed a temporal association between clinical progression and emergence of androgen receptor (AR) mutations activated by glucocorticoids in about 20% of patients progressing on abiraterone and prednisolone or dexamethasone. Resistant clones showed a complex dynamic with temporal and spatial heterogeneity, suggesting distinct mechanisms of resistance at different sites that emerged and regressed depending on treatment selection pressure. This introduces a management paradigm requiring sequential monitoring of advanced prostate cancer patients with plasma and tumor biopsies to ensure early discontinuation of agents when they become potential disease drivers. Copyright © 2014, American Association for the Advancement of Science.

  13. Non lethal Raine syndrome and differential diagnosis. (United States)

    Elalaoui, Siham Chafai; Al-Sheqaih, Nada; Ratbi, Ilham; Urquhart, Jill E; O'Sullivan, James; Bhaskar, Sanjeev; Williams, Simon S; Elalloussi, Mustapha; Lyahyai, Jaber; Sbihi, Leila; Cherkaoui Jaouad, Imane; Sbihi, Abdelhafid; Newman, William G; Sefiani, Abdelaziz


    Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. Defining the Synthetic Biology Supply Chain. (United States)

    Frazar, Sarah L; Hund, Gretchen E; Bonheyo, George T; Diggans, James; Bartholomew, Rachel A; Gehrig, Lindsey; Greaves, Mark

    Several recent articles have described risks posed by synthetic biology and spurred vigorous discussion in the scientific, commercial, and government communities about how to best detect, prevent, regulate, and respond to these risks. The Pacific Northwest National Laboratory's (PNNL) deep experience working with dual-use technologies for the nuclear industry has shown that analysis of supply chains can reveal security vulnerabilities and ways to mitigate security risk without hindering beneficial research and commerce. In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology to illustrate new insights about the effectiveness of current regulations, the possible need for different screening approaches, and new technical solutions that could help identify or mitigate risks in the synthetic biology supply chain.

  15. Visualizing Chemical Bonds in Synthetic Molecules (United States)

    Collins, Laura C.; Ruth, Anthony; Green, David B.; Janko, Boldizsar; Gomes, Kenjiro K.

    The use of synthetic quantum systems makes it possible to study phenomena that cannot be probed by conventional experiments. We created synthetic molecules using atomic manipulation and directly imaged the chemical bonds using tunneling spectroscopy. These synthetic systems allow us to probe the structure and electronic properties of chemical bonds in molecules, including those that would be unstable in nature, with unprecedented detail. The experimental images of electronic states in our synthetic molecules show a remarkable match to the charge distribution predicted by density functional theory calculations. The statistical analysis of the spectroscopy of these molecules can be adapted in the future to quantify aromaticity, which has been difficult to quantify universally thus far due to vague definitions. We can also study anti-aromatic molecules which are unstable naturally, to illuminate the electronic consequences of antiaromaticity.

  16. Liver transplantation for lethal genetic syndromes: a novel model of personalized genomic medicine. (United States)

    Petrowsky, Henrik; Brunicardi, F Charles; Leow, Voon Meng; Venick, Robert S; Agopian, Vatche; Kaldas, Fady M; Zarrinpar, Ali; Markovic, Daniela; McDiarmid, Sue V; Hong, Johnny C; Farmer, Douglas G; Hiatt, Jonathan R; Busuttil, Ronald W


    Our aim was to analyze our single-center experience with orthotopic liver transplantation for metabolic lethal genetic syndromes in children and adults. From 1984 to 2012, all pediatric (younger than 18 years) and adult (18 years and older) patients who underwent orthotopic liver transplantation for lethal genetic disorders were identified. Data on diagnostic pathways and specific outcomes were analyzed for both groups. Outcomes measures included recurrence rate as well as graft and patient survival. Metabolic lethal genetic syndrome was the primary indication for orthotopic liver transplantation in 152 of 4,564 patients (3.3%) at University of California, Los Angeles during the study period (74 pediatric patients and 78 adults). Genetic testing was performed in only 12% of the 152 patients and in 39% of patients after 2006. Two patients (1.3%) experienced a recurrence of the genetic disease. Overall 5- and 20-year survival rates were 89% and 77% for children and 73% and 50% for adults. Survival of pediatric patients was superior to adults (log-rank p < 0.009). Multivariate analysis identified age (hazard ratio = 2.18), preoperative life support (hazard ratio = 2.68), and earlier transplantation (hazard ratio = 3.41) as independent predictors of reduced survival. Orthotopic liver transplantation achieved excellent long-term survival in pediatric and adult patients with lethal genetic syndromes and represents a model of personalized genomic medicine by providing gene therapy through solid organ transplantation. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Synthetic guide star generation (United States)

    Payne, Stephen A [Castro Valley, CA; Page, Ralph H [Castro Valley, CA; Ebbers, Christopher A [Livermore, CA; Beach, Raymond J [Livermore, CA


    A system for assisting in observing a celestial object and providing synthetic guide star generation. A lasing system provides radiation at a frequency at or near 938 nm and radiation at a frequency at or near 1583 nm. The lasing system includes a fiber laser operating between 880 nm and 960 nm and a fiber laser operating between 1524 nm and 1650 nm. A frequency-conversion system mixes the radiation and generates light at a frequency at or near 589 nm. A system directs the light at a frequency at or near 589 nm toward the celestial object and provides synthetic guide star generation.

  18. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

    Kortbek, Jacob; Jensen, Jørgen Arendt; Gammelmark, Kim Løkke


    A synthetic aperture focusing (SAF) technique denoted Synthetic Aperture Sequential Beamforming (SASB) suitable for 2D and 3D imaging is presented. The technique differ from prior art of SAF in the sense that SAF is performed on pre-beamformed data contrary to channel data. The objective...... is stored. The second stage applies the focused image lines from the first stage as input data. The SASB method has been investigated using simulations in Field II and by off-line processing of data acquired with a commercial scanner. The performance of SASB with a static image object is compared with DRF...

  19. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh


    The widespread use of artificial insemination in cattle breeding Worldwide leads to reduced effective population sizes and increased inbreeding levels. Increased inbreeding result in increased probalility of expression of recessive defective alleles, which probably is reflected in a decline...... in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

  20. Pictures of Synthetic Biology : A reflective discussion of the representation of Synthetic Biology (SB) in the German-language media and by SB experts. (United States)

    Cserer, Amelie; Seiringer, Alexandra


    This article is concerned with the representation of Synthetic Biology in the media and by biotechnology experts. An analysis was made of German-language media articles published between 2004 and 2008, and interviews with biotechnology-experts at the Synthetic Biology conference SB 3.0 in Zurich 2007. The results have been reflected in terms of the definition of Synthetic Biology, applications of Synthetic Biology and the perspectives of opportunities and risks. In the media, Synthetic Biology is represented as a new scientific field of biology with an engineering-like thinking, while the scientists interviewed mostly define Synthetic Biology as contrary to nature and the natural system. Media articles present Synthetic Biology broadly with positive potential and inform the publics less about the potential risks than about the benefits of Synthetic Biology. In contrast, the experts interviewed reflect more on the risks than the opportunities of Synthetic Biology. Both used metaphors to describe Synthetic Biology and its aspects.

  1. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Oddershede, Niels


    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...

  2. CD4+ T cells targeting dominant and cryptic epitopes from Bacillus anthracis Lethal Factor

    Directory of Open Access Journals (Sweden)

    Stephanie eAscough


    Full Text Available Anthrax is an endemic infection in many countries, particularly in the developing world. The causative agent, Bacillus anthracis, mediates disease through the secretion of binary exotoxins. Until recently, research into adaptive immunity targeting this bacterial pathogen has largely focused on the humoral response to these toxins. There is, however, growing recognition that cellular immune responses involving IFNγ producing CD4+ T cells also contribute significantly to a protective memory response. An established concept in adaptive immunity to infection is that during infection of host cells, new microbial epitopes may be revealed, leading to immune recognition of so called ‘cryptic’ or ‘subdominant’ epitopes. We analysed the response to both cryptic and immunodominant T cell epitopes derived from the toxin component lethal factor and presented by a range of HLA-DR alleles. Using IFNγ-ELISPOT assays we characterised epitopes that elicited a response following immunisation with synthetic peptide and the whole protein and tested their capacities to bind purified HLA-DR molecules in vitro. We found that DR1 transgenics demonstrated T cell responses to a greater number of domain III cryptic epitopes than other HLA-DR transgenics, and that this pattern was repeated with the immunodominant epitopes, a greater proportion of these epitopes induced a T cell response when presented within the context of the whole protein. Immunodominant epitopes LF457-476 and LF467-487 were found to induce a T cell response to the peptide, as well as to the whole native LF protein in DR1 and DR15, but not in DR4 trangenics. The analysis of Domain I revealed the presence of several unique cryptic epitopes all of which showed a strong to moderate relative binding affinity to HLA-DR4 molecules. However, none of the cryptic epitopes from either domain III or I displayed notably high binding affinities across all HLA-DR alleles assayed. These responses were

  3. What Are Synthetic Cannabinoids? (United States)

    ... market and are intended to produce the same effects as illegal drugs. Some of these substances may have been around for years but have reentered the market in altered chemical forms, or due to renewed popularity. False Advertising Synthetic cannabinoid products are often labeled "not for ...

  4. Towards a synthetic chloroplast.

    Directory of Open Access Journals (Sweden)

    Christina M Agapakis


    Full Text Available The evolution of eukaryotic cells is widely agreed to have proceeded through a series of endosymbiotic events between larger cells and proteobacteria or cyanobacteria, leading to the formation of mitochondria or chloroplasts, respectively. Engineered endosymbiotic relationships between different species of cells are a valuable tool for synthetic biology, where engineered pathways based on two species could take advantage of the unique abilities of each mutualistic partner.We explored the possibility of using the photosynthetic bacterium Synechococcus elongatus PCC 7942 as a platform for studying evolutionary dynamics and for designing two-species synthetic biological systems. We observed that the cyanobacteria were relatively harmless to eukaryotic host cells compared to Escherichia coli when injected into the embryos of zebrafish, Danio rerio, or taken up by mammalian macrophages. In addition, when engineered with invasin from Yersinia pestis and listeriolysin O from Listeria monocytogenes, S. elongatus was able to invade cultured mammalian cells and divide inside macrophages.Our results show that it is possible to engineer photosynthetic bacteria to invade the cytoplasm of mammalian cells for further engineering and applications in synthetic biology. Engineered invasive but non-pathogenic or immunogenic photosynthetic bacteria have great potential as synthetic biological devices.

  5. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  6. Synthetic growth reference charts

    NARCIS (Netherlands)

    Hermanussen, Michael; Stec, Karol; Aßmann, Christian; Meigen, Christof; Van Buuren, Stef


    Objectives: To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts. Methods: Using a baseline set of 196 female and 197 male growth studies published since 1831, common

  7. A formidable synthetic challenge

    Indian Academy of Sciences (India)

    Isolation and characterization of maoecrystal V, a C19 terpenoid, having potent and selective cytotoxicity towards HeLa cells was recently reported. Unusually complex pentacyclic molecular structure, presence of spirofused rings and several stereogenic centres posed a great synthetic challenge. In this short review, efforts ...

  8. Synthetic antiferromagnetic spintronics (United States)

    Duine, R. A.; Lee, Kyung-Jin; Parkin, Stuart S. P.; Stiles, M. D.


    Spintronic and nanomagnetic devices often derive their functionality from layers of different materials and the interfaces between them. We discuss the opportunities that arise from synthetic antiferromagnets consisting of two or more ferromagnetic layers that are separated by metallic spacers or tunnel barriers and have antiparallel magnetizations.

  9. Genetics Home Reference: platyspondylic lethal skeletal dysplasia, Torrance type (United States)

    ... cause platyspondylic lethal skeletal dysplasia, torrance type, and define a novel subfamily within the type 2 collagenopathies. ... for Links Data Files & API Site Map Subscribe Customer Support Copyright Privacy Accessibility FOIA Viewers & ...

  10. Center on Survivability and Lethality (CSL) Research Faculty



    NPS has a strong history in teaching and research in aircraft survivability and air defense lethality. On Jan. 30, the Naval Postgraduate School (NPS) announced the creation of the Center for Survivability and Lethality. The new center builds upon the pioneering work of Distinguished Professor Emeritus Robert Ball, who founded the first and only course on all aspects of aircraft combat survivability at NPS in the 1970s and wrote the field’s ‘bible,’ The Fundamentals of Aircraft Comba...

  11. Sonographic features of lethal multiple pterygium syndrome at 14 weeks. (United States)

    Chen, Min; Chan, Gavin Shueng Wai; Lee, Chin Peng; Tang, Mary Hoi Yin


    Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports suggest that the diagnosis may be based on prenatal sonographic demonstration of severe limb flexion, absence of fetal motion, and a large cystic hygroma in the second and third trimesters. We present the sonographic features and postmortem features of a fetus with lethal multiple pterygium syndrome at 13 weeks of gestation, which shows that the condition can possibly be diagnosed in the first trimester of pregnancy.

  12. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics. (United States)

    Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl


    One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

  13. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer (United States)


    compelling evidence linking obesity to aggressive prostate cancer, but the underlying causes of this relationship are unclear. In this study we used whole...1 AWARD NUMBER: W81XWH-14-1-0250 TITLE: Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer PRINCIPAL INVESTIGATOR: Ericka...TITLE AND SUBTITLE Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0250

  14. Synthetic antifreeze peptide and synthetic gene coding for its production



    A synthetic antifreeze peptide and a synthetic gene coding for the antifreeze peptide have been produced. The antifreeze peptide has a greater number of repeating amino acid sequences than is present in the native antifreeze peptides from winter flounder upon which the synthetic antifreeze peptide was modeled. Each repeating amino acid sequence has two polar amino acid residues which are spaced a controlled distance apart so that the antifreeze peptide may inhibit ice formation. The synthetic...

  15. Measures of Effectiveness for Non-Lethal Weapons: Aligning Behavioral Experiments with Operational Success (United States)


    commonly known as TASERs), dazzling lasers , and flashbang grenades (Joint Non-Lethal Weapons Program (JNLWD), 2013). A NLW can cause a physiological...mission. Combat developers could repeat this analysis for other NLW systems in other military scenarios, such as dazzling lasers used at vehicle...Chauvin, D. J., Kuyk, T. K., Smith, P. A., Stringham, J. M., & Garcia, P. V. (2010). Warning and suppression with single and multiple laser optical

  16. Custom-Designed MLPA Using Multiple Short Synthetic Probes Application to Methylation Analysis of Five Promoter CpG Islands in Tumor and Urine Specimens from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Serizawa, R.R.; Ralfkiaer, U.; Dahl, C.


    this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis. (J Mol Diagn 2010, 12:402-408; DOI: 10.2353/jmoldx.2010.090152)......Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using......-stranded bacteriophage vector to introduce a sequence of defined length between the primer binding site and the specific target sequence. Here we demonstrate that differences in amplicon length can be achieved by using multiple short synthetic probes for each target sequence. When joined by a DNA ligase, these probes...

  17. Ecstasy tablets intoxication with lethal autcome

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana


    Full Text Available Background. Ecstasy, 3,4-methylenedioxymethamphetamine (MDMA, is a synthetic compound increasingly popular as a recreational drug. Tablets known as ecstasy contain MDMA, but may also contain caffeine, ephedrine, paramethoxyamphetamine, 3,4-methylenedioxyamphetamine (MDA, amphetamine, methamphetamine, and ketamine. After absorption MDMA is metabolized to MDA, 4-hydroxy-3- metoxymetamphetamine (HMMA and 4-hydroxy-3- metoxyamphetamine (HMA. After that HMMA and HMA are conjugated and excreted by urine. The aim of this report was to confirm by toxicological post mortem analyses of poisoned person organs that ecstasy had been the cause of his death. Case report. We reported the death of a 17-year-old boy after the ingestion of ecstasy. MDMA and metabolites were determined by multicolumn high performance liquid chromatography with UV spectral detection (HPLC-UV. Toxicological tests showed the presence of MDMA in all samples. When examining post mortem material (the organs, the highest concentrations were measured in the stomach (835,97 μg/g and kidney (801,14 μg/g. The minimal concentration was in the liver (22,26 μg/g. Conclusion. The obtained results of MDMA and its metabolites concentrations showed abuse of a high dose of ecstasy. .

  18. The virtual observatory service TheoSSA: Establishing a database of synthetic stellar flux standards . II. NLTE spectral analysis of the OB-type subdwarf Feige 110 (United States)

    Rauch, T.; Rudkowski, A.; Kampka, D.; Werner, K.; Kruk, J. W.; Moehler, S.


    Context. In the framework of the Virtual Observatory (VO), the German Astrophysical VO (GAVO) developed the registered service TheoSSA (Theoretical Stellar Spectra Access). It provides easy access to stellar spectral energy distributions (SEDs) and is intended to ingest SEDs calculated by any model-atmosphere code, generally for all effective temperatures, surface gravities, and elemental compositions. We will establish a database of SEDs of flux standards that are easily accessible via TheoSSA's web interface. Aims: The OB-type subdwarf Feige 110 is a standard star for flux calibration. State-of-the-art non-local thermodynamic equilibrium stellar-atmosphere models that consider opacities of species up to trans-iron elements will be used to provide a reliable synthetic spectrum to compare with observations. Methods: In case of Feige 110, we demonstrate that the model reproduces not only its overall continuum shape from the far-ultraviolet (FUV) to the optical wavelength range but also the numerous metal lines exhibited in its FUV spectrum. Results: We present a state-of-the-art spectral analysis of Feige 110. We determined , log g = 6.00 ± 0.20, and the abundances of He, N, P, S, Ti, V, Cr, Mn, Fe, Co, Ni, Zn, and Ge. Ti, V, Mn, Co, Zn, and Ge were identified for the first time in this star. Upper abundance limits were derived for C, O, Si, Ca, and Sc. Conclusions: The TheoSSA database of theoretical SEDs of stellar flux standards guarantees that the flux calibration of astronomical data and cross-calibration between different instruments can be based on models and SEDs calculated with state-of-the-art model-atmosphere codes. Based on observations with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26666. Based on observations made with the NASA-CNES-CSA Far Ultraviolet Spectroscopic Explorer. Table 2, Figs. 3 and

  19. Laboratory Measurements of Synthetic Pyroxenes and their Mixtures with Iron Sulfides as Inorganic Refractory Analogues for Rosetta/VIRTIS' Surface Composition Analysis of 67P/CG (United States)

    Markus, Kathrin; Arnold, Gabriele; Moroz, Ljuba; Henckel, Daniela; Kappel, David; Capaccioni, Fabrizio; Filacchione, Gianrico; Schmitt, Bernard; Tosi, Federico; Érard, Stéphane; Bockelee-Morvan, Dominique; Leyrat, Cedric; VIRTIS Team


    The Visible and InfraRed Thermal Imaging Spectrometer VIRTIS on board Rosetta provided 0.25-5.1 µm spectra of 67P/CG's surface (Capaccioni et al., 2015). Thermally corrected reflectance spectra display a low albedo of 0.06 at 0.65 µm, different red VIS and IR spectral slopes, and a broad 3.2 µm band. This absorption feature is due to refractory surface constituents attributed to organic components, but other refractory constituents influence albedo and spectral slopes. Possible contributions of inorganic components to spectral characteristics and spectral variations across the surface should be understood based on laboratory studies and spectral modeling. Although a wide range of silicate compositions was found in "cometary" anhydrous IDPs and cometary dust, Mg-rich crystalline mafic minerals are dominant silicate components. A large fraction of silicate grains are Fe-free enstatites and forsterites that are not found in terrestrial rocks but can be synthesized in order to provide a basis for laboratory studies and comparison with VIRTIS data. We report the results of the synthesis, analyses, and spectral reflectance measurements of Fe-free low-Ca pyroxenes (ortho- and clinoenstatites). These minerals are generally very bright and almost spectrally featureless. However, even trace amounts of Fe-ions produce a significant decrease in the near-UV reflectance and hence can contribute to slope variations. Iron sulfides (troilite, pyrrhotite) are among the most plausible phases responsible for the low reflectance of 67P's surface from the VIS to the NIR. The darkening efficiency of these opaque phases is strongly particle-size dependent. Here we present a series of reflectance spectra of fine-grained synthetic enstatite powders mixed in various proportions with iron sulfide powders. The influence of dark sulfides on reflectance in the near-UV to near-IR spectral ranges is investigated. This study can contribute to understand the shape of reflectance spectra of 67P

  20. Application of the Organic Synthetic Designs to Astrobiology (United States)

    Kolb, V. M.


    In this paper we propose a synthesis of the heterocyclic compounds and the insoluble materials on the meteorites. Our synthetic scheme involves the reaction of sugars and amino acids, the so-called Maillard reaction. We have developed this scheme based on the combined analysis of the regular and retrosynthetic organic synthetic principles. The merits of these synthetic methods for the prebiotic design are addressed.

  1. Standardization in synthetic biology. (United States)

    Müller, Kristian M; Arndt, Katja M


    Synthetic Biology is founded on the idea that complex biological systems are built most effectively when the task is divided in abstracted layers and all required components are readily available and well-described. This requires interdisciplinary collaboration at several levels and a common understanding of the functioning of each component. Standardization of the physical composition and the description of each part is required as well as a controlled vocabulary to aid design and ensure interoperability. Here, we describe standardization initiatives from several disciplines, which can contribute to Synthetic Biology. We provide examples of the concerted standardization efforts of the BioBricks Foundation comprising the request for comments (RFC) and the Registry of Standardized Biological parts as well as the international Genetically Engineered Machine (iGEM) competition.

  2. Optical synthetic aperture radar (United States)

    Ilovitsh, Asaf; Zach, Shlomo; Zalevsky, Zeev


    A method is proposed for increasing the resolution of an object and overcoming the diffraction limit of an optical system installed on top of a moving imaging system, such as an airborne platform or satellite. The resolution improvement is obtained via a two-step process. First, three low resolution differently defocused images are captured and the optical phase is retrieved using an improved iterative Gershberg-Saxton based algorithm. The phase retrieval allows numerical back propagation of the field to the aperture plane. Second, the imaging system is shifted and the first step is repeated. The obtained optical fields at the aperture plane are combined and a synthetically increased lens aperture is generated along the direction of movement, yielding higher imaging resolution. The method resembles a well-known approach from the microwave regime called the synthetic aperture radar in which the antenna size is synthetically increased along the platform propagation direction. The proposed method is demonstrated via Matlab simulation as well as through laboratory experiment.

  3. Three-dimensional microCT imaging of murine embryonic development from immediate post-implantation to organogenesis: application for phenotyping analysis of early embryonic lethality in mutant animals. (United States)

    Ermakova, Olga; Orsini, Tiziana; Gambadoro, Alessia; Chiani, Francesco; Tocchini-Valentini, Glauco P


    In this work, we applied three-dimensional microCT imaging to study murine embryogenesis in the range from immediate post-implantation period (embryonic day 5.5) to mid-gestation (embryonic day 12.5) with the resolution up to 1.4 µm/voxel. Also, we introduce an imaging procedure for non-invasive volumetric estimation of an entire litter of embryos within the maternal uterine structures. This method allows for an accurate, detailed and systematic morphometric analysis of both embryonic and extra-embryonic components during embryogenesis. Three-dimensional imaging of unperturbed embryos was performed to visualize the egg cylinder, primitive streak, gastrulation and early organogenesis stages of murine development in the C57Bl6/N mouse reference strain. Further, we applied our microCT imaging protocol to determine the earliest point when embryonic development is arrested in a mouse line with knockout for tRNA splicing endonuclease subunit Tsen54 gene. Our analysis determined that the embryonic development in Tsen54 null embryos does not proceed beyond implantation. We demonstrated that application of microCT imaging to entire litter of non-perturbed embryos greatly facilitate studies to unravel gene function during early embryogenesis and to determine the precise point at which embryonic development is arrested in mutant animals. The described method is inexpensive, does not require lengthy embryos dissection and can be applicable for detailed analysis of mutant mice at laboratory scale as well as for high-throughput projects.

  4. Synthetic cannabis and respiratory depression. (United States)

    Jinwala, Felecia N; Gupta, Mayank


    In recent years, synthetic cannabis use has been increasing in appeal among adolescents, and its use is now at a 30 year peak among high school seniors. The constituents of synthetic cannabis are difficult to monitor, given the drug's easy accessibility. Currently, 40 U.S. states have banned the distribution and use of some known synthetic cannabinoids, and have included these drugs in the Schedule I category. The depressive respiratory effect in humans caused by synthetic cannabis inhalation has not been thoroughly investigated in the medical literature. We are the first to report, to our knowledge, two cases of self-reported synthetic cannabis use leading to respiratory depression and necessary intubation.

  5. Radiation rescue: mesenchymal stromal cells protect from lethal irradiation.

    Directory of Open Access Journals (Sweden)

    Claudia Lange

    Full Text Available BACKGROUND: Successful treatment of acute radiation syndromes relies on immediate supportive care. In patients with limited hematopoietic recovery potential, hematopoietic stem cell (HSC transplantation is the only curative treatment option. Because of time consuming donor search and uncertain outcome we propose MSC treatment as an alternative treatment for severely radiation-affected individuals. METHODS AND FINDINGS: Mouse mesenchymal stromal cells (mMSCs were expanded from bone marrow, retrovirally labeled with eGFP (bulk cultures and cloned. Bulk and five selected clonal mMSCs populations were characterized in vitro for their multilineage differentiation potential and phenotype showing no contamination with hematopoietic cells. Lethally irradiated recipients were i.v. transplanted with bulk or clonal mMSCs. We found a long-term survival of recipients with fast hematopoietic recovery after the transplantation of MSCs exclusively without support by HSCs. Quantitative PCR based chimerism analysis detected eGFP-positive donor cells in peripheral blood immediately after injection and in lungs within 24 hours. However, no donor cells in any investigated tissue remained long-term. Despite the rapidly disappearing donor cells, microarray and quantitative RT-PCR gene expression analysis in the bone marrow of MSC-transplanted animals displayed enhanced regenerative features characterized by (i decreased proinflammatory, ECM formation and adhesion properties and (ii boosted anti-inflammation, detoxification, cell cycle and anti-oxidative stress control as compared to HSC-transplanted animals. CONCLUSIONS: Our data revealed that systemically administered MSCs provoke a protective mechanism counteracting the inflammatory events and also supporting detoxification and stress management after radiation exposure. Further our results suggest that MSCs, their release of trophic factors and their HSC-niche modulating activity rescue endogenous hematopoiesis

  6. Genome modularity and synthetic biology: Engineering systems. (United States)

    Mol, Milsee; Kabra, Ritika; Singh, Shailza


    Whole genome sequencing projects running in various laboratories around the world has generated immense data. A systematic phylogenetic analysis of this data shows that genome complexity goes on decreasing as it evolves, due to its modular nature. This modularity can be harnessed to minimize the genome further to reduce it with the bare minimum essential genes. A reduced modular genome, can fuel progress in the area of synthetic biology by providing a ready to use plug and play chassis. Advances in gene editing technology such as the use of tailor made synthetic transcription factors will further enhance the availability of synthetic devices to be applied in the fields of environment, agriculture and health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Tuning the dials of Synthetic Biology (United States)

    Arpino, James A. J.; Hancock, Edward J.; Anderson, James; Barahona, Mauricio; Stan, Guy-Bart V.; Polizzi, Karen


    Synthetic Biology is the ‘Engineering of Biology’ – it aims to use a forward-engineering design cycle based on specifications, modelling, analysis, experimental implementation, testing and validation to modify natural or design new, synthetic biology systems so that they behave in a predictable fashion. Motivated by the need for truly plug-and-play synthetic biological components, we present a comprehensive review of ways in which the various parts of a biological system can be modified systematically. In particular, we review the list of ‘dials’ that are available to the designer and discuss how they can be modelled, tuned and implemented. The dials are categorized according to whether they operate at the global, transcriptional, translational or post-translational level and the resolution that they operate at. We end this review with a discussion on the relative advantages and disadvantages of some dials over others. PMID:23704788

  8. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta


    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.


    Directory of Open Access Journals (Sweden)

    Silviu Eduard Dinca


    Full Text Available During the past few years, in the recent post-crisis aftermath, global asset managers are constantly searching new ways to optimize their investment portfolios while financial and banking institutions around the world are exploring new alternatives to better secure their financing and refinancing demands altogether with the enhancement of their risk management capabilities. We will exhibit herewith a comparison between the true-sale and synthetic CDO securitizations as financial markets-based funding, investment and risks mitigation techniques, highlighting certain key structuring and implementation specifics on each of them.

  10. Crossover suppressors and balanced recessive lethals in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Herman, R.K.


    Two dominant suppressors of crossing over have been identified following x-ray treatment of the small nematode C. elegans. They suppress crossing over in linkage group II (LGII) about 100-fold and 50-fold and are both tightly linked to LGII markers. One, called C1, segregates independently of all other linkage groups and is homozygous fertile. The other is a translocation involving LGII and X. The translocation also suppresses crossing over along the right half of X and is homozygous lethal. C1 has been used as a balancer of LGII recessive lethal and sterile mutations induced by EMS. The frequencies of occurrence of lethals and steriles were approximately equal. Fourteen mutations were assigned to complementation groups and mapped. They tended to map in the same region where LGII visibles are clustered

  11. Determination of the Median Lethal Dose and Electrophoretic Pattern of Hottentotta saulcyi (Scorpiones, Buthidae Scorpion Venom

    Directory of Open Access Journals (Sweden)

    ErsenAydın Yağmur


    Full Text Available Background: In this study, we investigated the lethal potency, electrophoretic protein pattern and in vivo effects of Hottentotta saulcyi scorpion venom in mice.Methods: Scorpions were collected at night, by using a UV lamp from Mardin Province, Turkey. Venom was obtained from mature H. saulcyi scorpions by electrical stimulation of the telson. The lethality of the venom was determined by i.v. injections using Swiss mice. In vivo effects of the venom were assessed by using the intraperitoneal route (ip injections into mice (20±1g and monitored for 24 h. The protein profiles of the scorpion venom were analyzed by NuPAGE® Novex® 4–12 % gradient Bis-Tris gel followed by Coomassie blue staining.Results: The lethal assay of the venom was 0.73 mg/kg in mice. We determined the electrophoretic protein pattern of this scorpion venom to be 4, 6, 9, 31, 35, 40, 46 and 69 kDa by SDS-PAGE. Analysis of electrophoresis indicated that H. saulcyi scorpion intoxicated mice exhibited autonomic nervous system symptoms (tachypnea, restlessness, hyperexcitability, convulsions, salivation, lacrimation, weakness.Conclusions: Hottentotta saulcyi scorpion venom includes short-chain neurotoxins and long-chain neurotoxins according to the electrophoretic protein patterns. The stings of H. saulcyi scorpion must be considered of risk for humans in the southeastern region, Turkey.

  12. 1H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

    International Nuclear Information System (INIS)

    Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J.; Simpson, Myrna J.


    1 H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-β-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised ∼65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - 1 H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

  13. Evaluation of toxic potential of acephate and chlorpyrifos by dominant lethal test on Culex quinquefasciatus. (United States)

    Bhinder, Preety; Chaudhry, Asha


    The present paper deals with the toxicity evaluation of pesticides acephate and chlorpyrifos by applying dominant lethal test (DLT) on mosquito Culex quinquefasciatus taken as an experimental model. For this, the adult male mosquitoes emerging from LC20 treated larval stock were allowed to crossmate with normal virgin females under controlled conditions of mosquito rearing laboratory along with the parallel controls, separately for each pesticide. The eggs obtained from such females were allowed to hatch after which they were examined under suitable magnification. The number of unhatched eggs was taken as the measure for calculating the dominant lethality caused by the pesticides and the data was analyzed statistically by applying Student's t-test. The statistical analysis of the results for acephate treated groups was 9.49 +/- 1.50 as against 3.92 +/- 0.41 in the control groups and chlorpyrifos treated groups gave the value 9.94 +/- 1.92 as against 4.26 +/- 0.35 in the control groups. The results indicated that these pesticides induced significant (p < 0.05) dominant lethality.

  14. X-ray-induced recessive lethal mutations in adult and foetal female mice

    International Nuclear Information System (INIS)

    Luening, K.G.; Eiche, A.


    Tests of X-ray-induced recessive lethal mutations in adult and foetal mouse females were performed. The tests were based on family analysis which provided a possibility of making a distinction between pre-existing recessive lethal mutations and newly arisen (spontaneous + induced) ones. The way the tests were carried out provided material for the estimation of the frequency of spontaneous lethal mutations per genome. The two different estimates from this material, 0.72 and 0.91%, respectively, are similar and fall within the range previously suggested by Luening. The difference, though statistically non-significant, between data from irradiated mature and maturing oocytes in adult females and material from the unirradiated part, indicates a mutation rate of 13 x 10 -5 per rad per gamete according to one estimate and 8-12 x 10 -5 according to the other in comparison with 9 x 10 -5 from irradiated spermatogonia. In the limited data obtained after foetal irradiation, there is no indication of oogonia and developing oocytes being more sensitive to irradiation than oocytes in adult females fertilized within 6 weeks of treatment. (orig.)

  15. Exome sequencing for gene discovery in lethal fetal disorders--harnessing the value of extreme phenotypes. (United States)

    Filges, Isabel; Friedman, Jan M


    Massively parallel sequencing has revolutionized our understanding of Mendelian disorders, and many novel genes have been discovered to cause disease phenotypes when mutant. At the same time, next-generation sequencing approaches have enabled non-invasive prenatal testing of free fetal DNA in maternal blood. However, little attention has been paid to using whole exome and genome sequencing strategies for gene identification in fetal disorders that are lethal in utero, because they can appear to be sporadic and Mendelian inheritance may be missed. We present challenges and advantages of applying next-generation sequencing approaches to gene discovery in fetal malformation phenotypes and review recent successful discovery approaches. We discuss the implication and significance of recessive inheritance and cross-species phenotyping in fetal lethal conditions. Whole exome sequencing can be used in individual families with undiagnosed lethal congenital anomaly syndromes to discover causal mutations, provided that prior to data analysis, the fetal phenotype can be correlated to a particular developmental pathway in embryogenesis. Cross-species phenotyping allows providing further evidence for causality of discovered variants in genes involved in those extremely rare phenotypes and will increase our knowledge about normal and abnormal human developmental processes. Ultimately, families will benefit from the option of early prenatal diagnosis. © 2014 John Wiley & Sons, Ltd.

  16. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy. (United States)

    Morin, L R; Herlicoviez, M; Loisel, J C; Jacob, B; Feuilly, C; Stanescu, V


    Lethal osteogenesis imperfecta was diagnosed at 27 weeks amenorrea in one fetus of a bichorial twin pregnancy. Sonographic findings included: short-limb dwarfism, hypotrophy and hypoechoic bones. The affected fetus was so translucent that only the normal fetus could be seen on plain in utero radiography. The affected fetus died immediately after birth. Postmortem radiography and histology were typical of lethal osteogenesis imperfecta of type IIA. Aids to the etiological diagnosis of in utero dwarfism are presented. Sonographic features correlated with neonatal death are described.

  17. Synthetic collective intelligence. (United States)

    Solé, Ricard; Amor, Daniel R; Duran-Nebreda, Salva; Conde-Pueyo, Núria; Carbonell-Ballestero, Max; Montañez, Raúl


    Intelligent systems have emerged in our biosphere in different contexts and achieving different levels of complexity. The requirement of communication in a social context has been in all cases a determinant. The human brain, probably co-evolving with language, is an exceedingly successful example. Similarly, social insects complex collective decisions emerge from information exchanges between many agents. The difference is that such processing is obtained out of a limited individual cognitive power. Computational models and embodied versions using non-living systems, particularly involving robot swarms, have been used to explore the potentiality of collective intelligence. Here we suggest a novel approach to the problem grounded in the genetic engineering of unicellular systems, which can be modified in order to interact, store memories or adapt to external stimuli in collective ways. What we label as Synthetic Swarm Intelligence defines a parallel approach to the evolution of computation and swarm intelligence and allows to explore potential embodied scenarios for decision making at the microscale. Here, we consider several relevant examples of collective intelligence and their synthetic organism counterparts. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Exploratory comparative study on the diffusion of synthetic cannabinoids and synthetic cathinones. (United States)

    Arfken, Cynthia L; Owens, Darlene; Madeja, Cheryl; DeAngelis, Christina


    The use of synthetic cannabinoids and cathinones in southeastern Michigan was explored using Roger's Diffusion of Innovation theory. A mixed methods approach after specific synthetic cannabinoids and cathinone compounds were scheduled was used that included analysis of treatment admissions for two years, surveys of 15 substance abuse treatment providers, and qualitative interviews with a purposive sample of 24 participants. The participant system norm supported trying new drugs, and both drugs were confirmed to have been easier to access than traditional drugs. The participants had negative views of synthetic cathinones due to one sensational news story without counterbalancing positive experiences in their social environment. Although synthetic cannabinoids were also linked to a sensational news story, it was counterbalanced by positive personal experiences. These differences contributed to greater use of synthetic cannabinoids compared to synthetic cathinones as evidenced by admissions, providers' reports, and participants' reports. All participants expressed a preference for traditional drugs, indicating that novel drugs had no relative advantage over other drugs of abuse. Diffusion of Innovation theory can provide a framework for understanding the differential use of novel drugs.

  19. Caffeine in your drink: natural or synthetic? (United States)

    Zhang, Lijun; Kujawinski, Dorothea M; Federherr, Eugen; Schmidt, Torsten C; Jochmann, Maik A


    Owing to possible adulteration and health concerns, it is important to discriminate between natural and synthetic food ingredients. A new method for compound-specific isotope analysis (CSIA) by coupling high-temperature reversed-phase liquid chromatography to isotope ratio mass spectrometry (HT-RPLC/IRMS) was developed for discrimination of natural and synthetic caffeine contained in all types of drinks. The analytical parameters such as stationary phase, column inner diameter, and column temperature were optimized for the separation of caffeine directly from drinks (without extraction). On the basis of the carbon isotope analysis of 42 natural caffeine samples including coffee beans, tea leaves, guaraná powder, and maté leaves, and 20 synthetic caffeine samples from different sources by high-temperature reversed-phase liquid chromatography coupled to isotope ratio mass spectrometry, it is concluded that there are two distinguishable groups of caffeine δ(13)C-values: one between -25 and -32‰ for natural caffeine, and the other between -33 and -38‰ for synthetic caffeine. Isotope analysis by HT-RPLC/IRMS has been applied to identify the caffeine source in 38 drinks. Four mislabeled products were detected due to added but nonlabeled synthetic caffeine with δ(13)C-values lower than -33‰. This work is the first application of HT-RPLC/IRMS to real-world food samples, which showed several advantages: simple sample preparation (only dilution), high throughput, long-term column stability, and high precision of δ(13)C-value. Thus, HT-RPLC/IRMS can be a very promising tool in stable isotope analysis of nonvolatile compounds.

  20. Catalytic efficiency of natural and synthetic compounds used as laccase-mediators in oxidising veratryl alcohol and a kraft lignin, estimated by electrochemical analysis

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez Arzola, K. [Department of Microbiology and Cell Biology, Faculty of Pharmacy, University of La Laguna, 38206 La Laguna, Tenerife (Spain); Arevalo, M.C. [Department of Physical Chemistry, Faculty of Chemistry, University of La Laguna, 38206 La Laguna, Tenerife (Spain)], E-mail:; Falcon, M.A. [Department of Microbiology and Cell Biology, Faculty of Pharmacy, University of La Laguna, 38206 La Laguna, Tenerife (Spain)], E-mail:


    The electrochemical properties of eighteen natural and synthetic compounds commonly used to expand the oxidative capacity of laccases were evaluated in an aqueous buffered medium using cyclic voltammetry. This clarifies which compounds fulfil the requisites to be considered as redox mediators or enhancers. Cyclic voltammetry was also applied as a rapid way to assess the catalytic efficiency (CE) of those compounds which oxidise a non-phenolic lignin model (veratryl alcohol, VA) and a kraft lignin (KL). With the exception of gallic acid and catechol, all assayed compounds were capable of oxidising VA with varying CE. However, only some of them were able to oxidise KL. Although the oxidised forms of HBT and acetovanillone were not electrochemically stable, their reduced forms were quickly regenerated in the presence of VA. They thus act as chemical catalysts. Importantly, HBT and HPI did not attack the KL via the same mechanism as in VA oxidation. Electrochemical evidence suggests that violuric acid oxidises both substrates by an electron transfer mechanism, unlike the other N-OH compounds HBT and HPI. Acetovanillone was found to be efficient in oxidising VA and KL, even better than the synthetic mediators TEMPO, violuric acid or ABTS. Most of the compounds produced a generalised increase in the oxidative charge of KL, probably attributed to chain reactions arising between the phenolic and non-phenolic components of this complex molecule.

  1. Analyzing temporal variation in the lethality of ETA

    Directory of Open Access Journals (Sweden)

    Sánchez-Cuenca, Ignacio


    Full Text Available This article analyzes time variation in the lethal violence of the terrorist organization ETA. Given the dynamic structure of the time series of fatalities, I look at the effect of a number of independent variables (the celebration of different types of elections, anti-ETA activity by extreme right-wing organizations and the GAL, police arrests, and other relevant events, such as the referendums on the Constitution and the Statute of Autonomy of Guernica. To do so, I have estimated several ARIMA models using the time series of fatalities between 1968 and 2007. Moreover, the results obtained are complemented by a historical-political analysis of the period of maximum violence, which took place during the Spanish transition to democracy.

    Este artículo analiza la variación temporal en la violencia letal de la organización terrorista ETA. Dada la estructura dinámica de la serie temporal de víctimas mortales, se estudia el efecto de una serie de variables independientes (celebración de distintos tipos de elecciones, actividad anti-ETA de la extrema derecha y del GAL, detenciones policiales y sucesos especiales como los referendos sobre la Constitución o el Estatuto de Autonomía de Guernica. Para ello, se estiman diversos modelos ARIMA con la serie trimestral de víctimas mortales entre 1968 y 2007. Además, se completan los resultados obtenidos con un análisis histórico-político del periodo de máxima violencia durante la transición a la democracia.

  2. Space Synthetic Biology Project (United States)

    Howard, David; Roman, Monsi; Mansell, James (Matt)


    Synthetic biology is an effort to make genetic engineering more useful by standardizing sections of genetic code. By standardizing genetic components, biological engineering will become much more similar to traditional fields of engineering, in which well-defined components and subsystems are readily available in markets. Specifications of the behavior of those components and subsystems can be used to model a system which incorporates them. Then, the behavior of the novel system can be simulated and optimized. Finally, the components and subsystems can be purchased and assembled to create the optimized system, which most often will exhibit behavior similar to that indicated by the model. The Space Synthetic Biology project began in 2012 as a multi-Center effort. The purpose of this project was to harness Synthetic Biology principals to enable NASA's missions. A central target for application was to Environmental Control & Life Support (ECLS). Engineers from NASA Marshall Space Flight Center's (MSFC's) ECLS Systems Development Branch (ES62) were brought into the project to contribute expertise in operational ECLS systems. Project lead scientists chose to pursue the development of bioelectrochemical technologies to spacecraft life support. Therefore, the ECLS element of the project became essentially an effort to develop a bioelectrochemical ECLS subsystem. Bioelectrochemical systems exploit the ability of many microorganisms to drive their metabolisms by direct or indirect utilization of electrical potential gradients. Whereas many microorganisms are capable of deriving the energy required for the processes of interest (such as carbon dioxide (CO2) fixation) from sunlight, it is believed that subsystems utilizing electrotrophs will exhibit smaller mass, volume, and power requirements than those that derive their energy from sunlight. In the first 2 years of the project, MSFC personnel conducted modeling, simulation, and conceptual design efforts to assist the

  3. Life after the synthetic cell

    DEFF Research Database (Denmark)

    Rasmussen, Steen


    Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self-replicating ......Nature asked eight synthetic-biology experts about the implications for science and society of the “synthetic cell” made by the J. Craig Venter Institute (JCVI). The institute's team assembled, modified and implanted a synthesized genome into a DNA-free bacterial shell to make a self...

  4. Synthetic biology and occupational risk. (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul


    Synthetic biology is an emerging interdisciplinary field of biotechnology that involves applying the principles of engineering and chemical design to biological systems. Biosafety professionals have done an excellent job in addressing research laboratory safety as synthetic biology and gene editing have emerged from the larger field of biotechnology. Despite these efforts, risks posed by synthetic biology are of increasing concern as research procedures scale up to industrial processes in the larger bioeconomy. A greater number and variety of workers will be exposed to commercial synthetic biology risks in the future, including risks to a variety of workers from the use of lentiviral vectors as gene transfer devices. There is a need to review and enhance current protection measures in the field of synthetic biology, whether in experimental laboratories where new advances are being researched, in health care settings where treatments using viral vectors as gene delivery systems are increasingly being used, or in the industrial bioeconomy. Enhanced worker protection measures should include increased injury and illness surveillance of the synthetic biology workforce; proactive risk assessment and management of synthetic biology products; research on the relative effectiveness of extrinsic and intrinsic biocontainment methods; specific safety guidance for synthetic biology industrial processes; determination of appropriate medical mitigation measures for lentiviral vector exposure incidents; and greater awareness and involvement in synthetic biology safety by the general occupational safety and health community as well as by government occupational safety and health research and regulatory agencies.

  5. Finding Hope in Synthetic Biology. (United States)

    Takala, Tuija


    For some, synthetic biology represents great hope in offering possible solutions to many of the world's biggest problems, from hunger to sustainable development. Others remain fearful of the harmful uses, such as bioweapons, that synthetic biology can lend itself to, and most hold that issues of biosafety are of utmost importance. In this article, I will evaluate these points of view and conclude that although the biggest promises of synthetic biology are unlikely to become reality, and the probability of accidents is fairly substantial, synthetic biology could still be seen to benefit humanity by enhancing our ethical understanding and by offering a boost to world economy.

  6. Synthetic Aperture Compound Imaging

    DEFF Research Database (Denmark)

    Hansen, Jens Munk

    Medical ultrasound imaging is used for many purposes, e.g. for localizing and classifying cysts, lesions, and other processes. Almost any mass is first observed using B-mode imaging and later classified using e.g. color flow, strain, or attenuation imaging. It is therefore important that the B......, it is demonstrated through theoretical considerations that the compound effect achieved is close to a theoretical maximum for the amount of compounding attainable and using a -pitch convex array transducer, the first in-vivo images are created. The computational demands for an implementation are massive...... and the limiting factor is the amount of memory IO resources available. An equally high demand for memory throughput is found in the computer gaming industry, where a large part of the processing takes place on the graphics processing unit (GPU). Using the GPU, a framework for synthetic aperture imaging...

  7. Synthetic antibiofilm peptides. (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W


    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.


    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  9. Perforated appendicitis presenting as a thigh abscess: A lethal ...

    African Journals Online (AJOL)

    Typical cases of acute appendicitis have excellent treatment outcomes, if managed appropriately.1 We discuss an unusual case of perforated retrocaecal appendicitis that presented as a right thigh abscess without prominent abdominal symptoms, which highlights the lethal nature of advanced appendicitis even when ...

  10. Perinatal lethal type II osteogenesis imperfecta: a case report | Ayadi ...

    African Journals Online (AJOL)

    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy ...

  11. The "Lethal Chamber": Further Evidence of the Euthanasia Option. (United States)

    Elks, Martin A.


    Historical discussions of the euthanasia or "lethal chamber" option in relation to people with mental retardation are presented. The paper concludes that eugenic beliefs in the primacy of heredity over environment and the positive role of natural selection may have condoned the poor conditions characteristic of large, segregated institutions and…

  12. [Generalized and lethal pentastomiasis due to Armillifer grandis (Hett, 1915)]. (United States)

    Cagnard, V; Nicolas-Randegger, J; Dago Akribi, A; Rain, B; Nozais, J P; Essoh Nomel, P; Ette, M; Doucet, J; Assale N'Dri, G


    The authors described a case of generalised and lethal Pentastomiasis by a five years old girl. The most heavy parasitised organs are the lungs and the brain. Considering the age of the child and the uncommon density of the parasites, the authors suggest that the symptoms may follow the casual ingestion of a gravid female worm.

  13. Lethality of the aqeous extracts of Acacia nilotica, Guiera ...

    African Journals Online (AJOL)

    Cytotoxic activity indicated by lethal effects (that is mortality rate) of aqueous extracts of fruits of Acacia nilotica, stem bark of Kigelia africana, roots of Securidaca longepedunculata, and leaves of Guiera senegalensis on the culex mosquito larva was investigated by direct contact method. Larvicidal effects were observed with ...

  14. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.


    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  15. Fighting Lethal Yellowing Disease for Coconut Farmers (CIFSRF ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Copra is the dried kernel of the coconut, which is used to extract coconut oil. Coconut is the main income source for the coastal region's poor farmers. Over the past 10 years, Côte d'Ivoire lethal yellowing disease has destroyed more than 350 hectares of coconut and caused losses of 12,000 tons of copra per year.

  16. Brine shrimp lethality bioassay of selected Indian medicinal plants. (United States)

    Padmaja, R; Arun, P C; Prashanth, D; Deepak, M; Amit, A; Anjana, M


    Ethanolic extracts of six Indian medicinal plants, piperine, guggulsterone E and guggulsterone Z were tested for cytotoxicity using brine shrimp lethality test. Piper longum showed most potent cytotoxic activity. Piperine, guggulsterone E and guggulsterone Z showed potent activity with LC(50) 2.4, 8.9 and 4.9, respectively. Copyright 2002 Elsevier Science B.V.

  17. Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

    NARCIS (Netherlands)

    Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.


    Papaya lethal yellowing virus (PLYV) é um dos três vírus descritos infectando mamoeiros (Carica papaya L.) no Brasil. Vasconcellea cauliflora (Jacq.) A. DC., antes denominada de Carica cauliflora (Jacq.), é uma reconhecida fonte de resistência natural ao Papaya ringspot virus (PRSV), causador da

  18. Median lethal dose (LD 50 ) evaluation of some polyherbal ...

    African Journals Online (AJOL)

    The polyherbal preparations reported here are traditionally used in Northern Nigeria for the treatment of wide range of illnesses. The aim of this study was to evaluate the acute toxicity potential of 70% ethanol extracts of forty polyherbal products by determining their median lethal dose (LD50) estimates intraperitoneally and ...

  19. Brine shrimp lethality and antimicrobial studies on the seeds of ...

    African Journals Online (AJOL)

    Garcinia kola (Family, Guttiferae) is employed in a variety of therapies ranging from skin, gastrointestinal, chest to tumour problems. Preparations of the stem and roots are used as antitumour in traditional medicine but the potential of the seeds as antitumour had not yet been investigated hence the brine-shrimp lethality and ...

  20. Brine Shrimp Lethality of Alkaloids from Croton sylvaticus Hoechst ...

    African Journals Online (AJOL)

    Euphorbiaceae) and evaluated for their brine shrimp lethality. Julocrotine, a glutarimide alkaloid, was very toxic in vitro with a LC50 (95% confidence interval) value of 0.074 (0.052-0.105) μg/ml. Lupeol and penduliflaworosin were not toxic. The structures ...

  1. Drosophila simulans Lethal hybrid rescue mutation (Lhr) rescues ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 86; Issue 3. Drosophila simulans Lethal hybrid rescue mutation (Lhr) rescues inviable hybrids by restoring X chromosomal dosage compensation and causes fluctuating asymmetry of development. R. N. Chatterjee P. Chatterjee A. Pal M. Pal-Bhadra. Research Article Volume 86 ...

  2. Drosophila simulans Lethal hybrid rescue mutation (Lhr) rescues ...

    Indian Academy of Sciences (India)

    in the hybrids. Materials and methods. Fly stocks .... toradiography following usual methods (see Chatterjee and. Mukherjee 1981). ... vigor as their sisters. It, therefore, appears that Lhr can sup- press the larval male lethality caused by presence of only melanogaster X chromosome in the hybrid genome. In re- ciprocal cross ...

  3. Radiographic and prenatal ultrasound features of perinatal lethal ...

    African Journals Online (AJOL)

    Hypophosphatasia is a genetic disorder that is characterised by deficient activity of the enzyme alkaline phosphatase. Clinically, it can present as a lethal infantile form, an intermediate childhood form with rachitic changes and premature deciduous tooth loss or a mild adult form with a tendency for fractures and bone pain.

  4. The Lethal "Femme Fatale" in the Noir Tradition. (United States)

    Boozer, Jack


    Traces the lethal seductress through Hollywood's "noir" history from "Double Indemnity" (1944) to "The Last Seduction" (1996). Examines how this figure largely abjures traditional romance and passive domesticity, choosing instead to apply her sexuality to homicidal plots toward greed. Argues that her narrative…

  5. Submandibular space infection: a potentially lethal infection. (United States)

    Boscolo-Rizzo, Paolo; Da Mosto, Maria Cristina


    The aims of this study were to review the clinical characteristics and management of submandibular space infections and to identify the predisposing factors of life-threatening complications. This was a retrospective study at a tertiary academic center. We retrieved and evaluated the records of all patients admitted to the University of Padua Otolaryngology Clinic at Treviso Regional Hospital with the diagnosis of submandibular space infection for the period 1998-2006. The following variables were reviewed: demographic data, pathogenesis, clinical presentation, associated systemic diseases, bacteriology, imaging studies, medical and surgical treatment, and complications. A multivariate logistic regression analysis was undertaken using a forward stepwise technique. Multivariate analysis identified four risk factors for complications. Anterior visceral space involvement (odds ratio (OR) 54.44; 95% confidence interval (CI) 5.80-511.22) and diabetes mellitus (OR 17.46; 95% CI 2.10-145.29) were the most important predictive factors in the model. Logistic regression analysis also confirmed other comorbidities (OR 11.66; 95% CI 1.35-100.10) and bilateral submandibular swelling (OR 10.67; 95% CI 2.73-41.75) as independent predictors for life-threatening complications. Airway obstruction and spread of the infection to the mediastinum are the most troublesome complications of submandibular space infections. Therefore, the maintenance of a secure airway is paramount. Patients with cellulitis and small abscesses can respond to antibiotics alone. Surgical drainage should be performed in patients with larger abscesses, Ludwig's angina, anterior visceral space involvement, and in those who do not respond to antibiotic treatment. Moreover, the clinical assessment in patients with comorbidities, especially diabetes mellitus, requires a high level of suspicion for potential life-threatening complications. Early surgical drainage should always be considered in these patients, even in

  6. Pathological Gambling and Suicidality: An Analysis of Severity and Lethality. (United States)

    Maccallum, Fiona; Blaszczynski, Alex


    Investigates the nature of suicidal behavior among treatment-seeking pathological gamblers and its relationship to gambling characteristics and depression. High rates of suicidal ideation, suicidal plans, and attempts were found; however, no clear relationship was observed between suicidality and indices of gambling behavior. (Contains 37…

  7. Microorganism Utilization for Synthetic Milk (United States)

    Morford, Megan A.; Khodadad, Christina L.; Caro, Janicce I.; Spencer, LaShelle E.; Richards, Jeffery T.; Strayer, Richard F.; Birmele, Michele N.; Wheeler, Raymond M.


    A desired architecture for long duration spaceflight, like aboard the International Space Station or for future missions to Mars, is to provide a supply of fresh food crops for the astronauts. However, some crops can create a high proportion of inedible plant waste. The main goal of the Synthetic Biology project, Cow in a Column, was to produce the components of milk (sugar, lipid, protein) from inedible plant waste by utilizing microorganisms (fungi, yeast, bacteria). Of particular interest was utilizing the valuable polysaccharide, cellulose, found in plant waste, to naturally fuel-through microorganism cellular metabolism- the creation of sugar (glucose), lipid (milk fat), and protein (casein) in order to produce a synthetic edible food product. Environmental conditions such as pH, temperature, carbon source, aeration, and choice microorganisms were optimized in the laboratory and the desired end-products, sugars and lipids, were analyzed. Trichoderma reesei, a known cellulolytic fungus, was utilized to drive the production of glucose, with the intent that the produced glucose would serve as the carbon source for milk fat production and be a substitute for the milk sugar lactose. Lipid production would be carried out by Rhodosporidium toruloides, yeast known to accumulate those lipids that are typically found in milk fat. Results showed that glucose and total lipid content were below what was expected during this phase of experimentation. In addition, individual analysis of six fatty acids revealed that the percentage of each fatty acid was lower than naturally produced bovine milk. Overall, this research indicates that microorganisms could be utilized to breakdown inedible solid waste to produce useable products. For future work, the production of the casein protein for milk would require the development of a genetically modified organism, which was beyond the scope of the original project. Additional trials would be needed to further refine the required

  8. Resveratrol Antagonizes Antimicrobial Lethality and Stimulates Recovery of Bacterial Mutants.

    Directory of Open Access Journals (Sweden)

    Yuanli Liu

    Full Text Available Reactive oxygen species (ROS; superoxide, peroxide, and hydroxyl radical are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. The possibility has been raised that consumption of antioxidants in food may interfere with the lethal action of antimicrobials. Whether nutritional supplements containing antioxidant activity are also likely to interfere with antimicrobial lethality is unknown. To examine this possibility, resveratrol, a popular antioxidant dietary supplement, was added to cultures of Escherichia coli and Staphylococcus aureus that were then treated with antimicrobial and assayed for bacterial survival and the recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Resveratrol, at concentrations likely to be present during human consumption, caused a 2- to 3-fold reduction in killing during a 2-hr treatment with moxifloxacin or kanamycin. At higher, but still subinhibitory concentrations, resveratrol reduced antimicrobial lethality by more than 3 orders of magnitude. Resveratrol also reduced the increase in reactive oxygen species (ROS characteristic of treatment with quinolone (oxolinic acid. These data support the general idea that the lethal activity of some antimicrobials involves ROS. Surprisingly, subinhibitory concentrations of resveratrol promoted (2- to 6-fold the recovery of rifampicin-resistant mutants arising from the action of ciprofloxacin, kanamycin, or daptomycin. This result is consistent with resveratrol reducing ROS to sublethal levels that are still mutagenic, while the absence of resveratrol allows ROS levels to high enough to kill mutagenized cells. Suppression of antimicrobial lethality and promotion of mutant recovery by resveratrol suggests that the antioxidant may contribute to the emergence of resistance to several antimicrobials, especially if new derivatives and/or formulations of resveratrol markedly increase bioavailability.

  9. A Multivariate Model of Stakeholder Preference for Lethal Cat Management (United States)

    Wald, Dara M.; Jacobson, Susan K.


    Identifying stakeholder beliefs and attitudes is critical for resolving management conflicts. Debate over outdoor cat management is often described as a conflict between two groups, environmental advocates and animal welfare advocates, but little is known about the variables predicting differences among these critical stakeholder groups. We administered a mail survey to randomly selected stakeholders representing both of these groups (n = 1,596) in Florida, where contention over the management of outdoor cats has been widespread. We used a structural equation model to evaluate stakeholder intention to support non-lethal management. The cognitive hierarchy model predicted that values influenced beliefs, which predicted general and specific attitudes, which in turn, influenced behavioral intentions. We posited that specific attitudes would mediate the effect of general attitudes, beliefs, and values on management support. Model fit statistics suggested that the final model fit the data well (CFI = 0.94, RMSEA = 0.062). The final model explained 74% of the variance in management support, and positive attitudes toward lethal management (humaneness) had the largest direct effect on management support. Specific attitudes toward lethal management and general attitudes toward outdoor cats mediated the relationship between positive (p<0.05) and negative cat-related impact beliefs (p<0.05) and support for management. These results supported the specificity hypothesis and the use of the cognitive hierarchy to assess stakeholder intention to support non-lethal cat management. Our findings suggest that stakeholders can simultaneously perceive both positive and negative beliefs about outdoor cats, which influence attitudes toward and support for non-lethal management. PMID:24736744

  10. Influence of temperature and pressure on the lethality of ultrasound

    International Nuclear Information System (INIS)

    Raso, J.; Pagan, R.; Condon, S.; Sala, F.J.


    A specially designed resistometer was constructed, and the lethal effect on Yersinia enterocolitica of ultrasonic waves (UW) at different static pressures (manosonication [MS]) and of combined heat-UW under pressure treatments (manothermosonication [MTS]) was investigated. During MS treatments at 30 degrees C and 200 kPa, the increase in the amplitude of UW of 20 kHz from 21 to 150 micrometers exponentially decreased decimal reduction time values (D(MS)) from 4 to 0.37 min. When pressure was increased from 0 to 600 kPa at a constant amplitude (150 micrometers) and temperature (30 degrees C), D(MS) values decreased from 1.52 to 0.20 min. The magnitude of this decrease in D(MS) declined progressively as pressure was increased. The influence of pressure on D(MS) values was greater with increased amplitude of UW. Pressure alone of as much as 600 kPa did not influence the heat resistance of Y. enterocolitica (D60 = 0.094; zeta = 5.65). At temperatures of as much as 58 degrees C, the lethality of UW under pressure was greater than that of heat treatment alone at the same temperature. At higher temperatures, this difference disappeared. Heat and UW under pressure seemed to act independently. The lethality of MTS treatments appeared to result from the added effects of UW under pressure and the lethal effect of heat. The individual contributions of heat and of UW under pressure to the total lethal effect of MTS depended on temperature. The inactivating effect of UW was not due to titanium particles eroded from the sonication horn. The addition to the MS media of cysteamine did not increase the resistance of Y. enterocolitica to MS treatment. MS treatment caused cell disruption

  11. Studying early lethality of 45,XO (Turner's syndrome embryos using human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Achia Urbach

    Full Text Available Turner's syndrome (caused by monosomy of chromosome X is one of the most common chromosomal abnormalities in females. Although 3% of all pregnancies start with XO embryos, 99% of these pregnancies terminate spontaneously during the first trimester. The common genetic explanation for the early lethality of monosomy X embryos, as well as the phenotype of surviving individuals is haploinsufficiency of pseudoautosomal genes on the X chromosome. Another possible mechanism is null expression of imprinted genes on the X chromosome due to the loss of the expressed allele. In contrast to humans, XO mice are viable, and fertile. Thus, neither cells from patients nor mouse models can be used in order to study the cause of early lethality in XO embryos. Human embryonic stem cells (HESCs can differentiate in culture into cells from the three embryonic germ layers as well as into extraembryonic cells. These cells have been shown to have great value in modeling human developmental genetic disorders. In order to study the reasons for the early lethality of 45,XO embryos we have isolated HESCs that have spontaneously lost one of their sex chromosomes. To examine the possibility that imprinted genes on the X chromosome play a role in the phenotype of XO embryos, we have identified genes that were no longer expressed in the mutant cells. None of these genes showed a monoallelic expression in XX cells, implying that imprinting is not playing a major role in the phenotype of XO embryos. To suggest an explanation for the embryonic lethality caused by monosomy X, we have differentiated the XO HESCs in vitro an in vivo. DNA microarray analysis of the differentiated cells enabled us to compare the expression of tissue specific genes in XO and XX cells. The tissue that showed the most significant differences between the clones was the placenta. Many placental genes are expressed at much higher levels in XX cells in compare to XO cells. Thus, we suggest that abnormal

  12. Ammoniacal nitrogen removal from groundwaters using natural and synthetic zeolites


    Matsiyevska, Oksana; Chverenchuk, Andrii; Soprunko, Svitlana; Berezyuk, Roman; Pidlisny, Bogdan


    In article results of ammoniacal nitrogen occurrence ways into groundwaters analysis was represented. NH4+ removing effectivity from simulative solutions by natural (Sokyrnytsia minefield, Ukraine) and synthetic zeolites was compared.

  13. A Synthetic Teammate for UAV Applications: A Prospective Look

    National Research Council Canada - National Science Library

    Gluck, Kevin A; Ball, Jerry T; Gunzelmann, Glenn; Krusmark, Michael A; Lyon, Don R; Cooke, Nancy J


    This report describes current progress and future plans for research and development in synthetic teammates for applications in training, analysis, and system design for Uninhabited Aerial Vehicle (UAV) operations...

  14. Synthetic biology and metabolic engineering. (United States)

    Stephanopoulos, Gregory


    Metabolic engineering emerged 20 years ago as the discipline occupied with the directed modification of metabolic pathways for the microbial synthesis of various products. As such, it deals with the engineering (design, construction, and optimization) of native as well as non-natural routes of product synthesis, aided in this task by the availability of synthetic DNA, the core enabling technology of synthetic biology. The two fields, however, only partially overlap in their interest in pathway engineering. While fabrication of biobricks, synthetic cells, genetic circuits, and nonlinear cell dynamics, along with pathway engineering, have occupied researchers in the field of synthetic biology, the sum total of these areas does not constitute a coherent definition of synthetic biology with a distinct intellectual foundation and well-defined areas of application. This paper reviews the origins of the two fields and advances two distinct paradigms for each of them: that of unit operations for metabolic engineering and electronic circuits for synthetic biology. In this context, metabolic engineering is about engineering cell factories for the biological manufacturing of chemical and pharmaceutical products, whereas the main focus of synthetic biology is fundamental biological research facilitated by the use of synthetic DNA and genetic circuits.

  15. Synthetic cannabinoids: new matrix addiction

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.


    Full Text Available the majority of synthetic cannabinoids (SC, belongs to the group of so-called designer drugs distributed through illegal online shopping. The first reports of this group of psychoactive substances appeared in the 70s of the last century. Today, according to various estimates, there are over 160 varieties of synthetic cannabinoids, and this figure is increasing annually due to the synthesis of new substances in the group. This group of substances is designed to «copy» the psychoactive effects of cannabis. Initially, these substances were created solely for research purposes, to study the endocannabinoid system of the person. Natural THC is a partial agonist of cannabinoid receptors. Synthetic cannabinoids are full agonists CB1R and CB2R types of cannabinoid receptors. Most countries in the world, including Russia, at the legislative level have taken restrictive measures for preventing the spread of this group of substances. In order to circumvent the legislative measures, the producers of synthetic cannabinoids regularly changing the chemical formula. Each year, an increasing number of emergency hospital admissions associated with the use of synthetic cannabinoids in the peer-reviewed literature describes the deaths directly attributable to medical complications after taking synthetic cannabinoids. Numerous studies have proven the possibility of developing psychological dependence due to the use of synthetic cannabinoids. The proposed review of the literature is presented for the purpose of organizing data in the field of synthetic cannabinoids.

  16. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)


    textabstractSynthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps

  17. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.


    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the

  18. Imaging with Synthetic Aperture Radar

    CERN Document Server

    Massonnet, Didier


    Describing a field that has been transformed by the recent availability of data from a new generation of space and airborne systems, the authors offer a synthetic geometrical approach to the description of synthetic aperture radar, one that addresses physicists, radar specialists, as well as experts in image processing.  

  19. Synthetic biology of polyketide synthases

    DEFF Research Database (Denmark)

    Yuzawa, Satoshi; Backman, Tyler W.H.; Keasling, Jay D.


    ). The modules are composed of enzymatic domains that share sequence and functional similarity across all known PKSs. We have used the nomenclature of synthetic biology to classify the enzymatic domains and modules as parts and devices, respectively, and have generated detailed lists of both. In addition, we...... realize the potential that synthetic biology approaches bring to this class of molecules....

  20. Synthetic biology for microbial heavy metal biosensors. (United States)

    Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun


    Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

  1. An Overview of Crowd Control Theory and Considerations for the Employment of Non-Lethal Weapons

    National Research Council Canada - National Science Library

    Grieger, Dion


    .... In campaigns such as these, there is a case for the use of non-lethal weapons to complement the existing range of traditional weapons in order to help bridge the gap between responding with lethal...

  2. Dominant lethal effect of gamma radiation of 60Co in Biomphalaria glabrata (SAY, 1818)

    International Nuclear Information System (INIS)

    Tallarico, Lenita de Freitas


    mutations. Dose range and post-irradiation crossings were defined in a preliminary experiment. In the crossing made 7 days after irradiation, there was an increase in the frequency of malformations with the three doses; in the crossings made 17 and 23 days after irradiation, the effect was detected with the two higher doses. The increase in the frequencies of malformations was directly proportional to the radiation dose. The stronger effect was detected in the first crossing and there was a decrease in the following ones until the crossing made after 30 days. After 23 days, a reduction in the crossing rates was observed with the higher dose. After 36 days, the frequencies of malformation decreased up to background levels. Based on the estimated chronology of spermatogenesis, we could conclude that cells at spermatids and spermatozoa stages were the most sensitive to the dominant lethal effect of radiation, followed by spermatocytes and secondary spermatogonia. Primary spermatogonia were the most sensitive to the cytotoxic effect of radiation. The response of spermatogenesis in B. glabrata to ionizing radiation followed, thus, the pattern observed in other systems. With the estimate of the chronology of spermatogenesis in B. glabrata made in this study, it will be possible to determine post-exposure crossings in the dominant lethal test. These data are also necessary in the interpretation of results obtained from the analysis of environmental samples, usually complex mixtures of many chemicals. (author)

  3. Development of non-lethal methods for investigation of actinide uptake by wildlife

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, M.; Child, D.; Davis, E.; Harrison, J.; Hotchkis, M.; Payne, T.; Thiruvoth, S. [Australian Nuclear Science and Technology Org. (Australia); Wood, M. [University of Salford (United Kingdom)


    contamination associated with a particular species. These biota 'contamination footprints' generally aligned with that of the soil contamination, but in some instances extended further likely due to routine movement of biota, seasonal migrations, predator transport after consumption of contaminated prey, and inter-generational transfer of contamination. Our results provide insights into the benefits, and limitations, of various non-lethal approaches for studies at terrestrial sites. In all of the cases we examined, the non-lethal approaches added an additional layer of variability over the more direct measurement of radionuclides in biotic compartments by lethal means. Some challenges were encountered in sample gathering, preparation, and analysis. However, the methods appear to have potential for adding new tools available for radioecological studies and further development of these approaches is recommended. Document available in abstract form only. (authors)

  4. Computing with synthetic protocells. (United States)

    Courbet, Alexis; Molina, Franck; Amar, Patrick


    In this article we present a new kind of computing device that uses biochemical reactions networks as building blocks to implement logic gates. The architecture of a computing machine relies on these generic and composable building blocks, computation units, that can be used in multiple instances to perform complex boolean functions. Standard logical operations are implemented by biochemical networks, encapsulated and insulated within synthetic vesicles called protocells. These protocells are capable of exchanging energy and information with each other through transmembrane electron transfer. In the paradigm of computation we propose, protoputing, a machine can solve only one problem and therefore has to be built specifically. Thus, the programming phase in the standard computing paradigm is represented in our approach by the set of assembly instructions (specific attachments) that directs the wiring of the protocells that constitute the machine itself. To demonstrate the computing power of protocellular machines, we apply it to solve a NP-complete problem, known to be very demanding in computing power, the 3-SAT problem. We show how to program the assembly of a machine that can verify the satisfiability of a given boolean formula. Then we show how to use the massive parallelism of these machines to verify in less than 20 min all the valuations of the input variables and output a fluorescent signal when the formula is satisfiable or no signal at all otherwise.

  5. Clinical characteristics of synthetic cannabinoid-induced psychosis in relation to schizophrenia: a single-center cross-sectional analysis of concurrently hospitalized patients

    Directory of Open Access Journals (Sweden)

    Altintas M


    Full Text Available Merih Altintas,1 Leman Inanc,2 Gamze Akcay Oruc,1 Selim Arpacioglu,1 Huseyin Gulec1 1Department of Psychiatry, Erenköy Mental and Neurological Diseases Training and Research Hospital, Istanbul, 2Department of Psychiatry, Dr Cevdet Aykan Mental Health and Diseases Hospital, Tokat, Turkey Background: This study aimed to evaluate synthetic cannabinoid (SC-induced psychosis in terms of patient profile and clinical characteristics with reference to concurrently hospitalized schizophrenic patients. Methods: A total of 81 male patients diagnosed with psychotic disorder induced by the use of SCs (n=50; mean (standard deviation [SD] age: 25.9 (5.5 years or with schizophrenia (n=31, mean (SD age: 42.9 (11.6 years based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnosis criteria who were concurrently hospitalized at Erenköy Mental and Neurological Diseases Training and Research Hospital were included in this cross-sectional study. Data on sociodemographic characteristics, Brief Psychiatric Rating Scale (BPRS, Positive and Negative Syndrome Scale (PANSS, Frontal Assessment Battery (FAB, Hamilton Rating Scale for Depression (HRSD, and Hamilton Anxiety Rating Scale (HAM-A were recorded in all the patients. Results: Mean (SD age at disease onset in SC-induced psychosis patients was 22.3 (5.6 years; 26.0% had suicidal ideation and 58.4% were hospitalized involuntarily. Marijuana was the most common first used substance (72.0%, and solitary use of SC was noted in 38.0% of patients. SC-induced psychosis patients had similar PANSS positive, BPRS, HRSD, and FAB scores and significantly lower PANSS negative scores (18.0 [6.5] vs 22.3 [6.0], P=0.004 than patients with schizophrenia, while they had similar HAM-A scores (17.8 [10.3] vs 21.6 [5.5], P=0.085 as young schizophrenics. Age at onset for SC (r=0.364, P=0.05 or substance (r=0.395, P=0.01 use was correlated positively with total FAB scores.Conclusion: In conclusion, our

  6. Custom-Designed MLPA Using Multiple Short Synthetic Probes Application to Methylation Analysis of Five Promoter CpG Islands in Tumor and Urine Specimens from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Serizawa, R.R.; Ralfkiaer, U.; Dahl, C.


    Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using p...... this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis.......Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using......-stranded bacteriophage vector to introduce a sequence of defined length between the primer binding site and the specific target sequence. Here we demonstrate that differences in amplicon length can be achieved by using multiple short synthetic probes for each target sequence. When joined by a DNA ligase, these probes...

  7. Synthetic biology: lessons from the history of synthetic organic chemistry. (United States)

    Yeh, Brian J; Lim, Wendell A


    The mid-nineteenth century saw the development of a radical new direction in chemistry: instead of simply analyzing existing molecules, chemists began to synthesize them--including molecules that did not exist in nature. The combination of this new synthetic approach with more traditional analytical approaches revolutionized chemistry, leading to a deep understanding of the fundamental principles of chemical structure and reactivity and to the emergence of the modern pharmaceutical and chemical industries. The history of synthetic chemistry offers a possible roadmap for the development and impact of synthetic biology, a nascent field in which the goal is to build novel biological systems.

  8. Simulation and Validation of Cisco Lethal Conditions in Minnesota Lakes under Past and Future Climate Scenarios Using Constant Survival Limits

    Directory of Open Access Journals (Sweden)

    Liping Jiang


    Full Text Available Fish habitat in lakes is strongly constrained by water temperature (T and available dissolved oxygen (DO that are changed under climate warming. A one dimensional, dynamic water quality model MINLAKE2012 was used for T and DO simulation over 48 years. A fish habitat model FishHabitat2013 using simulated T and DO profiles as input was developed to determine lethal conditions of cisco Corgenous artedi in Minnesota lakes. Twenty-three lakes that had observations of cisco mortality or survival in the unusually warm summer of 2006 were used for model validation. The cisco habitat model used a lethal temperature of 22.1 °C and DO survival limit of 3 mg/L determined through model validation and sensitivity analysis. Cisco lethal conditions in 12 shallow, 16 medium-depth, and 30 deep virtual lakes were then simulated. Isopleths of total number of years with cisco kill and average cisco kill days for the years with kills under past (1961–2008 and future climate were generated to understand/extrapolate climate impacts on cisco in 620 Minnesota lakes. Shallow and medium-depth lakes are projected to not be good candidates for cisco refuge lakes, but deep lakes are possible cisco refuge lakes based on lethal condition projection under future warmer climate.

  9. (1)H NMR-based metabolomics of Daphnia magna responses after sub-lethal exposure to triclosan, carbamazepine and ibuprofen. (United States)

    Kovacevic, Vera; Simpson, André J; Simpson, Myrna J


    Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100μg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. A quick method for testing recessive lethal damage with a diploid strain of Aspergillus nidulans

    International Nuclear Information System (INIS)

    Morpurgo, G.; Puppo, S.; Gualandi, G.; Conti, L.


    A simple method capable of detecting recessive lethal damage in a diploid strain of Aspergillus nidulans is described. The method scores the recessive lethals on the 1st, the 3rd and the 5th chromosomes, which represent about 40% of the total map of A. nidulans. Two examples of induced lethals, with ultraviolet irradiation and methyl methanesulfonate are shown. The frequency of lethals may reach 36% of the total population with UV irradiation. (Auth.)

  11. Synthetic cannabinoid: prevalence, mechanisms of addiction development, mental disorders associated with the use of synthetic cannabinoid

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.


    Full Text Available according to the authors among the new psychoactive substances, the number of which is growing every year, despite the measures aimed at the obstacles to their dissemination there discovered the most frequent violations of psychotic conditions associated with use of synthetic cannabinoid in clinical practice. On the black market, they are distributed through online shops, under the guise of herbal mixtures for Smoking. When ingested, this group of drugs at the peak of intoxication raises a number of mental (different according to the depth of impaired consciousness, auditory and visual hallucinations, panic attacks, acute psychotic paranoid disorders, catatonic stupor, polar affective disorders, acute polythematic delusional symptoms and somatic disorders (disorders of heart rhythm and conduction, acute ischemic disorders, hypertension, depression of respiratory activity, violation of thermoregulation, development of acute renal failure, vomiting, expressed cephalgia, clinic of hypokalemia. In the reviewed literature and authors own observations there have been discovered some cases of mental addiction development to synthetic cannabinoids. The analysis of new literature data and own clinical observations helped the authors to compare the psychotropic effects caused by this group of drugs, relative to other known surfactants. The toxic effects of CSC on the body greatly exceeds the use of plant cannabinoids, and it has almost the same effects as the synthetic cathinone’s. The speed of formation of psychological dependence is lower compared to synthetic cathinone. Developing current strategies for diagnosis, treatment, and rehabilitation of patients who use synthetic cannabinoids remains an important task for practical healthcare.

  12. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results. (United States)

    Marinetti, Laureen J; Antonides, Heather M


    To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode.

  13. Optimized methods for in vitro and in vivo anti-inflammatory assays and its applications in herbal and synthetic drug analysis. (United States)

    Nile, Shivraj Hariram; Park, Se Won


    Inflammatory diseases including, different types of rheumatic diseases are the major problems associated with the presently available non-steroidal anti-inflammatory agents. The numbers of plant derived drugs have been screened for their anti-inflammatory and anti-arthritic activity. Drug development in the recent times often relies on use of natural and synthetic drugs, which are promising candidates as therapeutic agents for prevention of diseases and disorders. These drugs possess different chemical structures, with wide range of therapeutic activities. The mechanism of Inflammation mainly involve in development of serious diseases, such as cancer, rheumatoid arthritis, sprains, bronchitis, muscle pains, chronic inflammatory bowel disease, persistent asthma, and liver fibrosis. Development of inflammatory events basically related to various chemicals, such as glucocorticoids (GCs) and mometasone furoate (MF); endogenous factors such as tumor necrosis factor alpha (TNF-α); enzymes and proteins such as copper and zinc-superoxide dismutase (SOD), proinflammatory peptide substance (PPS), RGD peptides, interleukin-4 (IL-4), IL-10, interferon-γ (IFN-γ), COX, LOX, cytokines such as interleukin-1 (IL-1); reactive oxygen species (ROS), nitric oxide (NO) and prostaglandin E2; as well as pro-inflammatory cells such as T and NK cells are well known to have an important role. Based on these correlations, numerous assays were used for inflammatory mechanism research, which was described in this paper.

  14. Revertant mutation releases confined lethal mutation, opening Pandora's box: a novel genetic pathogenesis.

    Directory of Open Access Journals (Sweden)

    Yasushi Ogawa


    Full Text Available When two mutations, one dominant pathogenic and the other "confining" nonsense, coexist in the same allele, theoretically, reversion of the latter may elicit a disease, like the opening of Pandora's box. However, cases of this hypothetical pathogenic mechanism have never been reported. We describe a lethal form of keratitis-ichthyosis-deafness (KID syndrome caused by the reversion of the GJB2 nonsense mutation p.Tyr136X that would otherwise have confined the effect of another dominant lethal mutation, p.Gly45Glu, in the same allele. The patient's mother had the identical misssense mutation which was confined by the nonsense mutation. The biological relationship between the parents and the child was confirmed by genotyping of 15 short tandem repeat loci. Haplotype analysis using 40 SNPs spanning the >39 kbp region surrounding the GJB2 gene and an extended SNP microarray analysis spanning 83,483 SNPs throughout chromosome 13 in the family showed that an allelic recombination event involving the maternal allele carrying the mutations generated the pathogenic allele unique to the patient, although the possibility of coincidental accumulation of spontaneous point mutations cannot be completely excluded. Previous reports and our mutation screening support that p.Gly45Glu is in complete linkage disequilibrium with p.Tyr136X in the Japanese population. Estimated from statisitics in the literature, there may be approximately 11,000 p.Gly45Glu carriers in the Japanese population who have this second-site confining mutation, which acts as natural genetic protection from the lethal disease. The reversion-triggered onset of the disesase shown in this study is a previously unreported genetic pathogenesis based on Mendelian inheritance.

  15. Scopolamine methylbromide mitigates radiation induced damage and lethality in zebrafish

    International Nuclear Information System (INIS)

    Shrivastava, Nitisha; Joshi, Jayadev; Ghosh, Subhajit; Dimri, Manali; Prem Kumar, Indracanti; Sehgal, Neeta


    In view of the strategic importance radiation countermeasures hold, the present study was undertaken to screen a collection of small molecule clinical compounds for possible radioprotective action using zebrafish as a model system. Preliminary screening in developing zebrafish embryos (24 hour post fertilization, (hpf)) using damage manifestations and survival as end point identified scopolamine methylbromide (SMB), a muscarinic receptor antagonist, as a potential radiomitigator. It was found to be optimal (60% survival advantage after 6 th post irradiation day) at a dose of 80 μM when added 3 h post 20 Gy exposure. Mechanistic studies suggested that SMB though exhibited no significant antioxidant potential, but was found to limit radiation induced apoptosis (pre G1 population) quantified through flow cytometry (6 and 5% reduction after 8 or 24 h after treatments) and annexin V staining (8% reduction). Further, quantitative analysis, using caspase 3 assay, revealed a 2.46 fold increase in apoptosis in irradiated group and treatment of irradiated zebrafish embryos with SMB led to a significant reduction in global apoptosis (1.7 fold; p<0.05) when compared to irradiated group. In silico studies based on structural and functional similarity with known radioprotectors suggested similarities with atropine, a known anti-inflammatory agent with muscarinic antagonism and radioprotective potential. In view of this SMB was tested, in silico, for possible anti-inflammatory action. Molecular docking studies revealed that SMB interacts (B.E-8.0 Kcal/mole) with cycloxygenase-2 (COX-2). In lieu of this, anti-inflammation activity was assessed through ChIN (chemically induced inflammation) method in 3 dpf (days post fertilization) embryos and SMB was found to significantly inhibit inflammation at all doses studied from 20-200 μM at 3 and 6 hpi (hours post inflammation). Overall the result suggests that scopolamine methylbromide mitigates radiation induced injury and lethality in

  16. An improved brine shrimp larvae lethality microwell test method. (United States)

    Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie


    This article described an improved brine shrimp larvae lethality microwell test method. A simply designed connecting vessel with alternative photoperiod was used to culture and collect high yield of active Artemia parthenogenetica nauplii for brine shrimp larvae lethality microwell test. Using this method, pure A. parthenogenetica nauplii suspension was easily cultured and harvested with high density about 100-150 larvae per milliliter and the natural mortality was reduced to near zero by elimination of unnecessary artificial disturbance. And its sensitivity was validated by determination of LC(50)-24 h of different reference toxicants including five antitumor agents, two pesticides, three organic pollutants, and four heavy metals salts, most of which exhibited LC(50)-24 h between 0.07 and 58.43 mg/L except for bleomycin and mitomycin C with LC(50)-24 h over 300 mg/L.

  17. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.


    Data on acute radiation lethality due to failure of the hematologic system in rats, mice, dogs, swine, monkeys and man are analyzed. Based on the available data, the mortality incidences for 1-100% levels can be computed directly if one has only an estimate of the dose lethal to 50% of the population (LD 50 ) for the mammalian strain and radiation environment of interest. The sole restriction is that the dose profile to the marrow be moderately uniform. If an LD 50 for any exposure situation has been measured, then one can readily scale to any desired situation through implicit-biological and empirical-physical relationships. The LD 50 for man, exposed to an isotropic cloud of photons, and knowledge of the bone-marrow dose profiles readily permit evaluation of the model for other levels of human mortality from different irradiating particles, partial body irradiation and spatially dependent and/or mixed radiation environments. (author)

  18. Dominant lethals following administration of tritium (THO) to rat males

    International Nuclear Information System (INIS)

    Yagova, A.; Baev, I.; Bajrakova, A.


    Adult rat males were given a single intraperitoneal tritium (THO) injection at 0,01 or 0,001 mCi/g body weight (1/100 or 1/1000 of LDsub(50/30), respectively). Twelve days after treatment each male was mated to 3-5 intact females, and the latter were replaced by fresh ones every 12 following days over a 120-day period. Mated females were killed to score conceptions, corpora lutea, and live and dead embryos. Estimations were made of F 1 prenatal death rate (according to Bateman, 1958) and the frequency of induction of dominant lethal mutations (according to Roehrborn, 1970). The results observed indicated paternal exposure to tritium (THO) to produce dominant lethals both in pre- and post-meiotic germ cells in the rat. The extent of the genetic damage studied was found to depend on the amount of activity administered as well as on the time interval between treatment and conception. (author)

  19. Spicing things up: synthetic cannabinoids. (United States)

    Spaderna, Max; Addy, Peter H; D'Souza, Deepak Cyril


    Recently, products containing synthetic cannabinoids, collectively referred to as Spice, are increasingly being used recreationally. The availability, acute subjective effects-including self-reports posted on Erowid-laboratory detection, addictive potential, and regulatory challenges of the Spice phenomenon are reviewed. Spice is sold under the guise of potpourri or incense. Unlike delta-9-tetrahydrocannabinol, the synthetic cannabinoids present in Spice are high-potency, high-efficacy, cannabinoid receptor full agonists. Since standard urine toxicology does not test for the synthetic cannabinoids in Spice, it is often used by those who want to avoid detection of drug use. These compounds have not yet been subjected to rigorous testing in humans. Acute psychoactive effects include changes in mood, anxiety, perception, thinking, memory, and attention. Adverse effects include anxiety, agitation, panic, dysphoria, psychosis, and bizarre behavior. Psychosis outcomes associated with Spice provide additional data linking cannabinoids and psychosis. Adverse events necessitating intervention by Poison Control Centers, law enforcement, emergency responders, and hospitals are increasing. Despite statutes prohibiting the manufacture, distribution, and sale of Spice products, manufacturers are replacing banned compounds with newer synthetic cannabinoids that are not banned. There is an urgent need for better research on the effects of synthetic cannabinoids to help clinicians manage adverse events and to better understand cannabinoid pharmacology in humans. The reported psychosis outcomes associated with synthetic cannabinoids contribute to the ongoing debate on the association between cannabinoids and psychosis. Finally, drug detection tests for synthetic cannabinoids need to become clinically available.

  20. Synthetic Biology and Personalized Medicine (United States)

    Jain, K.K.


    Synthetic biology, application of synthetic chemistry to biology, is a broad term that covers the engineering of biological systems with structures and functions not found in nature to process information, manipulate chemicals, produce energy, maintain cell environment and enhance human health. Synthetic biology devices contribute not only to improve our understanding of disease mechanisms, but also provide novel diagnostic tools. Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs. The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already pointed out during a lecture delivered at Kuwait University in 2005. Of two approaches to synthetic biology, top-down and bottom-up, the latter is more relevant to the development of personalized medicines as it provides more flexibility in constructing a partially synthetic cell from basic building blocks for a desired task. PMID:22907209

  1. Brine shrimp lethality bioassay of selected Centaurea L. species (Asteraceae

    Directory of Open Access Journals (Sweden)

    Janaćković P.


    Full Text Available Ether extracts of 15 Centaurea L. species (Asteraceae methanol extracts of 12species, and cnicin isolated from C. derventana were tested for general bioactivity using the brine shrimp lethality test. Cnicin showed the most potent activity with LC50 0.2. Also, ether extract of C. splendens showed significant activity with LC50 7.3, as did methanol extract of C. arenaria with LC50 12.4.

  2. Bistatic synthetic aperture radar (United States)

    Yates, Gillian

    Synthetic aperture radar (SAR) allows all-weather, day and night, surface surveillance and has the ability to detect, classify and geolocate objects at long stand-off ranges. Bistatic SAR, where the transmitter and the receiver are on separate platforms, is seen as a potential means of countering the vulnerability of conventional monostatic SAR to electronic countermeasures, particularly directional jamming, and avoiding physical attack of the imaging platform. As the receiving platform can be totally passive, it does not advertise its position by RF emissions. The transmitter is not susceptible to jamming and can, for example, operate at long stand-off ranges to reduce its vulnerability to physical attack. This thesis examines some of the complications involved in producing high-resolution bistatic SAR imagery. The effect of bistatic operation on resolution is examined from a theoretical viewpoint and analytical expressions for resolution are developed. These expressions are verified by simulation work using a simple 'point by point' processor. This work is extended to look at using modern practical processing engines for bistatic geometries. Adaptations of the polar format algorithm and range migration algorithm are considered. The principal achievement of this work is a fully airborne demonstration of bistatic SAR. The route taken in reaching this is given, along with some results. The bistatic SAR imagery is analysed and compared to the monostatic imagery collected at the same time. Demonstrating high-resolution bistatic SAR imagery using two airborne platforms represents what I believe to be a European first and is likely to be the first time that this has been achieved outside the US (the UK has very little insight into US work on this topic). Bistatic target characteristics are examined through the use of simulations. This also compares bistatic imagery with monostatic and gives further insight into the utility of bistatic SAR.

  3. Synthetic biology for therapeutic applications. (United States)

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin


    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  4. The Ethics of Synthetic Biology

    DEFF Research Database (Denmark)

    Christiansen, Andreas

    The dissertation analyses and discusses a number of ethical issues that have been raised in connection with the development of synthetic biology. Synthetic biology is a set of new techniques for DNA-level design and construction of living beings with useful properties. The dissertation especially......) popular responsesto them succeed, and whether the objections are ultimately persuasive.2. Given that synthetic biology is a new technology, there is a certain degree of uncertainty about its ultimate effects, and many perceive the technology as risky. I discuss two common approaches in risk regulation...

  5. Custom-Designed MLPA Using Multiple Short Synthetic Probes Application to Methylation Analysis of Five Promoter CpG Islands in Tumor and Urine Specimens from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Serizawa, R.R.; Ralfkiaer, U.; Dahl, C.


    this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis. (J Mol Diagn 2010, 12:402-408; DOI: 10.2353/jmoldx.2010.090152)......Ligation of two oligonucleotide probes hybridized adjacently to a DNA template has been widely used for detection of genome alterations. The multiplex ligation-dependent probe amplification (MLPA) technique allows simultaneous screening of multiple target sequences in a single reaction by using...... pairs of probes that carry tails for binding of common amplification primers. Resolution of the various targets is achieved by electrophoresis on the basis of pre-defined differences in amplicon length. In the conventional MLPA approach, one of the two target probes is generated by cloning in a single-stranded...

  6. The Structural Variation Is Associated with the Embryonic Lethality of a Novel Red Egg Mutant Fuyin-lre of Silkworm, Bombyx mori. (United States)

    Chen, Anli; Liao, Pengfei; Li, Qiongyan; Zhao, Qiaoling; Yang, Weike; Zhu, Shuifen; Wu, Fang; He, Rongfan; Dong, Zhanpeng; Huang, Ping


    Bombyx mori presents several types of egg color mutations, all of which have been extensively discussed in sericulture. While the red egg mutation has been previously observed, lethal red-egg mutants have not been reported. In the present work, the red egg mutant Fuyin-lre (Fuyin-lethal red egg) was discovered from the Fuyin germplasm resource of B. mori. This mutant features red-colored eggs and embryonic lethality. Genetic analysis showed that Fuyin-lre follows recessive inheritance, with the red egg gene re governing the egg color, and the embryonic lethality of Fuyin-lre may be caused by mutations of other genes closely linked to re. Digital gene expression (DGE) was employed to compare the transcription profiles of Fuyin and Fuyin-lre eggs after 24 and 48 h of incubation. A total of 48 differentially expressed genes followed the same expression patterns in both groups at both time points (FDR < 0.01 and log 2 Ratio ≥ 1). Further analyses indicated that 8 out of the 48 genes (including re) were closely linked to re. These 8 genes were highly expressed in wild-type Fuyin and the red egg mutant re but showed nearly absent expression in Fuyin-lre. Sequencing of the re gene confirmed that the re gene itself does not induce embryonic lethality, and structure analysis showed that the structural variation of the region where the 8 genes were located may be associated with the embryonic lethality of Fuyin-lre. The present work provides a good foundation for future studies on the mechanism of embryonic lethality and embryonic development in Fuyin-lre.

  7. The Structural Variation Is Associated with the Embryonic Lethality of a Novel Red Egg Mutant Fuyin-lre of Silkworm, Bombyx mori.

    Directory of Open Access Journals (Sweden)

    Anli Chen

    Full Text Available Bombyx mori presents several types of egg color mutations, all of which have been extensively discussed in sericulture. While the red egg mutation has been previously observed, lethal red-egg mutants have not been reported. In the present work, the red egg mutant Fuyin-lre (Fuyin-lethal red egg was discovered from the Fuyin germplasm resource of B. mori. This mutant features red-colored eggs and embryonic lethality. Genetic analysis showed that Fuyin-lre follows recessive inheritance, with the red egg gene re governing the egg color, and the embryonic lethality of Fuyin-lre may be caused by mutations of other genes closely linked to re. Digital gene expression (DGE was employed to compare the transcription profiles of Fuyin and Fuyin-lre eggs after 24 and 48 h of incubation. A total of 48 differentially expressed genes followed the same expression patterns in both groups at both time points (FDR < 0.01 and log 2 Ratio ≥ 1. Further analyses indicated that 8 out of the 48 genes (including re were closely linked to re. These 8 genes were highly expressed in wild-type Fuyin and the red egg mutant re but showed nearly absent expression in Fuyin-lre. Sequencing of the re gene confirmed that the re gene itself does not induce embryonic lethality, and structure analysis showed that the structural variation of the region where the 8 genes were located may be associated with the embryonic lethality of Fuyin-lre. The present work provides a good foundation for future studies on the mechanism of embryonic lethality and embryonic development in Fuyin-lre.

  8. Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for Liver Cancer Therapy (United States)


    extracted from Hep3B cells after an eight-hour treatment with FDG, DPI, and/or PER. The increase in the ADP/ATP and AMP /ATP ratios in response to the...response to FDG/DPI/PER treatment. (A) The HK2i/DPI/PER triple-combination decreases HCC cellular energy levels. After 8 h drug treatment, AMP , ADP, ATP

  9. A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells. (United States)

    Weïwer, Michel; Spoonamore, James; Wei, Jingqiang; Guichard, Boris; Ross, Nathan T; Masson, Kristina; Silkworth, Whitney; Dandapani, Sivaraman; Palmer, Michelle; Scherer, Christina A; Stern, Andrew M; Schreiber, Stuart L; Munoz, Benito


    The KRAS oncogene is found in up to 30% of all human tumors. In 2009, RNAi experiments revealed that lowering mRNA levels of a transcript encoding the serine/threonine kinase STK33 was selectively toxic to KRAS-dependent cancer cell lines, suggesting that small-molecule inhibitors of STK33 might selectively target KRAS-dependent cancers. To test this hypothesis, we initiated a high-throughput screen using compounds in the Molecular Libraries Small Molecule Repository (MLSMR). Several hits were identified, and one of these, a quinoxalinone derivative, was optimized. Extensive SAR studies were performed and led to the chemical probe ML281 that showed low nanomolar inhibition of purified recombinant STK33 and a distinct selectivity profile as compared to other STK33 inhibitors that were reported in the course of these studies. Even at the highest concentration tested (10 μM), ML281 had no effect on the viability of KRAS-dependent cancer cells. These results are consistent with other recent reports using small-molecule STK33 inhibitors. Small molecules having different chemical structures and kinase-selectivity profiles are needed to fully understand the role of STK33 in KRAS-dependent cancers. In this regard, ML281 is a valuable addition to small-molecule probes of STK33.

  10. Tissue Harmonic Synthetic Aperture Imaging

    DEFF Research Database (Denmark)

    Rasmussen, Joachim

    The main purpose of this PhD project is to develop an ultrasonic method for tissue harmonic synthetic aperture imaging. The motivation is to advance the field of synthetic aperture imaging in ultrasound, which has shown great potentials in the clinic. Suggestions for synthetic aperture tissue...... system complexity compared to conventional synthetic aperture techniques. In this project, SASB is sought combined with a pulse inversion technique for 2nd harmonic tissue harmonic imaging. The advantages in tissue harmonic imaging (THI) are expected to further improve the image quality of SASB....... The first part of the scientific contribution investigates an implementation of pulse inversion for THI on the experimental ultrasound system SARUS. The technique is initially implemented for linear array transducers and then expanded for convex array transducers. The technique is evaluated based on spatial...

  11. Adaptive Synthetic Forces: Situation Awareness

    National Research Council Canada - National Science Library

    Hill, Randall


    ...: perception, comprehension, and prediction. Building on these ideas, we developed techniques for improving the situation awareness in synthetic helicopter pilots for the ModSAF military simulation by giving them more human-like perception...

  12. Designing synthetic networks in silico

    NARCIS (Netherlands)

    Smith, Robert W.; Sluijs, van Bob; Fleck, Christian


    Background: Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused

  13. Synthetic Biology for Specialty Chemicals. (United States)

    Markham, Kelly A; Alper, Hal S


    In this review, we address recent advances in the field of synthetic biology and describe how those tools have been applied to produce a wide variety of chemicals in microorganisms. Here we classify the expansion of the synthetic biology toolbox into three different categories based on their primary function in strain engineering-for design, for construction, and for optimization. Next, focusing on recent years, we look at how chemicals have been produced using these new synthetic biology tools. Advances in producing fuels are briefly described, followed by a more thorough treatment of commodity chemicals, specialty chemicals, pharmaceuticals, and nutraceuticals. Throughout this review, an emphasis is placed on how synthetic biology tools are applied to strain engineering. Finally, we discuss organism and host strain diversity and provide a future outlook in the field.

  14. Is synthetic biology mechanical biology? (United States)

    Holm, Sune


    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  15. Programming languages for synthetic biology. (United States)

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S


    In the backdrop of accelerated efforts for creating synthetic organisms, the nature and scope of an ideal programming language for scripting synthetic organism in-silico has been receiving increasing attention. A few programming languages for synthetic biology capable of defining, constructing, networking, editing and delivering genome scale models of cellular processes have been recently attempted. All these represent important points in a spectrum of possibilities. This paper introduces Kera, a state of the art programming language for synthetic biology which is arguably ahead of similar languages or tools such as GEC, Antimony and GenoCAD. Kera is a full-fledged object oriented programming language which is tempered by biopart rule library named Samhita which captures the knowledge regarding the interaction of genome components and catalytic molecules. Prominent feature of the language are demonstrated through a toy example and the road map for the future development of Kera is also presented.

  16. In Vitro Evaluation of Sub-Lethal Concentrations of Plant-Derived Antifungal Compounds on FUSARIA Growth and Mycotoxin Production

    Directory of Open Access Journals (Sweden)

    Caterina Morcia


    Full Text Available Phytopathogenic fungi can lead to significant cereal yield losses, also producing mycotoxins dangerous for human and animal health. The fungal control based on the use of synthetic fungicides can be complemented by "green" methods for crop protection, based on the use of natural products. In this frame, the antifungal activities of bergamot and lemon essential oils and of five natural compounds recurrent in essential oils (citronellal, citral, cinnamaldehyde, cuminaldehyde and limonene have been evaluated against three species of mycotoxigenic fungi (Fusarium sporotrichioides, F. graminearum and F. langsethiae responsible for Fusarium Head Blight in small-grain cereals. The natural products concentrations effective for reducing or inhibiting the in vitro fungal growth were determined for each fungal species and the following scale of potency was found: cinnamaldehyde > cuminaldehyde > citral > citronellal > bergamot oil > limonene > lemon oil. Moreover, the in vitro mycotoxin productions of the three Fusaria strains exposed to sub-lethal concentrations of the seven products was evaluated. The three fungal species showed variability in response to the treatments, both in terms of inhibition of mycelial growth and in terms of modulation of mycotoxin production that can be enhanced by sub-lethal concentrations of some natural products. This last finding must be taken into account in the frame of an open field application of some plant-derived fungicides.

  17. Non Linearity in Dominant Lethals Induced with Irradiation in Drosophila Melanogaster Non Linearity in Dominant Lethals Induced with Irradiation in Drosophila Melanogaster

    Directory of Open Access Journals (Sweden)

    Hoenigsberg H. F.


    Full Text Available El nuevo diseño experimental aquí presentado hizo posible el estudio de cada uno de los grupos de células germinales en la espermatogénesis de Drosophila melanogaster Oregon R. Los recuentos de los letales dominantes inducidos con Irradiación X permitieron el análisis detallado de la hipótesis sobre dosis-frecuencia para anormalidades cromosómicas. The design in the experiments permitted the study of daily batches of sperm cells. Counts of dominant lethals induced with X-irradiation consented a more detail analysis of the dose-frequency hypothesis for chromosome abnormalities.

  18. Anthrax lethal toxin (LeTx) neutralization by PA domain specific antisera. (United States)

    Verma, Monika; Suryanarayana, Nagendra; Tuteja, Urmil; Thavachelvam, Kulanthaivel; Rao, M K; Bhargava, Rakesh; Shukla, Sangeeta


    Anthrax associated causalities in humans and animals are implicated mainly due to the action of two exotoxins that are secreted by the bacterium Bacillus antharcis during the infection. These exotoxins comprise of three protein components namely protective antigen (PA), lethal factor (LF) and edema factor (EF). The protective antigen is the common toxin component required to form both lethal toxin (LeTx) and edema toxin (EdTx). The LeTx is formed, when PA combines with LF and EdTx is formed when PA combines with EF. Therapeutic interventions aiming to neutralize these key effectors of anthrax pathology would therefore, provide an effective means to counter the toxicity imposed by the anthrax toxins on the host. The present work describes the lethal toxin neutralization potential of polyclonal antisera developed against the individual domains of the protective antigen component of the anthrax toxin. The individual domains were produced as recombinant proteins in E. coli and validated with peptide mass fingerprinting by MALDI-TOF analysis and corresponding mice polyclonal antisera by western blotting. Each domain specific antibody titre and isotype was ascertained by ELISA. The isotyping revealed the predominance of IgG1 isotype. The toxin neutralizing potential of these domain specific antisera were evaluated by in-vitro cell viability MTT assay, employing J774.1 mouse macrophage cell line against LeTx (0.25 μg ml -1 PA and 0.125 μg ml -1 LF concentrations). Among the four domain specific antisera, the antiserum against PA domain IV could neutralize LeTx with high efficiency. No significant neutralization of LeTx was observed with other domain specific antibodies. Results indicate that antibodies to r-PA domain IV could be explored further as therapeutic anti toxin molecule along with appropriate antibiotic regimens against anthrax. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Miniature synthetic-aperture radar system (United States)

    Stockton, Wayne; Stromfors, Richard D.


    Loral Defense Systems-Arizona has developed a high-performance synthetic-aperture radar (SAR) for small aircraft and unmanned aerial vehicle (UAV) reconnaissance applications. This miniature radar, called Miniature Synthetic-Aperture Radar (MSAR), is packaged in a small volume and has low weight. It retains key features of large SAR systems, including high-resolution imaging and all-weather operation. The operating frequency of MSAR can optionally be selected to provide foliage penetration capability. Many imaging radar configurations can be derived using this baseline system. MSAR with a data link provides an attractive UAV sensor. MSAR with a real-time image formation processor is well suited to installations where onboard processing and immediate image analysis are required. The MSAR system provides high-resolution imaging for short-to-medium range reconnaissance applications.

  20. Consequentialism and the Synthetic Biology Problem. (United States)

    Heavey, Patrick


    This article analyzes the ethics of synthetic biology (synbio) from a consequentialist perspective, examining potential effects on food and agriculture, and on medicine, fuel, and the advancement of science. The issues of biosafety and biosecurity are also examined. A consequentialist analysis offers an essential road map to policymakers and regulators as to how to deal with synbio. Additionally, the article discusses the limitations of consequentialism as a tool for analysing synbioethics. Is it possible to predict, with any degree of plausibility, what the consequences of synthetic biology will be in 50 years, or in 100, or in 500? Synbio may take humanity to a place of radical departure from what is known or knowable.

  1. Clinical intrafamilial variability in lethal familial neonatal seizure disorder caused by TBC1D24 mutations. (United States)

    Lozano, Reymundo; Herman, Kristin; Rothfuss, Melanie; Rieger, Hillary; Bayrak-Toydemir, Pinar; Aprile, Davide; Fruscione, Floriana; Zara, Federico; Fassio, Anna


    TBC1D24-related disorders include a wide phenotypic ranging from mild to lethal seizure disorders, non-syndromic deafness, and composite syndromes such as DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). The TBC1D24 gene has a role in cerebral cortex development and in presynaptic neurotransmission. Here, we present a familial case of a lethal early-onset epileptic encephalopathy, associated with two novel compound heterozygous missense variants on the TBC1D24 gene, which were detected by exome sequencing. The detailed clinical data of the three siblings is summarized in order to support the variability of the phenotype, severity, and progression of this disorder among these family members. Functional studies demonstrated that the identified novel missense mutations result in a loss of expression of the protein, suggesting a correlation between residual expression, and the disease severity. This indicates that protein expression analysis is important for interpreting genetic results when novel variants are found, as well as for complementing clinical assessment by predicting the functional impact. Further analysis is necessary to delineate the clinical presentation of individuals with TBC1D24 pathogenic variants, as well as to develop markers for diagnosis, prognosis, and potential targeted treatments. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Generating realistic synthetic meteoroid orbits (United States)

    Vida, Denis; Brown, Peter G.; Campbell-Brown, Margaret


    Context. Generating a synthetic dataset of meteoroid orbits is a crucial step in analysing the probabilities of random grouping of meteoroid orbits in automated meteor shower surveys. Recent works have shown the importance of choosing a low similarity threshold value of meteoroid orbits, some pointing out that the recent meteor shower surveys produced false positives due to similarity thresholds which were too high. On the other hand, the methods of synthetic meteoroid orbit generation introduce additional biases into the data, thus making the final decision on an appropriate threshold value uncertain. Aims. As a part of the ongoing effort to determine the nature of meteor showers and improve automated methods, it was decided to tackle the problem of synthetic meteoroid orbit generation, the main goal being to reproduce the underlying structure and the statistics of the observed data in the synthetic orbits. Methods. A new method of generating synthetic meteoroid orbits using the Kernel Density Estimation method is presented. Several types of approaches are recommended, depending on whether one strives to preserve the data structure, the data statistics or to have a compromise between the two. Results. The improvements over the existing methods of synthetic orbit generation are demonstrated. The comparison between the previous and newly developed methods are given, as well as the visualization tools one can use to estimate the influence of different input parameters on the final data.

  3. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991]. (United States)

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G


    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented.

  4. Synthetic jet flow control of two-dimensional NACA 65(1)-412 airfoil flow with finite-time lyapunov exponent analysis of Lagrangian coherent structures (United States)

    Jeong, Peter Inuk

    Synthetic jet (SJ) control of a low-Reynolds number, unsteady, compressible, viscous flow over a NACA 65-(1)412 airfoil, typical for unmanned air vehicles and gas turbines, has been investigated computationally. A particular focus was placed in the development and control of Lagrangian Coherent Structures (LCS) and the associated Finite-Time Lyapunov Exponent (FTLE) fields. The FTLE fields quantitatively measure of the repulsion rate in forward-time and the attraction rate in backward-time, and provide a unique perspective on effective flow control. A Discontinuous-Galerkin (DG) methods, high-fidelity Navier-Stokes solver performs direct numerical simulation (DNS) of the airfoil flow. Three SJ control strategies have been investigated: immediately downstream of flow separation, normal to the separated shear layer; near the leading edge, normal to the airfoil suction side; near the trailing edge, normal to the airfoil pressure side. A finite difference algorithm computes the FTLE from DNS velocity data. A baseline flow without SJ control is compared to SJ actuated flows. The baseline flow forms a regular, time-periodic, asymmetric von Karman vortex street in the wake. The SJ downstream of flow separation increases recirculation region vorticity and reduces the effective angle of attack. This decreases the time-averaged lift by 2:98% and increases the time-averaged drag by 5:21%. The leading edge SJ produces small vortices that deflect the shear layer downwards, and decreases the effective angle of attack. This reduces the time-averaged lift by 1:80%, and the time-averaged drag by 1:84%. The trailing edge SJ produces perturbations that add to pressure side vortices without affecting global flow characteristics. The time-averaged lift decreases by 0:47%, and the time-averaged drag increases by 0:20%. For all SJ cases, the aerodynamic performance is much more dependent on changes to the pressure distribution than changes to the skin friction distribution. No proposed

  5. Kinetics and mechanism of synthetic CoS oxidation process

    Directory of Open Access Journals (Sweden)

    Štrbac N.


    Full Text Available The results of investigation of kinetics and mechanism for synthetic a-CoS oxidation process are presented in this paper. Based on experimental data obtained using DTA and XRD analysis and constructed PSD diagrams for Co-S-O system, mechanism of synthetic a-CoS oxidation process is suggested. Characteristic kinetic parameters were obtained for experimental isothermal investigations of desulfurization degree using Sharp method.

  6. Relative potency estimation for synthetic petroleum skin carcinogens.


    Holland, J M; Wolf, D A; Clark, B R


    A procedure for quantitative analysis of skin carcinogenesis data, for the purpose of establishing carcinogenic potency, has been applied to observations obtained from C3H mice exposed continuously to synthetic and natural petroleums. The importance of total polynuclear aromatic (PNA) content to the skin carcinogenic activity of the crude materials was also examined. Of three synthetic petroleums evaluated, all were shown capable of inducing skin neoplasms within a two-year exposure period. U...

  7. Autonomy and Fear of Synthetic Biology: How Can Patients' Autonomy Be Enhanced in the Field of Synthetic Biology? A Qualitative Study with Stable Patients. (United States)

    Rakic, Milenko; Wienand, Isabelle; Shaw, David; Nast, Rebecca; Elger, Bernice S


    We analyzed stable patients' views regarding synthetic biology in general, the medical application of synthetic biology, and their potential participation in trials of synthetic biology in particular. The aim of the study was to find out whether patients' views and preferences change after receiving more detailed information about synthetic biology and its clinical applications. The qualitative study was carried out with a purposive sample of 36 stable patients, who suffered from diabetes or gout. Interviews were transcribed verbatim, translated and fully anonymized. Thematic analysis was applied in order to examine stable patients' attitudes towards synthetic biology, its medical application, and their participation in trials. When patients were asked about synthetic biology in general, most of them were anxious that something uncontrollable could be created. After a concrete example of possible future treatment options, patients started to see synthetic biology in a more positive way. Our study constitutes an important first empirical insight into stable patients' views on synthetic biology and into the kind of fears triggered by the term "synthetic biology." Our results show that clear and concrete information can change patients' initial negative feelings towards synthetic biology. Information should thus be transmitted with great accuracy and transparency in order to reduce irrational fears of patients and to minimize the risk that researchers present facts too positively for the purposes of persuading patients to participate in clinical trials. Potential participants need to be adequately informed in order to be able to autonomously decide whether to participate in human subject research involving synthetic biology.

  8. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project. (United States)

    Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H


    First introduced in 2011, the Synthetic Yeast Genome (Sc2.0) PROJECT is a large international synthetic genomics project that will culminate in the first eukaryotic cell (Saccharomyces cerevisiae) with a fully synthetic genome. With collaborators from across the globe and from a range of institutions spanning from do-it-yourself biology (DIYbio) to commercial enterprises, it is important that all scientists working on this project are cognizant of the ethical and policy issues associated with this field of research and operate under a common set of principles. In this commentary, we survey the current ethics and regulatory landscape of synthetic biology and present the Sc2.0 Statement of Ethics and Governance to which all members of the project adhere. This statement focuses on four aspects of the Sc2.0 PROJECT: societal benefit, intellectual property, safety, and self-governance. We propose that such project-level agreements are an important, valuable, and flexible model of self-regulation for similar global, large-scale synthetic biology projects in order to maximize the benefits and minimize potential harms. Copyright © 2015 by the Genetics Society of America.

  9. Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish. (United States)

    Yang, Liling; Zhou, Xiangjun; Huang, Weijuan; Fang, Qin; Hu, Jianlan; Yu, Linzhong; Ma, Ning; Zhang, Wenqing


    Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. This study provides a rationale for the

  10. Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

    Directory of Open Access Journals (Sweden)

    Liling Yang


    Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

  11. Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin A by synthetic peptides. (United States)

    Maina, Edward K; Hu, Dong-Liang; Asano, Krisana; Nakane, Akio


    Staphylococcus aureus is a major human pathogen producing different types of toxins. Enterotoxin A (SEA) is the most common type among clinical and food-related strains. The aim of the present study was to estimate functional regions of SEA that are responsible for emetic and superantigenic activities using synthetic peptides. A series of 13 synthetic peptides corresponding to specific regions of SEA were synthesized, and the effect of these peptides on superantigenic activity of SEA including interferon γ (IFN-γ) production in mouse spleen cells, SEA-induced lethal shock in mice, spleen cell proliferation in house musk shrew, and emetic activity in shrews were assessed. Pre-treatment of spleen cells with synthetic peptides corresponding to the regions 21-40, 35-50, 81-100, or 161-180 of SEA significantly inhibited SEA-induced IFN-γ production and cell proliferation. These peptides also inhibited SEA-induced lethal shock. Interestingly, peptides corresponding to regions 21-40, 35-50 and 81-100 significantly inhibited SEA-induced emesis in house musk shrews, but region 161-180 did not. These findings indicated that regions 21-50 and 81-100 of SEA are important for both superantigenic and emetic activities of SEA molecule while region 161-180 is involved in superantigenic activity but not emetic activity of SEA. These regions could be important targets for therapeutic intervention against SEA exposure. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Left ventricular function during lethal and sublethal endotoxemia in swine

    International Nuclear Information System (INIS)

    Goldfarb, R.D.; Nightingale, L.M.; Kish, P.; Weber, P.B.; Loegering, D.J.


    Previous studies suggested that after a median lethal dose (LD 50 ) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. The authors retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because of the hepatic circulation in this species is similar to that of humans. They compared cardiac mechanical function of pigs administered a high dose (250 μg/kg) or a low dose (100 μg/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardia depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. Myocardial perfusion was measured using radiolabeled microspheres infused into the left atria

  13. Meeting Report: Synthetic Biology Jamboree for Undergraduates (United States)

    Campbell, A. Malcolm


    The field of synthetic biology (the name is derived from an analogy to synthetic chemistry) has recognized itself as a "field" only since about 2002. Synthetic biology has gotten some high-profile attention recently, but most people are not aware the field even exists. Synthetic biologists apply engineering principles to genomic circuits to…

  14. Lethal subarachnoid bleeding under immunosuppressive therapy due to mycotic arteritis

    Energy Technology Data Exchange (ETDEWEB)

    Weigel, S.; Kloska, S.; Freund, M. [Dept. of Clinical Radiology, Univ. Hospital of Muenster, Muenster (Germany); Kehl, H.G. [Dept. of Pediatric Cardiology, Univ. Hospital of Muenster, Muenster (Germany)


    A subarachnoid haemorrhage (SAH) occurred 67 days after cardiac transplantation in 10-year-old girl with consecutive immunocompromising therapy. Neither digital subtraction angiography (DSA) nor computed tomographic angiography showed signs of intracranial vascular malformations. One month before the lethal SAH occurred, she had developed arterial hypertension and attacks of severe headache with cerebrospinal fluid (CSF) pleocytosis while CT scans showed an infarct of the left thalamus. Pathologic findings established the rare diagnosis of SAH due to aspergillosis-related mycotic arteritis. Imaging characteristics are presented. (orig.)

  15. Lethal and Legal The Ethics of Drone Strikes (United States)


    of warfare.6 Key rationales for the use of armed drones are that they are legal, effective, and ethical. According to White House spokesman James ...journalist James Foley in August 2014 was in retalia- tion for U.S. airstrikes in Iraq.98 These medium- and long-term second order effects caused by lethal...20Security%20 Detention%20in%20Non-International%20Armed%20Conflict.pdf. 36. Benjamin Wittes , “Amnesty International Responds,” Law- fare, October

  16. EXCALIBIR - A space experiment in orbital debris lethality (United States)

    Culp, Robert D.; Dickey, Michael R.


    The study proposes a space experiment using extended Space Shuttle external tanks to test the impact of orbital debris. The External Tank Calibrated Impact Response test, EXCALIBIR, is a low-cost low-risk, high-payoff approach to investigating the threat to resident space objects posed by untrackable orbital debris, to provide lethality data to the kinetic energy weapons community, and to aid in the testing of space and missile interceptor technology. This experiment is a feasible use of existing assets - the external tank, observation and data collection facilities, launch facilities, and interceptor technology and tests planned for other programs.

  17. Perinatal lethal type II osteogenesis imperfecta: a case report. (United States)

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra


    We report a new case of osteogenesis imperfecta (OI) type II which is a perinatal lethal form. First trimester ultrasound didn't identified abnormalities. Second trimester ultrasound showed incurved limbs, narrow chest, with hypomineralization and multiple fractures of ribs and long bones. Parents refused pregnancy termination; they felt that the diagnosis was late. At birth, the newborn presented immediate respiratory distress. Postnatal examination and bone radiography confirmed the diagnosis of OI type IIA. Death occurred on day 25 of life related to respiratory failure.

  18. Ultraviolet-B lethal damage on Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Degiorgi, C.F.; Fernandez, R.O.; Pizarro, R.A.


    Pseudomonas aeruginosa has shown an increased sensitivity compared with that of Escherichia coli and Enterobacter cloacae, when they were exposed to 0.4 kJ/m2 of ultraviolet-B radiation. The rapid decay in cell viability observed in Pseudomonas aeruginosa after the irradiation was influenced by factors such as culture media and the presence of pyocyanine during the irradiation. The radioinduced lethal damage could be prevented by photoreactivating treatment, indicating that pyrimidine dimer formation was the mechanism causing bacterial death. The results indicate that several environmental conditions may act as protective agents against ultraviolet-B-induced damage

  19. Synthetic biology: Novel approaches for microbiology. (United States)

    Padilla-Vaca, Felipe; Anaya-Velázquez, Fernando; Franco, Bernardo


    In the past twenty years, molecular genetics has created powerful tools for genetic manipulation of living organisms. Whole genome sequencing has provided necessary information to assess knowledge on gene function and protein networks. In addition, new tools permit to modify organisms to perform desired tasks. Gene function analysis is speed up by novel approaches that couple both high throughput data generation and mining. Synthetic biology is an emerging field that uses tools for generating novel gene networks, whole genome synthesis and engineering. New applications in biotechnological, pharmaceutical and biomedical research are envisioned for synthetic biology. In recent years these new strategies have opened up the possibilities to study gene and genome editing, creation of novel tools for functional studies in virus, parasites and pathogenic bacteria. There is also the possibility to re-design organisms to generate vaccine subunits or produce new pharmaceuticals to combat multi-drug resistant pathogens. In this review we provide our opinion on the applicability of synthetic biology strategies for functional studies of pathogenic organisms and some applications such as genome editing and gene network studies to further comprehend virulence factors and determinants in pathogenic organisms. We also discuss what we consider important ethical issues for this field of molecular biology, especially for potential misuse of the new technologies. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

  20. Colonization of America by Drosophila subobscura: association between Odh gene haplotypes, lethal genes and chromosomal arrangements. (United States)

    Mestres, Francesc; Abad, Laura; Sabater-Muñoz, Beatriz; Latorre, Amparo; Serra, Luís


    The colonization of America by Drosophila subobscura has been a unique exper iment in nature that has allowed us to explore the effects of evolution on a continental scale. To analyze this evolutionary event, nucleotide sequences of the Odh (Octanol dehydrogenase) gene were obtained for 43 lethal chromosomal lines from colonizing populations of North America and 5 from South America, in addition to 5 chromosomal lines from Europe with different viabilities and 2 from laboratory marker stocks. Since 10 different Odh haplotypes were found in America, the minimum number of colonizers would be 5 (or 3 mated females). Only one Odh haplotype was found in American O(5) inversions confirming that only one copy of this inversion was included among the sample of colonizers. The same Odh haplotypes were detected in association with the same chromosomal arrangements and with identical lethal genes in both North and South America indicating that exactly the same chromosome types reached both hemispheres. These observations indicate that the two continental colonizations are not independent. They are derived from the same colonization event. The population from which the colonization started should contain the O(5) inversion, a non-negligible frequency of the O(3+4+7) arrangement and all other arrangements found in America. So far the only populations that fulfill all these requirements are those from Greece, indicating that these populations can be considered good candidates as a starting point for an in depth analysis of the origin of the American colonization by D. subobscura.

  1. Lethal effects of solar radiation in proficient and deficient bacteria in repair systems

    International Nuclear Information System (INIS)

    Sousa Neto, A. de.


    A study of the lethal action of solar radiation on strains of E.coli K12, proficient or deficient in repair systems, as well as the wild type strain gene products are involved in repair of damage induced by solar radiation. The inactivation of the various bacterial strains (normalized to a dose equivalent to radiation at a wavelength 254 nm) suggests that the more energetic wavelengths of the solar spectrum (290-320 nm) could be responsible for the primary damage that occurs in the DNA. The reduction in the shoulder of the survival curve in wild type strains in indicative of induction of sub-lethal damage in this region of the curve. Analysing solar inactivation curves of the bacterial strains (normalised by spore dosimetry) together with those of the same strains irradiated with UV at 254 nm, it was evident that 254 nm is not the ideal wavelength for comparison. This analysis also indicated that in addition to damage to DNA, other factors are involved in the solar radiation inactivation of wild type strains. (author)

  2. Prevalence and lethality among patients with histoplasmosis and AIDS in the Midwest Region of Brazil. (United States)

    Silva, Thaísa C; Treméa, Carolina M; Zara, Ana Laura S A; Mendonça, Ana Flávia; Godoy, Cássia S M; Costa, Carolina R; Souza, Lúcia K H; Silva, Maria R R


    Histoplasmosis is a systemic mycosis that is considered an important public health problem. In this work, we performed a descriptive, observational, cross-sectional and retrospective study with a secondary data analysis of medical records from 2000 to 2012 at a tertiary hospital. The study sample consisted of 275 patients with laboratory-confirmed Disseminated Histoplasmosis (DH)/AIDS. The results showed that the prevalence of DH associated with AIDS was 4.4%. The majority of patients were young adult men with fever in 84.2%, cough in 63.4%, weight loss in 63.1%, diarrhoea in 44.8% and skin manifestations in 27.6% of patients. In the overall cohort, the CD4 counts were low, but not significantly different in survivors and non-survivors. Higher levels of urea and lower levels of haemoglobin and platelets were observed in non-survivor patients (<.05). The global lethality was 71.3% (196/275). The results with high prevalence and lethality highlight the need to adopt measures to facilitate early diagnosis, proper treatment and improved prognosis. © 2016 Blackwell Verlag GmbH.

  3. Human cathepsin L rescues the neurodegeneration and lethality incathepsin B/L double deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Sevenich, Lisa; Pennacchio, Len A.; Peters, Christoph; Reinheckel, Thomas


    Cathepsin B (CTSB) and cathepsin L (CTSL) are two widelyexpressed cysteine proteases thought to predominantly reside withinlysosomes. Functional analysis of CTSL in humans is complicated by theexistence of two CTSL-like homologues (CTSL and CTSL2), in contrast tomice which contain only one CTSL enzyme. Thus transgenic expression ofhuman CTSL in CTSL deficient mice provides an opportunity to study the invivo functions of this human protease without interference by its highlyrelated homologue. While mice with single gene deficiencies for murineCTSB or CTSL survive without apparent neuromuscular impairment, murineCTSB/CTSL double deficient mice display degeneration of cerebellarPurkinje cells and neurons of the cerebral cortex, resulting in severehypotrophy, motility defects, and lethality during their third to fourthweek of life. Here we show that expression of human CTSL through agenomic transgene results in widespread expression of human CTSL in themouse which is capable of rescuing the lethality found in CTSB/CTSLdouble-deficient animals. Human CTSL is expressed in the brain of thesecompound mutants predominantly in neurons of the cerebral cortex and inPurkinje cells of the cerebellum, where it appears to prevent neuronalcell death.

  4. Differential expression of the lethal gene Luteus-Pa in cacao of the Parinari series. (United States)

    Rehem, B C; Almeida, A-A F; Figueiredo, G S F; Gesteira, A S; Santos, S C; Corrêa, R X; Yamada, M M; Valle, R R


    The recessive lethal character Luteus-Pa is found in cacao (Theobroma cacao) genotypes of the Parinari series (Pa) and is characterized by expression of leaf chlorosis and seedling death. Several genotypes of the Pa series are bearers of the gene responsible for the expression of the Luteus-Pa character, which can be used as a tool for determining relationships between genotypes of this group. To evaluate this phenomenon, we analyzed the differential expression of genes between mutant seedlings and wild-type hybrid Pa 30 x 169 seedlings, with the aim of elucidating the possible lethal mechanisms of the homozygous recessive character Luteus-Pa. Plant material was harvested from leaves of wild and mutant seedlings at different periods to construct a subtractive library and perform quantitative analysis using real-time PCR. The 649 sequences obtained from the subtractive library had an average length of 500 bp, forming 409 contigs. The probable proteins encoded were grouped into 10 functional categories. Data from ESTs identified genes associated with Rubisco, peroxidases, and other proteins and enzymes related to carbon assimilation, respiration, and photosystem 2. Mutant seedlings were characterized by synthesizing defective PsbO and PsbA proteins, which were overexpressed from 15 to 20 days after seedling emergence.

  5. Synthetic biology, metaphors and responsibility. (United States)

    McLeod, Carmen; Nerlich, Brigitte


    Metaphors are not just decorative rhetorical devices that make speech pretty. They are fundamental tools for thinking about the world and acting on the world. The language we use to make a better world matters; words matter; metaphors matter. Words have consequences - ethical, social and legal ones, as well as political and economic ones. They need to be used 'responsibly'. They also need to be studied carefully - this is what we want to do through this editorial and the related thematic collection. In the context of synthetic biology, natural and social scientists have become increasingly interested in metaphors, a wave of interest that we want to exploit and amplify. We want to build on emerging articles and books on synthetic biology, metaphors of life and the ethical and moral implications of such metaphors. This editorial provides a brief introduction to synthetic biology and responsible innovation, as well as a comprehensive review of literature on the social, cultural and ethical impacts of metaphor use in genomics and synthetic biology. Our aim is to stimulate an interdisciplinary and international discussion on the impact that metaphors can have on science, policy and publics in the context of synthetic biology.

  6. Meta-Analysis of Attention-Deficit/Hyperactivity Disorder or Attention-Deficit/Hyperactivity Disorder Symptoms, Restriction Diet, and Synthetic Food Color Additives (United States)

    Nigg, Joel T.; Lewis, Kara; Edinger, Tracy; Falk, Michael


    Objective: The role of diet and of food colors in attention-deficit/hyperactivity disorder (ADHD) or its symptoms warrants updated quantitative meta-analysis, in light of recent divergent policy in Europe and the United States. Method: Studies were identified through a literature search using the PubMed, Cochrane Library, and PsycNET databases…

  7. Well-to-wheel analysis of renewable transport fuels: synthetic natural gas from wood gasification and hydrogen from concentrated solar energy[Dissertation 17437

    Energy Technology Data Exchange (ETDEWEB)

    Felder, R.


    In order to deal with problems such as climate change, an increasing energy demand and the finiteness of fossil resources, alternative CO{sub 2}-low technologies have to be found for a sustainable growing future. Laboratories at PSI are conducting research on two pathways delivering such car fuels: synthetic natural gas from wood gasification (SNG) and hydrogen from solar thermochemical ZnO dissociation (STD). The biofuel SNG is produced using wood in an auto-thermal gasification reactor. It can be supplied to the natural-gas grid and be used in a compressed natural gas (CNG) vehicle. STD is a long-term option, using concentrated solar radiation in a thermochemical reactor, producing zinc as solar energy carrier. Zinc can be used for hydrolysis, in order to produce hydrogen as a locally low-polluting future car fuel. In the frame of the thesis, both fuels are assessed using a life cycle assessment, i.e. investigating all environmental interactions from the extraction of resources over the processing and usage steps to the final disposal. Different methodologies are applied for a rating, compared to alternatives and standard fuels of today. In addition, costs of the technologies are calculated in order to assess economic competitiveness. The thesis is structured as follows: After an introduction giving an overview (chapter A), the methodology is presented (chapter B). It includes various life cycle impact assessment methods such as greenhouse gas emissions, the cumulative energy demand or comprehensive rating approaches. Calculations of the production and supply costs of the assessed fuels are included as well as the eco-efficiency, a combination of environmental with economic indicators. In addition, external costs caused by the emissions are quantified. Sensitivity studies investigate the importance of different parameters and substantiate conclusions. In chapter C, the production, supply and use of the assessed fuels is discussed, following the well

  8. US Competitiveness in Synthetic Biology. (United States)

    Gronvall, Gigi Kwik


    Synthetic biology is an emerging technical field that aims to make biology easier to engineer; the field has applications in strategically important sectors for the US economy. While the United States currently leads in synthetic biology R&D, other nations are heavily investing in order to boost their economies, which will inevitably diminish the US leadership position. This outcome is not entirely negative--additional investments will expand markets--but it is critical that the US government take steps to remain competitive: There are applications from which the US population and economy may benefit; there are specific applications with importance for national defense; and US technical leadership will ensure that US experts have a leading role in synthetic biology governance, regulation, and oversight. Measures to increase competitiveness in S&T generally are broadly applicable for synthetic biology and should be pursued. However, the US government will also need to take action on fundamental issues that will affect the field's development, such as countering anti-GMO (genetically modified organism) sentiments and anti-GMO legislation. The United States should maintain its regulatory approach so that it is the product that is regulated, not the method used to create a product. At the same time, the United States needs to ensure that the regulatory framework is updated so that synthetic biology products do not fall into regulatory gaps. Finally, the United States needs to pay close attention to how synthetic biology applications may be governed internationally, such as through the Nagoya Protocol of the Convention on Biological Diversity, so that beneficial applications may be realized.

  9. Synthetic biology as red herring. (United States)

    Preston, Beth


    It has become commonplace to say that with the advent of technologies like synthetic biology the line between artifacts and living organisms, policed by metaphysicians since antiquity, is beginning to blur. But that line began to blur 10,000 years ago when plants and animals were first domesticated; and has been thoroughly blurred at least since agriculture became the dominant human subsistence pattern many millennia ago. Synthetic biology is ultimately only a late and unexceptional offshoot of this prehistoric development. From this perspective, then, synthetic biology is a red herring, distracting us from more thorough philosophical consideration of the most truly revolutionary human practice-agriculture. In the first section of this paper I will make this case with regard to ontology, arguing that synthetic biology crosses no ontological lines that were not crossed already in the Neolithic. In the second section I will construct a parallel case with regard to cognition, arguing that synthetic biology as biological engineering represents no cognitive advance over what was required for domestication and the new agricultural subsistence pattern it grounds. In the final section I will make the case with regard to human existence, arguing that synthetic biology, even if wildly successful, is not in a position to cause significant existential change in what it is to be human over and above the massive existential change caused by the transition to agriculture. I conclude that a longer historical perspective casts new light on some important issues in philosophy of technology and environmental philosophy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Investigation of hexachlorophene for dominant lethal effects in the mouse. (United States)

    Kennedy, G L; Arnold, D W; Keplinger, M L; Calandra, J C


    Hexachlorophene (HCP) was studied for mutagenic effects in the dominant lethal test on mice. Groups of male mice were treated with either 2.5 or 5.0 mg hexachlorophene per kg body weight as a single intraperitoneal injection. Control animals were treated with the propylene glycol vehicle. Each male was mated with 3 untreated females for each of 8 consecutive weeks with the uterus of the females examined at mid-pregnancy for signs of early embryonic death. Treatment did not alter mating capacity and fertility of the males. The administration of hexachlorophene had no influence on pre- or post-implantation losses. An increase in early resorptions among female mice bred to males treated with the reference compound, methyl methanesulfonate (MMS) given a single i.p. injection of 100 mg/kg, indicated the susceptibility of the mouse strain used to a known mutagen. It is concluded that hexachlorophene at maximally tolerated doses is not mutagenic in the dominant lethal test in mice.

  11. Brine shrimp lethality bioassay of selected gymnosperm and angiosperm species

    Directory of Open Access Journals (Sweden)

    Janaćković Peđa T.


    Full Text Available Methanol extracts of selected species of flowering plants Anthemis cotula, A. ruthenica, Centaurea dubia (Asteraceae, Ajuga genevensis, A. chamaepitys, A. reptans, Micromeria albanica, M. cristata, M. dalmatica, M. juliana, Thymus tosevii (Lamiaceae and conifers - Abies alba, Picea omorika, Pinus heldreichii (Pinaceae and Taxus baccata (Taxaceae, as well as diethyl ether extracts of ten species Anthemis cotula, A. ruthenica, Centaurea dubia, Ajuga genevensis, A. chamaepitys, A. reptans, Micromeria albanica, M. cristata, M. dalmatica and M. juliana from two flowering plant families (Asteraceae and Lamiaceae were tested for general bioactivity using brine shrimp (Artemia salina lethality test. Lethal concentration (LC50 and 95% confidence intervals were determined by computer program LdP line. Out of fifteen tested methanol extracts, three possessed cytotoxic effect. Taxus baccata methanol extract showed the highest effect (LC50 = 18.60 μg/ml, while Thymus tosevii methanol extract expressed the lowest (LC50 = 842.50 μg/ml. All other analyzed species did not express significant cytotoxicity. Also, diethyl ether extracts of all tested species did not show significant cytotoxicity. The obtained results for methanol extracts which show certain cytotoxic effect could be guide for further phytochemical and pharmacological investigations. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173029

  12. Treatment of lethal acetylsalicylic acid poisoning without hemodialysis. (United States)

    Ueno, Masahito; Oda, Jun; Soeda, Hiroshi; Uesugi, Hirotaka; Ueno, Keiko; Fujise, Yo; Yukioka, Tetsuo


    A woman aged in her 20s ingested approximately 99 g acetylsalicylic acid, and was transported to our hospital 2 h later. She was lucid, but complained of hearing loss and tinnitus. We performed gastric lavage and gave her activated charcoal several times. We attempted to maintain the urinary pH at 7.5 and output above 100 mL/h while preparing for urgent hemodialysis. It was revealed after discharge that the blood concentration of acetylsalicylic acid was 103.8 mg/dL on admission (lethal dose level) and had decreased to 35.4 mg/dL by the next morning. The half-life was 8.5 h. Hemodialysis is strongly recommended for patients who take a lethal dose of acetylsalicylic acid. However, by carefully evaluating the vital signs and urinary output and pH, while preparing for emergency hemodialysis, we consider that it is possible to treat acetylsalicylic acid poisoning by alkaline diuresis and critical supportive care.

  13. Lethal action of thermal neutron to living cells

    International Nuclear Information System (INIS)

    Kawai, Kenichi; Akahoshi, Mitsuhiko


    Using Amoeba Proteus (DNA content was 5x10 -10 g/cell), action mechanism of thermal neutron was described by using death of cells as an index. Using mononuclear type (M-type) and polynuclear type (P-type) of Amoeba, investigation was made as to whether the number of nucleus contained in cell was related to death of cell by radiation. As compared to gamma-ray, marked difference between sensitivity of both types of Amoeba was not recognized. It was suggested that nucleus was important as a place of death of cell by thermal neutron. In order to demonstrate that reaction of 31 P(n, γ) 32 Pwas a main cause of lethality, the following experiment was carried out. 1) In order to investigate that radical reaction was not a main cause of lethal action by thermal neutron, increase and decrease of radical reaction were observed by adding AET, Cysteine and BudR. As to thermal neutron action, effect of its chemical factors did not appeared. 2) In order to demonstrate that nuclear reaction of constituent atom of living body played an important part in death of cell, increase and decrease of nuclear reaction within cell were observed by taking Na 2 , B 4 and O 7 into Amoeba. It was suggested that nuclear reaction of cell constituent atom itself was important in death of cell. 3) Potentiation effect of gamma-ray and thermal neutron was investigated and its mechanism was discussed. (K. Serizawa)

  14. An outbreak of lethal adenovirus infection among different otariid species. (United States)

    Inoshima, Yasuo; Murakami, Tomoaki; Ishiguro, Naotaka; Hasegawa, Kazuhiro; Kasamatsu, Masahiko


    An outbreak of fatal fulminant hepatitis at a Japanese aquarium involved 3 otariids: a California sea lion (Zalophus californianus), a South African fur seal (Arctocephalus pusillus) and a South American sea lion (Otaria flavescens). In a span of about a week in February 2012, 3 otariids showed diarrhea and were acutely low-spirited; subsequently, all three animals died within a period of 3 days. Markedly increased aspartate amino transferase and alanine amino transferase activities were observed. Necrotic hepatitis and eosinophilic intranuclear inclusion bodies in liver hepatocytes and intestinal epithelial cells were observed in the South American sea lion on histological examination. Otarine adenovirus DNA was detected from the livers of all three animals by polymerase chain reaction and determination of the sequences showed that all were identical. These results suggest that a single otarine adenovirus strain may have been the etiological agent of this outbreak of fatal fulminant hepatitis among the different otariid species, and it may be a lethal threat to wild and captive otariids. This is the first evidence of an outbreak of lethal adenovirus infection among different otariid species. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

    Directory of Open Access Journals (Sweden)

    Nithiuthai S


    Full Text Available Abstract Background Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. Results Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density or with increased transmission. Conclusions We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical

  16. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo


    Full Text Available Controlling structural organization and signaling motif display is of great importance to design the functional tissue regenerating materials. Synthetic phage, genetically engineered M13 bacteriophage has been recently introduced as novel tissue regeneration materials to display a high density of cell-signaling peptides on their major coat proteins for tissue regeneration purposes. Structural advantages of their long-rod shape and monodispersity can be taken together to construct nanofibrous scaffolds which support cell proliferation and differentiation as well as direct orientation of their growth in two or three dimensions. This review demonstrated how functional synthetic phage is designed and subsequently utilized for tissue regeneration that offers potential cell therapy.

  17. Synthetic methodologies for carbon nanomaterials. (United States)

    Liu, Zhaoping; Zhou, Xufeng; Qian, Yitai


    Carbon nanomaterials have advanced rapidly over the last two decades and are among the most promising materials that have already changed and will keep on changing human life. Development of synthetic methodologies for these materials, therefore, has been one of the most important subjects of carbon nanoscience and nanotechnology, and forms the basis for investigating the physicochemical properties and applications of carbon nanomaterials. In this Research News article, several synthetic strategies, including solvothermal reduction, solvothermal pyrolysis, hydrothermal carbonization, and soft-chemical exfoliation are specifically discussed and highlighted, which have been developed for the synthesis of novel carbon nanomaterials over the last decade.

  18. Exploratory Data Analysis of Synthetic Aperture Radar (SAR Measurements to Distinguish the Sea Surface Expressions of Naturally-Occurring Oil Seeps from Human-Related Oil Spills in Campeche Bay (Gulf of Mexico

    Directory of Open Access Journals (Sweden)

    Gustavo de Araújo Carvalho


    Full Text Available An Exploratory Data Analysis (EDA aims to use Synthetic Aperture Radar (SAR measurements for discriminating between two oil slick types observed on the sea surface: naturally-occurring oil seeps versus human-related oil spills—the use of satellite sensors for this task is poorly documented in scientific literature. A long-term RADARSAT dataset (2008–2012 is exploited to investigate oil slicks in Campeche Bay (Gulf of Mexico. Simple Classification Algorithms to distinguish the oil slick type are designed based on standard multivariate data analysis techniques. Various attributes of geometry, shape, and dimension that describe the oil slick Size Information are combined with SAR-derived backscatter coefficients—sigma-(σo, beta-(βo, and gamma-(γo naught. The combination of several of these characteristics is capable of distinguishing the oil slick type with ~70% of overall accuracy, however, the sole and simple use of two specific oil slick’s Size Information (i.e., area and perimeter is equally capable of distinguishing seeps from spills. The data mining exercise of our EDA promotes a novel idea bridging petroleum pollution and remote sensing research, thus paving the way to further investigate the satellite synoptic view to express geophysical differences between seeped and spilled oil observed on the sea surface for systematic use.


    Directory of Open Access Journals (Sweden)

    Isaac Tunde Omoniyi


    Full Text Available This study investigated the lethal toxicity of 2,2-dichlorovinyl dimethyl phosphate (DDVP on African mud catfish, Clarias gariepinus fingerlings (mean weight 7.02 ± 2.56 g and juveniles (mean weight 13.54 ± 1.46 g in a static renewable bioassay. DDVP, also known as Dichlorvos is an organophosphate pesticide. Each treatment in the lethal test was in triplicates with bioassay media concentrations (fingerlings: 0, 250, 275, 300, 325 µgL-1 and (juveniles: 0, 400, 450, 500, 600 µgL-1. Data on fish mortality as well as the physico-chemical parameters (temperature, pH, dissolved oxygen and electrical conductivity, EC of water were collected and subsequently subjected to a one way analysis of variance (ANOVA at 5% probability level. Duncan Multiple Range Test (DMRT was used to separate differences between means. The median lethal concentration (LC50 and median lethal time (LT50 were determined by probit analysis. The water quality parameters of the treatment tanks showed no significant difference with those of the control except for conductivity and pH. Behavioural responses in the fishes included erratic and uncoordinated swimming which were observed to be more pronounced in the juveniles. Bleached body was the only external change observed and this was more pronounced in the fingerlings. The 96-hr LC50 for fingerlings and juveniles were 275.2 and 492.0 µgL-1 respectively. The LT50 values for fingerlings were 48.10 and 7.77 hrs for concentrations 250 and 325 µgL-1 respectively; while those of juveniles were 25.54 and 5.34 hrs for 400 and 600 µgL-1 respectively. The results indicated that DDVP was 1.79 times more toxic to the fingerlings than the juveniles.

  20. Forward imaging for obstacle avoidance using ultrawideband synthetic aperture radar (United States)

    Nguyen, Lam H.; Wong, David C.; Stanton, Brian; Smith, Gregory


    In support of the Army vision for increased mobility, survivability, and lethality, we are investigating the use of ultra-wideband (UWB) synthetic aperture radar (SAR) technology to enhance unmanned ground vehicle missions. The ability of UWB radar technology to detect objects concealed by foilage could provide an important obstacle avoidance capability for robotic vehicles. This would improve the speed and maneuverability of these vehicles and consequently increase the probability of survivability of U.S. forces. This technology would address the particular challenges that confront robotic vehicles such as large rocks hidden in tall grass and voids such as ditches and bodies of water. ARL has designed and constructed an instrumentation-grade low frequency, UWB synthetic aperture radar for evaluation of the target signatures and underlying phenomenology of stationary tactical targets concealed by foilage and objects buried in the ground. The radar (named BoomSAR) is installed in teh basekt of a 30-ton boom lift and can be operated while the entire boom lift is driven forward slowly, with the boom arm extended as high as 45 m to generate a synthetic aperture. In this paper, we investigate the potential use of the UWB radar in the forward imaging configuration. The paper describes the forward imaging radar and test setup at Aberdeen Proving Ground, Maryland. We present imagery of "positive" obstacles such as trees, fences, wires, mines, etc., as well as "negative" obstacles such as ditches. Imagery of small targets such as plastic mines is also included. We provide eletromagnetic simulations of forward SAR imagery of plastic mines and compare that to the measurement data.

  1. Tylosin polyketide synthase module 3: stereospecificity, stereoselectivity and steady-state kinetic analysis of β-processing domains via diffusible, synthetic substrates. (United States)

    Fiers, William D; Dodge, Greg J; Li, Yang; Smith, Janet L; Fecik, Robert A; Aldrich, Courtney C


    Polyketide synthase (PKS) β-processing domains are responsible for much of the stereochemical complexity of polyketide natural products. Although the importance of β-processing domains has been well noted and significantly explored, key stereochemical details pertaining to cryptic stereochemistry and the impact of remote stereogenic centers have yet to be fully discerned. To uncover the inner workings of ketoreductases (KR) and dehydratases (DH) from the tylosin pathway a didomain composed of TylDH3-KR3 was recombinantly expressed and interrogated with full-length tetraketide substrates to probe the impact of vicinal and distal stereochemistry. In vitro product isolation analysis revealed the products of the cryptic KR as d-alcohols and of the DH as trans -olefins. Steady-state kinetic analysis of the dehydration reaction demonstrated a strict stereochemical tolerance at the β-position as d-configured substrates were processed more than 100 times more efficiently than l-alcohols. Unexpectedly, the k cat / K M values were diminished 14- to 45-fold upon inversion of remote ε- and ζ-stereocenters. This stereochemical discrimination is predicted to be driven by a combination of allylic A 1,3 strain that likely disfavors binding of the ε-epimer and a loss of electrostatic interactions with the ζ-epimer. Our results strongly suggest that dehydratases may play a role in refining the stereochemical outcomes of preceding modules through their substrate stereospecificity, honing the configurational purity of the final PKS product.

  2. A Systems Biology Approach to Link Nuclear Factor Kappa B Activation with Lethal Prostate Cancer (United States)


    indolent participants. For each cytokine, the threshold for being ‘high’ was determined as being above the third quartile of the combined indolent identify genes associated with lethal prostate cancer. There were 115 PHS patients (83 indolent , 32 lethal). The DASL data is expressed as...difference between the mean log expression in the lethal group and in the indolent group. When the expression is larger in the indolent group, the result

  3. Where Synthetic Biology Meets ET (United States)

    Rothschild, Lynn J.


    Synthetic biology - the design and construction of new biological parts and systems and the redesign of existing ones for useful purposes - has the potential to transform fields from pharmaceuticals to fuels. Our lab has focused on the potential of synthetic biology to revolutionize all three major parts of astrobiology: Where do we come from? Where are we going? and Are we alone? For the first and third, synthetic biology is allowing us to answer whether the evolutionary narrative that has played out on planet earth is likely to have been unique or universal. For example, in our lab we are re-evolving the biosynthetic pathways of amino acids in order to understand potential capabilities of an early organism with a limited repertoire of amino acids and developing techniques for the recovery of metals from spent electronics on other planetary bodies. And what about the limits for life? Can we create organisms that expand the envelope for life? In the future synthetic biology will play an increasing role in human activities both on earth, in fields as diverse as human health and the industrial production of novel bio-composites. Beyond earth, we will rely increasingly on biologically-provided life support, as we have throughout our evolutionary history. In order to do this, the field will build on two of the great contributions of astrobiology: studies of the origin of life and life in extreme environments.

  4. Future of synthetic aperture radar (United States)

    Barath, F. T.


    The present status of the applications of Synthetic Aperture Radars (SARs) is reviewed, and the technology state-of-the art as represented by the Seasat-A and SIR-A SARs examined. The potential of SAR applications, and the near- and longer-term technology trends are assessed.

  5. Digital 'faces' of synthetic biology. (United States)

    Friedrich, Kathrin


    In silicio design plays a fundamental role in the endeavour to synthesise biological systems. In particular, computer-aided design software enables users to manage the complexity of biological entities that is connected to their construction and reconfiguration. The software's graphical user interface bridges the gap between the machine-readable data on the algorithmic subface of the computer and its human-amenable surface represented by standardised diagrammatic elements. Notations like the Systems Biology Graphical Notation (SBGN), together with interactive operations such as drag & drop, allow the user to visually design and simulate synthetic systems as 'bio-algorithmic signs'. Finally, the digital programming process should be extended to the wet lab to manufacture the designed synthetic biological systems. By exploring the different 'faces' of synthetic biology, I argue that in particular computer-aided design (CAD) is pushing the idea to automatically produce de novo objects. Multifaceted software processes serve mutually aesthetic, epistemic and performative purposes by simultaneously black-boxing and bridging different data sources, experimental operations and community-wide standards. So far, synthetic biology is mainly a product of digital media technologies that structurally mimic the epistemological challenge to take both qualitative as well as quantitative aspects of biological systems into account in order to understand and produce new and functional entities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Synthetic peptides for diagnostic use

    NARCIS (Netherlands)

    Meloen, R.H.; Langedijk, J.P.M.; Langeveld, J.P.M.


    Synthetic peptides representing relevant B-cell epitopes are, potentially, ideal antigens to be used in diagnostic assays because of their superior properties with respect to quality control as compared to those of biologically derived molecules and the much higher specificity that sometimes can be

  7. Can Telescopes Help Leo Satellites Dodge Most Lethal Impacts? (United States)

    GUDIEL, ANDREA; Carroll, Joseph; Rowe, David


    Authors: Joseph Carroll and David RoweABSTRACT LEO objects are tracked by radar because it works day and night, in all weather. This fits military interest in potentially hostile objects. There is less interest in objects too small to be credible active threats. But accidental hypervelocity impact by even 5-10 mm objects can disable most LEO satellites. Such “cm-class” objects greatly outnumber objects of military interest, and will cause most accidental impact losses.Under good viewing conditions, a sunlit 5mm sphere with 0.15 albedo at 800 km altitude is a 19th magnitude object. A ground-based 0.5m telescope tracking it against a 20 mag/arcsec2 sky can see it in seconds, and provide population can be tracked frequently, accurately, and affordably enough to be avoided. The value of a conjunction warning service should scale with the number of lethal objects in its catalog. This should motivate a commercial service to find and catalog most lethal objects. There may already be >1 million such objects in LEO, nearly all debris fragments, mostly cm-class and at 600-1200 km altitude.Maintaining a ~million-item catalog requires a world-wide network of several dozen telescope sites with several telescopes at each site. Each telescope needs a mount capable of ~1,000,000 fast slews/year without wearing out.The paper discusses recent advances that make such a service far more feasible:1. Automated tasking and remote control of distributed telescope networks,2. Direct-drive mounts that can make millions of fast slews without wearing out,3. Telescope optics with low focal curvature that are in focus across large imagers,4. CMOS imagers with 95% peak QE and 1.5e- noise at 2E8 pix/sec readout rates,5. Methods for uncued detection of most lethal LEO debris (eg., >5 mm at 800 km),6. Initial orbit determination using 3 alt-az fixes made during the discovery pass,7. High-speed photometry to infer debris spin axis, to predict drag area changes,8. Better conjunction predictions

  8. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby


    Full Text Available Prions arise when the cellular prion protein (PrP(C undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrP(Sc. Frequently, PrP(Sc is protease-resistant but protease-sensitive (s prions have been isolated in humans and other animals. We report here that protease-sensitive, synthetic prions were generated in vitro during polymerization of recombinant (rec PrP into amyloid fibers. In 22 independent experiments, recPrP amyloid preparations, but not recPrP monomers or oligomers, transmitted disease to transgenic mice (n = 164, denoted Tg9949 mice, that overexpress N-terminally truncated PrP. Tg9949 control mice (n = 174 did not spontaneously generate prions although they were prone to late-onset spontaneous neurological dysfunction. When synthetic prion isolates from infected Tg9949 mice were serially transmitted in the same line of mice, they exhibited sPrP(Sc and caused neurodegeneration. Interestingly, these protease-sensitive prions did not shorten the life span of Tg9949 mice despite causing extensive neurodegeneration. We inoculated three synthetic prion isolates into Tg4053 mice that overexpress full-length PrP; Tg4053 mice are not prone to developing spontaneous neurological dysfunction. The synthetic prion isolates caused disease in 600-750 days in Tg4053 mice, which exhibited sPrP(Sc. These novel synthetic prions demonstrate that conformational changes in wild-type PrP can produce mouse prions composed exclusively of sPrP(Sc.

  9. Lethal now or lethal later: The natural history of Grade 4 blunt cerebrovascular injury. (United States)

    Lauerman, Margaret H; Feeney, Timothy; Sliker, Clint W; Saksobhavivat, Nitima; Bruns, Brandon R; Laser, Adriana; Tesoriero, Ronald; Brenner, Megan; Scalea, Thomas M; Stein, Deborah M


    Grade 4 blunt cerebrovascular injury (BCVI4) has a known, significant rate of stroke. However, little is known about the natural history of BCVI4 and the pathophysiology of subsequent stroke formation. A 4-year review of patients with BCVI4 at the R Adams Cowley Shock Trauma Center was performed. Rates of BCVI4-related stroke, stroke-related mortality, and overall mortality were calculated. The relationship of change in vessel characteristics and BCVI4-related stroke was examined, as was the mechanism of stroke formation. There were 82 BCVI4s identified, with 13 carotid artery (ICA) and 69 vertebral artery BCVI4s. BCVI4-related stroke rate was 2.9% in vertebral artery BCVI4 and 70% in ICA BCVI4 patients surviving to reimaging. Stroke mechanisms included embolic strokes, thrombotic strokes, and combined embolic and thrombotic strokes. Peristroke vessel recanalization and an embolic stroke mechanism were seen in 100% of ICA BCVI4-related strokes developing after admission. BCVI4-related stroke occurred within 10 hours of hospital admission in 67% of the patients with strokes. Contraindications to anticoagulation were present in most patients with BCVI4-related stroke developing after admission. Multiple etiologies of stroke formation exist in BCVI4. Early risk-benefit analysis for initiation of anticoagulation or antiplatelet agents should be performed in all patients with BCVI4, and the use of endovascular vessel occlusion should be considered in those with true contraindications to anticoagulation. However, more aggressive medical therapy may be needed to lessen BCVI4-related stroke development. Prognostic study, level IV; therapeutic study, level V.

  10. Lethal, potentially lethal, and nonlethal damage induction by heavy ions in cultured human cells

    International Nuclear Information System (INIS)

    Todd, P.; Wood, J.C.; Walker, J.T.; Weiss, S.J.


    In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus

  11. Sub-Lethal Dose of Shiga toxin 2 from Enterohemorrhagic Escherichia coli Affects Balance and Cerebellar Cythoarquitecture.

    Directory of Open Access Journals (Sweden)

    Luciana eD’Alessio


    Full Text Available Shiga toxin producing Escherichia coli may damage the central nervous system before or concomitantly to manifested hemolytic uremic syndrome symptoms. The cerebellum is frequently damaged during this syndrome, however the deleterious effects of Shiga toxin 2 has never been integrally reported by ultrastructural, physiological and behavioral means. The aim of this study was to determine the cerebellar compromise after intravenous administration of a sub-lethal dose of Shiga toxin 2 by measuring the cerebellar blood brain barrier permeability, behavioral task of cerebellar functionality (inclined plane test, and ultrastructural analysis (transmission electron microscope. Intravenous administration of vehicle (control group, sub-lethal dose of 0.5 ηg and 1 ηg of Stx2 per mouse were tested for behavioral and ultrastructural studies. A set of three independent experiments were performed for each study (n=6. Blood–Brain Barrier resulted damaged and consequently its permeability was significantly increased. Lower scores obtained in the inclined plane task denoted poor cerebellar functionality in comparison to their controls. The most significant lower score was obtained after 5 days of 1ηg of toxin administration. Transmission electron microscope micrographs from the Stx2-treated groups showed neurons with a progressive neurodegenerative condition in a dose dependent manner. As sub-lethal intravenous Shiga toxin 2 altered the blood brain barrier permeability in the cerebellum the toxin penetrated the cerebellar parenchyma and produced cell damaged with significant functional implications in the test balance.

  12. Standardization of anti-lethal toxin potency test of antivenoms prepared from two different Agkistrodon halys venoms

    Directory of Open Access Journals (Sweden)

    K. H. Lee


    Full Text Available In Korea, antivenoms for the treatment of patients bitten by venomous snakes have been imported from Japan or China. Although there is cross-reactivity between these antibodies and venoms from snakes indigenous to Korea (e.g. Agkistrodon genus, protection is not optimal. Antivenoms specifically prepared to neutralize Korean snake venoms could be more effective, with fewer side effects. To this end, we established an infrastructure to develop national standards and created a standardized method to evaluate the efficacy of two horse-derived antivenoms using mouse lethal toxin test. Additionally, we determined the antivenoms neutralizing activity against lethal doses (LD50 of Agkistrodon halys (from Japan and Jiangzhe Agkistrodon halys (from China venoms. We also performed cross-neutralization tests using probit analysis on each pairing of venom and antivenom in order to check the possibility of using Jiangzhe A. halys venom as a substitute for A. halys venom, the current standard. Slope of A. halys venom with A. halys antivenom was 10.2 and that of A. halys venom with Jiangzhe A. halys antivenom was 9.6. However, Slope of Jiangzhe A. halys venom with A. halys antivenom was 4.7 while that of Jiangzhe A. halys venom with Jiangzhe A. halys antivenom was 11.5. Therefore, the significant difference in slope patterns suggests that Jiangzhe A. halys venom cannot be used as a substitute for the standard venom to test the anti-lethal toxin activity of antivenoms (p<0.05.

  13. {sup 1}H NMR metabolomics of earthworm exposure to sub-lethal concentrations of phenanthrene in soil

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Sarah A.E.; McKelvie, Jennifer R.; Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.c [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, Ontario, M1C 1A4 (Canada)


    {sup 1}H NMR metabolomics was used to monitor earthworm responses to sub-lethal (50-1500 mg/kg) phenanthrene exposure in soil. Total phenanthrene was analyzed via soxhlet extraction, bioavailable phenanthrene was estimated by hydroxypropyl-beta-cyclodextrin (HPCD) and 1-butanol extractions and sorption to soil was assessed by batch equilibration. Bioavailable phenanthrene (HPCD-extracted) comprised approx65-97% of total phenanthrene added to the soil. Principal component analysis (PCA) showed differences in responses between exposed earthworms and controls after 48 h exposure. The metabolites that varied with exposure included amino acids (isoleucine, alanine and glutamine) and maltose. PLS models indicated that earthworm response is positively correlated to both total phenanthrene concentration and bioavailable (HPCD-extracted) phenanthrene in a freshly spiked, unaged soil. These results show that metabolomics is a powerful, direct technique that may be used to monitor contaminant bioavailability and toxicity of sub-lethal concentrations of contaminants in the environment. These initial findings warrant further metabolomic studies with aged contaminated soils. - {sup 1}H NMR metabolomics is used to directly monitor metabolic responses of Eisenia fetida after 48 h of exposure to sub-lethal concentrations of phenanthrene in soil.

  14. RACK1 depletion in a mouse model causes lethality, pigmentation deficits and reduction in protein synthesis efficiency. (United States)

    Volta, Viviana; Beugnet, Anne; Gallo, Simone; Magri, Laura; Brina, Daniela; Pesce, Elisa; Calamita, Piera; Sanvito, Francesca; Biffo, Stefano


    The receptor for activated C-kinase 1 (RACK1) is a conserved structural protein of 40S ribosomes. Strikingly, deletion of RACK1 in yeast homolog Asc1 is not lethal. Mammalian RACK1 also interacts with many nonribosomal proteins, hinting at several extraribosomal functions. A knockout mouse for RACK1 has not previously been described. We produced the first RACK1 mutant mouse, in which both alleles of RACK1 gene are defective in RACK1 expression (ΔF/ΔF), in a pure C57 Black/6 background. In a sample of 287 pups, we observed no ΔF/ΔF mice (72 expected). Dissection and genotyping of embryos at various stages showed that lethality occurs at gastrulation. Heterozygotes (ΔF/+) have skin pigmentation defects with a white belly spot and hypopigmented tail and paws. ΔF/+ have a transient growth deficit (shown by measuring pup size at P11). The pigmentation deficit is partly reverted by p53 deletion, whereas the lethality is not. ΔF/+ livers have mild accumulation of inactive 80S ribosomal subunits by polysomal profile analysis. In ΔF/+ fibroblasts, protein synthesis response to extracellular and pharmacological stimuli is reduced. These results highlight the role of RACK1 as a ribosomal protein converging signaling to the translational apparatus.

  15. A lethal disease model for hantavirus pulmonary syndrome in immunosuppressed Syrian hamsters infected with Sin Nombre virus. (United States)

    Brocato, Rebecca L; Hammerbeck, Christopher D; Bell, Todd M; Wells, Jay B; Queen, Laurie A; Hooper, Jay W


    Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs of disease. In this study, we demonstrate that immunosuppression of hamsters through the administration of a combination of dexamethasone and cyclophosphamide, followed by infection with SNV, results in a vascular leak syndrome that accurately mimics both HPS disease in humans and ANDV infection of hamsters. Immunosuppressed hamsters infected with SNV have a mean number of days to death of 13 and display clinical signs associated with HPS, including pulmonary edema. Viral antigen was widely detectable throughout the pulmonary endothelium. Histologic analysis of lung sections showed marked inflammation and edema within the alveolar septa of SNV-infected hamsters, results which are similar to what is exhibited by hamsters infected with ANDV. Importantly, SNV-specific neutralizing polyclonal antibody administered 5 days after SNV infection conferred significant protection against disease. This experiment not only demonstrated that the disease was caused by SNV, it also demonstrated the utility of this animal model for testing candidate medical countermeasures. This is the first report of lethal disease caused by SNV in an adult small-animal model.

  16. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer. (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A


    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  17. Autotaxin overexpression causes embryonic lethality and vascular defects.

    Directory of Open Access Journals (Sweden)

    Hiroshi Yukiura

    Full Text Available Autotaxin (ATX is a secretory protein, which converts lysophospholipids to lysophosphatidic acid (LPA, and is essential for embryonic vascular formation. ATX is abundantly detected in various biological fluids and its level is elevated in some pathophysiological conditions. However, the roles of elevated ATX levels remain to be elucidated. In this study, we generated conditional transgenic (Tg mice overexpressing ATX and examined the effects of excess LPA signalling. We found that ATX overexpression in the embryonic period caused severe vascular defects and was lethal around E9.5. ATX was conditionally overexpressed in the neonatal period using the Cre/loxP system, which resulted in a marked increase in the plasma LPA level. This resulted in retinal vascular defects including abnormal vascular plexus and increased vascular regression. Our findings indicate that the ATX level must be carefully regulated to ensure coordinated vascular formation.

  18. Autotaxin Overexpression Causes Embryonic Lethality and Vascular Defects (United States)

    Yukiura, Hiroshi; Kano, Kuniyuki; Kise, Ryoji; Inoue, Asuka; Aoki, Junken


    Autotaxin (ATX) is a secretory protein, which converts lysophospholipids to lysophosphatidic acid (LPA), and is essential for embryonic vascular formation. ATX is abundantly detected in various biological fluids and its level is elevated in some pathophysiological conditions. However, the roles of elevated ATX levels remain to be elucidated. In this study, we generated conditional transgenic (Tg) mice overexpressing ATX and examined the effects of excess LPA signalling. We found that ATX overexpression in the embryonic period caused severe vascular defects and was lethal around E9.5. ATX was conditionally overexpressed in the neonatal period using the Cre/loxP system, which resulted in a marked increase in the plasma LPA level. This resulted in retinal vascular defects including abnormal vascular plexus and increased vascular regression. Our findings indicate that the ATX level must be carefully regulated to ensure coordinated vascular formation PMID:25992708

  19. In vitro cell culture lethal dose submitted to gamma radiation

    International Nuclear Information System (INIS)

    Moreno, Carolina S.; Rogero, Sizue O.; Rogero, Jose Roberto; Ikeda, Tamiko I.; Cruz, Aurea S.


    The present study was designed to evaluate the in vitro effect of gamma radiation in cell culture of mouse connective tissue exposed to different doses of gamma radiation and under several conditions. The cell viability was analyzed by neutral red uptake methodology. This assay was developed for establish a methodology to be used in the future in the study of resveratrol radioprotection. Resveratrol (3,4',5- trihydroxystilbene), a phenolic phytoalexin that occurs naturally in some spermatophytes, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is found at high levels and is considered one of the highest antioxidant constituents. The intense antioxidant potential of resveratrol provides many pharmacological activities including cardioprotection, chemoprevention and anti-tumor effects. Our results demonstrated that 60 Co gamma radiation lethal dose (LD50) on NCTC clone 929 cells was about 340Gy. (author)

  20. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.


    The mutagenic and lethal effects of ionizing radiation on histidine-deficient auxotrophs of Salmonella typhimurium were studied to improve the understanding of radiation damage to DNA. The auxotrophs were divided into two groups - one which is sensitive to base-pair substitutions and another sensitive to frameshifts. These groups were composed of parent-daughter pairs in which the chemical mutagenicity enhancing plasmid, pKM101, is absent in the parent strain and present in the daughter. Co-60 #betta#-radiation and 250 kV x-rays were used to irradiate the bacteria. Irradiation of the frameshift - sensitive strains which carry the pKm101 plasmid doubled the absolute number of induced revertants whereas irradiation of the base-pair substitution sensitive strain which also carries the pKm101 plasmid produced nearly no change in the number of induced revertants. A nearly negligible effect on the mutation rate was observed for all parent strains

  1. Gastrointestinal decontamination in healthy and lethally irradiated monkeys

    International Nuclear Information System (INIS)

    Hendriks, W.D.H.


    In periods of extreme immunosuppression, infections which are often life-threatening, frequently occur. In an attempt to prevent such infections in lethally irradiated rhesus monkeys, the animals were subjected to strict reverse isolation prior to irradiation and administrated orally with nonabsorbable antibiotics in order to eliminate their microflora. The antibiotic combination was selected on the basis of a sensitivity test and was added to the liquid food supply. To rapidly achieve a high bactericidal concentration in the intestine, the same antibiotics were additionally given orally for 5 days. The microflora was reduced rapidly; within a few days sterile cultures were obtained. Particularly after discontinuation of the administration of the additional antibiotics were colonizations found. In contrast to colonizations persisting from the first day of treatment on, the first were rather easy to suppress. (Auth.)

  2. Lethal intragroup aggression by adult male spider monkeys (Ateles geoffroyi). (United States)

    Campbell, Christina J


    I report three cases of coalitionary aggression by adult male black-handed spider monkeys (Ateles geoffroyi) against subadult males within their community on Barro Colorado Island (BCI), Panama. Two of these cases were followed by the disappearance and presumed death of the victim. Similar behavior was recently reported by Valero et al. [in press], who suggested that this behavior may be the result of intense male reproductive competition. Like the single instance they reported, the cases I report all occurred when the operational sex ratio was approximately 1:1, which suggests that intense competition among males for access to reproductively viable females may be a contributing factor. Additionally the very low density of spider monkeys on BCI may play a significant role in the occurrence of this lethal aggression. Large numbers of adult males are not necessary to protect a territorial boundary against neighboring groups, and additional males may act merely as mating competition. (c) 2006 Wiley-Liss, Inc.

  3. Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

    Directory of Open Access Journals (Sweden)

    Yufan Cao


    Full Text Available Schistosomiasis is a neglected tropical disease of humans, and it is considered to be the second most devastating parasitic disease after malaria. Eggs produced by normally developed female worms are important in the transmission of the parasite, and they responsible for the pathogenesis of schistosomiasis. The tumor suppressor gene lethal giant larvae (lgl has an essential function in establishing apical-basal cell polarity, cell proliferation, differentiation, and tissue organization. In our earlier study, downregulation of the lgl gene induced a significant reduction in the egg hatching rate of Schistosoma japonicum (Sj eggs. In this study, the Sjlgl gene was used as a vaccine candidate against schistosomiasis, and vaccination achieved and maintained a stable reduction of the egg hatching rate, which is consistent with previous studies, in addition to reducing the worm burden and liver egg burden in some trials.

  4. Current re-vegetation patterns and restoration issues in degraded geological phosphorus-rich mountain areas: A synthetic analysis of Central Yunnan, SW China

    Directory of Open Access Journals (Sweden)

    Kai Yan


    Full Text Available China has the largest area of inland geological phosphorus-rich (GPR mountains in the world, where vegetation restoration is key to safeguarding the environment. We reviewed the published literature and collected new data in order to analyze re-vegetation patterns and the status of plant communities in central Yunnan. The aim of our analysis was to suggest future improvements to restoration strategies in GPR mountain regions. Our results showed that spontaneous recovery was the most widespread type of restoration. N-fixing species such as Coriaria nepalensis and Alnus nepalensis play a vital role in succession. In the past, monoculture tree plantation was the primary method used in afforestation activities in central Yunnan; in recent years however, several different methods of restoration have been introduced including the use of agroforestry systems. For practical restoration, we found that spontaneous recovery was capable of delivering the best results, but that during its early stages, restoration results were affected by several factors including erosion risk, the origin of propagates and environmental variation. In contrast, methods employing human-made communities performed better in their early stages, but were constrained by higher costs and vulnerability to degradation and erosion. The use of N-fixing species such as A. nepalensis and Acacia mearnsii in plantations were unsuccessful in restoring full ecosystem functions. The success of restoration activities in GPR mountain regions could be improved through the following measures: (1 developing a better understanding of the respective advantages and disadvantages of current natural and human-engineered restoration approaches; (2 elucidating the feedback mechanism between phosphorus-rich soil and species selected for restoration, especially N-fixing species; (3 introducing market incentives aimed at encouraging specific restoration activities such as agroforestry, and improving the

  5. Fast Gas Chromatography with Tandem Mass Spectrometry Analysis of Selected Persistent Organic Pollutants and Organophosphorus and Synthetic Pyrethroid Pesticides in Indian Prawn (Fenneropenaeus indicus) in Compliance with the EU-MRLs. (United States)

    Sawant, Durvesh; Kelkar, Jitendra; Rasam, Pratap; Datar, Ajit; Hase, Prashant; Handique, Dheeraj; Bhone, Ankush; Chiplunkar, Sanket; Hate, Manish


    A fast GC with tandem MS method was developed and validated for multiresidue determination of 95 chemical contaminants (24 synthetic pyrethroids, 17 organochlorines, 17 organophosphorus compounds, 18 polycyclic aromatic hydrocarbons, and 19 polychlorinated biphenyls) in Indian prawns (Fenneropenaeus indicus) as per the European Union maximum residual limit requirements. Chromatographic separation and MS determination were achieved within a short run time of 18 min, without compromising sensitivity and specificity. Our findings revealed a 2.5× reduction in the run time compared with conventional GC methods. Sample preparation involved a QuEChERS-based extraction of 10 g sample with 10 mL acidified acetonitrile (1% acetic acid) and phase separation with 6 g anhydrous magnesium sulfate and 1.5 g sodium acetate. The extract was cleaned in two steps, first by dispersive cleanup with primary secondary amine and then by C18 SPE cartridge. The regression coefficients of linearity (r2) for the concentration range of 5-50 ng/mL were >0.99 for all the compounds. Recoveries at 5 and 10 ng/g levels were within the acceptable range of 70-120%. The repeatability (RSDr) and within-laboratory reproducibility (RSDwR) precisions were ≤20%. The method was successfully applied for analysis of the real world samples for incurred residues.

  6. Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes

    Directory of Open Access Journals (Sweden)

    Blanford Simon


    Full Text Available Abstract Background Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to ‘prove concept’. Further, most attention has been paid to examining fungal virulence (lethality and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. Methods The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes’ propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Results and conclusions Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in

  7. Mapping the Emergence of Synthetic Biology. (United States)

    Raimbault, Benjamin; Cointet, Jean-Philippe; Joly, Pierre-Benoît


    In this paper, we apply an original scientometric analyses to a corpus comprising synthetic biology (SynBio) publications in Thomson Reuters Web of Science to characterize the emergence of this new scientific field. Three results were drawn from this empirical investigation. First, despite the exponential growth of publications, the study of population level statistics (newcomers proportion, collaboration network structure) shows that SynBio has entered a stabilization process since 2010. Second, the mapping of textual and citational networks shows that SynBio is characterized by high heterogeneity and four different approaches: the central approach, where biobrick engineering is the most widespread; genome engineering; protocell creation; and metabolic engineering. We suggest that synthetic biology acts as an umbrella term allowing for the mobilization of resources, and also serves to relate scientific content and promises of applications. Third, we observed a strong intertwinement between epistemic and socio-economic dynamics. Measuring scientific production and impact and using structural analysis data, we identified a core set of mostly American scientists. Biographical analysis shows that these central and influential scientists act as "boundary spanners," meaning that their importance to the field lies not only in their academic contributions, but also in their capacity to interact with other social spaces that are outside the academic sphere.

  8. Structure and Function of Iron-Loaded Synthetic Melanin

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yiwen; Xie, Yijun; Wang, Zhao; Zang, Nanzhi; Carniato, Fabio; Huang, Yuran; Andolina, Christopher M.; Parent, Lucas R.; Ditri, Treffly B.; Walter, Eric D.; Botta, Mauro; Rinehart, Jeffrey D.; Gianneschi, Nathan C.


    We describe a synthetic method for increasing and controlling the iron loading of synthetic melanin nanoparticles and use the resulting materials to perform a systematic quantitative investigation on their structure- property relationship. A comprehensive analysis by magnetometry, electron paramagnetic resonance, and nuclear magnetic relaxation dispersion reveals the complexities of their magnetic behavior and how these intraparticle magnetic interactions manifest in useful material properties such as their performance as MRI contrast agents. This analysis allows predictions of the optimal iron loading through a quantitative modeling of antiferromagnetic coupling that arises from proximal iron ions. This study provides a detailed understanding of this complex class of synthetic biomaterials and gives insight into interactions and structures prevalent in naturally occurring melanins.

  9. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lim Yiting [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M. [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Kastan, Michael B. [Department of Oncology, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, North Carolina (United States); Matsui, William, E-mail: [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); DeWeese, Theodore L., E-mail: [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)


    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 {mu}g per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  10. Synthetic LDL as targeted drug delivery vehicle (United States)

    Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA


    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  11. Synthetic biology character and impact

    CERN Document Server

    Pade, Christian; Wigger, Henning; Gleich, Arnim


    Synthetic Biology is already an object of intensive debate. However, to a great extent the discussion to date has been concerned with fundamental ethical, religious and philosophical questions. By contrast, based on an investigation of the field’s scientific and technological character, this book focuses on new functionalities provided by synthetic biology and explores the associated opportunities and risks. Following an introduction to the subject and a discussion of the most central paradigms and methodologies, the book provides an overview of the structure of this field of science and technology. It informs the reader about the current stage of development, as well as topical problems and potential opportunities in important fields of application. But not only the science itself is in focus. In order to investigate its broader impact, ecological as well as ethical implications will be considered, paving the way for a discussion of responsibilities in the context of a field at a transitional crossroads be...

  12. Design Automation in Synthetic Biology. (United States)

    Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas


    Design automation refers to a category of software tools for designing systems that work together in a workflow for designing, building, testing, and analyzing systems with a target behavior. In synthetic biology, these tools are called bio-design automation (BDA) tools. In this review, we discuss the BDA tools areas-specify, design, build, test, and learn-and introduce the existing software tools designed to solve problems in these areas. We then detail the functionality of some of these tools and show how they can be used together to create the desired behavior of two types of modern synthetic genetic regulatory networks. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  13. Engineering Ecosystems and Synthetic Ecologies# (United States)

    Mee, Michael T; Wang, Harris H


    Microbial ecosystems play an important role in nature. Engineering these systems for industrial, medical, or biotechnological purposes are important pursuits for synthetic biologists and biological engineers moving forward. Here, we provide a review of recent progress in engineering natural and synthetic microbial ecosystems. We highlight important forward engineering design principles, theoretical and quantitative models, new experimental and manipulation tools, and possible applications of microbial ecosystem engineering. We argue that simply engineering individual microbes will lead to fragile homogenous populations that are difficult to sustain, especially in highly heterogeneous and unpredictable environments. Instead, engineered microbial ecosystems are likely to be more robust and able to achieve complex tasks at the spatial and temporal resolution needed for truly programmable biology. PMID:22722235

  14. Synthetic greenhouse gases under control

    International Nuclear Information System (INIS)

    Horisberger, B.; Karlaganis, G.


    This article discusses new Swiss regulations on the use of synthetic materials that posses a considerable greenhouse-warming potential. Synthetic materials such as hydro-chlorofluorocarbons HCFCs, perfluoride-hydrocarbons and sulphur hexafluoride have, in recent years, replaced chlorofluorocarbons CFCs, which were banned on account of their ozone depletion characteristics. The use of these persistent substances is now being limited to applications where more environment-friendly alternatives are not available. The measures decreed in the legislation, which include a general ban on HCFCs as of 2004 and a ban on the export of installations and equipment that use ozone-depleting refrigerants are described. Details on the legislation's effects on the Swiss refrigeration industry are listed and discussed

  15. Compounding in synthetic aperture imaging

    DEFF Research Database (Denmark)

    Hansen, J. M.; Jensen, J. A.


    from multiple spherical emissions to synthesize multiple transmit and receive apertures, corresponding to imaging the tissue from multiple directions. The many images are added incoherently, to produce a single compound image. Using a 192-element, 3.5-MHz, λ-pitch transducer, it is demonstrated from...... tissue-phantom measurements that the speckle is reduced and the contrast resolution improved when applying synthetic aperture compound imaging. At a depth of 4 cm, the size of the synthesized apertures is optimized for lesion detection based on the speckle information density. This is a performance...... measure for tissue contrast resolution which quantifies the tradeoff between resolution loss and speckle reduction. The speckle information density is improved by 25% when comparing synthetic aperture compounding to a similar setup for compounding using dynamic receive focusing. The cystic resolution...

  16. Synthetic thermoelectric materials comprising phononic crystals (United States)

    El-Kady, Ihab F; Olsson, Roy H; Hopkins, Patrick; Reinke, Charles; Kim, Bongsang


    Synthetic thermoelectric materials comprising phononic crystals can simultaneously have a large Seebeck coefficient, high electrical conductivity, and low thermal conductivity. Such synthetic thermoelectric materials can enable improved thermoelectric devices, such as thermoelectric generators and coolers, with improved performance. Such synthetic thermoelectric materials and devices can be fabricated using techniques that are compatible with standard microelectronics.

  17. Steel desulphurization with synthetic slag

    Energy Technology Data Exchange (ETDEWEB)

    Heput, T.; Ardelean, E.; Socalici, A.; Maksay, S.; Gavanescu, A.


    Generally speaking, sulfur is considered a harmful element for steel quality, reason why all the technological steps are being taken in order to eliminate it from the metal bath. This paper deals with the influence of the chemical composition, on the slag quantity and of the batch stirring condition upon the desulfurization process in the casting ladle by treatment with synthetic slag. The experiments were made at an open-hearth plant with the steel tapping in two ladles (the desulfurization was made with synthetic slag at one ladle while the other one was considered standard) and at the electric steel plant and for the synthetic slag formation a mix was used, made, according to several receipts, of : lime (50-75%), fluorine (0-17%); bauxite (0-32%) and aluminous slag (8-22%). The data were processed in the calculation programs EXCEL and MATLAB, which resulted in a series of correlations between the desulfurization degree and the chemical composition of the slag, respectively the slag quantity both for the charges bubbled with Argon and the un bubbled ones. (Author) 5 refs.

  18. Hydrogen speciation in synthetic quartz (United States)

    Aines, R.D.; Kirby, S.H.; Rossman, G.R.


    The dominant hydrogen impurity in synthetic quartz is molecular H2O. H-OH groups also occur, but there is no direct evidence for the hydrolysis of Si-O-Si bonds to yield Si-OH HO-Si groups. Molecular H2O concentrations in the synthetic quartz crystals studied range from less than 10 to 3,300 ppm (H/Si), and decrease smoothly by up to an order of magnitude with distance away from the seed. OH- concentrations range from 96 to 715 ppm, and rise smoothly with distance away from the seed by up to a factor of three. The observed OH- is probably all associated with cationic impurities, as in natural quartz. Molecular H2O is the dominant initial hydrogen impurity in weak quartz. The hydrolytic weakening of quartz may be caused by the transformation H2O + Si-O-Si ??? 2SiOH, but this may be a transitory change with the SiOH groups recombining to form H2O, and the average SiOH concentration remaining very low. Synthetic quartz is strengthened when the H2O is accumulated into fluid inclusions and cannot react with the quartz framework. ?? 1984 Springer-Verlag.

  19. Crowd Behavior, Crowd Control, and the Use of Non-Lethal Weapons

    National Research Council Canada - National Science Library

    Kenny, John M; McPhail, Clark; Waddington, Peter; Heal, Sid; Ijames, Steve; Farrer, Donald N; Taylor, Jim; Odenthal, Dick


    .... This is a leading core capability sought by the Joint Non-lethal Weapons Program. The need to thoroughly examine crowd behavior grew out of the Panel's previous assessments of non-lethal weapons, which are being designed for crowd control...

  20. Acute-lethal toxicity (LC50) effect of Moringa oleifera (Lam.) Fresh ...

    African Journals Online (AJOL)


    aquaculture. This study assessed the acute-lethal toxicity (LC50) effect of Moringa oleifera fresh root-bark extract on fresh water fish, Oreochromis niloticus juveniles for 96-h under renewal toxicity exposure. Median. Lethal Concentration (LC50) for O. niloticus juvenile was 97.61 mgl-1 and high mortality was obtained at 200.