WorldWideScience

Sample records for synthetic lethal inference

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

    Directory of Open Access Journals (Sweden)

    Faty Mahamadou

    2008-01-01

    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.

  2. Synthetically lethal nanoparticles for treatment of endometrial cancer

    Science.gov (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.

    2018-01-01

    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.

  3. Antiangiogenic Resistance and Cancer Metabolism: Opportunities for Synthetic Lethality.

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

    2016-01-01

    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.

  4. Synthetic Lethality Triggered by Combining Olaparib with BRCA2-Rad51 Disruptors.

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    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

    2017-10-20

    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.

  5. Malignancy of Cancers and Synthetic Lethal Interactions Associated With Mutations of Cancer Driver Genes.

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

    2016-02-01

    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

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

    National Research Council Canada - National Science Library

    Bellows, David S

    2004-01-01

    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...

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

    National Research Council Canada - National Science Library

    Bellows, David S

    2006-01-01

    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...

  8. The population genetics of X-autosome synthetic lethals and steriles.

    Science.gov (United States)

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

    2011-11-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Andrei Zinovyev

    2013-04-01

    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.

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

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    Maranas Costas D

    2010-12-01

    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

  11. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells.

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    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

    2009-05-29

    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.

  12. Exploiting Synthetic Lethality for the Therapy of ABC Diffuse Large B Cell Lymphoma

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    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.

    2014-01-01

    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

  13. Synthetic lethal interaction between the tumour suppressor STAG2 and its paralog STAG1.

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

    2017-06-06

    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.

  14. A Synthetic Lethal Screen Identifies DNA Repair Pathways that Sensitize Cancer Cells to Combined ATR Inhibition and Cisplatin Treatments

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

    2015-01-01

    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

  15. 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

    2013-01-01

    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)

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

    Science.gov (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

    2017-08-29

    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.

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

    Directory of Open Access Journals (Sweden)

    Chen-Ju Lin

    2012-04-01

    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.

  18. 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

    2017-01-01

    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....

  19. ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

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

    2018-05-01

    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.

  20. A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.

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

    2015-01-01

    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.

  1. 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.

    2015-01-01

    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...

  2. Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

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

    2015-09-29

    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.

  3. 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

    2012-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Tsang Patricia S

    2012-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Khong-Loon Tiong

    2014-05-01

    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.

  6. 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.

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

    Science.gov (United States)

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

    2009-12-01

    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.

  8. Inference

    DEFF Research Database (Denmark)

    Møller, Jesper

    2010-01-01

    Chapter 9: This contribution concerns statistical inference for parametric models used in stochastic geometry and based on quick and simple simulation free procedures as well as more comprehensive methods based on a maximum likelihood or Bayesian approach combined with markov chain Monte Carlo...... (MCMC) techniques. Due to space limitations the focus is on spatial point processes....

  9. Inference

    DEFF Research Database (Denmark)

    Møller, Jesper

    (This text written by Jesper Møller, Aalborg University, is submitted for the collection ‘Stochastic Geometry: Highlights, Interactions and New Perspectives', edited by Wilfrid S. Kendall and Ilya Molchanov, to be published by ClarendonPress, Oxford, and planned to appear as Section 4.1 with the ......(This text written by Jesper Møller, Aalborg University, is submitted for the collection ‘Stochastic Geometry: Highlights, Interactions and New Perspectives', edited by Wilfrid S. Kendall and Ilya Molchanov, to be published by ClarendonPress, Oxford, and planned to appear as Section 4.......1 with the title ‘Inference'.) This contribution concerns statistical inference for parametric models used in stochastic geometry and based on quick and simple simulation free procedures as well as more comprehensive methods using Markov chain Monte Carlo (MCMC) simulations. Due to space limitations the focus...

  10. 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

    2015-09-01

    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.

  11. 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

  12. Synthetic

    Directory of Open Access Journals (Sweden)

    Anna Maria Manferdini

    2010-06-01

    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.

  13. 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

    2004-01-01

    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

  14. Lethal Epistaxis.

    Science.gov (United States)

    Byard, Roger W

    2016-09-01

    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.

  15. Protection Against Lethal Sendai Virus Infection by in vivo Priming of Virus-Specific Cytotoxic T Lymphocytes with a Free Synthetic Peptide

    Science.gov (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.

    1991-03-01

    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.

  16. 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

    Science.gov (United States)

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

    2005-01-01

    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

  17. 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: anderson.ryan@oncology.ox.ac.uk

    2016-06-01

    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.

  18. Protease Addiction and Synthetic Lethality in Cancer

    International Nuclear Information System (INIS)

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

    2011-01-01

    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. A direct carbon budgeting approach to infer carbon sources and sinks. Design and synthetic application to complement the NACP observation network

    International Nuclear Information System (INIS)

    Crevoisier, Cyril; Gloor, Manuel; Gloaguen, Erwan; Sarmiento, Jorge L.

    2006-01-01

    In order to exploit the upcoming regular measurements of vertical carbon dioxide (CO 2 ) profiles over North America implemented in the framework of the North American Carbon Program (NACP), we design a direct carbon budgeting approach to infer carbon sources and sinks over the continent using model simulations. Direct budgeting puts a control volume on top of North America, balances air mass in- and outflows into the volume and solves for the surface fluxes. The flows are derived from the observations through a geostatistical interpolation technique called Kriging combined with transport fields from weather analysis. The use of CO 2 vertical profiles simulated by the atmospheric transport model MOZART-2 at the planned 19 stations of the NACP network has given an estimation of the error of 0.39 GtC/yr within the model world. Reducing this error may be achieved through a better estimation of mass fluxes associated with convective processes affecting North America. Complementary stations in the north-west and the north-east are also needed to resolve the variability of CO 2 in these regions. For instance, the addition of a single station near 52 deg N; 110 deg W is shown to decrease the estimation error to 0.34 GtC/yr

  20. Distributional Inference

    NARCIS (Netherlands)

    Kroese, A.H.; van der Meulen, E.A.; Poortema, Klaas; Schaafsma, W.

    1995-01-01

    The making of statistical inferences in distributional form is conceptionally complicated because the epistemic 'probabilities' assigned are mixtures of fact and fiction. In this respect they are essentially different from 'physical' or 'frequency-theoretic' probabilities. The distributional form is

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

    Directory of Open Access Journals (Sweden)

    Ollivier Emmanuelle

    2010-06-01

    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.

  2. 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, ...

  3. Suicide Lethality: A Concept Analysis.

    Science.gov (United States)

    DeBastiani, Summer; De Santis, Joseph P

    2018-02-01

    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.

  4. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

    Science.gov (United States)

    2012-03-01

    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

  5. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

    Science.gov (United States)

    2014-05-01

    Next, lithium acetylide addition to 3 provides 4, which was subsequently reduced to the E-olefin 5 in excellent yield. Manganese dioxide oxidation of...al. 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

  6. Statistical inference

    CERN Document Server

    Rohatgi, Vijay K

    2003-01-01

    Unified treatment of probability and statistics examines and analyzes the relationship between the two fields, exploring inferential issues. Numerous problems, examples, and diagrams--some with solutions--plus clear-cut, highlighted summaries of results. Advanced undergraduate to graduate level. Contents: 1. Introduction. 2. Probability Model. 3. Probability Distributions. 4. Introduction to Statistical Inference. 5. More on Mathematical Expectation. 6. Some Discrete Models. 7. Some Continuous Models. 8. Functions of Random Variables and Random Vectors. 9. Large-Sample Theory. 10. General Meth

  7. Synthetic Plant Defense Elicitors

    Directory of Open Access Journals (Sweden)

    Yasemin eBektas

    2015-01-01

    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.

  8. Inferring transcriptional compensation interactions in yeast via stepwise structure equation modeling

    Directory of Open Access Journals (Sweden)

    Wang Woei-Fuh

    2008-03-01

    Full Text Available Abstract Background With the abundant information produced by microarray technology, various approaches have been proposed to infer transcriptional regulatory networks. However, few approaches have studied subtle and indirect interaction such as genetic compensation, the existence of which is widely recognized although its mechanism has yet to be clarified. Furthermore, when inferring gene networks most models include only observed variables whereas latent factors, such as proteins and mRNA degradation that are not measured by microarrays, do participate in networks in reality. Results Motivated by inferring transcriptional compensation (TC interactions in yeast, a stepwise structural equation modeling algorithm (SSEM is developed. In addition to observed variables, SSEM also incorporates hidden variables to capture interactions (or regulations from latent factors. Simulated gene networks are used to determine with which of six possible model selection criteria (MSC SSEM works best. SSEM with Bayesian information criterion (BIC results in the highest true positive rates, the largest percentage of correctly predicted interactions from all existing interactions, and the highest true negative (non-existing interactions rates. Next, we apply SSEM using real microarray data to infer TC interactions among (1 small groups of genes that are synthetic sick or lethal (SSL to SGS1, and (2 a group of SSL pairs of 51 yeast genes involved in DNA synthesis and repair that are of interest. For (1, SSEM with BIC is shown to outperform three Bayesian network algorithms and a multivariate autoregressive model, checked against the results of qRT-PCR experiments. The predictions for (2 are shown to coincide with several known pathways of Sgs1 and its partners that are involved in DNA replication, recombination and repair. In addition, experimentally testable interactions of Rad27 are predicted. Conclusion SSEM is a useful tool for inferring genetic networks, and the

  9. Synthetic Cannabinoids

    Directory of Open Access Journals (Sweden)

    Aslihan Okan Ibiloglu

    2017-09-01

    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

  10. MIDLINE LETHAL GRANULOMA COMPLICATING PREGNANCY ...

    African Journals Online (AJOL)

    Kateee

    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 ...

  11. [The "lethal white foal" syndrome].

    Science.gov (United States)

    Blendinger, C; Müller, G; Bostedt, H

    1994-06-01

    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.

  12. Synthetic oils

    Science.gov (United States)

    Hatton, R. E.

    1973-01-01

    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.

  13. Synthetic environments

    Science.gov (United States)

    Lukes, George E.; Cain, Joel M.

    1996-02-01

    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.

  14. Inferring network structure from cascades

    Science.gov (United States)

    Ghonge, Sushrut; Vural, Dervis Can

    2017-07-01

    Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

  15. Synthetic Rutile

    International Nuclear Information System (INIS)

    Burastero, J.

    1975-01-01

    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

  16. Electroshock weapons can be lethal!

    Science.gov (United States)

    Lundquist, Marjorie

    2008-03-01

    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).

  17. Synthetic Genetic Targeting of Genome Instability in Cancer

    International Nuclear Information System (INIS)

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

    2013-01-01

    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

  18. 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: ...

  19. accessions resistants to lethal yellowing disease

    African Journals Online (AJOL)

    Administrator

    2007-02-19

    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.

  20. Synthetic Cannabinoids.

    Science.gov (United States)

    Mills, Brooke; Yepes, Andres; Nugent, Kenneth

    2015-07-01

    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.

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

    Directory of Open Access Journals (Sweden)

    D V Goryachev

    2009-01-01

    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

  2. Synthetic Botany.

    Science.gov (United States)

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

    2017-07-05

    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.

  3. Synthetic Brainbows

    KAUST Repository

    Wan, Y.

    2013-06-01

    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.

  4. SICK: THE SPECTROSCOPIC INFERENCE CRANK

    International Nuclear Information System (INIS)

    Casey, Andrew R.

    2016-01-01

    There exists an inordinate amount of spectral data in both public and private astronomical archives that remain severely under-utilized. The lack of reliable open-source tools for analyzing large volumes of spectra contributes to this situation, which is poised to worsen as large surveys successively release orders of magnitude more spectra. In this article I introduce sick, the spectroscopic inference crank, a flexible and fast Bayesian tool for inferring astrophysical parameters from spectra. sick is agnostic to the wavelength coverage, resolving power, or general data format, allowing any user to easily construct a generative model for their data, regardless of its source. sick can be used to provide a nearest-neighbor estimate of model parameters, a numerically optimized point estimate, or full Markov Chain Monte Carlo sampling of the posterior probability distributions. This generality empowers any astronomer to capitalize on the plethora of published synthetic and observed spectra, and make precise inferences for a host of astrophysical (and nuisance) quantities. Model intensities can be reliably approximated from existing grids of synthetic or observed spectra using linear multi-dimensional interpolation, or a Cannon-based model. Additional phenomena that transform the data (e.g., redshift, rotational broadening, continuum, spectral resolution) are incorporated as free parameters and can be marginalized away. Outlier pixels (e.g., cosmic rays or poorly modeled regimes) can be treated with a Gaussian mixture model, and a noise model is included to account for systematically underestimated variance. Combining these phenomena into a scalar-justified, quantitative model permits precise inferences with credible uncertainties on noisy data. I describe the common model features, the implementation details, and the default behavior, which is balanced to be suitable for most astronomical applications. Using a forward model on low-resolution, high signal

  5. sick: The Spectroscopic Inference Crank

    Science.gov (United States)

    Casey, Andrew R.

    2016-03-01

    There exists an inordinate amount of spectral data in both public and private astronomical archives that remain severely under-utilized. The lack of reliable open-source tools for analyzing large volumes of spectra contributes to this situation, which is poised to worsen as large surveys successively release orders of magnitude more spectra. In this article I introduce sick, the spectroscopic inference crank, a flexible and fast Bayesian tool for inferring astrophysical parameters from spectra. sick is agnostic to the wavelength coverage, resolving power, or general data format, allowing any user to easily construct a generative model for their data, regardless of its source. sick can be used to provide a nearest-neighbor estimate of model parameters, a numerically optimized point estimate, or full Markov Chain Monte Carlo sampling of the posterior probability distributions. This generality empowers any astronomer to capitalize on the plethora of published synthetic and observed spectra, and make precise inferences for a host of astrophysical (and nuisance) quantities. Model intensities can be reliably approximated from existing grids of synthetic or observed spectra using linear multi-dimensional interpolation, or a Cannon-based model. Additional phenomena that transform the data (e.g., redshift, rotational broadening, continuum, spectral resolution) are incorporated as free parameters and can be marginalized away. Outlier pixels (e.g., cosmic rays or poorly modeled regimes) can be treated with a Gaussian mixture model, and a noise model is included to account for systematically underestimated variance. Combining these phenomena into a scalar-justified, quantitative model permits precise inferences with credible uncertainties on noisy data. I describe the common model features, the implementation details, and the default behavior, which is balanced to be suitable for most astronomical applications. Using a forward model on low-resolution, high signal

  6. Factors influencing circadian rhythms in acetaminophen lethality.

    Science.gov (United States)

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

    1984-01-01

    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.

  7. SEMANTIC PATCH INFERENCE

    DEFF Research Database (Denmark)

    Andersen, Jesper

    2009-01-01

    Collateral evolution the problem of updating several library-using programs in response to API changes in the used library. In this dissertation we address the issue of understanding collateral evolutions by automatically inferring a high-level specification of the changes evident in a given set...... specifications inferred by spdiff in Linux are shown. We find that the inferred specifications concisely capture the actual collateral evolution performed in the examples....

  8. Command and Control for Distributed Lethality

    Science.gov (United States)

    2017-06-01

    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

  9. Experiences in therapy for lethal midline granuloma

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-01

    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.

  10. Inference in `poor` languages

    Energy Technology Data Exchange (ETDEWEB)

    Petrov, S.

    1996-10-01

    Languages with a solvable implication problem but without complete and consistent systems of inference rules (`poor` languages) are considered. The problem of existence of finite complete and consistent inference rule system for a ``poor`` language is stated independently of the language or rules syntax. Several properties of the problem arc proved. An application of results to the language of join dependencies is given.

  11. Bayesian statistical inference

    Directory of Open Access Journals (Sweden)

    Bruno De Finetti

    2017-04-01

    Full Text Available This work was translated into English and published in the volume: Bruno De Finetti, Induction and Probability, Biblioteca di Statistica, eds. P. Monari, D. Cocchi, Clueb, Bologna, 1993.Bayesian statistical Inference is one of the last fundamental philosophical papers in which we can find the essential De Finetti's approach to the statistical inference.

  12. Geometric statistical inference

    International Nuclear Information System (INIS)

    Periwal, Vipul

    1999-01-01

    A reparametrization-covariant formulation of the inverse problem of probability is explicitly solved for finite sample sizes. The inferred distribution is explicitly continuous for finite sample size. A geometric solution of the statistical inference problem in higher dimensions is outlined

  13. Practical Bayesian Inference

    Science.gov (United States)

    Bailer-Jones, Coryn A. L.

    2017-04-01

    Preface; 1. Probability basics; 2. Estimation and uncertainty; 3. Statistical models and inference; 4. Linear models, least squares, and maximum likelihood; 5. Parameter estimation: single parameter; 6. Parameter estimation: multiple parameters; 7. Approximating distributions; 8. Monte Carlo methods for inference; 9. Parameter estimation: Markov chain Monte Carlo; 10. Frequentist hypothesis testing; 11. Model comparison; 12. Dealing with more complicated problems; References; Index.

  14. Knowledge and inference

    CERN Document Server

    Nagao, Makoto

    1990-01-01

    Knowledge and Inference discusses an important problem for software systems: How do we treat knowledge and ideas on a computer and how do we use inference to solve problems on a computer? The book talks about the problems of knowledge and inference for the purpose of merging artificial intelligence and library science. The book begins by clarifying the concept of """"knowledge"""" from many points of view, followed by a chapter on the current state of library science and the place of artificial intelligence in library science. Subsequent chapters cover central topics in the artificial intellig

  15. Logical inference and evaluation

    International Nuclear Information System (INIS)

    Perey, F.G.

    1981-01-01

    Most methodologies of evaluation currently used are based upon the theory of statistical inference. It is generally perceived that this theory is not capable of dealing satisfactorily with what are called systematic errors. Theories of logical inference should be capable of treating all of the information available, including that not involving frequency data. A theory of logical inference is presented as an extension of deductive logic via the concept of plausibility and the application of group theory. Some conclusions, based upon the application of this theory to evaluation of data, are also given

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

    Directory of Open Access Journals (Sweden)

    Carlos Silva Forné

    2017-11-01

    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.

  17. Probability and Statistical Inference

    OpenAIRE

    Prosper, Harrison B.

    2006-01-01

    These lectures introduce key concepts in probability and statistical inference at a level suitable for graduate students in particle physics. Our goal is to paint as vivid a picture as possible of the concepts covered.

  18. Introductory statistical inference

    CERN Document Server

    Mukhopadhyay, Nitis

    2014-01-01

    This gracefully organized text reveals the rigorous theory of probability and statistical inference in the style of a tutorial, using worked examples, exercises, figures, tables, and computer simulations to develop and illustrate concepts. Drills and boxed summaries emphasize and reinforce important ideas and special techniques.Beginning with a review of the basic concepts and methods in probability theory, moments, and moment generating functions, the author moves to more intricate topics. Introductory Statistical Inference studies multivariate random variables, exponential families of dist

  19. Guidebook for non-lethal experimentation

    NARCIS (Netherlands)

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

    2011-01-01

    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

    Science.gov (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.

    1991-01-01

    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. Can Telescopes Help Leo Satellites Dodge Most Lethal Impacts?

    Science.gov (United States)

    GUDIEL, ANDREA; Carroll, Joseph; Rowe, David

    2018-01-01

    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

  3. Plant synthetic biology.

    Science.gov (United States)

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    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.

  4. 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 ...

  5. Synthetic observations of protostellar multiple systems

    Science.gov (United States)

    Lomax, O.; Whitworth, A. P.

    2018-04-01

    Observations of protostars are often compared with synthetic observations of models in order to infer the underlying physical properties of the protostars. The majority of these models have a single protostar, attended by a disc and an envelope. However, observational and numerical evidence suggests that a large fraction of protostars form as multiple systems. This means that fitting models of single protostars to observations may be inappropriate. We produce synthetic observations of protostellar multiple systems undergoing realistic, non-continuous accretion. These systems consist of multiple protostars with episodic luminosities, embedded self-consistently in discs and envelopes. We model the gas dynamics of these systems using smoothed particle hydrodynamics and we generate synthetic observations by post-processing the snapshots using the SPAMCART Monte Carlo radiative transfer code. We present simulation results of three model protostellar multiple systems. For each of these, we generate 4 × 104 synthetic spectra at different points in time and from different viewing angles. We propose a Bayesian method, using similar calculations to those presented here, but in greater numbers, to infer the physical properties of protostellar multiple systems from observations.

  6. Synthetic antifreeze peptide

    OpenAIRE

    1991-01-01

    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. [SYNTHETIC PEPTIDE VACCINES].

    Science.gov (United States)

    Sergeyev, O V; Barinsky, I F

    2016-01-01

    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.

  8. Making Type Inference Practical

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Oxhøj, Nicholas; Palsberg, Jens

    1992-01-01

    We present the implementation of a type inference algorithm for untyped object-oriented programs with inheritance, assignments, and late binding. The algorithm significantly improves our previous one, presented at OOPSLA'91, since it can handle collection classes, such as List, in a useful way. A......-oriented languages practical....

  9. Type Inference with Inequalities

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff

    1991-01-01

    of (monotonic) inequalities on the types of variables and expressions. A general result about systems of inequalities over semilattices yields a solvable form. We distinguish between deciding typability (the existence of solutions) and type inference (the computation of a minimal solution). In our case, both...

  10. Inference as Prediction

    Science.gov (United States)

    Watson, Jane

    2007-01-01

    Inference, or decision making, is seen in curriculum documents as the final step in a statistical investigation. For a formal statistical enquiry this may be associated with sophisticated tests involving probability distributions. For young students without the mathematical background to perform such tests, it is still possible to draw informal…

  11. 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)

    1986-02-15

    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.

  12. Lethal Interpersonal Violence in the Middle Pleistocene

    OpenAIRE

    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

    2015-01-01

    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 ...

  13. 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)

    2012-11-15

    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)

  14. Non-Lethal Weapons (NLW) Reference Book

    Science.gov (United States)

    2012-01-01

    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

  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.

    Science.gov (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

    2015-01-01

    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. Irony as Inferred Contradiction

    Directory of Open Access Journals (Sweden)

    Лаура Альба-Хуес

    2014-12-01

    Full Text Available “If we acknowledge the existence of an Irony Principle, we should also acknowledge another ‘higher-order principle’ which has the opposite effect. While irony is an apparently friendly way of being offensive (mock politeness, the type of verbal behaviour known as ‘banter’ is an offensive way of being friendly (mock impoliteness.” Geoffrey Leech, Principles of Pragmatics (1983: 144 In this work I present some theoretical considerations about what I consider to be a permanent and ever-present feature of verbal irony, namely, inferred contradiction , which has to be distinguished from plain, direct (non-inferred contradiction as well as from indirect negation , for a contradiction which is directly expressed cannot be interpreted as ironical (since it lacks a crucial component: inference, and an indirect negation may or may not be ironic (depending on the situation, and thus cannot be considered a permanent feature of the phenomenon. In spite of the fact that many scholars have proposed different theories in order to capture the essence of this intricate and complex phenomenon, not all of them have managed to find a feature or characteristic that applies to or is found in all possible occurrences of irony. I briefly discuss the tenets of some of the best-known of these theories, namely the Classical theories (Socrates, Cicero, Quintilian, the Echoic-Mention Theory (later Echoic Theory, the Echoic Reminder Theory, the Pretence Theory and the Relevant Inappropriateness Theory, trying to show that in all the types of irony emerging from these proposals (e.g. echoic irony, pretence irony, etc. it can be observed that the irony is triggered by inferred contradiction . The one theory that according to my view and knowledge- seems to capture its whole essence to date is Attardo’s (2000 Relevant Inappropriateness Theory, to whose proposal I adhere, but I argue at the same time that inferred contradiction is another feature of irony (which

  18. Causal inference in econometrics

    CERN Document Server

    Kreinovich, Vladik; Sriboonchitta, Songsak

    2016-01-01

    This book is devoted to the analysis of causal inference which is one of the most difficult tasks in data analysis: when two phenomena are observed to be related, it is often difficult to decide whether one of them causally influences the other one, or whether these two phenomena have a common cause. This analysis is the main focus of this volume. To get a good understanding of the causal inference, it is important to have models of economic phenomena which are as accurate as possible. Because of this need, this volume also contains papers that use non-traditional economic models, such as fuzzy models and models obtained by using neural networks and data mining techniques. It also contains papers that apply different econometric models to analyze real-life economic dependencies.

  19. Stochastic processes inference theory

    CERN Document Server

    Rao, Malempati M

    2014-01-01

    This is the revised and enlarged 2nd edition of the authors’ original text, which was intended to be a modest complement to Grenander's fundamental memoir on stochastic processes and related inference theory. The present volume gives a substantial account of regression analysis, both for stochastic processes and measures, and includes recent material on Ridge regression with some unexpected applications, for example in econometrics. The first three chapters can be used for a quarter or semester graduate course on inference on stochastic processes. The remaining chapters provide more advanced material on stochastic analysis suitable for graduate seminars and discussions, leading to dissertation or research work. In general, the book will be of interest to researchers in probability theory, mathematical statistics and electrical and information theory.

  20. Multiple Instance Fuzzy Inference

    Science.gov (United States)

    2015-12-02

    and learn the fuzzy inference system’s parameters [24, 25]. In this later technique, supervised and unsupervised learning algorithms are devised to...algorithm ( unsupervised learning ) can be used to identify local contexts of the input space, and a linear classifier (supervised learning ) can be used...instance level (patch-level) labels and would require the image to be correctly segmented and labeled prior to learning . Figure 1.1: Example of an image

  1. INFERENCE BUILDING BLOCKS

    Science.gov (United States)

    2018-02-15

    whether unsupervised (such as clustering) or supervised (such as Naive Bayes). We observed the following advantages: 1 APPROVED FOR PUBLIC RELEASE...section, we explain our research in relation to DARPA’s Probabilistic Programming for Advancing Machine Learning (PPAML) program and other approaches...develop machine- learning applications by combining probabilistic models and inference techniques. On one hand, a probabilistic model is a mathematical

  2. Active inference and learning.

    Science.gov (United States)

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Continuous Integrated Invariant Inference Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will develop a new technique for invariant inference and embed this and other current invariant inference and checking techniques in an...

  4. Multimodel inference and adaptive management

    Science.gov (United States)

    Rehme, S.E.; Powell, L.A.; Allen, Craig R.

    2011-01-01

    Ecology is an inherently complex science coping with correlated variables, nonlinear interactions and multiple scales of pattern and process, making it difficult for experiments to result in clear, strong inference. Natural resource managers, policy makers, and stakeholders rely on science to provide timely and accurate management recommendations. However, the time necessary to untangle the complexities of interactions within ecosystems is often far greater than the time available to make management decisions. One method of coping with this problem is multimodel inference. Multimodel inference assesses uncertainty by calculating likelihoods among multiple competing hypotheses, but multimodel inference results are often equivocal. Despite this, there may be pressure for ecologists to provide management recommendations regardless of the strength of their study’s inference. We reviewed papers in the Journal of Wildlife Management (JWM) and the journal Conservation Biology (CB) to quantify the prevalence of multimodel inference approaches, the resulting inference (weak versus strong), and how authors dealt with the uncertainty. Thirty-eight percent and 14%, respectively, of articles in the JWM and CB used multimodel inference approaches. Strong inference was rarely observed, with only 7% of JWM and 20% of CB articles resulting in strong inference. We found the majority of weak inference papers in both journals (59%) gave specific management recommendations. Model selection uncertainty was ignored in most recommendations for management. We suggest that adaptive management is an ideal method to resolve uncertainty when research results in weak inference.

  5. [From synthetic biology to synthetic humankind].

    Science.gov (United States)

    Nouvel, Pascal

    2015-01-01

    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.

  6. Synthetic Cathinones ("Bath Salts")

    Science.gov (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. Brave New Warfare: Autonomy in Lethal UAVs

    Science.gov (United States)

    2011-03-01

    Executions,” United Nations General Assembly, May 28, 2010, http://www2.ohchr.org/english/ 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

  8. Issues surrounding lethal injection as a means of capital punishment.

    Science.gov (United States)

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

    2008-12-01

    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.

  9. Nonparametric statistical inference

    CERN Document Server

    Gibbons, Jean Dickinson

    2010-01-01

    Overall, this remains a very fine book suitable for a graduate-level course in nonparametric statistics. I recommend it for all people interested in learning the basic ideas of nonparametric statistical inference.-Eugenia Stoimenova, Journal of Applied Statistics, June 2012… one of the best books available for a graduate (or advanced undergraduate) text for a theory course on nonparametric statistics. … a very well-written and organized book on nonparametric statistics, especially useful and recommended for teachers and graduate students.-Biometrics, 67, September 2011This excellently presente

  10. Nanotechnology and statistical inference

    Science.gov (United States)

    Vesely, Sara; Vesely, Leonardo; Vesely, Alessandro

    2017-08-01

    We discuss some problems that arise when applying statistical inference to data with the aim of disclosing new func-tionalities. A predictive model analyzes the data taken from experiments on a specific material to assess the likelihood that another product, with similar structure and properties, will exhibit the same functionality. It doesn't have much predictive power if vari-ability occurs as a consequence of a specific, non-linear behavior. We exemplify our discussion on some experiments with biased dice.

  11. Generic patch inference

    DEFF Research Database (Denmark)

    Andersen, Jesper; Lawall, Julia

    2010-01-01

    A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

  12. Foundations of Inference

    Directory of Open Access Journals (Sweden)

    Kevin H. Knuth

    2012-06-01

    Full Text Available We present a simple and clear foundation for finite inference that unites and significantly extends the approaches of Kolmogorov and Cox. Our approach is based on quantifying lattices of logical statements in a way that satisfies general lattice symmetries. With other applications such as measure theory in mind, our derivations assume minimal symmetries, relying on neither negation nor continuity nor differentiability. Each relevant symmetry corresponds to an axiom of quantification, and these axioms are used to derive a unique set of quantifying rules that form the familiar probability calculus. We also derive a unique quantification of divergence, entropy and information.

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

    Czech Academy of Sciences Publication Activity Database

    Vymětalová, Ladislava; Kryštof, Vladimír

    2015-01-01

    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

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

    OpenAIRE

    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

    2017-01-01

    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...

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

    OpenAIRE

    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

    2017-01-01

    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.) ...

  16. Genomewide Screen for Synthetic Lethal Interactions with Mutant KRAS in Lung Cancer

    Science.gov (United States)

    2017-11-01

    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

  17. Synthetic Lethal Therapeutic Approaches for ARID1A-Mutated Ovarian Cancer

    Science.gov (United States)

    2017-10-01

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

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

    Science.gov (United States)

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

    2006-09-01

    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.

  19. Design of synthetic bacterial communities for predictable plant phenotypes.

    Science.gov (United States)

    Herrera Paredes, Sur; Gao, Tianxiang; Law, Theresa F; Finkel, Omri M; Mucyn, Tatiana; Teixeira, Paulo José Pereira Lima; Salas González, Isaí; Feltcher, Meghan E; Powers, Matthew J; Shank, Elizabeth A; Jones, Corbin D; Jojic, Vladimir; Dangl, Jeffery L; Castrillo, Gabriel

    2018-02-01

    Specific members of complex microbiota can influence host phenotypes, depending on both the abiotic environment and the presence of other microorganisms. Therefore, it is challenging to define bacterial combinations that have predictable host phenotypic outputs. We demonstrate that plant-bacterium binary-association assays inform the design of small synthetic communities with predictable phenotypes in the host. Specifically, we constructed synthetic communities that modified phosphate accumulation in the shoot and induced phosphate starvation-responsive genes in a predictable fashion. We found that bacterial colonization of the plant is not a predictor of the plant phenotypes we analyzed. Finally, we demonstrated that characterizing a subset of all possible bacterial synthetic communities is sufficient to predict the outcome of untested bacterial consortia. Our results demonstrate that it is possible to infer causal relationships between microbiota membership and host phenotypes and to use these inferences to rationally design novel communities.

  20. Quantum synthetic aperture radar

    Science.gov (United States)

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

    2017-05-01

    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.

  1. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

    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.

  2. Inferring horizontal gene transfer.

    Directory of Open Access Journals (Sweden)

    Matt Ravenhall

    2015-05-01

    Full Text Available Horizontal or Lateral Gene Transfer (HGT or LGT is the transmission of portions of genomic DNA between organisms through a process decoupled from vertical inheritance. In the presence of HGT events, different fragments of the genome are the result of different evolutionary histories. This can therefore complicate the investigations of evolutionary relatedness of lineages and species. Also, as HGT can bring into genomes radically different genotypes from distant lineages, or even new genes bearing new functions, it is a major source of phenotypic innovation and a mechanism of niche adaptation. For example, of particular relevance to human health is the lateral transfer of antibiotic resistance and pathogenicity determinants, leading to the emergence of pathogenic lineages. Computational identification of HGT events relies upon the investigation of sequence composition or evolutionary history of genes. Sequence composition-based ("parametric" methods search for deviations from the genomic average, whereas evolutionary history-based ("phylogenetic" approaches identify genes whose evolutionary history significantly differs from that of the host species. The evaluation and benchmarking of HGT inference methods typically rely upon simulated genomes, for which the true history is known. On real data, different methods tend to infer different HGT events, and as a result it can be difficult to ascertain all but simple and clear-cut HGT events.

  3. The interaction between daughterless and sex-lethal in triploids: a lethal sex-transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster.

    Science.gov (United States)

    Cline, T W

    1983-02-01

    Regulation of Drosophila sex determination and X-chromosome dosage compensation in response to the X-chromosome/autosome (X/A) balance of the zygote is shown to require proper functioning of both the da+ gene in the mother and the Sxl+ gene in the zygote. Previous studies led to the hypothesis that zygotic Sxl+ alleles are differentially active in females (XXAA) vs males (XYAA) in response to the X/A balance, and that maternal da+ gene product acts as a positive regulator in this connection. Sxl+ activity was proposed to impose the female developmental sequence on cells which would follow the male sequence in its absence. Important predictions of this proposal are verified. This study focuses primarily on the phenotype of triploid intersexes (XXAAA, X/A = 0.67). They are shown here to survive effects of da and Sxl mutations that would be lethal to diploids. The ambiguous X/A signal of intersexes normally causes them to develop as phenotypic mosaics of male and female tissue. Loss of maternal da+ or zygotic Sxl+ gene function shifts their somatic sexual phenotype to the male alternative. A gain-of-function mutation at Sxl has the opposite effect, imposing female development regardless of the maternal genotype with respect to da. It also reduces their rate of X-linked gene expression. The effects of a duplication of Sxl+ resemble those of the constitutive Sxl allele, but are less extreme. The role of these genes in the process of X-chromosome dosage compensation is inferred indirectly from the strict dependence of the mutations' lethal effects on the X/A balance in haploids, diploids, and triploids, and more directly from the effects of the mutations on the phenotypes of the X-linked neomorphic mutations, Bar and Hairy-wing. The relationship of da+ and Sxl+ gene functions to those of other sex-specific lethal loci in D. melanogaster, and to sex determination mechanisms in other species, is discussed.

  4. Information-Theoretic Inference of Large Transcriptional Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Meyer Patrick

    2007-01-01

    Full Text Available The paper presents MRNET, an original method for inferring genetic networks from microarray data. The method is based on maximum relevance/minimum redundancy (MRMR, an effective information-theoretic technique for feature selection in supervised learning. The MRMR principle consists in selecting among the least redundant variables the ones that have the highest mutual information with the target. MRNET extends this feature selection principle to networks in order to infer gene-dependence relationships from microarray data. The paper assesses MRNET by benchmarking it against RELNET, CLR, and ARACNE, three state-of-the-art information-theoretic methods for large (up to several thousands of genes network inference. Experimental results on thirty synthetically generated microarray datasets show that MRNET is competitive with these methods.

  5. Information-Theoretic Inference of Large Transcriptional Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Patrick E. Meyer

    2007-06-01

    Full Text Available The paper presents MRNET, an original method for inferring genetic networks from microarray data. The method is based on maximum relevance/minimum redundancy (MRMR, an effective information-theoretic technique for feature selection in supervised learning. The MRMR principle consists in selecting among the least redundant variables the ones that have the highest mutual information with the target. MRNET extends this feature selection principle to networks in order to infer gene-dependence relationships from microarray data. The paper assesses MRNET by benchmarking it against RELNET, CLR, and ARACNE, three state-of-the-art information-theoretic methods for large (up to several thousands of genes network inference. Experimental results on thirty synthetically generated microarray datasets show that MRNET is competitive with these methods.

  6. Lethal photosensitization of biofilm-grown bacteria

    Science.gov (United States)

    Wilson, Michael

    1997-12-01

    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.

  7. Lethal fish hook attachment - An unusual occurrence.

    Science.gov (United States)

    Byard, Roger W

    2013-02-01

    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.

  8. Statistical inferences in phylogeography

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Beaumont, Mark A

    2009-01-01

    can randomly lead to multiple different genealogies. Likewise, the same gene trees can arise under different demographic models. This problem has led to the emergence of many statistical methods for making phylogeographic inferences. A popular phylogeographic approach based on nested clade analysis...... is challenged by the fact that a certain amount of the interpretation of the data is left to the subjective choices of the user, and it has been argued that the method performs poorly in simulation studies. More rigorous statistical methods based on coalescence theory have been developed. However, these methods...... may also be challenged by computational problems or poor model choice. In this review, we will describe the development of statistical methods in phylogeographic analysis, and discuss some of the challenges facing these methods....

  9. Immunopathologic responses to non-lethal sepsis.

    Science.gov (United States)

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

    1999-08-01

    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.

  10. Synthetic biological networks

    International Nuclear Information System (INIS)

    Archer, Eric; Süel, Gürol M

    2013-01-01

    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)

  11. Synthetic Base Fluids

    Science.gov (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.

  12. Admissibility of logical inference rules

    CERN Document Server

    Rybakov, VV

    1997-01-01

    The aim of this book is to present the fundamental theoretical results concerning inference rules in deductive formal systems. Primary attention is focused on: admissible or permissible inference rules the derivability of the admissible inference rules the structural completeness of logics the bases for admissible and valid inference rules. There is particular emphasis on propositional non-standard logics (primary, superintuitionistic and modal logics) but general logical consequence relations and classical first-order theories are also considered. The book is basically self-contained and

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

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    1983-03-01

    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.

  14. Synthetic Biological Membrane (SBM)

    Data.gov (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...

  15. Hybridization with synthetic oligonucleotides

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-01-01

    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)

  16. Mammalian Synthetic Biology

    OpenAIRE

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

    2016-01-01

    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...

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

    Science.gov (United States)

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

    2017-10-01

    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.

  18. 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.

  19. Modular Spectral Inference Framework Applied to Young Stars and Brown Dwarfs

    Science.gov (United States)

    Gully-Santiago, Michael A.; Marley, Mark S.

    2017-01-01

    In practice, synthetic spectral models are imperfect, causing inaccurate estimates of stellar parameters. Using forward modeling and statistical inference, we derive accurate stellar parameters for a given observed spectrum by emulating a grid of precomputed spectra to track uncertainties. Spectral inference as applied to brown dwarfs re: Synthetic spectral models (Marley et al 1996 and 2014) via the newest grid spans a massive multi-dimensional grid applied to IGRINS spectra, improving atmospheric models for JWST. When applied to young stars(10Myr) with large starpots, they can be measured spectroscopically, especially in the near-IR with IGRINS.

  20. Gauging Variational Inference

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahn, Sungsoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of); Shin, Jinwoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of)

    2017-05-25

    Computing partition function is the most important statistical inference task arising in applications of Graphical Models (GM). Since it is computationally intractable, approximate methods have been used to resolve the issue in practice, where meanfield (MF) and belief propagation (BP) are arguably the most popular and successful approaches of a variational type. In this paper, we propose two new variational schemes, coined Gauged-MF (G-MF) and Gauged-BP (G-BP), improving MF and BP, respectively. Both provide lower bounds for the partition function by utilizing the so-called gauge transformation which modifies factors of GM while keeping the partition function invariant. Moreover, we prove that both G-MF and G-BP are exact for GMs with a single loop of a special structure, even though the bare MF and BP perform badly in this case. Our extensive experiments, on complete GMs of relatively small size and on large GM (up-to 300 variables) confirm that the newly proposed algorithms outperform and generalize MF and BP.

  1. Multistability and perceptual inference.

    Science.gov (United States)

    Gershman, Samuel J; Vul, Edward; Tenenbaum, Joshua B

    2012-01-01

    Ambiguous images present a challenge to the visual system: How can uncertainty about the causes of visual inputs be represented when there are multiple equally plausible causes? A Bayesian ideal observer should represent uncertainty in the form of a posterior probability distribution over causes. However, in many real-world situations, computing this distribution is intractable and requires some form of approximation. We argue that the visual system approximates the posterior over underlying causes with a set of samples and that this approximation strategy produces perceptual multistability--stochastic alternation between percepts in consciousness. Under our analysis, multistability arises from a dynamic sample-generating process that explores the posterior through stochastic diffusion, implementing a rational form of approximate Bayesian inference known as Markov chain Monte Carlo (MCMC). We examine in detail the most extensively studied form of multistability, binocular rivalry, showing how a variety of experimental phenomena--gamma-like stochastic switching, patchy percepts, fusion, and traveling waves--can be understood in terms of MCMC sampling over simple graphical models of the underlying perceptual tasks. We conjecture that the stochastic nature of spiking neurons may lend itself to implementing sample-based posterior approximations in the brain.

  2. 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

    2016-01-01

    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

  3. Tumor clone dynamics in lethal prostate cancer.

    Science.gov (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

    2014-09-17

    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.

  4. Non lethal Raine syndrome and differential diagnosis.

    Science.gov (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

    2016-11-01

    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.

  5. Synthetic Genetic Arrays: Automation of Yeast Genetics.

    Science.gov (United States)

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

    2016-04-01

    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.

  6. An Inference Language for Imaging

    DEFF Research Database (Denmark)

    Pedemonte, Stefano; Catana, Ciprian; Van Leemput, Koen

    2014-01-01

    We introduce iLang, a language and software framework for probabilistic inference. The iLang framework enables the definition of directed and undirected probabilistic graphical models and the automated synthesis of high performance inference algorithms for imaging applications. The iLang framework...... is composed of a set of language primitives and of an inference engine based on a message-passing system that integrates cutting-edge computational tools, including proximal algorithms and high performance Hamiltonian Markov Chain Monte Carlo techniques. A set of domain-specific highly optimized GPU...

  7. Optimization methods for logical inference

    CERN Document Server

    Chandru, Vijay

    2011-01-01

    Merging logic and mathematics in deductive inference-an innovative, cutting-edge approach. Optimization methods for logical inference? Absolutely, say Vijay Chandru and John Hooker, two major contributors to this rapidly expanding field. And even though ""solving logical inference problems with optimization methods may seem a bit like eating sauerkraut with chopsticks. . . it is the mathematical structure of a problem that determines whether an optimization model can help solve it, not the context in which the problem occurs."" Presenting powerful, proven optimization techniques for logic in

  8. Synthetic guide star generation

    Science.gov (United States)

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

    2008-06-10

    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.

  9. Synthetic Aperture Sequential Beamforming

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  10. An algebra-based method for inferring gene regulatory networks.

    Science.gov (United States)

    Vera-Licona, Paola; Jarrah, Abdul; Garcia-Puente, Luis David; McGee, John; Laubenbacher, Reinhard

    2014-03-26

    The inference of gene regulatory networks (GRNs) from experimental observations is at the heart of systems biology. This includes the inference of both the network topology and its dynamics. While there are many algorithms available to infer the network topology from experimental data, less emphasis has been placed on methods that infer network dynamics. Furthermore, since the network inference problem is typically underdetermined, it is essential to have the option of incorporating into the inference process, prior knowledge about the network, along with an effective description of the search space of dynamic models. Finally, it is also important to have an understanding of how a given inference method is affected by experimental and other noise in the data used. This paper contains a novel inference algorithm using the algebraic framework of Boolean polynomial dynamical systems (BPDS), meeting all these requirements. The algorithm takes as input time series data, including those from network perturbations, such as knock-out mutant strains and RNAi experiments. It allows for the incorporation of prior biological knowledge while being robust to significant levels of noise in the data used for inference. It uses an evolutionary algorithm for local optimization with an encoding of the mathematical models as BPDS. The BPDS framework allows an effective representation of the search space for algebraic dynamic models that improves computational performance. The algorithm is validated with both simulated and experimental microarray expression profile data. Robustness to noise is tested using a published mathematical model of the segment polarity gene network in Drosophila melanogaster. Benchmarking of the algorithm is done by comparison with a spectrum of state-of-the-art network inference methods on data from the synthetic IRMA network to demonstrate that our method has good precision and recall for the network reconstruction task, while also predicting several of the

  11. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh

    2015-01-01

    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...

  12. The toxic mechanism of high lethality of herbicide butachlor in marine flatfish flounder, Paralichthys olivaceus

    Science.gov (United States)

    Guo, Huarong; Yin, Licheng; Zhang, Shicui; Feng, Wenrong

    2010-09-01

    The toxic mechanism of herbicide butachlor to induce extremely high lethality in marine flatfish flounder, Paralichthys Olivaceus, was analyzed by histopathological examination, antioxidant enzymes activities and ATP content assay. Histopathological examination of gill, liver and kidney of exposed fishes showed that gill was a target organ of butachlor. The butachlor seriously impaired the respiration of gills by a series of lesions such as edema, lifting and detachment of lamellar epithelium, breakdown of pillar cells, and blood congestion. The dysfunction of gill respiration caused suffocation to the exposed flounder with extremely high acute lethality. Antioxidant enzyme activity assay of the in vitro cultured flounder gill (FG) cells exposed to butachlor indicated that butachlor markedly inhibited the antioxidant enzyme activities of Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX). Furthermore, along with the decline of antioxidant enzyme activities, ATP content in the exposed FG cells decreased, too. This infers that the oxidative stress induced by butachlor can inhibit the production of cellular ATP. Similar decrease of ATP content was also observed in the exposed flounder gill tissues. Taken together, as in FG cells, butachlor possibly induced a short supply of ATP in pillar cells by inhibiting the antioxidant enzyme activities and then affecting the contractibility of the pillar cells, which in turn resulted in the blood congestion and suffocation of exposed flounder.

  13. Statistical inference via fiducial methods

    OpenAIRE

    Salomé, Diemer

    1998-01-01

    In this thesis the attention is restricted to inductive reasoning using a mathematical probability model. A statistical procedure prescribes, for every theoretically possible set of data, the inference about the unknown of interest. ... Zie: Summary

  14. On principles of inductive inference

    OpenAIRE

    Kostecki, Ryszard Paweł

    2011-01-01

    We propose an intersubjective epistemic approach to foundations of probability theory and statistical inference, based on relative entropy and category theory, and aimed to bypass the mathematical and conceptual problems of existing foundational approaches.

  15. Statistical inference for stochastic processes

    National Research Council Canada - National Science Library

    Basawa, Ishwar V; Prakasa Rao, B. L. S

    1980-01-01

    The aim of this monograph is to attempt to reduce the gap between theory and applications in the area of stochastic modelling, by directing the interest of future researchers to the inference aspects...

  16. Bayesian Inference: with ecological applications

    Science.gov (United States)

    Link, William A.; Barker, Richard J.

    2010-01-01

    This text provides a mathematically rigorous yet accessible and engaging introduction to Bayesian inference with relevant examples that will be of interest to biologists working in the fields of ecology, wildlife management and environmental studies as well as students in advanced undergraduate statistics.. This text opens the door to Bayesian inference, taking advantage of modern computational efficiencies and easily accessible software to evaluate complex hierarchical models.

  17. What Are Synthetic Cannabinoids?

    Science.gov (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 ...

  18. Towards a synthetic chloroplast.

    Directory of Open Access Journals (Sweden)

    Christina M Agapakis

    2011-04-01

    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.

  19. 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...

  20. Synthetic growth reference charts

    NARCIS (Netherlands)

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

    2016-01-01

    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

  1. 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 ...

  2. Synthetic antiferromagnetic spintronics

    Science.gov (United States)

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

    2018-03-01

    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.

  3. Feasibility of Using Synthetic Aperture Radar to Aid UAV Navigation

    OpenAIRE

    Nitti, Davide O.; Bovenga, Fabio; Chiaradia, Maria T.; Greco, Mario; Pinelli, Gianpaolo

    2015-01-01

    This study explores the potential of Synthetic Aperture Radar (SAR) to aid Unmanned Aerial Vehicle (UAV) navigation when Inertial Navigation System (INS) measurements are not accurate enough to eliminate drifts from a planned trajectory. This problem can affect medium-altitude long-endurance (MALE) UAV class, which permits heavy and wide payloads (as required by SAR) and flights for thousands of kilometres accumulating large drifts. The basic idea is to infer position and attitude of an aeria...

  4. Active inference, communication and hermeneutics.

    Science.gov (United States)

    Friston, Karl J; Frith, Christopher D

    2015-07-01

    Hermeneutics refers to interpretation and translation of text (typically ancient scriptures) but also applies to verbal and non-verbal communication. In a psychological setting it nicely frames the problem of inferring the intended content of a communication. In this paper, we offer a solution to the problem of neural hermeneutics based upon active inference. In active inference, action fulfils predictions about how we will behave (e.g., predicting we will speak). Crucially, these predictions can be used to predict both self and others--during speaking and listening respectively. Active inference mandates the suppression of prediction errors by updating an internal model that generates predictions--both at fast timescales (through perceptual inference) and slower timescales (through perceptual learning). If two agents adopt the same model, then--in principle--they can predict each other and minimise their mutual prediction errors. Heuristically, this ensures they are singing from the same hymn sheet. This paper builds upon recent work on active inference and communication to illustrate perceptual learning using simulated birdsongs. Our focus here is the neural hermeneutics implicit in learning, where communication facilitates long-term changes in generative models that are trying to predict each other. In other words, communication induces perceptual learning and enables others to (literally) change our minds and vice versa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Active inference, communication and hermeneutics☆

    Science.gov (United States)

    Friston, Karl J.; Frith, Christopher D.

    2015-01-01

    Hermeneutics refers to interpretation and translation of text (typically ancient scriptures) but also applies to verbal and non-verbal communication. In a psychological setting it nicely frames the problem of inferring the intended content of a communication. In this paper, we offer a solution to the problem of neural hermeneutics based upon active inference. In active inference, action fulfils predictions about how we will behave (e.g., predicting we will speak). Crucially, these predictions can be used to predict both self and others – during speaking and listening respectively. Active inference mandates the suppression of prediction errors by updating an internal model that generates predictions – both at fast timescales (through perceptual inference) and slower timescales (through perceptual learning). If two agents adopt the same model, then – in principle – they can predict each other and minimise their mutual prediction errors. Heuristically, this ensures they are singing from the same hymn sheet. This paper builds upon recent work on active inference and communication to illustrate perceptual learning using simulated birdsongs. Our focus here is the neural hermeneutics implicit in learning, where communication facilitates long-term changes in generative models that are trying to predict each other. In other words, communication induces perceptual learning and enables others to (literally) change our minds and vice versa. PMID:25957007

  6. Genetics Home Reference: platyspondylic lethal skeletal dysplasia, Torrance type

    Science.gov (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 USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

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

    OpenAIRE

    2013-01-01

    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...

  8. Sonographic features of lethal multiple pterygium syndrome at 14 weeks.

    Science.gov (United States)

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

    2005-06-01

    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.

  9. Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

    Science.gov (United States)

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

    2014-12-01

    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

  10. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

    Science.gov (United States)

    2015-09-01

    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

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

    OpenAIRE

    1991-01-01

    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...

  12. Ecstasy tablets intoxication with lethal autcome

    Directory of Open Access Journals (Sweden)

    Đorđević Snežana

    2007-01-01

    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. .

  13. Standardization in synthetic biology.

    Science.gov (United States)

    Müller, Kristian M; Arndt, Katja M

    2012-01-01

    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.

  14. Optical synthetic aperture radar

    Science.gov (United States)

    Ilovitsh, Asaf; Zach, Shlomo; Zalevsky, Zeev

    2013-06-01

    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.

  15. Lethal means access and assessment among suicidal emergency department patients

    Science.gov (United States)

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

    2016-01-01

    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

  16. Locative inferences in medical texts.

    Science.gov (United States)

    Mayer, P S; Bailey, G H; Mayer, R J; Hillis, A; Dvoracek, J E

    1987-06-01

    Medical research relies on epidemiological studies conducted on a large set of clinical records that have been collected from physicians recording individual patient observations. These clinical records are recorded for the purpose of individual care of the patient with little consideration for their use by a biostatistician interested in studying a disease over a large population. Natural language processing of clinical records for epidemiological studies must deal with temporal, locative, and conceptual issues. This makes text understanding and data extraction of clinical records an excellent area for applied research. While much has been done in making temporal or conceptual inferences in medical texts, parallel work in locative inferences has not been done. This paper examines the locative inferences as well as the integration of temporal, locative, and conceptual issues in the clinical record understanding domain by presenting an application that utilizes two key concepts in its parsing strategy--a knowledge-based parsing strategy and a minimal lexicon.

  17. Object-Oriented Type Inference

    DEFF Research Database (Denmark)

    Schwartzbach, Michael Ignatieff; Palsberg, Jens

    1991-01-01

    We present a new approach to inferring types in untyped object-oriented programs with inheritance, assignments, and late binding. It guarantees that all messages are understood, annotates the program with type information, allows polymorphic methods, and can be used as the basis of an op-timizing......We present a new approach to inferring types in untyped object-oriented programs with inheritance, assignments, and late binding. It guarantees that all messages are understood, annotates the program with type information, allows polymorphic methods, and can be used as the basis of an op...

  18. Eight challenges in phylodynamic inference

    Directory of Open Access Journals (Sweden)

    Simon D.W. Frost

    2015-03-01

    Full Text Available The field of phylodynamics, which attempts to enhance our understanding of infectious disease dynamics using pathogen phylogenies, has made great strides in the past decade. Basic epidemiological and evolutionary models are now well characterized with inferential frameworks in place. However, significant challenges remain in extending phylodynamic inference to more complex systems. These challenges include accounting for evolutionary complexities such as changing mutation rates, selection, reassortment, and recombination, as well as epidemiological complexities such as stochastic population dynamics, host population structure, and different patterns at the within-host and between-host scales. An additional challenge exists in making efficient inferences from an ever increasing corpus of sequence data.

  19. Statistical Inference for Fractional Diffusion Processes

    CERN Document Server

    Rao, B L S Prakasa

    2010-01-01

    Statistical Inference for Fractional Diffusion Processes looks at statistical inference for stochastic processes modeled by stochastic differential equations driven by fractional Brownian motion. Other related processes, such as sequential inference, nonparametric and non parametric inference and parametric estimation are also discussed. The book will deal with Fractional Diffusion Processes (FDP) in relation to statistical influence for stochastic processes. The books main focus is on parametric and non parametric inference problems for fractional diffusion processes when a complete path of t

  20. Synthetic cannabis and respiratory depression.

    Science.gov (United States)

    Jinwala, Felecia N; Gupta, Mayank

    2012-12-01

    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.

  1. Inference Optimization using Relational Algebra

    NARCIS (Netherlands)

    Evers, S.; Fokkinga, M.M.; Apers, Peter M.G.

    Exact inference procedures in Bayesian networks can be expressed using relational algebra; this provides a common ground for optimizations from the AI and database communities. Specifically, the ability to accomodate sparse representations of probability distributions opens up the way to optimize

  2. Mixed normal inference on multicointegration

    NARCIS (Netherlands)

    Boswijk, H.P.

    2009-01-01

    Asymptotic likelihood analysis of cointegration in I(2) models, see Johansen (1997, 2006), Boswijk (2000) and Paruolo (2000), has shown that inference on most parameters is mixed normal, implying hypothesis test statistics with an asymptotic 2 null distribution. The asymptotic distribution of the

  3. Statistical inference on variance components

    NARCIS (Netherlands)

    Verdooren, L.R.

    1988-01-01

    In several sciences but especially in animal and plant breeding, the general mixed model with fixed and random effects plays a great role. Statistical inference on variance components means tests of hypotheses about variance components, constructing confidence intervals for them, estimating them,

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

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    1983-03-01

    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.

  5. Synthetic cannabinoids revealing adrenoleukodystrophy.

    Science.gov (United States)

    Fellner, Avi; Benninger, Felix; Djaldetti, Ruth

    2016-02-01

    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.

  6. CASH vs. SYNTHETIC CDOs

    Directory of Open Access Journals (Sweden)

    Silviu Eduard Dinca

    2015-12-01

    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.

  7. Crossover suppressors and balanced recessive lethals in Caenorhabditis elegans

    International Nuclear Information System (INIS)

    Herman, R.K.

    1978-01-01

    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

  8. 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.

    1987-01-01

    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

  9. Prenatal diagnosis of lethal osteogenesis imperfecta in twin pregnancy.

    Science.gov (United States)

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

    1991-06-01

    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.

  10. Synthetic collective intelligence.

    Science.gov (United States)

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

    2016-10-01

    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.

  11. Space Synthetic Biology Project

    Science.gov (United States)

    Howard, David; Roman, Monsi; Mansell, James (Matt)

    2015-01-01

    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

  12. Functional networks inference from rule-based machine learning models.

    Science.gov (United States)

    Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume

    2016-01-01

    Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The

  13. Life after the synthetic cell

    DEFF Research Database (Denmark)

    Rasmussen, Steen

    2010-01-01

    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...

  14. Synthetic biology and occupational risk.

    Science.gov (United States)

    Howard, John; Murashov, Vladimir; Schulte, Paul

    2017-03-01

    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.

  15. Finding Hope in Synthetic Biology.

    Science.gov (United States)

    Takala, Tuija

    2017-04-01

    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.

  16. Bayesian inference with ecological applications

    CERN Document Server

    Link, William A

    2009-01-01

    This text is written to provide a mathematically sound but accessible and engaging introduction to Bayesian inference specifically for environmental scientists, ecologists and wildlife biologists. It emphasizes the power and usefulness of Bayesian methods in an ecological context. The advent of fast personal computers and easily available software has simplified the use of Bayesian and hierarchical models . One obstacle remains for ecologists and wildlife biologists, namely the near absence of Bayesian texts written specifically for them. The book includes many relevant examples, is supported by software and examples on a companion website and will become an essential grounding in this approach for students and research ecologists. Engagingly written text specifically designed to demystify a complex subject Examples drawn from ecology and wildlife research An essential grounding for graduate and research ecologists in the increasingly prevalent Bayesian approach to inference Companion website with analyt...

  17. Statistical inference on residual life

    CERN Document Server

    Jeong, Jong-Hyeon

    2014-01-01

    This is a monograph on the concept of residual life, which is an alternative summary measure of time-to-event data, or survival data. The mean residual life has been used for many years under the name of life expectancy, so it is a natural concept for summarizing survival or reliability data. It is also more interpretable than the popular hazard function, especially for communications between patients and physicians regarding the efficacy of a new drug in the medical field. This book reviews existing statistical methods to infer the residual life distribution. The review and comparison includes existing inference methods for mean and median, or quantile, residual life analysis through medical data examples. The concept of the residual life is also extended to competing risks analysis. The targeted audience includes biostatisticians, graduate students, and PhD (bio)statisticians. Knowledge in survival analysis at an introductory graduate level is advisable prior to reading this book.

  18. Bayesian Inference on Proportional Elections

    Science.gov (United States)

    Brunello, Gabriel Hideki Vatanabe; Nakano, Eduardo Yoshio

    2015-01-01

    Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software. PMID:25786259

  19. Nonparametric Bayesian inference in biostatistics

    CERN Document Server

    Müller, Peter

    2015-01-01

    As chapters in this book demonstrate, BNP has important uses in clinical sciences and inference for issues like unknown partitions in genomics. Nonparametric Bayesian approaches (BNP) play an ever expanding role in biostatistical inference from use in proteomics to clinical trials. Many research problems involve an abundance of data and require flexible and complex probability models beyond the traditional parametric approaches. As this book's expert contributors show, BNP approaches can be the answer. Survival Analysis, in particular survival regression, has traditionally used BNP, but BNP's potential is now very broad. This applies to important tasks like arrangement of patients into clinically meaningful subpopulations and segmenting the genome into functionally distinct regions. This book is designed to both review and introduce application areas for BNP. While existing books provide theoretical foundations, this book connects theory to practice through engaging examples and research questions. Chapters c...

  20. Statistical inference an integrated approach

    CERN Document Server

    Migon, Helio S; Louzada, Francisco

    2014-01-01

    Introduction Information The concept of probability Assessing subjective probabilities An example Linear algebra and probability Notation Outline of the bookElements of Inference Common statistical modelsLikelihood-based functions Bayes theorem Exchangeability Sufficiency and exponential family Parameter elimination Prior Distribution Entirely subjective specification Specification through functional forms Conjugacy with the exponential family Non-informative priors Hierarchical priors Estimation Introduction to decision theoryBayesian point estimation Classical point estimation Empirical Bayes estimation Comparison of estimators Interval estimation Estimation in the Normal model Approximating Methods The general problem of inference Optimization techniquesAsymptotic theory Other analytical approximations Numerical integration methods Simulation methods Hypothesis Testing Introduction Classical hypothesis testingBayesian hypothesis testing Hypothesis testing and confidence intervalsAsymptotic tests Prediction...

  1. Bayesian inference on proportional elections.

    Directory of Open Access Journals (Sweden)

    Gabriel Hideki Vatanabe Brunello

    Full Text Available Polls for majoritarian voting systems usually show estimates of the percentage of votes for each candidate. However, proportional vote systems do not necessarily guarantee the candidate with the most percentage of votes will be elected. Thus, traditional methods used in majoritarian elections cannot be applied on proportional elections. In this context, the purpose of this paper was to perform a Bayesian inference on proportional elections considering the Brazilian system of seats distribution. More specifically, a methodology to answer the probability that a given party will have representation on the chamber of deputies was developed. Inferences were made on a Bayesian scenario using the Monte Carlo simulation technique, and the developed methodology was applied on data from the Brazilian elections for Members of the Legislative Assembly and Federal Chamber of Deputies in 2010. A performance rate was also presented to evaluate the efficiency of the methodology. Calculations and simulations were carried out using the free R statistical software.

  2. Causal inference based on counterfactuals

    Directory of Open Access Journals (Sweden)

    Höfler M

    2005-09-01

    Full Text Available Abstract Background The counterfactual or potential outcome model has become increasingly standard for causal inference in epidemiological and medical studies. Discussion This paper provides an overview on the counterfactual and related approaches. A variety of conceptual as well as practical issues when estimating causal effects are reviewed. These include causal interactions, imperfect experiments, adjustment for confounding, time-varying exposures, competing risks and the probability of causation. It is argued that the counterfactual model of causal effects captures the main aspects of causality in health sciences and relates to many statistical procedures. Summary Counterfactuals are the basis of causal inference in medicine and epidemiology. Nevertheless, the estimation of counterfactual differences pose several difficulties, primarily in observational studies. These problems, however, reflect fundamental barriers only when learning from observations, and this does not invalidate the counterfactual concept.

  3. Using pattern recognition to infer parameters governing mantle convection

    Science.gov (United States)

    Atkins, Suzanne; Valentine, Andrew P.; Tackley, Paul J.; Trampert, Jeannot

    2016-08-01

    The results of mantle convection simulations are fully determined by the input parameters and boundary conditions used. These input parameters can be for initialisation, such as initial mantle temperature, or can be constant values, such as viscosity exponents. However, knowledge of Earth-like values for many input parameters are very poorly constrained, introducing large uncertainties into the simulation of mantle flow. Convection is highly non-linear, therefore linearised inversion methods cannot be used to recover past configurations over more than very short periods of time, which makes finding both initial and constant simulation input parameters very difficult. In this paper, we demonstrate a new method for making inferences about simulation input parameters from observations of the mantle temperature field after billions of years of convection. The method is fully probabilistic. We use prior sampling to construct probability density functions for convection simulation input parameters, which are represented using neural networks. Assuming smoothness, we need relatively few samples to make inferences, making this approach much more computationally tractable than other probabilistic inversion methods. As a proof of concept, we show that our method can invert the amplitude spectra of temperature fields from 2D convection simulations, to constrain yield stress, surface reference viscosity and the initial thickness of primordial material at the CMB, for our synthetic test cases. The best constrained parameter is yield stress. The reference viscosity and initial thickness of primordial material can also be inferred reasonably well after several billion years of convection.

  4. Racing for conditional independence inference

    Czech Academy of Sciences Publication Activity Database

    Bouckaert, R. R.; Studený, Milan

    2005-01-01

    Roč. 3571, - (2005), s. 221-232 ISSN 0302-9743. [ECSQARU 2005. European Conference /8./. Barcelona, 06.07.2005-08.07.2005] R&D Projects: GA ČR GA201/04/0393; GA MŠk 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : conditional independence inference * imset * racing algorithms Subject RIV: BA - General Mathematics

  5. Statistical inference a short course

    CERN Document Server

    Panik, Michael J

    2012-01-01

    A concise, easily accessible introduction to descriptive and inferential techniques Statistical Inference: A Short Course offers a concise presentation of the essentials of basic statistics for readers seeking to acquire a working knowledge of statistical concepts, measures, and procedures. The author conducts tests on the assumption of randomness and normality, provides nonparametric methods when parametric approaches might not work. The book also explores how to determine a confidence interval for a population median while also providing coverage of ratio estimation, randomness, and causal

  6. On Quantum Statistical Inference, II

    OpenAIRE

    Barndorff-Nielsen, O. E.; Gill, R. D.; Jupp, P. E.

    2003-01-01

    Interest in problems of statistical inference connected to measurements of quantum systems has recently increased substantially, in step with dramatic new developments in experimental techniques for studying small quantum systems. Furthermore, theoretical developments in the theory of quantum measurements have brought the basic mathematical framework for the probability calculations much closer to that of classical probability theory. The present paper reviews this field and proposes and inte...

  7. Nonparametric predictive inference in reliability

    International Nuclear Information System (INIS)

    Coolen, F.P.A.; Coolen-Schrijner, P.; Yan, K.J.

    2002-01-01

    We introduce a recently developed statistical approach, called nonparametric predictive inference (NPI), to reliability. Bounds for the survival function for a future observation are presented. We illustrate how NPI can deal with right-censored data, and discuss aspects of competing risks. We present possible applications of NPI for Bernoulli data, and we briefly outline applications of NPI for replacement decisions. The emphasis is on introduction and illustration of NPI in reliability contexts, detailed mathematical justifications are presented elsewhere

  8. 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...

  9. Transionospheric synthetic aperture imaging

    CERN Document Server

    Gilman, Mikhail; Tsynkov, Semyon

    2017-01-01

    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. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    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.

  11. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    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.

  12. 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 ...

  13. 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 ...

  14. The "Lethal Chamber": Further Evidence of the Euthanasia Option.

    Science.gov (United States)

    Elks, Martin A.

    1993-01-01

    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…

  15. [Generalized and lethal pentastomiasis due to Armillifer grandis (Hett, 1915)].

    Science.gov (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

    1979-01-01

    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.

  16. 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 ...

  17. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    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

  18. 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.

  19. Brine shrimp lethality bioassay of selected Indian medicinal plants.

    Science.gov (United States)

    Padmaja, R; Arun, P C; Prashanth, D; Deepak, M; Amit, A; Anjana, M

    2002-10-01

    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.

  20. Papaya Lethal Yellowing Virus (PLYV) Infects Vasconcellea cauliflora

    NARCIS (Netherlands)

    Amaral, P.P.R.; Resende, de R.O.; Souza, M.T.

    2006-01-01

    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

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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 ...

  6. 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.

  7. The Lethal "Femme Fatale" in the Noir Tradition.

    Science.gov (United States)

    Boozer, Jack

    2000-01-01

    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…

  8. Computational Neuropsychology and Bayesian Inference.

    Science.gov (United States)

    Parr, Thomas; Rees, Geraint; Friston, Karl J

    2018-01-01

    Computational theories of brain function have become very influential in neuroscience. They have facilitated the growth of formal approaches to disease, particularly in psychiatric research. In this paper, we provide a narrative review of the body of computational research addressing neuropsychological syndromes, and focus on those that employ Bayesian frameworks. Bayesian approaches to understanding brain function formulate perception and action as inferential processes. These inferences combine 'prior' beliefs with a generative (predictive) model to explain the causes of sensations. Under this view, neuropsychological deficits can be thought of as false inferences that arise due to aberrant prior beliefs (that are poor fits to the real world). This draws upon the notion of a Bayes optimal pathology - optimal inference with suboptimal priors - and provides a means for computational phenotyping. In principle, any given neuropsychological disorder could be characterized by the set of prior beliefs that would make a patient's behavior appear Bayes optimal. We start with an overview of some key theoretical constructs and use these to motivate a form of computational neuropsychology that relates anatomical structures in the brain to the computations they perform. Throughout, we draw upon computational accounts of neuropsychological syndromes. These are selected to emphasize the key features of a Bayesian approach, and the possible types of pathological prior that may be present. They range from visual neglect through hallucinations to autism. Through these illustrative examples, we review the use of Bayesian approaches to understand the link between biology and computation that is at the heart of neuropsychology.

  9. Continuous Integrated Invariant Inference, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed project will develop a new technique for invariant inference and embed this and other current invariant inference and checking techniques in an...

  10. Variational inference & deep learning : A new synthesis

    NARCIS (Netherlands)

    Kingma, D.P.

    2017-01-01

    In this thesis, Variational Inference and Deep Learning: A New Synthesis, we propose novel solutions to the problems of variational (Bayesian) inference, generative modeling, representation learning, semi-supervised learning, and stochastic optimization.

  11. Variations on Bayesian Prediction and Inference

    Science.gov (United States)

    2016-05-09

    inference 2.2.1 Background There are a number of statistical inference problems that are not generally formulated via a full probability model...problem of inference about an unknown parameter, the Bayesian approach requires a full probability 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND...the problem of inference about an unknown parameter, the Bayesian approach requires a full probability model/likelihood which can be an obstacle

  12. 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.

  13. A Multivariate Model of Stakeholder Preference for Lethal Cat Management

    Science.gov (United States)

    Wald, Dara M.; Jacobson, Susan K.

    2014-01-01

    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

  14. Influence of temperature and pressure on the lethality of ultrasound

    International Nuclear Information System (INIS)

    Raso, J.; Pagan, R.; Condon, S.; Sala, F.J.

    1998-01-01

    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

  15. Synthetic biology and metabolic engineering.

    Science.gov (United States)

    Stephanopoulos, Gregory

    2012-11-16

    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.

  16. Synthetic cannabinoids: new matrix addiction

    Directory of Open Access Journals (Sweden)

    Antsyborov A.V.

    2017-04-01

    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.

  17. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    N.D. Zegers (Netty)

    1995-01-01

    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

  18. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    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

  19. Imaging with Synthetic Aperture Radar

    CERN Document Server

    Massonnet, Didier

    2008-01-01

    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.  

  20. Synthetic biology of polyketide synthases

    DEFF Research Database (Denmark)

    Yuzawa, Satoshi; Backman, Tyler W.H.; Keasling, Jay D.

    2018-01-01

    ). 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....

  1. Computational Neuropsychology and Bayesian Inference

    Directory of Open Access Journals (Sweden)

    Thomas Parr

    2018-02-01

    Full Text Available Computational theories of brain function have become very influential in neuroscience. They have facilitated the growth of formal approaches to disease, particularly in psychiatric research. In this paper, we provide a narrative review of the body of computational research addressing neuropsychological syndromes, and focus on those that employ Bayesian frameworks. Bayesian approaches to understanding brain function formulate perception and action as inferential processes. These inferences combine ‘prior’ beliefs with a generative (predictive model to explain the causes of sensations. Under this view, neuropsychological deficits can be thought of as false inferences that arise due to aberrant prior beliefs (that are poor fits to the real world. This draws upon the notion of a Bayes optimal pathology – optimal inference with suboptimal priors – and provides a means for computational phenotyping. In principle, any given neuropsychological disorder could be characterized by the set of prior beliefs that would make a patient’s behavior appear Bayes optimal. We start with an overview of some key theoretical constructs and use these to motivate a form of computational neuropsychology that relates anatomical structures in the brain to the computations they perform. Throughout, we draw upon computational accounts of neuropsychological syndromes. These are selected to emphasize the key features of a Bayesian approach, and the possible types of pathological prior that may be present. They range from visual neglect through hallucinations to autism. Through these illustrative examples, we review the use of Bayesian approaches to understand the link between biology and computation that is at the heart of neuropsychology.

  2. An Overview of Crowd Control Theory and Considerations for the Employment of Non-Lethal Weapons

    National Research Council Canada - National Science Library

    Grieger, Dion

    2003-01-01

    .... 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...

  3. Computing with synthetic protocells.

    Science.gov (United States)

    Courbet, Alexis; Molina, Franck; Amar, Patrick

    2015-09-01

    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.

  4. Synthetic biology: lessons from the history of synthetic organic chemistry.

    Science.gov (United States)

    Yeh, Brian J; Lim, Wendell A

    2007-09-01

    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.

  5. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    2013-01-01

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  6. Bayesian inference for Hawkes processes

    DEFF Research Database (Denmark)

    Rasmussen, Jakob Gulddahl

    The Hawkes process is a practically and theoretically important class of point processes, but parameter-estimation for such a process can pose various problems. In this paper we explore and compare two approaches to Bayesian inference. The first approach is based on the so-called conditional...... intensity function, while the second approach is based on an underlying clustering and branching structure in the Hawkes process. For practical use, MCMC (Markov chain Monte Carlo) methods are employed. The two approaches are compared numerically using three examples of the Hawkes process....

  7. Inference in hybrid Bayesian networks

    DEFF Research Database (Denmark)

    Lanseth, Helge; Nielsen, Thomas Dyhre; Rumí, Rafael

    2009-01-01

    Since the 1980s, Bayesian Networks (BNs) have become increasingly popular for building statistical models of complex systems. This is particularly true for boolean systems, where BNs often prove to be a more efficient modelling framework than traditional reliability-techniques (like fault trees a...... decade's research on inference in hybrid Bayesian networks. The discussions are linked to an example model for estimating human reliability....... and reliability block diagrams). However, limitations in the BNs' calculation engine have prevented BNs from becoming equally popular for domains containing mixtures of both discrete and continuous variables (so-called hybrid domains). In this paper we focus on these difficulties, and summarize some of the last...

  8. Type Inference of Turbo Pascal

    DEFF Research Database (Denmark)

    Hougaard, Ole Ildsgaard; Schwartzbach, Michael I; Askari, Hosein

    1995-01-01

    Type inference is generally thought of as being an exclusive property of the functional programming paradigm. We argue that such a feature may be of significant benefit for also standard imperative languages. We present a working tool (available by WWW) providing these benefits for a full version...... of Turbo Pascal. It has the form of a preprocessor that analyzes programs in which the type annotations are only partial or even absent. The resulting program has full type annotations, will be accepted by the standard Turbo Pascal compiler, and has polymorphic use of procedures resolved by means of code...

  9. Automated Design Framework for Synthetic Biology Exploiting Pareto Optimality.

    Science.gov (United States)

    Otero-Muras, Irene; Banga, Julio R

    2017-07-21

    In this work we consider Pareto optimality for automated design in synthetic biology. We present a generalized framework based on a mixed-integer dynamic optimization formulation that, given design specifications, allows the computation of Pareto optimal sets of designs, that is, the set of best trade-offs for the metrics of interest. We show how this framework can be used for (i) forward design, that is, finding the Pareto optimal set of synthetic designs for implementation, and (ii) reverse design, that is, analyzing and inferring motifs and/or design principles of gene regulatory networks from the Pareto set of optimal circuits. Finally, we illustrate the capabilities and performance of this framework considering four case studies. In the first problem we consider the forward design of an oscillator. In the remaining problems, we illustrate how to apply the reverse design approach to find motifs for stripe formation, rapid adaption, and fold-change detection, respectively.

  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.

    1978-01-01

    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. An improved brine shrimp larvae lethality microwell test method.

    Science.gov (United States)

    Zhang, Yi; Mu, Jun; Han, Jinyuan; Gu, Xiaojie

    2012-01-01

    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.

  12. Hematologic syndrome in man modeled from mammalian lethality

    International Nuclear Information System (INIS)

    Jones, T.D.

    1981-01-01

    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)

  13. Dominant lethals following administration of tritium (THO) to rat males

    International Nuclear Information System (INIS)

    Yagova, A.; Baev, I.; Bajrakova, A.

    1976-01-01

    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)

  14. Spicing things up: synthetic cannabinoids.

    Science.gov (United States)

    Spaderna, Max; Addy, Peter H; D'Souza, Deepak Cyril

    2013-08-01

    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.

  15. Synthetic Biology and Personalized Medicine

    Science.gov (United States)

    Jain, K.K.

    2013-01-01

    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

  16. Droplet interface bilayer characteristics formed over a synthetic porous substrate

    Science.gov (United States)

    Creasy, M. Austin; Leo, Donald J.

    2009-03-01

    Phospholipid molecules are the fundamental building blocks of cell membranes in living organisms. These molecules are amphipathic with two hydrophobic fatty acid chains (tails) linked to a phosphate containing hydrophilic group (head) that can spontaneously form a bilayer lipid membrane (BLM) with a 6-10 nm thickness in water. BLMs have been classified using some porous synthetic substrate for support. Droplet interface bilayers (DIB) have allowed researchers to study BLMs formed without the use of a porous synthetic substrate. The DIBs are formed at the interface of water droplets and a non-polar solvent. The phospholipids will form a monolayer around the water droplets and when two droplets are brought into contact with each other, a single bilayer will form. DIBs have been used to form networks of BLMs that can be used for multiple purposes. The exact size of the BLM between two droplets is inferred from electrical measurements. The two droplets can be connected through a pore in a synthetic substrate of known dimensions that can limit the area of the BLM. This paper will present the results of forming a BLM on a synthetic substrate by using the DIB method of formation.

  17. Subjective randomness as statistical inference.

    Science.gov (United States)

    Griffiths, Thomas L; Daniels, Dylan; Austerweil, Joseph L; Tenenbaum, Joshua B

    2018-06-01

    Some events seem more random than others. For example, when tossing a coin, a sequence of eight heads in a row does not seem very random. Where do these intuitions about randomness come from? We argue that subjective randomness can be understood as the result of a statistical inference assessing the evidence that an event provides for having been produced by a random generating process. We show how this account provides a link to previous work relating randomness to algorithmic complexity, in which random events are those that cannot be described by short computer programs. Algorithmic complexity is both incomputable and too general to capture the regularities that people can recognize, but viewing randomness as statistical inference provides two paths to addressing these problems: considering regularities generated by simpler computing machines, and restricting the set of probability distributions that characterize regularity. Building on previous work exploring these different routes to a more restricted notion of randomness, we define strong quantitative models of human randomness judgments that apply not just to binary sequences - which have been the focus of much of the previous work on subjective randomness - but also to binary matrices and spatial clustering. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Brine shrimp lethality bioassay of selected Centaurea L. species (Asteraceae

    Directory of Open Access Journals (Sweden)

    Janaćković P.

    2008-01-01

    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.

  19. Bistatic synthetic aperture radar

    Science.gov (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.

  20. Synthetic biology for therapeutic applications.

    Science.gov (United States)

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2015-02-02

    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.

  1. 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...

  2. Bayesian Inference of Tumor Hypoxia

    Science.gov (United States)

    Gunawan, R.; Tenti, G.; Sivaloganathan, S.

    2009-12-01

    Tumor hypoxia is a state of oxygen deprivation in tumors. It has been associated with aggressive tumor phenotypes and with increased resistance to conventional cancer therapies. In this study, we report on the application of Bayesian sequential analysis in estimating the most probable value of tumor hypoxia quantification based on immunohistochemical assays of a biomarker. The `gold standard' of tumor hypoxia assessment is a direct measurement of pO2 in vivo by the Eppendorf polarographic electrode, which is an invasive technique restricted to accessible sites and living tissues. An attractive alternative is immunohistochemical staining to detect proteins expressed by cells during hypoxia. Carbonic anhydrase IX (CAIX) is an enzyme expressed on the cell membrane during hypoxia to balance the immediate extracellular microenvironment. CAIX is widely regarded as a surrogate marker of chronic hypoxia in various cancers. The study was conducted with two different experimental procedures. The first data set was a group of three patients with invasive cervical carcinomas, from which five biopsies were obtained. Each of the biopsies was fully sectioned and from each section, the proportion of CAIX-positive cells was estimated. Measurements were made by image analysis of multiple deep sections cut through these biopsies, labeled for CAIX using both immunofluorescence and immunohistochemical techniques [1]. The second data set was a group of 24 patients, also with invasive cervical carcinomas, from which two biopsies were obtained. Bayesian parameter estimation was applied to obtain a reliable inference about the proportion of CAIX-positive cells within the carcinomas, based on the available biopsies. From the first data set, two to three biopsies were found to be sufficient to infer the overall CAIX percentage in the simple form: best estimate±uncertainty. The second data-set led to a similar result in 70% of the cases. In the remaining cases Bayes' theorem warned us

  3. Development of a Synthetic Lethal Drug Combination That Targets the Energy Generation Triangle for Liver Cancer Therapy

    Science.gov (United States)

    2017-09-01

    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

  4. A Potent and Selective Quinoxalinone-Based STK33 Inhibitor Does Not Show Synthetic Lethality in KRAS-Dependent Cells.

    Science.gov (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

    2012-12-13

    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.

  5. 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...

  6. Adaptive Synthetic Forces: Situation Awareness

    National Research Council Canada - National Science Library

    Hill, Randall

    2001-01-01

    ...: 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...

  7. Designing synthetic networks in silico

    NARCIS (Netherlands)

    Smith, Robert W.; Sluijs, van Bob; Fleck, Christian

    2017-01-01

    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

  8. Synthetic Biology for Specialty Chemicals.

    Science.gov (United States)

    Markham, Kelly A; Alper, Hal S

    2015-01-01

    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.

  9. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    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.

  10. Programming languages for synthetic biology.

    Science.gov (United States)

    Umesh, P; Naveen, F; Rao, Chanchala Uma Maheswara; Nair, Achuthsankar S

    2010-12-01

    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.

  11. 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

    2017-07-01

    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.

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

    Science.gov (United States)

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

    2017-12-05

    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: journals.permissions@oup.com.

  13. Spontaneous Trait Inferences on Social Media.

    Science.gov (United States)

    Levordashka, Ana; Utz, Sonja

    2017-01-01

    The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

  14. Sociolinguistic Perception as Inference Under Uncertainty.

    Science.gov (United States)

    Kleinschmidt, Dave F; Weatherholtz, Kodi; Florian Jaeger, T

    2018-03-15

    Social and linguistic perceptions are linked. On one hand, talker identity affects speech perception. On the other hand, speech itself provides information about a talker's identity. Here, we propose that the same probabilistic knowledge might underlie both socially conditioned linguistic inferences and linguistically conditioned social inferences. Our computational-level approach-the ideal adapter-starts from the idea that listeners use probabilistic knowledge of covariation between social, linguistic, and acoustic cues in order to infer the most likely explanation of the speech signals they hear. As a first step toward understanding social inferences in this framework, we use a simple ideal observer model to show that it would be possible to infer aspects of a talker's identity using cue distributions based on actual speech production data. This suggests the possibility of a single formal framework for social and linguistic inferences and the interactions between them. Copyright © 2018 Cognitive Science Society, Inc.

  15. Statistical inference for financial engineering

    CERN Document Server

    Taniguchi, Masanobu; Ogata, Hiroaki; Taniai, Hiroyuki

    2014-01-01

    This monograph provides the fundamentals of statistical inference for financial engineering and covers some selected methods suitable for analyzing financial time series data. In order to describe the actual financial data, various stochastic processes, e.g. non-Gaussian linear processes, non-linear processes, long-memory processes, locally stationary processes etc. are introduced and their optimal estimation is considered as well. This book also includes several statistical approaches, e.g., discriminant analysis, the empirical likelihood method, control variate method, quantile regression, realized volatility etc., which have been recently developed and are considered to be powerful tools for analyzing the financial data, establishing a new bridge between time series and financial engineering. This book is well suited as a professional reference book on finance, statistics and statistical financial engineering. Readers are expected to have an undergraduate-level knowledge of statistics.

  16. Inferring echolocation in ancient bats.

    Science.gov (United States)

    Simmons, Nancy B; Seymour, Kevin L; Habersetzer, Jörg; Gunnell, Gregg F

    2010-08-19

    Laryngeal echolocation, used by most living bats to form images of their surroundings and to detect and capture flying prey, is considered to be a key innovation for the evolutionary success of bats, and palaeontologists have long sought osteological correlates of echolocation that can be used to infer the behaviour of fossil bats. Veselka et al. argued that the most reliable trait indicating echolocation capabilities in bats is an articulation between the stylohyal bone (part of the hyoid apparatus that supports the throat and larynx) and the tympanic bone, which forms the floor of the middle ear. They examined the oldest and most primitive known bat, Onychonycteris finneyi (early Eocene, USA), and argued that it showed evidence of this stylohyal-tympanic articulation, from which they concluded that O. finneyi may have been capable of echolocation. We disagree with their interpretation of key fossil data and instead argue that O. finneyi was probably not an echolocating bat.

  17. Inference and uncertainty in radiology.

    Science.gov (United States)

    Sistrom, Chris

    2006-05-01

    This paper seeks to enhance understanding of the philosophical underpinnings of our discipline and the resulting practical implications. Radiology reports exist in order to convey new knowledge about a patient's condition based on empiric observations from anatomic or functional images of the body. The route to explanation and prediction from empiric evidence is mostly through inference based on inductive (and sometimes abductive) arguments. The conclusions of inductive arguments are, by definition, contingent and provisional. Therefore, it is necessary to deal in some way with the uncertainty of inferential conclusions (i.e. interpretations) made in radiology reports. Two paradigms for managing uncertainty in natural sciences exist in dialectic tension with each other. These are the frequentist and Bayesian theories of probability. Tension between them is mirrored during routine interactions among radiologists and clinicians. I will describe these core issues and argue that they are quite relevant to routine image interpretation and reporting.

  18. Polynomial Regressions and Nonsense Inference

    Directory of Open Access Journals (Sweden)

    Daniel Ventosa-Santaulària

    2013-11-01

    Full Text Available Polynomial specifications are widely used, not only in applied economics, but also in epidemiology, physics, political analysis and psychology, just to mention a few examples. In many cases, the data employed to estimate such specifications are time series that may exhibit stochastic nonstationary behavior. We extend Phillips’ results (Phillips, P. Understanding spurious regressions in econometrics. J. Econom. 1986, 33, 311–340. by proving that an inference drawn from polynomial specifications, under stochastic nonstationarity, is misleading unless the variables cointegrate. We use a generalized polynomial specification as a vehicle to study its asymptotic and finite-sample properties. Our results, therefore, lead to a call to be cautious whenever practitioners estimate polynomial regressions.

  19. Type inference for correspondence types

    DEFF Research Database (Denmark)

    Hüttel, Hans; Gordon, Andy; Hansen, Rene Rydhof

    2009-01-01

    We present a correspondence type/effect system for authenticity in a π-calculus with polarized channels, dependent pair types and effect terms and show how one may, given a process P and an a priori type environment E, generate constraints that are formulae in the Alternating Least Fixed......-Point (ALFP) logic. We then show how a reasonable model of the generated constraints yields a type/effect assignment such that P becomes well-typed with respect to E if and only if this is possible. The formulae generated satisfy a finite model property; a system of constraints is satisfiable if and only...... if it has a finite model. As a consequence, we obtain the result that type/effect inference in our system is polynomial-time decidable....

  20. Generating realistic synthetic meteoroid orbits

    Science.gov (United States)

    Vida, Denis; Brown, Peter G.; Campbell-Brown, Margaret

    2017-11-01

    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.

  1. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Chavira, Mark; Darwiche, Adnan

    2004-01-01

    We describe a system for exact inference with relational Bayesian networks as defined in the publicly available \\primula\\ tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference by evaluating...... and differentiating these circuits in time linear in their size. We report on experimental results showing the successful compilation, and efficient inference, on relational Bayesian networks whose {\\primula}--generated propositional instances have thousands of variables, and whose jointrees have clusters...

  2. Bayesian Inference Methods for Sparse Channel Estimation

    DEFF Research Database (Denmark)

    Pedersen, Niels Lovmand

    2013-01-01

    of Bayesian inference algorithms for sparse channel estimation. Sparse inference methods aim at finding the sparse representation of a signal given in some overcomplete dictionary of basis vectors. Within this context, one of our main contributions to the field of SBL is a hierarchical representation...... and computational complexity. We also analyze the impact of transceiver filters on the sparseness of the channel response, and propose a dictionary design that permits the deployment of sparse inference methods in conditions of low bandwidth....

  3. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    Science.gov (United States)

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    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. Inference Attacks and Control on Database Structures

    Directory of Open Access Journals (Sweden)

    Muhamed Turkanovic

    2015-02-01

    Full Text Available Today’s databases store information with sensitivity levels that range from public to highly sensitive, hence ensuring confidentiality can be highly important, but also requires costly control. This paper focuses on the inference problem on different database structures. It presents possible treats on privacy with relation to the inference, and control methods for mitigating these treats. The paper shows that using only access control, without any inference control is inadequate, since these models are unable to protect against indirect data access. Furthermore, it covers new inference problems which rise from the dimensions of new technologies like XML, semantics, etc.

  5. Freedom and Responsibility in Synthetic Genomics: The Synthetic Yeast Project.

    Science.gov (United States)

    Sliva, Anna; Yang, Huanming; Boeke, Jef D; Mathews, Debra J H

    2015-08-01

    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.

  6. Bayesian Inference for Linear Parabolic PDEs with Noisy Boundary Conditions

    KAUST Repository

    Ruggeri, Fabrizio

    2016-01-06

    In this work we develop a hierarchical Bayesian setting to infer unknown parameters in initial-boundary value problems (IBVPs) for one-dimensional linear parabolic partial differential equations. Noisy boundary data and known initial condition are assumed. We derive the likelihood function associated with the forward problem, given some measurements of the solution field subject to Gaussian noise. Such function is then analytically marginalized using the linearity of the equation. Gaussian priors have been assumed for the time-dependent Dirichlet boundary values. Our approach is applied to synthetic data for the one-dimensional heat equation model, where the thermal diffusivity is the unknown parameter. We show how to infer the thermal diffusivity parameter when its prior distribution is lognormal or modeled by means of a space-dependent stationary lognormal random field. We use the Laplace method to provide approximated Gaussian posterior distributions for the thermal diffusivity. Expected information gains and predictive posterior densities for observable quantities are numerically estimated for different experimental setups.

  7. Bayesian Inference for Linear Parabolic PDEs with Noisy Boundary Conditions

    KAUST Repository

    Ruggeri, Fabrizio

    2015-01-07

    In this work we develop a hierarchical Bayesian setting to infer unknown parameters in initial-boundary value problems (IBVPs) for one-dimensional linear parabolic partial differential equations. Noisy boundary data and known initial condition are assumed. We derive the likelihood function associated with the forward problem, given some measurements of the solution field subject to Gaussian noise. Such function is then analytically marginalized using the linearity of the equation. Gaussian priors have been assumed for the time-dependent Dirichlet boundary values. Our approach is applied to synthetic data for the one-dimensional heat equation model, where the thermal diffusivity is the unknown parameter. We show how to infer the thermal diffusivity parameter when its prior distribution is lognormal or modeled by means of a space-dependent stationary lognormal random field. We use the Laplace method to provide approximated Gaussian posterior distributions for the thermal diffusivity. Expected information gains and predictive posterior densities for observable quantities are numerically estimated for different experimental setups.

  8. Comparison of evolutionary algorithms in gene regulatory network model inference.

    LENUS (Irish Health Repository)

    2010-01-01

    ABSTRACT: BACKGROUND: The evolution of high throughput technologies that measure gene expression levels has created a data base for inferring GRNs (a process also known as reverse engineering of GRNs). However, the nature of these data has made this process very difficult. At the moment, several methods of discovering qualitative causal relationships between genes with high accuracy from microarray data exist, but large scale quantitative analysis on real biological datasets cannot be performed, to date, as existing approaches are not suitable for real microarray data which are noisy and insufficient. RESULTS: This paper performs an analysis of several existing evolutionary algorithms for quantitative gene regulatory network modelling. The aim is to present the techniques used and offer a comprehensive comparison of approaches, under a common framework. Algorithms are applied to both synthetic and real gene expression data from DNA microarrays, and ability to reproduce biological behaviour, scalability and robustness to noise are assessed and compared. CONCLUSIONS: Presented is a comparison framework for assessment of evolutionary algorithms, used to infer gene regulatory networks. Promising methods are identified and a platform for development of appropriate model formalisms is established.

  9. Inhibition of emetic and superantigenic activities of staphylococcal enterotoxin A by synthetic peptides.

    Science.gov (United States)

    Maina, Edward K; Hu, Dong-Liang; Asano, Krisana; Nakane, Akio

    2012-11-01

    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.

  10. Statistical inference for noisy nonlinear ecological dynamic systems.

    Science.gov (United States)

    Wood, Simon N

    2010-08-26

    Chaotic ecological dynamic systems defy conventional statistical analysis. Systems with near-chaotic dynamics are little better. Such systems are almost invariably driven by endogenous dynamic processes plus demographic and environmental process noise, and are only observable with error. Their sensitivity to history means that minute changes in the driving noise realization, or the system parameters, will cause drastic changes in the system trajectory. This sensitivity is inherited and amplified by the joint probability density of the observable data and the process noise, rendering it useless as the basis for obtaining measures of statistical fit. Because the joint density is the basis for the fit measures used by all conventional statistical methods, this is a major theoretical shortcoming. The inability to make well-founded statistical inferences about biological dynamic models in the chaotic and near-chaotic regimes, other than on an ad hoc basis, leaves dynamic theory without the methods of quantitative validation that are essential tools in the rest of biological science. Here I show that this impasse can be resolved in a simple and general manner, using a method that requires only the ability to simulate the observed data on a system from the dynamic model about which inferences are required. The raw data series are reduced to phase-insensitive summary statistics, quantifying local dynamic structure and the distribution of observations. Simulation is used to obtain the mean and the covariance matrix of the statistics, given model parameters, allowing the construction of a 'synthetic likelihood' that assesses model fit. This likelihood can be explored using a straightforward Markov chain Monte Carlo sampler, but one further post-processing step returns pure likelihood-based inference. I apply the method to establish the dynamic nature of the fluctuations in Nicholson's classic blowfly experiments.

  11. 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.

    1986-01-01

    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

  12. Meeting Report: Synthetic Biology Jamboree for Undergraduates

    Science.gov (United States)

    Campbell, A. Malcolm

    2005-01-01

    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…

  13. 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)

    2003-12-01

    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.)

  14. Lethal and Legal The Ethics of Drone Strikes

    Science.gov (United States)

    2015-12-01

    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

  15. EXCALIBIR - A space experiment in orbital debris lethality

    Science.gov (United States)

    Culp, Robert D.; Dickey, Michael R.

    1991-01-01

    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.

  16. Perinatal lethal type II osteogenesis imperfecta: a case report.

    Science.gov (United States)

    Ayadi, Imene Dahmane; Hamida, Emira Ben; Rebeh, Rania Ben; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    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.

  17. Ultraviolet-B lethal damage on Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Degiorgi, C.F.; Fernandez, R.O.; Pizarro, R.A.

    1996-01-01

    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

  18. Control theory meets synthetic biology.

    Science.gov (United States)

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

    2016-07-01

    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. Synthetic biology, metaphors and responsibility.

    Science.gov (United States)

    McLeod, Carmen; Nerlich, Brigitte

    2017-08-29

    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.

  20. LAIT: a local ancestry inference toolkit.

    Science.gov (United States)

    Hui, Daniel; Fang, Zhou; Lin, Jerome; Duan, Qing; Li, Yun; Hu, Ming; Chen, Wei

    2017-09-06

    Inferring local ancestry in individuals of mixed ancestry has many applications, most notably in identifying disease-susceptible loci that vary among different ethnic groups. Many software packages are available for inferring local ancestry in admixed individuals. However, most of these existing software packages require specific formatted input files and generate output files in various types, yielding practical inconvenience. We developed a tool set, Local Ancestry Inference Toolkit (LAIT), which can convert standardized files into software-specific input file formats as well as standardize and summarize inference results for four popular local ancestry inference software: HAPMIX, LAMP, LAMP-LD, and ELAI. We tested LAIT using both simulated and real data sets and demonstrated that LAIT provides convenience to run multiple local ancestry inference software. In addition, we evaluated the performance of local ancestry software among different supported software packages, mainly focusing on inference accuracy and computational resources used. We provided a toolkit to facilitate the use of local ancestry inference software, especially for users with limited bioinformatics background.

  1. Forward and backward inference in spatial cognition.

    Directory of Open Access Journals (Sweden)

    Will D Penny

    Full Text Available This paper shows that the various computations underlying spatial cognition can be implemented using statistical inference in a single probabilistic model. Inference is implemented using a common set of 'lower-level' computations involving forward and backward inference over time. For example, to estimate where you are in a known environment, forward inference is used to optimally combine location estimates from path integration with those from sensory input. To decide which way to turn to reach a goal, forward inference is used to compute the likelihood of reaching that goal under each option. To work out which environment you are in, forward inference is used to compute the likelihood of sensory observations under the different hypotheses. For reaching sensory goals that require a chaining together of decisions, forward inference can be used to compute a state trajectory that will lead to that goal, and backward inference to refine the route and estimate control signals that produce the required trajectory. We propose that these computations are reflected in recent findings of pattern replay in the mammalian brain. Specifically, that theta sequences reflect decision making, theta flickering reflects model selection, and remote replay reflects route and motor planning. We also propose a mapping of the above computational processes onto lateral and medial entorhinal cortex and hippocampus.

  2. Fiducial inference - A Neyman-Pearson interpretation

    NARCIS (Netherlands)

    Salome, D; VonderLinden, W; Dose,; Fischer, R; Preuss, R

    1999-01-01

    Fisher's fiducial argument is a tool for deriving inferences in the form of a probability distribution on the parameter space, not based on Bayes's Theorem. Lindley established that in exceptional situations fiducial inferences coincide with posterior distributions; in the other situations fiducial

  3. Uncertainty in prediction and in inference

    NARCIS (Netherlands)

    Hilgevoord, J.; Uffink, J.

    1991-01-01

    The concepts of uncertainty in prediction and inference are introduced and illustrated using the diffraction of light as an example. The close re-lationship between the concepts of uncertainty in inference and resolving power is noted. A general quantitative measure of uncertainty in

  4. Reinforcement learning or active inference?

    Science.gov (United States)

    Friston, Karl J; Daunizeau, Jean; Kiebel, Stefan J

    2009-07-29

    This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain.

  5. Reinforcement learning or active inference?

    Directory of Open Access Journals (Sweden)

    Karl J Friston

    2009-07-01

    Full Text Available This paper questions the need for reinforcement learning or control theory when optimising behaviour. We show that it is fairly simple to teach an agent complicated and adaptive behaviours using a free-energy formulation of perception. In this formulation, agents adjust their internal states and sampling of the environment to minimize their free-energy. Such agents learn causal structure in the environment and sample it in an adaptive and self-supervised fashion. This results in behavioural policies that reproduce those optimised by reinforcement learning and dynamic programming. Critically, we do not need to invoke the notion of reward, value or utility. We illustrate these points by solving a benchmark problem in dynamic programming; namely the mountain-car problem, using active perception or inference under the free-energy principle. The ensuing proof-of-concept may be important because the free-energy formulation furnishes a unified account of both action and perception and may speak to a reappraisal of the role of dopamine in the brain.

  6. Extended likelihood inference in reliability

    International Nuclear Information System (INIS)

    Martz, H.F. Jr.; Beckman, R.J.; Waller, R.A.

    1978-10-01

    Extended likelihood methods of inference are developed in which subjective information in the form of a prior distribution is combined with sampling results by means of an extended likelihood function. The extended likelihood function is standardized for use in obtaining extended likelihood intervals. Extended likelihood intervals are derived for the mean of a normal distribution with known variance, the failure-rate of an exponential distribution, and the parameter of a binomial distribution. Extended second-order likelihood methods are developed and used to solve several prediction problems associated with the exponential and binomial distributions. In particular, such quantities as the next failure-time, the number of failures in a given time period, and the time required to observe a given number of failures are predicted for the exponential model with a gamma prior distribution on the failure-rate. In addition, six types of life testing experiments are considered. For the binomial model with a beta prior distribution on the probability of nonsurvival, methods are obtained for predicting the number of nonsurvivors in a given sample size and for predicting the required sample size for observing a specified number of nonsurvivors. Examples illustrate each of the methods developed. Finally, comparisons are made with Bayesian intervals in those cases where these are known to exist

  7. Inferring evoked brain connectivity through adaptive perturbation.

    Science.gov (United States)

    Lepage, Kyle Q; Ching, ShiNung; Kramer, Mark A

    2013-04-01

    Inference of functional networks-representing the statistical associations between time series recorded from multiple sensors-has found important applications in neuroscience. However, networksexhibiting time-locked activity between physically independent elements can bias functional connectivity estimates employing passive measurements. Here, a perturbative and adaptive method of inferring network connectivity based on measurement and stimulation-so called "evoked network connectivity" is introduced. This procedure, employing a recursive Bayesian update scheme, allows principled network stimulation given a current network estimate inferred from all previous stimulations and recordings. The method decouples stimulus and detector design from network inference and can be suitably applied to a wide range of clinical and basic neuroscience related problems. The proposed method demonstrates improved accuracy compared to network inference based on passive observation of node dynamics and an increased rate of convergence relative to network estimation employing a naïve stimulation strategy.

  8. EI: A Program for Ecological Inference

    Directory of Open Access Journals (Sweden)

    Gary King

    2004-09-01

    Full Text Available The program EI provides a method of inferring individual behavior from aggregate data. It implements the statistical procedures, diagnostics, and graphics from the book A Solution to the Ecological Inference Problem: Reconstructing Individual Behavior from Aggregate Data (King 1997. Ecological inference, as traditionally defined, is the process of using aggregate (i.e., "ecological" data to infer discrete individual-level relationships of interest when individual-level data are not available. Ecological inferences are required in political science research when individual-level surveys are unavailable (e.g., local or comparative electoral politics, unreliable (racial politics, insufficient (political geography, or infeasible (political history. They are also required in numerous areas of ma jor significance in public policy (e.g., for applying the Voting Rights Act and other academic disciplines ranging from epidemiology and marketing to sociology and quantitative history.

  9. Microfluidic Technologies for Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Sung Kuk Lee

    2011-06-01

    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.

  10. US Competitiveness in Synthetic Biology.

    Science.gov (United States)

    Gronvall, Gigi Kwik

    2015-01-01

    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.

  11. Synthetic biology as red herring.

    Science.gov (United States)

    Preston, Beth

    2013-12-01

    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.

  12. Investigation of hexachlorophene for dominant lethal effects in the mouse.

    Science.gov (United States)

    Kennedy, G L; Arnold, D W; Keplinger, M L; Calandra, J C

    1975-11-01

    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.

  13. Killing Range: Explaining Lethality Variance within a Terrorist Organization.

    Science.gov (United States)

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

    2015-04-01

    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.

  14. Brine shrimp lethality bioassay of selected gymnosperm and angiosperm species

    Directory of Open Access Journals (Sweden)

    Janaćković Peđa T.

    2016-01-01

    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

  15. Treatment of lethal acetylsalicylic acid poisoning without hemodialysis.

    Science.gov (United States)

    Ueno, Masahito; Oda, Jun; Soeda, Hiroshi; Uesugi, Hirotaka; Ueno, Keiko; Fujise, Yo; Yukioka, Tetsuo

    2015-04-01

    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.

  16. Lethal action of thermal neutron to living cells

    International Nuclear Information System (INIS)

    Kawai, Kenichi; Akahoshi, Mitsuhiko

    1975-01-01

    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)

  17. An outbreak of lethal adenovirus infection among different otariid species.

    Science.gov (United States)

    Inoshima, Yasuo; Murakami, Tomoaki; Ishiguro, Naotaka; Hasegawa, Kazuhiro; Kasamatsu, Masahiko

    2013-08-30

    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.

  18. 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

    2004-09-01

    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

  19. Synthetic Phage for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    So Young Yoo

    2014-01-01

    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.

  20. Synthetic biology and its promises

    Directory of Open Access Journals (Sweden)

    José Manuel De Cózar Escalante

    2016-12-01

    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.

  1. Synthetic methodologies for carbon nanomaterials.

    Science.gov (United States)

    Liu, Zhaoping; Zhou, Xufeng; Qian, Yitai

    2010-05-04

    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.

  2. Forward imaging for obstacle avoidance using ultrawideband synthetic aperture radar

    Science.gov (United States)

    Nguyen, Lam H.; Wong, David C.; Stanton, Brian; Smith, Gregory

    2003-09-01

    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.

  3. AD-LIBS: inferring ancestry across hybrid genomes using low-coverage sequence data.

    Science.gov (United States)

    Schaefer, Nathan K; Shapiro, Beth; Green, Richard E

    2017-04-04

    Inferring the ancestry of each region of admixed individuals' genomes is useful in studies ranging from disease gene mapping to speciation genetics. Current methods require high-coverage genotype data and phased reference panels, and are therefore inappropriate for many data sets. We present a software application, AD-LIBS, that uses a hidden Markov model to infer ancestry across hybrid genomes without requiring variant calling or phasing. This approach is useful for non-model organisms and in cases of low-coverage data, such as ancient DNA. We demonstrate the utility of AD-LIBS with synthetic data. We then use AD-LIBS to infer ancestry in two published data sets: European human genomes with Neanderthal ancestry and brown bear genomes with polar bear ancestry. AD-LIBS correctly infers 87-91% of ancestry in simulations and produces ancestry maps that agree with published results and global ancestry estimates in humans. In brown bears, we find more polar bear ancestry than has been published previously, using both AD-LIBS and an existing software application for local ancestry inference, HAPMIX. We validate AD-LIBS polar bear ancestry maps by recovering a geographic signal within bears that mirrors what is seen in SNP data. Finally, we demonstrate that AD-LIBS is more effective than HAPMIX at inferring ancestry when preexisting phased reference data are unavailable and genomes are sequenced to low coverage. AD-LIBS is an effective tool for ancestry inference that can be used even when few individuals are available for comparison or when genomes are sequenced to low coverage. AD-LIBS is therefore likely to be useful in studies of non-model or ancient organisms that lack large amounts of genomic DNA. AD-LIBS can therefore expand the range of studies in which admixture mapping is a viable tool.

  4. A Systems Biology Approach to Link Nuclear Factor Kappa B Activation with Lethal Prostate Cancer

    Science.gov (United States)

    2014-05-01

    indolent participants. For each cytokine, the threshold for being ‘high’ was determined as being above the third quartile of the combined indolent and...to 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

  5. Where Synthetic Biology Meets ET

    Science.gov (United States)

    Rothschild, Lynn J.

    2016-01-01

    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.

  6. Future of synthetic aperture radar

    Science.gov (United States)

    Barath, F. T.

    1978-01-01

    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.

  7. Digital 'faces' of synthetic biology.

    Science.gov (United States)

    Friedrich, Kathrin

    2013-06-01

    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.

  8. Synthetic peptides for diagnostic use

    NARCIS (Netherlands)

    Meloen, R.H.; Langedijk, J.P.M.; Langeveld, J.P.M.

    1997-01-01

    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

  9. Analysis of the Synthetic Jet

    Czech Academy of Sciences Publication Activity Database

    Dančová, Petra; Vít, Tomáš

    2009-01-01

    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

  10. Methods for preparing synthetic freshwaters.

    Science.gov (United States)

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

    2002-03-01

    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.

  11. Inference and the introductory statistics course

    Science.gov (United States)

    Pfannkuch, Maxine; Regan, Matt; Wild, Chris; Budgett, Stephanie; Forbes, Sharleen; Harraway, John; Parsonage, Ross

    2011-10-01

    This article sets out some of the rationale and arguments for making major changes to the teaching and learning of statistical inference in introductory courses at our universities by changing from a norm-based, mathematical approach to more conceptually accessible computer-based approaches. The core problem of the inferential argument with its hypothetical probabilistic reasoning process is examined in some depth. We argue that the revolution in the teaching of inference must begin. We also discuss some perplexing issues, problematic areas and some new insights into language conundrums associated with introducing the logic of inference through randomization methods.

  12. Compiling Relational Bayesian Networks for Exact Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred; Darwiche, Adnan; Chavira, Mark

    2006-01-01

    We describe in this paper a system for exact inference with relational Bayesian networks as defined in the publicly available PRIMULA tool. The system is based on compiling propositional instances of relational Bayesian networks into arithmetic circuits and then performing online inference...... by evaluating and differentiating these circuits in time linear in their size. We report on experimental results showing successful compilation and efficient inference on relational Bayesian networks, whose PRIMULA--generated propositional instances have thousands of variables, and whose jointrees have clusters...

  13. Protease-sensitive synthetic prions.

    Directory of Open Access Journals (Sweden)

    David W Colby

    2010-01-01

    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.

  14. Metabolomic Footprints of Lethal Versus Indolent Prostate Cancer

    Science.gov (United States)

    2014-10-01

    biomarkers and writing up manuscripts. 15. SUBJECT TERMS Prostate cancer survivorship, metabolite profiling, metabolic biomarkers 16. SECURITY ...either by NHS laboratory staff or a central security desk (nights and weekends). Physicians’ Health Study. Blood collection kits were sent to all...Polymorphisme Humain (CEPH) collection) to infer expected genotype counts for each marker locus. MACH quality scores and R2 values were more than 0.85

  15. Parental response to severe or lethal prenatal diagnosis

    DEFF Research Database (Denmark)

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

    2017-01-01

    . 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...

  16. 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.

  17. Autotaxin Overexpression Causes Embryonic Lethality and Vascular Defects

    Science.gov (United States)

    Yukiura, Hiroshi; Kano, Kuniyuki; Kise, Ryoji; Inoue, Asuka; Aoki, Junken

    2015-01-01

    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

  18. 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.

    2009-01-01

    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)

  19. Radiation-induced mutagenicity and lethality in Salmonella typhimurium

    International Nuclear Information System (INIS)

    Isildar, M.; Bakale, G.

    1983-01-01

    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

  20. Gastrointestinal decontamination in healthy and lethally irradiated monkeys

    International Nuclear Information System (INIS)

    Hendriks, W.D.H.

    1980-01-01

    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.)

  1. Lethal intragroup aggression by adult male spider monkeys (Ateles geoffroyi).

    Science.gov (United States)

    Campbell, Christina J

    2006-12-01

    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.

  2. A novel poxvirus lethal to red squirrels (Sciurus vulgaris).

    Science.gov (United States)

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

    2003-12-01

    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.

  3. Mechanisms of Lethal Cerebrovascular Accidents in Turner Syndrome.

    Science.gov (United States)

    Byard, Roger W

    2016-05-01

    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.

  4. Evaluation of Lethal Giant Larvae as a Schistosomiasis Vaccine Candidate

    Directory of Open Access Journals (Sweden)

    Yufan Cao

    2016-01-01

    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.

  5. Experimental evidence for circular inference in schizophrenia

    Science.gov (United States)

    Jardri, Renaud; Duverne, Sandrine; Litvinova, Alexandra S.; Denève, Sophie

    2017-01-01

    Schizophrenia (SCZ) is a complex mental disorder that may result in some combination of hallucinations, delusions and disorganized thinking. Here SCZ patients and healthy controls (CTLs) report their level of confidence on a forced-choice task that manipulated the strength of sensory evidence and prior information. Neither group's responses can be explained by simple Bayesian inference. Rather, individual responses are best captured by a model with different degrees of circular inference. Circular inference refers to a corruption of sensory data by prior information and vice versa, leading us to `see what we expect' (through descending loops), to `expect what we see' (through ascending loops) or both. Ascending loops are stronger for SCZ than CTLs and correlate with the severity of positive symptoms. Descending loops correlate with the severity of negative symptoms. Both loops correlate with disorganized symptoms. The findings suggest that circular inference might mediate the clinical manifestations of SCZ.

  6. Artificial Hydrocarbon Networks Fuzzy Inference System

    Directory of Open Access Journals (Sweden)

    Hiram Ponce

    2013-01-01

    Full Text Available This paper presents a novel fuzzy inference model based on artificial hydrocarbon networks, a computational algorithm for modeling problems based on chemical hydrocarbon compounds. In particular, the proposed fuzzy-molecular inference model (FIM-model uses molecular units of information to partition the output space in the defuzzification step. Moreover, these molecules are linguistic units that can be partially understandable due to the organized structure of the topology and metadata parameters involved in artificial hydrocarbon networks. In addition, a position controller for a direct current (DC motor was implemented using the proposed FIM-model in type-1 and type-2 fuzzy inference systems. Experimental results demonstrate that the fuzzy-molecular inference model can be applied as an alternative of type-2 Mamdani’s fuzzy control systems because the set of molecular units can deal with dynamic uncertainties mostly present in real-world control applications.

  7. SEBINI: Software Environment for BIological Network Inference.

    Science.gov (United States)

    Taylor, Ronald C; Shah, Anuj; Treatman, Charles; Blevins, Meridith

    2006-11-01

    The Software Environment for BIological Network Inference (SEBINI) has been created to provide an interactive environment for the deployment and evaluation of algorithms used to reconstruct the structure of biological regulatory and interaction networks. SEBINI can be used to compare and train network inference methods on artificial networks and simulated gene expression perturbation data. It also allows the analysis within the same framework of experimental high-throughput expression data using the suite of (trained) inference methods; hence SEBINI should be useful to software developers wishing to evaluate, compare, refine or combine inference techniques, and to bioinformaticians analyzing experimental data. SEBINI provides a platform that aids in more accurate reconstruction of biological networks, with less effort, in less time. A demonstration website is located at https://www.emsl.pnl.gov/NIT/NIT.html. The Java source code and PostgreSQL database schema are available freely for non-commercial use.

  8. Inferring Domain Plans in Question-Answering

    National Research Council Canada - National Science Library

    Pollack, Martha E

    1986-01-01

    The importance of plan inference in models of conversation has been widely noted in the computational-linguistics literature, and its incorporation in question-answering systems has enabled a range...

  9. 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

    2012-11-01

    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

  10. Artificial Hydrocarbon Networks Fuzzy Inference System

    OpenAIRE

    Ponce, Hiram; Ponce, Pedro; Molina, Arturo

    2013-01-01

    This paper presents a novel fuzzy inference model based on artificial hydrocarbon networks, a computational algorithm for modeling problems based on chemical hydrocarbon compounds. In particular, the proposed fuzzy-molecular inference model (FIM-model) uses molecular units of information to partition the output space in the defuzzification step. Moreover, these molecules are linguistic units that can be partially understandable due to the organized structure of the topology and metadata param...

  11. Efficient algorithms for conditional independence inference

    Czech Academy of Sciences Publication Activity Database

    Bouckaert, R.; Hemmecke, R.; Lindner, S.; Studený, Milan

    2010-01-01

    Roč. 11, č. 1 (2010), s. 3453-3479 ISSN 1532-4435 R&D Projects: GA ČR GA201/08/0539; GA MŠk 1M0572 Institutional research plan: CEZ:AV0Z10750506 Keywords : conditional independence inference * linear programming approach Subject RIV: BA - General Mathematics Impact factor: 2.949, year: 2010 http://library.utia.cas.cz/separaty/2010/MTR/studeny-efficient algorithms for conditional independence inference.pdf

  12. Probabilistic inferences related to the measurement process

    International Nuclear Information System (INIS)

    Rossi, G. B.

    2010-01-01

    In measurement indications from a measuring system are acquired and, on the basis of them, some inference about the measurand is made. The final result may be the assignment of a probability distribution for the possible values of the measurand. We discuss the logical structure of such an inference and some of its epistemological consequences. In particular, we propose a new solution to the problem of systematic effects in measurement.

  13. Polynomial Chaos Surrogates for Bayesian Inference

    KAUST Repository

    Le Maitre, Olivier

    2016-01-06

    The Bayesian inference is a popular probabilistic method to solve inverse problems, such as the identification of field parameter in a PDE model. The inference rely on the Bayes rule to update the prior density of the sought field, from observations, and derive its posterior distribution. In most cases the posterior distribution has no explicit form and has to be sampled, for instance using a Markov-Chain Monte Carlo method. In practice the prior field parameter is decomposed and truncated (e.g. by means of Karhunen- Lo´eve decomposition) to recast the inference problem into the inference of a finite number of coordinates. Although proved effective in many situations, the Bayesian inference as sketched above faces several difficulties requiring improvements. First, sampling the posterior can be a extremely costly task as it requires multiple resolutions of the PDE model for different values of the field parameter. Second, when the observations are not very much informative, the inferred parameter field can highly depends on its prior which can be somehow arbitrary. These issues have motivated the introduction of reduced modeling or surrogates for the (approximate) determination of the parametrized PDE solution and hyperparameters in the description of the prior field. Our contribution focuses on recent developments in these two directions: the acceleration of the posterior sampling by means of Polynomial Chaos expansions and the efficient treatment of parametrized covariance functions for the prior field. We also discuss the possibility of making such approach adaptive to further improve its efficiency.

  14. On the criticality of inferred models

    International Nuclear Information System (INIS)

    Mastromatteo, Iacopo; Marsili, Matteo

    2011-01-01

    Advanced inference techniques allow one to reconstruct a pattern of interaction from high dimensional data sets, from probing simultaneously thousands of units of extended systems—such as cells, neural tissues and financial markets. We focus here on the statistical properties of inferred models and argue that inference procedures are likely to yield models which are close to singular values of parameters, akin to critical points in physics where phase transitions occur. These are points where the response of physical systems to external perturbations, as measured by the susceptibility, is very large and diverges in the limit of infinite size. We show that the reparameterization invariant metrics in the space of probability distributions of these models (the Fisher information) are directly related to the susceptibility of the inferred model. As a result, distinguishable models tend to accumulate close to critical points, where the susceptibility diverges in infinite systems. This region is the one where the estimate of inferred parameters is most stable. In order to illustrate these points, we discuss inference of interacting point processes with application to financial data and show that sensible choices of observation time scales naturally yield models which are close to criticality

  15. Synthetic LDL as targeted drug delivery vehicle

    Science.gov (United States)

    Forte, Trudy M [Berkeley, CA; Nikanjam, Mina [Richmond, CA

    2012-08-28

    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.

  16. Synthetic biology character and impact

    CERN Document Server

    Pade, Christian; Wigger, Henning; Gleich, Arnim

    2015-01-01

    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...

  17. Design Automation in Synthetic Biology.

    Science.gov (United States)

    Appleton, Evan; Madsen, Curtis; Roehner, Nicholas; Densmore, Douglas

    2017-04-03

    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.

  18. Engineering Ecosystems and Synthetic Ecologies#

    Science.gov (United States)

    Mee, Michael T; Wang, Harris H

    2012-01-01

    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

  19. Synthetic greenhouse gases under control

    International Nuclear Information System (INIS)

    Horisberger, B.; Karlaganis, G.

    2003-01-01

    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

  20. Compounding in synthetic aperture imaging

    DEFF Research Database (Denmark)

    Hansen, J. M.; Jensen, J. A.

    2012-01-01

    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...

  1. Characterization of Synthetic Peptides by Mass Spectrometry.

    Science.gov (United States)

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

    2015-01-01

    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.

  2. Synthetic thermoelectric materials comprising phononic crystals

    Science.gov (United States)

    El-Kady, Ihab F; Olsson, Roy H; Hopkins, Patrick; Reinke, Charles; Kim, Bongsang

    2013-08-13

    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.

  3. Steel desulphurization with synthetic slag

    Energy Technology Data Exchange (ETDEWEB)

    Heput, T.; Ardelean, E.; Socalici, A.; Maksay, S.; Gavanescu, A.

    2007-07-01

    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.

  4. Hydrogen speciation in synthetic quartz

    Science.gov (United States)

    Aines, R.D.; Kirby, S.H.; Rossman, G.R.

    1984-01-01

    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.

  5. 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

    2001-01-01

    .... 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...

  6. Acute-lethal toxicity (LC50) effect of Moringa oleifera (Lam.) Fresh ...

    African Journals Online (AJOL)

    SH

    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.

  7. Acute-lethal toxicity (LC 50 ) effect of Moringa oleifera (Lam.) Fresh ...

    African Journals Online (AJOL)

    Acute-lethal toxicity is a tool used in piscicide bio-safety assessment in fish farming prior to its proper application in sustainable aquaculture. Piscicides of plant origin are usually considered for bio-safety assessment because of their effects on non-target aquatic species in fish pond. Acute-lethal toxicity is an indication of ...

  8. Examining the Impact of Psychiatric Diagnosis and Comorbidity on the Medical Lethality of Adolescent "Suicide Attempts"

    Science.gov (United States)

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

    2012-01-01

    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…

  9. 77 FR 6548 - Notice of Availability of Ballistic Survivability, Lethality and Vulnerability Analyses

    Science.gov (United States)

    2012-02-08

    ... Department of the Army Notice of Availability of Ballistic Survivability, Lethality and Vulnerability... survivability, lethality and vulnerability (SLV) analyses. ARL/SLAD conducts SLV analyses, using the MUVES-S2 vulnerability model, to quantify system, subsystem and/or component level vulnerabilities of ground and air...

  10. Acute and sub-lethal response to mercury in Arctic and boreal calanoid copepods.

    Science.gov (United States)

    Overjordet, Ida Beathe; Altin, Dag; Berg, Torunn; Jenssen, Bjørn Munro; Gabrielsen, Geir Wing; Hansen, Bjørn Henrik

    2014-10-01

    Acute lethal toxicity, expressed as LC50 values, is a widely used parameter in risk assessment of chemicals, and has been proposed as a tool to assess differences in species sensitivities to chemicals between climatic regions. Arctic Calanus glacialis and boreal Calanus finmarchicus were exposed to mercury (Hg(2+)) under natural environmental conditions including sea temperatures of 2° and 10°C, respectively. Acute lethal toxicity (96 h LC50) and sub-lethal molecular response (GST expression; in this article gene expression is used as a synonym of gene transcription, although it is acknowledged that gene expression is also regulated, e.g., at translation and protein stability level) were studied. The acute lethal toxicity was monitored for 96 h using seven different Hg concentrations. The sub-lethal experiment was set up on the basis of nominal LC50 values for each species using concentrations equivalent to 50, 5 and 0.5% of their 96 h LC50 value. No significant differences were found in acute lethal toxicity between the two species. The sub-lethal molecular response revealed large differences both in response time and the fold induction of GST, where the Arctic species responded both faster and with higher mRNA levels of GST after 48 h exposure. Under the natural exposure conditions applied in the present study, the Arctic species C. glacialis may potentially be more susceptible to mercury exposure on the sub-lethal level. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2009-01-01

    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. Foal with Overo lethal white syndrome born to a registered quarter horse mare

    OpenAIRE

    Lightbody, Tamara

    2002-01-01

    A 16-hour-old white foal, born to a registered quarter horse mare, was examined for signs of colic. The foal had Overo lethal white syndrome, which causes ileocolonic agangliosis. This was confirmed by DNA testing. Since there is no treatment for Overo lethal white syndrome, the foal was euthanized.

  13. Foal with Overo lethal white syndrome born to a registered quarter horse mare.

    Science.gov (United States)

    Lightbody, Tamara

    2002-09-01

    A 16-hour-old white foal, born to a registered quarter horse mare, was examined for signs of colic. The foal had Overo lethal white syndrome, which causes ileocolonic agangliosis. This was confirmed by DNA testing. Since there is no treatment for Overo lethal white syndrome, the foal was euthanized.

  14. Inferring properties of disordered chains from FRET transfer efficiencies

    Science.gov (United States)

    Zheng, Wenwei; Zerze, Gül H.; Borgia, Alessandro; Mittal, Jeetain; Schuler, Benjamin; Best, Robert B.

    2018-03-01

    Förster resonance energy transfer (FRET) is a powerful tool for elucidating both structural and dynamic properties of unfolded or disordered biomolecules, especially in single-molecule experiments. However, the key observables, namely, the mean transfer efficiency and fluorescence lifetimes of the donor and acceptor chromophores, are averaged over a broad distribution of donor-acceptor distances. The inferred average properties of the ensemble therefore depend on the form of the model distribution chosen to describe the distance, as has been widely recognized. In addition, while the distribution for one type of polymer model may be appropriate for a chain under a given set of physico-chemical conditions, it may not be suitable for the same chain in a different environment so that even an apparently consistent application of the same model over all conditions may distort the apparent changes in chain dimensions with variation of temperature or solution composition. Here, we present an alternative and straightforward approach to determining ensemble properties from FRET data, in which the polymer scaling exponent is allowed to vary with solution conditions. In its simplest form, it requires either the mean FRET efficiency or fluorescence lifetime information. In order to test the accuracy of the method, we have utilized both synthetic FRET data from implicit and explicit solvent simulations for 30 different protein sequences, and experimental single-molecule FRET data for an intrinsically disordered and a denatured protein. In all cases, we find that the inferred radii of gyration are within 10% of the true values, thus providing higher accuracy than simpler polymer models. In addition, the scaling exponents obtained by our procedure are in good agreement with those determined directly from the molecular ensemble. Our approach can in principle be generalized to treating other ensemble-averaged functions of intramolecular distances from experimental data.

  15. fastBMA: scalable network inference and transitive reduction.

    Science.gov (United States)

    Hung, Ling-Hong; Shi, Kaiyuan; Wu, Migao; Young, William Chad; Raftery, Adrian E; Yeung, Ka Yee

    2017-10-01

    Inferring genetic networks from genome-wide expression data is extremely demanding computationally. We have developed fastBMA, a distributed, parallel, and scalable implementation of Bayesian model averaging (BMA) for this purpose. fastBMA also includes a computationally efficient module for eliminating redundant indirect edges in the network by mapping the transitive reduction to an easily solved shortest-path problem. We evaluated the performance of fastBMA on synthetic data and experimental genome-wide time series yeast and human datasets. When using a single CPU core, fastBMA is up to 100 times faster than the next fastest method, LASSO, with increased accuracy. It is a memory-efficient, parallel, and distributed application that scales to human genome-wide expression data. A 10 000-gene regulation network can be obtained in a matter of hours using a 32-core cloud cluster (2 nodes of 16 cores). fastBMA is a significant improvement over its predecessor ScanBMA. It is more accurate and orders of magnitude faster than other fast network inference methods such as the 1 based on LASSO. The improved scalability allows it to calculate networks from genome scale data in a reasonable time frame. The transitive reduction method can improve accuracy in denser networks. fastBMA is available as code (M.I.T. license) from GitHub (https://github.com/lhhunghimself/fastBMA), as part of the updated networkBMA Bioconductor package (https://www.bioconductor.org/packages/release/bioc/html/networkBMA.html) and as ready-to-deploy Docker images (https://hub.docker.com/r/biodepot/fastbma/). © The Authors 2017. Published by Oxford University Press.

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

    Science.gov (United States)

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

    2012-08-01

    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. Terrorist attacks escalate in frequency and fatalities preceding highly lethal attacks.

    Science.gov (United States)

    Martens, Andy; Sainudiin, Raazesh; Sibley, Chris G; Schimel, Jeff; Webber, David

    2014-01-01

    Highly lethal terrorist attacks, which we define as those killing 21 or more people, account for 50% of the total number of people killed in all terrorist attacks combined, yet comprise only 3.5% of terrorist attacks. Given the disproportionate influence of these incidents, uncovering systematic patterns in attacks that precede and anticipate these highly lethal attacks may be of value for understanding attacks that exact a heavy toll on life. Here we examined whether the activity of terrorist groups escalates--both in the number of people killed per attack and in the frequency of attacks--leading up to highly lethal attacks. Analyses of terrorist attacks drawn from a state-of-the-art international terrorism database (The Global Terrorism Database) showed evidence for both types of escalation leading up to highly lethal attacks, though complexities to the patterns emerged as well. These patterns of escalation do not emerge among terrorist groups that never commit a highly lethal attack.

  18. A symmetry-based method to infer structural brain networks from probabilistic tractography data

    Directory of Open Access Journals (Sweden)

    Kamal Shadi

    2016-11-01

    Full Text Available Recent progress in diffusion MRI and tractography algorithms as well as the launch of the Human Connectome Project (HCP have provided brain research with an abundance of structural connectivity data. In this work, we describe and evaluate a method that can infer the structural brain network that interconnects a given set of Regions of Interest (ROIs from probabilistic tractography data. The proposed method, referred to as Minimum Asymmetry Network Inference Algorithm (MANIA, does not determine the connectivity between two ROIs based on an arbitrary connectivity threshold. Instead, we exploit a basic limitation of the tractography process: the observed streamlines from a source to a target do not provide any information about the polarity of the underlying white matter, and so if there are some fibers connecting two voxels (or two ROIs X and Y, tractography should be able in principle to follow this connection in both directions, from X to Y and from Y to X. We leverage this limitation to formulate the network inference process as an optimization problem that minimizes the (appropriately normalized asymmetry of the observed network. We evaluate the proposed method using both the FiberCup dataset and based on a noise model that randomly corrupts the observed connectivity of synthetic networks. As a case-study, we apply MANIA on diffusion MRI data from 28 healthy subjects to infer the structural network between 18 corticolimbic ROIs that are associated with various neuropsychiatric conditions including depression, anxiety and addiction.

  19. Hierarchical modeling and inference in ecology: The analysis of data from populations, metapopulations and communities

    Science.gov (United States)

    Royle, J. Andrew; Dorazio, Robert M.

    2008-01-01

    A guide to data collection, modeling and inference strategies for biological survey data using Bayesian and classical statistical methods. This book describes a general and flexible framework for modeling and inference in ecological systems based on hierarchical models, with a strict focus on the use of probability models and parametric inference. Hierarchical models represent a paradigm shift in the application of statistics to ecological inference problems because they combine explicit models of ecological system structure or dynamics with models of how ecological systems are observed. The principles of hierarchical modeling are developed and applied to problems in population, metapopulation, community, and metacommunity systems. The book provides the first synthetic treatment of many recent methodological advances in ecological modeling and unifies disparate methods and procedures. The authors apply principles of hierarchical modeling to ecological problems, including * occurrence or occupancy models for estimating species distribution * abundance models based on many sampling protocols, including distance sampling * capture-recapture models with individual effects * spatial capture-recapture models based on camera trapping and related methods * population and metapopulation dynamic models * models of biodiversity, community structure and dynamics.

  20. Recombinant thrombomodulin protects mice against histone-induced lethal thromboembolism.

    Directory of Open Access Journals (Sweden)

    Mayumi Nakahara

    Full Text Available INTRODUCTION: Recent studies have shown that histones, the chief protein component of chromatin, are released into the extracellular space during sepsis, trauma, and ischemia-reperfusion injury, and act as major mediators of the death of an organism. This study was designed to elucidate the cellular and molecular basis of histone-induced lethality and to assess the protective effects of recombinant thrombomodulin (rTM. rTM has been approved for the treatment of disseminated intravascular coagulation (DIC in Japan, and is currently undergoing a phase III clinical trial in the United States. METHODS: Histone H3 levels in plasma of healthy volunteers and patients with sepsis and DIC were measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected intravenously with purified histones, and pathological examinations were performed. The protective effects of rTM against histone toxicity were analyzed both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of healthy volunteers, but significant levels were observed in patients with sepsis and DIC. These levels were higher in non-survivors than in survivors. Extracellular histones triggered platelet aggregation, leading to thrombotic occlusion of pulmonary capillaries and subsequent right-sided heart failure in mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and bleeding. Platelet depletion protected mice from histone-induced death in the first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might be responsible for death during the early phase. Furthermore, rTM bound to extracellular histones, suppressed histone-induced platelet aggregation, thrombotic occlusion of pulmonary capillaries, and dilatation of the right ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS: Extracellular histones cause massive

  1. Estimating uncertainty of inference for validation

    Energy Technology Data Exchange (ETDEWEB)

    Booker, Jane M [Los Alamos National Laboratory; Langenbrunner, James R [Los Alamos National Laboratory; Hemez, Francois M [Los Alamos National Laboratory; Ross, Timothy J [UNM

    2010-09-30

    We present a validation process based upon the concept that validation is an inference-making activity. This has always been true, but the association has not been as important before as it is now. Previously, theory had been confirmed by more data, and predictions were possible based on data. The process today is to infer from theory to code and from code to prediction, making the role of prediction somewhat automatic, and a machine function. Validation is defined as determining the degree to which a model and code is an accurate representation of experimental test data. Imbedded in validation is the intention to use the computer code to predict. To predict is to accept the conclusion that an observable final state will manifest; therefore, prediction is an inference whose goodness relies on the validity of the code. Quantifying the uncertainty of a prediction amounts to quantifying the uncertainty of validation, and this involves the characterization of uncertainties inherent in theory/models/codes and the corresponding data. An introduction to inference making and its associated uncertainty is provided as a foundation for the validation problem. A mathematical construction for estimating the uncertainty in the validation inference is then presented, including a possibility distribution constructed to represent the inference uncertainty for validation under uncertainty. The estimation of inference uncertainty for validation is illustrated using data and calculations from Inertial Confinement Fusion (ICF). The ICF measurements of neutron yield and ion temperature were obtained for direct-drive inertial fusion capsules at the Omega laser facility. The glass capsules, containing the fusion gas, were systematically selected with the intent of establishing a reproducible baseline of high-yield 10{sup 13}-10{sup 14} neutron output. The deuterium-tritium ratio in these experiments was varied to study its influence upon yield. This paper on validation inference is the

  2. Deep Learning for Population Genetic Inference.

    Directory of Open Access Journals (Sweden)

    Sara Sheehan

    2016-03-01

    Full Text Available Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data to the output (e.g., population genetic parameters of interest. We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history. Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme.

  3. Deep Learning for Population Genetic Inference

    Science.gov (United States)

    Sheehan, Sara; Song, Yun S.

    2016-01-01

    Given genomic variation data from multiple individuals, computing the likelihood of complex population genetic models is often infeasible. To circumvent this problem, we introduce a novel likelihood-free inference framework by applying deep learning, a powerful modern technique in machine learning. Deep learning makes use of multilayer neural networks to learn a feature-based function from the input (e.g., hundreds of correlated summary statistics of data) to the output (e.g., population genetic parameters of interest). We demonstrate that deep learning can be effectively employed for population genetic inference and learning informative features of data. As a concrete application, we focus on the challenging problem of jointly inferring natural selection and demography (in the form of a population size change history). Our method is able to separate the global nature of demography from the local nature of selection, without sequential steps for these two factors. Studying demography and selection jointly is motivated by Drosophila, where pervasive selection confounds demographic analysis. We apply our method to 197 African Drosophila melanogaster genomes from Zambia to infer both their overall demography, and regions of their genome under selection. We find many regions of the genome that have experienced hard sweeps, and fewer under selection on standing variation (soft sweep) or balancing selection. Interestingly, we find that soft sweeps and balancing selection occur more frequently closer to the centromere of each chromosome. In addition, our demographic inference suggests that previously estimated bottlenecks for African Drosophila melanogaster are too extreme. PMID:27018908

  4. Computationally efficient Bayesian inference for inverse problems.

    Energy Technology Data Exchange (ETDEWEB)

    Marzouk, Youssef M.; Najm, Habib N.; Rahn, Larry A.

    2007-10-01

    Bayesian statistics provides a foundation for inference from noisy and incomplete data, a natural mechanism for regularization in the form of prior information, and a quantitative assessment of uncertainty in the inferred results. Inverse problems - representing indirect estimation of model parameters, inputs, or structural components - can be fruitfully cast in this framework. Complex and computationally intensive forward models arising in physical applications, however, can render a Bayesian approach prohibitive. This difficulty is compounded by high-dimensional model spaces, as when the unknown is a spatiotemporal field. We present new algorithmic developments for Bayesian inference in this context, showing strong connections with the forward propagation of uncertainty. In particular, we introduce a stochastic spectral formulation that dramatically accelerates the Bayesian solution of inverse problems via rapid evaluation of a surrogate posterior. We also explore dimensionality reduction for the inference of spatiotemporal fields, using truncated spectral representations of Gaussian process priors. These new approaches are demonstrated on scalar transport problems arising in contaminant source inversion and in the inference of inhomogeneous material or transport properties. We also present a Bayesian framework for parameter estimation in stochastic models, where intrinsic stochasticity may be intermingled with observational noise. Evaluation of a likelihood function may not be analytically tractable in these cases, and thus several alternative Markov chain Monte Carlo (MCMC) schemes, operating on the product space of the observations and the parameters, are introduced.

  5. Printability of Synthetic Papers by Electrophotography

    Directory of Open Access Journals (Sweden)

    Rozália Szentgyörgyvölgyi

    2010-04-01

    Full Text Available This paper deals with the printability of synthetic papers by the electrophotography technique. Prints of cmyk colour fields from 20% to 100% raster tone values were printed on three types of synthetic papers (one film synthetic paper and two fiber synthetic papers. The investigation of the appearance included densitometric measurement of the cmyk prints. The results have shown differences in the optical density and optical tone value between cmyk prints made on various synthetic papers. The highest optical density and the increase of the optical tone value were observed on the film synthetic paper, where cmyk prints were more saturated. The highest abrasion resistance of cmyk prints was obtained from the fibre synthetic paper.

  6. Synthetic biology: Emerging bioengineering in Indonesia

    Science.gov (United States)

    Suhandono, Sony

    2017-05-01

    The development of synthetic biology will shape the new era of science and technology. It is an emerging bioengineering technique involving genetic engineering which can alter the phenotype and behavior of the cell or the new product. Synthetic biology may produce biomaterials, drugs, vaccines, biosensors, and even a recombinant secondary metabolite used in herbal and complementary medicine, such as artemisinin, a malaria drug which is usually extracted from the plant Artemisia annua. The power of synthetic biology has encouraged scientists in Indonesia, and is still in early development. This paper also covers some research from an Indonesian research institute in synthetic biology such as observing the production of bio surfactants and the enhanced production of artemisinin using a transient expression system. Synthetic biology development in Indonesia may also be related to the iGEM competition, a large synthetic biology research competition which was attended by several universities in Indonesia. The application of synthetic biology for drug discovery will be discussed.

  7. Using Alien Coins to Test Whether Simple Inference Is Bayesian

    Science.gov (United States)

    Cassey, Peter; Hawkins, Guy E.; Donkin, Chris; Brown, Scott D.

    2016-01-01

    Reasoning and inference are well-studied aspects of basic cognition that have been explained as statistically optimal Bayesian inference. Using a simplified experimental design, we conducted quantitative comparisons between Bayesian inference and human inference at the level of individuals. In 3 experiments, with more than 13,000 participants, we…

  8. Lethal effect of glucose load on malignant cells

    International Nuclear Information System (INIS)

    Shmakova, N.L.; Yarmonenko, S.P.; Kozubek, S.

    1987-01-01

    Ehrlich ascites tumor (EAT) cells were treated with glucose load under anoxic conditions (for 15 or 60 min) and/or with γ radiation (20 Gy). The efficiency of the treatment was judged from the tumorigenic activity of EAT cell inocula. The markedly increased efficiency of the combined treatment of EAT cells using glucose load in anoxia and γ radiation is due to the additive action of both agents. The glucose load in anoxia leads to extensive desintegration of tumor cells. Further, the lethal effect of various pH values on EAT cells was investigated. Different pH values were obtained by means of both glucose load and phosphate buffers. The effect was investigated by determining the tumorigenic activity of EAT cells tested in vivo in mice and by determining the radiosensitivity of treated EAT cells. The results allowed us to conclude that the same values of pH lead to the same effect on EAT cells independently of the way by which the given pH value was reached. (author). 5 figs., 2 tabs., 12 refs

  9. Lethal Lullabies: A History of Opium Use in Infants.

    Science.gov (United States)

    Obladen, Michael

    2016-02-01

    Poppy extract accompanied the human infant for more than 3 millenia. Motives for its use included excessive crying, suspected pain, and diarrhea. In antiquity, infantile sleeplessness was regarded as a disease. When treatment with opium was recommended by Galen, Rhazes, and Avicenna, baby sedation made its way into early medical treatises and pediatric instructions. Dabbing maternal nipples with bitter substances and drugging the infant with opium were used to hasten weaning. A freerider of gum lancing, opiates joined the treatment of difficult teething in the 17th century. Foundling hospitals and wet-nurses used them extensively. With industrialization, private use was rampant among the working class. In German-speaking countries, poppy extracts were administered in soups and pacifiers. In English-speaking countries, proprietary drugs containing opium were marketed under names such as soothers, nostrums, anodynes, cordials, preservatives, and specifics and sold at the doorstep or in grocery stores. Opium's toxicity for infants was common knowledge; thousands of cases of lethal intoxication had been reported from antiquity. What is remarkable is that the willingness to use it in infants persisted and that physicians continued to prescribe it for babies. Unregulated trade, and even that protected by governments, led to greatly increased private use of opiates during the 19th century. Intoxication became a significant factor in infant mortality. As late as 1912, the International Hague Convention forced governments to implement legislation that effectively curtailed access to opium and broke the dangerous habit of sedating infants. © The Author(s) 2015.

  10. Sticky foam as a less-than-lethal technology

    Energy Technology Data Exchange (ETDEWEB)

    Scott, S.H.

    1996-12-31

    Sandia National Labs (SNL) in 1994 completed a project funded by the National Institute of Justice (NIJ) to determine the applicability of sticky foam for correctional applications. Sticky foam is an extremely tacky, tenacious material used to block, entangle, and impair individuals. The NIJ project developed a gun capable of firing multiple shots of sticky foam, tested the gun and sticky foam effectiveness on SNL volunteers acting out prison and law enforcement scenarios, and had the gun and sticky foam evaluated by correctional representatives. Based on the NIJ project work, SNL supported the Marine Corps Mission, Operation United Shield, with sticky foam guns and supporting equipment to assist in the withdrawal of UN Peacekeepers from Somalia. Prior to the loan of the equipment, the Marines were given training in sticky foam characterization, toxicology, safety issues, cleanup and waste disposal, use limitations, use protocol and precautions, emergency facial clean-up, skin cleanup, gun filling, targeting and firing, and gun cleaning. The Marine Corps successfully used the sticky foam guns as part of that operation. This paper describes these recent developments of sticky foam for non-lethal uses and some of the lessons learned from scenario and application testing.

  11. Single board system for fuzzy inference

    Science.gov (United States)

    Symon, James R.; Watanabe, Hiroyuki

    1991-01-01

    The very large scale integration (VLSI) implementation of a fuzzy logic inference mechanism allows the use of rule-based control and decision making in demanding real-time applications. Researchers designed a full custom VLSI inference engine. The chip was fabricated using CMOS technology. The chip consists of 688,000 transistors of which 476,000 are used for RAM memory. The fuzzy logic inference engine board system incorporates the custom designed integrated circuit into a standard VMEbus environment. The Fuzzy Logic system uses Transistor-Transistor Logic (TTL) parts to provide the interface between the Fuzzy chip and a standard, double height VMEbus backplane, allowing the chip to perform application process control through the VMEbus host. High level C language functions hide details of the hardware system interface from the applications level programmer. The first version of the board was installed on a robot at Oak Ridge National Laboratory in January of 1990.

  12. A Learning Algorithm for Multimodal Grammar Inference.

    Science.gov (United States)

    D'Ulizia, A; Ferri, F; Grifoni, P

    2011-12-01

    The high costs of development and maintenance of multimodal grammars in integrating and understanding input in multimodal interfaces lead to the investigation of novel algorithmic solutions in automating grammar generation and in updating processes. Many algorithms for context-free grammar inference have been developed in the natural language processing literature. An extension of these algorithms toward the inference of multimodal grammars is necessary for multimodal input processing. In this paper, we propose a novel grammar inference mechanism that allows us to learn a multimodal grammar from its positive samples of multimodal sentences. The algorithm first generates the multimodal grammar that is able to parse the positive samples of sentences and, afterward, makes use of two learning operators and the minimum description length metrics in improving the grammar description and in avoiding the over-generalization problem. The experimental results highlight the acceptable performances of the algorithm proposed in this paper since it has a very high probability of parsing valid sentences.

  13. Statistical inference based on divergence measures

    CERN Document Server

    Pardo, Leandro

    2005-01-01

    The idea of using functionals of Information Theory, such as entropies or divergences, in statistical inference is not new. However, in spite of the fact that divergence statistics have become a very good alternative to the classical likelihood ratio test and the Pearson-type statistic in discrete models, many statisticians remain unaware of this powerful approach.Statistical Inference Based on Divergence Measures explores classical problems of statistical inference, such as estimation and hypothesis testing, on the basis of measures of entropy and divergence. The first two chapters form an overview, from a statistical perspective, of the most important measures of entropy and divergence and study their properties. The author then examines the statistical analysis of discrete multivariate data with emphasis is on problems in contingency tables and loglinear models using phi-divergence test statistics as well as minimum phi-divergence estimators. The final chapter looks at testing in general populations, prese...

  14. Grammatical inference algorithms, routines and applications

    CERN Document Server

    Wieczorek, Wojciech

    2017-01-01

    This book focuses on grammatical inference, presenting classic and modern methods of grammatical inference from the perspective of practitioners. To do so, it employs the Python programming language to present all of the methods discussed. Grammatical inference is a field that lies at the intersection of multiple disciplines, with contributions from computational linguistics, pattern recognition, machine learning, computational biology, formal learning theory and many others. Though the book is largely practical, it also includes elements of learning theory, combinatorics on words, the theory of automata and formal languages, plus references to real-world problems. The listings presented here can be directly copied and pasted into other programs, thus making the book a valuable source of ready recipes for students, academic researchers, and programmers alike, as well as an inspiration for their further development.>.

  15. Automatic transformations in the inference process

    Energy Technology Data Exchange (ETDEWEB)

    Veroff, R. L.

    1980-07-01

    A technique for incorporating automatic transformations into processes such as the application of inference rules, subsumption, and demodulation provides a mechanism for improving search strategies for theorem proving problems arising from the field of program verification. The incorporation of automatic transformations into the inference process can alter the search space for a given problem, and is particularly useful for problems having broad rather than deep proofs. The technique can also be used to permit the generation of inferences that might otherwise be blocked and to build some commutativity or associativity into the unification process. Appropriate choice of transformations, and new literal clashing and unification algorithms for applying them, showed significant improvement on several real problems according to several distinct criteria. 22 references, 1 figure.

  16. Uncertainty in prediction and in inference

    International Nuclear Information System (INIS)

    Hilgevoord, J.; Uffink, J.

    1991-01-01

    The concepts of uncertainty in prediction and inference are introduced and illustrated using the diffraction of light as an example. The close relationship between the concepts of uncertainty in inference and resolving power is noted. A general quantitative measure of uncertainty in inference can be obtained by means of the so-called statistical distance between probability distributions. When applied to quantum mechanics, this distance leads to a measure of the distinguishability of quantum states, which essentially is the absolute value of the matrix element between the states. The importance of this result to the quantum mechanical uncertainty principle is noted. The second part of the paper provides a derivation of the statistical distance on the basis of the so-called method of support

  17. Examples in parametric inference with R

    CERN Document Server

    Dixit, Ulhas Jayram

    2016-01-01

    This book discusses examples in parametric inference with R. Combining basic theory with modern approaches, it presents the latest developments and trends in statistical inference for students who do not have an advanced mathematical and statistical background. The topics discussed in the book are fundamental and common to many fields of statistical inference and thus serve as a point of departure for in-depth study. The book is divided into eight chapters: Chapter 1 provides an overview of topics on sufficiency and completeness, while Chapter 2 briefly discusses unbiased estimation. Chapter 3 focuses on the study of moments and maximum likelihood estimators, and Chapter 4 presents bounds for the variance. In Chapter 5, topics on consistent estimator are discussed. Chapter 6 discusses Bayes, while Chapter 7 studies some more powerful tests. Lastly, Chapter 8 examines unbiased and other tests. Senior undergraduate and graduate students in statistics and mathematics, and those who have taken an introductory cou...

  18. Inferences from counterfactual threats and promises.

    Science.gov (United States)

    Egan, Suzanne M; Byrne, Ruth M J

    2012-01-01

    We examine how people understand and reason from counterfactual threats, for example, "if you had hit your sister, I would have grounded you" and counterfactual promises, for example, "if you had tidied your room, I would have given you ice-cream." The first experiment shows that people consider counterfactual threats, but not counterfactual promises, to have the illocutionary force of an inducement. They also make the immediate inference that the action mentioned in the "if" part of the counterfactual threat and promise did not occur. The second experiment shows that people make more negative inferences (modus tollens and denial of the antecedent) than affirmative inferences (modus ponens and affirmation of the consequent) from counterfactual threats and promises, unlike indicative threats and promises. We discuss the implications of the results for theories of the mental representations and cognitive processes that underlie conditional inducements.

  19. Synthetic Biology Guides Biofuel Production

    Directory of Open Access Journals (Sweden)

    Michael R. Connor

    2010-01-01

    Full Text Available The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges.

  20. Synthetic Fourier transform light scattering.

    Science.gov (United States)

    Lee, Kyeoreh; Kim, Hyeon-Don; Kim, Kyoohyun; Kim, Youngchan; Hillman, Timothy R; Min, Bumki; Park, Yongkeun

    2013-09-23

    We present synthetic Fourier transform light scattering, a method for measuring extended angle-resolved light scattering (ARLS) from individual microscopic samples. By measuring the light fields scattered from the sample plane and numerically synthesizing them in Fourier space, the angle range of the ARLS patterns is extended up to twice the numerical aperture of the imaging system with unprecedented sensitivity and precision. Extended ARLS patterns of individual microscopic polystyrene beads, healthy human red blood cells (RBCs), and Plasmodium falciparum-parasitized RBCs are presented.

  1. Synthetic carbonaceous fuels and feedstocks

    Science.gov (United States)

    Steinberg, Meyer

    1980-01-01

    This invention relates to the use of a three compartment electrolytic cell in the production of synthetic carbonaceous fuels and chemical feedstocks such as gasoline, methane and methanol by electrolyzing an aqueous sodium carbonate/bicarbonate solution, obtained from scrubbing atmospheric carbon dioxide with an aqueous sodium hydroxide solution, whereby the hydrogen generated at the cathode and the carbon dioxide liberated in the center compartment are combined thermocatalytically into methanol and gasoline blends. The oxygen generated at the anode is preferably vented into the atmosphere, and the regenerated sodium hydroxide produced at the cathode is reused for scrubbing the CO.sub.2 from the atmosphere.

  2. Synthetic Biology Guides Biofuel Production

    Science.gov (United States)

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  3. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Villagómez Hoyos, Carlos Armando

    The main objective of this project was to continue the development of a synthetic aperture vector flow estimator. This type of estimator is capable of overcoming two of the major limitations in conventional ultrasound systems: 1) the inability to scan large region of interest with high temporal......, this thesis showed that novel information can be obtained with vector velocity methods providing quantitative estimates of blood flow and insight into the complexity of the hemodynamics dynamics. This could give the clinician a new tool in assessment and treatment of a broad range of diseases....

  4. Synthetic Aperture Vector Flow Imaging

    DEFF Research Database (Denmark)

    Oddershede, Niels

    2008-01-01

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

  5. Protease-Sensitive Synthetic Prions

    OpenAIRE

    Colby, David W.; Wain, Rachel; Baskakov, Ilia V.; Legname, Giuseppe; Palmer, Christina G.; Nguyen, Hoang-Oanh B.; Lemus, Azucena; Cohen, Fred E.; DeArmond, Stephen J.; Prusiner, Stanley B.

    2010-01-01

    Prions arise when the cellular prion protein (PrPC) undergoes a self-propagating conformational change; the resulting infectious conformer is designated PrPSc. Frequently, PrPSc 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 no...

  6. IMAGINE: Interstellar MAGnetic field INference Engine

    Science.gov (United States)

    Steininger, Theo

    2018-03-01

    IMAGINE (Interstellar MAGnetic field INference Engine) performs inference on generic parametric models of the Galaxy. The modular open source framework uses highly optimized tools and technology such as the MultiNest sampler (ascl:1109.006) and the information field theory framework NIFTy (ascl:1302.013) to create an instance of the Milky Way based on a set of parameters for physical observables, using Bayesian statistics to judge the mismatch between measured data and model prediction. The flexibility of the IMAGINE framework allows for simple refitting for newly available data sets and makes state-of-the-art Bayesian methods easily accessible particularly for random components of the Galactic magnetic field.

  7. Improved Inference of Heteroscedastic Fixed Effects Models

    Directory of Open Access Journals (Sweden)

    Afshan Saeed

    2016-12-01

    Full Text Available Heteroscedasticity is a stern problem that distorts estimation and testing of panel data model (PDM. Arellano (1987 proposed the White (1980 estimator for PDM with heteroscedastic errors but it provides erroneous inference for the data sets including high leverage points. In this paper, our attempt is to improve heteroscedastic consistent covariance matrix estimator (HCCME for panel dataset with high leverage points. To draw robust inference for the PDM, our focus is to improve kernel bootstrap estimators, proposed by Racine and MacKinnon (2007. The Monte Carlo scheme is used for assertion of the results.

  8. Inferring causality from noisy time series data

    DEFF Research Database (Denmark)

    Mønster, Dan; Fusaroli, Riccardo; Tylén, Kristian

    2016-01-01

    Convergent Cross-Mapping (CCM) has shown high potential to perform causal inference in the absence of models. We assess the strengths and weaknesses of the method by varying coupling strength and noise levels in coupled logistic maps. We find that CCM fails to infer accurate coupling strength...... and even causality direction in synchronized time-series and in the presence of intermediate coupling. We find that the presence of noise deterministically reduces the level of cross-mapping fidelity, while the convergence rate exhibits higher levels of robustness. Finally, we propose that controlled noise...

  9. Likelihood inference for unions of interacting discs

    DEFF Research Database (Denmark)

    Møller, Jesper; Helisova, K.

    2010-01-01

    This is probably the first paper which discusses likelihood inference for a random set using a germ-grain model, where the individual grains are unobservable, edge effects occur and other complications appear. We consider the case where the grains form a disc process modelled by a marked point...... with respect to a given marked Poisson model (i.e. a Boolean model). We show how edge effects and other complications can be handled by considering a certain conditional likelihood. Our methodology is illustrated by analysing Peter Diggle's heather data set, where we discuss the results of simulation......-based maximum likelihood inference and the effect of specifying different reference Poisson models....

  10. Declines in the lethality of suicide attempts explain the decline in suicide deaths in Australia.

    Directory of Open Access Journals (Sweden)

    Matthew J Spittal

    Full Text Available BACKGROUND: To investigate the epidemiology of a steep decrease in the incidence of suicide deaths in Australia. METHODS: National data on suicide deaths and deliberate self-harm for the period 1994-2007 were obtained from the Australian Institute of Health and Welfare. We calculated attempt and death rates for five major methods and the lethality of these methods. Negative binomial regression was used to estimate the size and significance of method-specific time-trends in attempts and lethality. RESULTS: Hanging, motor vehicle exhaust and firearms were the most lethal methods, and together accounted for 72% of all deaths. The lethality of motor vehicle exhaust attempts decreased sharply (RR = 0.94 per year, 95% CI 0.93-0.95 while the motor vehicle exhaust attempt rate changed little; this combination of motor vehicle exhaust trends explained nearly half of the overall decline in suicide deaths. Hanging lethality also decreased sharply (RR = 0.96 per year, 95% CI 0.956-0.965 but large increases in hanging attempts negated the effect on death rates. Firearm lethality changed little while attempts decreased. CONCLUSION: Declines in the lethality of suicide attempts-especially attempts by motor vehicle exhaust and hanging-explain the remarkable decline in deaths by suicide in Australia since 1997.

  11. Tracking the emergence of synthetic biology.

    Science.gov (United States)

    Shapira, Philip; Kwon, Seokbeom; Youtie, Jan

    2017-01-01

    Synthetic biology is an emerging domain that combines biological and engineering concepts and which has seen rapid growth in research, innovation, and policy interest in recent years. This paper contributes to efforts to delineate this emerging domain by presenting a newly constructed bibliometric definition of synthetic biology. Our approach is dimensioned from a core set of papers in synthetic biology, using procedures to obtain benchmark synthetic biology publication records, extract keywords from these benchmark records, and refine the keywords, supplemented with articles published in dedicated synthetic biology journals. We compare our search strategy with other recent bibliometric approaches to define synthetic biology, using a common source of publication data for the period from 2000 to 2015. The paper details the rapid growth and international spread of research in synthetic biology in recent years, demonstrates that diverse research disciplines are contributing to the multidisciplinary development of synthetic biology research, and visualizes this by profiling synthetic biology research on the map of science. We further show the roles of a relatively concentrated set of research sponsors in funding the growth and trajectories of synthetic biology. In addition to discussing these analyses, the paper notes limitations and suggests lines for further work.

  12. Repurposing ribosomes for synthetic biology.

    Science.gov (United States)

    Liu, Yi; Kim, Do Soon; Jewett, Michael C

    2017-10-01

    The translation system is the cell's factory for protein biosynthesis, stitching together hundreds to thousands of amino acids into proteins, which are required for the structure, function, and regulation of living systems. The extraordinary synthetic capability of this system, which includes the ribosome and its associated factors required for polymerization, has driven extensive efforts to harness it for societal use in areas as diverse as energy, materials, and medicine. A powerful example is recombinant protein production, which has impacted the lives of patients through the synthesis of biopharmaceuticals such as insulin. In nature, however, only limited sets of monomers are utilized, thereby resulting in limited sets of biopolymers (i.e., proteins). Expanding nature's repertoire of ribosomal monomers could yield new classes of enzymes, therapeutics, materials, and chemicals with diverse, genetically encoded chemistry. Here, we discuss recent progress towards engineering ribosomes both in vivo and in vitro. These fundamental and technical breakthroughs open doors for advanced applications in biotechnology and synthetic biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. DNA recognition by synthetic constructs.

    Science.gov (United States)

    Pazos, Elena; Mosquera, Jesús; Vázquez, M Eugenio; Mascareñas, José L

    2011-09-05

    The interaction of transcription factors with specific DNA sites is key for the regulation of gene expression. Despite the availability of a large body of structural data on protein-DNA complexes, we are still far from fully understanding the molecular and biophysical bases underlying such interactions. Therefore, the development of non-natural agents that can reproduce the DNA-recognition properties of natural transcription factors remains a major and challenging goal in chemical biology. In this review we summarize the basics of double-stranded DNA recognition by transcription factors, and describe recent developments in the design and preparation of synthetic DNA binders. We mainly focus on synthetic peptides that have been designed by following the DNA interaction of natural proteins, and we discuss how the tools of organic synthesis can be used to make artificial constructs equipped with functionalities that introduce additional properties to the recognition process, such as sensing and controllability. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Towards developing algal synthetic biology.

    Science.gov (United States)

    Scaife, Mark Aden; Smith, Alison Gail

    2016-06-15

    The genetic, physiological and metabolic diversity of microalgae has driven fundamental research into photosynthesis, flagella structure and function, and eukaryotic evolution. Within the last 10 years these organisms have also been investigated as potential biotechnology platforms, for example to produce high value compounds such as long chain polyunsaturated fatty acids, pigments and antioxidants, and for biodiesel precursors, in particular triacylglycerols (TAGs). Transformation protocols, molecular tools and genome sequences are available for a number of model species including the green alga Chlamydomonas reinhardtii and the diatom Phaeodactylum tricornutum, although for both species there are bottlenecks to be overcome to allow rapid and predictable genetic manipulation. One approach to do this would be to apply the principles of synthetic biology to microalgae, namely the cycle of Design-Build-Test, which requires more robust, predictable and high throughput methods. In this mini-review we highlight recent progress in the areas of improving transgene expression, genome editing, identification and design of standard genetic elements (parts), and the use of microfluidics to increase throughput. We suggest that combining these approaches will provide the means to establish algal synthetic biology, and that application of standard parts and workflows will avoid parallel development and capitalize on lessons learned from other systems. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  15. Shape analysis of synthetic diamond

    CERN Document Server

    Mullan, C

    1997-01-01

    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...

  16. Photoreactivable sector of lethal damage in ultraviolet-irradiated Escherichia coli cells

    International Nuclear Information System (INIS)

    Balgavy, P.

    1976-01-01

    The photoreactivable sector of lethal damage in Escherichia coli Bsub(s-1), Escherichia coli B/r Hcr - and Escherichia coli B/r Hcr + cells after ultraviolet irradiation at 254 nm is 0.823 +- 0.004, 0.70 +- 0.01 and 0.53 +- 0.06, respectively, at 99% confidence limits. For the low values of the photoreactivable sector in the B/r Hcr - and B/r Hcr + strains are likely to be responsible dark repair processes which eliminate lethal damage, brought about by pyrimidine dimers, preferably in comparison with lethal damage caused by photoproducts of another type. (author)

  17. 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

  18. Analyzing temporal variation in the lethality of ETA

    Directory of Open Access Journals (Sweden)

    Sánchez-Cuenca, Ignacio

    2009-12-01

    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.

  19. Activated entomopathogenic nematode infective juveniles release lethal venom proteins.

    Directory of Open Access Journals (Sweden)

    Dihong Lu

    2017-04-01

    Full Text Available Entomopathogenic nematodes (EPNs are unique parasites due to their symbiosis with entomopathogenic bacteria and their ability to kill insect hosts quickly after infection. It is widely believed that EPNs rely on their bacterial partners for killing hosts. Here we disproved this theory by demonstrating that the in vitro activated infective juveniles (IJs of Steinernema carpocapsae (a well-studied EPN species release venom proteins that are lethal to several insects including Drosophila melanogaster. We confirmed that the in vitro activation is a good approximation of the in vivo process by comparing the transcriptomes of individual in vitro and in vivo activated IJs. We further analyzed the transcriptomes of non-activated and activated IJs and revealed a dramatic shift in gene expression during IJ activation. We also analyzed the venom proteome using mass spectrometry. Among the 472 venom proteins, proteases and protease inhibitors are especially abundant, and toxin-related proteins such as Shk domain-containing proteins and fatty acid- and retinol-binding proteins are also detected, which are potential candidates for suppressing the host immune system. Many of the venom proteins have conserved orthologs in vertebrate-parasitic nematodes and are differentially expressed during IJ activation, suggesting conserved functions in nematode parasitism. In summary, our findings strongly support a new model that S. carpocapsae and likely other Steinernema EPNs have a more active role in contributing to the pathogenicity of the nematode-bacterium complex than simply relying on their symbiotic bacteria. Furthermore, we propose that EPNs are a good model system for investigating vertebrate- and human-parasitic nematodes, especially regarding the function of excretory/secretory products.

  20. Double jeopardy in inferring cognitive processes.

    Science.gov (United States)

    Fific, Mario

    2014-01-01

    Inferences we make about underlying cognitive processes can be jeopardized in two ways due to problematic forms of aggregation. First, averaging across individuals is typically considered a very useful tool for removing random variability. The threat is that averaging across subjects leads to averaging across different cognitive strategies, thus harming our inferences. The second threat comes from the construction of inadequate research designs possessing a low diagnostic accuracy of cognitive processes. For that reason we introduced the systems factorial technology (SFT), which has primarily been designed to make inferences about underlying processing order (serial, parallel, coactive), stopping rule (terminating, exhaustive), and process dependency. SFT proposes that the minimal research design complexity to learn about n number of cognitive processes should be equal to 2 (n) . In addition, SFT proposes that (a) each cognitive process should be controlled by a separate experimental factor, and (b) The saliency levels of all factors should be combined in a full factorial design. In the current study, the author cross combined the levels of jeopardies in a 2 × 2 analysis, leading to four different analysis conditions. The results indicate a decline in the diagnostic accuracy of inferences made about cognitive processes due to the presence of each jeopardy in isolation and when combined. The results warrant the development of more individual subject analyses and the utilization of full-factorial (SFT) experimental designs.

  1. Colligation, Or the Logical Inference of Interconnection

    DEFF Research Database (Denmark)

    Falster, Peter

    1998-01-01

    laws or assumptions. Yet interconnection as an abstract concept seems to be without scientific underpinning in pure logic. Adopting a historical viewpoint, our aim is to show that the reasoning of interconnection may be identified with a neglected kind of logical inference, called "colligation...

  2. Colligation or, The Logical Inference of Interconnection

    DEFF Research Database (Denmark)

    Franksen, Ole Immanuel; Falster, Peter

    2000-01-01

    laws or assumptions. Yet interconnection as an abstract concept seems to be without scientific underpinning in oure logic. Adopting a historical viewpoint, our aim is to show that the reasoning of interconnection may be identified with a neglected kind of logical inference, called "colligation...

  3. Investigating Mathematics Teachers' Thoughts of Statistical Inference

    Science.gov (United States)

    Yang, Kai-Lin

    2012-01-01

    Research on statistical cognition and application suggests that statistical inference concepts are commonly misunderstood by students and even misinterpreted by researchers. Although some research has been done on students' misunderstanding or misconceptions of confidence intervals (CIs), few studies explore either students' or mathematics…

  4. Theory change and Bayesian statistical inference

    NARCIS (Netherlands)

    Romeijn, Jan-Willem

    2005-01-01

    This paper addresses the problem that Bayesian statistical inference cannot accommodate theory change, and proposes a framework for dealing with such changes. It first presents a scheme for generating predictions from observations by means of hypotheses. An example shows how the hypotheses represent

  5. lems that arise in statistical inference. Ther

    African Journals Online (AJOL)

    Administrateur

    ample, may require the integration of the nuisance parameters. Also, several optimization problems in statistical inference use numerical integration steps, such as EM algorithm in [6] and [2]. Here we are concerned with simulation based integration methods that uses the generation of random variables. Such methods are.

  6. Eleusis: complexity and interaction in inductive inference

    NARCIS (Netherlands)

    Kurzen, L.; Arrazola, X.; Ponte, M.

    2010-01-01

    This paper analyzes the computational complexity of the inductive inference game Eleusis. Eleusis is a card game in which one player constructs a secret rule which has to be discovered by the other players. We determine the complexity of various decision problems that arise in Eleusis. We show that

  7. Quasi-Experimental Designs for Causal Inference

    Science.gov (United States)

    Kim, Yongnam; Steiner, Peter

    2016-01-01

    When randomized experiments are infeasible, quasi-experimental designs can be exploited to evaluate causal treatment effects. The strongest quasi-experimental designs for causal inference are regression discontinuity designs, instrumental variable designs, matching and propensity score designs, and comparative interrupted time series designs. This…

  8. Conditional Inference and Advanced Mathematical Study

    Science.gov (United States)

    Inglis, Matthew; Simpson, Adrian

    2008-01-01

    Many mathematicians and curriculum bodies have argued in favour of the theory of formal discipline: that studying advanced mathematics develops one's ability to reason logically. In this paper we explore this view by directly comparing the inferences drawn from abstract conditional statements by advanced mathematics students and well-educated arts…

  9. Culture and Pragmatic Inference in Interpersonal Communication

    African Journals Online (AJOL)

    cognitive process, and that the human capacity for inference is crucially important in interpersonal communication in these contexts. Generally, communication involves 'the transmission of messages between individuals acting consciously and intentionally for that end' (Harder, 2009, p. 62). It is an integral part of our ...

  10. Understanding COBOL systems using inferred types

    NARCIS (Netherlands)

    A. van Deursen (Arie); L.M.F. Moonen (Leon)

    1999-01-01

    textabstractIn a typical COBOL program, the data division consists of 50 of the lines of code. Automatic type inference can help to understand the large collections of variable declarations contained therein, showing how variables are related based on their actual usage. The most problematic aspect

  11. Efficient Bayesian inference for ARFIMA processes

    Science.gov (United States)

    Graves, T.; Gramacy, R. B.; Franzke, C. L. E.; Watkins, N. W.

    2015-03-01

    Many geophysical quantities, like atmospheric temperature, water levels in rivers, and wind speeds, have shown evidence of long-range dependence (LRD). LRD means that these quantities experience non-trivial temporal memory, which potentially enhances their predictability, but also hampers the detection of externally forced trends. Thus, it is important to reliably identify whether or not a system exhibits LRD. In this paper we present a modern and systematic approach to the inference of LRD. Rather than Mandelbrot's fractional Gaussian noise, we use the more flexible Autoregressive Fractional Integrated Moving Average (ARFIMA) model which is widely used in time series analysis, and of increasing interest in climate science. Unlike most previous work on the inference of LRD, which is frequentist in nature, we provide a systematic treatment of Bayesian inference. In particular, we provide a new approximate likelihood for efficient parameter inference, and show how nuisance parameters (e.g. short memory effects) can be integrated over in order to focus on long memory parameters, and hypothesis testing more directly. We illustrate our new methodology on the Nile water level data, with favorable comparison to the standard estimators.

  12. Diet elucidation: Supplementary inferences from mysid feeding ...

    African Journals Online (AJOL)

    Comparison of the structure of the feeding appendages of these two marine mysid species allows dietary inferences supplementing data derived from gut content analyses. Both species occur in abundance in the surf zone off sandy beaches where they contribute significantly to energy transfer through the food web.

  13. Theory Change and Bayesian Statistical Inference

    NARCIS (Netherlands)

    Romeyn, Jan-Willem

    2008-01-01

    This paper addresses the problem that Bayesian statistical inference cannot accommodate theory change, and proposes a framework for dealing with such changes. It first presents a scheme for generating predictions from observations by means of hypotheses. An example shows how the hypotheses represent

  14. Ignorability in Statistical and Probabilistic Inference

    DEFF Research Database (Denmark)

    Jaeger, Manfred

    2005-01-01

    When dealing with incomplete data in statistical learning, or incomplete observations in probabilistic inference, one needs to distinguish the fact that a certain event is observed from the fact that the observed event has happened. Since the modeling and computational complexities entailed by ma...

  15. Spurious correlations and inference in landscape genetics

    Science.gov (United States)

    Samuel A. Cushman; Erin L. Landguth

    2010-01-01

    Reliable interpretation of landscape genetic analyses depends on statistical methods that have high power to identify the correct process driving gene flow while rejecting incorrect alternative hypotheses. Little is known about statistical power and inference in individual-based landscape genetics. Our objective was to evaluate the power of causalmodelling with partial...

  16. Abduction and Inference to the Best Explanation

    Directory of Open Access Journals (Sweden)

    Valeriano Iranzo

    2009-12-01

    Full Text Available The paper deals with the relation between abduction and inference to the best explanation (IBE. A heuristic and a normative interpretation of IBE are distinguished. Besides, two different normative interpretations —those vindicated by I. Niiniluoto and S. Psillos— are discussed. I conclude that, in principle, Aliseda’s theory of abduction fits better with a heuristic account of IBE

  17. Supplementary inferences from mysid feeding appendage morphology

    African Journals Online (AJOL)

    Diet elucidation: Supplementary inferences from mysid feeding appendage morphology. P. Webb* and T.H. Wooldridge. Institute of Coastal Research and Department of Zoology, University of Port Elizabeth, P.O. Box 1600, Port Elizabeth,. 6000 Republic of South Africa. Received 9 August 1988; accepted 24 October 1988.

  18. Inference and the Introductory Statistics Course

    Science.gov (United States)

    Pfannkuch, Maxine; Regan, Matt; Wild, Chris; Budgett, Stephanie; Forbes, Sharleen; Harraway, John; Parsonage, Ross

    2011-01-01

    This article sets out some of the rationale and arguments for making major changes to the teaching and learning of statistical inference in introductory courses at our universities by changing from a norm-based, mathematical approach to more conceptually accessible computer-based approaches. The core problem of the inferential argument with its…

  19. Protein Inference Using Peptide Quantification Patterns

    NARCIS (Netherlands)

    Lukasse, P.N.J.; America, A.H.P.

    2014-01-01

    Determining the list of proteins present in a sample, based on the list of identified peptides, is a crucial step in the untargeted proteomics LC-MS/MS data-processing pipeline. This step, commonly referred to as protein inference, turns out to be a very challenging problem because many peptide

  20. Inferring motion and location using WLAN RSSI

    NARCIS (Netherlands)

    Kavitha Muthukrishnan, K.; van der Zwaag, B.J.; Havinga, Paul J.M.; Fuller, R.; Koutsoukos, X.

    2009-01-01

    We present novel algorithms to infer movement by making use of inherent fluctuations in the received signal strengths from existing WLAN infrastructure. We evaluate the performance of the presented algorithms based on classification metrics such as recall and precision using annotated traces

  1. Creating biological nanomaterials using synthetic biology.

    Science.gov (United States)

    Rice, MaryJoe K; Ruder, Warren C

    2014-02-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  2. Word selection affects perceptions of synthetic biology

    Directory of Open Access Journals (Sweden)

    Tonidandel Scott

    2011-07-01

    Full Text Available Abstract Members of the synthetic biology community have discussed the significance of word selection when describing synthetic biology to the general public. In particular, many leaders proposed the word "create" was laden with negative connotations. We found that word choice and framing does affect public perception of synthetic biology. In a controlled experiment, participants perceived synthetic biology more negatively when "create" was used to describe the field compared to "construct" (p = 0.008. Contrary to popular opinion among synthetic biologists, however, low religiosity individuals were more influenced negatively by the framing manipulation than high religiosity people. Our results suggest that synthetic biologists directly influence public perception of their field through avoidance of the word "create".

  3. Synthetic biology - the state of play.

    Science.gov (United States)

    Kitney, Richard; Freemont, Paul

    2012-07-16

    Just over two years ago there was an article in Nature entitled "Five Hard Truths for Synthetic Biology". Since then, the field has moved on considerably. A number of economic commentators have shown that synthetic biology very significant industrial potential. This paper addresses key issues in relation to the state of play regarding synthetic biology. It first considers the current background to synthetic biology, whether it is a legitimate field and how it relates to foundational biological sciences. The fact that synthetic biology is a translational field is discussed and placed in the context of the industrial translation process. An important aspect of synthetic biology is platform technology, this topic is also discussed in some detail. Finally, examples of application areas are described. Copyright © 2012. Published by Elsevier B.V.

  4. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Rice, MaryJoe K; Ruder, Warren C

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

  5. Structural influence of gene networks on their inference: analysis of C3NET

    Directory of Open Access Journals (Sweden)

    Emmert-Streib Frank

    2011-06-01

    Full Text Available Abstract Background The availability of large-scale high-throughput data possesses considerable challenges toward their functional analysis. For this reason gene network inference methods gained considerable interest. However, our current knowledge, especially about the influence of the structure of a gene network on its inference, is limited. Results In this paper we present a comprehensive investigation of the structural influence of gene networks on the inferential characteristics of C3NET - a recently introduced gene network inference algorithm. We employ local as well as global performance metrics in combination with an ensemble approach. The results from our numerical study for various biological and synthetic network structures and simulation conditions, also comparing C3NET with other inference algorithms, lead a multitude of theoretical and practical insights into the working behavior of C3NET. In addition, in order to facilitate the practical usage of C3NET we provide an user-friendly R package, called c3net, and describe its functionality. It is available from https://r-forge.r-project.org/projects/c3net and from the CRAN package repository. Conclusions The availability of gene network inference algorithms with known inferential properties opens a new era of large-scale screening experiments that could be equally beneficial for basic biological and biomedical research with auspicious prospects. The availability of our easy to use software package c3net may contribute to the popularization of such methods. Reviewers This article was reviewed by Lev Klebanov, Joel Bader and Yuriy Gusev.

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

    Directory of Open Access Journals (Sweden)

    Stephanie eAscough

    2016-01-01

    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

  7. Active inference, sensory attenuation and illusions.

    Science.gov (United States)

    Brown, Harriet; Adams, Rick A; Parees, Isabel; Edwards, Mark; Friston, Karl

    2013-11-01

    Active inference provides a simple and neurobiologically plausible account of how action and perception are coupled in producing (Bayes) optimal behaviour. This can be seen most easily as minimising prediction error: we can either change our predictions to explain sensory input through perception. Alternatively, we can actively change sensory input to fulfil our predictions. In active inference, this action is mediated by classical reflex arcs that minimise proprioceptive prediction error created by descending proprioceptive predictions. However, this creates a conflict between action and perception; in that, self-generated movements require predictions to override the sensory evidence that one is not actually moving. However, ignoring sensory evidence means that externally generated sensations will not be perceived. Conversely, attending to (proprioceptive and somatosensory) sensations enables the detection of externally generated events but precludes generation of actions. This conflict can be resolved by attenuating the precision of sensory evidence during movement or, equivalently, attending away from the consequences of self-made acts. We propose that this Bayes optimal withdrawal of precise sensory evidence during movement is the cause of psychophysical sensory attenuation. Furthermore, it explains the force-matching illusion and reproduces empirical results almost exactly. Finally, if attenuation is removed, the force-matching illusion disappears and false (delusional) inferences about agency emerge. This is important, given the negative correlation between sensory attenuation and delusional beliefs in normal subjects--and the reduction in the magnitude of the illusion in schizophrenia. Active inference therefore links the neuromodulatory optimisation of precision to sensory attenuation and illusory phenomena during the attribution of agency in normal subjects. It also provides a functional account of deficits in syndromes characterised by false inference

  8. A synthetic zero air standard

    Science.gov (United States)

    Pearce, Ruth

    2016-04-01

    A Synthetic Zero Air Standard R. E. Hill-Pearce, K. V. Resner, D. R. Worton, P. J. Brewer The National Physical Laboratory Teddington, Middlesex TW11 0LW UK We present work towards providing traceability for measurements of high impact greenhouse gases identified by the World Meteorological Organisation (WMO) as critical for global monitoring. Standards for these components are required with challengingly low uncertainties to improve the quality assurance and control processes used for the global networks to better assess climate trends. Currently the WMO compatibility goals require reference standards with uncertainties of < 100 nmolmol-1 for CO2 (northern hemisphere) and < 2 nmolmol-1 for CH4 and CO. High purity zero gas is required for both the balance gas in the preparation of reference standards and for baseline calibrations of instrumentation. Quantification of the amount fraction of the target components in the zero gas is a significant contributor to the uncertainty and is challenging due to limited availability of reference standard at the amount fraction of the measurand and limited analytical techniques with sufficient detection limits. A novel dilutor was used to blend NPL Primary Reference Gas Mixtures containing CO2, CH4 and CO at atmospheric amount fractions with a zero gas under test. Several mixtures were generated with nominal dilution ratios ranging from 2000:1 to 350:1. The baseline of two cavity ring down spectrometers was calibrated using the zero gas under test after purification by oxidative removal of CO and hydrocarbons to < 1 nmolmol-1 (SAES PS15-GC50) followed by the removal of CO2 and water vapour to < 100 pmolmol-1 (SAES MC190). Using the standard addition method.[1] we have quantified the amount fraction of CO, CO2, and CH4 in scrubbed whole air (Scott Marrin) and NPL synthetic zero air. This is the first synthetic zero air standard with a matrix of N2, O2 and Ar closely matching ambient composition with gravimetrically assigned

  9. Synthetic approaches to uniform polymers.

    Science.gov (United States)

    Ali, Monzur; Brocchini, Steve

    2006-12-30

    Uniform polymers are characterised by a narrow molecular weight distribution (MWD). Uniformity is also defined by chemical structure in respect of (1) monomer orientation, sequence and stereo-regularity, (2) polymer shape and morphology and (3) chemical functionality. The function of natural polymers such as polypeptides and polynucleotides is related to their conformational structure (e.g. folded tertiary structure). This is only possible because of their high degree of uniformity. While completely uniform synthetic polymers are rare, polymers with broad structure and MWD are widely used in medicine and the biomedical sciences. They are integral components in final dosage forms, drug delivery systems (DDS) and in implantable devices. Increasingly uniform polymers are being used to develop more complex medicines (e.g. delivery of biopharmaceuticals, enhanced formulations or DDS's for existing actives). In addition to the function imparted by any new polymer it will be required to meet stringent specifications in terms of cost containment, scalability, biocompatibility and performance. Synthetic polymers with therapeutic activity are also being developed to exploit their polyvalent properties, which is not possible with low molecular weight molecules. There is need to utilise uniform polymers for applications where the polymer may interact with the systemic circulation, tissues or cellular environment. There are also potential applications (e.g. stimuli responsive coatings) where uniform polymers may be used for their more defined property profile. While it is not yet practical to prepare synthetic polymers to the same high degree of uniformity as proteins, nature also effectively utilises many polymers with lower degrees of uniformity (e.g. polysaccharides, poly(amino acids), polyhydroxyalkanoates). In recent years it has become possible to prepare with practical experimental protocols sufficient quantities of polymers that display many aspects of uniformity. This

  10. Geo synthetic-reinforced Pavement systems

    International Nuclear Information System (INIS)

    Zornberg, J. G.

    2014-01-01

    Geo synthetics have been used as reinforcement inclusions to improve pavement performance. while there are clear field evidence of the benefit of using geo synthetic reinforcements, the specific conditions or mechanisms that govern the reinforcement of pavements are, at best, unclear and have remained largely unmeasured. Significant research has been recently conducted with the objectives of: (i) determining the relevant properties of geo synthetics that contribute to the enhanced performance of pavement systems, (ii) developing appropriate analytical, laboratory and field methods capable of quantifying the pavement performance, and (iii) enabling the prediction of pavement performance as a function of the properties of the various types of geo synthetics. (Author)

  11. Veterans Affairs Suicide Prevention Synthetic Dataset

    Data.gov (United States)

    Department of Veterans Affairs — The VA's Veteran Health Administration, in support of the Open Data Initiative, is providing the Veterans Affairs Suicide Prevention Synthetic Dataset (VASPSD). The...

  12. Characterization of Synthetic Peptides by Mass Spectrometry

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...

  13. Synthetic biology assemblies for sustainable space exploration

    Data.gov (United States)

    National Aeronautics and Space Administration — The work utilized synthetic biology to create sustainable food production processes by developing technology to efficiently convert inedible crop waste to...

  14. Crystal Structure of Protein Reveals Target for Drugs Against Lethal MERS Virus | FNLCR Staging

    Science.gov (United States)

    A research team of scientists from the National Cancer Institute and the Frederick National Laboratory for Cancer Research recently identified the structure of a key protein of the virus that causes the highly lethal Middle East Respiratory Syndrome.

  15. Comparative influence of dose rate and radiation nature, on lethality after big mammals irradiation

    International Nuclear Information System (INIS)

    Destombe, C.; Le Fleche, Ph.; Grasseau, A.; Reynal, A.

    1997-01-01

    For the same dose and the 30 days lethality as biological criterion, the dose rate influence is more important than the radiation nature on the results of an big mammals total body irradiation. (authors)

  16. The Effects of Posture, Body Armor and Other Equipment on Rifleman Lethality

    National Research Council Canada - National Science Library

    Kramlich, Gary R., II

    2005-01-01

    ...? This study quantifies the effects of Soldier equipment on lethality through multi-factor logistic regression using data from range experiments with the 1st Brigade, 1st Infantry Division (Mechanized...

  17. CDC Vital Signs: Making Health Care Safer -- Stop Infections from Lethal CRE Germs Now

    Science.gov (United States)

    ... Making Health Care Safer Stop Infections from Lethal CRE Germs Now Recommend on Facebook Tweet Share Compartir ... hospitals had at least one patient with a CRE (carbapenem-resistant Enterobacteriaceae) infection during the first half ...

  18. Lethal effects of Helianthemum lippii (L.) on Acanthamoeba castellanii cysts in vitro.

    Science.gov (United States)

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

    2014-06-01

    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.

  19. Synthetic biology: engineering molecular computers

    CERN Document Server

    CERN. Geneva

    2018-01-01

    Complicated systems cannot survive the rigors of a chaotic environment, without balancing mechanisms that sense, decide upon and counteract the exerted disturbances. Especially so with living organisms, forced by competition to incredible complexities, escalating also their self-controlling plight. Therefore, they compute. Can we harness biological mechanisms to create artificial computing systems? Biology offers several levels of design abstraction: molecular machines, cells, organisms... ranging from the more easily-defined to the more inherently complex. At the bottom of this stack we find the nucleic acids, RNA and DNA, with their digital structure and relatively precise interactions. They are central enablers of designing artificial biological systems, in the confluence of engineering and biology, that we call Synthetic biology. In the first part, let us follow their trail towards an overview of building computing machines with molecules -- and in the second part, take the case study of iGEM Greece 201...

  20. Preparation of synthetic standard minerals

    International Nuclear Information System (INIS)

    Herrick, C.C.; Bustamante, S.J.; Charls, R.W.; Cowan, R.E.; Hakkila, E.A.; Hull, D.E.; Olinger, B.W.; Roof, R.B.; Sheinberg, H.; Herrick, G.C.

    1978-01-01

    A number of techniques for synthetic mineral preparations have been examined. These techniques include hot-pressing in graphite dies at moderate pressures, high-pressure, high-temperature synthesis in a piston and cylinder apparatus, isostatic pressing under helium gas pressures, hydrous mineral preparations using water as the pressure medium, explosion-generated shock waves, and radiofrequency heating. Minerals suitable for equation-of-state studies (three-inch, high-density discs), for thermodynamic property determinations (low-density powders) and for microprobe standards (fusion-cast microbeads) have been prepared. Mechanical stress-strain calculations in the piston-cylinder apparatus have been initiated and their integration with thermal stress calculations is currently under investigation

  1. Synthetic biology of antimicrobial discovery

    Science.gov (United States)

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  2. Synthetic aperture interferometry: error analysis

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Amiya; Coupland, Jeremy

    2010-07-10

    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.

  3. Synthetic aperture interferometry: error analysis

    International Nuclear Information System (INIS)

    Biswas, Amiya; Coupland, Jeremy

    2010-01-01

    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.

  4. Targeting cyclin-dependent kinase 1 (CDK1) but not CDK4/6 or CDK2 is selectively lethal to MYC-dependent human breast cancer cells

    International Nuclear Information System (INIS)

    Kang, Jian; Sergio, C Marcelo; Sutherland, Robert L; Musgrove, Elizabeth A

    2014-01-01

    Although MYC is an attractive therapeutic target for breast cancer treatment, it has proven challenging to inhibit MYC directly, and clinically effective pharmaceutical agents targeting MYC are not yet available. An alternative approach is to identify genes that are synthetically lethal in MYC-dependent cancer. Recent studies have identified several cell cycle kinases as MYC synthetic-lethal genes. We therefore investigated the therapeutic potential of specific cyclin-dependent kinase (CDK) inhibition in MYC-driven breast cancer. Using small interfering RNA (siRNA), MYC expression was depleted in 26 human breast cancer cell lines and cell proliferation evaluated by BrdU incorporation. MYC-dependent and MYC-independent cell lines were classified based on their sensitivity to siRNA-mediated MYC knockdown. We then inhibited CDKs including CDK4/6, CDK2 and CDK1 individually using either RNAi or small molecule inhibitors, and compared sensitivity to CDK inhibition with MYC dependence in breast cancer cells. Breast cancer cells displayed a wide range of sensitivity to siRNA-mediated MYC knockdown. The sensitivity was correlated with MYC protein expression and MYC phosphorylation level. Sensitivity to siRNA-mediated MYC knockdown did not parallel sensitivity to the CDK4/6 inhibitor PD0332991; instead MYC-independent cell lines were generally sensitive to PD0332991. Cell cycle arrest induced by MYC knockdown was accompanied by a decrease in CDK2 activity, but inactivation of CDK2 did not selectively affect the viability of MYC-dependent breast cancer cells. In contrast, CDK1 inactivation significantly induced apoptosis and reduced viability of MYC-dependent cells but not MYC- independent cells. This selective induction of apoptosis by CDK1 inhibitors was associated with up-regulation of the pro-apoptotic molecule BIM and was p53-independent. Overall, these results suggest that further investigation of CDK1 inhibition as a potential therapy for MYC-dependent breast cancer

  5. Synthetic Seismograms Derived from Oceanographic Data in the Campeche Canyon, Deepwater Gulf of Mexico

    Science.gov (United States)

    Gonzalez-Orduno, A.; Fucugauchi, J. U.; Monreal, M.; Perez-Cruz, G.; Salas de León, D. A.

    2013-05-01

    The seismic reflection method has been successfully applied worldwide to investigate subsurface conditions to support important business decisions in the oil industry. When applied in the marine environment, useful reflection information is limited to events on and below the sea floor; Information from the water column, if any, is disregarded. Seismic oceanography is emerging as a new technique that utilize the reflection information within the water column to infer thermal-density contrasts associated with oceanographic processes, such as cyclonic-anticyclonic eddies, ascending-descending water flows, and water flows related to rapid topographic changes on the sea floor. A seismic investigation to infer such oceanographic changes in one sector of the Campeche Canyon is in progress as a research matter at the Instituto de Ciencias del Mar y Limnologia from the University of Mexico (UNAM). First steps of the investigation consisted of creating synthetic seismograms based on oceanographic information (temperature and density) derived from direct observation on a series of close spaced depth points along vertical profiles. Details of the selected algorithms used for the transformation of the oceanographic data to acoustic impedances data sets and further construction of synthetic seismograms on each site and their representation as synthetic seismic sections, are presented in this work, as well as the road ahead in the investigation.

  6. Microorganism Utilization for Synthetic Milk

    Science.gov (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.

    2014-01-01

    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

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

    OpenAIRE

    Ya?mur, Ersen Ayd?n; ?zkan, ?zcan; Karaer, K Zafer

    2015-01-01

    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...

  8. Lethal isotherms of cryoablation in a phantom study: effects of heat load, probe size, and number.

    Science.gov (United States)

    Littrup, Peter J; Jallad, Bassel; Vorugu, Vinaya; Littrup, Gunnar; Currier, Brandt; George, Mikhail; Herring, Donald

    2009-10-01

    To assess the effects on the proportions of lethal ice (ie, colder than -30 degrees C) in phantoms with different heat loads created by varying the size and number of cryoprobes spaced 2 cm apart. Thermocouples at 0.5-, 1.0-, and 1.5-cm intervals from 1.7- or 2.4-mm-diameter cryoprobes were held by jigs accommodating a maximum of four cryoprobes. Agar phantoms (N = 24) used three sets of baseline temperatures: approximately 6 degrees C, 24 degrees C, and 39 degrees C. Temperatures during 15-minute freeze cycles were correlated with actual thermocouple locations seen within the ice by computed tomography (CT). Diameters and surface areas of the -30 degrees C lethal isotherm were assessed over time as percentages of the overall ice ball. The high-heat load phantom experiments (39 degrees C) showed the greatest impact on lethal zones by percentage for all probe configurations. At 15 minutes, single-, double-, triple-, and quadruple-probe arrangements of 2.4-mm cryoprobes had average lethal ice diameters of 1.2, 3.3, 4.1, and 4.9 cm, respectively, comprising 13%, 46%, 51%, and 56% surface areas of lethal ice, respectively. Surface areas and diameters of lethal ice made by 1.7-mm cryoprobes were 71% and 84% of those made by 2.4-mm cryoprobes, respectively. Lethal ice resides less than 1 cm behind the leading edge for nearly all probe configurations and heat loads. Single cryoprobes create very low percentages of lethal ice. Multiple cryoprobes overcome the high heat load of body temperature phantoms and help compensate for the lower freeze capacity of thinner cryoprobes.

  9. Flexible, Smart, and Lethal: Adapting US SEAD Doctrine to Changing Threats

    Science.gov (United States)

    2016-01-01

    Summer 2016 | 65 Flexible , Smart, and Lethal Adapting US SEAD Doctrine to Changing Threats 2nd Lt Elliot M. Bucki, USAF* Disclaimer: The views and...difficult than in the past. Moreover, it specifically mentions how the mobility Summer 2016 | 67 Flexible , Smart, and Lethal of an IADS has made... flexibility is built into the targeting process and the ATO.4 Planning that incorporates decentralized execution is critical to any SEAD effort in an A2

  10. Recovery from UV-induced potentially lethal damage in systemic lupus erythematosus skin fibroblasts

    International Nuclear Information System (INIS)

    Zamansky, G.B.

    1986-01-01

    The repair of ultraviolet light-induced potentially lethal damage was investigated in density-inhibited skin fibroblast cell strains derived from patients with systemic lupus erythematosus. The effect of exposure to polychromatic ultraviolet light composed of environmentally relevant wavelengths or to the more commonly studied, short wavelength (254 nm) ultraviolet light was studied. Systemic lupus erythematosus cells, which are hypersensitive to ultraviolet light under growth promoting conditions, were able to repair potentially lethal damage as well as normal cells. (author)

  11. 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

    2014-01-01

    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

  12. Materials Applications for Non-Lethal: Aqueous Foams

    International Nuclear Information System (INIS)

    GOOLSBY, TOMMY D.; SCOTT, STEVEN H.

    1999-01-01

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In the mid-1990s, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate (foaming agent) with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objectives were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might be

  13. Materials Applications for Non-Lethal: Aqueous Foams

    Energy Technology Data Exchange (ETDEWEB)

    GOOLSBY,TOMMY D.; SCOTT,STEVEN H.

    1999-09-15

    High expansion aqueous foam is an aggregation of bubbles that has the appearance of soap suds and is used to isolate individuals both visually and acoustically. It was developed in the 1920's in England to fight coal mine fires and has been widely used since for fire fighting and dust suppression. It was developed at Sandia National Laboratories (SNL) in the 1970's for nuclear safeguards and security applications. In the mid-1990s, the National Institute of Justice (NIJ), the research arm of the Department of Justice, began a project with SNL to determine the applicability of high expansion aqueous foam for correctional applications. NIJ funded the project as part of its search for new and better less-than-lethal weapons for responding to violent and dangerous individuals, where other means of force could lead to serious injuries. The phase one objectives of the project were to select a low-to-no toxicity foam concentrate (foaming agent) with physical characteristics suited for use in a single cell or large prison disturbances, and to determine if the selected foam concentrate could serve as a carrier for Oleoresin Capsicum (OC) irritant. The phase two objectives were to conduct an extensive toxicology review of the selected foam concentrate and OC irritant, and to conduct respiration simulation experiments in the selected high expansion aqueous foam. The phase three objectives were to build a prototype individual cell aqueous foam system and to study the feasibility of aqueous foams for large prison facility disturbances. The phase four and five objectives were to use the prototype system to do large scale foam physical characteristics testing of the selected foam concentrate, and to have the prototype single cell system further evaluated by correctional representatives. Prison rather than street scenarios were evaluated as the first and most likely place for using the aqueous foam since prisons have recurrent incidents where officers and inmates might

  14. Identification of a cryptic lethal mutation in the mouse t(w73) haplotype.

    Science.gov (United States)

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

    2004-12-01

    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.

  15. Reproductive-phase and interphase lethal cell damage after irradiation and treatment with cytostatics

    International Nuclear Information System (INIS)

    Hagemann, G.

    1979-01-01

    After X-ray irradiation of manual cells, two lethal fractions occur due to reproductive and interphase death under low and high radiation doses. The damage kinetics on which this fact is based is compared with hypothetical tumour frequencies and leucemia induction caused in experiments. The reproductive-lethal damage can be manifested by means of colony size spectrometry, with the median colony size class differences (MCD) serving as measure for the damage found. The simultaneous effects of the cytostatics BLEOMYCIN or ICRF 159 and X-rays on reproductive lethal and interphase-lethal damage are measured by means of MCD and survival fraction, and the additive and intensifying effect' is judged with the help of suitably defined terms. This shows that the clinically used ICRF 159 has an additive effect on interphase-lethal and a sub-additive effect on reproductive-lethal cell damage. Thus, favourable results may be expected for the electivity factor in fractionated irradiation and with regard to delayed damage in healthy tissue. (orig.) 891 MG/orig. 892 RDG [de

  16. Genome-wide scale-free network inference for Candida albicans

    Directory of Open Access Journals (Sweden)

    Robert eAltwasser

    2012-02-01

    Full Text Available Discovery of essential genes in pathogenic organisms is an important step in the development of new medication. Despite a growing number of genome data available, still little is known about C. albicans, the major fungal pathogen. Most of the human population carries C. albicans as commensal, but it can cause systemic infection that may lead to the death of the host if the immune system is deteriorated. In many organisms central nodes in the interaction network (hubs play a crucial role for information and energy transport. Indeed, knock-outs of such hubs often leads to lethal phenotypes making them interesting drug targets. To identify these central genes via topological analysis, we inferred gene regulatory networks that are of sparse and scale-free. We collected information from various sources of information as prior knowledge to complement the limited expression data available. We utilise a linear regression algorithm to infer genome-wide gene regulatory interaction networks. To evaluate the predictive power of our approach, we used an automated text-mining system that scanned full-text research papers for known interactions. With the help of the compendium of known interactions, we also optimise the influence of the prior knowledge we obtained and the sparseness of the model to achieve best results. We compare the results of our approach with those of other state-of-the-art network inference methods and show that we outperform these methods. Finally we identified a number of hubs in the genome of the fungus and investigate their biological relevance.

  17. Cytotoxic effect of some natural compounds isolated from Lauraceae plants and synthetic derivatives.

    Science.gov (United States)

    Cuca, Luis Enrique; Coy, Ericsson David; Alarcón, Marlén Andrea; Fernández, Andrés; Aristizábal, Fabio Ancízar

    2011-01-01

    The antiproliferative effect of eleven neolignans, two lignans and one diterpene isolated from three Lauraceae plants, four benzofurans and two bicyclooctanes synthetic derivatives was evaluated in vitro on a set of five human cancer cells from solid tumors with a high incidence in Colombia. To evaluate the cytotoxic effect of twenty compounds on the tumor cell lines HeLa, A-549, Hep-2, PC-3, and MCF-7. MATERIALS AND METHODS. Fourteen natural compounds were isolated by chromatographic techniques from three native Colombian plants (Pleurothyrium cinereum, Ocotea macrophylla and Nectandra amazonum), whose structures were established by spectroscopic methods; six synthetic derivatives were prepared by oxyarylation and diazomethane methylation. Antiproliferative effect and cell recovery were performed by means of in vitro treatment of tumor cell lines with test compounds, evaluating cell viability by resazurin staining. Among test compounds, only neolignans ocophyllal A, cinerin D, kaurenoic acid, two benzofuran-derivatives, and synthetic (-)-cinerin A were found to have antiproliferative effect at different levels. Bicyclooctanoids as well as kaurenoic acid exhibited activity against all human cancer cells while benzofuranoids showed selective activity against HeLa. Furthermore, compounds (-)-cinerin A and kaurenoic acid exhibited total lethal effect against all-five cell lines and PC-3, Hep-2, and A549 cell lines, respectively. Test compounds exhibiting antiproliferative activity showed interesting results, which would promote their use as lead compounds on further studies for anticancer agents development.

  18. Inferences on Children’s Reading Groups

    Directory of Open Access Journals (Sweden)

    Javier González García

    2009-05-01

    Full Text Available This article focuses on the non-literal information of a text, which can be inferred from key elements or clues offered by the text itself. This kind of text is called implicit text or inference, due to the thinking process that it stimulates. The explicit resources that lead to information retrieval are related to others of implicit information, which have increased their relevance. In this study, during two courses, how two teachers interpret three stories and how they establish a debate dividing the class into three student groups, was analyzed. The sample was formed by two classes of two urban public schools of Burgos capital (Spain, and two of public schools of Tampico (Mexico. This allowed us to observe an increasing percentage value of the group focused in text comprehension, and a lesser percentage of the group perceiving comprehension as a secondary objective.

  19. Working with sample data exploration and inference

    CERN Document Server

    Chaffe-Stengel, Priscilla

    2014-01-01

    Managers and analysts routinely collect and examine key performance measures to better understand their operations and make good decisions. Being able to render the complexity of operations data into a coherent account of significant events requires an understanding of how to work well with raw data and to make appropriate inferences. Although some statistical techniques for analyzing data and making inferences are sophisticated and require specialized expertise, there are methods that are understandable and applicable by anyone with basic algebra skills and the support of a spreadsheet package. By applying these fundamental methods themselves rather than turning over both the data and the responsibility for analysis and interpretation to an expert, managers will develop a richer understanding and potentially gain better control over their environment. This text is intended to describe these fundamental statistical techniques to managers, data analysts, and students. Statistical analysis of sample data is enh...

  20. Likelihood inference for unions of interacting discs

    DEFF Research Database (Denmark)

    Møller, Jesper; Helisová, Katarina

    To the best of our knowledge, this is the first paper which discusses likelihood inference or a random set using a germ-grain model, where the individual grains are unobservable edge effects occur, and other complications appear. We consider the case where the grains form a disc process modelled...... is specified with respect to a given marked Poisson model (i.e. a Boolean model). We show how edge effects and other complications can be handled by considering a certain conditional likelihood. Our methodology is illustrated by analyzing Peter Diggle's heather dataset, where we discuss the results...... of simulation-based maximum likelihood inference and the effect of specifying different reference Poisson models....

  1. Bayesianism and inference to the best explanation

    Directory of Open Access Journals (Sweden)

    Valeriano IRANZO

    2008-01-01

    Full Text Available Bayesianism and Inference to the best explanation (IBE are two different models of inference. Recently there has been some debate about the possibility of “bayesianizing” IBE. Firstly I explore several alternatives to include explanatory considerations in Bayes’s Theorem. Then I distinguish two different interpretations of prior probabilities: “IBE-Bayesianism” (IBE-Bay and “frequentist-Bayesianism” (Freq-Bay. After detailing the content of the latter, I propose a rule for assessing the priors. I also argue that Freq-Bay: (i endorses a role for explanatory value in the assessment of scientific hypotheses; (ii avoids a purely subjectivist reading of prior probabilities; and (iii fits better than IBE-Bayesianism with two basic facts about science, i.e., the prominent role played by empirical testing and the existence of many scientific theories in the past that failed to fulfil their promises and were subsequently abandoned.

  2. An emergent approach to analogical inference

    Science.gov (United States)

    Thibodeau, Paul H.; Flusberg, Stephen J.; Glick, Jeremy J.; Sternberg, Daniel A.

    2013-03-01

    In recent years, a growing number of researchers have proposed that analogy is a core component of human cognition. According to the dominant theoretical viewpoint, analogical reasoning requires a specific suite of cognitive machinery, including explicitly coded symbolic representations and a mapping or binding mechanism that operates over these representations. Here we offer an alternative approach: we find that analogical inference can emerge naturally and spontaneously from a relatively simple, error-driven learning mechanism without the need to posit any additional analogy-specific machinery. The results also parallel findings from the developmental literature on analogy, demonstrating a shift from an initial reliance on surface feature similarity to the use of relational similarity later in training. Variants of the model allow us to consider and rule out alternative accounts of its performance. We conclude by discussing how these findings can potentially refine our understanding of the processes that are required to perform analogical inference.

  3. Inferring genetic interactions from comparative fitness data.

    Science.gov (United States)

    Crona, Kristina; Gavryushkin, Alex; Greene, Devin; Beerenwinkel, Niko

    2017-12-20

    Darwinian fitness is a central concept in evolutionary biology. In practice, however, it is hardly possible to measure fitness for all genotypes in a natural population. Here, we present quantitative tools to make inferences about epistatic gene interactions when the fitness landscape is only incompletely determined due to imprecise measurements or missing observations. We demonstrate that genetic interactions can often be inferred from fitness rank orders, where all genotypes are ordered according to fitness, and even from partial fitness orders. We provide a complete characterization of rank orders that imply higher order epistasis. Our theory applies to all common types of gene interactions and facilitates comprehensive investigations of diverse genetic interactions. We analyzed various genetic systems comprising HIV-1, the malaria-causing parasite Plasmodium vivax , the fungus Aspergillus niger , and the TEM-family of β-lactamase associated with antibiotic resistance. For all systems, our approach revealed higher order interactions among mutations.

  4. Pointwise probability reinforcements for robust statistical inference.

    Science.gov (United States)

    Frénay, Benoît; Verleysen, Michel

    2014-02-01

    Statistical inference using machine learning techniques may be difficult with small datasets because of abnormally frequent data (AFDs). AFDs are observations that are much more frequent in the training sample that they should be, with respect to their theoretical probability, and include e.g. outliers. Estimates of parameters tend to be biased towards models which support such data. This paper proposes to introduce pointwise probability reinforcements (PPRs): the probability of each observation is reinforced by a PPR and a regularisation allows controlling the amount of reinforcement which compensates for AFDs. The proposed solution is very generic, since it can be used to robustify any statistical inference method which can be formulated as a likelihood maximisation. Experiments show that PPRs can be easily used to tackle regression, classification and projection: models are freed from the influence of outliers. Moreover, outliers can be filtered manually since an abnormality degree is obtained for each observation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Statistical inference from imperfect photon detection

    International Nuclear Information System (INIS)

    Audenaert, Koenraad M R; Scheel, Stefan

    2009-01-01

    We consider the statistical properties of photon detection with imperfect detectors that exhibit dark counts and less than unit efficiency, in the context of tomographic reconstruction. In this context, the detectors are used to implement certain positive operator-valued measures (POVMs) that would allow us to reconstruct the quantum state or quantum process under consideration. Here we look at the intermediate step of inferring outcome probabilities from measured outcome frequencies, and show how this inference can be performed in a statistically sound way in the presence of detector imperfections. Merging outcome probabilities for different sets of POVMs into a consistent quantum state picture has been treated elsewhere (Audenaert and Scheel 2009 New J. Phys. 11 023028). Single-photon pulsed measurements as well as continuous wave measurements are covered.

  6. An Intuitive Dashboard for Bayesian Network Inference

    International Nuclear Information System (INIS)

    Reddy, Vikas; Farr, Anna Charisse; Wu, Paul; Mengersen, Kerrie; Yarlagadda, Prasad K D V

    2014-01-01

    Current Bayesian network software packages provide good graphical interface for users who design and develop Bayesian networks for various applications. However, the intended end-users of these networks may not necessarily find such an interface appealing and at times it could be overwhelming, particularly when the number of nodes in the network is large. To circumvent this problem, this paper presents an intuitive dashboard, which provides an additional layer of abstraction, enabling the end-users to easily perform inferences over the Bayesian networks. Unlike most software packages, which display the nodes and arcs of the network, the developed tool organises the nodes based on the cause-and-effect relationship, making the user-interaction more intuitive and friendly. In addition to performing various types of inferences, the users can conveniently use the tool to verify the behaviour of the developed Bayesian network. The tool has been developed using QT and SMILE libraries in C++

  7. Dopamine, reward learning, and active inference

    Directory of Open Access Journals (Sweden)

    Thomas eFitzgerald

    2015-11-01

    Full Text Available Temporal difference learning models propose phasic dopamine signalling encodes reward prediction errors that drive learning. This is supported by studies where optogenetic stimulation of dopamine neurons can stand in lieu of actual reward. Nevertheless, a large body of data also shows that dopamine is not necessary for learning, and that dopamine depletion primarily affects task performance. We offer a resolution to this paradox based on an hypothesis that dopamine encodes the precision of beliefs about alternative actions, and thus controls the outcome-sensitivity of behaviour. We extend an active inference scheme for solving Markov decision processes to include learning, and show that simulated dopamine dynamics strongly resemble those actually observed during instrumental conditioning. Furthermore, simulated dopamine depletion impairs performance but spares learning, while simulated excitation of dopamine neurons drives reward learning, through aberrant inference about outcome states. Our formal approach provides a novel and parsimonious reconciliation of apparently divergent experimental findings.

  8. Automated Change Detection for Synthetic Aperture Sonar

    Science.gov (United States)

    2014-01-01

    2014 2. REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Automated Change Detection for Synthetic Aperture Sonar...R. Azimi-Sadjadi and S. Srinivasan, “Coherent Change Detection and Classification in Synthetic Aper - ture Radar Imagery Using Canonical Correlation

  9. Synthetic aperture radar: principles and applications

    International Nuclear Information System (INIS)

    Khan, N.A.; Yahya, K.M.

    2003-01-01

    In this paper an introduction to synthetic aperture radar is presented. Synthetic aperture radar is a relatively new remote sensing platform and the technology has matured a lot in the last two decades. This paper introduces the concepts behind SAR principles as well as the major areas where this new technology has shown additional information. (author)

  10. Synthetic Biology in Health and Disease

    NARCIS (Netherlands)

    Passel, van M.W.J.; Lam, C.M.C.; Martins dos Santos, V.A.P.; Suarez Diez, M.

    2014-01-01

    Synthetic biology draws on the understanding from genetics, biology, chemistry, physics, engineering, and computational sciences to (re-)design and (re-)engineer biological functions. Here we address how synthetic biology can be possibly deployed to promote health and tackle disease. We discuss how

  11. Metal immobilization in soils using synthetic zeolites

    NARCIS (Netherlands)

    Osté, L.A.; Lexmond, T.M.; Riemsdijk, van W.H.

    2002-01-01

    In situ immobilization of heavy metals in contaminated soils is a technique to improve soil quality. Synthetic zeolites are potentially useful additives to bind heavy metals. This study selected the most effective zeolite in cadmium and zinc binding out of six synthetic zeolites (mordenite-type,

  12. Synthetic biology: from mainstream to counterculture.

    Science.gov (United States)

    Sleator, Roy D

    2016-09-01

    Existing at the interface of science and engineering, synthetic biology represents a new and emerging field of mainstream biology. However, there also exists a counterculture of Do-It-Yourself biologists, citizen scientists, who have made significant inroads, particularly in the design and development of new tools and techniques. Herein, I review the development and convergence of synthetic biology's mainstream and countercultures.

  13. Synergistic Synthetic Biology: Units in Concert

    Science.gov (United States)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications. PMID:25022769

  14. Synergistic Synthetic Biology: Units in Concert

    International Nuclear Information System (INIS)

    Trosset, Jean-Yves; Carbonell, Pablo

    2013-01-01

    Synthetic biology aims at translating the methods and strategies from engineering into biology in order to streamline the design and construction of biological devices through standardized parts. Modular synthetic biology devices are designed by means of an adequate elimination of cross-talk that makes circuits orthogonal and specific. To that end, synthetic constructs need to be adequately optimized through in silico modeling by choosing the right complement of genetic parts and by experimental tuning through directed evolution and craftsmanship. In this review, we consider an additional and complementary tool available to the synthetic biologist for innovative design and successful construction of desired circuit functionalities: biological synergies. Synergy is a prevalent emergent property in biological systems that arises from the concerted action of multiple factors producing an amplification or cancelation effect compared with individual actions alone. Synergies appear in domains as diverse as those involved in chemical and protein activity, polypharmacology, and metabolic pathway complementarity. In conventional synthetic biology designs, synergistic cross-talk between parts and modules is generally attenuated in order to verify their orthogonality. Synergistic interactions, however, can induce emergent behavior that might prove useful for synthetic biology applications, like in functional circuit design, multi-drug treatment, or in sensing and delivery devices. Synergistic design principles are therefore complementary to those coming from orthogonal design and may provide added value to synthetic biology applications. The appropriate modeling, characterization, and design of synergies between biological parts and units will allow the discovery of yet unforeseeable, novel synthetic biology applications.

  15. Inferring Genetic Ancestry: Opportunities, Challenges, and Implications

    OpenAIRE

    Royal, Charmaine D.; Novembre, John; Fullerton, Stephanie M.; Goldstein, David B.; Long, Jeffrey C.; Bamshad, Michael J.; Clark, Andrew G.

    2010-01-01

    Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of “ancestry” is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How ...

  16. Inferring ontology graph structures using OWL reasoning.

    Science.gov (United States)

    Rodríguez-García, Miguel Ángel; Hoehndorf, Robert

    2018-01-05

    Ontologies are representations of a conceptualization of a domain. Traditionally, ontologies in biology were represented as directed acyclic graphs (DAG) which represent the backbone taxonomy and additional relations between classes. These graphs are widely exploited for data analysis in the form of ontology enrichment or computation of semantic similarity. More recently, ontologies are developed in a formal language such as the Web Ontology Language (OWL) and consist of a set of axioms through which classes are defined or constrained. While the taxonomy of an ontology can be inferred directly from the axioms of an ontology as one of the standard OWL reasoning tasks, creating general graph structures from OWL ontologies that exploit the ontologies' semantic content remains a challenge. We developed a method to transform ontologies into graphs using an automated reasoner while taking into account all relations between classes. Searching for (existential) patterns in the deductive closure of ontologies, we can identify relations between classes that are implied but not asserted and generate graph structures that encode for a large part of the ontologies' semantic content. We demonstrate the advantages of our method by applying it to inference of protein-protein interactions through semantic similarity over the Gene Ontology and demonstrate that performance is increased when graph structures are inferred using deductive inference according to our method. Our software and experiment results are available at http://github.com/bio-ontology-research-group/Onto2Graph . Onto2Graph is a method to generate graph structures from OWL ontologies using automated reasoning. The resulting graphs can be used for improved ontology visualization and ontology-based data analysis.

  17. Context recognition for a hyperintensional inference machine

    Science.gov (United States)

    Duží, Marie; Fait, Michal; Menšík, Marek

    2017-07-01

    The goal of this paper is to introduce the algorithm of context recognition in the functional programming language TIL-Script, which is a necessary condition for the implementation of the TIL-Script inference machine. The TIL-Script language is an operationally isomorphic syntactic variant of Tichý's Transparent Intensional Logic (TIL). From the formal point of view, TIL is a hyperintensional, partial, typed λ-calculus with procedural semantics. Hyperintensional, because TIL λ-terms denote procedures (defined as TIL constructions) producing set-theoretic functions rather than the functions themselves; partial, because TIL is a logic of partial functions; and typed, because all the entities of TIL ontology, including constructions, receive a type within a ramified hierarchy of types. These features make it possible to distinguish three levels of abstraction at which TIL constructions operate. At the highest hyperintensional level the object to operate on is a construction (though a higher-order construction is needed to present this lower-order construction as an object of predication). At the middle intensional level the object to operate on is the function presented, or constructed, by a construction, while at the lowest extensional level the object to operate on is the value (if any) of the presented function. Thus a necessary condition for the development of an inference machine for the TIL-Script language is recognizing a context in which a construction occurs, namely extensional, intensional and hyperintensional context, in order to determine the type of an argument at which a given inference rule can be properly applied. As a result, our logic does not flout logical rules of extensional logic, which makes it possible to develop a hyperintensional inference machine for the TIL-Script language.

  18. Inferring ontology graph structures using OWL reasoning

    KAUST Repository

    Rodriguez-Garcia, Miguel Angel

    2018-01-05

    Ontologies are representations of a conceptualization of a domain. Traditionally, ontologies in biology were represented as directed acyclic graphs (DAG) which represent the backbone taxonomy and additional relations between classes. These graphs are widely exploited for data analysis in the form of ontology enrichment or computation of semantic similarity. More recently, ontologies are developed in a formal language such as the Web Ontology Language (OWL) and consist of a set of axioms through which classes are defined or constrained. While the taxonomy of an ontology can be inferred directly from the axioms of an ontology as one of the standard OWL reasoning tasks, creating general graph structures from OWL ontologies that exploit the ontologies\\' semantic content remains a challenge.We developed a method to transform ontologies into graphs using an automated reasoner while taking into account all relations between classes. Searching for (existential) patterns in the deductive closure of ontologies, we can identify relations between classes that are implied but not asserted and generate graph structures that encode for a large part of the ontologies\\' semantic content. We demonstrate the advantages of our method by applying it to inference of protein-protein interactions through semantic similarity over the Gene Ontology and demonstrate that performance is increased when graph structures are inferred using deductive inference according to our method. Our software and experiment results are available at http://github.com/bio-ontology-research-group/Onto2Graph .Onto2Graph is a method to generate graph structures from OWL ontologies using automated reasoning. The resulting graphs can be used for improved ontology visualization and ontology-based data analysis.

  19. Thermodynamics of statistical inference by cells.

    Science.gov (United States)

    Lang, Alex H; Fisher, Charles K; Mora, Thierry; Mehta, Pankaj

    2014-10-03

    The deep connection between thermodynamics, computation, and information is now well established both theoretically and experimentally. Here, we extend these ideas to show that thermodynamics also places fundamental constraints on statistical estimation and learning. To do so, we investigate the constraints placed by (nonequilibrium) thermodynamics on the ability of biochemical signaling networks to estimate the concentration of an external signal. We show that accuracy is limited by energy consumption, suggesting that there are fundamental thermodynamic constraints on statistical inference.

  20. Constrained bayesian inference of project performance models

    OpenAIRE

    Sunmola, Funlade

    2013-01-01

    Project performance models play an important role in the management of project success. When used for monitoring projects, they can offer predictive ability such as indications of possible delivery problems. Approaches for monitoring project performance relies on available project information including restrictions imposed on the project, particularly the constraints of cost, quality, scope and time. We study in this paper a Bayesian inference methodology for project performance modelling in ...