Evolutionary and revolutionary effects of transcomputation

Mathematics in Defence 2011 Abstract. We review transreal arithmetic and present transcomplex arithmetic. These arithmetics have no exceptions. This leads to incremental improvements in computer hardware and software. For example, the range of real numbers, encoded by floating-point bits, is doubled when all of the Not-a-Number(NaN) states, in IEEE 754 arithmetic, are replaced with real numbers. The task of programming such systems is simplified and made safer by discarding the unordered relational operator,leaving only the operators less-than, equal-to, and greater than. The advantages of using a transarithmetic in a computation, or transcomputation as we prefer to call it, may be had by making small changes to compilers and processor designs. However, radical change is possible by exploiting the reliability of transcomputations to make pipelined dataflow machines with a large number of cores. Our initial designs are for a machine with order one million cores. Such a machine can complete the execution of multiple in-line programs each clock tick

Molecular archaeology of Flaviviridae untranslated regions: duplicated RNA structures in the replication enhancer of flaviviruses and pestiviruses emerged via convergent evolution.

RNA secondary structures in the 3'untranslated regions (3'UTR) of the viruses of the family Flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3'UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3'UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV). RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3'UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3'UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3'UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs.

Ixodes ricinus (Ixodidae), an occasional phoront on necrophagous and coprophagous beetles in Europe

For ticks, phoretic behaviour using insects associated with vertebrates might offer an alternative strategy to host-seeking. Here we report for the first time the presence of immature stages of the most widespread tick species in Western Europe, Ixodes ricinus (Acari: Ixodidae), on three beetle species belonging to families Silphidae and Geotrupidae (Coleoptera). Specimens were collected while performing fieldwork surveys on insect diversity during the peak of tick’s questing behaviour, therefore, in July and August of 2009 and 2010. The collections took place in two Natural Parks, the Aiako Harria, Guipúzcoa in Northern Spain and Wellington Country Park, Berkshire, in England. The silphid species Nicrophorus vespilloides, together with the geotrupid Trypocopris pyrenaeus were both collected from pig-carcasses and both carried nymphs of I. ricinus; while, the geotrupid Anoplotrupes stercorosus was carrying a tick larva while feeding on Red deer dung. These findings revealed an unnoticed but common relation of ticks not only with decomposed animals but also with insect scavengers. We discuss the rationale of this phenomenon.

Transmathematical basis of infinitely scalable pipeline machines

We describe infinitely scalable pipeline machines with perfect parallelism, in the sense that every instruction of an inline program is executed, on successive data, on every clock tick. Programs with shared data effectively execute in less than a clock tick. We show that pipeline machines are faster than single or multi-core, von Neumann machines for sufficiently many program runs of a sufficiently time consuming program. Our pipeline machines exploit the totality of transreal arithmetic and the known waiting time of statically compiled programs to deliver the interesting property that they need no hardware or software exception handling.

Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity

The molecular mechanism of factor Xa (FXa) inhibition by Alboserpin, the major salivary gland anticoagulant from the mosquito and yellow fever vector Aedes albopictus, has been characterized. cDNA of Alboserpin predicts a 45-kDa protein that belongs to the serpin family of protease inhibitors. Recombinant Alboserpin displays stoichiometric, competitive, reversible and tight binding to FXa (picomolar range). Binding is highly specific and is not detectable for FX, catalytic site-blocked FXa, thrombin, and 12 other enzymes. Alboserpin displays high affinity binding to heparin (K(D) similar to 20 nM), but no change in FXa inhibition was observed in the presence of the cofactor, implying that bridging mechanisms did not take place. Notably, Alboserpin was also found to interact with phosphatidylcholine and phosphatidylethanolamine but not with phosphatidylserine. Further, annexin V (in the absence of Ca(2+)) or heparin outcompetes Alboserpin for binding to phospholipid vesicles, suggesting a common binding site. Consistent with its activity, Alboserpin blocks prothrombinase activity and increases both prothrombin time and activated partial thromboplastin time in vitro or ex vivo. Furthermore, Alboserpin prevents thrombus formation provoked by ferric chloride injury of the carotid artery and increases bleeding in a dose-dependent manner. Alboserpin emerges as an atypical serpin that targets FXa and displays unique phospholipid specificity. It conceivably uses heparin and phosphatidylcholine/phosphatidylethanolamine as anchors to increase protein localization and effective concentration at sites of injury, cell activation, or inflammation.

The Immunomodulatory Action of Sialostatin L on Dendritic Cells Reveals Its Potential to Interfere with Autoimmunity

Sialostatin L (SialoL) is a secreted cysteine protease inhibitor identified in the salivary glands of the Lyme disease vector Ixodes scapularis. In this study, we reveal the mechanisms of SialoL immunomodulatory actions on the vertebrate host. LPS-induced maturation of dendritic cells from C57BL/6 mice was significantly reduced in the presence of SialoL. Although OVA degradation was not affected by the presence of SialoL in dendritic cell cultures, cathepsin S activity was partially inhibited, leading to an accumulation of a 10-kDa invariant chain intermediate in these cells. As a consequence, in vitro Ag-specific CD4(+) T cell proliferation was inhibited in a time-dependent manner by SialoL, and further studies engaging cathepsin S(-/-) or cathepsin L(-/-) dendritic cells confirmed that the immunomodulatory actions of SialoL are mediated by inhibition of cathepsin S. Moreover, mice treated with SialoL displayed decreased early T cell expansion and recall response upon antigenic stimulation. Finally, SialoL administration during the immunization phase of experimental autoimmune encephalomyelitis in mice significantly prevented disease symptoms, which was associated with impaired IFN-gamma and IL-17 production and specific T cell proliferation. These results illuminate the dual mechanism by which a human disease vector protein modulates vertebrate host immunity and reveals its potential in prevention of an autoimmune disease. The Journal of Immunology, 2009, 182: 7422-7429.

Comparison of two methods for collecting free-living ticks in the Amazonian forest

In the present study, we compared 2 methods for collecting ixodid ticks on the verges of animal trails in a primary Amazon forest area in northern Brazil. (i) Dragging: This method was based on passing a 1-m(2) white flannel over the vegetation and checking the flannel for the presence of caught ticks every 5-10 m. (ii) Visual search: This method consisted of looking for guesting ticks on the tips of leaves of the vegetation bordering animal trails in the forest. A total of 103 adult ticks belonging to 4 Amblyomma species were collected by the visual search method on 5 collecting dates, while only 44 adult ticks belonging to 3 Amblyomma species were collected by dragging on 5 other collecting dates. These values were statistically different (Mann-Whitney Test, P = 0.0472). On the other hand, dragging was more efficient for subadult ticks, since no larva or nymph was collected by visual search, whereas 18 nymphs and 7 larvae were collected by dragging. The visual search method proved to be suitable for collecting adult ticks in the Amazon forest: however, field studies should include a second method, such as dragging in order to maximize the collection of subadult ticks. Indeed, these 2 methods can be performed by a single investigator at the same time, while he/she walks on an animal trail in the forest. (C) 2010 Elsevier GmbH. All rights reserved.

Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model

Background: The expression levels of the clotting initiator protein Tissue Factor (TF) correlate with vessel density and the histological malignancy grade of glioma patients. Increased procoagulant tonus in high grade tumors (glioblastomas) also indicates a potential role for TF in progression of this disease, and suggests that anticoagulants could be used as adjuvants for its treatment. Objectives: We hypothesized that blocking of TF activity with the tick anticoagulant Ixolaris might interfere with glioblastoma progression. Methods and results: TF was identified in U87-MG cells by flow-cytometric and functional assays (extrinsic tenase). In addition, flow-cytometric analysis demonstrated the exposure of phosphatidylserine in the surface of U87-MG cells, which supported the assembly of intrinsic tenase (FIXa/FVIIIa/FX) and prothrombinase (FVa/FXa/prothrombin) complexes, accounting for the production of FXa and thrombin, respectively. Ixolaris effectively blocked the in vitro TF-dependent procoagulant activity of the U87-MG human glioblastoma cell line and attenuated multimolecular coagulation complexes assembly. Notably, Ixolaris inhibited the in vivo tumorigenic potential of U87-MG cells in nude mice, without observable bleeding. This inhibitory effect of Ixolaris on tumor growth was associated with downregulation of VEGF and reduced tumor vascularization. Conclusion: Our results suggest that Ixolaris might be a promising agent for anti-tumor therapy in humans.

Are price limits on futures markets that cool? evidence from the brazilian merchantile & futures exchange

This paper investigates the impact of price limits on the Brazil- ian future markets using high frequency data. The aim is to identify whether there is a cool-off or a magnet effect. For that purpose, we examine a tick-by-tick data set that includes all contracts on the São Paulo stock index futures traded on the Brazilian Mercantile and Futures Exchange from January 1997 to December 1999. Our main finding is that price limits drive back prices as they approach the lower limit. There is a strong cool-off effect of the lower limit on the conditional mean, whereas the upper limit seems to entail a weak magnet effect on the conditional variance. We then build a trading strategy that accounts for the cool-off effect so as to demonstrate that the latter has not only statistical, but also economic signifi- cance. The resulting Sharpe ratio indeed is way superior to the buy-and-hold benchmarks we consider.

Volatility modelling in the forex market: an empirical evaluation

We compare three frequently used volatility modelling techniques: GARCH, Markovian switching and cumulative daily volatility models. Our primary goal is to highlight a practical and systematic way to measure the relative effectiveness of these techniques. Evaluation comprises the analysis of the validity of the statistical requirements of the various models and their performance in simple options hedging strategies. The latter puts them to test in a "real life" application. Though there was not much difference between the three techniques, a tendency in favour of the cumulative daily volatility estimates, based on tick data, seems dear. As the improvement is not very big, the message for the practitioner - out of the restricted evidence of our experiment - is that he will probably not be losing much if working with the Markovian switching method. This highlights that, in terms of volatility estimation, no clear winner exists among the more sophisticated techniques.

Are price limits on futures markets that cool?: evidence from the Brazilian Mercantile and Futures Exchange

This paper investigates the impact of price limits on the Brazilian futures markets using high frequency data. The aim is to identify whether there is a cool-off or a magnet effect. For that purpose, we examine a tick-by-tick data set that includes all contracts on the S˜ao Paulo stock index futures traded on the Brazilian Mercantile and Futures Exchange from January 1997 to December 1999. The results indicate that the conditional mean features a floor cool-off effect, whereas the conditional variance significantly increases as the price approaches the upper limit. We then build a trading strategy that accounts for the cool-off effect in the conditional mean so as to demonstrate that the latter has not only statistical, but also economic significance. The in-sample Sharpe ratio indeed is way superior to the buy-and-hold benchmarks we consider, whereas out-of-sample results evince similar performances.

Análise do desempenho de regras da análise técnica aplicada ao mercado intradiário do contrato futuro do índice Ibovespa

Este artigo tem como objetivo verificar a robustez do contéudo preditivo de regras da análise técnica, usando informações intradiárias do mercado futuro do índice de ações da Bolsa de Valores de São Paulo (Ibovespa Futuro). A metodologia sugerida foi a avaliacão em grupos, conforme os resultados de Baptista (2002), tal que as regras são obtidas conforme os resultados em alguns dos subperíodos estudados, sendo testadas em períodos subsequentes. Como resultado, obteve-se robustez ao longo do tempo e à taxa de amostragem dos dados no desempenho das regras acima do benchmark (buy-and-hold), porém considerações realistas acerca do momento de compra, assim como da corretagem (exceto grande investidor), podem reduzir substancialmente os ganhos

As intervenções do Banco do Central do Brasil no mercado de câmbio e seus efeitos no nível intradiário da taxa de câmbio

Este trabalho tem como objetivo investigar o efeito das intervenções cambiais realizadas pelo Banco Central do Brasil sobre o nível intradiário da taxa de câmbio no Brasil. Para isso é utilizada uma abordagem de estudo de eventos, cruzando as cotações tick-by-tick dos contratos de dólar futuro negociados na BM&FBOVESPA com o instante em que ocorreram as intervenções, no período de outubro de 2011 a março de 2014. Foram considerados nas análises não apenas o momento da intervenção como também o momento do anúncio. Os resultados indicaram que o mercado reage de forma distinta a cada tipo de intervenção, sendo a reação acentuada quando a intervenção não é anunciada previamente ao mercado. As intervenções via swap cambial ou dólar pronto geraram efeitos significativos e relevantes no nível da taxa de câmbio. Por outro lado, as intervenções através de leilão de linha não afetaram significativamente a taxa de câmbio.

Desenvolvimento e composição mineral do picão-preto sob diferentes níveis de pH

Visando estudar a tolerância do picão-preto (Bidens pilosa) a diferentes níveis de pH do substrato, conduziu-se um ensaio em condições de câmara de crescimento e utilizando-se a técnica de hidroponia, no qual três plântulas foram transplantadas para recipientes contendo solução nutritiva de Hoagland & Arnon, com pH ajustado para 3,5, 4,0, 5,0, 6,0, 7,0 e 8,0. O delineamento experimental utilizado foi o inteiramente casualizado com três repetições. Ao final do período experimental, 42 dias após o transplante, observou-se que as plantas que se desenvolveram nos pHs 3,5 e 8,0 apresentaram-se menores, com menor comprimento e volume do sistema radicular, menor número de folhas vivas e, consequentemente, menor peso de matéria seca das folhas, caule e raízes. Os teores de N e S nas raízes diminuiram com o aumento do pH do substrato, enquanto os de Ca e Mg aumentaram e os de K e P diminuiram no pH 5,0 a 6,0. No caule, apenas o teor de Mg foi afetado pelo pH, mostrando resposta positiva. Na folha obteve-se os maiores teores de P, S, Ca e Mg quando a planta se desenvolveu em pH 6,0. Não se constatou diferença significativa entre os efeitos dos pHs 5,0, 6,0 e 7,0 nos parâmetros avaliados, sendo que foi no pH 6,0 que se estimou, através de análise de regressão, melhor desenvolvimento do picão-preto. Concluiu-se que o picãopreto apresenta melhor desenvolvimento em pHs próximo ao neutro, com certa tolerância a pHs extremos (3,5 e 8,0).

Características do pelame de vacas Holandesas em ambiente tropical: um estudo genético e adaptativo

As características do pelame (espessura da capa, comprimento médio dos pêlos, número de pêlos por unidade de área, densidade de massa dos pêlos, ângulo de inclinação dos pêlos com respeito a superfície da epiderme e diâmetro médio do pêlos) foram avaliadas em 973 vacas da raça Holandesa, entre novembro de 2000 e abril de 2001, numa área localizada 20cm abaixo da coluna vertebral, no centro do tronco, tanto nas malhas brancas como nas negras. As amostras de pêlos foram obtidas com um alicate comum adaptado. O método da Máxima Verossimilhança Restrita (REML) foi usado para estimar os componentes de variância e covariância sob modelo animal, sendo empregado o sistema MTDFREML. Os resultados mostraram que as características do pelame preto são diferentes das do branco, quando os animais são criados em ambiente tropical. O pelame preto apresentou-se menos denso, com pêlos mais curtos e grossos devido à maior necessidade de perder calor, enquanto que, o pelame branco é mais denso e com pêlos mais compridos, oferecendo uma melhor proteção contra à radiação solar direta. A seleção de vacas predominantemente negras pode ser uma boa escolha para aumentar a resistência do gado Holandês às condições do ambiente tropical, principalmente à radiação solar, quando esses animais são criados a campo, devido a que a epiderme sob esse tipo de malhas é altamente pigmentada. Tal seleção pode ser facilmente realizada, considerando a alta herdabilidade (h²=0,75) para a proporção de malhas negras. Esta seleção deve ser realizada no sentido de um pelame menos denso, com pêlos curtos e grossos favorecendo as perdas de calor sensível e calor latente.