128 research outputs found

    Use of Flight Simulators for Pilot-Control Problems

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    Comparisons have been made between actual flight results and results obtained with fixed and moving flight simulators in a number of phases of flying airplanes with a wide range of characteristics. These results have been used to study the importance of providing motion stimuli in a simulator in order that the pilot operate the simulator in a realistic manner. Regions of airplane characteristics where motion stimuli are either mandatory or desirable are indicated

    Cytosine-to-Uracil Deamination by SssI DNA Methyltransferase

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    The prokaryotic DNA(cytosine-5)methyltransferase M.SssI shares the specificity of eukaryotic DNA methyltransferases (CG) and is an important model and experimental tool in the study of eukaryotic DNA methylation. Previously, M.SssI was shown to be able to catalyze deamination of the target cytosine to uracil if the methyl donor S-adenosyl-methionine (SAM) was missing from the reaction. To test whether this side-activity of the enzyme can be used to distinguish between unmethylated and C5-methylated cytosines in CG dinucleotides, we re-investigated, using a sensitive genetic reversion assay, the cytosine deaminase activity of M.SssI. Confirming previous results we showed that M.SssI can deaminate cytosine to uracil in a slow reaction in the absence of SAM and that the rate of this reaction can be increased by the SAM analogue 5’-amino-5’-deoxyadenosine. We could not detect M.SssI-catalyzed deamination of C5-methylcytosine (m5C). We found conditions where the rate of M.SssI mediated C-to-U deamination was at least 100-fold higher than the rate of m5C-to-T conversion. Although this difference in reactivities suggests that the enzyme could be used to identify C5-methylated cytosines in the epigenetically important CG dinucleotides, the rate of M.SssI mediated cytosine deamination is too low to become an enzymatic alternative to the bisulfite reaction. Amino acid replacements in the presumed SAM binding pocket of M.SssI (F17S and G19D) resulted in greatly reduced methyltransferase activity. The G19D variant showed cytosine deaminase activity in E. coli, at physiological SAM concentrations. Interestingly, the C-to-U deaminase activity was also detectable in an E. coli ung+ host proficient in uracil excision repair

    Paleointensity Results From Pliocene Lavas of the Lesser Caucasus Obtained Using the Multispecimen Parallel Differential pTRM Method: A Comparison With Thellier- Thellier and IZZI Data

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    We report paleointensity results obtained with the multispecimen method (MSP) over the Pliocene sequence of Apnia (Georgia) which records a polarity reversal. Paleointensity determinations with the multispecimen technique were performed on 12 flows with the original (MSP-DB) and the domain-state corrected (MSP-DSC) protocol. Eight MSP-DSC determinations passed the proposed quality criteria. To obtain highly reliable data through the agreement between intensity values from different methods, MSP results were combined with paleointensities from a previous study with Thellier-type methods and especially strict selection criteria (RCRIT) on same flows (SĂĄnchez-Moreno et al., 2020). Application of this multimethod procedure resulted in three new paleointensities including both MSP and Thellier-type results and an additional one obtained with two different Thellier-type methods, yielding one paleointensity of 36.9 ”T in the normal-polarity, and three paleointensities between 19.2 and 24.1 ”T in the reverse-polarity section. Additionally, Thellier-type data have been reinterpreted in this study with more flexible criteria (TTP) and the results combined with the MSP data. As a result, four flows yield paleointensities including MSP and Thellier-type determinations and seven include paleointensities obtained with two different Thellier-type methods. Results range from 37.2 and 44.3 ÎŒT in the normal-polarity and from 12.5 to 24.6 ÎŒT in the reverse-polarity section. Comparison of results from the four flows yielding multimethod determinations applying RCRIT criteria with those from the same flows under TTP criteria yields no significant difference in paleointensity values and their experimental uncertainty. Thus, application of a multimethod approach supports the possibility of using TTP criteria.Project PID2019-105796/10.13039/501100011033 (Agencia Estatal de InvestigaciĂłn, Spain), project BU066U16 (Junta de Castilla y LeĂłn, Spain) and pre-doctoral grant BES-2013-064060 (MINECO, Spain). MCR acknowledges funding from the Fulbright Commission and the Spanish Ministry of Science, Innovation and Universities for a research stay at Hawaii University at Manoa. AG is grateful to the financial support given by DGAPA-PAPIIT IN101717. At Montpellier laboratory, the FUReMAG rapid furnace construction was supported by the French National Agency for Research (ANR-12-BS06-0015)

    A comparison of Thellier-type and multispecimen paleointensity determinations on Pleistocene and historical lava flows from Lanzarote (Canary Islands, Spain)

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    Sixteen Miocene, Pleistocene, and historic lava flows have been sampled in Lanzarote (Canary Islands) for paleointensity analysis with both the Coe and multispecimen methods. Besides obtaining new data, the main goal of the study was the comparison of paleointensity results determined with two different techniques. Characteristic Remanent Magnetization (ChRM) directions were obtained in 15 flows, and 12 were chosen for paleointensity determination. In Thellier-type experiments, a selection of reliable paleointensity determinations (43 of 78 studied samples) was performed using sets of criteria of different stringency, trying to relate the quality of results to the strictness of the chosen criteria. Uncorrected and fraction and domain-state corrected multispecimen paleointensity results were obtained in all flows. Results with the Coe method on historical flows either agree with the expected values or show moderately lower ones, but multispecimen determinations display a large deviation from the expected result in one case. No relation can be detected between correct or anomalous results and paleointensity determination quality or rock-magnetic properties. However, results on historical flows suggest that agreement between both methods could be a good indicator of correct determinations. Comparison of results obtained with both methods on seven Pleistocene flows yields an excellent agreement in four and disagreements in three cases. Pleistocene determinations were only accepted if either results from both methods agreed or a result was based on a sufficiently large number (n>4) of individual Thellier-type determinations. In most Pleistocene flows, a VADM around 5 31022 Am2 was observed, although two flows displayed higher values around 931022 Am2.project CGL2012-32149 (Ministerio de Econom ıa y Competitividad, Spain), project 320/2011 (Ministerio de Medio Ambiente y Medio Rural y Marino, Spain) and the European Regional Development Fund (ERDF)

    Further progress in the study of epsilon iron oxide in archaeological baked clays

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    The occurrence of Δ-Fe2O3 in archaeological samples that have been subjected to high temperatures is gradually being detected by the use of micrometric structural characterization techniques. This work provides new information by revealing that the Δ-Fe2O3 is formed as a response to temperature, the aggregation state and the position within the baked clay with respect to the nearest heat source. In addition, depending mainly on the atmospheric environment, the temperature reached by the combustion structure, the distance from the heating source and the particle aggregation, other iron oxide magnetic phases are produced. In the baked clay studied here, hematite is found over the whole range of samples studied but its magnetic contribution is negligible. Magnetite is observed at the sample surface, probably due to local atmospheric environment closest to the combustion source. Maghemite is found at all depths up to 6 cm below the sample surface. Δ-Fe2O3 has a limited distribution, found within 2–3 cm of the sample surface. Furthermore, the viability of this compound as a palaeofield marker has been evaluated in both archaeological and synthetic samples. The results indicate that Δ-Fe2O3 is able to register the direction of the magnetic field. Linear palaeointensity plots have been obtained in synthetic samples, although the value of the palaeofield could be, sometimes, overestimated

    The Impact of Error-Management Climate, Error Type and Error Originator on Auditors’ Reporting Errors Discovered on Audit Work Papers

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    We examine factors affecting the auditor’s willingness to report their own or their peers’ self-discovered errors in working papers subsequent to detailed working paper review. Prior research has shown that errors in working papers are detected in the review process; however, such detection rates only rarely exceed 50% of the seeded errors. Hence, measures that encourage auditors to be alert to their own (or their peers’) potential errors any time they revisit the audit working papers may be valuable in detecting such residual errors and potentially correcting them before damage occurs to the audit firm or its client. We hypothesize that three factors affect the auditor’s willingness to report post detailed review discovered errors: the local office error-management climate (open versus blame), the type of error (mechanical versus conceptual) and who committed the error (the individual who committed the error (self) or a peer). Local office error-management climate is said to be open and supportive where errors and mistakes are accepted as part of everyday life as long as they are learned from and not repeated. In alternative, a blame error-management climate focuses on a “get it right the first time” culture where mistakes are not tolerated and blame gets attached to those admitting to or found committing such errors. We find that error-management climate has a significant overall effect on auditor willingness to report errors, as does who committed the error originally. We find both predicted and unpredicted significant interactions among the three factors that qualify these observed significant main effects. We discuss implications for audit practice and further research

    Epigenetic polypharmacology: from combination therapy to multitargeted drugs

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    The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed
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