Analysis of a Permo-Triassic polarity transition in different absolute reconstructions of Pangaea, considering a model with features of the present Earth magnetic field

The main objective of this paper is to show that the distribution of transitional palaeomagnetic data recorded at 250 Ma are in agreement with simulated data that depend on the sampling site, using a model that considers features of the Present Earth magnetic field. The analysis was performed comparing simulated reversals with the Permo-Triassic polarity transition recorded in the Siberian Trap Basalts. The palaeomagnetic data were corrected according to the Palaeo-latitude and Palaeo-longitude of Siberia (absolute reconstruction) at 250 Ma using hotspot tracks. To obtain the motion of Siberia relative to hotspots from the Present time back to 250 Ma, three different Pangaea models were considered (Pangaea A, Pangaea A2, Pangaea B). In spite of the uncertainties associated with the use of hotspot frameworks and Pangaea configurations, both the modelled and recorded data show a remarkable fit when absolute reconstructions of Pangaea A and A2 configurations are performed. The agreement between both simulated and recorded data suggests that similar features to that of the Present Earth magnetic field could have been involved in reversals since the Permo-Triassic

KBE Application for the Design and Manufacture of HSM Fixtures

The design of machining fixtures for aeronautical parts is strongly based in the knowledge of the fixture designer, and it comprises certain repetitive tasks. An analysis of the design process allows us to state its suitability for developing Knowledge Based Engineering (KBE) applications in order to capture the knowledge, and to systematize and automate the designs.This work justifies the importance of fixtures for High Speed Milling (HSM), and explains the development of a KBE application to automate the design and manufacturing of such elements. The application is the outcome of a project carried out in collaboration with the company EADS.In the development process, a specific methodology was used in order to represent the knowledge in a semi-structured way and to document the information needed to define the system. The developed KBE application is independent of the parts design system. This makes it necessary to use an interface to input the part geometry into the KBE application, where it is analyzed in order to extract the relevant information for the fixture design process. The results obtained from the application come in three different ways: raw material drawings, fixture 3D solid models, and text files (Bill Of Materials – BOM, and Numerical Control – NC programs). All the results are exported to other applications for use in other tasks. The designer interacts with the application through an ad hoc interface, where he is asked to select or input some data and where the results are also visualized. The prototype KBE application has been carried out in the ICAD development environment and the main interface is with the CAD/CAM system CATIA V4.

Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis

Background: Metabolic flux profiling based on the analysis of distribution of stable isotope tracer in metabolites is an important method widely used in cancer research to understand the regulation of cell metabolism and elaborate new therapeutic strategies. Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells. Results: The study of 13C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in ¿5% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis de novo, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program. Conclusion: The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy

Fixture knowledge model development and implementation based on a functional design approach

The development of a knowledge model applied to fixture design is a complex task. The main purpose of such model is the development of a knowledge-based application to assist fixture designers. It comprises a detailed specification of the types and structures of data involved in the execution of the inference process needed to create a fixture solution for machining a raw part. A development method together with a knowledge model for automating fixture design is proposed. The development was divided into three parts: Design Process Model, definition of Top-level functional functions and Product Knowledge Model. Adopting a functional design approach, the fixture design solution was created in two levels: functional and detailed. The functional level is based on fixture functional elements and the detailed one is based on fixture commercial elements. The definitions and concepts used in the application are specified in several Units of Knowledge (UoK) that comprises the Fixture Knowledge Model. Common Knowledge Analysis and Design Structuring (CommonKADS), Methodology and software tools Oriented to KBE Applications (MOKA), Integrated DEFinition for Function Modelling (IDEF0) and Unified Modelling Language (UML) are the methodologies and techniques used in the proposed method. Finally, a prototype KBE application for fixture design was developed

Integration of design tools and knowledge capture into a CAD system: a case study

onceptual design phase is partially supported by product lifecycle management/computer-aided design (PLM/CAD) systems causing discontinuity of the design information flow: customer needs — functional requirements — key characteristics — design parameters (DPs) — geometric DPs. Aiming to address this issue, it is proposed a knowledge-based approach is proposed to integrate quality function deployment, failure mode and effects analysis, and axiomatic design into a commercial PLM/CAD system. A case study, main subject of this article, was carried out to validate the proposed process, to evaluate, by a pilot development, how the commercial PLM/CAD modules and application programming interface could support the information flow, and based on the pilot scheme results to propose a full development framework

Histone deacetylase inhibition results in a common metabolic profile associated with HT29 differentiation

Cell differentiation is an orderly process that begins with modifications in gene expression. This process is regulated by the acetylation state of histones. Removal of the acetyl groups of histones by specific enzymes (histone deacetylases, HDAC) usually downregulates expression of genes that can cause cells to differentiate, and pharmacological inhibitors of these enzymes have been shown to induce differentiation in several colon cancer cell lines. Butyrate at high (mM) concentration is both a precursor for acetyl-CoA and a known HDAC inhibitor that induces cell differentiation in colon cells. The dual role of butyrate raises the question whether its effects on HT29 cell differentiation are due to butyrate metabolism or to its HDAC inhibitor activity. To distinguish between these two possibilities, we used a tracer-based metabolomics approach to compare the metabolic changes induced by two different types of HDAC inhibitors (butyrate and the non-metabolic agent trichostatin A) and those induced by other acetyl-CoA precursors that do not inhibit HDAC (caprylic and capric acids). [1,2-13C2]-d-glucose was used as a tracer and its redistribution among metabolic intermediates was measured to estimate the contribution of glycolysis, the pentose phosphate pathway and the Krebs cycle to the metabolic profile of HT29 cells under the different treatments. The results demonstrate that both HDAC inhibitors (trichostatin A and butyrate) induce a common metabolic profile that is associated with histone deacetylase inhibition and differentiation of HT29 cells whereas the metabolic effects of acetyl-CoA precursors are different from those of butyrate. The experimental findings support the concept of crosstalk between metabolic and cell signalling events, and provide an experimental approach for the rational design of new combined therapies that exploit the potential synergism between metabolic adaptation and cell differentiation processes through modification of HDAC activity

Evidence for t\bar{t}\gamma Production and Measurement of \sigma_t\bar{t}\gamma / \sigma_t\bar{t}

Using data corresponding to 6.0/fb of ppbar collisions at sqrt(s) = 1.96 TeV collected by the CDF II detector, we present a cross section measurement of top-quark pair production with an additional radiated photon. The events are selected by looking for a lepton, a photon, significant transverse momentum imbalance, large total transverse energy, and three or more jets, with at least one identified as containing a b quark. The ttbar+photon sample requires the photon to have 10 GeV or more of transverse energy, and to be in the central region. Using an event selection optimized for the ttbar+photon candidate sample we measure the production cross section of, and the ratio of cross sections of the two samples. Control samples in the dilepton+photon and lepton+photon+\met, channels are constructed to aid in decay product identification and background measurements. We observe 30 ttbar+photon candidate events compared to the standard model expectation of 26.9 +/- 3.4 events. We measure the ttbar+photon cross section to be 0.18+0.08 pb, and the ratio of the cross section of ttbar+photon to ttbar to be 0.024 +/- 0.009. Assuming no ttbar+photon production, we observe a probability of 0.0015 of the background events alone producing 30 events or more, corresponding to 3.0 standard deviations.Comment: 9 pages, 3 figure

Observation of Exclusive Gamma Gamma Production in p pbar Collisions at sqrt{s}=1.96 TeV

We have observed exclusive \gamma\gamma production in proton-antiproton collisions at \sqrt{s}=1.96 TeV, using data from 1.11 \pm 0.07 fb^{-1} integrated luminosity taken by the Run II Collider Detector at Fermilab. We selected events with two electromagnetic showers, each with transverse energy E_T > 2.5 GeV and pseudorapidity |\eta| < 1.0, with no other particles detected in -7.4 < \eta < +7.4. The two showers have similar E_T and azimuthal angle separation \Delta\phi \sim \pi; 34 events have two charged particle tracks, consistent with the QED process p \bar{p} to p + e^+e^- + \bar{p} by two-photon exchange, while 43 events have no charged tracks. The number of these events that are exclusive \pi^0\pi^0 is consistent with zero and is < 15 at 95% C.L. The cross section for p\bar{p} to p+\gamma\gamma+\bar{p} with |\eta(\gamma)| < 1.0 and E_T(\gamma) > 2.5$ GeV is 2.48^{+0.40}_{-0.35}(stat)^{+0.40}_{-0.51}(syst) pb.Comment: 7 pages, 4 figure

Measurement of the WZWZ Cross Section and Triple Gauge Couplings in ppˉp \bar p Collisions at s=1.96\sqrt{s} = 1.96 TeV

This Letter describes the current most precise measurement of the $WZ$ production cross section as well as limits on anomalous $WWZ$ couplings at a center-of-mass energy of 1.96 TeV in proton-antiproton collisions for the Collider Detector at Fermilab (CDF). $WZ$ candidates are reconstructed from decays containing three charged leptons and missing energy from a neutrino, where the charged leptons are either electrons or muons. Using data collected by the CDF II detector (7.1 fb$^{-1}$ of integrated luminosity), 63 candidate events are observed with the expected background contributing $8 \pm 1$ events. The measured total cross section $\sigma (p \bar p \to WZ) = 3.93_{-0.53}^{+0.60}(\text{stat})_{-0.46}^{+0.59}(\text{syst})$ pb is in good agreement with the standard model prediction of $3.50\pm 0.21$. The same sample is used to set limits on anomalous $WWZ$ couplings.Comment: Resubmission to PRD-RC after acceptance (27 July 2012