392 research outputs found

    Circuit Based Quantification: Back to State Set Manipulation within Unbounded Model Checking

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    In this paper a non-canonical circuit-based state set representation is used to efficiently perform quantifier elimination. The novelty of this approach lies in adapting equivalence checking and logic synthesis techniques, to the goal of compacting circuit based state set representations resulting from existential quantification. The method can be efficiently combined with other verification approaches such as inductive and SAT-based pre-image verifications

    Consolidation of a collar truss with a steel cable system

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    Post-tensioning techniques for strengthening existing timber elements have been used throughout history with excellent results. Former applications on wooden trusses have already shown some of the advantages of such a consolidating system, but very few tests were performed on the topic. During an experimental campaign, a full-scale historical timber truss was deeply analysed and tested in its original (unreinforced) condition, reaching a considerable level of damage. It was later repaired with a steel cable system, using prestresses to recover the structure bearing capacity, and tested again. The results show that the repair allowed a recovery of at least the 80% of the ultimate load-carrying capacity. The complete failure was not achieved, but it is likely to be presumed that the structure could have regained the totality of its strength. The data acquired in both tests were later compared in order to understand in detail the behavior of the truss.The present work was made within a Master thesis of the Erasmus Mundus Advanced Masters course in Structural Analysis of Monuments and Historical Constructions. The authors acknowledge also the support and assistance of Augusto de Oliveira Ferreira e Companhia Lda (AOF)

    Derivation of nearest-neighbor DNA parameters in magnesium from single-molecule experiments

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    DNA hybridization is an essential molecular reaction in biology with many applications. The nearest-neighbor (NN) model for nucleic acids predicts DNA thermodynamics using energy values for the different base pair motifs. These values have been derived from melting experiments in monovalent and divalent salt and applied to predict melting temperatures of oligos within a few degrees. However, an improved determination of the NN energy values and their salt dependencies in magnesium is still needed for current biotechnological applications seeking high selectivity in the hybridization of synthetic DNAs. We developed a methodology based on single molecule unzipping experiments to derive accurate NN energy values and initiation factors for DNA. A new set of values in magnesium is derived, which reproduces unzipping data and improves melting temperature predictions for all available oligo lengths, in a range of temperature and salt conditions where correlation effects between the magnesium bound ions are weak. The NN salt correction parameters are shown to correlate to the GC content of the NN motifs. Our study shows the power of single-molecule force spectroscopy assays to unravel novel features of nucleic acids such as sequence-dependent salt corrections

    Use of Electrical Impedance Tomography (EIT) to estimate tidal volume in Anaesthetized horses undergoing elective surgery

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    This study explores the application of electric impedance tomography (EIT) to estimate tidal volume (VT) by measuring impedance change per breath (∆Zbreath). Seventeen healthy horses were anaesthetised and mechanically ventilated for elective procedures requiring dorsal recumbency. Spirometric VT (VTSPIRO) and ∆Zbreath were recorded periodically; up to six times throughout anaesthesia. Part 1 assessed these variables at incremental delivered VT of 10, 12 and 15 mL/kg. Part 2 estimated VT (VTEIT) in litres from ∆Zbreath at three additional measurement points using a line of best fit obtained from Part 1. During part 2, VT was adjusted to maintain end-tidal carbon dioxide between 45–55 mmHg. Linear regression determined the correlation between VTSPIRO and ∆Zbreath (part 1). Estimated VTEIT was assessed for agreement with measured VTSPIRO using Bland Altman analysis (part 2). Marked variability in slope and intercepts was observed across horses. Strong positive correlation between ∆Zbreath and VTSPIRO was found in each horse (R2 0.9–0.99). The agreement between VTEIT and VTSPIRO was good with bias (LOA) of 0.26 (−0.36–0.88) L. These results suggest that, in anaesthetised horses, EIT can be used to monitor and estimate VT after establishing the individual relationship between these variables

    Vertically-Aligned Functionalized Silicon Micropillars for 3D Culture of Human Pluripotent Stem Cell-Derived Cortical Progenitors

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    Silicon is a promising material for tissue engineering since it allows to produce micropatterned scaffolding structures resembling biological tissues. Using specific fabrication methods, it is possible to build aligned 3D network-like structures. In the present study, we exploited vertically-aligned silicon micropillar arrays as culture systems for human iPSC-derived cortical progenitors. In particular, our aim was to mimic the radially-oriented cortical radial glia fibres that during embryonic development play key roles in controlling the expansion, radial migration and differentiation of cortical progenitors, which are, in turn, pivotal to the establishment of the correct multilayered cerebral cortex structure. Here we show that silicon vertical micropillar arrays efficiently promote expansion and stemness preservation of human cortical progenitors when compared to standard monolayer growth conditions. Furthermore, the vertically-oriented micropillars allow the radial migration distinctive of cortical progenitors in vivo. These results indicate that vertical silicon micropillar arrays can offer an optimal system for human cortical progenitors' growth and migration. Furthermore, similar structures present an attractive platform for cortical tissue engineering

    32-Channel silicon strip detection module for combined X-ray fluorescence spectroscopy and X-ray diffractometry analysis

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    A compact detection module for the simultaneous measurement of XRF and XRD in portable analytical applications, in particular in the mining sector, is presented. The detector head is based on 32 silicon strip detectors, fabricated with a low-leakage technology by FBK and readout by two 16-channel low-noise CUBE charge-sensitive amplifiers. The design of the module and its characterization are reported. Multiple configurations are experimentally compared in terms of strip length, spacing, collimation and charge sharing effects. The optimal configuration for a strip length of 6 mm and pitch 0.2 mm is thus identified. It offers an energy resolution of better than 200 eV at 5.9 keV with moderate cooling (−10°C) and peaking time of 14 μs

    From free energy measurements to thermodynamic inference in nonequilibrium small systems

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    Fluctuation theorems (FTs), such as the Crooks or Jarzynski equalities (JEs), have become an important tool in single-molecule biophysics where they allow experimentalists to exploit thermal fluctuations and measure free-energy differences from non-equilibrium pulling experiments. The rich phenomenology of biomolecular systems has stimulated the development of extensions to the standard FTs, to encompass different experimental situations. Here we discuss an extension of the Crooks fluctuation relation that allows the thermodynamic characterization of kinetic molecular states. This extension can be connected to the generalized JE under feedback. Finally we address the recently introduced concept of thermodynamic inference or how FTs can be used to extract the total entropy production distribution in nonequilibrium systems from partial entropy production measurements. We discuss the significance of the concept of effective temperature in this context and show how thermodynamic inference provides a unifying comprehensive picture in several nonequilibrium problems

    Epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer: A multicentric phase I-II study

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    Background The combination of anthracyclines and taxanes is currently considered the first choice chemotherapy in advanced breast cancer (ABC) and considerable emphasis has been placed on programs exploring the safest and most efficient way to integrate these classes of drugs in both the metastatic and, more recently, the adjuvant setting. We report here the overall results of the combination of epidoxorubicin (E) 90 mg/m2 and docetaxel (D) 75 mg/m2 as first-line chemotherapy in ABC. Patients and methods A total of 70 patients were entered in the initial dose-finding study (20 patients) and in the subsequent extended phase II trial (50 patients). Overall 54% of patients had dominant visceral disease and 57% had at least two metastatic sites. Adjuvant anthracyclines were allowed in the phase II part of the study based on the lack of cardiac toxicity observed in the phase I study at a median cumulative E dose of 480 mg/m2 A maximum of eight cycles of the combination was allowed, and cardiac function was monitored at baseline and after every second course by echocardiography. Results Overall, the median number of cycles administered with the combination was 4 (range 3-8). Neutropenia was confirmed to be the main haematological toxicity, with granulocyte colony-stimulating factor (G-CSF) support required in 44% of the cycles. Febrile neutropenia occurred in 12% of cycles of the combination but 52% of the episodes could be managed on an outpatient basis with oral antibiotics. Overall, the median cumulative dose of E, including prior adjuvant anthracyclines, was 495 mg/m2 (range 270-1020 mg/m2. One patient who received adjuvant E together with radiotherapy to the left chest wall developed fully reversible clinical signs of cardiotoxicity and a significant decrease of LVEF to 35% after a cumulative E dose of 870 mg/m2, with four additional patients (6%) developing asymptomatic and transient decline of resting LVEF. The overall response rate (ORR) in 68 evaluable patients was 66% (95% confidence interval (95% CI): 54%-73%). A comparable antitumour activity of 71% was reported in the group of patients with a prior adjuvant chemotherapy with anthracyclines. After an overall median follow-up time of 22 months (range 4−39+), the median time to progression (TTP) was 4.5 months and the median duration of response was 8 months (range 3-16). No pharmacokinetic (Pk) interaction could be demonstrated between E and D when given simultaneously and sequentially with a one-hour interval. Conclusions The combination of E and D in a multi-institutional setting is an active and safe regimen in poor-prognosis patients with ABC. New combinations and schedules are worth considering in an attempt to further improve disease response and long-term control of the diseas
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