Molecular modeling and QSAR studies of a set of indole and benzimidazole derivatives as H(4) receptor antagonists

Histamine is an important biogenic amine, which acts with a group of four G-protein coupled receptors (GPCRs), namely H(1) to H(4) (H(1)R - H(4)R) receptors. The actions of histamine at H(4)R are related to immunological and inflammatory processes, particularly in pathophysiology of asthma, and H(4)R ligands having antagonistic properties could be helpful as antiinflammatory agents. In this work, molecular modeling and QSAR studies of a set of 30 compounds, indole and benzimidazole derivatives, as H(4)R antagonists were performed. The QSAR models were built and optimized using a genetic algorithm function and partial least squares regression (WOLF 5.5 program). The best QSAR model constructed with training set (N = 25) presented the following statistical measures: r (2) = 0.76, q (2) = 0.62, LOF = 0.15, and LSE = 0.07, and was validated using the LNO and y-randomization techniques. Four of five compounds of test set were well predicted by the selected QSAR model, which presented an external prediction power of 80%. These findings can be quite useful to aid the designing of new anti-H(4) compounds with improved biological response.

Synthesis, antichagasic in vitro evaluation, cytotoxicity assays, molecular modeling and SAR/QSAR studies of a 2-phenyl-3-(1-phenyl-1H-pyrazol-4-yl)-acrylic acid benzylidene-carbohydrazide series

Chagas disease (American trypanosomiasis) is one of the most important parasitic diseases with serious social and economic impacts mainly on Latin America. This work reports the synthesis, in vitro trypanocidal evaluation, cytotoxicity assays, and molecular modeling and SAR/QSAR studies of a new series of N-phenylpyrazole benzylidene-carbohydrazides. The results pointed 6k (X = H, Y = p-NO(2), pIC(50) = 4.55 M) and 6l (X = F, Y = p-CN, pIC(50) = 4.27 M) as the most potent derivatives compared to crystal violet (pIC(50) = 3.77 M). The halogen-benzylidene-carbohydrazide presented the lowest potency whereas 6l showed the most promising pro. le with low toxicity (0% of cell death). The best equation from the 4D-QSAR analysis (Model 1) was able to explain 85% of the activity variability. The QSAR graphical representation revealed that bulky X-substituents decreased the potency whereas hydrophobic and hydrogen bond acceptor Y-substituents increased it. (C) 2008 Elsevier Ltd. All rights reserved.

Effects of frequency and inspiratory plateau pressure during recruitment manoeuvres on lung and distal organs in acute lung injury

To evaluate the effects of frequency and inspiratory plateau pressure (Pplat) during recruitment manoeuvres (RMs) on lung and distal organs in acute lung injury (ALI). We studied paraquat-induced ALI rats. At 24 h, rats were anesthetized and RMs were applied using continuous positive airway pressure (CPAP, 40 cmH(2)O/40 s) or three-different sigh strategies: (a) 180 sighs/h and Pplat = 40 cmH(2)O (S180/40), (b) 10 sighs/h and Pplat = 40 cmH(2)O (S10/40), and (c) 10 sighs/h and Pplat = 20 cmH(2)O (S10/20). S180/40 yielded alveolar hyperinflation and increased lung and kidney epithelial cell apoptosis as well as type III procollagen (PCIII) mRNA expression. S10/40 resulted in a reduction in epithelial cell apoptosis and PCIII expression. Static elastance and alveolar collapse were higher in S10/20 than S10/40. The reduction in sigh frequency led to a protective effect on lung and distal organs, while the combination with reduced Pplat worsened lung mechanics and histology.

Dopant extraction from scanning capacitance microscopy measurements of p-n junctions using combined inverse modeling and forward simulation

This article proposes a more accurate approach to dopant extraction using combined inverse modeling and forward simulation of scanning capacitance microscopy (SCM) measurements on p-n junctions. The approach takes into account the essential physics of minority carrier response to the SCM probe tip in the presence of lateral electric fields due to a p-n junction. The effects of oxide fixed charge and interface state densities in the grown oxide layer on the p-n junction samples were considered in the proposed method. The extracted metallurgical and electrical junctions were compared to the apparent electrical junction obtained from SCM measurements. (C) 2002 American Institute of Physics.

Vibration instability in rolling mills: Modeling and experimental results

Models for the occurrence of the vibrational instability during rolling known as third octave chatter are presented and discussed. An analysis of rolling mill chatter was performed for the purpose of identifying characteristics of the vibrations and to determine any dependency on the rolling schedule. In particular, a stability criterion for the critical rolling speed is used to predict the maximum rolling speed without chatter instability on schedules from a 5 stand tandem mill rolling thin steel product. The results correlate well with measurements of critical speed occurring on the mill using a vibration monitor: This research provides significant insights into the chatter phenomena and has been used to investigate control methods for suppression of the instability.

Identification of tsunami-induced deposits using numerical modeling and rock magnetism techniques: A study case of the 1755 Lisbon tsunami in Algarve, Portugal

Storm- and tsunami-deposits are generated by similar depositional mechanisms making their discrimination hard to establish using classic sedimentologic methods. Here we propose an original approach to identify tsunami-induced deposits by combining numerical simulation and rock magnetism. To test our method, we investigate the tsunami deposit of the Boca do Rio estuary generated by the 1755 earthquake in Lisbon which is well described in the literature. We first test the 1755 tsunami scenario using a numerical inundation model to provide physical parameters for the tsunami wave. Then we use concentration (MS. SIRM) and grain size (chi(ARM), ARM, B1/2, ARM/SIRM) sensitive magnetic proxies coupled with SEM microscopy to unravel the magnetic mineralogy of the tsunami-induced deposit and its associated depositional mechanisms. In order to study the connection between the tsunami deposit and the different sedimentologic units present in the estuary, magnetic data were processed by multivariate statistical analyses. Our numerical simulation show a large inundation of the estuary with flow depths varying from 0.5 to 6 m and run up of similar to 7 m. Magnetic data show a dominance of paramagnetic minerals (quartz) mixed with lesser amount of ferromagnetic minerals, namely titanomagnetite and titanohematite both of a detrital origin and reworked from the underlying units. Multivariate statistical analyses indicate a better connection between the tsunami-induced deposit and a mixture of Units C and D. All these results point to a scenario where the energy released by the tsunami wave was strong enough to overtop and erode important amount of sand from the littoral dune and mixed it with reworked materials from underlying layers at least 1 m in depth. The method tested here represents an original and promising tool to identify tsunami-induced deposits in similar embayed beach environments.

Modeling, control and simulation of full-power converter wind turbines equipped with permanent magnet synchronous generator

In this paper, two wind turbines equipped with a permanent magnet synchronous generator (PMSG) and respectively with a two-level or a multilevel converter are simulated in order to access the malfunction transient performance. Three different drive train mass models, respectively, one, two and three mass models, are considered in order to model the bending flexibility of the blades. Moreover, a fractional-order control strategy is studied comparatively to a classical integer-order control strategy. Computer simulations are carried out, and conclusions about the total harmonic distortion (THD) of the electric current injected into the electric grid are in favor of the fractional-order control strategy.

Identification of tsunami-induced deposits using numerical modeling and rock magnetism techniques: A study case of the 1755 Lisbon tsunami in Algarve, Portugal

Storm- and tsunami-deposits are generated by similar depositional mechanisms making their discrimination hard to establish using classic sedimentologic methods. Here we propose an original approach to identify tsunami-induced deposits by combining numerical simulation and rock magnetism. To test our method, we investigate the tsunami deposit of the Boca do Rio estuary generated by the 1755 earthquake in Lisbon which is well described in the literature. We first test the 1755 tsunami scenario using a numerical inundation model to provide physical parameters for the tsunami wave. Then we use concentration (MS. SIRM) and grain size (chi(ARM), ARM, B1/2, ARM/SIRM) sensitive magnetic proxies coupled with SEM microscopy to unravel the magnetic mineralogy of the tsunami-induced deposit and its associated depositional mechanisms. In order to study the connection between the tsunami deposit and the different sedimentologic units present in the estuary, magnetic data were processed by multivariate statistical analyses. Our numerical simulation show a large inundation of the estuary with flow depths varying from 0.5 to 6 m and run up of similar to 7 m. Magnetic data show a dominance of paramagnetic minerals (quartz) mixed with lesser amount of ferromagnetic minerals, namely titanomagnetite and titanohematite both of a detrital origin and reworked from the underlying units. Multivariate statistical analyses indicate a better connection between the tsunami-induced deposit and a mixture of Units C and D. All these results point to a scenario where the energy released by the tsunami wave was strong enough to overtop and erode important amount of sand from the littoral dune and mixed it with reworked materials from underlying layers at least 1 m in depth. The method tested here represents an original and promising tool to identify tsunami-induced deposits in similar embayed beach environments.

Identification of tsunami-induced deposits using numerical modeling and rock magnetism techniques: Astudy case of the 1755 Lisbon tsunami in Algarve, Portugal (vol 182, pg 187, 2010)

Storm- and tsunami-deposits are generated by similar depositional mechanisms making their discrimination hard to establish using classic sedimentologic methods. Here we propose an original approach to identify tsunami-induced deposits by combining numerical simulation and rock magnetism. To test our method, we investigate the tsunami deposit of the Boca do Rio estuary generated by the 1755 earthquake in Lisbon which is well described in the literature. We first test the 1755 tsunami scenario using a numerical inundation model to provide physical parameters for the tsunami wave. Then we use concentration (MS. SIRM) and grain size (chi(ARM), ARM, B1/2, ARM/SIRM) sensitive magnetic proxies coupled with SEM microscopy to unravel the magnetic mineralogy of the tsunami-induced deposit and its associated depositional mechanisms. In order to study the connection between the tsunami deposit and the different sedimentologic units present in the estuary, magnetic data were processed by multivariate statistical analyses. Our numerical simulation show a large inundation of the estuary with flow depths varying from 0.5 to 6 m and run up of similar to 7 m. Magnetic data show a dominance of paramagnetic minerals (quartz) mixed with lesser amount of ferromagnetic minerals, namely titanomagnetite and titanohematite both of a detrital origin and reworked from the underlying units. Multivariate statistical analyses indicate a better connection between the tsunami-induced deposit and a mixture of Units C and D. All these results point to a scenario where the energy released by the tsunami wave was strong enough to overtop and erode important amount of sand from the littoral dune and mixed it with reworked materials from underlying layers at least 1 m in depth. The method tested here represents an original and promising tool to identify tsunami-induced deposits in similar embayed beach environments.

User modeling and recommendation strategies for tourism

Mestrado em Engenharia Informática

Monte Carlo modeling and simulations of the High Definition (HD120) micro MLC and validation against measurements for a 6 MV beam

Purpose: The most recent Varian® micro multileaf collimator(MLC), the High Definition (HD120) MLC, was modeled using the BEAMNRCMonte Carlo code. This model was incorporated into a Varian medical linear accelerator, for a 6 MV beam, in static and dynamic mode. The model was validated by comparing simulated profiles with measurements. Methods: The Varian® Trilogy® (2300C/D) accelerator model was accurately implemented using the state-of-the-art Monte Carlo simulation program BEAMNRC and validated against off-axis and depth dose profiles measured using ionization chambers, by adjusting the energy and the full width at half maximum (FWHM) of the initial electron beam. The HD120 MLC was modeled by developing a new BEAMNRC component module (CM), designated HDMLC, adapting the available DYNVMLC CM and incorporating the specific characteristics of this new micro MLC. The leaf dimensions were provided by the manufacturer. The geometry was visualized by tracing particles through the CM and recording their position when a leaf boundary is crossed. The leaf material density and abutting air gap between leaves were adjusted in order to obtain a good agreement between the simulated leakage profiles and EBT2 film measurements performed in a solid water phantom. To validate the HDMLC implementation, additional MLC static patterns were also simulated and compared to additional measurements. Furthermore, the ability to simulate dynamic MLC fields was implemented in the HDMLC CM. The simulation results of these fields were compared with EBT2 film measurements performed in a solid water phantom. Results: Overall, the discrepancies, with and without MLC, between the opened field simulations and the measurements using ionization chambers in a water phantom, for the off-axis profiles are below 2% and in depth-dose profiles are below 2% after the maximum dose depth and below 4% in the build-up region. On the conditions of these simulations, this tungsten-based MLC has a density of 18.7 g cm− 3 and an overall leakage of about 1.1 ± 0.03%. The discrepancies between the film measured and simulated closed and blocked fields are below 2% and 8%, respectively. Other measurements were performed for alternated leaf patterns and the agreement is satisfactory (to within 4%). The dynamic mode for this MLC was implemented and the discrepancies between film measurements and simulations are within 4%. Conclusions: The Varian® Trilogy® (2300 C/D) linear accelerator including the HD120 MLC was successfully modeled and simulated using the Monte CarloBEAMNRC code by developing an independent CM, the HDMLC CM, either in static and dynamic modes.

Multimedia fate modeling and comparative impact on freshwater ecosystems of pharmaceuticals from biosolids-amended soils

This study modeled the impact on freshwater ecosystems of pharmaceuticals detected in biosolids following application on agricultural soils. The detected sulfonamides and hydrochlorothiazide displayed comparatively moderate retention in solid matrices and, therefore, higher transfer fractions from biosolids to the freshwater compartment. However, the residence times of these pharmaceuticals in freshwater were estimated to be short due to abiotic degradation processes. The non-steroidal anti-inflammatory mefenamic acid had the highest environmental impact on aquatic ecosystems and warrants further investigation. The estimation of the solid-water partitioning coefficient was generally the most influential parameter of the probabilistic comparative impact assessment. These results and the modeling approach used in this study serve to prioritize pharmaceuticals in the research effort to assess the risks and the environmental impacts on aquatic biota of these emerging pollutants.

Modeling and worst-case dimensioning of cluster-tree wireless sensor networks

Time-sensitive Wireless Sensor Network (WSN) applications require finite delay bounds in critical situations. This paper provides a methodology for the modeling and the worst-case dimensioning of cluster-tree WSNs. We provide a fine model of the worst-case cluster-tree topology characterized by its depth, the maximum number of child routers and the maximum number of child nodes for each parent router. Using Network Calculus, we derive “plug-and-play” expressions for the endto- end delay bounds, buffering and bandwidth requirements as a function of the WSN cluster-tree characteristics and traffic specifications. The cluster-tree topology has been adopted by many cluster-based solutions for WSNs. We demonstrate how to apply our general results for dimensioning IEEE 802.15.4/Zigbee cluster-tree WSNs. We believe that this paper shows the fundamental performance limits of cluster-tree wireless sensor networks by the provision of a simple and effective methodology for the design of such WSNs.

Modeling and control of a dragonfly-like robot

Dragonflies demonstrate unique and superior flight performances than most of the other insect species and birds. They are equipped with two pairs of independently controlled wings granting an unmatchable flying performance and robustness. In this paper, the dynamics of a dragonfly-inspired robot is studied. The system performance is analyzed in terms of time response and robustness. The development of computational simulation based on the dynamics of the robotic dragonfly allows the test of different control algorithms. We study different movements, the dynamics, and the level of dexterity in wing motion of the dragonfly. The results are positive for the construction of flying platforms that effectively mimic the kinematics and dynamics of dragonflies and potentially exhibit superior flight performance than existing flying platforms.