Modeling, control and experimental validation of a novel actuator based on shape memory alloys

The paper presents the development of a mechanical actuator using a shape memory alloy with a cooling system based on the thermoelectric effect (Seebeck-Peltier effect). Such a method has the advantage of reduced weight and requires a simpler control strategy as compared to other forced cooling systems. A complete mathematical model of the actuator was derived, and an experimental prototype was implemented. Several experiments are used to validate the model and to identify all parameters. A robust and nonlinear controller, based on sliding-mode theory, was derived and implemented. Experiments were used to evaluate the actuator closed-loop performance, stability, and robustness properties. The results showed that the proposed cooling system and controller are able to improve the dynamic response of the actuator. (C) 2009 Elsevier Ltd. All rights reserved.

Molecular dynamics, density functional, ADMET predictions, virtual screening, and molecular interaction field studies for identification and evaluation of novel potential CDK2 inhibitors in cancer therapy

In this work, we have used molecular dynamics, density functional theory, virtual screening, ADMET predictions, and molecular interaction field studies to design and propose eight novel potential inhibitors of CDK2. The eight molecules proposed showed interesting structural characteristics that are required for inhibiting the CDK2 activity and show potential as drug candidates for the treatment of cancer. The parameters related to the Rule of Five were calculated, and only one of the molecules violated more than one parameter. One of the proposals and one of the drug-like compounds selected by virtual screening indicated to be promising candidates for CDK2-based cancer therapy.

Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when Compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by LIS, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer. (C) 2009 Elsevier Inc. All rights reserved.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Nested diets: a novel pattern of individual-level resource use

Many generalist populations may actually be composed of relatively specialist individuals. This `individual specialization` may have important ecological and evolutionary implications. Although this phenomenon has been documented in more than one hundred taxa, it is still unclear how individuals within a population actually partition resources. Here we applied several methods based on network theory to investigate the intrapopulation patterns of resource use in the gracile mouse opossum Gracilinanus microtarsus. We found evidence of significant individual specialization in this species and that the diets of specialists are nested within the diets of generalists. This novel pattern is consistent with a recently proposed model of optimal foraging and implies strong asymmetry in the interactions among individuals of a population.

A novel approach for distributed application scheduling based on prediction of communication events

The evolution of commodity computing lead to the possibility of efficient usage of interconnected machines to solve computationally-intensive tasks, which were previously solvable only by using expensive supercomputers. This, however, required new methods for process scheduling and distribution, considering the network latency, communication cost, heterogeneous environments and distributed computing constraints. An efficient distribution of processes over such environments requires an adequate scheduling strategy, as the cost of inefficient process allocation is unacceptably high. Therefore, a knowledge and prediction of application behavior is essential to perform effective scheduling. In this paper, we overview the evolution of scheduling approaches, focusing on distributed environments. We also evaluate the current approaches for process behavior extraction and prediction, aiming at selecting an adequate technique for online prediction of application execution. Based on this evaluation, we propose a novel model for application behavior prediction, considering chaotic properties of such behavior and the automatic detection of critical execution points. The proposed model is applied and evaluated for process scheduling in cluster and grid computing environments. The obtained results demonstrate that prediction of the process behavior is essential for efficient scheduling in large-scale and heterogeneous distributed environments, outperforming conventional scheduling policies by a factor of 10, and even more in some cases. Furthermore, the proposed approach proves to be efficient for online predictions due to its low computational cost and good precision. (C) 2009 Elsevier B.V. All rights reserved.

An Information Theory framework for two-stage binary image operator design

The design of translation invariant and locally defined binary image operators over large windows is made difficult by decreased statistical precision and increased training time. We present a complete framework for the application of stacked design, a recently proposed technique to create two-stage operators that circumvents that difficulty. We propose a novel algorithm, based on Information Theory, to find groups of pixels that should be used together to predict the Output Value. We employ this algorithm to automate the process of creating a set of first-level operators that are later combined in a global operator. We also propose a principled way to guide this combination, by using feature selection and model comparison. Experimental results Show that the proposed framework leads to better results than single stage design. (C) 2009 Elsevier B.V. All rights reserved.

Effects of a novel calcium aluminate cement on the early events of the progression of osteogenic cell cultures

The present study evaluated the progression of osteogenic cell cultures exposed to a novel calcium aluminate cement (CAC+) in comparison with the gold standard mineral trioxide aggregate (MTA). Cells were enzimatically isolated from newborn rat calvarial bone, plated on glass coverslips containing either CAC+ or a control MTA samples in the center, and grown under standard osteogenic conditions. Over the 10-day culture period, roundening of sample edges was clearly noticed only for MTA group. Although both cements supported osteogenic cell adhesion, spreading, and proliferation, CAC+-exposed cultures showed significantly higher values in terms of total cell number at days 3 and 7, and total protein content and alkaline phosphatase activity at day 10. The present in vitro results indicate that the exposure to CAC+ supports a higher differentiation of osteogenic cells compared with the ones exposed to MTA. Further experimental studies should consider CAC+ as a potential alternative to MTA when the repair of mineralized tissues is one of the desired outcomes in endodontic therapy.

A novel bioactive glass-ceramic for treating dentin hypersensitivity

Dentin hypersensitivity (DH) is a painful response to stimulus applied to the open dentinal tubules of a vital tooth. It's a common oral condition, however, without an ideal treatment available yet. This work evaluated in vitro the effect of micron-sized particles from a novel bioactive glass-ceramic (Biosilicate) in occluding open dentinal tubules. A dentin disc model was employed to observe comparatively, using scanning electron microscopy (SEM), dentinal tubule occlusion by different products and deposition of hydroxyl carbonate apatite (HCA) on dentin surface by Biosilicate, after a single application: G1 - Dentifrice with potassium nitrate and fluoride; G2 - Two-step calcium phosphate precipitation treatment; G3 - Water-free gel containing Biosilicate particles (1%); G4 - Biosilicate particles mixed with distilled water in a 1:10 ratio; all of them after 1, 12 and 24 hours of immersion in artificial saliva. Fourier transform infrared spectroscopy (FTIR) was performed to detect HCA formation on dentin discs filled with Biosilicate after 2 minutes, 30 minutes and 12 hours of immersion in artificial saliva. SEM showed a layer of HCA formed on dentin surface after 24 hours by G4. G1, G2 and G3 promoted not total occlusion of open dentinal tubules after 24 hours. FTIR showed HCA precipitation on the dentin surface induced by Biosilicate after 30 minutes. The micron-sized particles from the bioactive glass-ceramic thus were able to induce HCA deposition in open dentinal tubules in vitro. This finding suggests that Biosilicate may provide a new option for treating DH.

A novel A2 allele found in Leishmania (Leishmania) infantum chagasi

Visceral leishmaniasis (VL) is a widely spread zoonotic disease. In Brazil the disease is caused by Leishmania (Leishmania) infantum chagasi. Peridomestic sandflies acquire the etiological agent by feeding on blood of infected reservoir animals, such as dogs or wildlife. The disease is endemic in Brazil and epidemic foci have been reported in densely populated cities all over the country. Many clinical features of Leishmania infection are related to the host-parasite relationship, and many candidate virulence factors in parasites that cause VL have been studied such as A2 genes. The A2 gene was first isolated in 1994 and then in 2005 three new alleles were described in Leishmania (Leishmania) infantum. In the present study we amplified by polymerase chain reaction (PCR) and sequenced the A2 gene from the genome of a clonal population of L. (L.) infantum chagasi VL parasites. The L. (L.) infantum chagasi A2 gene was amplified, cloned, and sequenced in. The amplified fragment showed approximately 90% similarity with another A2 allele amplified in Leishmania (Leishmania) donovani and in L.(L.) infantum described in literature. However, nucleotide translation shows differences in protein amino acid sequence, which may be essential to determine the variability of A2 genes in the species of the L. (L.) donovani complex and represents an additional tool to help understanding the role this gene family may have in establishing virulence and immunity in visceral leishmaniasis. This knowledge is important for the development of more accurate diagnostic tests and effective tools for disease control.

A novel missense mutation p.L76P in the GJB2 gene causing nonsyndromic recessive deafness in a Brazilian family

Mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries. We report here on a novel point mutation in GJB2, p.L76P (c.227C>T), in compound heterozygosity with a c.35delG mutation, in two Brazilian sibs, one presenting mild and the other profound nonsyndromic neurosensorial hearing impairment. Their father, who carried a wild-type allele and a p.L76P mutation, had normal hearing. The mutation leads to the substitution of leucine (L) by proline (P) at residue 76, an evolutionarily conserved position in Cx26 as well as in other connexins. This mutation is predicted to affect the first extracellular domain (EC1) or the second transmembrane domain (TM2). EC1 is important for connexon-connexon interaction and for the control of channel voltage gating. The segregation of the c.227C>T (p.L76P) mutation together with c.35delG in this family indicates a recessive mode of inheritance. The association between the p.L76P mutation and hearing impairment is further supported by its absence in a normal hearing control group of 100 individuals, 50 European-Brazilians and 50 African-Brazilians.

Synthesis of novel O-acylated-D-ribono-1,5-lactones and structural assignment supported by conventional NOESY-NMR and x-ray analysis

A practical method for the structural assignment of 3,4-O-benzylidene-D-ribono-1,5-lactones and analogues using conventional NMR techniques and NOESY measurements in solution is described. 2-O-Acyl-3,4-O-benzylidene-D-ribono-1,5-lactones were prepared in good yields by acylation of Zinner’s lactone with acyl chlorides under mildly basic conditions. Structural determination of 2-O-(4-nitrobenzoyl)-3,4-O-benzylidene-D-ribono-1,5-lactone was achieved by single crystal x-ray diffraction, which supports the results based on spectroscopic data.

Pulsar binary systems in a nonsymmetric theory of gravitation II. Dipole radiation

This paper deals with the emission of gravitational radiation in the context of a previously studied metric nonsymmetric theory of gravitation. The part coming from the symmetric part of the metric coincides with the mass quadrupole moment result of general relativity. The one associated to the antisymmetric part of the metric involves the dipole moment of the fermionic charge of the system. The results are applied to binary star systems and the decrease of the period of the elliptical motion is calculated.

Nonexistence of regular stationary solution in a metric nonsymmetric theory of gravitation

It is proven that the field equations of a previously studied metric nonsymmetric theory of gravitation do not admit any non-singular stationary solution which represents a field of non-vanishing total mass and non-vanishing total fermionic charge.

Analyzing the n→π* Electronic Transition of Formaldehyde in Water. A Sequential Monte Carlo/Time-Dependent Density Functional Theory

The n→π* absorption transition of formaldehyde in water is analyzed using combined and sequential classical Monte Carlo (MC) simulations and quantum mechanics (QM) calculations. MC simulations generate the liquid solute-solvent structures for subsequent QM calculations. Using time-dependent density functional theory in a localized set of gaussian basis functions (TD-DFT/6-311++G(d,p)) calculations are made on statistically relevant configurations to obtain the average solvatochromic shift. All results presented here use the electrostatic embedding of the solvent. The statistically converged average result obtained of 2300 cm-1 is compared to previous theoretical results available. Analysis is made of the effective dipole moment of the hydrogen-bonded shell and how it could be held responsible for the polarization of the solvent molecules in the outer solvation shells.