The role of exon shuffling in shaping protein-protein interaction networks

Background: Physical protein-protein interaction (PPI) is a critical phenomenon for the function of most proteins in living organisms and a significant fraction of PPIs are the result of domain-domain interactions. Exon shuffling, intron-mediated recombination of exons from existing genes, is known to have been a major mechanism of domain shuffling in metazoans. Thus, we hypothesized that exon shuffling could have a significant influence in shaping the topology of PPI networks. Results: We tested our hypothesis by compiling exon shuffling and PPI data from six eukaryotic species: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Cryptococcus neoformans and Arabidopsis thaliana. For all four metazoan species, genes enriched in exon shuffling events presented on average higher vertex degree (number of interacting partners) in PPI networks. Furthermore, we verified that a set of protein domains that are simultaneously promiscuous (known to interact to multiple types of other domains), self-interacting (able to interact with another copy of themselves) and abundant in the genomes presents a stronger signal for exon shuffling. Conclusions: Exon shuffling appears to have been a recurrent mechanism for the emergence of new PPIs along metazoan evolution. In metazoan genomes, exon shuffling also promoted the expansion of some protein domains. We speculate that their promiscuous and self-interacting properties may have been decisive for that expansion.

Autocatalysis in the open circuit interaction of alcohol molecules with oxidized Pt surfaces

We studied the open circuit interaction of methanol and ethanol with oxidized platinum electrodes using in situ infrared spectroscopy. For methanol, it was found that formic acid is the main species formed in the initial region of the transient and that the steep decrease of the open circuit potential coincides with an explosive increase in the CO(2) production, which is followed by an increase in the coverage of adsorbed CO. For ethanol, acetaldehyde was the main product detected and only traces of dissolved CO(2) and adsorbed CO were found after the steep potential decay. In both cases, the transients were interpreted in terms of (a) the emergence of sub-surface oxygen in the beginning of the transient, where the oxide content is high, and (b) the autocatalytic production of free platinum sites for lower oxide content during the steep decay of the open circuit potential.

Evaluation of grinding methods for pellets preparation aiming at the analysis of plant materials by laser induced breakdown spectrometry

It has been demonstrated that laser induced breakdown spectrometry (LIBS) can be used as an alternative method for the determination of macro (P, K. Ca, Mg) and micronutrients (B, Fe, Cu, Mn, Zn) in pellets of plant materials. However, information is required regarding the sample preparation for plant analysis by LIBS. In this work, methods involving cryogenic grinding and planetary ball milling were evaluated for leaves comminution before pellets preparation. The particle sizes were associated to chemical sample properties such as fiber and cellulose contents, as well as to pellets porosity and density. The pellets were ablated at 30 different sites by applying 25 laser pulses per site (Nd:YAG@1064 nm, 5 ns, 10 Hz, 25J cm(-2)). The plasma emission collected by lenses was directed through an optical fiber towards a high resolution echelle spectrometer equipped with an ICCD. Delay time and integration time gate were fixed at 2.0 and 4.5 mu s, respectively. Experiments carried out with pellets of sugarcane, orange tree and soy leaves showed a significant effect of the plant species for choosing the most appropriate grinding conditions. By using ball milling with agate materials, 20 min grinding for orange tree and soy, and 60 min for sugarcane leaves led to particle size distributions generally lower than 75 mu m. Cryogenic grinding yielded similar particle size distributions after 10 min for orange tree, 20 min for soy and 30 min for sugarcane leaves. There was up to 50% emission signal enhancement on LIBS measurements for most elements by improving particle size distribution and consequently the pellet porosity. (C) 2011 Elsevier B.V. All rights reserved.

Heparin affects the interaction of kininogen on endothelial cells

In the plasma kallikrein-kinin system, it has been shown that when plasma prekallikrein (PM) and high molecular weight kininogen (HK) assemble on endothelial cells, plasma kallikrein (huPK) becomes available to cleave HK, releasing bradykinin, a potent mediator of the inflammatory response. Because the formation of soluble glycosaminoglycans occurs concomitantly during the inflammatory processes, the effect of these polysaccharides on the interaction of HK on the cell surface or extracellular matrix (ECM) of two endothelial cell lines (ECV304 and RAEC) was investigated. In the presence of Zn(+2), HK binding to the surface or ECM of RAEC was abolished by heparin; reduced by heparan sulfate, keratan sulfate, chondroitin 4-sulfate or dermatan sulfate; and not affected by chondroitin 6-sulfate. By contrast, only heparin reduced HK binding to the ECV304 cell surface or ECM. Using heparin-correlated molecules such as low molecular weight dextran sulfate, low molecular weight heparin and N-desulfated heparin, we suggest that these effects were mainly dependent on the charge density and on the N-sulfated glucosamine present in heparin. Surprisingly, PM binding to cell- or ECM-bound-HK and PM activation was not modified by heparin. However, the hydrolysis of HK by huPK, releasing BK in the fluid phase, was augmented by this glycosaminoglycan in the presence of Zn(2+). Thus, a functional dichotomy exists in which soluble glycosaminoglycans may possibly either increase or decrease the formation of BK. In conclusion, glycosaminoglycans that accumulated in inflammatory fluids or used as a therapeutic drug (e.g., heparin) could act as pro- or anti-inflammatory mediators depending on different factors within the cell environment. (C) 2011 Elsevier Masson SAS. All rights reserved.

Fatigue in Brazilian cancer patients, caregivers, and nursing students: a psychometric validation study of the Piper Fatigue Scale-Revised

The objective of this study was to validate the Piper Fatigue Scale-Revised (PFS-R) for use in Brazilian culture. Translation of the PFS-R into Portuguese and validity and reliability tests were performed. Convenience samples in Brazil we as follows: 584 cancer patients (mean age 57 +/- 13 years; 51.3% female); 184 caregivers (mean age 50 +/- 12.7 years; 65.8% female); and 189 undergraduate nursing students (mean age 21.6 +/- 2.8 years; 96.2% female); Instruments used were as follows: Brazilian PFS, Beck Depression Inventory (BDI), and Karnofsky Performance Scale (KPS). The 22 items of the Brazilian PFS loaded well (factor loading > 0.35) on three dimensions identified by factor analysis (behavioral, affective, and sensorial-psychological). These dimensions explained 65% of the variance. Internal consistency reliability was very good (Cronbach`s alpha ranged from 0.841 to 0.943 for the total scale and its dimensions). Cancer patients and their caregivers completed the Brazilian PFS twice for test-retest reliability and results showed good stability (Pearson`s r a parts per thousand yenaEuro parts per thousand 0,60, p < 0,001). Correlations among the Brazilian PFS and other scales were significant, in hypothesized directions, and mostly moderate contributing to divergent (Brazilian PFS x KPS) and convergent validity (Brazilian PFS x BDI). Mild, moderate, and severe fatigue in patients were reported by 73 (12.5%), 167 (28.6%), and 83 (14.2%), respectively. Surprisingly, students had the highest mean total fatigue scores; no significant differences were observed between patients and caregivers showing poor discriminant validity. While the Brazilian PFS is a reliable and valid instrument to measure fatigue in Brazilian cancer patients, further work is needed to evaluate the discriminant validity of the scale in Brazil.

Manipulation of rest period length induces different causes of fatigue in vertical jumping

The aim of this study was to directly compare the causes of fatigue after a short- and a long-rest interval between consecutive stretch-shortening cycle exercises. Eleven healthy males jumped with different resting period lengths (short = 6.1 +/- 1 s, long = 8.6 +/- 0.9 s), performing countermovement jumps at 95% of their maximal jump height until they were unable to sustain the target height. After short- and long-rest, the maximal voluntary isometric contraction knee extension torque decreased (-7%; p = 0.04), comparing to values obtained before exercise protocols. No change was seen from pre- to post-exercise, for either short- or long-rest, in biceps femoris coactivation (-1%; p = 0.95), peak-to-peak amplitude (1%; p = 0.95) and duration (-8%; p = 0.92) of the compound muscle action potential of the vastus lateralis. Evoked peak twitch torque reduced after both exercise protocols (short = -26%, long = -32%; p = 0.003) indicating peripheral fatigue. However, central fatigue occurred only after short-rest evidenced by a reduction in voluntary activation of the quadriceps muscle (-14%; p = 0.013) measured using the interpolated twitch technique. In conclusion, after Stretch-shortening cycle exercise using short rest period length, the cause of fatigue was central and peripheral, while after using long rest period length, the cause of fatigue was peripheral.

Evaluation of three brands of drug interaction software for use in intensive care units

Objective To evaluate drug interaction software programs and determine their accuracy in identifying drug-drug interactions that may occur in intensive care units. Setting The study was developed in Brazil. Method Drug interaction software programs were identified through a bibliographic search in PUBMED and in LILACS (database related to the health sciences published in Latin American and Caribbean countries). The programs` sensitivity, specificity, and positive and negative predictive values were determined to assess their accuracy in detecting drug-drug interactions. The accuracy of the software programs identified was determined using 100 clinically important interactions and 100 clinically unimportant ones. Stockley`s Drug Interactions 8th edition was employed as the gold standard in the identification of drug-drug interaction. Main outcome Sensitivity, specificity, positive and negative predictive values. Results The programs studied were: Drug Interaction Checker (DIC), Drug-Reax (DR), and Lexi-Interact (LI). DR displayed the highest sensitivity (0.88) and DIC showed the lowest (0.69). A close similarity was observed among the programs regarding specificity (0.88-0.92) and positive predictive values (0.88-0.89). The DIC had the lowest negative predictive value (0.75) and DR the highest (0.91). Conclusion The DR and LI programs displayed appropriate sensitivity and specificity for identifying drug-drug interactions of interest in intensive care units. Drug interaction software programs help pharmacists and health care teams in the prevention and recognition of drug-drug interactions and optimize safety and quality of care delivered in intensive care units.

Thermal error evaluation and modelling of a CNC cylindrical grinding machine

With the relentless quest for improved performance driving ever tighter tolerances for manufacturing, machine tools are sometimes unable to meet the desired requirements. One option to improve the tolerances of machine tools is to compensate for their errors. Among all possible sources of machine tool error, thermally induced errors are, in general for newer machines, the most important. The present work demonstrates the evaluation and modelling of the behaviour of the thermal errors of a CNC cylindrical grinding machine during its warm-up period.

Industrial challenges in grinding

This keynote paper aims at analyzing relevant industrial demands for grinding research. The chosen focus is to understand what are the main research challenges in the extensive industrial use of the process. Since the automotive applications are the most important driving forces for grinding development, the paper starts with an analysis on the main trends in more efficient engines and the changes in their components that will affect the grinding performance. A view from 23 machine tool builders is also presented based on a survey made in interviews and during the EMO and IMTS machine tool shows. Case studies received by the STC G members were used to show how research centers and industries are collaborating. A view from the authors and the final conclusions show hot topics for future grinding research. (C) 2009 CIRP.

Effects of sulfur additive EP in ester coolants during friction with CBN

A study was undertaken to investigate the effects of the EP additives during tribological tests using a CBN tool against steel. Ester oil with and without sulfur additive were used as lubricants in a tribometer. Tribochemical interactions between the S additive and steel have been investigated under boundary lubrication conditions by SEM and EDX analysis. The relative abundance of different elements on the surface of the CBN tools, which are present in the workpiece material such as Fe (iron) and Cr (chromium), suggests that adhesion occurred when the ester oil without sulfur additive was tested. Tribochemical interactions between the additive and the steel could be observed when using the ester oil containing the sulfur additive. These interactions contribute to the formation of a uniform layer on the CBN tool. This layer is composed by S (sulfur), Fe, and O (oxygen). The presence of these elements indicate that FeO (iron oxide) and FeS (iron sulfide) were formed.

Coupled reliability and boundary element model for probabilistic fatigue life assessment in mixed mode crack propagation

Fatigue and crack propagation are phenomena affected by high uncertainties, where deterministic methods fail to predict accurately the structural life. The present work aims at coupling reliability analysis with boundary element method. The latter has been recognized as an accurate and efficient numerical technique to deal with mixed mode propagation, which is very interesting for reliability analysis. The coupled procedure allows us to consider uncertainties during the crack growth process. In addition, it computes the probability of fatigue failure for complex structural geometry and loading. Two coupling procedures are considered: direct coupling of reliability and mechanical solvers and indirect coupling by the response surface method. Numerical applications show the performance of the proposed models in lifetime assessment under uncertainties, where the direct method has shown faster convergence than response surface method. (C) 2010 Elsevier Ltd. All rights reserved.

A coupled boundary element/differential equation method formulation for plate-beam interaction analysis

In this work, a new boundary element formulation for the analysis of plate-beam interaction is presented. This formulation uses a three nodal value boundary elements and each beam element is replaced by its actions on the plate, i.e., a distributed load and end of element forces. From the solution of the differential equation of a beam with linearly distributed load the plate-beam interaction tractions can be written as a function of the nodal values of the beam. With this transformation a final system of equation in the nodal values of displacements of plate boundary and beam nodes is obtained and from it, all unknowns of the plate-beam system are obtained. Many examples are analyzed and the results show an excellent agreement with those from the analytical solution and other numerical methods. (C) 2009 Elsevier Ltd. All rights reserved.

Design and Characterization of Novel Wear Resistant Multilayer CVD Coatings with Improved Adhesion Between Al(2)O(3) and Ti(C,N)

Multilayer CVD coatings for high speed cutting applications were designed to achieve high wear and heat resistance during machining of steel alloys. In this work the microstructure and cutting performance of these novel multilayer CVD coatings are investigated and compared with standard CVD multilayer coatings. 3D-FIB tomography is used to characterize the microstructure of the layers, especially the transition between the Ti(C,N) and the Al(2)O(3) layer. The 3D reconstruction of the surface of the Ti(C,N) layer shows the formation of protruded Ti(C,N) grains with a very particular architecture, which penetrate into the Al(2)O(3) top-layer, providing a mechanical anchoring between both layers. Cemented carbides coated with the novel CVD multilayer present reduced crater and flank wear as well as improved adherence between the Al(2)O(3) top-layer and the Ti(C,N) layer leading to a dramatic improvement of cutting performance.

Ion nitriding of a superaustenitic stainless steel: Wear and corrosion characterization

The superiority of superaustenitic stainless steel (SASS) lies in its good weldability and great resistance to stress corrosion and pitting, because of its higher chromium, molybdenum, and nitrogen contents, when compared to general stainless steels. However, some of its applications are limited by very poor wear behavior. Plasma-nitriding is a very effective treatment for producing wear resistant and hard surface layers on stainless steels without compromising the corrosion resistance. In this work, UNS S31254 SASS samples were plasma-nitrided at three different temperatures (400, 450, and 500 degrees C), under a pressure of 500 Pa, for 5 h, in order to verify the influence of the temperature on the morphology, wear, and corrosion behavior of the modified surface layers. The plasma-nitrided samples were analyzed by means of optical microscopy, micro-hardness. X-ray diffraction, wear, and corrosion tests. Wear tests were conducted in a fixed ball micro-wear machine and corrosion behavior was carried out in natural sea water by means of potentiodynamic polarization curves. For the sample which was plasma-nitrided at 400 degrees C, only the expanded austenite phase was observed, and for the treatments performed at 450 and 500 degrees C, chromium nitrides (CrN and Cr(2)N) were formed in addition to the expanded austenite. Wear volume and Knoop surface hardness increased as the plasma-nitriding temperature increased. Higher wear rates were observed at high temperatures, probably due to the increment on layer fragility. The sample modified at 400 degrees C exhibited the best corrosion behavior among all the plasma-nitriding conditions. (C) 2010 Elsevier B.V. All rights reserved.

Dendritic Arm Spacing Affecting Mechanical Properties and Wear Behavior of Al-Sn and Al-Si Alloys Directionally Solidified under Unsteady-State Conditions

Alloys of Al-Sn and Al-Si are widely used in tribological applications such as cylinder liners and journal bearings. Studies of the influence of the as-cast microstructures of these alloys on the final mechanical properties and wear resistance can be very useful for planning solidification conditions in order to permit a desired level of final properties to be achieved. The aim of the present study was to contribute to a better understanding about the relationship between the scale of the dendritic network and the corresponding mechanical properties and wear behavior. The Al-Sn (15 and 20 wt pct Sn) and Al-Si (3 and 5 wt pct Si) alloys were directionally solidified under unsteady-state heat flow conditions in water-cooled molds in order to permit samples with a wide range of dendritic spacings to be obtained. These samples were subjected to tensile and wear tests, and experimental quantitative expressions correlating the ultimate tensile strength (UTS), yield tensile strength, elongation, and wear volume to the primary dendritic arm spacing (DAS) have been determined. The wear resistance was shown to be significantly affected by the scale of primary dendrite arm spacing. For Al-Si alloys, the refinement of the dendritic array improved the wear resistance, while for the Al-Sn alloys, an opposite effect was observed, i.e., the increase in primary dendrite arm spacing improved the wear resistance. The effect of inverse segregation, which is observed for Al-Sn alloys, on the wear resistance is also discussed.