Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Wastewater reclamation through a combination of natural systems (infiltration-percolation and constructed wetlands): a solution for small communities.

The decision on technologies used for reclaiming wastewater appears as important as a consequence of the implications on the economic, environmental and health conditions of societies. The problem arises when deciding how to deal with wastewater in small communities, because the costs of implementing and operating small, intensive wastewater treatment plants are unacceptable and can lead to financing and operation problems. Extensive treatment systems can be a good solution, where space is available. This paper presents the combination of two soft technologies (infiltration-percolation and constructed wetlands) to treat and reclaim wastewater. The obtained results show that the infiltration-percolation effluent presents a quality enough to be reused for irrigation of industrial crops, nurseries, fodder, cereals and oleaginous seeds, ornamental flower production; industrial cooling; impoundments, water bodies, and streams for recreational use in which the public's contact with the water is not permitted; and irrigation of forested areas, landscape areas and restricted access areas. Moreover, the combination of infiltration-percolation and constructed wetlands increases the list of final reclamation to the following: irrigation of pasture for milk or meat animals, crops for canning industry, crops not raw-consumed, fruit trees except by sprinkling, aquaculture; and aquifer recharge by localised percolation through the soil.     

Discovering social structures of local influence by using tweetStimuli

Information diffusion in large-scale networks has been studied to identify the users influence. The influence has been targeted as a key feature either to reach large populations or influencing public opinion. Through the use of micro-blogs, such as Twitter, global influencers have been identified and ranked based on message propagation (retweets). In this paper, a new application is presented, which allows to find first and classify then the local influence on Twitter: who have influenced you and who have been influenced by you. Until now, social structures of tweets’ original authors that have been either retweeted or marked as favourites are unobservable. Throughout this application, these structures can be discovered and they reveal the existence of communities formed by users of similar profile (that are connected among them) interrelated with other similar profile users’ communities.     

Solving weighted CSPs with meta-constraints by reformulation into satisfiability modulo theories

We introduce WSimply, a new framework for modelling and solving Weighted Constraint Satisfaction Problems (WCSP) using Satisfiability Modulo Theories (SMT) technology. In contrast to other well-known approaches designed for extensional representation of goods or no-goods, and with few declarative facilities, our approach aims to follow an intensional and declarative syntax style. In addition, our language has built-in support for some meta-constraints, such as priority and homogeneity, which allows the user to easily specify rich requirements on the desired solutions, such as preferences and fairness. We propose two alternative strategies for solving these WCSP instances using SMT. The first is the reformulation into Weighted SMT (WSMT) and the application of satisfiability test based algorithms from recent contributions in the Weighted Maximum Satisfiability field. The second one is the reformulation into an operation research-like style which involves an optimisation variable or objective function and the application of optimisation SMT solvers. We present experimental results of two well-known problems: the Nurse Rostering Problem (NRP) and a variant of the Balanced Academic Curriculum Problem (BACP), and provide some insights into the impact of the addition of meta-constraints on the quality of the solutions and the solving time.     

The efforts in the forearm during the use of anti-vibration gloves in simulated work tasks

The objective of this article is to analyze the levels of forearm muscular contraction associated with the use of anti-vibration gloves, in which the contraction levels with gloves and without gloves are compared. Two different vibrating tools - a Bosch Compact Duty Multi-Cutter and a Bosch Rotary Hammer carrying an Ø20 mm bit - were used in a simulated work environment. Standard operations were performed by each subject (n = 14) in an 80 × 40 mm pine bar (cross-sectional cuts with the Multi-Cutter) and on a concrete slab 2 × 2 m, 70 mm thick (20 mm holes with the Rotary Hammer). The forearm muscular efforts were measured by surface electromyography (EMG) in four different muscles: the flexor digitorum superficialis (FDS), flexor carpi ulnaris (FCU), extensor carpi radialis longus (ECRL) and extensor carpi ulnaris (ECU). For the flexor muscles (FDS and FCU), a decrease tendency (p > 0.05) in the measured EMG was observed when the operations are performed with gloves relative to the bare hand (a reduction of 5-23% in the percentage of maximum voluntary exertion (%MVE)). For the extensor muscles (ECU), a tendency toward increased (p > 0.05) muscular contraction was observed when the operations were performed with gloves (an increase of 3-20% in the %MVE). No such tendency was found in the ECRL muscle. The ECU was the muscle with the highest %MVE for 10 and 11 operators (n = 14), during the operations, respectively, with the Multi-Cutter and the Rotary Hammer. As a final conclusion from the study, anti-vibration gloves may increase forearm fatigue in the posterior forearm (ECU muscle) and decrease forearm fatigue in the FDS muscle during operations with the above-mentioned tools.

Relevance to industry

Anti-vibration gloves have been applied in industry to reduce the vibration transmitted into the hand and arms through the palms and fingers. This study analyzed forearm muscular efforts during simulated work tasks performed with two different vibrating tools, operated with the bare hand and with three different gloves, based on the analysis of EMG data.     

A Systematic Study of Restorative Crown-Materials Combinations for Dental Implants: Characterization of Mechanical Properties under Dynamic Loads

This study aimed to find the optimum mechanical characteristics of the restorative materials for the manufacture of implant crowns subjected to impact loading when different combinations of materials are used for the inner and outer crown. Several combinations of external–internal crown restorative materials were analyzed. The dynamic stresses at eight different zones of a dental implant subjected to an impact load and the influence of several mechanical properties, such as the Young’s modulus, Poisson’s ratio, density, and initial velocity, were analyzed and compared. A detailed 3D model was created, including the crown, the retention screw, the implant, and a mandible section. The model was then built by importing the 3D geometries from CAD software. The whole 3D model was carefully created in order to guarantee a finite element mesh that produced results adjusted to physical reality. Then, we conducted a numerical simulation using the finite element method (FEM). The results of the FEM analysis allowed for evaluating the effect that different combinations of restorative materials and mechanical properties had on the stress distribution in various regions of the implant. The choice of restorative material is a factor to be considered in order to preserve the integrity of osseointegration. Restorative materials transfer more or less stress to the dental implant and surrounding bone, depending on their stiffness. Therefore, an inadequate Young’s modulus of the rehabilitation material can affect the survival of the implant over time. Eight interactive graphics were provided on a web-based surface platform to help clinical dentists, researchers, and manufacturers to select the best restorative materials combination for the crown.     

Experimentation with a water tank including a PCM module

Storage of heat is seen as a major issue for the development of solar energy for house heating and cooling under all climates. Most of the storage systems available on the market use water as the storage medium. The idea studied here was to add a phase change material (PCM) module at the top of a hot-water storage tank with stratification. An experimental solar pilot plant was constructed to test the PCM behaviour in real conditions. The PCM module geometry adopted was to use several cylinders. A granular PCM–graphite compound was chosen as the PCM for the experiments presented here.     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

Multi‐phosphorylation of the Intrinsically Disordered Unique Domain of c‐Src Studied by In‐Cell and Real‐Time NMR Spectroscopy

Intrinsically disordered regions (IDRs) are preferred sites for post‐translational modifications essential for regulating protein function. The enhanced local mobility of IDRs facilitates their observation by NMR spectroscopy in vivo. Phosphorylation events can occur at multiple sites and respond dynamically to changes in kinase–phosphatase networks. Here we used real‐time NMR spectroscopy to study the effect of kinases and phosphatases present in Xenopus oocytes and egg extracts on the phosphorylation state of the “unique domain” of c‐Src. We followed the phosphorylation of S17 in oocytes, and of S17, S69, and S75 in egg extracts by NMR spectroscopy, MS, and western blotting. Addition of specific kinase inhibitors showed that S75 and S69 are phosphorylated by CDKs (cyclin‐dependent kinases) differently from Cdk1. Moreover, although PKA (cAMP‐dependent protein kinase) can phosphorylate S17 in vitro, this was not the major S17 kinase in egg extracts. Changes in PKA activity affected the phosphorylation levels of CDK‐dependent sites, thus suggesting indirect effects of kinase–phosphatase networks. This study provides a proof‐of‐concept of the use of real‐time in vivo NMR spectroscopy to characterize kinase/phosphatase effects on intrinsically disordered regulatory domains.     

Fe(PyTACN)‐Catalyzed cis‐Dihydroxylation of Olefins with Hydrogen Peroxide

A family of iron complexes with general formula [Fe(II)(^R,Y,XPyTACN)(CF₃SO₃)₂], where ^R,Y,XPyTACN=1‐[2′‐(4‐Y‐6‐X‐pyridyl)methyl]‐4,7‐dialkyl‐1,4,7‐triazacyclononane, X and Y refer to the groups at positions 4 and 6 of the pyridine, respectively, and R refers to the alkyl substitution at N‐4 and N‐7 of the triazacyclononane ring, are shown to be catalysts for efficient and selective alkene oxidation (epoxidation and cis‐dihydroxylation) employing hydrogen peroxide as oxidant. Complex [Fe(II)(^Me,Me,HPyTACN)(CF₃SO₃)₂] ( 7 ), was identified as the most efficient and selective cis‐dihydroxylation catalyst among the family. The high activity of 7 allows the oxidation of alkenes to proceed rapidly (30 min) at room temperature and under conditions where the olefin is not used in large amounts but instead is the limiting reagent. In the presence of 3 mol% of 7 , 2 equiv. of H₂O₂ as oxidant and 15 equiv. of water, in acetonitrile solution, alkenes are cis‐dihydroxylated reaching yields that might be interesting for synthetic purposes. Competition experiments show that 7 exhibits preferential selectivity towards the oxidation of cis olefins over the trans analogues, and also affords better yields and high [syn‐diol]/[epoxide] ratios when cis olefins are oxidized. For aliphatic substrates, reaction yields attained with the present system compare favourably with state of the art Fe‐catalyzed cis‐dihydroxylation systems, and it can be regarded as an attractive complement to the iron and manganese systems described recently and which show optimum activity against electron‐deficient and aromatic olefins.