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As civil engineering structures are growing in dimension and longevity, there is an associated increase in concern regarding the maintenance of such structures. Bridges, in particular, are critical links in today’s transportation networks and hence fundamental for the development of society. In this context, the demand for novel damage detection techniques and reliable structural health monitoring systems is currently high. This paper presents a model-free damage detection approach based on machine learning techniques. The method is applied to data on the structural condition of a fictitious railway bridge gathered in a numerical experiment using a three-dimensional finite element model. Data are collected from the dynamic response of the structure, which is simulated in the course of the passage of a train, considering the bridge in healthy and two different damaged scenarios. In the first stage of the proposed method, artificial neural networks are trained with an unsupervised learning approach with input data composed of accelerations gathered on the healthy bridge. Based on the acceleration values at previous instants in time, the networks are able to predict future accelerations. In the second stage, the prediction errors of each network are statistically characterized by a Gaussian process that supports the choice of a damage detection threshold. Subsequent to this, by comparing damage indices with said threshold, it is possible to discriminate between different structural conditions, namely between healthy and damaged. From here and for each damage case scenario, receiver operating characteristic curves that illustrate the trade-off between true and false positives can be obtained. Lastly, based on the Bayes’ Theorem, a simplified method for the calculation of the expected total cost of the proposed strategy, as a function of the chosen threshold, is suggested.

Flexible docking and scoring using the internal coordinate mechanics software (ICM) was benchmarked for ligand binding mode prediction against the 85 co-crystal structures in the modified Astex data set. The ICM virtual ligand screening was tested against the 40 DUD target benchmarks and 11-target WOMBAT sets. The self-docking accuracy was evaluated for the top 1 and top 3 scoring poses at each ligand binding site with near native conformations below 2 Å RMSD found in 91 and 95% of the predictions, respectively. The virtual ligand screening using single rigid pocket conformations provided the median area under the ROC curves equal to 69.4 with 22.0% true positives recovered at 2% false positive rate. Significant improvements up to ROC AUC = 82.2 and ROC (2%)  = 45.2 were achieved following our best practices for flexible pocket refinement and out-of-pocket binding rescore. The virtual screening can be further improved by considering multiple conformations of the target.

Middle- and inner-ear surgery is a vital treatment option in hearing loss, infections, and tumors of the lateral skull base. Segmentation of otologic structures from computed tomography (CT) has many potential applications for improving surgical planning but can be an arduous and time-consuming task. We propose an end-to-end solution for the automated segmentation of temporal bone CT using convolutional neural networks (CNN). Using 150 manually segmented CT scans, a comparison of 3 CNN models (AH-Net, U-Net, ResNet) was conducted to compare Dice coefficient, Hausdorff distance, and speed of segmentation of the inner ear, ossicles, facial nerve and sigmoid sinus. Using AH-Net, the Dice coefficient was 0.91 for the inner ear; 0.85 for the ossicles; 0.75 for the facial nerve; and 0.86 for the sigmoid sinus. The average Hausdorff distance was 0.25, 0.21, 0.24 and 0.45 mm, respectively. Blinded experts assessed the accuracy of both techniques, and there was no statistical difference between the ratings for the two methods (p = 0.93). Objective and subjective assessment confirm good correlation between automated segmentation of otologic structures and manual segmentation performed by a specialist. This end-to-end automated segmentation pipeline can help to advance the systematic application of augmented reality, simulation, and automation in otologic procedures.

Abstract Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects’ tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies. Resumo Em todo o mundo, a agricultura convencional faz uso extensivo de pesticidas. Embora os efeitos dos herbicidas sejam relativamente bem conhecidos em termos de impactos ambientais em organismos não-alvo, há pouca evidência científica sobre os impactos de resíduos de herbicidas em artrópodes aquáticos de áreas de conservação tropicais. Este estudo avalia pela primeira vez a toxicidade dos herbicidas ametryn, atrazine e clomazone sobre o inseto aquático Limnocoris submontandoni (Hemiptera: Naucoridae). A concentração letal (LC50) de herbicidas foi avaliada para esses insetos, bem como o efeito dos herbicidas nos tecidos e testículos dos insetos. A LC50 estimada foi de 1012,41, 192,42 e 46,09 mg/L para clomazone, atrazine e ametryn, respectivamente. Alterações nos espermatócitos e espermátides foram observadas sob o efeito de atrazine, e efeitos na espermatogênese foram observados para algumas concentrações de clomazone, com aparente recuperação após um curto período de tempo. Nossos resultados fornecem informações úteis sobre os efeitos de resíduos de herbicidas em sistemas aquáticos. Essas informações podem ajudar a minimizar o risco de efeitos reprodutivos de longo prazo em espécies não-alvo que foram negligenciadas anteriormente em estudos de ecotoxicologia.

Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ) protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.

Brazil is the largest sugarcane producer in the world, mainly due to the development of different management strategies. Recently, microbial-plant related studies revealed that bacterial isolates belonging to the genus Burkholderia are mainly associated with this plant and are responsible for a range of physiological activity. In this study, we properly evaluate the physiological activity and genetic diversity of endophytic and rhizospheric Burkholderia spp. isolates from sugarcane roots grown in the field in Brazil. In total, 39 isolates previously identified as Burkholderia spp. were firstly evaluated for the capability to fix nitrogen, produce siderophores, solubilise inorganic phosphates, produce indole-acetic acid and inhibit sugarcane phytopathogens in vitro. These results revealed that all isolates present at least two positive evaluated activities. Furthermore, a phylogenetic study was carried out using 16S rRNA and gyr B genes revealing that most of the isolates were affiliated with the Burkholderia cepacia complex. Hence, a clear separation given by endophytic or rhizospheric niche occupation was not observed. These results presented an overview about Burkholderia spp. isolates from sugarcane roots and supply information about the physiological activity and genetic diversity of this genus, given direction for further studies related to achieve more sustainable cultivation of sugarcane.

Cyanobacteria are commonly found in drinking water supplies, and are responsible by numerous cases of humans’ intoxications. Geitlerinema is a genus described as unable to form blooms, however, it is very frequent in Sao Paulo’s reservoirs, the most densely populated area in Brazil. During the search for bioactive substances from strains maintained in the Cyanobacteria Culture Collection of the Institute of Botany, Sao Paulo, Brazil, three strains of Geitlerinema spp. (CCIBt920, CCIBt1044—G. amphibium; CCIBt939—G. splendidum) showed toxicity in mouse bioassay (i.p.). The symptoms observed in this bioassay were very distinct from those presented by animals poisoned with the already known cyanotoxins. In such cases, histological analysis of vital organs is very important to determine the cause of deaths and intoxication. Histological analyses were performed in mice administrated with CCIBt920 and CCIBt1044 methanol extract (ME), and CCIBt939 0.1 M acetic acid extract (AE). All extracts caused very similar histopathological features: hemorrhagic focuses, edema, alveolar collapse and hyperplasia in the lungs, due to an increase in the number of immune system cells (macrophages); disorganization of the hepatic parenchyma, necrosis, loss of vein endothelium, presence of polymorphonuclear cells in the liver; alterations in the convoluted tubules and necrotic areas in the kidneys of mice intoxicated with CCIBt939 AE, while the other G. amphibium extracts had no major effects in this organ. The histopathological findings indicate the occurrence of inflammatory processes in the mice treated with these cyanobacteria extracts. Taken together, our results suggest the presence of new cyanotoxins(s), different from the known cyanotoxins. The isolation and characterization of this toxin(s) are in progress in our laboratories.

CXCR4 is a G-protein coupled receptor for CXCL12 that plays an important role in human immunodeficiency virus infection, cancer growth and metastasization, immune cell trafficking and WHIM syndrome. In the absence of an X-ray crystal structure, theoretical modeling of the CXCR4 receptor remains an important tool for structure–function analysis and to guide the discovery of new antagonists with potential clinical use. In this study, the combination of experimental data and molecular modeling approaches allowed the development of optimized ligand-receptor models useful for elucidation of the molecular determinants of small molecule binding and functional antagonism. The ligand-guided homology modeling approach used in this study explicitly re-shaped the CXCR4 binding pocket in order to improve discrimination between known CXCR4 antagonists and random decoys. Refinement based on multiple test-sets with small compounds from single chemotypes provided the best early enrichment performance. These results provide an important tool for structure-based drug design and virtual ligand screening of new CXCR4 antagonists.

The performance of heavy-timber structures in earthquakes depends strongly on the inelastic behavior of the mechanical connections. Nevertheless, the nonlinear behavior of timber structures is only considered in the design phase indirectly through the use of an R-factor or a q-factor, which reduces the seismic elastic response spectrum. To improve the estimation of this, the seismic performance of a three-story building designed with ring-doweled moment resisting connections is analyzed here. Connections and members were designed to fulfill the seismic detailing requirements present in Eurocode 5 and Eurocode 8 for high ductility class structures. The performance of the structure is evaluated through a probabilistic approach, which accounts for uncertainties in mechanical properties of members and connections. Nonlinear static analyses and multi-record incremental dynamic analyses were performed to characterize the q-factor and develop fragility curves for different damage levels. The results indicate that the detailing requirements of Eurocode 5 and Eurocode 8 are sufficient to achieve the required performance, even though they also indicate that these requirements may be optimized to achieve more cost-effective connections and members. From the obtained fragility curves, it was verified that neglecting modeling uncertainties may lead to overestimation of the collapse capacity.

A new class of insecticide derived from fermentation of Sacharopolyspora spinosa - spinosad, has been indicated as being of low toxicity and a natural alternative to classical pesticides. In order to elucidate several aspects related to the morphophysiological changes induced by spinosad in Artibeus lituratus, the effects of a seven-day administration on plasma glucose, glycogen, protein and lipid concentrations were evaluated, and possible changes in liver cells were examined by histological analysis. Animals were fed with spinosyn-contaminated fruit through immersion in a solution. Data reporting on metabolism revealed a decrease in hind limb muscle lipid concentration in the treated group. Morphological analysis indicated a significant increase in liver cell diameter in treated animals compared to the control group. This study indicates that spinosyn, used at its recommended dose, does not affect general energy metabolism in A. lituratus but may affect some ultrastructural characteristics of liver cells. Uma nova classe de inseticida derivado da fermentação de Sacharopolyspora spinosa - espinosade - tem sido indicada como uma alternativa natural de baixa toxicidade aos agrotóxicos clássicos. A fim de elucidar diversos aspectos relacionados às mudanças morfofisiológicas induzidas por espinosade Artibeus lituratus, os efeitos da administração durante sete dias sobre a glicose plasmática, proteína de glicogênio, e as concentrações de lipídios foram avaliados, assim como possíveis alterações nas células do fígado foram examinadas por análise histológica. Os animais foram alimentados com frutas contaminadas com espinosade por meio de imersão em uma solução. Os dados sobre o metabolismo revelaram um decréscimo na concentração de lipídios dos músculos das patas posteriores dos animais do grupo tratado. A análise morfológica indicou um aumento significativo no diâmetro das células do fígado dos animais tratados em relação ao controle. Este estudo indica que o espinosade, utilizado na dose recomendada, não afeta o metabolismo energético em geral de A. lituratus, mas pode afetar algumas características ultraestruturais das células hepáticas.