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Showing papers in "Scientific Reports in 2019"


Journal ArticleDOI
TL;DR: In the present study, 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples collected in a bus station and an outdoor site, showing low cancer risk incidence and incremental lifetime cancer risk (ILCR) calculated for both places.
Abstract: Polycyclic aromatic compounds (PACs) are known due to their mutagenic activity. Among them, 2-nitrobenzanthrone (2-NBA) and 3-nitrobenzanthrone (3-NBA) are considered as two of the most potent mutagens found in atmospheric particles. In the present study 2-NBA, 3-NBA and selected PAHs and Nitro-PAHs were determined in fine particle samples (PM 2.5) collected in a bus station and an outdoor site. The fuel used by buses was a diesel-biodiesel (96:4) blend and light-duty vehicles run with any ethanol-to-gasoline proportion. The concentrations of 2-NBA and 3-NBA were, on average, under 14.8 µg g−1 and 4.39 µg g−1, respectively. In order to access the main sources and formation routes of these compounds, we performed ternary correlations and multivariate statistical analyses. The main sources for the studied compounds in the bus station were diesel/biodiesel exhaust followed by floor resuspension. In the coastal site, vehicular emission, photochemical formation and wood combustion were the main sources for 2-NBA and 3-NBA as well as the other PACs. Incremental lifetime cancer risk (ILCR) were calculated for both places, which presented low values, showing low cancer risk incidence although the ILCR values for the bus station were around 2.5 times higher than the ILCR from the coastal site.

5,412 citations


Journal ArticleDOI
Daniel Conroy-Beam1, David M. Buss2, Kelly Asao2, Agnieszka Sorokowska3, Agnieszka Sorokowska4, Piotr Sorokowski4, Toivo Aavik5, Grace Akello6, Mohammad Madallh Alhabahba7, Charlotte Alm8, Naumana Amjad9, Afifa Anjum9, Chiemezie S. Atama10, Derya Atamtürk Duyar11, Richard Ayebare, Carlota Batres12, Mons Bendixen13, Aicha Bensafia14, Boris Bizumic15, Mahmoud Boussena14, Marina Butovskaya16, Marina Butovskaya17, Seda Can18, Katarzyna Cantarero19, Antonin Carrier20, Hakan Cetinkaya21, Ilona Croy3, Rosa María Cueto22, Marcin Czub4, Daria Dronova17, Seda Dural18, İzzet Duyar11, Berna Ertuğrul23, Agustín Espinosa22, Ignacio Estevan24, Carla Sofia Esteves25, Luxi Fang26, Tomasz Frackowiak4, Jorge Contreras Garduño27, Karina Ugalde González, Farida Guemaz, Petra Gyuris28, Mária Halamová29, Iskra Herak20, Marina Horvat30, Ivana Hromatko31, Chin Ming Hui26, Jas Laile Suzana Binti Jaafar32, Feng Jiang33, Konstantinos Kafetsios34, Tina Kavčič35, Leif Edward Ottesen Kennair13, Nicolas Kervyn20, Truong Thi Khanh Ha19, Imran Ahmed Khilji36, Nils C. Köbis37, Hoang Moc Lan19, András Láng28, Georgina R. Lennard15, Ernesto León22, Torun Lindholm8, Trinh Thi Linh19, Giulia Lopez38, Nguyen Van Luot19, Alvaro Mailhos24, Zoi Manesi39, Rocio Martinez40, Sarah L. McKerchar15, Norbert Meskó28, Girishwar Misra41, Conal Monaghan15, Emanuel C. Mora42, Alba Moya-Garófano40, Bojan Musil30, Jean Carlos Natividade43, Agnieszka Niemczyk4, George Nizharadze, Elisabeth Oberzaucher44, Anna Oleszkiewicz3, Anna Oleszkiewicz4, Mohd Sofian Omar-Fauzee45, Ike E. Onyishi10, Barış Özener11, Ariela Francesca Pagani38, Vilmante Pakalniskiene46, Miriam Parise38, Farid Pazhoohi47, Annette Pisanski42, Katarzyna Pisanski4, Katarzyna Pisanski48, Edna Lúcia Tinoco Ponciano, Camelia Popa49, Pavol Prokop50, Pavol Prokop51, Muhammad Rizwan, Mario Sainz52, Svjetlana Salkičević31, Ruta Sargautyte46, Ivan Sarmány-Schuller53, Susanne Schmehl44, Shivantika Sharad41, Razi Sultan Siddiqui54, Franco Simonetti55, Stanislava Stoyanova56, Meri Tadinac31, Marco Antonio Correa Varella57, Christin-Melanie Vauclair25, Luis Diego Vega, Dwi Ajeng Widarini, Gyesook Yoo58, Marta Zaťková29, Maja Zupančič59 
University of California, Santa Barbara1, University of Texas at Austin2, Dresden University of Technology3, University of Wrocław4, University of Tartu5, Gulu University6, Middle East University7, Stockholm University8, University of the Punjab9, University of Nigeria, Nsukka10, Istanbul University11, Franklin & Marshall College12, Norwegian University of Science and Technology13, University of Algiers14, Australian National University15, Russian State University for the Humanities16, Russian Academy of Sciences17, İzmir University of Economics18, University of Social Sciences and Humanities19, Université catholique de Louvain20, Ankara University21, Pontifical Catholic University of Peru22, Cumhuriyet University23, University of the Republic24, ISCTE – University Institute of Lisbon25, The Chinese University of Hong Kong26, National Autonomous University of Mexico27, University of Pécs28, University of Constantine the Philosopher29, University of Maribor30, University of Zagreb31, University of Malaya32, Central University of Finance and Economics33, University of Crete34, University of Primorska35, Institute of Molecular and Cell Biology36, University of Amsterdam37, Catholic University of the Sacred Heart38, VU University Amsterdam39, University of Granada40, University of Delhi41, University of Havana42, Pontifical Catholic University of Rio de Janeiro43, University of Vienna44, Universiti Utara Malaysia45, Vilnius University46, University of British Columbia47, University of Sussex48, Romanian Academy49, Comenius University in Bratislava50, Slovak Academy of Sciences51, University of Monterrey52, SAS Institute53, DHA Suffa University54, Pontifical Catholic University of Chile55, South-West University "Neofit Rilski"56, University of São Paulo57, Kyung Hee University58, University of Ljubljana59
TL;DR: This work combines this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets and finds that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
Abstract: Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.

1,827 citations


Journal ArticleDOI
TL;DR: In this article, the authors show that the Louvain algorithm may yield arbitrarily badly connected communities and, in the worst case, communities may even be disconnected, especially when running the algorithm iteratively.
Abstract: Community detection is often used to understand the structure of large and complex networks. One of the most popular algorithms for uncovering community structure is the so-called Louvain algorithm. We show that this algorithm has a major defect that largely went unnoticed until now: the Louvain algorithm may yield arbitrarily badly connected communities. In the worst case, communities may even be disconnected, especially when running the algorithm iteratively. In our experimental analysis, we observe that up to 25% of the communities are badly connected and up to 16% are disconnected. To address this problem, we introduce the Leiden algorithm. We prove that the Leiden algorithm yields communities that are guaranteed to be connected. In addition, we prove that, when the Leiden algorithm is applied iteratively, it converges to a partition in which all subsets of all communities are locally optimally assigned. Furthermore, by relying on a fast local move approach, the Leiden algorithm runs faster than the Louvain algorithm. We demonstrate the performance of the Leiden algorithm for several benchmark and real-world networks. We find that the Leiden algorithm is faster than the Louvain algorithm and uncovers better partitions, in addition to providing explicit guarantees.

1,776 citations


Journal ArticleDOI
TL;DR: The phylogenetic analysis complemented with synteny analyses suggests that Bmp2, -4 and -16 are remnants of a gene quartet that originated during the two rounds of whole-genome duplication (2R-WGD) early in vertebrate evolution.
Abstract: The vertebrate gene repertoire is characterized by “cryptic” genes whose identification has been hampered by their absence from the genomes of well-studied species. One example is the Bmp16 gene, a paralog of the developmental key genes Bmp2 and -4. We focus on the Bmp2/4/16 group of genes to study the evolutionary dynamics following gen(om)e duplications with special emphasis on the poorly studied Bmp16 gene. We reveal the presence of Bmp16 in chondrichthyans in addition to previously reported teleost fishes and reptiles. Using comprehensive, vertebrate-wide gene sampling, our phylogenetic analysis complemented with synteny analyses suggests that Bmp2, -4 and -16 are remnants of a gene quartet that originated during the two rounds of whole-genome duplication (2R-WGD) early in vertebrate evolution. We confirm that Bmp16 genes were lost independently in at least three lineages (mammals, archelosaurs and amphibians) and report that they have elevated rates of sequence evolution. This finding agrees with their more “flexible” deployment during development; while Bmp16 has limited embryonic expression domains in the cloudy catshark, it is broadly expressed in the green anole lizard. Our study illustrates the dynamics of gene family evolution by integrating insights from sequence diversification, gene repertoire changes, and shuffling of expression domains.

1,376 citations


Journal ArticleDOI
TL;DR: It is shown that the lacquer used to cover warriors and certain parts of weapons is rich in chromium, and it is demonstrated that chromium on the metals is contamination from nearby lacquer after burial, and the chromium anti-rust treatment theory should be abandoned.
Abstract: For forty years, there has been a widely held belief that over 2,000 years ago the Chinese Qin developed an advanced chromate conversion coating technology (CCC) to prevent metal corrosion. This belief was based on the detection of chromium traces on the surface of bronze weapons buried with the Chinese Terracotta Army, and the same weapons’ very good preservation. We analysed weapons, lacquer and soils from the site, and conducted experimental replications of CCC and accelerated ageing. Our results show that surface chromium presence is correlated with artefact typology and uncorrelated with bronze preservation. Furthermore we show that the lacquer used to cover warriors and certain parts of weapons is rich in chromium, and we demonstrate that chromium on the metals is contamination from nearby lacquer after burial. The chromium anti-rust treatment theory should therefore be abandoned. The good metal preservation probably results from the moderately alkaline pH and very small particle size of the burial soil, in addition to bronze composition.

1,097 citations


Journal ArticleDOI
TL;DR: Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature and highlight the importance of having in place a genetic monitoring program during releases to detect un-anticipated outcomes.
Abstract: In an attempt to control the mosquito-borne diseases yellow fever, dengue, chikungunya, and Zika fevers, a strain of transgenically modified Aedes aegypti mosquitoes containing a dominant lethal gene has been developed by a commercial company, Oxitec Ltd. If lethality is complete, releasing this strain should only reduce population size and not affect the genetics of the target populations. Approximately 450 thousand males of this strain were released each week for 27 months in Jacobina, Bahia, Brazil. We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27–30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.

884 citations


Journal ArticleDOI
TL;DR: The ENCODE blacklist is defined- a comprehensive set of regions in the human, mouse, worm, and fly genomes that have anomalous, unstructured, or high signal in next-generation sequencing experiments independent of cell line or experiment.
Abstract: Functional genomics assays based on high-throughput sequencing greatly expand our ability to understand the genome. Here, we define the ENCODE blacklist- a comprehensive set of regions in the human, mouse, worm, and fly genomes that have anomalous, unstructured, or high signal in next-generation sequencing experiments independent of cell line or experiment. The removal of the ENCODE blacklist is an essential quality measure when analyzing functional genomics data.

850 citations


Journal ArticleDOI
TL;DR: It is shown that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, and the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech.
Abstract: Mechanistic hypotheses about airborne infectious disease transmission have traditionally emphasized the role of coughing and sneezing, which are dramatic expiratory events that yield both easily visible droplets and large quantities of particles too small to see by eye. Nonetheless, it has long been known that normal speech also yields large quantities of particles that are too small to see by eye, but are large enough to carry a variety of communicable respiratory pathogens. Here we show that the rate of particle emission during normal human speech is positively correlated with the loudness (amplitude) of vocalization, ranging from approximately 1 to 50 particles per second (0.06 to 3 particles per cm3) for low to high amplitudes, regardless of the language spoken (English, Spanish, Mandarin, or Arabic). Furthermore, a small fraction of individuals behaves as "speech superemitters," consistently releasing an order of magnitude more particles than their peers. Our data demonstrate that the phenomenon of speech superemission cannot be fully explained either by the phonic structures or the amplitude of the speech. These results suggest that other unknown physiological factors, varying dramatically among individuals, could affect the probability of respiratory infectious disease transmission, and also help explain the existence of superspreaders who are disproportionately responsible for outbreaks of airborne infectious disease.

750 citations


Journal ArticleDOI
TL;DR: Coexistence of Fe-doped C12A7:e− related active sites with reduced graphene oxide (rGO) with pyridinic-nitrogen, and their strong coupling consequence along their porous morphology textures assist rapid diffusion of molecules to catalyst active sites quickly makes it highly desirable, precious-metal free electrocatalyst in ORR.
Abstract: Since the last decades, non-precious metal catalysts (NPMC), especially iron based electrocatalysts show sufficient activity, potentially applicant in oxygen reduction reaction (ORR), however they only withstand considerable current densities at low operating potentials. On the other hand iron based electrocatalysts are not stable at elevated cathode potentials, which is essential for high energy competence, and its remains difficult to deal. Therefore, via this research a simple approach is demonstrated that allows synthesis of nanosize Fe-doped mayenite electride, [Ca24Al28O64]4+·(e−)4 (can also write as, C12A7−xFex:e−, where doping level, x = 1) (thereafter, Fe-doped C12A7:e−), consist of abundantly available elements with gram level powder material production, based on simple citrate sol-gel method. The maximum achieved conductivity of this first time synthesized Fe-doped C12A7:e− composite materials was 249 S/cm. Consequently, Fe-doped C12A7:e− composite is cost-effective, more active and highly durable precious-metal free electrocatalyst, with 1.03 V onset potential, 0.89 V (RHE) half-wave potential, and ~5.9 mA/cm2 current density, which is higher than benchmark 20% Pt/C (5.65 mA/cm2, and 0.84 V). The Fe-doped C12A7:e− has also higher selectivity for desired 4e− pathway, and more stable than 20 wt% Pt/C electrode with higher immunity towards methanol poisoning. Fe-doped C12A7:e− loses was almost zero of its original activity after passing 11 h compared to the absence of methanol case, indicates that to introduce methanol has almost negligible consequence for ORR performance, which makes it highly desirable, precious-metal free electrocatalyst in ORR. This is primarily described due to coexistence of Fe-doped C12A7:e− related active sites with reduced graphene oxide (rGO) with pyridinic-nitrogen, and their strong coupling consequence along their porous morphology textures. These textures assist rapid diffusion of molecules to catalyst active sites quickly. In real system maximum power densities reached to 243 and 275 mW/cm2 for Pt/C and Fe-doped C12A7:e− composite, respectively.

512 citations


Journal ArticleDOI
TL;DR: In this article, the authors developed an end-to-end deep learning algorithm that can accurately detect breast cancer on screening mammograms using an "end to end" training approach that efficiently leverages training datasets with either complete clinical annotation or only the cancer status (label) of the whole image.
Abstract: The rapid development of deep learning, a family of machine learning techniques, has spurred much interest in its application to medical imaging problems. Here, we develop a deep learning algorithm that can accurately detect breast cancer on screening mammograms using an "end-to-end" training approach that efficiently leverages training datasets with either complete clinical annotation or only the cancer status (label) of the whole image. In this approach, lesion annotations are required only in the initial training stage, and subsequent stages require only image-level labels, eliminating the reliance on rarely available lesion annotations. Our all convolutional network method for classifying screening mammograms attained excellent performance in comparison with previous methods. On an independent test set of digitized film mammograms from the Digital Database for Screening Mammography (CBIS-DDSM), the best single model achieved a per-image AUC of 0.88, and four-model averaging improved the AUC to 0.91 (sensitivity: 86.1%, specificity: 80.1%). On an independent test set of full-field digital mammography (FFDM) images from the INbreast database, the best single model achieved a per-image AUC of 0.95, and four-model averaging improved the AUC to 0.98 (sensitivity: 86.7%, specificity: 96.1%). We also demonstrate that a whole image classifier trained using our end-to-end approach on the CBIS-DDSM digitized film mammograms can be transferred to INbreast FFDM images using only a subset of the INbreast data for fine-tuning and without further reliance on the availability of lesion annotations. These findings show that automatic deep learning methods can be readily trained to attain high accuracy on heterogeneous mammography platforms, and hold tremendous promise for improving clinical tools to reduce false positive and false negative screening mammography results. Code and model available at: https://github.com/lishen/end2end-all-conv .

449 citations


Journal ArticleDOI
TL;DR: A generative adversarial network, which is composed of a bidirectional long short-term memory and convolutional neural network, referred as BiLSTM-CNN, to generate synthetic ECG data that agree with existing clinical data so that the features of patients with heart disease can be retained.
Abstract: Heart disease is a malignant threat to human health. Electrocardiogram (ECG) tests are used to help diagnose heart disease by recording the heart’s activity. However, automated medical-aided diagnosis with computers usually requires a large volume of labeled clinical data without patients' privacy to train the model, which is an empirical problem that still needs to be solved. To address this problem, we propose a generative adversarial network (GAN), which is composed of a bidirectional long short-term memory(LSTM) and convolutional neural network(CNN), referred as BiLSTM-CNN,to generate synthetic ECG data that agree with existing clinical data so that the features of patients with heart disease can be retained. The model includes a generator and a discriminator, where the generator employs the two layers of the BiLSTM networks and the discriminator is based on convolutional neural networks. The 48 ECG records from individuals of the MIT-BIH database were used to train the model. We compared the performance of our model with two other generative models, the recurrent neural network autoencoder(RNN-AE) and the recurrent neural network variational autoencoder (RNN-VAE). The results showed that the loss function of our model converged to zero the fastest. We also evaluated the loss of the discriminator of GANs with different combinations of generator and discriminator. The results indicated that BiLSTM-CNN GAN could generate ECG data with high morphological similarity to real ECG recordings.

Journal ArticleDOI
TL;DR: Positive associations between recreational nature contact in the last seven days and self-reported health and well-being were consistent across key groups including older adults and those with long-term health issues.
Abstract: Spending time in natural environments can benefit health and well-being, but exposure-response relationships are under-researched. We examined associations between recreational nature contact in the last seven days and self-reported health and well-being. Participants (n = 19,806) were drawn from the Monitor of Engagement with the Natural Environment Survey (2014/15–2015/16); weighted to be nationally representative. Weekly contact was categorised using 60 min blocks. Analyses controlled for residential greenspace and other neighbourhood and individual factors. Compared to no nature contact last week, the likelihood of reporting good health or high well-being became significantly greater with contact ≥120 mins (e.g. 120–179 mins: ORs [95%CIs]: Health = 1.59 [1.31–1.92]; Well-being = 1.23 [1.08–1.40]). Positive associations peaked between 200–300 mins per week with no further gain. The pattern was consistent across key groups including older adults and those with long-term health issues. It did not matter how 120 mins of contact a week was achieved (e.g. one long vs. several shorter visits/week). Prospective longitudinal and intervention studies are a critical next step in developing possible weekly nature exposure guidelines comparable to those for physical activity.

Journal ArticleDOI
TL;DR: The fractal and particle analysis provide a relevant methodological framework to further the understanding of the spatial effects of economic pressure on forestry.
Abstract: The ever decreasing area of forests has lead to environmental and economical challenges and has brought with it a renewed interest in developing methodologies that quantify the extent of deforestation and reforestation. In this study we analyzed the deforested areas of the Apuseni Mountains, which has been under economic pressure in recent years and resulted in widespread deforestation as a means of income. Deforested surface dynamics modeling was based on images contained in the Global Forest Database, provided by the Department of Geographical Sciences at Maryland University between 2000 and 2014. The results of the image particle analysis and modelling were based on Total Area (ha), Count of patches and Average Size whereas deforested area distribution was based on the Local Connected Fractal Dimension, Fractal Fragmentation Index and Tug-of-War Lacunarity as indicators of forest fragmentation or heterogeneity. The major findings of the study indicated a reduction of the tree cover area by 3.8%, an increase in fragmentation of 17.7% and an increase in heterogeneity by 29%, while fractal connectivity decreased only by 0.1%. The fractal and particle analysis showed a clustering of forest loss areas with an average increase from 1.1 to 3.0 ha per loss site per year. In conclusion, the fractal and particle analysis provide a relevant methodological framework to further our understanding of the spatial effects of economic pressure on forestry.

Journal ArticleDOI
TL;DR: Synthesized Ag-NPs exhibited strong antibacterial activity against multidrug-resistant bacteria (Escherichia coli and Bacillus cereus) as well as cytotoxic effects against both human breast and human colon cancer cell lines.
Abstract: Using aqueous cyanobacterial extracts in the synthesis of silver nanoparticle is looked as green, ecofriendly, low priced biotechnology that gives advancement over both chemical and physical methods. In the current study, an aqueous extract of Oscillatoria limnetica fresh biomass was used for the green synthesis of Ag-NPs, since O. limnetica extract plays a dual part in both reducing and stabilizing Oscillatoria-silver nanoparticles (O-AgNPs). The UV-Visible absorption spectrum, Fourier transforms infrared (FT-IR), transmission electron microscopy (TEM) and scanning electron microscope (SEM) were achieved for confirming and characterizing the biosynthesized O-AgNPs. TEM images detected the quasi-spherical Ag-NPs shape with diverse size ranged within 3.30–17.97 nm. FT-IR analysis demonstrated the presence of free amino groups in addition to sulfur containing amino acid derivatives acting as stabilizing agents as well as the presence of either sulfur or phosphorus functional groups which possibly attaches silver. In this study, synthesized Ag-NPs exhibited strong antibacterial activity against multidrug-resistant bacteria (Escherichia coli and Bacillus cereus) as well as cytotoxic effects against both human breast (MCF-7) cell line giving IC50 (6.147 µg/ml) and human colon cancer (HCT-116) cell line giving IC50 (5.369 µg/ml). Hemolytic activity of Ag-NPs was investigated and confirmed as being non- toxic to human RBCs in low concentrations.

Journal ArticleDOI
TL;DR: The data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections are compared.
Abstract: In this study, we investigated lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in C57BL/6J mice by using behavioral tests, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and Western blot. We found that LPS treatment leads to sickness behavior and cognitive impairment in mice as shown in the Morris water maze and passive avoidance test, and these effects were accompanied by microglia activation (labeled by ionized calcium binding adaptor molecule-1, IBA-1) and neuronal cell loss (labeled by microtubule-associated protein 2, MAP-2) in the hippocampus. The levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in the serum and brain homogenates were reduced by the LPS treatment, while the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE2) and nitric oxide (NO) were increased. In addition, LPS promoted the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the brain homogenates. The Western blot analysis showed that the nuclear factor kappa B (NF-κB) signaling pathway was activated in the LPS groups. Furthermore, VIPER, which is a TLR-4-specific inhibitory peptide, prevented the LPS-induced neuroinflammation and cognitive impairment. These data suggest that LPS induced cognitive impairment and neuroinflammation via microglia activation by activating the NF-kB signaling pathway; furthermore, we compared the time points, doses, methods and outcomes of LPS administration between intraperitoneal and intracerebroventricular injections of LPS in LPS-induced neuroinflammation and cognitive impairment, and these data may provide additional insight for researchers performing neuroinflammation research.

Journal ArticleDOI
TL;DR: It is shown that in several CT segmentation tasks performance is improved significantly, especially in out-of-distribution (noncontrast CT) data, which will be valuable to medical imaging researchers to reduce manual segmentation effort and cost in CT imaging.
Abstract: Labeled medical imaging data is scarce and expensive to generate. To achieve generalizable deep learning models large amounts of data are needed. Standard data augmentation is a method to increase generalizability and is routinely performed. Generative adversarial networks offer a novel method for data augmentation. We evaluate the use of CycleGAN for data augmentation in CT segmentation tasks. Using a large image database we trained a CycleGAN to transform contrast CT images into non-contrast images. We then used the trained CycleGAN to augment our training using these synthetic non-contrast images. We compared the segmentation performance of a U-Net trained on the original dataset compared to a U-Net trained on the combined dataset of original data and synthetic non-contrast images. We further evaluated the U-Net segmentation performance on two separate datasets: The original contrast CT dataset on which segmentations were created and a second dataset from a different hospital containing only non-contrast CTs. We refer to these 2 separate datasets as the in-distribution and out-of-distribution datasets, respectively. We show that in several CT segmentation tasks performance is improved significantly, especially in out-of-distribution (noncontrast CT) data. For example, when training the model with standard augmentation techniques, performance of segmentation of the kidneys on out-of-distribution non-contrast images was dramatically lower than for in-distribution data (Dice score of 0.09 vs. 0.94 for out-of-distribution vs. in-distribution data, respectively, p < 0.001). When the kidney model was trained with CycleGAN augmentation techniques, the out-of-distribution (non-contrast) performance increased dramatically (from a Dice score of 0.09 to 0.66, p < 0.001). Improvements for the liver and spleen were smaller, from 0.86 to 0.89 and 0.65 to 0.69, respectively. We believe this method will be valuable to medical imaging researchers to reduce manual segmentation effort and cost in CT imaging.

Journal ArticleDOI
TL;DR: The combined pollen and speleothems proxy data indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by a less seasonal rainfall regime from the subtropics to the equatorial region.
Abstract: The origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex, Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal range of 30°S to 0°S. In addition, Principal Component Analysis and Species Distribution Modelling were used to represent past and modern habitat suitability for Podocarpus and Araucaria. The data reveals two long-distance patterns of plant migration connecting south/southeast to northeastern Brazil and Amazonia with a third short route extending from one of them. Their paleofloristic compositions suggest a climatic scenario of abundant rainfall and relative lower continental surface temperatures, possibly intensified by the effects of polar air incursions forming cold fronts into the Brazilian Highlands. Although these taxa are sensitive to changes in temperature, the combined pollen and speleothems proxy data indicate that this montane rainforest expansion during Heinrich Stadial 1 Event was triggered mainly by a less seasonal rainfall regime from the subtropics to the equatorial region.

Journal ArticleDOI
TL;DR: The observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.
Abstract: Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between gut microbiome and autism-like behaviors. Modifying the gut microbiome is a potential route to improve gastrointestinal (GI) and behavioral symptoms in children with ASD, and fecal microbiota transplant could transform the dysbiotic gut microbiome toward a healthy one by delivering a large number of commensal microbes from a healthy donor. We previously performed an open-label trial of Microbiota Transfer Therapy (MTT) that combined antibiotics, a bowel cleanse, a stomach-acid suppressant, and fecal microbiota transplant, and observed significant improvements in GI symptoms, autism-related symptoms, and gut microbiota. Here, we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. Important changes in gut microbiota at the end of treatment remained at follow-up, including significant increases in bacterial diversity and relative abundances of Bifidobacteria and Prevotella. Our observations demonstrate the long-term safety and efficacy of MTT as a potential therapy to treat children with ASD who have GI problems, and warrant a double-blind, placebo-controlled trial in the future.

Journal ArticleDOI
TL;DR: It is found that most of the ocean is experiencing significantly increasing cumulative impact, in particular due to climate change but also from fishing, land-based pollution and shipping.
Abstract: Humans interact with the oceans in diverse and profound ways. The scope, magnitude, footprint and ultimate cumulative impacts of human activities can threaten ocean ecosystems and have changed over time, resulting in new challenges and threats to marine ecosystems. A fundamental gap in understanding how humanity is affecting the oceans is our limited knowledge about the pace of change in cumulative impact on ocean ecosystems from expanding human activities – and the patterns, locations and drivers of most significant change. To help address this, we combined high resolution, annual data on the intensity of 14 human stressors and their impact on 21 marine ecosystems over 11 years (2003–2013) to assess pace of change in cumulative impacts on global oceans, where and how much that pace differs across the ocean, and which stressors and their impacts contribute most to those changes. We found that most of the ocean (59%) is experiencing significantly increasing cumulative impact, in particular due to climate change but also from fishing, land-based pollution and shipping. Nearly all countries saw increases in cumulative impacts in their coastal waters, as did all ecosystems, with coral reefs, seagrasses and mangroves at most risk. Mitigation of stressors most contributing to increases in overall cumulative impacts is urgently needed to sustain healthy oceans.

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TL;DR: The recombination zone was well confined inside the emitting layer and the recombination rate was most efficient in a 2CbzTAZ-based OLED, which exhibited the lowest driving voltage and the highest efficiencies.
Abstract: In this study, we demonstrated a blue phosphorescent organic light-emitting diode (BPOLED) based on a host with two carbazole and one trizole (2CbzTAZ) moiety, 9,9′-(2-(4,5-diphenyl-4H-1,2,4-triazol-3-yl)-1,3-phenylene)bis(9H-carbazole), that exhibits bipolar transport characteristics. Compared with the devices with a carbazole host (N,N’-dicarbazolyl-3,5-benzene, (mCP)), triazole host (3-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-4-phenyl-4H-1,2,4-triazole, (TAZ)), or a physical mixture of mCP:TAZ, which exhibit hole, electron, and bipolar transport characteristics, respectively, the BPOLED with the bipolar 2CbzTAZ host exhibited the lowest driving voltage (6.55 V at 10 mA/cm2), the highest efficiencies (maximum current efficiency of 52.25 cd/A and external quantum efficiency of 23.89%), and the lowest efficiency roll-off, when doped with bis[2-(4,6-difluorophenyl)pyridinato-C2,N](picolinato)iridium(III) (FIrpic) as blue phosphor. From analyses of light leakage of the emission spectra of electroluminescence, transient electroluminescence, and partially doped OLEDs, it was found that the recombination zone was well confined inside the emitting layer and the recombination rate was most efficient in a 2CbzTAZ-based OLED. For the other cases using mCP, TAZ, and mCP:TAZ as hosts, electrons and holes transported with different routes that resulted in carrier accumulation on different organic molecules and lowered the recombination rate.

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TL;DR: The efficacy of four kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality are compared to serve as a guide to choose and further optimize exosomal isolation methods for their desired downstream applications.
Abstract: Exosomes have received significant attention for their role in pathobiological processes and are being explored as a tool for disease diagnosis and management. Consequently, various isolation methods based on different principles have been developed for exosome isolation. Here we compared the efficacy of four kits from Invitrogen, 101Bio, Wako and iZON along with conventional ultracentrifugation-based method for exosome yield, purity and quality. Cell culture supernatant was used as an abundant source of exosomes, and exosome quantity, size-distribution, zeta-potential, marker-expression and RNA/protein quality were determined. The Invitrogen kit gave the highest yield but the preparation showed broader size-distribution likely due to microvesicle co-precipitation and had the least dispersion stability. Other preparations showed <150 nm size range and good stability. Preparation from iZON column; however, had a broader size-distribution in the lower size range suggestive of some impurities of non-vesicular aggregates. RNA quality from all preparations was comparable; however, proteins from Invitrogen method-based exosomal preparation showed polyethylene glycol (PEG) contamination in mass spectrometry. Chemical impurities from the precipitant could also be the cause of toxicity of Invitrogen method-based exosomal preparation in biological growth measurement assay. Together, these findings should serve as a guide to choose and further optimize exosome isolation methods for their desired downstream applications.

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TL;DR: In this article, the MRgFUS with intravenously injected microbubbles can temporarily and repeatedly disrupt the blood-brain barrier (BBB) in a targeted fashion, without open surgery.
Abstract: The blood-brain barrier (BBB) has long limited therapeutic access to brain tumor and peritumoral tissue. In animals, MR-guided focused ultrasound (MRgFUS) with intravenously injected microbubbles can temporarily and repeatedly disrupt the BBB in a targeted fashion, without open surgery. Our objective is to demonstrate safety and feasibility of MRgFUS BBB opening with systemically administered chemotherapy in patients with glioma in a phase I, single-arm, open-label study. Five patients with previously confirmed or suspected high-grade glioma based on imaging underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to their scheduled surgical resection. Samples of “sonicated” and “unsonicated” tissue were measured for the chemotherapy by liquid-chromatography-mass spectrometry. Complete follow-up was three months. The procedure was well-tolerated, with no adverse clinical or radiologic events related to the procedure. The BBB within the target volume showed radiographic evidence of opening with an immediate 15–50% increased contrast enhancement on T1-weighted MRI, and resolution approximately 20 hours after. Biochemical analysis of sonicated versus unsonicated tissue suggest chemotherapy delivery is feasible. In this study, we demonstrated transient BBB opening in tumor and peritumor tissue using non-invasive low-intensity MRgFUS with systemically administered chemotherapy was safe and feasible. The characterization of therapeutic delivery and clinical response to this treatment paradigm requires further investigation.

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TL;DR: It is found that single active ingredient (AI) treatments can successfully eliminate cockroaches if starting resistance levels are low, and it is established that rotation treatments intuitively reduce selection pressure, and are effective when insecticides with no/low resistance are used.
Abstract: The German cockroach (Blattella germanica L.) is a worldwide pest that lives exclusively in human environments. B. germanica threatens human health by producing asthma-triggering allergens, vectoring pathogenic/antibiotic-resistant microbes, and by contributing to unhealthy indoor environments. While insecticides are essential for reducing cockroach populations and improving health outcomes, insecticide resistance has been a consistent barrier to cockroach control since the 1950s. We conducted seminal field studies to compare three insecticide resistance intervention strategies for cockroaches and evaluated resistance evolution across multiple generations. Using pre-treatment resistance assessment to drive decisions, we found that single active ingredient (AI) treatments can successfully eliminate cockroaches if starting resistance levels are low. We further established that rotation treatments intuitively reduce selection pressure, and are effective when insecticides with no/low resistance are used. We also found that mixture products containing thiamethoxam + λ-cyhalothrin AIs were universally ineffective and highly repellent; and finally, evolution of cross-resistance among AIs is a significant, previously unrealized challenge.

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TL;DR: It is found that the total precipitation from these intense events almost doubles per degree of warming, mainly due to changes in frequency, while the intensity changes are relatively weak, in accordance to previous studies.
Abstract: The intensity of the heaviest extreme precipitation events is known to increase with global warming. How often such events occur in a warmer world is however less well established, and the combined effect of changes in frequency and intensity on the total amount of rain falling as extreme precipitation is much less explored, in spite of potentially large societal impacts. Here, we employ observations and climate model simulations to document strong increases in the frequencies of extreme precipitation events occurring on decadal timescales. Based on observations we find that the total precipitation from these intense events almost doubles per degree of warming, mainly due to changes in frequency, while the intensity changes are relatively weak, in accordance to previous studies. This shift towards stronger total precipitation from extreme events is seen in observations and climate models, and increases with the strength – and hence the rareness – of the event. Based on these results, we project that if historical trends continue, the most intense precipitation events observed today are likely to almost double in occurrence for each degree of further global warming. Changes to extreme precipitation of this magnitude are dramatically stronger than the more widely communicated changes to global mean precipitation.

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TL;DR: The exposure of humans to indoor airborne microplastics using a Breathing Thermal Manikin is addressed and the potential direct human exposure to microplastic contamination via indoor air is highlighted.
Abstract: Humans are potentially exposed to microplastics through food, drink, and air. The first two pathways have received quite some scientific attention, while little is known about the latter. We address the exposure of humans to indoor airborne microplastics using a Breathing Thermal Manikin. Three apartments were investigated, and samples analysed through FPA-µFTIR-Imaging spectroscopy followed by automatic analyses down to 11 µm particle size. All samples were contaminated with microplastics, with concentrations between 1.7 and 16.2 particles m−3. Synthetic fragments and fibres accounted, on average, for 4% of the total identified particles, while nonsynthetic particles of protein and cellulose constituted 91% and 4%, respectively. Polyester was the predominant synthetic polymer in all samples (81%), followed by polyethylene (5%), and nylon (3%). Microplastics were typically of smaller size than nonsynthetic particles. As the identified microplastics can be inhaled, these results highlight the potential direct human exposure to microplastic contamination via indoor air.

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TL;DR: It is shown that El Niño - Southern Oscillation (ENSO) is a main driver of the interannual variability in salinity and plankton biomass during winter and spring and is closely interlinked with ENSO-induced changes in Salinity, plankon biomass, and coastal circulation across the northern GoM.
Abstract: The northern Gulf of Mexico (GoM) is a region strongly influenced by river discharges of freshwater and nutrients, which promote a highly productive coastal ecosystem that host commercially valuable marine species. A variety of climate and weather processes could potentially influence the river discharges into the northern GoM. However, their impacts on the coastal ecosystem remain poorly described. By using a regional ocean-biogeochemical model, complemented with satellite and in situ observations, here we show that El Nino - Southern Oscillation (ENSO) is a main driver of the interannual variability in salinity and plankton biomass during winter and spring. Composite analysis of salinity and plankton biomass anomalies shows a strong asymmetry between El Nino and La Nina impacts, with much larger amplitude and broader areas affected during El Nino conditions. Further analysis of the model simulation reveals significant coastal circulation anomalies driven by changes in salinity and winds. The coastal circulation anomalies in turn largely determine the spatial extent and distribution of the ENSO-induced plankton biomass variability. These findings highlight that ENSO-induced changes in salinity, plankton biomass, and coastal circulation across the northern GoM are closely interlinked and may significantly impact the abundance and distribution of fish and invertebrates.

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TL;DR: Wash trials at real scale were performed on commercial clothes by using a household washing machine in order to gain reliable data about the release of microplastics, and to identify possible influences of textile characteristics on the release.
Abstract: Microplastic pollution caused by washing processes of synthetic textiles has recently been assessed as the main source of primary microplastics in the oceans. Therefore, understanding the effective contribution of the washing process of synthetic clothes to this environmental problem, is of great importance. In this study, wash trials at real scale were performed on commercial clothes by using a household washing machine in order to gain reliable data about the release of microplastics, and to identify possible influences of textile characteristics on the release. The wastewater was collected and filtered through subsequent filters with decreasing porosity, and the amount and dimensions of microfibres were determined. Microfibre release was analysed in relation to the nature and characteristics of the washed clothes. Results showed that microfibres released during washing range from 124 to 308 mg for kg of washed fabric depending from the type of washed garment that corresponds to a number of microfibres ranging from 640,000 to 1,500,000. Some textile characteristics, such as the type of fibres constituting the yarns and their twist, influenced the release of microfibres during washing. A great amount of microfibres of cellulosic nature was also released during washing of clothes made with a blend of polyester/cellulose. Finally the most abundant fraction of microfibres shed was retained by filters with pore size of 60 µm, presenting an average length of 360–660 μm and an average diameter of 12–16 μm, indicating dimensions that could pass through wastewater treatment plants and pose a threat for marine organisms.

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TL;DR: The greater tolerance of Xida 889 to heat and drought stresses was attributed to strong antioxidant defense system, higher osmolyte accumulation, and maintenance of photosynthetic pigments and nutrient balance compared with Xida 319.
Abstract: Maize is a sensitive crop to drought and heat stresses, particularly at the reproductive stages of development. The present study investigated the individual and interactive effects of drought (50% field capacity) and heat (38 °C/30 °C) stresses on morpho-physiological growth, yield, nutrient uptake and oxidative metabolism in two maize hybrids i.e., ‘Xida 889’ and ‘Xida 319’. The stress treatments were applied at tasseling stage for 15 days. Drought, heat and drought + heat stress caused oxidative stress by the over-production of ROS (O2−, H2O2, OH−) and enhanced malondialdehyde contents, which led to reduced photosynthetic components, nutrients uptake and yield attributes. The concurrent occurrence of drought and heat was more severe for maize growth than the single stress. However, both stresses induced the metabolites accumulation and enzymatic and non-enzymatic antioxidants to prevent the oxidative damage. The performance of Xida 899 was more prominent than the Xida 319. The greater tolerance of Xida 889 to heat and drought stresses was attributed to strong antioxidant defense system, higher osmolyte accumulation, and maintenance of photosynthetic pigments and nutrient balance compared with Xida 319.

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TL;DR: A detrimental effect of chronic alcohol is confirmed and a model of alcohol-induced cognitive decline following long-term voluntary intake is established that may be used for future intervention studies.
Abstract: Chronic alcohol use is associated with cognitive decline that impedes behavioral change during rehabilitation. Despite this, addiction therapy does not address cognitive deficits, and there is poor understanding regarding the mechanisms that underlie this decline. We established a rodent model of chronic voluntary alcohol use to measure ensuing cognitive effects and underlying pathology. Rats had intermittent access to alcohol or an isocaloric solution in their home cage under voluntary 2-bottle choice conditions. In Experiments 1 and 2 cognition was assessed using operant touchscreen chambers. We examined performance in a visual discrimination and reversal task (Experiment 1), and a 5-choice serial reaction time task (Experiment 2). For Experiment 3, rats were perfused immediately after cessation of alcohol access period, and volume, cell density and microglial populations were assessed in the prefrontal cortex and striatum. Volume was assessed using the Cavalieri probe, while cell and microglial counts were estimated using unbiased stereology with an optical fractionator. Alcohol-exposed and control rats showed comparable acquisition of pairwise discrimination; however, performance was impaired when contingencies were reversed indicating reduced behavioral flexibility. When tested in a 5-choice serial reaction time task alcohol-exposed rats showed increased compulsivity and increased attentional bias towards a reward associated cue. Consistent with these changes, we observed decreased cell density in the prefrontal cortex. These findings confirm a detrimental effect of chronic alcohol and establish a model of alcohol-induced cognitive decline following long-term voluntary intake that may be used for future intervention studies.

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TL;DR: Examination of two abundant particle feeders in this ecosystem, pelagic red crabs and giant larvaceans, showed that microplastic particles readily flow from the environment into coupled water column and seafloor food webs, suggesting that one of the largest and currently underappreciated reservoirs of marine microplastics may be contained within theWater column and animal communities of the deep sea.
Abstract: Plastic waste has been documented in nearly all types of marine environments and has been found in species spanning all levels of marine food webs. Within these marine environments, deep pelagic waters encompass the largest ecosystems on Earth. We lack a comprehensive understanding of the concentrations, cycling, and fate of plastic waste in sub-surface waters, constraining our ability to implement effective, large-scale policy and conservation strategies. We used remotely operated vehicles and engineered purpose-built samplers to collect and examine the distribution of microplastics in the Monterey Bay pelagic ecosystem at water column depths ranging from 5 to 1000 m. Laser Raman spectroscopy was used to identify microplastic particles collected from throughout the deep pelagic water column, with the highest concentrations present at depths between 200 and 600 m. Examination of two abundant particle feeders in this ecosystem, pelagic red crabs (Pleuroncodes planipes) and giant larvaceans (Bathochordaeus stygius), showed that microplastic particles readily flow from the environment into coupled water column and seafloor food webs. Our findings suggest that one of the largest and currently underappreciated reservoirs of marine microplastics may be contained within the water column and animal communities of the deep sea.