Pulmonary myeloid cell uptake of biodegradable nanoparticles conjugated with an anti-fibrotic agent provides a novel strategy for treating chronic allergic airways disease

Asthma (chronic allergic airways disease, AAD) is characterized by airway inflammation (AI), airway remodeling (AWR) and airway hyperresponsiveness (AHR). Current treatments for AAD mainly focus on targeting AI and its contribution AHR, with the use of corticosteroids. However, there are no therapies for the direct treatment of AWR, which can contribute to airway obstruction, AHR and corticosteroid resistance independently of AI. The acute heart failure drug, serelaxin (recombinant human gene-2 relaxin, RLX), has potential anti-remodeling and anti-fibrotic effects but only when continuously infused or injected to overcome its short half-life. To alleviate this limitation, we conjugated serelaxin to biodegradable and noninflammatory nanoparticles (NP-RLX) and evaluated their therapeutic potential on measures of AI, AWR and AHR, when intranasally delivered to a preclinical rodent model of chronic AAD and TGF-β1-stimulated collagen gel contraction from asthma patient-derived myofibroblasts. NP-RLX was preferentially taken-up by CD206+-infiltrating and CD68+-tissue resident alveolar macrophages. Furthermore, NP-RLX ameliorated the chronic AAD-induced AI, pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), chemokines (CCL2, CCL11) and the pro-fibrotic TGF-β1/IL-1β axis on AWR and resulting AHR, as well as human myofibroblast-induced collagen gel contraction, to a similar extent as unconjugated RLX. Hence, NP-RLX represents a novel strategy for treating the central features of asthma

Orthorectification of WorldView-3 Satellite Image Using Airborne Laser Scanning Data

Satellite images have been widely used to produce land use and land cover maps and to generate other thematic layers through image processing. However, images acquired by sensors onboard various satellite platforms are affected by a systematic sensor and platform-induced geometry errors, which introduce terrain distortions, especially when the sensor does not point directly at the nadir location of the sensor. To this extent, an automated processing chain of WorldView-3 image orthorectification is presented using rational polynomial coefficient (RPC) model and laser scanning data. The research is aimed at analyzing the effects of varying resolution of the digital surface model (DSM) derived from high-resolution laser scanning data, with a novel orthorectification model. The proposed method is validated on actual data in an urban environment with complex structures. This research suggests that a DSM of 0.31 m spatial resolution is optimum to achieve practical results (root-mean-square error = 0.69   m ) and decreasing the spatial resolution to 20 m leads to poor results (root-mean-square error = 7.17 ). Moreover, orthorectifying WorldView-3 images with freely available digital elevation models from Shuttle Radar Topography Mission (SRTM) (30 m) can result in an RMSE of 7.94 m without correcting the distortions in the building. This research can improve the understanding of appropriate image processing and improve the classification for feature extraction in urban areas.</jats:p

An optimized Deep Neural Network Approach for Vehicular Traffic Noise Trend Modelling

Vehicular traffic plays a significant role in terms of economic development; however, it is also a major source of noise pollution. Therefore, it is highly imperative to model traffic noise, especially for expressways due to their high traffic volume and speed, which produce very-high level of traffic noise. Previous traffic prediction models are mostly based on the regression approach and the artificial neural network (ANN), which often fail to describe the trends of noise. In this paper, a deep neural network-based optimization approach is implemented in two ways: i) using different algorithms for training and activation, and ii) integrating with feature selection methods such as correlation-based feature selection (CFS) and wrapper for feature-subset selection (WFS) methods. These methods are integrated to produce traffic noise maps for different time of the day on weekdays, including morning, afternoon, evening, and night. The novelty of this study is the integration of the feature selection method with the deep neural network for vehicular traffic noise modelling. New Klang Valley Expressway (NKVE) in Malaysia was used as a case study due to its increasing heavy and light vehicles, and the motorbike during peak hours, which result in high traffic noise. The results from the models indicate that the WFS-DNN model has the least mean-absolute-deviation (MAD) of 2.28, and the least root-mean-square-error (RMSE) of 3.97. Also, this model shows the best result compared to the other models such as DNN without integration with feature selection methods, CFS-DNN and the ANN networks (MLP and RBF). MAD improvement of 27&#x0025; - 47&#x0025; and RMSE improvement of 25&#x0025; - 38&#x0025; was achieved compared to other methods. The study provides a generic approach to key parameter selection and dimension reduction with novel trend descriptor which could be useful for future such modelling applications

Quora Insincere Questions Classification Using Attention Based Model

The online platform has evolved into an unparalleled storehouse of infor-mation. People use various social question-and-answer websites such as Quora, Form-spring, Stack-Overflow, Twitter, and Beepl to ask questions, clarify doubts, and share ideas and expertise with others. An increase in in-appropriate and insincere comments by users without a genuine motive is a major issue with such Q & A websites. Individuals tend to share harmful and toxic content intended to make a statement rather than look for helpful answers. In the world of natural language processing (NLP), Bidirectional Encoder Representations from Transformers (BERT) has been a game-changer. It has dominated performance benchmarks and thereby pushed the limits of researchers' ability to experiment and produce similar models. This resulted in improvements in language models by introducing lighter models while maintaining efficiency and performance. This study utilized pre-trained state-of-the-art language models for understanding whether posted questions are sincere or insincere with limited computation. To overcome the high computation problem of NLP, the BERT, XLNet, StructBERT, and DeBERTa models were trained on three samples of data. The metrics proved that even with limited resources, recent transformer-based models outscore previous studies with remarkable results. Amongst the four, DeBERTa stands out with the highest balanced accuracy, macro, and weighted f1-score of 80%, 0.83 and 0.96, respectively

Alpha-particle-induced complex chromosome exchanges transmitted through extra-thymic lymphopoiesis in vitro show evidence of emerging genomic instability

Human exposure to high-linear energy transfer α-particles includes environmental (e.g. radon gas and its decay progeny), medical (e.g. radiopharmaceuticals) and occupational (nuclear industry) sources. The associated health risks of α-particle exposure for lung cancer are well documented however the risk estimates for leukaemia remain uncertain. To further our understanding of α-particle effects in target cells for leukaemogenesis and also to seek general markers of individual exposure to α-particles, this study assessed the transmission of chromosomal damage initially-induced in human haemopoietic stem and progenitor cells after exposure to high-LET α-particles. Cells surviving exposure were differentiated into mature T-cells by extra-thymic T-cell differentiation in vitro. Multiplex fluorescence in situ hybridisation (M-FISH) analysis of naïve T-cell populations showed the occurrence of stable (clonal) complex chromosome aberrations consistent with those that are characteristically induced in spherical cells by the traversal of a single α-particle track. Additionally, complex chromosome exchanges were observed in the progeny of irradiated mature T-cell populations. In addition to this, newly arising de novo chromosome aberrations were detected in cells which possessed clonal markers of α-particle exposure and also in cells which did not show any evidence of previous exposure, suggesting ongoing genomic instability in these populations. Our findings support the usefulness and reliability of employing complex chromosome exchanges as indicators of past or ongoing exposure to high-LET radiation and demonstrate the potential applicability to evaluate health risks associated with α-particle exposure.This work was supported by the Department of Health, UK. Contract RRX95 (RMA NSDTG)

Oxygen isotope heterogeneity of the mantle beneath the Canary Islands : insights from olivine phenocrysts

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Contributions to Mineralogy and Petrology 162 (2011): 349-363, doi:10.1007/s00410-010-0600-5.A relatively narrow range of oxygen isotopic ratios (δ18O = 5.05.4‰) is preserved in olivine of mantle xenoliths, mid-ocean ridge (MORB) and most ocean island basalts (OIB). The values in excess of this range are generally attributed either to the presence of a recycled component in the Earth’s mantle or to shallow level contamination processes. A viable way forward to trace source heterogeneity is to find a link between chemical (elemental and isotopic) composition of the earlier crystallized mineral phases (olivine) and the composition of their parental magmas, then using them to reconstruct the composition of source region. The Canary hotspot is one of a few that contains ~1-2 Ga old recycled ocean crust that can be traced to the core-mantle boundary using seismic tomography and whose origin is attributed to the mixing of at least three main isotopically distinct mantle components i.e., HIMU, DMM and EM. This work reports ion microprobe and single crystal laser fluorination oxygen isotope data of 148 olivine grains also analyzed for major and minor elements in the same spot. The olivines are from 20 samples resembling the most primitive shield stage picrite through alkali basalt to basanite series erupted on Gran Canaria, Tenerife, La Gomera, La Palma and El Hierro, Canary Islands, for which shallow level contamination processes were not recognized. A broad range of δ18Oolivine values from 4.6 to 6.1‰ was obtained and explained by stable, long-term oxygen isotope heterogeneity of crystal cumulates present under different volcanoes. These cumulates are thought to have crystallized from mantle derived magmas uncontaminated at crustal depth, representing oxygen isotope heterogeneity of source region. A relationship between Ni×FeO/MgO and δ18Oolivine values found in one basanitic lava erupted on El Hierro, the westernmost island of the Canary Archipelago, was used to estimate oxygen isotope compositions of partial melts presumably originated from peridotite (HIMU-type component inherited its radiogenic isotope composition from ancient, ~12 Ga, recycled ocean crust) and pyroxenite (young, <1 Ga, recycled oceanic crust preserved as eclogite with depleted MORB-type isotopic signature) components of the Canary plume. The model calculations yield 5.2 and 5.9±0.3‰ for peridotite and pyroxenite derived melts, respectively, which appeared to correspond closely to the worldwide HIMU-type OIB and upper limit N-MORB δ18O values. This difference together with the broad range of δ18O variations found in the Canarian olivines cannot be explained by thermodynamic effects of oxygen isotopic fractionation and are believed to represent true variations in the mantle, due to oceanic crust and continental lithosphere recycling.This work was supported by the CNRS “poste rouge” grant to AG, the NSF EAR-CAREER-0844772 grant to IB and the CRPG-CNRS and at its initial stage by the DFG (grant SCHM 250/64) and the Alexander von Humboldt Foundation (Wolfgang Paul Award to A.V. Sobolev who provided access to the electron microprobe at the Max Planck Institute, Mainz, Germany)

Sub-Lethal Irradiation of Human Colorectal Tumor Cells Imparts Enhanced and Sustained Susceptibility to Multiple Death Receptor Signaling Pathways

Background: Death receptors (DR) of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. Methodology/Principal Findings: The ability of radiation to modulate the expression of multiple death receptors (Fas/ CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTbR) was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTbR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fasinduced apoptosis, but not LTbR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation di