1,374 research outputs found
Cell bystander effect induced by radiofrequency electromagnetic fields and magnetic nanoparticles
Induced effects by direct exposure to ionizing radiation (IR) are a central
issue in many fields like radiation protection, clinic diagnosis and
oncological therapies. Direct irradiation at certain doses induce cell death,
but similar effects can also occur in cells no directly exposed to IR, a
mechanism known as bystander effect. Non-IR (radiofrequency waves) can induce
the death of cells loaded with MNPs in a focused oncological therapy known as
magnetic hyperthermia. Indirect mechanisms are also able to induce the death of
unloaded MNPs cells. Using in vitro cell models, we found that colocalization
of the MNPs at the lysosomes and the non-increase of the temperature induces
bystander effect under non-IR. Our results provide a landscape in which
bystander effects are a more general mechanism, up to now only observed and
clinically used in the field of radiotherapy.Comment: 16 pages, 4 figures, submitted to International Journal of Radiation
Biolog
Enhancing Interferon Regulatory Factor 7 Mediated Antiviral Responses and Decreasing Nuclear Factor Kappa B Expression Limit HIV-1 Replication in Cervical Tissues
Establishment of a productive HIV-1 infection in the female reproductive tract likely depends on the balance between anti-viral and pro-inflammatory responses leading to activation and proliferation of HIV target cells. Immune modulators that boost anti-viral and depress pro-inflammatory immune responses may decrease HIV-1 infection or replication. Polyinosinic: polycytidylic [Poly (I:C)] has been reported to down-regulate HIV-1 replication in immune cell subsets and lymphoid tissues, yet the scope and mechanisms of poly (I:C) regulation of HIV-1 replication in the cervicovaginal mucosa, the main portal of viral entry in women remain unknown. Using a relevant, underexplored ex vivo cervical tissue model, we demonstrated that poly (I:C) enhanced Interferon Regulatory Factor (IRF)7 mediated antiviral responses and decreased tissue Nuclear Factor Kappa B (NF κ B) RNA expression. This pattern of cellular transcription factor expression correlated with decreased HIV-1 transcription and viral release. Reducing IRF7 expression up-regulated HIV-1 and NFκB transcription, providing proof of concept for the critical involvement of IRF7 in cervical tissues. By combining poly (I:C) with a suboptimal concentration of tenofovir, the leading anti-HIV pro-phylactic microbicide candidate, we demonstrated an earlier and greater decrease in HIV replication in poly (I:C)/tenofovir treated tissues compared with tissues treated with tenofovir alone, indicating overall improved efficacy. Poly (I:C) decreases HIV-1 replication by stimulating IRF7 mediated antiviral responses while reducing NFκB expression. Early during the infection, poly (I:C) improved the anti-HIV-1 activity of suboptimal concentrations of tenofovir likely to be present during periods of poor adherence i.e. inconsistent or inadequate drug use. Understanding interactions between anti-viral and pro-inflammatory immune responses in the genital mucosa will provide crucial insights for the identification of targets that can be harnessed to develop preventative combination strategies to improve the efficacy of topical or systemic antiviral prophylactic agents and protect women from HIV-1 and other sexually transmitted infections
The Respiratory Syncytial Virus G Protein Conserved Domain Induces a Persistent and Protective Antibody Response in Rodents
Respiratory syncytial virus (RSV) is an important cause of severe upper and lower respiratory disease in infants and in the elderly. There are 2 main RSV subtypes A and B. A recombinant vaccine was designed based on the central domain of the RSV-A attachment G protein which we had previously named G2Na (aa130–230). Here we evaluated immunogenicity, persistence of antibody (Ab) response and protective efficacy induced in rodents by: (i) G2Na fused to DT (Diphtheria toxin) fragments in cotton rats. DT fusion did not potentiate neutralizing Ab responses against RSV-A or cross-reactivity to RSV-B. (ii) G2Nb (aa130–230 of the RSV-B G protein) either fused to, or admixed with G2Na. G2Nb did not induce RSV-B-reactive Ab responses. (iii) G2Na at low doses. Two injections of 3 µg G2Na in Alum were sufficient to induce protective immune responses in mouse lungs, preventing RSV-A and greatly reducing RSV-B infections. In cotton rats, G2Na-induced RSV-reactive Ab and protective immunity against RSV-A challenge that persisted for at least 24 weeks. (iv) injecting RSV primed mice with a single dose of G2Na/Alum or G2Na/PLGA [poly(D,L-lactide-co-glycolide]. Despite the presence of pre-existing RSV-specific Abs, these formulations effectively boosted anti-RSV Ab titres and increased Ab titres persisted for at least 21 weeks. Affinity maturation of these Abs increased from day 28 to day 148. These data indicate that G2Na has potential as a component of an RSV vaccine formulation
Green Roofs in Arid Cities. Efficiency as Energy Saving Strategy in Summer and Winter
Los techos vegetados constituyen estrategias de enverdecimiento que a escala edilicia controlan las altas temperaturas estivales en espacios interiores y a escala urbana contribuyen a mitigar el fenómeno isla de calor. Este trabajo evalúa, el efecto de cubiertas vegetadas con especies adaptadas -Aptenia cordifolia, Sedum spectabile- a climas cálido-secos sobre el comportamiento térmico de espacios interiores y su consecuente ahorro energético. Metodológicamente se ha monitoreado el desempeño térmico durante verano e invierno en tres box experimentales -uno con cubierta tradicional y dos vegetados-. Los resultados indican que las cubiertas vegetadas en verano disminuyen la temperatura interior 1,6 °C generando ahorros medios de energía para refrigeración del 30-35 %. En invierno si bien no hay variaciones notables, se observan ahorros energéticos diurnos del 2-4 %. El diseño de esta tecnología requiere evaluarse a nivel local para maximizar su eficiencia energética y garantizar la sustentabilidad urbano-edilicio según los recursos y tecnologías disponibles.Green roofs are greening strategies that controls the high summer temperatures in the indoor spaces at building scale and help mitigate the heat island phenomenon in urban scale. This work evaluates the effect of vegetated roofs with adapted species -Aptenia cordifolia, Sedum spectabile- in warm-dry climate in relation to the thermal behavior of indoors spaces and the consequent energy savings.
Methodologically the thermal performance during summer and winter has monitored, in three experimental boxes- one with a traditional roof and two with vegetated roofs-. The results indicate that in the green roofs, indoor summer temperature decreases of 1,6 °C generate energy savings for refrigeration of 30 to 35%. In winter, although there are not notable variations, diurnal energy savings of 2-4% is observed. The design of these new technologies should be assessed at local level to maximize energy efficiency and ensure urban-building sustainability according to resources and technologies available.Eje: Eficiencia energética edilicia (Actas).Facultad de Arquitectura y Urbanism
D-branes on Group Manifolds and Deformation Quantization
Recently M. Kontsevich found a combinatorial formula defining a star-product
of deformation quantization for any Poisson manifold. Kontsevich's formula has
been reinterpreted physically as quantum correlation functions of a topological
sigma model for open strings as well as in the context of D-branes in flat
backgrounds with a Neveu-Schwarz B-field. Here the corresponding Kontsevich's
formula for the dual of a Lie algebra is derived in terms of the formalism of
D-branes on group manifolds. In particular we show that that formula is encoded
at the two-point correlation functions of the Wess-Zumino-Witten effective
theory with Dirichlet boundary conditions. The B-field entering in the
formalism plays an important role in this derivation.Comment: 20 pages, harvmac file, no figures, corrected typo
Deep Learning-based Modeling for Preclinical Drug Safety Assessment.
In drug development, assessing the toxicity of candidate compounds is crucial for successfully transitioning from preclinical research to early-stage clinical trials. Drug safety is typically assessed using animal models with a manual histopathological examination of tissue sections to characterize the dose-response relationship of the compound - a time-intensive process prone to inter-observer variability and predominantly involving tedious review of cases without abnormalities. Artificial intelligence (AI) methods in pathology hold promise to accelerate this assessment and enhance reproducibility and objectivity. Here, we introduce TRACE, a model designed for toxicologic liver histopathology assessment capable of tackling a range of diagnostic tasks across multiple scales, including situations where labeled data is limited. TRACE was trained on 15 million histopathology images extracted from 46,734 digitized tissue sections from 157 preclinical studies conducted on Rattus norvegicus. We show that TRACE can perform various downstream toxicology tasks spanning histopathological response assessment, lesion severity scoring, morphological retrieval, and automatic dose-response characterization. In an independent reader study, TRACE was evaluated alongside ten board-certified veterinary pathologists and achieved higher concordance with the consensus opinion than the average of the pathologists. Our study represents a substantial leap over existing computational models in toxicology by offering the first framework for accelerating and automating toxicological pathology assessment, promoting significant progress with faster, more consistent, and reliable diagnostic processes
Neural network modelling of RC deep beam shear strength
YesA 9 x 18 x 1 feed-forward neural network (NN) model
trained using a resilient back-propagation algorithm and
early stopping technique is constructed to predict the
shear strength of deep reinforced concrete beams. The
input layer covering geometrical and material properties
of deep beams has nine neurons, and the corresponding output is the shear strength. Training, validation and testing of the developed neural network have been
achieved using a comprehensive database compiled from
362 simple and 71 continuous deep beam specimens.
The shear strength predictions of deep beams obtained
from the developed NN are in better agreement with
test results than those determined from strut-and-tie
models. The mean and standard deviation of the ratio between predicted capacities using the NN and measured shear capacities are 1.028 and 0.154, respectively, for simple deep beams, and 1.0 and 0.122, respectively, for continuous deep beams. In addition, the
trends ascertained from parametric study using the developed NN have a consistent agreement with those observed in other experimental and analytical investigations
Compressed representation of a partially defined integer function over multiple arguments
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
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