1,722 research outputs found

    Bio-inspired functional surface fabricated by electrically assisted micro-embossing of AZ31 magnesium alloy

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    Developing bio-inspired functional surfaces on engineering metals is of extreme importance, involving different industrial sectors, like automotive or aeronautics. In particular, micro-embossing is one of the efficient and large-scale processes for manufacturing bio-inspired textures on metallic surfaces. However, this process faces some problems, such as filling defects and die breakage due tocsize effect, which restrict this technology for some components. Electrically assisted micro-forming has demonstrated the ability of reducing size effects, improving formability and decreasing flow stress, making it a promising hybrid process to control the filling quality of micro-scale features. This research focuses on the use of different current densities to perform embossed micro-channels of 7 um and sharklet patterns of 10 um in textured bulk metallic glass dies. These dies are prepared by thermoplastic forming based on the compression of photolithographic silicon molds. The results show that large areas of bio-inspired textures could be fabricated on magnesium alloy when current densities higher than 6 A/mm2 (threshold) are used. The optimal surface quality scenario is obtained for a current density of 13 A/mm2. Additionally, filling depth and depth–width ratio nonlinearly increases when higher current densities are used, where the temperature is a key parameter to control, keeping it below the temperature of the glass transition to avoid melting or an early breakage of the die.Peer ReviewedPostprint (published version

    the impact of different occupational exposure limits

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    Funding Information: This project received funding from the COST Action CA18218 European Burden of Disease Network, supporting the first author with a Short-Term Scientific Mission to the National Food Institute, Technical University of Denmark, with the aim of improving knowledge and applying the appropriate methodology on burden of disease on this project.The authors would like to thank the researchers from the Research Group for Risk Benefit from the National Food Institute, Technical University of Denmark for raising questions to improve the robustness of the research project, as well as the COST Action CA18218 European Burden of Disease Network for funding and supporting the project, and to the researchers Carla Martins from NOVA National School of Public Health and Ricardo Assunção from Egas Moniz Cooperativa de Ensino Superior for contributing to the initial brainstorming on the disease pathology. Publisher Copyright: © 2023 The AuthorsBackground: Exposure to hexavalent chromium [Cr(VI)] occurs widely in occupational settings across the EU and is associated with lung cancer. In 2025, the occupational exposure limit is set to change to 5 μg/m3. Current exposure limits are higher, with 10 μg/m3 as a general limit and 25 μg/m3 for the welding industry. We aimed to assess the current burden of lung cancer caused by occupational exposure to Cr(VI) and to evaluate the impact of the recently established EU regulation by analysing different occupational exposure limits. Methods: Data were extracted from the literature, the Global Burden of Disease 2019) study, and Eurostat. We estimated the cases of cancer attributable to workplace exposure to Cr(VI) by combining exposure-effect relationships with exposure data, and calculated related DALYs and health costs in scenarios with different occupational exposure limits. Results: With current EU regulations, 253 cases (95%UI 250.96–255.71) of lung cancer were estimated to be caused by Cr(VI) in 2019, resulting in 4684 DALYs (95%UI 4683.57–4704.08). In case the welding industry adopted 10 μg/m3, a decrease of 43 cases and 797 DALYs from current values is expected. The predicted application of a 5 μg/m3 limit would cause a decrease of 148 cases and 2746 DALYs. Current costs are estimated to amount to 12.47 million euros/year (95%UI 10.19–453.82), corresponding to 39.97 million euros (95%UI 22.75–70.10) when considering costs per DALY. The limits implemented in 2025 would lead to a decrease of 23.35 million euros when considering DALYs, with benefits of introducing a limit value occurring after many decades. Adopting a 1 μg/m3 limit would lower costs to 1.04 million euros (95%UI 0.85–37.67) and to 3.33 million euros for DALYs (95%UI 1.89–5.84). Discussion: Assessing different scenarios with different Cr(VI) occupational exposure limits allowed to understand the impact of EU regulatory actions. These findings make a strong case for adapting even stricter exposure limits to protect workers’ health and avoid associated costs.publishersversionpublishe

    1000 fps computational ghost imaging using LED-based structured illumination

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    : Single-pixel imaging uses a single-pixel detector, rather than a focal plane detector array, to image a scene. It provides advantages for applications such as multi-wavelength, three-dimensional imaging. However, low frame rates have been a major obstacle inhibiting the use of computational ghost imaging technique in wider applications since its invention one decade ago. To address this problem, a computational ghost imaging scheme, which utilizes an LED-based, high-speed illumination module is presented in this work. At 32 × 32 pixel resolution, the proof-of-principle system achieved continuous imaging with 1000 fps frame rate, approximately two orders larger than those of other existing ghost imaging systems. The proposed scheme provides a cost-effective and high-speed imaging technique for dynamic imaging application

    Revisit the calibration errors on experimental slant total electron content (TEC) determined with GPS

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    This is a pre-print of an article published in GPS Solutions. The final authenticated version is available online at: https://doi.org/10.1007/s10291-018-0753-7. The study is funded by National Key Research and Development Program of China (2016YFB0501902), National Natural Science Foundation of China (41574025, 41574013, 41731069), Spanish Ministry of Science and Innovation project (CGL2015-66410-P), The Hong Kong RGC Joint Research Scheme (E-PolyU501/16) and State Key Laboratory of Geo-Information Engineering (SKLGIE2015-M-2-2).The calibration errors on experimental slant total electron content (TEC) determined with global positioning system (GPS) observations is revisited. Instead of the analysis of the calibration errors on the carrier phase leveled to code ionospheric observable, we focus on the accuracy analysis of the undifferenced ambiguity-fixed carrier phase ionospheric observable determined from a global distribution of permanent receivers. The results achieved are: (1) using data from an entire month within the last solar cycle maximum, the undifferenced ambiguity-fixed carrier phase ionospheric observable is found to be over one order of magnitude more accurate than the carrier phase leveled to code ionospheric observable and the raw code ionospheric observable. The observation error of the undifferenced ambiguity-fixed carrier phase ionospheric observable ranges from 0.05 to 0.11 total electron content unit (TECU) while that of the carrier phase leveled to code and the raw code ionospheric observable is from 0.65 to 1.65 and 3.14 to 7.48 TECU, respectively. (2) The time-varying receiver differential code bias (DCB), which presents clear day boundary discontinuity and intra-day variability pattern, contributes the most part of the observation error. This contribution is assessed by the short-term stability of the between-receiver DCB, which ranges from 0.06 to 0.17 TECU in a single day. (3) The remaining part of the observation errors presents a sidereal time cycle pattern, indicating the effects of the multipath. Further, the magnitude of the remaining part implies that the code multipath effects are much reduced. (4) The intra-day variation of the between-receiver DCB of the collocated stations suggests that estimating DCBs as a daily constant can have a mis-modeling error of at least several tenths of 1 TECU.Peer ReviewedPostprint (author's final draft

    Free energy landscape for the binding process of Huperzine A to acetylcholinesterase

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    Drug-target residence time (t = 1/koff, where koff is the dissociation rate constant) has become an important index in discovering betteror best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, koff and activation free energy of dissociation (ΔG≠ off). In this paper, energy landscape theory that has been developed to understand protein folding and function is extended to develop a generally applicable computational framework that is able to construct a complete ligand-target binding free energy landscape. This enables both the binding affinity and the binding kinetics to be accurately estimated.We applied this method to simulate the binding event of the anti-Alzheimer’s disease drug (−)−Huperzine A to its target acetylcholinesterase (AChE). The computational results are in excellent agreement with our concurrent experimental measurements. All of the predicted values of binding free energy and activation free energies of association and dissociation deviate from the experimental data only by less than 1 kcal/ mol. The method also provides atomic resolution information for the (−)−Huperzine A binding pathway, which may be useful in designing more potent AChE inhibitors. We expect thismethodology to be widely applicable to drug discovery and development

    Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human dperm capacitation

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    Mammalian sperm require to spend a limited period of time in the female reproductive tract to become competent to fertilize in a process called capacitation. It is well established that HCO3 − is essential for capacitation because it activates the atypical soluble adenylate cyclase ADCY10 leading to cAMP production, and promotes alkalinization of cytoplasm, and membrane hyperpolarization. However, how HCO3 − is transported into the sperm is not well understood. There is evidence that CFTR activity is involved in the human sperm capacitation but how this channel is integrated in the complex signaling cascades associated with this process remains largely unknown. In the present work, we have analyzed the extent to which CFTR regulates different events in human sperm capacitation. We observed that inhibition of CFTR affects HCO3 −-entrance dependent events resulting in lower PKA activity. CFTR inhibition also affected cAMP/PKA-downstream events such as the increase in tyrosine phosphorylation, hyperactivated motility, and acrosome reaction. In addition, we demonstrated for the first time, that CFTR and PKA activity are essential for the regulation of intracellular pH, and membrane potential in human sperm. Addition of permeable cAMP partially recovered all the PKA-dependent events altered in the presence of inh-172 which is consistent with a role of CFTR upstream of PKA activation.Fil: Puga Molina, Lis del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pinto, Nicolás Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Torres Rodríguez, Paulina. Universidad Nacional Autónoma de México; MéxicoFil: Romarowski, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Vicens Sanchez, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Visconti, Pablo E.. University of Massachussets; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México; MéxicoFil: Treviño, Claudia L.. Universidad Nacional Autónoma de México; MéxicoFil: Buffone, Mariano Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

    Experimental demonstration of a unidirectional reflectionless parity-time metamaterial at optical frequencies

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    Invisibility by metamaterials is of great interest, where optical properties are manipulated in the real permittivity– permeability plane. However, the most effective approach to achieving invisibility in various military applications is to absorb the electromagnetic waves emitted from radar to minimize the corresponding reflection and scattering, such that no signal gets bounced back. Here, we show the experimental realization of chip-scale unidirectional reflectionless optical metamaterials near the spontaneous parity-time symmetry phase transition point where reflection from one side is significantly suppressed. This is enabled by engineering the corresponding optical properties of the designed paritytime metamaterial in the complex dielectric permittivity plane. Numerical simulations and experimental verification consistently exhibit asymmetric reflection with high contrast ratios around a wavelength of of 1,550 nm. The demonstrated unidirectional phenomenon at the corresponding parity-time exceptional point on-a-chip confirms the feasibility of creating complicated on-chip parity-time metamaterials and optical devices based on their properties

    Light scattering from self-affine fractal silver surfaces with nanoscale cutoff: Far-field and near-field calculations

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    We study the light scattered from randomly rough, one-dimensional self-affine fractal silver surfaces with nanoscale lower cutoff, illuminated by s- or p-polarized Gaussian beams a few microns wide. By means of rigorous numerical calculations based on the Green theorem integral equation formulation, we obtain both the far- and near-field scattered intensities. The influence of diminishing the fractal lower scale cutoff (from below a hundred, down to a few nanometers) is analyzed in the case of both single realizations and ensemble average magnitudes. For s polarization, variations are small in the far field, being only significant in the higher spatial frequency components of evanescent character in the near field. In the case of p polarization, however, the nanoscale cutoff has remarkable effects stemming from the roughness-induced excitation of surface-plasmon polaritons. In the far field, the effect is noticed both in the speckle pattern variation and in the decrease of the total reflected energy upon ensemble averaging, due to increased absorption. In the near field, more efficient excitation of localized optical modes is achieved with smaller cutoff, which in turn leads to huge surface electric field enhancements.Comment: REVTeX 4, 10 page

    The release of toxic oligomers from α-synuclein fibrils induces dysfunction in neuronal cells.

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    The self-assembly of α-synuclein (αS) into intraneuronal inclusion bodies is a key characteristic of Parkinson's disease. To define the nature of the species giving rise to neuronal damage, we have investigated the mechanism of action of the main αS populations that have been observed to form progressively during fibril growth. The αS fibrils release soluble prefibrillar oligomeric species with cross-β structure and solvent-exposed hydrophobic clusters. αS prefibrillar oligomers are efficient in crossing and permeabilize neuronal membranes, causing cellular insults. Short fibrils are more neurotoxic than long fibrils due to the higher proportion of fibrillar ends, resulting in a rapid release of oligomers. The kinetics of released αS oligomers match the observed kinetics of toxicity in cellular systems. In addition to previous evidence that αS fibrils can spread in different brain areas, our in vitro results reveal that αS fibrils can also release oligomeric species responsible for an immediate dysfunction of the neurons in the vicinity of these species

    Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

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    Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2 −/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2 −/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K 572 cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis
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