Protozoan diseases continue to be a worldwide social and economic health problem. Increased drug resistance, emerging cross resistance, and lack of new drugs with novel mechanisms of action ...significantly reduce the effectiveness of current antiprotozoal therapies. While drug resistance associated to anti-infective agents is a reality, society seems to remain unaware of its proportions and consequences. Parasites usually develops ingenious and innovative mechanisms to achieve drug resistance, which requires more research and investment to fight it. In this review, drug resistance developed by protozoan parasites
,
and
will be discussed.
Passive damping treatments using viscoelastic materials (VEMs) are widely applied as addon solutions to control the dynamic response of light structures. These surface treatments are simple, ...reliable, and can be optimized by using proper design rules and simulation tools. In this work, a new treatment configuration is proposed, simulated, and assessed, being compared with the most effective configuration currently used. The novelty resides in the VEM layer’s geometry, which in the proposed configuration assumes a waved shape. This waved shape is imposed to the viscoelastic layer due to indentations created in the inner faces of the host structure and the constraining layer. The results demonstrate that the wavy configuration, designated as corrugated viscoelastic layer (CVL), outperforms the typical damping treatments for relatively thick host structures and when using thick VEM layers. In addition, this new configuration reduces the stiffness decoupling effect due to the soft VEM layer, restoring the flexural stiffness of the original undamped structure.
Synthetic organic chemistry underpins several areas of chemistry, including drug discovery, chemical biology, materials science and engineering. However, the execution of complex chemical syntheses ...in itself requires expert knowledge, usually acquired over many years of study and hands-on laboratory practice. The development of technologies with potential to streamline and automate chemical synthesis is a half-century-old endeavour yet to be fulfilled. Renewed interest in artificial intelligence (AI), driven by improved computing power, data availability and algorithms, is overturning the limited success previously obtained. In this Review, we discuss the recent impact of AI on different tasks of synthetic chemistry and dissect selected examples from the literature. By examining the underlying concepts, we aim to demystify AI for bench chemists in order that they may embrace it as a tool rather than fear it as a competitor, spur future research by pinpointing the gaps in knowledge and delineate how chemical AI will run in the era of digital chemistry.Artificial intelligence has recently seen numerous applications in synthetic organic chemistry. Advanced pattern-recognition heuristics may facilitate the access to chemical matter of interest and complement chemical intuition in the near future.
In Portugal, more than 98% of domestic cooking oil is disposed of improperly every day. This avoids recycling/reconverting into another energy. Is also may become a potential harmful contaminant of ...soil and water. Driven by the utility of recycled cooking oil, and leveraging the exponential growth of ubiquitous computing approaches, we propose an IoT smart solution for domestic used cooking oil (UCO) collection bins. We call this approach SWAN, which stands for Smart Waste Accumulation Network. It is deployed and evaluated in Portugal. It consists of a countrywide network of collection bin units, available in public areas. Two metrics are considered to evaluate the system's success: (i) user engagement, and (ii) used cooking oil collection efficiency. The presented system should (i) perform under scenarios of temporary communication network failures, and (ii) be scalable to accommodate an ever-growing number of installed collection units. Thus, we choose a disruptive approach from the traditional cloud computing paradigm. It relies on edge node infrastructure to process, store, and act upon the locally collected data. The communication appears as a delay-tolerant task, i.e., an edge computing solution. We conduct a comparative analysis revealing the benefits of the edge computing enabled collection bin vs. a cloud computing solution. The studied period considers four years of collected data. An exponential increase in the amount of used cooking oil collected is identified, with the developed solution being responsible for surpassing the national collection totals of previous years. During the same period, we also improved the collection process as we were able to more accurately estimate the optimal collection and system's maintenance intervals.
Indoor air quality (IAQ) problems in school environments are very common and have significant impacts on students' performance, development and health. Indoor air conditions depend on the adopted ...ventilation practices, which in Mediterranean countries are essentially based on natural ventilation controlled through manual window opening. Citizen science projects directed to school communities are effective strategies to promote awareness and knowledge acquirement on IAQ and adequate ventilation management. Our multidisciplinary research team has developed a framework-SchoolAIR-based on low-cost sensors and a scalable IoT system architecture to support the improvement of IAQ in schools. The SchoolAIR framework is based on do-it-yourself sensors that continuously monitor air temperature, relative humidity, concentrations of carbon dioxide and particulate matter in school environments. The framework was tested in the classrooms of University Fernando Pessoa, and its deployment and proof of concept took place in a high school in the north of Portugal. The results obtained reveal that CO
concentrations frequently exceed reference values during classes, and that higher concentrations of particulate matter in the outdoor air affect IAQ. These results highlight the importance of real-time monitoring of IAQ and outdoor air pollution levels to support decision-making in ventilation management and assure adequate IAQ. The proposed approach encourages the transfer of scientific knowledge from universities to society in a dynamic and active process of social responsibility based on a citizen science approach, promoting scientific literacy of the younger generation and enhancing healthier, resilient and sustainable indoor environments.
This integrated study presents a thorough investigation into a novel class of electrets known as thermoformed magnetic-piezoelectrets (TMPs) devices. The research focuses on evaluating capacitance, ...quality factor, and the impact of magnetic fields on these devices. Fabricated by fusing fluoroethylene propylene (FEP) films and integrating magnetic strips, the TMP devices exhibit both magnetostrictive and piezoelectric effects in response to external magnetic fields. The study encompasses the latest advancements in material synthesis, fabrication techniques, characterization methods, and potential device applications. Measurements conducted under various electric currents and frequencies revealed that higher capacitance values are associated with increased electric charge storage in TMP devices. The devices demonstrated exceptional quality factors, particularly in the MHz range, suggesting their potential as efficient electric charge storage devices. Further investigation focused on the influence of magnetic fields on the magneto-piezoelectric response of TMPs. Thermoformed piezoelectrets, featuring open-tubular channels and an additional magnetic layer, were explored for their potential as sensors for detecting magnetic fields. While the magneto-piezoelectric response exhibited linearity in the presence of magnetic fields, a decrease in charge storage capacity was observed due to mechanical stress on the tubular channels. The TMPs displayed a maximum resistance of approximately 0.75 T against magnetic fields, reaching complete saturation at a magnetic field strength of 0.8 T. Beyond this point, the relationship between variables became nonlinear, resulting in a null magneto-piezoelectric response. This comprehensive study contributes to a deeper understanding of the capacitance, quality factor, and magnetic field influence on magneto-piezoelectret sensors. The insights gained from this research have significant implications for potential applications in advanced technologies that demand high-frequency operation and magnetic field detection.
Chronic obstructive pulmonary disease (COPD) is a major increasing health problem and the World Health Organization (WHO) reports COPD as the fifth leading cause of death worldwide. COPD refers to a ...condition of inflammation and progressive weakening of the structure of the lung as well as irreversible narrowing of the airways. Current treatment is only palliative and no available drug halts the progression of the disease. Human neutrophil elastase (HNE) is a serine protease, which plays a major role in the COPD inflammatory process. The protease/anti‐protease imbalance leads to an excess of extracellular HNE hydrolyzing elastin, the structural protein that confers elasticity to the lung tissue. Although HNE was identified as a therapeutic target for COPD more than 30 years ago, only Sivelestat (ONO‐5046), an HNE inhibitor from Ono Pharmaceutical, has been approved for clinical use. Nevertheless, Sivelestat is only approved in Japan and its development in the USA was terminated in 2003. Other inhibitors in pre‐clinical or phase I trials were discontinued for various reasons. Hence, there is an urgent need for low‐molecular‐weight synthetic elastase inhibitors and the present review discusses the recent advances on this field covering acylating agents, transition‐state inhibitors, mechanism‐based inhibitors, relevant natural products, and major patent disclosures.
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•New methods were developed at atmospheric pressure and high pressures for predicting BD viscosity.•They have better predictive ability than those commonly used in literature.•At ...atmospheric pressure, performance of LSDU1 model has average relative deviation of 2%.•At high pressure performance of AVR model has average relative deviation of 2%.
Fuel viscosity is an important property that has a significant effect in fuel injection, spray development and combustion in Compression Ignition (CI) engines. Current and future injector designs of diesel engines (such as rail injection systems) work at high pressures (>100 MPa), meaning that fuel viscosity increases substantially over the atmospheric values. The estimation of biodiesel (BD) viscosity based on the knowledge of its composition would be of great potential in the optimization of biodiesel production processes, particularly in the blending of raw materials and refined products. In this work, comprehensive data sets were chosen from literature regarding several BD classes, in order to establish new correlations and new predictive methods of viscosity. The proposed methodologies were validated using available viscosity data of BDs having different chemical compositions in wide ranges of temperature and pressure. The new methods developed at atmospheric pressure for predicting BD viscosity were found to have better predictive ability than those commonly used in literature. In particular, the models developed with the Lewis and Squires equation fitted to biodiesel feedstock (LSDB model) and the same equation using the predicted degree of unsaturation (DU) (LSDU1 model) presented a very good performance with average relative deviation (ARD) < 2.5%. The results of those models were comparable to the uncertainty of the experimental measurements reported in the literature. For high pressure, the methods developed in the literature for oils and (in particular) vegetable oils were adapted here for biodiesel. A new method presented in this work using Avramov equation (AVR model) was able to predict the viscosity of different BD classes with ARD < 3%, which is better than that (ARD < 5%) predicted by the only method reported so far in literature.
Accumulation of mutated superoxide dismutase 1 (mSOD1) in amyotrophic lateral sclerosis (ALS) involves injury to motor neurons (MNs), activation of glial cells and immune unbalance. However, ...neuroinflammation, besides its detrimental effects, also plays beneficial roles in ALS pathophysiology. Therefore, the targeting of microglia to modulate the release of inflammatory neurotoxic mediators and their exosomal dissemination, while strengthening cell neuroprotective properties, has gained growing interest. We used the N9 microglia cell line to identify phenotype diversity upon the overexpression of wild-type (WT; hSOD1
) and mutated G93A (hSOD1
) protein. To investigate how each transduced cell respond to an inflammatory stimulus, N9 microglia were treated with lipopolysaccharide (LPS). Glycoursodeoxycholic acid (GUDCA) and dipeptidyl vinyl sulfone (VS), known to exert neuroprotective properties, were tested for their immunoregulatory properties. Reduced Fizz1, IL-10 and TLR4 mRNAs were observed in both transduced cells. However, in contrast with hSOD1
-induced decreased of inflammatory markers, microglia transduced with hSOD1
showed upregulation of pro-inflammatory (TNF-α/IL-1β/HMGB1/S100B/iNOS) and membrane receptors (MFG-E8/RAGE). Importantly, their derived exosomes were enriched in HMGB1 and SOD1. When inflammatory-associated miRNAs were evaluated, increased miR-146a in cells with overexpressed hSOD1
was not recapitulated in their exosomes, whereas hSOD1
triggered elevated exosomal miR-155/miR-146a, but no changes in cells. LPS stimulus increased M1/M2 associated markers in the naïve microglia, including MFG-E8, miR-155 and miR-146a, whose expression was decreased in both hSOD1
and hSOD1
cells treated with LPS. Treatment with GUDCA or VS led to a decrease of TNF-α, IL-1β, HMGB1, S100B and miR-155 in hSOD1
microglia. Only GUDCA was able to increase cellular IL-10, RAGE and TLR4, together with miR-21, while decreased exosomal miR-155 cargo. Conversely, VS reduced MMP-2/MMP-9 activation, as well as upregulated MFG-E8 and miR-146a, while producing miR-21 shuttling into exosomes. The current study supports the powerful role of overexpressed hSOD1
in attenuating M1/M2 activation, and that of hSOD1
in switching microglia from the steady state into a reactive phenotype with low responsiveness to stimuli. This work further reveals GUDCA and VS as promising modulators of microglia immune response by eliciting common and compound-specific molecular mechanisms that may promote neuroregeneration.
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