In this paper, the experimental protocol which we disclose is designed to identify the values for both the constant in the Kozeny/Carman model, which relates to the linear component of permeability, and the variable kinetic coefficient in the newly minted Q- modified Ergun model, which relates to the non-linear components of permeability, without involving any new theoretical development. Moreover, kinetic contributions to measured pressure gradient, which are not accounted for in some currently accepted empirical fluid flow equations, such as Poiseuille’s for flow in empty conduits and Kozeny/Carman for flow in packed conduits, but which nevertheless contribute to measured pressure drop and thus hamper the identification of the value of the constant relative to the laminar component, are captured and lumped together into a single variable kinetic parameter-the kinetic coefficient.

In this paper we develop from first principles a unique law pertaining to the flow of fluids through closed conduits. This law, which we call “Quinn’s Law”, may be described as follows: When fluids are forced to flow through closed conduits under the driving force of a pressure gradient, there is a linear relationship between the normalized dimensionless pressure gradient, P_Q, and the normalized dimensionless fluid current, C_Q. The relationship is expressed mathematically as: P_Q = k₁ +k₂C_Q. This linear relationship remains the same whether the conduit is filled with or devoid of solid obstacles. The law differentiates, however, between a packed and an empty conduit by virtue of the tortuosity of the fluid path, which is seamlessly accommodated within the normalization framework of the law itself. When movement of the fluid is very close to being at rest, i.e., very slow, this relationship has the unique minimum constant value of k₁, and as the fluid acceleration increases, it varies with a slope of k₂ as a function of normalized fluid current. Quinn’s Law is validated herein by applying it to the data from published classical studies of measured permeability in both packed and empty conduits, as well as to the data generated by home grown experiments performed in the author’s own laboratory.

The research results presented in the article were carried out during the realization of the project, the aim of which is to develop a method of drying cellulose insulation in power transformers with the use of synthetic ester. This method uses a very high water absorption of the ester. During the drying of transformers, the ester is systematically contaminated with mineral oil, which gradually loses its ability to absorb water. Information on the oil concentration in the mixture is needed in two cases: at the stage of making a decision on the treatment of the mixture and during its treatment. The article presents the results of investigations of two methods: 1) based on the measurement of the mixture density, and 2) based on the measurement of the capacitance of the capacitor immersed in the mixture. The conducted research shows that the method of measuring the density of the mixture gives an uncertainty of 2.6 p. %, while the method of measuring the capacitance of a capacitor gives an uncertainty of 2.2 p. %. A significant advantage of the method of measuring the capacitance is the possibility of using it online to control the ester treatment process.

The problem of event detection in general noisy signals arises in many applications; usually, either a functional form for the event is available, or a previous annotated sample with instances of the event that can be used to train a classification algorithm. There are situations, however, where neither functional forms nor annotated samples are available; then it is necessary to apply other strategies to separate and characterize events. In this work, we analyze 15 minute-long samples of an acoustic signal, and are interested in separating sections, or segments, of the signal which are likely to contain significative events. For that, we apply a sequential algorithm with the only assumption that an event alters the energy of the signal. The algorithm is entirely based on Bayesian methods.

Energy communities are key actors in the energy transition since they optimally interconnect renewable energy capacities with the consumers. Despite versatile objectives, they usually aim at improving the self-consumption of renewable electricity within low voltage grids to maximize revenues. In addition, energy communities are an excellent opportunity to supply renewable electricity to regional and national energy systems. However, effective price signals have to be designed to coordinate the needs of the energy infrastructure with the interests of these local stakeholders. The aim of this paper is to demonstrate the integration of energy communities at the national level with a bottom-up approach. District energy systems with a building scale resolution are modelled in a mixed integer linear programming problem. The Dantzig-Wolfe decomposition is applied to reduce the computational time. The methodology lies within the framework of renewable energy hub, characterized by a high share of photovoltaic capacities. Both investments into equipment and its operation are considered. The model is applied on a set of five typical districts and weather locations representative of the Swiss building stock. The extrapolation to the national scale revealed a heterogeneous photovoltaic potential throughout the country. Present electricity tariffs promote a maximal investment into photovoltaic panels in every region, reaching an installed capacity of 67.2 GW and generating 80 TWh per year. Since the national PV capacity needed is forecast at 15.4 GW peak, coordinated investments between local and national actors are needed to prevent dispensable expenses. An uncoordinated design is expected to increase the total costs for residential energy systems by 43.2% and curtails 48.2% of local renewable electricity.

The bulk backscattering ratio ($\tilde{b_{bp}}$) is commonly used as a descriptor of the bulk real refractive index of the particulate assemblage in natural waters. Based on numerical simulations, we analyze the impact of heterogeneity of phytoplankton cells on $\tilde{b_{bp}}$. $\tilde{b_{bp}}$ is modeled considering viruses, heterotrophic bacteria, phytoplankton, detritus, and minerals. Three study cases are defined according to the relative abundance of these different components. Two study cases represent typical situations in open ocean, outside (No-B/No-M) and inside bloom (B/No-M). The third study case is typical of coastal waters with the presence of minerals. Phytoplankton cells are modeled by a two-layered spherical geometry representing a chloroplast surrounding the cytoplasm. The $\tilde{b_{bp}}$ values are higher when heterogeneity is considered because the contribution of coated spheres to backscattering is higher than homogeneous spheres. The impact of heterogeneity is however strongly conditioned by the hyperbolic slope $\xi$ of the particle size distribution. Even if the relative concentration of phytoplankton is small (<1%), $\tilde{b_{bp}}$ increases by about 60% (for $\xi=4.3$ and for the No-B/No-M water body), when the heterogeneity is taken into account, in comparison with a particulate population only composed by homogeneous spheres. As expected, heterogeneity has a much smaller impact (about 5$\%$ for $\xi=4.3$) on $\tilde{b_{bp}}$ when minerals are added.

Background. Green spaces contribute to a significant life quality and maintain the sustainability of cities. In Benin, despite the political greening willingness, municipalities are experiencing technical issues in finding suitable spaces to achieve this goal. This study should serve many other towns. It aims at identifying suitable areas for green spaces to integrate landscaping into urban planning in Abomey-Calavi district. Methods. The multi-criteria analysis combining GIS and the hierarchical classification approach were performed. Six factors (land use, altitude, slope, distance from main roads, proximity to urban centres and distance from flood zones, water bodies) were combined using the ArcGIS "Spatial Analysis" extension to generate a map of green space suitability. Results. large areas of land, of which 23.27% are very suitable and 26.06% are suitable for landscaping in this municipality. The ranking of the factors revealed altitude, proximity to road networks, large conurbations and distance from wetlands accounting for 18%, compared with 14% for the other factors regarding the study environment. However, the use of these results must take into account the existing inhabited areas for a good site selection. Conclusion. These outputs guidance to decision-makers in choosing suitable sites for green spaces there and integrating them into sustainable development.

Bacteriophages, viruses that are widespread throughout the world, are highly specific for bacteria, usually of a single species and often of a particular strain. After being discovered and isolated 100 years ago, their use, called phage therapy, was instituted in medicine two years later and quickly used around the world to treat various bacterial infections. In the West, phage therapy was overshadowed in the second half of the 20th century by antibiotic therapy, which was then thought to be the definitive solution. But because of the increase in bacterial resistance to antibiotics, the idea of using bacteriophages in medicine has been reawakened. The innumerable observations reported over the years in the literature constitute an invaluable experience. We and some of our colleagues have, in the last decade treated some patients compassionately. With the available documentation and our own experience we discuss the potential indications and limitations of phage therapy. The observation of the increasing number of therapeutic failures in the announced perspective of a post-antibiotic era, we believe, that the introduction of bacteriophages into the therapeutic arsenal seems conceivable today to two preconditions: that their production as biologic drug meets current regulatory standards and that the benefit-risk assessment was conducted in a modern setting. Phage therapy could be applied as a substitution or supplement to antibiotic therapy under multiple circumstances in different modes, precise indications and limits.

Today, satellite imagery has made a major contribution to the reconstruction and spatial prediction of sensitive or complex areas such as Pendjari and W Transboundary Reserves which constitute biodiversity reservoirs and habitats for wildlife conservation. Despite the protection to which they are subject, they remain dependent on climatic hazards that can influence their stability. This study has applied remote sensing techniques, combined with climate records from the last thirty years, to analyze the past dynamics of land use and climate changes, to predict the future states of the vegetation cover of the two national parks in Benin, as well as their periphery. The methodology used remote sensing and GIS techniques that allowed the supervised classification of Landsat images of 1985, 2000 and 2015. Climatic data were combined in R software to identify the break periods for climatic parameters. Finally, the predictive vegetation cover for the year 2030 was made by combining vegetation and climate in the "Land Change Modeler" extension. Ten land use and land cover classes were obtained. These are the agglomerations, mosaics of fields and fallows, water bodies, dense forests, gallery forests, clear forests and wooded savannahs, swamp forests and shrubby wooded savannahs, saxicolous savannahs and bare ground. The natural vegetation decreased from 90.85% in 1985 to 83.54% in 2000 then to 79.56% in 2015, a decline of 11.39% over a 30-year period. The analysis of the climatic curves revealed the presence of break, meaning drought frequency. The predictive modeling revealed that land use units projected to 2030 are consistent with past trends, but with the continued expansion of fields and fallows (2%) at the expense of vegetation cover. This study will motivate many others in the field.

The flywheel is a widespread mechanical component used for the storage of kinetic energy and angular momentum. It typically consists of a cylindrical inertia rotating about its axis on rolling bearings, which involves undesired friction, lubrication, and wear. This paper presents an alternative mechanism that is functionally equivalent to a classical flywheel while relying exclusively on limited-stroke flexure-joints. This novel 1-degrees-of-freedom zero-stiffness mechanism has no wear and requires no lubrication: it is thus compatible with extreme environments, such as vacuum, cryogenics, or ionizing radiation. The mechanism is composed of two coupled pivoting rigid bodies whose individual angular momenta vary during motion but whose sum is constant at all times when the pivoting rate is constant. The quantitative comparison of the flexure-based flywheel to classical ones based on a hollow cylinder as inertia shows that the former stores typically 6 times less angular momentum and kinetic energy for the same mass while occupying typically 10 times more volume. The freedom of design of the shape of the rigid bodies offers the possibility of modifying the ratio of the kinetic energy stored versus angular momentum, which is not possible with classical flywheels. For example, a flexure-based flywheel with rigid pivoting bodies in the shape of thin discs stores 100 times more kinetic energy than a classical flywheel with the same angular momentum. A proof-of-concept prototype was successfully built and characterized in terms of reaction moment generation, which validates the presented analytical model.

Front-of-pack labelling (FOPL) systems, such as the Nutri-Score, play a crucial role in promoting healthy diets and raising consumer awareness. Our study aimed to gather the opinions of Polish experts on the Nutri-Score and its relation to an ideal information system. We conducted a Poland-wide expert opinion study using a cross-sectional design survey with 75 participants, who had an average of 18±13 years of experience and were mainly employed at medical and agricultural universities. The data were collected with CAWI method. The results showed that the most important features of an FOPL system were clarity, simplicity, consistency with healthy eating recommendations, and the ability to objectively compare products within the same group. While more than half of the respondents believed that the Nutri-Score provides an overall assessment of a product’s nutritional value and facilitates quick purchasing decisions, it falls short in helping consumers compose a balanced diet and cannot be applied to all product groups. The experts also expressed concerns about the system’s ability to account for a product’s degree of processing, full nutritional value and carbon footprint. In conclusion, Poland’s current labelling system needs expansion, but the Nutri-Score requires significant and deep changes and validation against national guidelines and expert expectations before implementation.

The use of Hyperspectral (HS) and LiDAR acquisitions has a great potential to enhance mapping and monitoring practices of endangered grasslands habitats, beyond conventional botanical field surveys. In this study we assess the potentiality of Recursive Feature Elimination (RFE) in combination with Random Forest (RF) classification in extracting the main HS and LiDAR features needed to map selected Natura 2000 grasslands along Polish lowland river valleys, in particular alluvial meadows 6440, lowland hay meadows 6510 and xeric and calcareous grasslands 6120. We developed an automated RFE-RF system capable to combine the potentials of both techniques and applied it to multiple acquisitions. Several LiDAR-based products and different Spectral Indexes (SI) were computed and used as input in the system, with the aim of shedding light on the best-to-use features. Results showed a remarkable increase in classification accuracy when LiDAR and SI products are added to the HS dataset, strengthening in particular the importance of employing LiDAR in combination with HS. Using only the 24 optimal features selection generalized over the three study areas, strongly linked to the highly heterogeneous characteristics of the habitats and landscapes investigated, it was possible to achieve rather high classification results (K around 0.7-0.77 and habitats F1 accuracy around 0.8-0.85), indicating that the selected Natura 2000 meadows and dry grasslands habitats can be automatically mapped by airborne HS and LiDAR data. Similar approaches might be considered for future monitoring activities in the context of habitats protection and conservation

Climate change is affecting the planet, compromising survival and altering forest ecosystems. Investigating climatic variations in all regions is important. The aim of this research was to assess such variations in the W and Pendjari Biosphere Reserves in Benin from 1985 to 2015 and predict climate up to 2045. Drought frequency was assessed by using the Standardized Precipitation and Evapotranspiration Index (SPEI) and correlation was performed between climatic variables. Then a predictive analysis was computed. From 1985 to 2015, there was change in the climate with few severe dry and wet years while no extreme climatic condition was noticed. Most of the years showed nearly normal climatic conditions. The predicted climate indicates an absence of extreme conditions up to 2045 but an increase in the annual humidity is expected. A low decrease in annual mean temperature with high confidence is expected. Decision-makers can better organize adaptation programs and sensitize people in the reserves on their role in environmental conservation and mitigation of climate change using these outputs.

Objective: The goal of the present study was to evaluate the treatment with Canephron® after the diagnosis of acute cystitis or urinary tract infection (UTI) with regards to the risk of a sporadic recurrent UTI, frequent recurrent UTIs, UTI associated sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis) compared to standard antibiotic treatment. Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 in general practitioner (GP), gynecologist, or urologist practices from which data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI associated sick leave, amount of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson Comorbidity Score (CCI). Results: 2,320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with less sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58–0.72), as well as with less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and with minor additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16) and occurrences of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real world data show that Canephron® is an effective and safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment in particular also to strengthen antimicrobial stewardship strategies.

(1) Background: To substantiate the clinical efficacy and investigate the real-world effectiveness of the herbal medicinal product BNO 1016 in acute rhinosinusitis (ARS) in the context of antibiotic stewardship. (2) Methods: Clinical efficacy: We performed a meta-analysis of the clinical trials ARhiSi-1 and ARhiSi-2 comprising 676 patients, analysing the reduction of the Major Symptom Score (MSS) and improvement of SNOT-20. Real-world effectiveness: In addition, we performed a retrospective cohort study including 203,382 patients, comparing the real-life effectiveness of BNO 1016 in reducing ARS-related adverse outcomes in comparison to antibiotics and several other established therapies. (3) Results: Clinical efficacy: Treatment with BNO 1016 ameliorated symptoms of ARS by reducing MSS by 1.9 points (p&lt;0.0001) and improved quality of life (QoL) for patients by improving SNOT-20 by 3.5 points (p=0.001) in comparison to placebo. In patients with moderate/severe symptoms, the positive effects of BNO 1016 were even more pronounced (MSS: –2.3 points (p&lt;0.0001); SNOT-20: –4.9 points (p=0.0158)) compared to placebo. Real-world effectiveness: Treatment with BNO 1016 was as effective or significantly more effective in reducing the risk for adverse ARS-related outcomes such as follow-up antibiotic prescriptions, sick leave ≥7 days or medical appointments due to ARS, especially when compared to antibiotics. (4) Conclusions: BNO 1016 is a safe and effective treatment for ARS that can help reduce the overuse of antibiotics.

Carbon concrete PAN/lignin-based CF composites are a new promising material class for the building industry. The replacement of the traditional heavy and corroding steel reinforcement by carbon fiber (CF) based reinforcements offers many significant advantages: a higher protection of environmental resources because of lower CO2 consumption during cement production, a longer lifecycle and thus muss less damage in structural components and a higher degree of design freedom because lightweight solutions can be realized. However, due to cost pressure in civil engineering, completely new process chains are required to manufacture CF based reinforcement structures for concrete. The article describes the necessary process steps in order to develop CF reinforcement: (1) the production of cost-effective CF using novel carbon fiber lines, (2) the fabrication of CF rebars with different geometry profiles. It was found that PAN/lignin-based CF is currently the most promising material in order to meet the future market demands. However, significant research needs to be undertaken in order to improve the properties of lignin-based and PAN/lignin-based CF, respectively. The CF can be manufactured to CF-based rebars using different manufacturing technologies which have been developed on prototype level in this study.

In this paper we explore extending the concept of common cross-study Common Data Element concepts beyond simple demographics to cover disease-specific concepts relevant to imaging. We test interactively linking the resulting database to the associated images in a federated manner. We examine the use of existing standards, not only for terminology, but for interchange of serialized data in forms familiar to imaging and clinical trials specialists and their dedicated systems. Our intent is to perform preliminary work to inform both the upcoming Imaging Data Commons specifically, as well as more general integration projects beyond imaging.

Excessive use of antibiotics to control colibacillosis on poultry farms in Morocco contributes to the development of multiresistant avian pathogenic E. coli. Autogenous vaccines are an alternative to antibiotic usage; the main goal of this study was to assess the efficacy of this approach to control recurrent outbreaks of colibacillosis in a large broiler production flow. A tetravalent autogenous vaccine (serotypes O78, O88, O91, and O185) was produced from E. coli strains isolated from clinical lesions in breeding hens and used on two farms (65,000 breeding hens in total). On each farm, contemporaneous groups were included: groups vaccinated twice (12 and 18 weeks of age) and unvaccinated control groups. The performances of these flocks, as well as the performances of broilers hatched from these breeders (12 farms, over 600,000 broilers in total), were recorded. A significant reduction in lesion scores, mortality rate and a significant increase in the number of saleable day-old chicks were observed among vaccinated hens. In broilers, body weight at slaughter, lesion scores, food conversion ratio, mortality and condemnation rates were significantly improved. This is the first field observation of a lasting effect of breeder hens immunization with an autogenous vaccine against E. coli on their offspring.

The production of biomass fly ash has been increasing every year in Europe, reaching 5.5 million tons in 2020. Biomass fly ash is not yet accepted in the standards as a substitute material for cement in mortar and concrete. In a first approach, the substitution limit of biomass fly ash is determined by comparing the mechanical strengths, fresh state properties and hardened properties of mortars produced with biomass fly ash to those of mortars produced with classical coal fly ash. Then, masonry and rendering mortars have been designed with different substitution rates of biomass fly ashes from wood combustion in thermal power plant. Although there is an overall decrease in performance, mortars made with biomass ash retain properties that make them suitable for use in masonry or rendering.

Background: Informal caregivers' own quality of life, health status, and determinants are poorly understood despite their concerns for the health of the individuals they assist. Objectives: To compare the quality of life and the health determinants of older informal caregivers with those of older adults without caregiving responsibilities. Methods: An online survey was designed to investigate the quality of life and the health determinants of people aged 65 years and over, with a focus on informal caregivers. In addition to socio-demographic data, the number of informal caregiver and the Zarit scale of caregiver burden were collected. Quality of life (SF-12) and health determinants (access to technology and level of physical activity (IPAQ)) were assessed and compared between informal caregivers and the others. Results: A total of 111 participants (70 ± 3.83 years, 71.2% of women). The majority of respondents (91.8%) were Belgian. One third of the respondents identified themselves as informal caregiver and declared to have severe burden (61.9±15.2/88). Socio-demographic characteristics and access to technology were similar between informal caregivers and non-caregivers (p>0.05). However, informal caregivers have a lower SF-12 score in the mental score domain (44.3±10.2 vs; 50.7±7.0; p=0.004) and a lower level of physical activity (434±312 METS/min/week vs.1126±815 METS/min/week; p=0.01) than their peers. Conclusions: Informal caregivers reported lower quality of life and lower level of physical activity than their peers. Given the recognized importance of physical activity for overall health, this survey highlights the need to promote physical activity among older informal caregivers.

Recent years brought great focus in the field of development of extracellular vesicles (EVs) based drug-delivery systems. Considering possible applications of EVs as a drug carriers the isolation process is a crucial step. To solve problems related with EV isolation, we created and validated a new EVs isolation method – Low Vacuum Filtration (LVF) and compared it with two commonly applied procedures - differential centrifugation (DC) and ultracentrifugation (UC). EVs isolated from endothelial cells culture media have been characterized by a) transmission electron microscopy (TEM) b) nanoparticle tracking analysis (NTA), c) western blot and d) Fourier-Transform Infrared Spectroscopy (FTIR). Additionally, the membrane surface have been imaged with Environmental Scanning Electron Microscopy (ESEM). We showed that LVF is reproducible and efficient method for EVs isolation form conditioned media. Additionally, we observed correlation between ATR-FTIR spectra quality and the EVs and proteins concentration. ESEM imaging confirmed that actual pore diameter are close to the values calculated theoretically. LVF method is an easy, fast and inexpensive EVs isolation method which allows for isolation of both ectosomes and exosomes from high volume sources with good repeatability. We think that it could be an efficient alternative for commonly applied methods.

We address Multi-Wall Carbon NanoTubes (MWCNTs) for structural health monitoring in adhesive bonds such as in building structures. MWCNT-loaded composites are employed to sense strain changes under tension load using an AC impedance measurement setup. Different weight percentages of 1, 1.5, 2 and 3 wt.% MWCNT are added to the base epoxy resin using different dispersion times, i.e. 5, 10 and 15 minutes. The equivalent parallel resistance of the specimens is measured by applying an alternating voltage at different frequencies. To determine the mechanical as well as sensory properties, the specimens are subjected to a tensile test with concurrent impedance measurement. Using alternating voltage, a higher sensitivity of the impedance reading can be achieved. Employing these sensors in buildings and combining the readings of a network of such devices can significantly improve the buildings’ safety. Additionally, networks of such sensors can be used to identify necessary maintenance actions and locations.

The direct measurements of the magnetic flux density in steel blocks within Compact Muon Solenoid (CMS) magnet yoke are performed with 22 flux loops installed in selected regions of the yoke. The 10,000-ton CMS magnet flux return yoke encloses a 4 T superconducting solenoid with a 6-m-diameter by 12.5-m-length free bore and consists of five dodecagonal three-layered barrel wheels and four end-cap disks at each end. The yoke steel blocks, mostly up to 620 mm thick, serve as the absorber plates of the muon detection system. A TOSCA 3-D model of the CMS magnet has been developed to describe the magnetic field everywhere outside of the tracking volume which was measured with a field-mapping machine. In the present study, for the first time, the reliable reconstruction of the magnetic flux density in the steel blocks of the yoke is performed using the CMS magnet standard discharges from the operational magnet current of 18.164 kA. To provide this reconstruction, the voltages induced in the flux loops (with amplitudes of 20–250 mV) have been measured with six 16-bit DAQ modules and integrated offline over time. The results of the flux loop measurements during three magnet ramp downs are presented and discussed.

The modification of GFP-CaaL sensor proteins by geranylgeranyl groups in plants requires an active plastidial mevalonate (MVA)-independent pathway. As a consequence, fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose (DX)-5 phosphate reductoisomerase/DXR, the second enzyme in this so-called methylerythritol phosphate (MEP) pathway, impedes protein prenylation, which results in GFP-labeling of nuclei instead of the plasma membrane. In tobacco cells, a visual screen of conditions that allowed membrane localization of GFP-CaaL proteins in the presence of fosmidomycin, pinpointed jasmonic acid methyl esther (Me-JA) as a chemical able to overcome the inhibition in a gradual manner. Using Arabidopsis protein prenyltransferase loss-of-function mutant lines expressing GFP-CaaL proteins, we demonstrated that Me-JA induces a modification in protein substrate recognition by protein farnesyltransferase (PFT). Similar to Me-JA, farnesol and MVA also alter the protein substrate specificity of PFT, whereas DX and geranylgeraniol have limited or no effect. Our data indicate that stimulation of the MVA pathway adjusts the protein substrate specificity of PFT, which is corroborated with metabolic cross-talk of the origin of the prenyl group used to modify the protein. To illustrate how activation of the MVA pathway impacting PFT substrate specificity benefits a plant under stress conditions, a model is proposed.

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

This paper concerns a new methodology for accuracy assessment of global positioning system verified experimentally with LiDAR (Light Detection and Ranging) data alignment at continent scale for autonomous driving safety analysis. Accuracy of GPS (Global Positioning System) positioning of an autonomous driving vehicle within a lane on the road is one of the key safety considerations. Safety is addressed as a geometry of the problem, where the aim is to maintain knowledge that the vehicle (its bounding box) is within its lane. Accuracy of GPS positioning is checked by comparing it with mobile mapping tracks in the recorded high definition source. The aim of the comparison is to see if the GPS positioning remains accurate up to the dimensions of the lane where the vehicle is driving. For this reason, a new methodology is proposed. Methodology is composed of six elements: 1) Mobile mapping system minimal setup, 2) Global positioning data processing, 3) LiDAR data processing, 4) Alignment algorithm, 5) Accuracy assessment confirmation and 6) Autonomous driving safety analysis. The research challenge is to assess positioning accuracy of moving cars taking into account the constraints of the coverage of limited access highways in the United States of America. The available coverage limits the possibility of repeatable measurements and introduces an important challenge being the lack the ground truth data. State-of-the-art methods are not applicable for this particular application, therefore a novel approach is proposed. The method is to align all the available LiDAR car trajectories to confirm the GNSS+INS (Global Navigation Satellite System + Inertial Navigation System) accuracy. For this reason, the use of LiDAR metric measurements for data alignment implemented using SLAM (Simultaneous Localization and Mapping) was investigated, assuring no systematic drift by applying GNSS+INS constraints. SLAM implementation used state-of-the-art observation equations and the Weighted Non-Linear Least Square optimization technique that enables integration of the required constraints. The methodology was verified experimentally using arbitrarily chosen measurement instruments (NovAtel GNSS+INS, LiDAR Velodyne HDL32) mounted onto mobile mapping systems. The accuracy was assessed and confirmed by the alignment of 32785 trajectories with total length of 1,159,956.9~km and of total $186.4*10^{9}$~optimized parameters (six degrees of freedom of poses) that cover the United States region in the 2016--2019 period. It is demonstrated that the alignment improves the trajectories, thus final map is consistent. The proposed methodology extends the existing methods of global positioning system accuracy assessment focusing on realistic environmental and driving conditions. The impact of global positioning system accuracy on autonomous car safety is discussed. It is shown that 99\% of the assessed data satisfies the safety requirements (driving within lanes of 3.6~m) for Mid-Size (width 1.85~m, length 4.87~m) vehicle and 95\% for 6-Wheel Pickup (width 2.03--2.43~m, length 5.32--6.76~m). The conclusion is that this methodology has great potential for global positioning accuracy assessment at global scale for autonomous driving applications. LiDAR data alignment is introduced as a novel approach to GNSS+INS accuracy confirmation. Further research is needed to solve the identified challenges.

Abstract: Filipendula ulmaria, commonly known as meadowsweet, is a wild herbaceous flowering plant widely distributed in Europe. A range of salicylic acid derivatives and flavonol glycosides have been previously associated with the antirheumatic and diuretic properties of F. ulmaria. In the present work, an hydroalcoholic extract of F. ulmaria aerial parts was extensively profiled using an efficient NMR-based dereplication strategy. The approach involves fractionation of the crude extract by centrifugal partition chromatography (CPC), ¹³C NMR analysis of the fractions, 2D-cluster mapping of the whole NMR dataset and finally, structure elucidation using a natural metabolite database, validated by 2D NMR data interpretation and liquid chromatography coupled to mass spectrometry. The chemodiversity of the aerial parts was quite broad, with 28 compounds unambiguously identified, belonging to various biosynthetic classes. The F.ulmaria extract and CPC fractions were screened for their potential to improve skin epidermal barrier function and also skin renewal properties using in vitro assays performed on Normal Human Epidermal Keratinocytes. Fractions containing quercetin, kaempferol glycosides, ursolic acid, pomolic acid, naringenin, β-sitosterol, and tellimagrandins I and II were found to be responsible for the up-regulation of genes related to skin barrier function, epidermal renewal and stress responses. This research is significant as it could provide a natural solution for improving hydration and skin renewal properties.

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n=51) and BPH patients (n=48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using quantitative real-time polymerase chain reaction (qRT‒PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a down-regulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility as clinical diagnostic markers.

Natural laterite fixed-bed column intercalated with activated carbon prepared from Balanites ae-gyptiaca (BA-AC) was used for As(III) removal from an aqueous solution. Investigations were carried out to solve the problem of column clogging which appears during water percolation through the column. Experimental tests were conducted to evaluate the hydraulic conductivity and the effects of various parameters such as grain size, bed height, and initial As(III) concentra-tion. The breakthrough increased from 15 to 85 h with the increase of the bed height from 20 to 40 cm, and decreased from 247 to 32 h with the increase of initial As(III) concentration from 0.5 to 2 mg/L. The permeability data showed that the fixed-bed column filled with laterites layers intercalated with activated carbon performs much better than the non-intercalated adsorbent col-umn. The Bohart-Adams model showed that increasing the bed height induced a decrease in kAB and N0 values. The critical bed depths determined using the bed depth service time (BDST) mod-el for As(III) removal were 15.23 and 7.98 cm for 1 and 20% breakthrough, respectively. The re-sults showed that the new low-cost filtration system, based on laterite layers alternated with BA-AC layers, could be used for the treatment of arsenic-contaminated water.

VNREDSat-1 is the first Vietnamese satellite allowing the survey of environmental parameters such as vegetation and water coverages, or surface water quality at medium spatial resolution (from 2.5 to 10 meters depending on the considered channel). The NAOMI sensor on board VNREDSat-1 has the required spectral bands to assess the suspended particulate matter concentration, SPM. Because recent studies have shown that the remote sensing reflectance, Rrs(), at the blue (450 – 520 nm), green (530 – 600 nm), and red (620 – 690 nm) spectral bands can be assessed from NAOMI with a good accuracy, the present study is dedicated to the development and validation of an algorithm (hereafter referred to as V1SPM) to assess SPM from Rrs() over inland and coastal waters of Vietnam. For that purpose, an in situ data set of hyper-spectral Rrs() and SPM (from 0.47 to 240.14 g.m-3) measurements collected at 205 coastal and inland stations has been gathered. Among the different approaches, including 4 historical algorithms, the polynomial algorithms involving the red-to-green reflectance ratio presents the best performance on the validation data set (MAPD of 18,7%). Compared to the use of a single spectral band, the band ratio allows to reduce the scatter around the polynomial fit as well as the impact of imperfect atmospheric corrections. Due to the lack of matchup data points with VNREDSat-1, the full VNREDSat-1 processing chain (RED-NIR and V1SPM) aiming at estimate SPM from the top-of-atmosphere signal has been applied to the Landsat-8/OLI match-up data points with relatively low to moderate SPM concentration (3.33-15.25 g.m-3) showing a MAPD of 15,8%. An illustration of the use of this VNREDSat-1 processing chain during a flooding event occurring in Vietnam is provided.

In early 2020 from April to early June, the metropolitan area of Sydney as well as the rest of New South Wales (NSW, Australia) experienced a period of lockdown to prevent the spread of Covid-19 virus in the community. The effect of reducing anthropogenic activities including transportation had an impact on the urban environment in term of air quality which is shown to have improved for a number of pollutants, such as nitrogen dioxides (NO2) and carbon monoxide (CO), based on monitoring data on ground and from satellite. Besides primary pollutants CO and NOx emitted from mobile sources, PM2.5 (primary and secondary) and secondary ozone (O3) during the lockdown period will also be analysed using both air quality data and modelling method. The results show that NO2, CO and PM2.5 levels decreased during the lockdown, but O3 instead increased. The change in the concentration levels however are small considering the large reduction in traffic volume of ~30%. By estimate the decrease in traffic volume in Sydney region, the corresponding decrease in emission input to the WRF-CMAQ (Weather Research and Forecasting - Community Multiscale Air Quality Modeling System) air quality model is then used to estimate the effect of lockdown on the air quality especially CO, NO2, O3 and PM2.5 in the Greater Metropolitan Region (GMR) of Sydney. COVID-19 lockdown period is an ideal case to study the effect of motor vehicle and mobile source contribution to air pollutants such as those listed above in the GMR.

Bovine whey cheese (WC) is a product from southern European countries that presents some challenges: their elaboration process involves high energy inputs, the yield is low and WC has a short shelf-life. The application of ultrafiltration to bovine whey before its manufacture and the employment of protective cultures can reduce these disadvantages. The aim of this work was to manufacture whey cheeses using ultrafiltrated (UF) concentrated bovine cheese whey with added probiotics or probiotics plus protective cultures. Three types of WC were produced: control, without any addition (C); with the addition of the probiotic Lactobacillus acidophilus (LA5); with the addition of Lactobacillus acidophilus plus a protective culture containing Lactobacillus paracasei and Lactobacillus rhamnosus (LA5FQ4). The WCs were stored under refrigerated conditions for 28 days. The products with added cultures presented a lower pH and a higher titratable acidity when compared to the control. Sample LA5 presented the lowest pH and the highest titratable acidity while LA5FQ4 presented intermediate values. Slight differences were observed between products regarding color parameters, chiefly as a result of storage time. The samples with added cultures were firmer when compared to the control, showing LA5 cheeses the highest values at the end of the storage. Lactobacilli and lactococci counts were of the order of log 8-9 CFU/g for the products with added cultures. Lower levels of yeasts and moulds were detected on the sample with the protective culture (LA5FQ4), that by the end of storage presented counts one log cycle lower than C and LA5. Hence, it is evident the beneficial impact of the protective culture on the shelf life of the product. In what concerns to sensory evaluation, LA5FQ4 cheeses obtained the highest scores regarding all parameters evaluated. It could be concluded that the use of UF associated to the addition of protective cultures can be very useful to reduce the energy consumption of the process, prolong the shelf life of WC, and to improve its sensory properties.

Yaws is a skin debilitating disease caused by Treponema pallidum subspecies pertenue with most cases reported in children. World Health Organization (WHO) aims at total eradication of this disease through mass treatment of suspected cases followed by an intensive follow-up program. However, effective diagnosis is pivotal in the successful implementation of this control program. Recombinase polymerase amplification (RPA), an isothermal nucleic acid amplification technique offers a wider range of differentiation of pathogens including those isolated from chronic skin ulcers with similar characteristics such as Haemophilus ducreyi (H. ducreyi). We have developed a duplex RPA assay for the simultaneous detection of Treponema pallidum (T. pallidum) and H. ducreyi (TPHD-RPA). TPHD-RPA assay demonstrated no cross-reaction with other pathogens and enable detection of T. pallidum and H. ducreyi within 15 minutes at 42 oC. The duplex RPA assay was validated with 49 clinical samples from individuals confirmed to have yaws by serological tests. Compared with commercial multiplex real-time PCR, the TPHD-RPA assay demonstrated 94-95% sensitivity for T. pallidum and H. ducreyi confirmed samples, respectively and 100% specificity. This simple novel TPHD-RPA assay enables the rapid detection of both T. pallidum and H. ducreyi in yaws-like lesions. This test could support the yaws eradication programs by ensuring effective diagnosis as well as enable monitoring of eradication efforts success or failure and planning of follow-up interventions at the community level.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

Acute myeloid leukemia (AML) is a malignant disease of the blood and bone marrow that is characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells. Nucleophosmin 1 (NPM1) gene mutations are the most common genetic abnormality in AML, detectable in blast cells from about one third of adults with AML. AML NPM1mut is recognized as a separate entity in the World Health Organization (WHO) classification of AML. Clinical and survival data suggest that patients with this form of AML often have a more favorable prognosis, which may be due to the immunogenicity created by the mutations in the NPM1 protein. Consequently, AML with NPM1mut can be considered an immunogenic subtype of AML. However, the underlying mechanisms of this immunogenicity and associated favorable survival outcomes need to be further investigated. Immune checkpoint molecules, such as the programmed cell death-1 (PD-1) protein and its ligand, PD-L1, play important roles in leukemogenesis through their maintenance of an immunosuppressive tumor microenvironment. Preclinical trials have shown that the use of PD-1/PD-L1 (PDx) checkpoint inhibitors in solid tumors and lymphoma work best in novel therapy combinations. Patients with NPM1mut AML may be better suited to immunogenic strategies that are based on the inhibition of the immune checkpoint pathway of PDx than patients without this mutation, suggesting the genetic landscape of patients may also inform best practice for the use of PDx inhibitors.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

Several studies have shown that tapering or stopping disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients in sustained remission is feasible. However, tapering/stopping bears the risk of decline in physical function as some patients may relapse and face increased disease activity. Here we analysed the impact of tapering or stopping DMARD treatment on the physical function of RA patients. The study was a posthoc analysis of physical functional worsening for 282 patients with RA in sustained remission tapering and stopping DMARD treatment in the prospective randomized RETRO study. HAQ and DAS-28 scores were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and HAQ and DAS-28 scores were evaluated every 3 months. The effect of treatment reduction strategy on functional worsening was assessed in a recurrent-event Cox regression model with a study-group (control, taper, taper/stop) as the predictor. 282 patients were analysed. In 58 patients, functional worsening was observed. The incidences suggest a higher probability of functional worsening in patients tapering and/or stopping DMARDs, which is likely due to higher relapse rates in these individuals. At the end of the study, however, functional worsening was similar among the groups. Point estimates and survival curves show that functional decline after tapering or stopping DMARDs in RA patients with stable remission is small and related to relapses but to on overall functional decline.