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While blood-based tests are readily available for various conditions, including cardiovascular diseases, type 2 diabetes, and common cancers, Alzheimer’s disease (AD) and other neurodegenerative diseases lack an early blood-based screening test that can be used in primary care. Major efforts have been made towards the investigation of approaches that may lead to minimally invasive, cost-effective, and reliable tests capable of measuring brain pathological status. Here, we review past and current technologies developed to investigate biomarkers of AD, including novel blood-based approaches and the more established cerebrospinal fluid and neuroimaging biomarkers of disease. The utility of blood as a source of AD-related biomarkers in both clinical practice and interventional trials is discussed, supported by a comprehensive list of clinical trials for AD drugs and interventions that list biomarkers as primary or secondary endpoints. We highlight that identifying individuals in early preclinical AD using blood-based biomarkers will improve clinical trials and the optimization of therapeutic treatments as they become available. Lastly, we discuss challenges that remain in the field and address new approaches being developed, such as the examination of cargo packaged within extracellular vesicles of neuronal origin isolated from peripheral blood.

ABSTRACT Aging phenomenon has a key role in the deterioration of the asphalt mixtures performance. The modification of asphalt binders with nanomaterials that can retard the aging process can be [...]

A sedentary lifestyle, coupled with a decrease in estrogen, impairs bone homeostasis, favoring to the development of osteopenia and osteoporosis, both recognized as risk factors for fractures. Here, we investigated the quality of the femur, particularly the femur neck region, and the ambulation performance of senescent rats subjected to three different physical training protocols during the periestropause period. Forty-eight female rats, 18 months of age, were subjected to a 120-day training period, three times a week. The rats were distributed into four groups: aerobic training (AT), strength training (ST), concurrent training (CT), or no training (NT). After the experimental period, at 21 months of age, ambulation performance and femur were analyzed using microtomography, Raman stereology, densitometry, and mechanical strength tests. The results demonstrated greater remodeling activity and improvement in resistance and bone microarchitecture in the femur neck of senescent female rats after undergoing physical training. Our verified higher intensities of bands related to collagen, phosphate, amide III, and amide I. Furthermore, the analysis of the secondary collagen structures indicated alterations in the collagen network due to the exercise, resulting in increased bone strength. Both AT and strength-based training proved beneficial, with AT showing greater adaptations in bone density and stiffness in the femur, while strength-based training greater adaptations in trabecular and cortical structure. These insights contribute to the understanding of the potential interventions for preventing osteopenia and osteoporosis, which are critical risk factors for fractures.

ABSTRACTThe design of bituminous mixtures has been improved with new analytical methods and enhanced laboratory tests. However, the adoption of these methods increases the complexity and cost of the design [...]

ABSTRACT The objective of this study is to evaluate the effects of nanomodifications in the asphalt mixture performance. Three types of nanoparticles were used: silica, zero-valent iron and bentonite. The [...]

ABSTRACT Environmental conditions as well as traffic loads lead to the deterioration of asphalt pavements during their service life. For this reason, the use of nanomaterials that improve the mixtures [...]

ABSTRACT This research aimed to evaluate bituminous mixtures made with a high percentage of ultrafine- size rubber particles (Asphalt Rubber Concrete, ARC) using the dry process. Laboratory tests were performed [...]

The mechanical properties and corrosion resistance of annealed superferritic stainless steel model alloy 25Cr–6Mo–5Ni were investigated in 0.6 M NaCl solution. The microstructure consisted of a ferrite matrix and eutectoid phase with a lamellar structure distributed at grain boundaries and within the ferrite grains with a spherical morphology. Tensile and impact results suggested brittle behavior of the model alloy. Fractography analysis revealed typical cleavage facets, river patterns and micro-cracks at grain boundaries and across the ferrite grains. Pitting corrosion began within the eutectoid phase, which contains in chrome depletion zones. Electrochemical impedance spectroscopy measurements suggest that the breakdown of passive films was more susceptible in the eutectoid phase.

Despite the vast presence of the furan-fused naphthopyrone (FFN) skeleton in many bioactive natural products, such as lasionectrin, at present, a general approach to FFNs has not been developed yet. For that reason, a simple and straightforward synthetic approach consisting of a sequential procedure of a Diels–Alder reaction between 1,3-dimethoxy-benzocyclobutenol Iand furan-fused-α,β-unsaturated-δ-lactones II(via an ο-quinodimethane intermediate III) followed by an oxidative aromatization of the corresponding Diels–Alder adduct IVis reported. Subsequently, the formal synthesis of the (+)-lasionectrin and its C12-epimer was achieved, the latter in only six steps.

In this article, a study on the use of a commercial global-flash LiDAR sensor in active debris removal operations is presented. This type of activity requires precise knowledge of the position and orientation of the target to be removed. For these missions, relative navigation devices, such as cameras or LiDAR sensors are typically regarded. In this study, the mission profile defined in the e.Deorbit System Requirements Review was considered, and data acquisition and processing from a commercial ASC GSFL-16KS LiDAR sensor were simulated. As the main novelty of this work, the use of multilayer perceptron neural networks for the processing of LiDAR depth images is proposed in order to obtain an estimate of the pose of the target. Using the results of the neural networks, an iterative closest point algorithm is applied to refine the calculation of the pose. The accuracy and computation time of the system were evaluated, obtaining robust and computationally efficient results in the proposed study cases.

The accumulation of soluble oligomers of the amyloid-β peptide (AβOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer’s disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AβOs and shows minimal reactivity to Aβ monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AβO binding to neurons and AβO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer’s disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AβO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer’s disease.

Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.

The rational design of lipid nanoparticles (LNPs) for enhanced gene delivery remains challenging because of incomplete knowledge of their formulation–structure relationship that impacts their intracellular behavior and consequent function. Small-angle neutron scattering has been used in this work to investigate the structure of LNPs encapsulating plasmid DNA upon their acidification (from pH 7.4 to 4.0), as would be encountered during endocytosis. The results revealed the acidification-induced structure evolution (AISE) of the LNPs on different dimension scales, involving protonation of the ionizable lipid, volume expansion and redistribution of aqueous and lipid components. A similarity analysis using an LNP’s structural feature space showed a strong positive correlation between function (measured by intracellular luciferase expression) and the extent of AISE, which was further enhanced by the fraction of unsaturated helper lipid. Our findings reveal molecular and nanoscale changes occurring during AISE that underpin the LNPs’ formulation–nanostructure–function relationship, aiding the rational design of application-directed gene delivery vehicles.

Maritime transport remains a large source of airborne pollutants, including exhaust particles that can act as cloud condensation nuclei (CCN). While primary diesel engine exhaust particles are generally considered hydrophobic, international regulations targeting a reduction of particulate emissions from ships may have secondary effects, and therefore influence how exhaust interacts within the atmosphere. The effect of international fuel sulfur content (FSC) regulations on the cloud forming abilities of exhaust particles was investigated using a marine test engine operating on compliant low FSC fuels, non-compliant high FSC distillate fuels and in conjunction with a marine wet scrubber (fresh- and seawater). Particle sizing and liquid droplet activation measurements reveal that compliance measures can have opposing effects on the CCN activity of exhaust particles. For a non-compliant, high FSC fuel, wet scrubbing leads to an increase in CCN activity but not to significant increases in CCN emission factors. However, switching to low FSC fuels resulted in emissions of highly hydrophobic particles, causing a significant reduction in CCN activity resulting in smaller CCN emission factors by at least one order of magnitude. Our observations are supported by chemical analysis of exhaust particles using scanning transmission X-ray microscopy and near edge X-ray absorption fine structure (STXM/NEXAFS) spectra. Potential implications of effects on ship exhaust particles for cloud and climate interactions due to different compliance measures are discussed.

Pedestrian safety has become an important concern for urban planners. However, some factors affecting that safety remain unexplored, especially those affecting urban infrastructure and macro-level land-use features.

ABSTRACT This study focus on the probahilistic modelling of mechanical properties of prestressing strands based on data collected from tensile tests carried out in Laboratorio Nacional de Engenharia Civil (LNEC), [...]

Noise management in industrial plants can be facilitated by making noise maps and by using computer acoustic models of these plants. For new plant sites, noise specifications can be predefined resulting in tolerable noise levels and cost savings. On the other hand, effective compliance to environmental regulations can be achieved by existing plants.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cor.2008.11.005 Byline: Luis Santos (a)(c), Joao Coutinho-Rodrigues (a)(c), John R. Current (b)(c) Abstract: The capacitated arc routing problem (CARP) is an important and practical problem in the OR literature. In short, the problem is to identify routes to service (e.g., pickup or deliver) demand located along the edges of a network such that the total cost of the routes is minimized. In general, a single route cannot satisfy the entire demand due to capacity constraints on the vehicles. CARP belongs to the set of NP-hard problems; consequently numerous heuristic and metaheuristic solution approaches have been developed to solve it. In this paper an "ellipse rule" based heuristic is proposed for the CARP. This approach is based on the path-scanning heuristic, one of the mostly used greedy-add heuristics for this problem. The innovation consists basically of selecting edges only inside ellipses when the vehicle is near the end of each route. This new approach was implemented and tested on three standard datasets and the solutions are compared against: (i) the original path-scanning heuristic; (ii) two other path-scanning heuristics and (iii) the three best known metaheuristics. The results indicate that the "ellipse rule" approach lead to improvements over the three path-scanning heuristics, reducing the average distance to the lower bound in the test problems by about 44%. Author Affiliation: (a) Department of Civil Engineering, Faculty of Sciences and Technology, Polo II, University of Coimbra, 3030-788 Coimbra, Portugal (b) Department of Management Sciences, The Fisher College of Business, The Ohio State University, 632 Fisher Hall, 2100 Neil Avenue, Columbus. OH 43210-1144, USA (c) INESC-Coimbra, R. Antero Quental, 199, 3000-033 Coimbra, Portugal

ABSTRACTThis study aimed to determine the effect of penalties on attack frequency in high-level judo matches. The study investigated 194 matches (74 women’s and 120 men’s matches) where at least one of the two competitors received the second shido. The penalties affected the attack frequency (F2, 360 = 30.81, p < 0.001). The attack frequency was the highest after the second shido, while it was the lowest before athletes were penalised with the first shido. The increase in nage-wazaattack frequency increased the possibility of winning a match twice (odds ratio (OR) = 2.01), and the increase in the number of ne-wazaattacks per minute increased the possibility of winning a match 3 times (OR = 3.13). Moreover, the increase in the attack frequency especially following the second shidosignificantly increased the possibility of winning compared to previous penalties (OR = 1.13). Thus, the current study concludes that penalties affect match dynamics, and the change in the number and frequency of attacks affects match outcome. It is suggested that athletes should perform positive activities to increase the possibility of winning. Coaches could plan tactical trainings by taking the number of penalties into account.

Valorar cuantitativamente la capacidad de aprendizaje en soporte vital básico (teórica y práctica) de escolares de 8-12 años con un programa de formación adaptado a las escuelas.

Aircrafts damages caused by lightning strikes have been known since the early days of aviation. However, the physical effects on the aircraft structure are still being investigated. This work seeks to evaluate the lightning strike effects in the aluminum alloy 7075-T6. Samples were submitted to lightning strike simulation in laboratory and the damages evaluated through characterization techniques. Ultrasound and profilometry tests have shown material loss to 0.272 mm depth in the damaged region. In addition, it was detected the material accumulation occurrence in the damage vicinity of the region. Below the damage, it was found a region where metallurgical changes were identified. The tensile and microhardness tests results have shown reduction in the percentage elongation and hardness increasing in the material affected by lightning. These results are corroborated by the X-Ray Diffraction (XRD) and Rietveld Method (red line) that indicated an increasing in dislocation density and micro-deformation in the material matrix. Optical microscopy results have shown the presence of microcracks on the normal and cross-section surface of the samples damaged. The Energy Dispersive X-Ray Spectroscopy (EDXS) and Electron Backscattered Diffraction Test (EBSD) found coarse intermetallic phases and precipitates compounds with dimensions greater than 1 μm in length. They were responsible for nucleation of the microcracks that propagate along the material grain boundaries.

The thermoplastic and thermoset laminates reinforced with different fibers generate variations in the laminated composite mechanical behavior. This work aims to analyze thermoplastic and thermoset composites creep behavior with a reduced number of experiments, applying curve-fitting analytical models (Weibull and Findley) and statistical approach (ANOVA, F-test, and SRM) in order to describe creep behavior. Creep tests were carried out using a design of experiments to define parameter levels, aiming to reduce the number of the experiments, keeping reliability relevance. The temperature shows a stronger influence of creep deformation compared with the use of distinct materials. Thermoplastic matrices seem to be more sensitive to deformation, decreasing the reinforcement contribution. On the other hand, the creep resistance of the thermoset matrix conducts a significant contribution of strain behavior for the reinforcement used. The Findley model showed a temperature-dependent response. While, the Weibull-based model exhibits temperature and material-dependence, ensuring a greater sensitivity range of the parameters applied, an essential factor for a more realistic method description.

This work has been developed for a comparative purpose concerning the processing and respective mechanical performance of CFRP composites processed by resin transfer molding (RTM) and compression molding (CM) techniques. Thermal and viscosimetric tests before processing certified the optimal parameter procedure. Both composites were submitted to short-beam shear tests and through microscopy to determine failure mechanisms. CM specimens presented a decrease of 27% in shear strength caused by the presence of macro porosity that induced crack initiation and connection of different delamination plies, causing the speeding up of crack propagation and jump of the interlaminar layer. The low capillary effect and higher viscous force were responsible for macro porosity, inducing heterogeneous impregnation in CM and to the direction reduce in mechanical behavior. On the other hand, more homogeneous impregnation in RTM specimens was responsible for the absence of macro porosity, ensuring higher values of shear strength and lower void volume fraction.

Young–Laplace equation-based algorithms for simulating capillary-driven flow have been used in porous media research for more than two decades. However, the lack of a uniform mathematical description hinders a wider application of these algorithms, as well as impede their comparison. After conducting a detailed review of the most important publications in the area, we propose a unified algorithm. This resulting framework is capable of handling four distinct physical situations: drainage and imbibition with either compressible or incompressible displacement fluid. Additionally, there is no restriction regarding the geometry or the initial fluid distribution used. The proposed algorithm can simulate variable or mixed wettability, even for imbibition, which has not already been described in the literature. Finally, at the end of the manuscript, we provide an efficient open-source C +  + code for the proposed unified algorithm and also many examples of its use.

Supersolid states simultaneously feature properties typically associated with a solid and with a superfluid. Like a solid, they possess crystalline order, manifesting as a periodic modulation of the particle density; but unlike a typical solid, they also have superfluid properties, resulting from coherent particle delocalization across the system. Such states were initially envisioned in the context of bulk solid helium, as a possible answer to the question of whether a solid could have superfluid properties1–5. Although supersolidity has not been observed in solid helium (despite much effort)6, ultracold atomic gases provide an alternative approach, recently enabling the observation and study of supersolids with dipolar atoms7–16. However, unlike the proposed phenomena in helium, these gaseous systems have so far only shown supersolidity along a single direction. Here we demonstrate the extension of supersolid properties into two dimensions by preparing a supersolid quantum gas of dysprosium atoms on both sides of a structural phase transition similar to those occurring in ionic chains17–20, quantum wires21,22and theoretically in chains of individual dipolar particles23,24. This opens the possibility of studying rich excitation properties25–28, including vortex formation29–31, and ground-state phases with varied geometrical structure7,32in a highly flexible and controllable system.

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for more than 5,000 genes, including 2,850 novel null, 2,987 novel conditional-ready and 4,433 novel reporter alleles.

Early product development phases are decisive to determine the environmental impacts of an aircraft during its life cycle. In order to reduce overall environmental impacts, the designers and engineers must be able to assess the consequences of their design choices. In this research, an aircraft eco-design tool was developed to support the decision-making process during the aircraft conceptual design phase. The tool uses a streamlined Life Cycle Assessment (LCA) approach to calculate cradle-to-grave environmental impacts of the aircraft’s life cycle using its design parameters and the ecoinvent database as inputs. The tool performs Uncertainty Analysis via Monte Carlo Simulation (MCS), giving the practitioner insight on the distribution and uncertainty of the results. Input parameters are fitted to Beta-PERT distributions and randomly sampled for each iteration of the MCS. The tool was used to analyze different concepts for a freighter aircraft and a "what-if" scenario, the manufacturing of a composite airframe. The results are coherent with other LCA studies, showing predominance of the operation life cycle stage in all midpoint and endpoint indicators. Furthermore, visualizing the results as distributions rather than single values is of key importance in the decision-making process. The tool is demonstrated to be a versatile eco-design asset for evaluation and comparison of aircraft environmental impacts during the conceptual design phase and may contribute to designing aircraft with minimal environmental impacts.

Cada vez hay más niños escolarizados con enfermedades crónicas, por lo que los profesores deben ser conscientes de esta nueva realidad y de las necesidades especiales que pueden tener estos alumnos. Sin embargo, tenemos muy poca información sobre los conocimientos, actitudes y preocupaciones de los profesores ante una posible situación de riesgo en un escolar con alguna enfermedad crónica, motivo por el que se ha realizado el presente estudio.

This study examined the effects of sacubitril/valsartan on N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response.

The objective of the InMEDIATE study was to evaluate the change in intensity of traumatic pain over the first 20 min in adult patients treated with methoxyflurane versus standard analgesic treatment in Spain. This the first randomized, active-controlled, multicenter trial of methoxyflurane in the emergency setting in Europe.

The fall armyworm Spodoptera frugiperdaJ. E. Smith (Lepidoptera: Noctuidae) is one of the most damaging pests of maize production in tropical areas. Leaf damage caused by its feeding depends greatly on chemical and physical leaf traits. In the present study, the degree of leaf damage by S. frugiperdain three maize landraces (Chimbo, Elotillo and San Pableño) and three commercial cultivars (Vs-536, Dekalb 390 and Impacto) was evaluated in a naturally infested field experiment. Morphological leaf traits were measured and associated with the degree of leaf damage at three sample dates 15, 30 and 45 days after emergence when developmental stages of plants were V5, V8 and V12, respectively. Overall, maize landraces showed lower leaf damage than commercial cultivars. Particularly, the landraces Chimbo and Elotillo had the lowest leaf damage, calculated by the area under the severity progress curve. Morphological leaf traits varied significantly (p< 0.05) among maize genotypes, but their patterns were not consistent in all sample dates. Pearson correlation analysis showed that leaf damage was negatively correlated with leaf toughness (rs= − 0.45, p< 0.001) at the developmental stage V12 and positively correlated with trichome density (rs= 0.44, p< 0.001) at developmental stage V8.

Atypical enteropathogenic (serotypes O4:H16, O8:H25, O68:H2, O105:H7, and OR:H25) and Shigatoxigenic (ONT:H46) Escherichia coliwere isolated from samples of ground beef and poultry breast purchased in Botucatu, Brazil. Phenotypic and molecular characterization indicated the potential of these isolates to adhere to host epithelial cells and cause damage.

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio–nano papers, the community responds.

This work aims to provide reliable heat capacities for ethylene glycol and selected oligo(ethylene glycol)s (diethylene glycol, triethylene glycol, tetraethylene glycol, pentaethylene glycol, and hexaethylene glycol), which are industrially important chemicals produced on a large scale. Besides, new data extend the database needed for a better understanding of complex behavior of compounds capable of forming hydrogen bonds. Isobaric heat capacities of ethylene glycols were measured with a Tian–Calvet-type calorimeter in the temperature range of 260 to 358 K. The phase behavior was investigated with a heat-flux differential scanning calorimeter. A simple additive estimation method for liquid heat capacity of oligo(ethylene glycol)s was developed and tested through comparison with newly measured liquid heat capacities of polyethylene glycols 400 and 600.

Some biomaterial scaffolds can positively interfere with tissue regeneration and are being developed to successfully repair the tissue function. The possibility of using epithelial cells combined with biomaterials appears to be a new option as therapeutic application. This combination emerges as a possibility for patients with Mayer–Rokitansky–Kuster–Hauser syndrome which requires vaginal repair and can be performed with tissue-engineered solution containing cells and biomaterials. It is expected that tissue-engineered solution containing cells and biomaterials would promote tissue repair in a more efficient, modern, and safe way. This study tested the efficiency of tissue-engineered solution containing human malignant melanoma cell line (HMV-II) and different biomaterials, including Cellprene®, Membracel®, and poly lactic-co-glycolic acid/epoxidized polyisoprene. The cells adhered better on poly lactic-co-glycolic acid/epoxidized polyisoprene, and it was found that tissue-engineered solution may also contain mesenchymal stem cells cultivated on poly lactic-co-glycolic acid/epoxidized polyisoprene. Histological, immunofluorescence, and scanning electron microscopy analyses were performed. These initial in vitro results suggest that tissue-engineered solution containing cells and poly lactic-co-glycolic acid/epoxidized polyisoprene is a potential for tissue reconstruction.

The present work was carried out to gain insight into the chemical defense of maize against phytophagous insects. Leaves of sixteen landrace populations were extracted with ethanol. Deterrent activity of extracts was evaluated on Spodoptera littoralisand Rhopalosiphum padiunder laboratory conditions. Most of the ethanolic extracts negatively affected settling of R. padi, but only the extract Xn-69 affected feeding of S. littoralis. Active extracts were combined based on their TLC pattern. Bioassay-guided fractionation using biomass gain (ΔB) and food consumption (ΔI) of S. littoralisshowed that the active fraction contained three phytosterols: sitosterol, stigmasterol and campesterol as the major constituents. These compounds might be responsible for the negative effects of extracts on biomass gain through the inhibition of food consumption of S. littoralislarvae. These phytosterols might provide in maize nonpreference resistance mechanism against insect pests.

Carbonization is the process in which the wood is heated in a closed environment with controlled amount of air, producing charcoal as a solid product of the process and secreting water vapor, organic liquids and non-condensable gases. The burning of these gases generates energy that can be used for the drying wood to be carbonized or for the generation of electric power in the carbonization plant itself. The present study had the purpose to conduct an energetic survey of the fractions from the charcoal production process, aiming to subsidize and to encourage the technological development of equipment for the energetic use of the carbonization gases. The results showed that the energy contained in non-condensed gases and in pyroligneous liquid corresponds to a total of 31% of the wood energy used. Two scenarios of synchronism of four kilns were studied in pyrolysis and a maximum and constant potential of 9.7 MW was obtained in scenario 2. The burner was efficient in the emission control, the CO and CH4 reductions were in the range of 97-99% and 68-91% respectively. Thus, the burner is a promising technology for the reduction of greenhouse gases and for the generation of thermal energy from carbonization co-products.

The TEMPO oxoammonium cation has been proven to be both an efficient oxidizing reagent and an electrophilic substrate frequently found in organic reactions. Here, we report that this versatile chemical reagent can also be used as an efficient promoter for C- and N-glycosylation reactions through a Ferrier rearrangement with moderate to high yields. This unprecedented reactivity is explained in terms of a Lewis acid activation of glycal by TEMPO+forming a type of glycal–TEMPO+mesomeric structure, which occurs through an extended vinylogous hyperconjugation toward the π*(O═N+)orbital [LP(O1)→ π*(C1═C2), π*(C1═C2)→ σ*(C3–O3), and LP(O6)→ π*(O═N+)]. This enables the formation of the respective Ferrier glycosyl cation, which is trapped by various nucleophiles. The extended hyperconjugation (or double hyperconjugation) toward the π*(O═N+)orbital, which confers the Lewis acid character of the TEMPO cation, was supported by natural bond orbital analysis at the M06-2X/6-311+G** level of theory.

Single monoclonal antibodies (mAbs) can be expressed in vivothrough gene delivery of their mRNA formulated with lipid nanoparticles (LNPs). However, delivery of a mAb combination could be challenging due to the risk of heavy and light variable chain mispairing. We evaluated the pharmacokinetics of a three mAb combination against Staphylococcus aureusfirst in single chain variable fragment scFv-Fc and then in immunoglobulin G 1 (IgG1) format in mice. Intravenous delivery of each mRNA/LNP or the trio (1 mg/kg each) induced functional antibody expression after 24 h (10–100 μg/mL) with 64%–78% cognate-chain paired IgG expression after 3 days, and an absence of non-cognate chain pairing for scFv-Fc. We did not observe reduced neutralizing activity for each mAb compared with the level of expression of chain-paired mAbs. Delivery of the trio mRNA protected mice in an S. aureus-induced dermonecrosis model. Intravenous administration of the three mRNA in non-human primates achieved peak serum IgG levels ranging between 2.9 and 13.7 μg/mL with a half-life of 11.8–15.4 days. These results suggest nucleic acid delivery of mAb combinations holds promise and may be a viable option to streamline the development of therapeutic antibodies.

Supplemental Digital Content is available in the text.

Avian pathogenic Escherichia coli(APEC) isolates from apparently healthy free range helmeted guineafowl were characterized. Most of them had a high frequency of virulence associated genes, multi drug resistance and high pathogenicity. We demonstrated that helmeted guineafowl have potential to transmit antibiotic resistant APEC to other species including humans.

Los profesores pueden tener un papel esencial en la formación en reanimación cardiopulmonar básica (RCP-B) de los escolares. Sin embargo, se dispone de pocos datos acerca de la capacidad de aprendizaje de la RCP-B por estos profesionales.

AbstractShiga toxin–producing Escherichia coli(STEC) is a group of emerging pathogens that can cause human diseases, including hemolytic uremic syndrome (HUS) and hemorrhagic colitis (HC). Monitoring slaughtering stages and checking contamination points are crucial for the production of safe food. In this context, the aim of this study was to verify contamination by STEC strains, to determine the contamination points and evaluate the resistance profile to 12 antimicrobials used in both veterinary and human medicine. A total of 80 samples were obtained from eight collection points (pen floor, rectum, hide, carcass swabs and esophagus, diaphragm, masseter, and retail beef tissue samples). The isolates were collected by dilution plating on MacConkey agar with sorbitol, cefixime, and tellurite and analyzed by multiplex polymerase chain reaction for virulence genes. Serotyping of non-O157 was performed, and testing for 12 antibiotics by disk diffusion was carried out. A total of 18 STEC strains were isolated, presenting different virulence profiles. Contamination by STEC was observed in the rectum (5/18), carcass surface (5/18), hide (3/18), diaphragm (2/18), retail beef (2/18), and masseter muscle (1/18). Pen floor swabs and esophagus tissues showed no STEC contamination. Moreover, three strains were identified as O26 and three as O113:H21 strains, which have been linked to HUS and HC outbreak cases in Brazil. All STEC isolates were susceptible to all evaluated antimicrobials, except streptomycin. The presence of STEC strains is a direct risk to the consumer, especially when isolated from retail beef, and contamination can occur during different slaughter stages. However, antimicrobial resistance profiles did not identify multidrug-resistant strains, limiting potential antimicrobial resistance transmission to other pathogens.

Additive manufacturing (AM) processes, such as Selective Laser Sintering (SLS), have enabled the fabrication of geometrically complicated designs. However, undesired distortions due to thermally-induced residual stresses may lead to loss of tolerance or failure of the part. One potential failure mode is buckling, particularly when realizing high aspect ratio features, like for infill, to minimize weight. In this paper, we address distortions and part failures due to buckling by using a finite element model to predict residual stress distributions and sintering induced distortions. Initially, we conduct a transient thermal simulation to determine the Heat Affected Zone (HAZ), which is then used in the thermomechanical simulation. In addition, we imposed perturbations on the mechanical mesh based on the buckling eigenmodes. Finally, a thermomechanical viscoplastic analysis was performed layer-by-layer to obtain the final residual stress state and subsequent distortions that occur after cooling down to ambient temperature. A model was used to describe the evolution of porosity due to laser sintering, and then a model of the effects of porosity on the viscoplastic constitutive properties of the sintered material was used in the thermomechanical simulation. Modeling results are compared against experimental specimens using a Durelli (aka, Theta) specimen geometry fabricated with a 3D Systems ProX 200 Selective Laser Sintering (SLS) machine. The geometry of the specimen represents an internal feature with a high aspect ratio that is prone to buckling, and the dimensions were modified based on the simulation results to confirm the ability of the modeling approach to provide accurate mitigation of buckling-induced distortions.

•Grape bark and arrowroot starch were used in panettone production.•Panettones with good nutritional, technological, and functional qualities were developed.•Bioactive compound powder can be a green alternative to synthetic colorants.•Panettones were developed with the feasibility of being incorporated into the food industry.