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As the need to minimize environmental impacts continues to rise, it is essential to incorporate, advance, and adopt renewable energy sources and materials to attain climate neutrality in industrial operations. It is established that economic growth is built upon infrastructure, where the cement industry plays a crucial role. However, it is also known that this industry is actively looking for ways to transition toward low-carbon practices to encourage sustainable and environmentally conscious practices. To this end, the use of refuse-derived fuels to substitute fossil fuels is very appealing, as these have the potential to lower clinker production costs and CO2 emissions. Bearing this in mind, the primary objective of this work is to gain insights into the combustion behavior in an industrial rotary kiln by studying real-life scenarios and to assess the potential of substituting alternative fuels for fossil fuels to reduce CO2 emissions. A 3D CFD turbulent combustion model was formulated in Ansys® considering a Pillard NOVAFLAM® burner, where refuse-derived and petcoke fuels were used, and different secondary air mass flows were considered. From the obtained results, it was possible to conclude that the outcome of the combustion process is greatly influenced by the fuel-to-air ratio. Increasing the secondary air mass flow promotes the occurrence of a complete and efficient combustion process, leading to enhanced fuel conversion and the decreased formation of pollutants such as CO, soot, and unburned hydrocarbons. An increase in combustion efficiency from 93% to 96% was observed, coupled with a slight decrease in the pollutant mass fraction in the flue gas.

Material optimization was one of the challenges for achieving cost-competitive solutions when concrete was introduced in construction, leading to new structural shapes for both civil works and buildings. As concrete construction became dominant, saving material was given less significance, and the selection of the structural typology was mostly influenced by construction or architectural considerations. Simple and non-time-consuming methods for building thus arose as the dominant criteria for design, and this led to the construction of less efficient structures. Currently, the awareness of the environmental footprint in concrete construction has brought the focus again to the topic of structural efficiency and material optimization. In addition, knowledge of material technology is pushing the use of cements and binders with lower environmental impact. Within this framework, Fiber-Reinforced Concrete (FRC) has been identified as a promising evolution of ordinary concrete construction. In this paper, a discussion is presented on the structural properties required for efficient design, focusing on the toughness and deformation capacity of the material. By means of several examples, the benefits and potential application of limit analysis to design at the Ultimate Limit State with FRC are shown. On this basis, the environmental impact of a tailored mix design and structural typology is investigated for the case of slabs in buildings, showing the significant impact that might be expected (potentially reducing CO2-eq emissions to half or even less in slabs when compared to ordinary solutions).

The current energy and climate crisis calls for immediate action in replacing fossil fuels with those derived from renewable sources. The Energreen process performs the direct liquefaction of biomass to produce a liquid biofuel for the cement industry and an aqueous solution of added-value compounds for further processing. The present work details the development of an Aspen Plus® model to simulate this biomass liquefaction process. The proposed model describes the Energreen liquefaction process using simplified reaction kinetics and thermodynamic models. The model was validated using data from a real liquefaction pilot plant with a deviation of 6.4%. The simulation, conducted with several biomass samples of variable compositions, showed that the process is robust enough to deal with different compositions and, due to the substitution of the fossil fuels presently used in the cement plant, it will allow savings of up to USD 102,000 per year to be achieved. Several analyses of the sensitivity of the results to the process variables were performed and it was possible to identify the reactor temperature and the reaction activation energy as the most impactful parameters on the process output. Overall, the results allow us to conclude that the proposed model is a solid framework for the optimization of industrial liquefaction processes.

Gema Requena,1 Victoria Banks,2 Alexandrosz Czira,1 Robert Wood,2 Theo Tritton,2 Rosie Wild,2 Chris Compton,1 Maria Duarte,1 Afisi S Ismaila3,4 1Value Evidence and Outcomes, Epidemiology, GSK, R&D Global Medical, Brentford, Middlesex, UK; 2Real-world Evidence, Adelphi Real World, Bollington, Cheshire, UK; 3Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Gema Requena, Epidemiology, Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, UK, Tel +44 20 80476893, Email gema.x.requena@gsk.comPurpose: Treatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-inhaler dual therapies remain unclear. We aimed to describe characteristics, prescribed treatments, healthcare resource use (HCRU) and costs of patients with COPD who initiated single-inhaler long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy in primary care in England.Patients and Methods: Retrospective study using linked data from Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. Patients with COPD with ≥ 1 single-inhaler LAMA/LABA prescription between June 2015 and December 2018 (index) were included. Demographic and clinical characteristics, prescribed treatments, HCRU and costs were evaluated in the 12 months pre-index. Data are presented for patients not receiving concomitant inhaled corticosteroids at index (non-triple users).Results: Of 10,991 patients initiating LAMA/LABA, 9888 were non-triple users, of whom 21.3% (n=2109) received aclidinium bromide/formoterol, 18.1% (n=1785) received indacaterol/glycopyrronium, 12.0% (n=1189) received tiotropium bromide/olodaterol and 48.6% (n=4805) received umeclidinium/vilanterol. Demographic and clinical characteristics were similar across indexed therapies. LAMA monotherapy was the most frequently prescribed respiratory therapy at 12 (18.4– 25.8% of patients) and 3 months (23.9– 33.7% of patients) pre-index across indexed therapies; 42.5– 59.0% of patients were prescribed no respiratory therapy at these time points. COPD-related HCRU during the 12 months pre-index was similar across indexed therapies (general practitioner consultations: 62.0– 68.6% patients; inpatient stays: 19.3– 26.1% patients). Pre-index COPD-related costs were similar across indexed therapies, with inpatient stays representing the highest contribution. Mean total direct annual COPD-related costs ranged from £ 805–£ 1187.Conclusion: Characteristics of patients newly initiating single-inhaler LAMA/LABA dual therapy were highly consistent across indexed therapies. As half of non-triple users were not receiving respiratory therapy one year prior to LAMA/LABA initiation, there may be an opportunity for early optimization of treatment to relieve clinical burden versus current prescribing patterns in primary care in England.Keywords: COPD, initial maintenance therapy, primary care setting, patient characteristics, single-inhaler LAMA/LABA dual therapy, treatment patterns

The performance of FFC-NMR power supplies is evaluated not only considering the technique requirements but also comparing efficiencies and power consumption. Since the characteristics of FFC-NMR power supplies depend on the power circuit topology and on the control solutions, the control design is a core aspect for the development of new FFC systems. A new hybrid solution is described that allows controlling the power of semiconductors by switches (ON/OFF mode) or as a linear device. The approach avoids over-design of the power supply and makes it possible to implement new low power solutions constituting a novel design by joining a continuous match between the ON/OFF mode and the linear control of the power semiconductor devices.

Exercise induces structural and functional adaptations in skeletal muscle that involve transcriptomic remodeling, including of miRNA expression. Here the authors examine the expression of miRNAs in human muscle following exercise training and investigate the functions of miR-19b-3p on glucose metabolism in cells and mouse muscle.

Abstract Background Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential. Results Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca2+) and Ca2+-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca2+-releasing channels inositol 1,4,5-trisphosphate receptors (IP3Rs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein. Conclusion We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.

Abstract Background Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia. Methods We analyzed gene expression data from muscle of mice or human patients with diverse muscle pathologies and identified LMCD1 as a gene strongly associated with skeletal muscle function. We transiently expressed or silenced LMCD1 in mouse gastrocnemius muscle or in mouse primary muscle cells and determined muscle/cell size, targeted gene expression, kinase activity with kinase arrays, protein immunoblotting, and protein synthesis levels. To evaluate force, calcium handling, and fatigue, we transduced the flexor digitorum brevis muscle with a LMCD1-expressing adenovirus and measured specific force and sarcoplasmic reticulum Ca2+ release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling. Results Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease. Conclusions Our gain- and loss-of-function studies show that LMCD1 controls protein synthesis, muscle fiber size, specific force, Ca2+ handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.

PGC-1α is activated by exercise and promotes resistance to fatigue in muscles. Here, the authors show that PGC-1α activates the malate-aspartate shuttle, and allows muscle to utilise kynurenine, leading to more efficient glucose oxidation and mitochondrial respiration.

The electrolysis of black liquor (BL) has emerged as a new form to valorize this byproduct from the pulp and paper industry. BL electrolysis produces a green fuel, hydrogen, and lignin, a high added-value compound. In opposition to water electrolysis, a symmetric process with two different gases produced at the electrodes, hydrogen and oxygen, BL electrolysis is seen as an asymmetric process, as hydrogen is the only gas generated (at the cathode), while solid lignin is electrodeposited at the anode. The present work intended to develop a model in Aspen Plus® to simulate BL electrolysis and consequently evaluate the performance of the BL electrolyzer. Aspen Plus® does not include a package for electrolyzers, so it was necessary to use the Aspen Custom Modeler (ACM) tool. The model developed in ACM is valid for the following conditions: nickel electrodes with 2 cm interelectrode distance, cell voltage between 1.5 V and 2.0 V, and temperatures between 25 and 35 °C for batch operation and 25 and 65 °C for continuous operation. Sensitivity analysis demonstrated that the optimum working temperature for batch operation is 35 °C, whereas it is 45 °C for continuous operation. An economic analysis was carried out, calculating the real gross profit (RGP) for the process and the electricity cost. A 2 kW electrolyzer with 80 cells and an active area of 0.3 m2 was simulated. For the electrolyzer in batch operation, RGP values of 1056 €/year and 1867 €/year for the worst and the best scenario were obtained, respectively, and the electricity cost was 1431 €/year. For continuous operation, the RGP values were 2064 €/year and 3648 €/year for the worst and best scenario, respectively, and 2967 €/year for the electricity costs.

The kynurenine pathway of tryptophan (TRP) degradation (KP) generates metabolites with effects on metabolism, immunity, and mental health. Endurance exercise training can change KP metabolites by changing the levels of KP enzymes in skeletal muscle. This leads to a metabolite pattern that favors energy expenditure and an anti-inflammatory immune cell profile and reduces neurotoxic metabolites. Here, we aimed to understand if TRP supplementation in untrained vs. trained subjects affects KP metabolite levels and biological effects. Our data show that chronic TRP supplementation in mice increases all KP metabolites in circulation, and that exercise reduces the neurotoxic branch of the pathway. However, in addition to increasing wheel running, we did not observe other effects of TRP supplementation on training adaptations, energy metabolism or behavior in mice. A similar increase in KP metabolites was seen in trained vs. untrained human volunteers that took a TRP drink while performing a bout of aerobic exercise. With this acute TRP administration, TRP and KYN were higher in the trained vs. the untrained group. Considering the many biological effects of the KP, which can lead to beneficial or deleterious effects to health, our data encourage future studies of the crosstalk between TRP supplementation and physical exercise.

This paper reports an experimental comparison between the use of the refrigerants R409A and R437A in a heat pump unit designed and developed to work with R12. Although the use of both refrigerants in new equipments were abolished in EU and US according the new F-Gas Regulation of EU and SNAP, they still being used as options for R12 in old equipments, especially in developing countries. Both refrigerants were studied for the same test conditions, according to two groups of tests: group A (variation of the heat source temperature) and group B (variation of refrigerant flow rate). The results obtained showed that the R437A presents a higher discharge pressure and a lower discharge temperature. The heating and cooling capacities of both refrigerants were similar, as well as the exergetic efficiency. For the group A of tests the COP of both refrigerants was similar and for the group B of tests the R409A presented an average COP 15% higher. According to the results obtained it is recommended the use of R409A in old equipments (as transition refrigerant) until the acquisition of equipments operating with refrigerants with low-GWP becomes technically and economic feasible.

The present work determines the chemical and thermal characteristics as well as the phytochemical and antioxidant potential of the polar extractives of the Picea abies bark from an industrial mill, their wood and bark components and also different bark fractions obtained by mechanical fractionation (fine B1, Φ

The aim of this work is to develop a measurement methodology to perform a vibration analysis of a vehicle. It proposes new setups in the suspension systems, including springs, shock absorbers, and rubber mountings of the engine system, to improve the passengers’ comfort levels. The influence of each of these modifications in the vibration levels at specific points is analyzed. The importance of human interaction analysis is clear as, in the past, it was frequently left aside. This is because only the vehicle dynamic behavior is generally emphasized in the vehicles designed. Therefore, this work stresses that concerns about human vibration levels result in vehicles with good performance also in comfort levels, focusing on the users’ well-being. A combination of different sets of rubber mountings, springs, and shock absorbers are tested. The changes proposed in this paper are analyzed in sequence and, based on the results, the best combination is proposed.

The use of functional excipients such as ionic liquids (ILs) and the encapsulation of drugs into nanocarriers are useful strategies to overcome poor drug solubility. The aim of this work was to evaluate the potential of IL-polymer nanoparticle hybrid systems as tools to deliver poorly soluble drugs. These systems were obtained using a methodology previously developed by our group and improved herein to produce IL-polymer nanoparticle hybrid systems. Two different choline-based ILs and poly (lactic-co-glycolic acid) (PLGA) 50:50 or PLGA 75:25 were used to load rutin into the delivery system. The resulting rutin-loaded IL-polymer nanoparticle hybrid systems presented a diameter of 250−300 nm, with a low polydispersity index and a zeta potential of about −40 mV. The drug association efficiency ranged from 51% to 76%, which represents a good achievement considering the poor solubility of rutin. No significant particle aggregation was obtained upon freeze-drying. The presence of the IL in the nanosystem does not affect its sustained release properties, achieving about 85% of rutin released after 72 h. The cytotoxicity studies showed that the delivery system was not toxic to HaCat cells. Our findings may open a new paradigm on the therapy improvement of diseases treated with poorly soluble drugs.

This paper describes an innovative solution for the power supply of a fast field cycling (FFC) nuclear magnetic resonance (NMR) spectrometer considering its low power consumption, portability and low cost. In FFC cores, the magnetic flux density must be controlled in order to perform magnetic flux density cycles with short transients, while maintaining the magnetic flux density levels with high accuracy and homogeneity. Typical solutions in the FFC NMR literature use current control to get the required magnetic flux density cycles, which correspond to an indirect magnetic flux density control. The main feature of this new relaxometer is the direct control of the magnetic flux density instead of the magnet current, in contrast with other equipment available in the market. This feature is a great progress because it improves the performance. With this solution it is possible to compensate magnetic field disturbances and parasitic magnetic fields guaranteeing, among other possibilities, a field control below the earth magnetic field. Experimental results validating the developed solution and illustrating the real operation of this type of equipment are shown.

A simple method based on sucrose density gradient centrifugation is proposed here for the fractionation of colloidal silver nanotriangles. This method afforded particle fractions with surface plasmon resonances, spanning from red to infrared spectral ranges that could be used to tune optical properties for plasmonic applications. This feature was exemplified by selecting silver nanotriangle samples with spectral overlap with Atto-655 dye’s absorption and emission in order to assemble dye-particle plasmophores. The emission brightness of an individual plasmophore, as characterized by fluorescence correlation spectroscopy, is at least 1000-fold more intense than that of a single Atto-655 dye label, which renders them as promising platforms for the development of fluorescence-based nanosensors.

The search for sustainable catalytic oxidation processes remains a challenge. One process of utmost industrial and economic importance is the selective oxidation of cyclohexane, in the route of nylon-6,6 production, which requires urgent improvement. Herein, Au nanotriangles (Au NTs) were prepared following a three-step (seed preparation, growth and shaping) procedure and applied, for the first time, as catalysts for the selective oxidation of neat cyclohexane to ketone and alcohol (KA) oil (cyclohexanol and cyclohexanone mixture). The Au NTs successfully yield KA oil (up to 14%) under mild conditions (50 °C), using an alternative energy source (microwave irradiation) as reaction promotor.

Large eddy simulation of the wind surface layer above and within vegetation was conducted in the presence of an idealised forest fire by using an equivalent volumetric heat source. Firebrand’s particles are represented as spherical particles with a wide range of sizes, which were located into the combustion volume in a random fashion and are convected in the ascending plume as Lagrangian points. The thermally thin particles undergo drag relative to the flow and moisture loss as they are dried and pyrolysis, char-combustion, and mass loss as they burn. The particle momentum, heat and mass transfer, and combustion governing equations were computed along particle trajectories in the unsteady 3D wind field until their deposition on the ground. The spotting distances are compared with the maximum spotting distance obtained with Albini model for several idealised line grass or torching trees fires scenarios. The prediction of the particle maximum spotting distance for a 2000 kW/m short grass fire compared satisfactorily with results from Albini model and underpredicted by 40% the results for a high intensity 50000 kW/m fire. For the cases of single and four torching trees the model predicts the maximum distances consistently but for slightly different particle diameter.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p

BACKGROUND: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and involved in the (dys)regulation of cell survival, proliferation, differentiation and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon cancer. In the present study, we evaluated the role of miR-143 overexpression on the growth of human colon carcinoma cells xenografted in nude mice (immunodeficient mouse strain: N: NIH(s) II-nu/nu). METHODOLOGY/PRINCIPAL FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143) and control (Empty) cells were subcutaneously injected into the flanks of nude mice, and tumor growth was evaluated over time. Tumors arose ∼ 14 days after tumor cell implantation, and the experiment was ended at 40 days after implantation. miR-143 was confirmed to be significantly overexpressed in Over-143 versus Empty xenografts, by TaqMan® Real-time PCR (p