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Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17‐82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex. cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts. In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.

[EN] Passive pre-chamber ignition concept has been proven to be an excellent strategy to increase the ignition energy and enhance the combustion velocity even when spark-ignition engines are operating in diluted conditions. Other benefits of this system are the increased combustion stability and combustion efficiency, reducing hydrocarbons and carbon monoxide emissions. However, these advantages are limited at some operation conditions such as low engine load or diluted conditions since both the energy available in the pre-chamber and the scavenge of combustion products are compromised. In this framework, numerical studies using two different computational tools, based on one-dimensional modeling, are utilized to gain knowledge about the governing parameters and to improve the design of a pre-chamber when the engine operates at these restrictive conditions. In particular, the impact of the pre-chamber volume, the total cross sectional area of the holes and tangential angle of the nozzles have been numerically evaluated. Different pre-chamber designs were proposed and experimentally tested in a single-cylinder, high compression ratio turbocharged spark-ignition engine fueled with compressed natural gas and operating on Miller cycle. Results give valuable insight into the key aspects of the internal geometry and some relevant design paths to follow for a suitable pre-chamber definition.

[EN] In view of the increasing restrictions for CO2 mitigation, the evaluation of alternative fuels to ensure sustainability of transportation is becoming increasingly important. Since some of these alternatives can be refined from renewable sources, they are interesting from the perspective of both: the use of the current power-plants and the CO2 emission. In this sense, natural gas arises as an interesting propellant to substitute fossil fuels. Therefore, combining this fuel with specific combustion strategies can help to decrease the environmental footprint of transportation in the broadest sense. In this paper, an evaluation of the possible advantages of this combination has been conducted. The investigation has been carried out in a port fueled turbocharged spark-ignition engine, using compressed natural gas (CNG) and a passive pre-chamber ignition system. The effects of the CNG fuel properties on combustion have been analyzed and the global impact of using CNG for transportation has been appraised by means of the life cycle assessment. Results show that combustion of CNG refined by different renewable sources not only reduces the global CO2 emission but also can contribute to remove the existent pollution. In addition, they show an increase of the engine thermal efficiency when combining CNG and the pre-chamber ignition concept.

[EN] Hydrogen is one of the most promising alternative fuels for the transportation industry. The use of hydrogen to enable lean burn in internal combustion engines is an attractive solution for reducing CO2 emissions from two points of views: the substitution of carbon-based fuels and the increased thermal efficiency due to lean operation. Combining this strategy with the passive pre-chamber ignition system with gasoline/hydrogen blends is even more interesting. The main limitations of the passive pre-chamber concept in a high compression ratio spark-ignition engine were shown through engine experiments. A numerical study was then performed to evaluate the chance of extending the dilution limit by using hydrogen along with this technology. Results show how the use of hydrogen provides considerable benefits in the main chamber combustion process by enhancing the thermo-chemical properties of the mixture, increasing the flame speed, and improving the flame structure. Using an adequate gasoline-hydrogen blend proved to enable optimum burning rates at lean conditions, leading to a relevant thermal efficiency gain.

[EN] In this paper, a computational study was performed using a combination of several numerical tools to better understand the limiting aspects of combustion in a passive pre-chamber ignition system when operating at lean conditions. A specific methodology was developed to analyze in detail the scavenging and combustion processes of this ignition concept. Results show how the scavenging of passive pre-chambers is primarily dependent on the force that the piston makes on the gas during the compression stroke, being independent of the pre-chamber geometry as along as the ratio between the total cross sectional area of the pre-chamber holes and the prechamber volume is kept within a suitable range. Moreover, a successful lean combustion, with an air-to-fuel ratio around 2, cannot be achieved as the burning rates inside the pre-chamber significantly decrease due to the low laminar flame speeds, that results in low quality jets. Further results show that increasing the flow temperature can help to recover competitive combustion rates when knocking combustion is not a limiting factor. The contribution of the heat losses through the pre-chamber walls to the overall energy balance of the pre-chamber has been estimated, showing that their impact is negligible (< 5%). Alternatives for increasing the laminar flame speed were proposed in order to improve combustion inside the pre-chamber. Although the pre-chamber combustion profile was successfully improved, none of the proposed solutions were able to completely burn the main chamber charge with the current pre-chamber design.

[EN] The pre-chamber ignition concept is an attractive strategy to enable the operation of spark-ignition engines in lean or diluted conditions keeping a suitable combustion process. According to the results the benefits in lean conditions include the combustion process shortening, the improvement of combustion stability and the increase of combustion efficiency by lowering carbon monoxide and hydrocarbons emissions. Thus, the pre-chamber ignition concept, especially in its passive version, arises as a promising alternative for future spark-ignition engines for passenger car applications. In this framework, an experimental investigation has been carried out to evaluate the potential of passive pre-chamber ignition concept in a high compression ratio, turbocharged, port fueled spark-ignition engine, using 95 Research Octane Number gasoline. As a first step, a 1D Wave Action Model was generated to design the pre-chamber geometry taking the fuel available at the start of pre-chamber combustion and the pressure difference between the main chamber and pre-chamber as key parameters. In a second step, these pre-chamber designs were experimentally validated at high load/speed conditions (4500¿rpm, 12.5¿bar Indicated Mean Effective Pressure) and compared with the conventional spark-ignition concept. Experimental results show how the passive pre-chamber concept increases efficiency with good combustion stability and high combustion efficiency in stoichiometric conditions. Nevertheless, maximum lambda attainable with the passive system is similar than that of the conventional spark and much lower compared to the maximum levels reported for the active system.

BACKGROUND: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. METHODS: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. RESULTS: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. CONCLUSION: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Discovering the genetic changes underlying species differences is a central goal in evolutionary genetics. However, hybrid crosses between species in mammals often suffer from hybrid sterility, greatly complicating genetic mapping of trait variation across species. Here, we describe a simple, robust, and transgene-free technique to generate “in vitro crosses” in hybrid mouse embryonic stem (ES) cells by inducing random mitotic cross-overs with the drug ML216, which inhibits the DNA helicase Bloom syndrome (BLM). Starting with an interspecific F1 hybrid ES cell line between the Mus musculus laboratory mouse and Mus spretus (∼1.5 million years of divergence), we mapped the genetic basis of drug resistance to the antimetabolite tioguanine to a single region containing hypoxanthine–guanine phosphoribosyltransferase (Hprt) in as few as 21 d through “flow mapping” by coupling in vitro crosses with fluorescence-activated cell sorting (FACS). We also show how our platform can enable direct study of developmental variation by rederiving embryos with contribution from the recombinant ES cell lines. We demonstrate how in vitro crosses can overcome major bottlenecks in mouse complex trait genetics and address fundamental questions in evolutionary biology that are otherwise intractable through traditional breeding due to high cost, small litter sizes, and/or hybrid sterility. In doing so, we describe an experimental platform toward studying evolutionary systems biology in mouse and potentially in human and other mammals, including cross-species hybrids.

Peanut allergy, the most common cause of fatal-food-related anaphylaxis, is a lifelong disorder and the only existing therapy is avoidance of allergen-containing food. Detection of Ara h 1, the most important peanut allergen, is commonly performed by immunoassay techniques relying on the use of expensive and relatively unstable antibodies. Aptamers can overcome these drawbacks and offer a great potential for the development of reliable biosensors. Therefore, we will present a novel aptamer-based sensor for the label-free detection of Ara h 1. Amino (NH2)-terminated Ara h 1 aptamers were covalently attached to carboxylated gold surfaces employing carbodiimide chemistry. This functionalization procedure was followed in real time by electrochemical impedance spectroscopy and quartz crystal microbalance with dissipation monitoring. Subsequently, the functionalized surfaces were exposed to Ara h 1 solutions in TGK buffer. By combining the two techniques, we can measure in a wide concentration regime varying from the low nanomolar range (1-15 nM) via electrochemical impedance spectroscopy to the higher concentrations (25-250 nM) by microgravimetric detection. In summary, a fast, low-cost and sensitive sensor platform for Ara h 1 detection has been developed, which can be operated as a ‘stand-alone device’, making it well suited for applications such as the screening of trace allergens.