Abnormal carnitine distribution in the muscles of patients with idiopathic inflammatory myopathy

OBJECTIVE: To analyze the levels of free carnitine and carnitine esters in the muscles of patients with inflammatory myopathies. METHODS: Six men and 7 women with inflammatory myopathy and 25 age-matched healthy controls were studied. Free carnitine and carnitine esters in muscle homogenates were measured by a radiochemical procedure. Muscle histochemical staining and measurement of respiratory chain enzyme activity were also performed. RESULTS: Eleven patients had muscle carnitine insufficiency. Five of them had subsarcolemmal oxidative accumulations, 5 had lipid droplets, and 4 had defects of the respiratory chain enzyme complexes. CONCLUSION: Abnormal distribution of muscle carnitine is present in patients with inflammatory myopathies and could impair muscle function. Coexistent mitochondrial dysfunction may contribute to carnitine insufficiency.     

Losses of volatile compounds during fermentation

The ability of fermentative CO₂ to blow off the volatile compounds that are synthesized during fermentation has been studied. Model solutions simulating a fermenting must were purged at different CO₂ flow rates and temperatures, and the amount of volatile compounds blown off by the stream of CO₂ was recorded by high-resolution gas chromatography. Data showed that under normal fermenting conditions, fatty acid ethyl esters and some fusel alcohol acetates are blown off the solution at a high rate. The maximum loss rate was observed for ethyl decanoate. The purging speed is doubled when temperature increases from 17 °C to 27 °C. Losses can be interpreted by a linear model and are a function of the compound and the flow rate of CO₂. These models allow us to reconstruct the volatile synthesis vs time functions through graphic calculus and to estimate the proportion of volatile material retained, hydrolysed and purged. Synthesis takes place during the tumultuous period of fermentation together with CO₂ production that blows off the volatile material. Hydrolysis takes place in the last stages of fermentation. In a 10-1 open fermenter, up to 80% of volatile material can be blown off while an average of 10% is retained. Residual esterase activity accounts for about 20% of the total amount of ester synthesized.     

Modeling of the condyle elements within a biomechanical knee model

The development of a computational multibody knee model able to capture some of the fundamental properties of the human knee articulation is presented. This desideratum is reached by including the kinetics of the real knee articulation. The research question is whether an accurate modeling of the condyle contact in the knee will lead to reproduction of the complex combination of flexion/extension, abduction/adduction, and tibial rotation observed in the real knee. The model is composed by two anatomic segments, the tibia and the femur, whose characteristics are functions of the geometric and anatomic properties of the real bones. The biomechanical model characterization is developed under the framework of multibody systems methodologies using Cartesian coordinates. The type of approach used in the proposed knee model is the joint surface contact conditions between ellipsoids, representing the two femoral condyles, and points, representing the tibial plateau and the menisci. These elements are closely fitted to the actual knee geometry. This task is undertaken by considering a parameter optimization process to replicate experimental data published in the literature, namely that by Lafortune and his coworkers in 1992. Then kinematic data in the form of flexion/extension patterns are imposed on the model corresponding to the stance phase of the human gait. From the results obtained, by performing several computational simulations, it can be observed that the knee model approximates the average secondary motion patterns observed in the literature. Because the literature reports considerable inter-individual differences in the secondary motion patterns, the knee model presented here is also used to check whether it is possible to reproduce the observed differences with reasonable variations of bone shape parameters. This task is accomplished by a parameter study, in which the main variables that define the geometry of condyles are taken into account. It was observed that the data reveal a difference in secondary kinematics of the knee in flexion versus extension. The likely explanation for this fact is the elastic component of the secondary motions created by the combination of joint forces and soft tissue deformations. The proposed knee model is, therefore, used to investigate whether this observed behavior can be explained by reasonable elastic deformations of the points representing the menisci in the model.     

Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

Effect of cold environment on hepatic microsomal Δ6 and Δ9 desaturase activity of male rats

Male rats maintained at 24 C and then shifted to 5 C for 5 days increased food intake and decreased in growth rate and food conversion. No modification was observed in Δ6 desaturase activity, while Δ9 desaturase activity decreased after this period of time. These results were confirmed by liver microsomal and mitochondrial fatty acid composition. The phospholipid composition of liver microsomes was unaltered, whereas in mitochondria, phosphatidylcholine and sphingomyelin decreased and phosphatidylethanolamine increased due to the cold environment. The influence of food intake and weight changes on fatty acid metabolism was studied using (i) rats maintained at 5 C with restricted food intake to match the food intake of those kept at 24 C with food ad libitum and (ii) rats maintained at 24 C whose food intake was also restricted so that their growth rate would be the same as that of rats maintained at 5 C with food ad libitum, respectively. These results indicate that the negative metabolic balance state of these cold conditions is not an active factor modifier of Δ6 desaturase activity, whereas it decreases Δ9 desaturase activity, reflecting the lipogenic characteristics of the latter enzyme.     

Electrodialytic extraction of Cu,Pb and Cl from municipal solid waste incineration fly ash suspended in water

The possibility of using fly ash from municipal solid waste incineration (MSWI) in, for example, concrete is considered. MSWI fly ash, however, has too high a concentration of heavy metals, which may cause leaching problems during use or problems with waste handling at the end of the lifetime of the concrete. The Cl content in MSWI fly ash is also too high and will cause corrosion problems in reinforced concrete. The possibility of removing some of the unwanted heavy metals (Cu and Pb) together with Cl from an MSWI fly ash suspended in water using an electrodialytic separation method was investigated. The removal of Pb and Cu was found to be highly pH dependent and the highest contents removed were 41 and 90%, respectively. The Cu concentration of the ash decreased from 2200 to 860 mg kg^?1 but the Pb concentration increased from 8560 to 16 800 mg kg^?1, showing that Pb is mainly found in the ash fraction that is least soluble. Hence electrodialytic treatment of the ash suspended in water is not a solution to improve the ash quality in terms of Pb. The water‐soluble Cl content per unit weight of the original ash was 12.4%. The removal of water‐soluble Cl was efficient and >98% of Cl was removed (calculated on the basis of mean initial and final concentrations). This result indicates that electrodialytic extraction may be a method that can be used for the removal of Cl from ash prior to its utilization in concrete. Copyright © 2006 Society of Chemical Industry     

A web-based platform for biosignal visualization and annotation

With the advent of wearable sensing and mobile technologies, biosignals have seen an increasingly growing number of application areas, leading to the collection of large volumes of data. One of the difficulties in dealing with these data sets, and in the development of automated machine learning systems which use them as input, is the lack of reliable ground truth information. In this paper we present a new web-based platform for visualization, retrieval and annotation of biosignals by non-technical users, aimed at improving the process of ground truth collection for biomedical applications. Moreover, a novel extendable and scalable data representation model and persistency framework is presented. The results of the experimental evaluation with possible users has further confirmed the potential of the presented framework.     

On Hypotheses Testing for the Selection of Spatio‐Temporal Models

Abstract. Several models have been proposed in recent years for analysing spatial data and also, to some extent, spatio‐temporal data. One of the important problems, namely the choice of an appropriate model for describing real data sets, remains unsolved. Here we consider the analysis of spatio‐temporal processes from which observations over space and time are available. We propose statistical tests for discriminating between space–time autoregressive processes and multivariate autoregressive processes. The sampling properties of the proposed tests are considered. We illustrate the methods with a real example. We use the above tests to find the best model to describe spatio‐temporal variations of hourly carbon monoxide measurements at four locations in London in January 2004.     

Capture device identification from digital images using Kullback-Leibler divergence

Multimedia Tools and Applications - It is proposed a forensic method for the capture device identification from digital images, which requires two elements: i) a digital image subject to...