Dealkylation of various 14-alkylsterols by the nematodeCaenorhabditis elegans

The metabolism of 4 dietary 24-alkylsterols was investigated in the free-living nematodeCaenorhabditis elegans. The major unesterified sterols ofC. elegans in media supplemented with either campesterol, 22-dihydrobrassicasterol or stigmasterol included cholesta-5,7-dienol, cholesterol, cholest-7-enol, and 4α-methylcholest-8(14)-enol. Dietary stigmastanol yielded cholest-7-enol, cholestanol, cholest-8(14)-enol, and 4α-methylcholest-8(14)-enol as major unesterified sterols. Esterified sterols comprised less than 22% of the total sterol. Removal of a C-24 ethyl substituent of sterols was neither hindered by the presence of a Δ²²-bond in the sterol side chain nor was it depedent on unsaturation in ring B of the steroid nucleus.C. elegans reduced a Δ²²-bond during its metabolism of stigmasterol; it did not introduce a Δ²²-bond during stigmastanol metabolism.C. elegans was capable of removing a C-24 methyl substituent regardless of its stereochemical orientation. Metabolic processes involving the steroid ring system of cholesterol (C-7 dehydrogenation, Δ⁵-bond, 4α-methylation, Δ⁸⁽¹⁴⁾-isomerization inC. elegans were not hindered by the presence of a 24-methyl group; various 24-methylsterol metabolites from campesterol were detected, mostly 24-methylcholesta-5,7-dienol. In contrast, no 24-ethylsterol metabolites from the dietary ethylsterols were found. More dietary 24-methylsterol remained unmetabolized than did dietary 24-ethylsterol. A 24α-ethyl group and a 24β-methyl group were dealkylated to a greater extent byC. elegans than was a 24α-methyl group, perhaps reflecting the substrate specificity of the dealkylation enzyme system, or suggesting different enzymes altogether.     

Computing the energy balance of a statue of bronze: The San Marco's horses as a case study

The energy balance is discussed for the complex case of bronze or marble statuary horses and particularly the four horses of San Marco in Venice. Having computed the coefficient of exchange between bronze and the atmosphere, the daytime overheating is evaluated for different seasons and orientations of the statues. The equations can be solved with reasonable approximation and both the past and future overheatings can be evaluated as a function of the growing surface weathering and blackening. Therefore, the present analysis points out the chief characteristics of both the diurnal cycle and the variation over the centuries of the response of the bronzes to atmospheric variables.     

High‐pressure processing effects on the mechanical,barrier and mass transfer properties of food packaging flexible structures: a critical review

Food products can be high‐pressure processed (HPP) either in bulk or prepackaged in flexible or semi‐rigid packaging materials. In the latter case the packaging material is subjected, together with the food, to high‐pressure treatment. A number of studies have been performed to quantify the effects of high‐pressure processing on the physical and barrier properties of the packaging material, since the integrity of the package during and after processing is of paramount importance to the safety and quality of the food product. This article reviews the results of published research concerning the effect of HPP on packaging materials. Copyright © 2004 John Wiley & Sons, Ltd.     

Modelling and experimental investigation of devolatilizing wood in a fluidized bed combustor

A two-dimensional model is developed for the determination of devolatilization time and char yield of cylindrical wood particles in a bubbling fluidized bed combustor. By using the concept of shape factor, the model is extended to particles of cuboid shape. The model prediction of the devolatilization time agrees with the measured data (present and those reported in the literature) for cylindrical and cuboidal shaped particles within ±20% while the char yield is predicted within ±17%. Influence of some important parameters namely, thermal diffusivity, external heat transfer coefficient and shrinkage, on the devolatilization time and char yield are studied. Thermal diffusivity shows noticeable influence on devolatilization time. The external heat transfer coefficient shows little influence beyond a value of 300 W/(m² K). However particle shrinkage shows negligible effect on the devolatilization time but has a significant influence on the char yield.     

Low-cost, redundant proximity sensor system for spatial sensing andcolour perception

The authors describe their approach to the design of redundant proximity sensor systems that are capable of extracting geometrical information about the surrounding environment and perceiving other relevant features of the reflecting objects, e.g. colour. Potential applications of the proposed sensorial systems are in the field of robotics and autonomous mobility     

Parallel Computation of High-Dimensional Robust Correlation and Covariance Matrices

The computation of covariance and correlation matrices are critical to many data mining applications and processes. Unfortunately the classical covariance and correlation matrices are very sensitive to outliers. Robust methods, such as Quadrant Correlation (QC) and the Maronna method, have been proposed. However, existing algorithms for QC only give acceptable performance when the dimensionality of the matrix is in the hundreds; and the Maronna method is rarely used in practice because of its high computational cost. In this paper we develop parallel algorithms for both QC and the Maronna method. We evaluate these parallel algorithms using a real data set of the gene expression of over 6000 genes, giving rise to a matrix of over 18 million entries. In our experimental evaluation, we explore scalability in dimensionality and in the number of processors, and the trade-offs between accuracy and computational efficiency. We also compare the parallel behaviours of the two methods. From a statistical standpoint, the Maronna method is more robust than QC. From a computational standpoint, while QC requires less computation, interestingly the Maronna method is much more parallelizable than QC. After a thorough experimentation, we conclude that for many data mining applications, both QC and Maronna are viable options. Less robust, but faster, QC is the recommended choice for small parallel platforms. On the other hand, the Maronna method is the recommended choice when a high degree of robustness is required, or when the parallel platform features a large number of processors (e.g., 32).     

Energy-Efficient Thermal-Aware Autonomic Management of Virtualized HPC Cloud Infrastructure

Virtualized datacenters and clouds are being increasingly considered for traditional High-Performance Computing (HPC) workloads that have typically targeted Grids and conventional HPC platforms. However, maximizing energy efficiency and utilization of datacenter resources, and minimizing undesired thermal behavior while ensuring application performance and other Quality of Service (QoS) guarantees for HPC applications requires careful consideration of important and extremely challenging tradeoffs. Virtual Machine (VM) migration is one of the most common techniques used to alleviate thermal anomalies (i.e., hotspots) in cloud datacenter servers as it reduces load and, hence, the server utilization. In this article, the benefits of using other techniques such as voltage scaling and pinning (traditionally used for reducing energy consumption) for thermal management over VM migrations are studied in detail. As no single technique is the most efficient to meet temperature/performance optimization goals in all situations, an autonomic approach that performs energy-efficient thermal management while ensuring the QoS delivered to the users is proposed. To address the problem of VM allocation that arises during VM migrations, an innovative application-centric energy-aware strategy for Virtual Machine (VM) allocation is proposed. The proposed strategy ensures high resource utilization and energy efficiency through VM consolidation while satisfying application QoS by exploiting knowledge obtained through application profiling along multiple dimensions (CPU, memory, and network bandwidth utilization). To support our arguments, we present the results obtained from an experimental evaluation on real hardware using HPC workloads under different scenarios.     

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.     

Is LRP2 Involved in Leptin Transport over the Blood-Brain Barrier and Development of Obesity?

The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described.