Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

Influence of the intrinsic layer characteristics on a-Si:H p–i–n solar cell performance analysed by means of a computer simulation

In this paper a set of one-dimensional simulations of a-Si:H p–i–n junctions under different illumination conditions and with different intrinsic layer are presented. The simulation program ASCA permits the analysis of the internal electrical behaviour of the cell allowing a comparison among the different internal configurations determined by a change in the input set. Results about the internal electric configuration will be presented and discussed outlining their influence on the current tension characteristic curve. Considerations about the drift–diffusion and the generation–recombination balance distributions, outlined by the simulation, can be used to explain the correlation between the basic device output, the i-layer characteristics (thickness and DOS), the incident radiation intensity and photon energy.     

Synthesis and thermal stability of ball-milled and melt-quenched amorphous and nanostructured Al-Ni-Nd-Co alloys

In this work the Al₈₅Ni₉Nd₄Co₂ alloy was used as a starting point for examining the possibility of forming bulk glassy Al-based materials by combining rapid quenching and ball milling techniques. Fine glassy powders were obtained by ball milling melt-spun amorphous ribbons using a severe cryogenic processing regime. The thermal stability data of the powders as obtained by constant-rate heating and isothermal DSC experiments together with viscosity measurements are discussed with respect to feasible consolidation conditions. The powder compaction was done by two methods (uni-axial hot pressing and extrusion) at 513 K for up to 15 min. Only the uni-axial hot pressing led to bulk Al₈₅Ni₉Nd₄Co₂ samples with similar glassy structure and Vickers microhardness values comparable to those of the initial melt-spun ribbons.     

On the number of broadcast schemes in networks

Broadcasting is the process of spreading one piece of information among a group of individuals connected by an interconnection network. In this paper we give exact lower and upper bounds for the number of broadcast schemes in arbitrary networks. Also, we give the exact value for complete bipartite graphs and an upper bound for regular networks. Based on the counting method we describe a new random algorithm for broadcasting in networks.     

Kinetic modelling of textural changes in ready-to-eat breakfast cereals during soaking in semi-skimmed milk

Summary Ready‐to‐eat breakfast cereals immersed in milk undergo undesirable changes in texture because of sudden moisture uptake. The textural changes are ascribable to a plasticizing effect of water, which modifies the mechanical strength of products by softening the starch/protein matrix. In this work, some textural parameters of different cereal flakes were derived from the force–displacement curves monitored during 300 s of immersion in milk. Hardness loss, deformability increment and changes in the force–displacement curve profile were calculated and plotted against soaking time. The application of a sugar coating process to a model cereal flake increased the initial product hardness and improved the preservation of the textural parameters during immersion. The Peleg model closely fitted the experimental data, with regression coefficients from 0.967 to 0.999.     

Effects of freezing and frozen storage on the physicochemical and sensory characteristics of four types of goat's cheese

Summary Physicochemical and organoleptic properties were studied in two batches of four different types of goat's milk cheese: fresh, washed curd, soft with surface flora, and Majorero, frozen for four months prior to ripening and/or chilled storage. Frozen storage did not produce significant changes in the rheological or sensory characteristics of the cheeses, except in the case of fresh cheese, the textural characteristics of which were adversely affected. The level of proteolysis, estimated from the amino-acid nitrogen, was higher in the pre-frozen washed curd, soft with surface flora, and Majorero cheeses. The level of lipolysis was comparable, except in the soft cheese with surface flora, which presented higher levels of free fatty acids when stored frozen before ripening.

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Einfluß des Gefrierens und der Gefrierlagerung auf die physikalisch-chemischen und organoleptischen Eigenschaften von vier Ziegenkäsen

Zusammenfassung Aus Ziegenmilch wurden jeweils zwei Chargen von vier spanischen Käsesorten hergestellt: Frischkäse, gewaschene Käsemasse, Weichkäse mit Oberflächenflora und Majorero -Käse. Von jeder Charge wurde die Hälfte gefroren gelagert und erst nach vier Monaten auf die übliche Weise gereift und/oder gekühlt aufbewahrt. Die physikalisch-chemischen und organoleptischen Eigenschaften wurden danach untersucht. Im Vergleich mit Käsen, die nicht gefroren gewesen waren, ergaben sich keine wesentlichen Unterschiede in den rheologischen und sensorischen Eigenschaften, mit Ausnahme bei den Frischkäsen, bei dem sich die Textur durch die Aufbewahrung in gefrorenem Zustand verschlechtert hatte. Der Gehalt an freien Aminosäuren, ein Maß für die Proteolyse, war höher in der gewaschenen Käsemasse, in dem Weichkäse mit Oberflächenflora und in dem Majorero-Käse, die vier Monate gefroren gewesen waren. Durch die Gefrierlagerung hatte sich der Fettabbau nicht verändert, mit Ausnahme bei dem Käse mit Oberflächenflora, bei dem der Gehalt an freien Fettsäuren erhöht war im Vergleich mit dem Käse, der nicht vier Monate gefriergelagert worden war.

     

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.     

The Effect of Small Additions of Fe and Heavy Deformation on the Precipitation in an Al–1.1Mg–0.5Cu–0.3Si At. Pct Alloy

Metallurgical and Materials Transactions A - The effect of 0.03 and 0.08 at. pct Fe additions on the formation of secondary phases in an Al–1.1Mg–0.5Cu–0.3Si at. pct alloy was...