Gravesengottlieb9268

It has been preclinically and clinically proven that anticancer agent-incorporating (ACA-incorporating) polymeric micelles selectively accumulate in tumor via the enhanced permeability and retention (EPR) effect, yielding a wider therapeutic window and greater safety than conventional low-molecular weight ACAs. To increase the antitumor effect of these safer micelle formulations, epirubicin-incorporating polymer micelles (NC-6300) conjugated with monoclonal antibodies (mAbs) have been prepared. In this study, we used two types of mAb an anti-tissue factor (TF) mAb that does not exert a direct cytocidal effect, and an anti-HER2 mAb that has a direct cytocidal effect. We compared the antitumor effects and pharmacological properties of the two types of antibody conjugated to NC-6300. Immunomicelles conjugated to anti-TF mAb exerted greater antitumor activity toward TF-positive stomach cancer than the combination of anti-TF mAb and NC-6300, and were distributed more uniformly throughout TF-positive tumor tissue than NC-6300. On the other hand, immunomicelles conjugated to anti-HER2 mAb did not exert significant antitumor activity toward HER2-positive stomach cancer relative to the combined use of anti-HER2 mAb and NC-6300. Thus, this immunomicelle-based strategy may be useful for antibodies that target cancer as pilot molecules even when the antibodies themselves do not have an antitumor effect. V.In this paper, we develop a mathematical model for the early stage of atherosclerosis, as a chronic inflammatory disease. It includes also processes that are relevant for the "thickening" of the vessel walls, and prepares a more complete model including also the later stages of atherosclerosis. The model consists of partial differential equations Navier-Stokes equations modeling blood flow, Biot equations modeling the fluid flow inside the poroelastic vessel wall, and convection/chemotaxis-reaction-diffusion equations modeling transport, signaling and interaction processes initiating inflammation and atherosclerosis. The main innovations of this model are a) quantifying the endothelial permeability to low-density-lipoproteins (LDL) and to the monocytes as a function of WSS, cytokines and LDL on the endothelial surface; b) transport of monocytes on the endothelial surface, mimicking the monocytes adhesion and rolling; c) the monocytes influx in the lumen, as a function of factor increasing monocytopoiesis; d) coupling between Navier-Stokes system, Biot system and convection/chemotaxis-reaction-diffusion equations. learn more Numerical simulations of a simplified model were performed in an idealized two-dimensional geometry in order to investigate the dynamics of endothelial permeability, and the growth and spread of immune cells populations and their dependence in particular on low-density-lipoprotein and wall-shear stress. Reverse transcriptase (RT) enzymes are indispensable tools for interrogating diverse aspects of RNA metabolism and transcriptome composition. Due to the growing interest in sequence and structural complexity of long RNA molecules, processive RT enzymes are now required for preserving linkage and information content in mixed populations of transcripts, and the low-processivity RT enzymes that are commercially available cannot meet this need. MarathonRT is encoded within a eubacterial group II intron and it has been shown to efficiently copy highly structured long RNA molecules in a single pass. In this work, we systematically characterize MarathonRT as a tool enzyme and optimize its performance in a variety of applications that include single cycle reverse-transcription of long RNAs, in-cell SHAPE-MaP using ultra-long amplicons and the detection of natural RNA base modifications. By diversifying MarathonRT reaction protocols, we provide an upgraded suite of tools for cutting-edge RNA research and clinical application. BACKGROUND We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been associated with clinical efficacy. OBJECTIVE We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups. METHODS Pre- and post-SLIT sera were assessed for rMal d 1-specific IgG antibodies in ELISA and for their ability to inhibit apple allergen-induced upregulation of CD63 on basophils from non-treated individuals with birch pollen-related apple allergy. Post-SLIT sera depleted of IgG1 or IgG4 were compared for their IgE-blocking activity. IgG1-binding to rMal d 1 was competed with rMal d 1 and rBet v 1 in ELISA. RESULTS SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1-specific IgG1-4 antibodies. Only post-rMal d 1-SLIT sera displayed IgE-blocking activity which was significantly reduced by depletion of IgG1 and less so by IgG4-depletion. In competition ELISA, IgG1-binding to Mal d 1 in post-rMal d 1-SLIT sera was fully inhibited with rMal d 1 but not with rBet v 1. Correspondingly, Bet v 1 was the more potent competitor for IgG1-binding to Mal d 1 in post-rBet v 1-SLIT sera. CONCLUSION Sixteen-week rMal d 1-SLIT induced functional, primarily Mal d 1-specific IgE-blocking antibodies whereas rBet v 1-SLIT induced Bet v 1-specific, Mal d 1-cross-reactive IgG antibodies with limited cross-blocking activity. These results provide a possible explanation for the limited effectiveness of birch pollen immunotherapy on birch pollen-related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment. Starch gelatinization is an endothermic transition arising during rice cooking, which significantly influences rice eating and cooking quality (ECQ). The nature of starch (especially amylose) fine molecular structures that gives rise to this endotherm is however currently unclear. A modified Gomperz model was developed in this study to fit the differential scanning calorimetry (DSC) thermograms, resulting complementary information to the traditional DSC parameters. Correlation analysis between DSC parameters with starch chain-length distributions (CLDs) from 14 different rice starches showed for the first time that although amylose CLDs didn't affect starch gelatinization temperatures, the relative length of amylose medium chains was negatively correlated with the gelatinization temperature range. Furthermore, gelatinization onset and peak temperature as well as maximum gelatinization rate were negatively correlated with the relative length of amylopectin short chains, while the conclusion temperature were related to the relative length of amylopectin medium chains.