Association of IgG1 Antibody Clearance with FcγRIIA Polymorphism and Platelet Count in Infliximab-Treated Patients

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn’s disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 10⁹/L, respectively, to ≈13 days (both HR and RR) at 350 × 10⁹/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.     

Concreteness training reduces dysphoria: Proof-of-principle for repeated cognitive bias modification in depression.

A tendency toward abstract and overgeneral processing is a cognitive bias hypothesized to causally contribute to symptoms of depression. This hypothesis predicts that training dysphoric individuals to become more concrete and specific in their thinking would reduce depressive symptoms. To test this prediction, 60 participants with dysphoria were randomly allocated either to (a) concreteness training; (b) bogus concreteness training, matched with concreteness training for treatment rationale, experimenter contact, and treatment duration but without active engagement in concrete thinking; (c) a waiting-list, no training control. Concreteness training resulted in significantly greater decreases in depressive symptoms and significantly greater increases in concrete thinking than the waiting-list and the bogus training control, and significantly greater decreases in rumination than the waiting-list control. These findings suggest that concreteness training has potential as a guided self-help intervention for mild-to-moderate depressive symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bilayer Forming Phospholipids as Targets for Cancer Therapy

Phospholipids represent a crucial component for the structure of cell membranes. Phosphatidylcholine and phosphatidylethanolamine are two phospholipids that comprise the majority of cell membranes. De novo biosynthesis of phosphatidylcholine and phosphatidylethanolamine occurs via the Kennedy pathway, and perturbations in the regulation of this pathway are linked to a variety of human diseases, including cancer. Altered phosphatidylcholine and phosphatidylethanolamine membrane content, phospholipid metabolite levels, and fatty acid profiles are frequently identified as hallmarks of cancer development and progression. This review summarizes the research on how phospholipid metabolism changes over oncogenic transformation, and how phospholipid profiling can differentiate between human cancer and healthy tissues, with a focus on colorectal cancer, breast cancer, and non-small cell lung cancer. The potential for phospholipids to serve as biomarkers for diagnostics, or as anticancer therapy targets, is also discussed.     

High‐Pressure Thermal Sterilization: Food Safety and Food Quality of Baby Food Puree

The benefits that high‐pressure thermal sterilization offers as an emerging technology could be used to produce a better overall food quality. Due to shorter dwell times and lower thermal load applied to the product in comparison to the thermal retorting, lower numbers and quantities of unwanted food processing contaminants (FPCs), for example, furan, acrylamide, HMF, and MCPD‐esters could be formed. Two spore strains were used to test the technique; Geobacillus stearothermophilus and Bacillus amyloliquefaciens, over the temperature range 90 to 121 °C at 600 MPa. The treatments were carried out in baby food puree and ACES‐buffer. The treatments at 90 and 105 °C showed that G. stearothermophilus is more pressure‐sensitive than B. amyloliquefaciens. The formation of FPCs was monitored during the sterilization process and compared to the amounts found in retorted samples of the same food. The amounts of furan could be reduced between 81% to 96% in comparison to retorting for the tested temperature pressure combination even at sterilization conditions of F₀‐value in 7 min.     

Predicting Survival Outcomes in the Presence of Unlabeled Data

Many clinical studies require the follow-up of patients over time. This is challenging: apart from frequently observed drop-out, there are often also organizational and financial challenges, which can lead to reduced data collection and, in turn, can complicate subsequent analyses. In contrast, there is often plenty of baseline data available of patients with similar characteristics and background information, e.g., from patients that fall outside the study time window. In this article, we investigate whether we can benefit from the inclusion of such unlabeled data instances to predict accurate survival times. In other words, we introduce a third level of supervision in the context of survival analysis, apart from fully observed and censored instances, we also include unlabeled instances. We propose three approaches to deal with this novel setting and provide an empirical comparison over fifteen real-life clinical and gene expression survival datasets. Our results demonstrate that all approaches are able to increase the predictive performance over independent test data. We also show that integrating the partial supervision provided by censored data in a semi-supervised wrapper approach generally provides the best results, often achieving high improvements, compared to not using unlabeled data.

     

Air-dictated bottom spray process: impact of fluid dynamics on granule growth and morphology

Background: Growing interest in the use of the less-explored bottom spray technique for fluidized bed granulation provided impetus for this study. Aim: The impact of fluid dynamics (air accelerator insert diameter; partition gap) and wetting (binder spray rate) on granule properties were investigated. Method: In this 3³ full factorial study, the results were fitted to a quadratic model using response surface methodology. The air velocity at the spray granulation zone for the investigated conditions was measured using a pitot tube. Results: Air accelerator insert diameter correlated to measured air velocity at the spray granulation zone and was found to not only dictate growth but also influence granule morphology. The partition gap was found to play important roles in regulating particle movement into the spray granulation zone and optimizing process yields, whereas binder spray rate significantly affected granule morphology but not granule size. Conclusions: Unlike conventional fluidized bed granulation, ease of modulation of fluid dynamics and insensitivity of the bottom spray process to wetting allow flexible control of granule size, shape, and flow. Its good drying ability also indicated potential use in granulating moisture-sensitive materials.     

Growth of one-dimensional Si/SiGe heterostructures by thermal CVD

The first results on a simple new process for the direct fabrication of one-dimensional superlattices using common CVD chambers are presented. The experiments were carried out in a 200?mm industrial Centura reactor (Applied Materials). Low dimensionality and superlattices allow a significant increase in the figure of merit of thermoelectrics by controlling the transport of phonons and electrons. The monocrystalline nanowires produced according to this process are both one-dimensional and present heterostructures, with very thin layers (40?nm) of Si and SiGe. Concentrations up to 30?at.% Ge were obtained in the SiGe parts. Complementary techniques including transmission electronic microscopy (TEM), selected area electron diffraction (SAED), energy dispersive x-ray spectroscopy (EDS), scanning transmission electron microscopy (STEM) in bright field and high angle annular dark field (HAADF STEM), and energy-filtered transmission electron microscopy (EF-TEM) were used to characterize the nanoheterostructures.