Fraunhofer Society

About: Fraunhofer Society is a government organization based out in Munich, Germany. It is known for research contribution in the topics: Laser & Silicon. The organization has 24736 authors who have published 40168 publications receiving 820894 citations.

Critical review of the migration potential of nanoparticles in food contact plastics

Abstract: Background The development of applications using nanomaterials is accompanied by safety concerns due to gaps in understanding the toxicology. In case of incorporation in food contact polymers, the first step to consumer exposure is the transfer of nanomaterials from the polymer to the food. Thus, in order to evaluate the risk the key questions are whether nanoparticles can be released from food contact polymers and under which conditions. Scope and Approach This article critically reviews the published nanomaterial migration studies which are partly contradictory. The influence of analytical techniques and the experimental design on the results are discussed. Theoretical approaches by mathematical modelling are addressed. Furthermore, a short overview on nanomaterial applications for food contact materials and on the regulatory situation in Europe and USA is given. Key findings and conclusions Distinguishing between particle release and migration of dissolved ions is crucial for proper interpretation of migration results. Nanosilver which is the mostly investigated species, and other metals are easily oxidized to ions but can re-form nanoparticles at slightly reductive conditions, e.g. at sample preparation, pretending particle migration. At cutting edges the particles may be released due to weak binding to the surface. Nanoparticles which are completely encapsulated in the host polymer matrix do not have a potential to migrate into food. Thus, consumers will not be exposed to nanoparticles from food contact polymers when those are completely embedded in polymer and the contact surface is not altered by mechanical surface stress during application.

Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study.

Abstract: Aims Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models. The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study (NCT04045405). Methods and results Patients had left ventricular ejection fraction between ≥30% and 125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each. CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed a median 23.3% NT-proBNP reduction, vs. a 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and encouraging positive trends for relevant cardiac fibrosis biomarkers. Conclusion This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. Although this study is limited by the small patient numbers, the indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.

RASE: recognition of alternatively spliced exons in C.elegans

Abstract: Motivation: Eukaryotic pre-mRNAs are spliced to form mature mRNA. Pre-mRNA alternative splicing greatly increases the complexity of gene expression. Estimates show that more than half of the human genes and at least one-third of the genes of less complex organisms, such as nematodes or flies, are alternatively spliced. In this work, we consider one major form of alternative splicing, namely the exclusion of exons from the transcript. It has been shown that alternatively spliced exons have certain properties that distinguish them from constitutively spliced exons. Although most recent computational studies on alternative splicing apply only to exons which are conserved among two species, our method only uses information that is available to the splicing machinery, i.e. the DNA sequence itself. We employ advanced machine learning techniques in order to answer the following two questions: (1) Is a certain exon alternatively spliced? (2) How can we identify yet unidentified exons within known introns? Results: We designed a support vector machine (SVM) kernel well suited for the task of classifying sequences with motifs having positional preferences. In order to solve the task (1), we combine the kernel with additional local sequence information, such as lengths of the exon and the flanking introns. The resulting SVM-based classifier achieves a true positive rate of 48.5% at a false positive rate of 1%. By scanning over single EST confirmed exons we identified 215 potential alternatively spliced exons. For 10 randomly selected such exons we successfully performed biological verification experiments and confirmed three novel alternatively spliced exons. To answer question (2), we additionally used SVM-based predictions to recognize acceptor and donor splice sites. Combined with the above mentioned features we were able to identify 85.2% of skipped exons within known introns at a false positive rate of 1%. Availability: Datasets, model selection results, our predictions and additional experimental results are available at http://www.fml.tuebingen.mpg.de/~raetsch/RASE Contact: Gunnar.Raetsch@tuebingen.mpg.de Supplementary information: http://www.fml.tuebingen.mpg.de/raetsch/RASE

Characterization of murine lung interstitial macrophages in comparison with alveolar macrophages in vitro.

Abstract: The present study was performed to characterize the immunologic potential of interstitial macrophages (INT) in comparison with alveolar macrophages (AL). The data showed that AL, compared with INT, have a more efficient phagocytic potential. In addition, they have a strong microbicidal activity and secrete large amounts of reactive oxygen radicals, nitric oxides, TNF, and IFN on appropriate stimulation. They also exert strong tumoricidal and parasiticidal activities. In contrast, INT are more efficient in releasing immunoregulatory cytokines such as IL-1 and IL-6. As determined by Ab staining, INT express more MHC class II molecules and are more effective in functioning as accessory cells for mitogen-stimulated lymphocyte proliferation compared with AL. Thus, AL appear to be particularly effective as nonspecific first line defense cells against infectious agents, whereas INT are equipped to cooperate with interstitial lymphocytes in inducing a specific immune reaction.