Design for Electromagnetic Compatibility--In a Nutshell

This open access book provides practicing electrical engineers and students a practical – and mathematically sound – introduction to the topic of electromagnetic compatibility (EMC). The author enables readers to understand better how to overcome commonly failed EMC tests for radiated emission, radiated immunity, and electrostatic discharge (ESD), while providing concrete EMC design guidelines. The book also presents an overview of EMC standards and regulations and how to test for a global market access

Design for Electromagnetic Compatibility--In a Nutshell

This open access book provides practicing electrical engineers and students a practical – and mathematically sound – introduction to the topic of electromagnetic compatibility (EMC). The author enables readers to understand better how to overcome commonly failed EMC tests for radiated emission, radiated immunity, and electrostatic discharge (ESD), while providing concrete EMC design guidelines. The book also presents an overview of EMC standards and regulations and how to test for a global market access

SU-G-IeP4-13: PET Image Noise Variability and Its Consequences for Quantifying Tumor Hypoxia.

PURPOSE The values in a PET image which represent activity concentrations of a radioactive tracer are influenced by a large number of parameters including patient conditions as well as image acquisition and reconstruction. This work investigates noise characteristics in PET images for various image acquisition and image reconstruction parameters. METHODS Different phantoms with homogeneous activity distributions were scanned using several acquisition parameters and reconstructed with numerous sets of reconstruction parameters. Images from six PET scanners from different vendors were analyzed and compared with respect to quantitative noise characteristics. Local noise metrics, which give rise to a threshold value defining the metric of hypoxic fraction, as well as global noise measures in terms of noise power spectra (NPS) were computed. In addition to variability due to different reconstruction parameters, spatial variability of activity distribution and its noise metrics were investigated. Patient data from clinical trials were mapped onto phantom scans to explore the impact of the scanner's intrinsic noise variability on quantitative clinical analysis. RESULTS Local noise metrics showed substantial variability up to an order of magnitude for different reconstruction parameters. Investigations of corresponding NPS revealed reconstruction dependent structural noise characteristics. For the acquisition parameters, noise metrics were guided by Poisson statistics. Large spatial non-uniformity of the noise was observed in both axial and radial direction of a PET image. In addition, activity concentrations in PET images of homogeneous phantom scans showed intriguing spatial fluctuations for most scanners. The clinical metric of the hypoxic fraction was shown to be considerably influenced by the PET scanner's spatial noise characteristics. CONCLUSION We showed that a hypoxic fraction metric based on noise characteristics requires careful consideration of the various dependencies in order to justify its quantitative validity. This work may result in recommendations for harmonizing QA of PET imaging for multi-institutional clinical trials

Allergen motifs and the prediction of allergenicity

We have recently shown that the majority of allergens can be represented by allergen motifs. This observation prompted us to experimentally investigate the synthesized peptides corresponding to the in silico motifs with regard to potential IgE binding and cross-reactions with allergens. Two motifs were selected as examples to conduct in vitro studies. From the first motif, derived from allergenic MnSOD sequences, the motif stretch of the allergen Asp f 6 was selected and synthesized as a peptide (MnSOD Mot). The corresponding full-length MnSOD was also expressed in Escherichia coli and both were compared for IgE reactivity with sera of patients reacting to the MnSOD of Aspergillus fumigatus or Malassezia sympodialis. For the second motif, the invertebrate tropomyosin sequences were aligned and a motif consensus sequence was expressed as a recombinant protein (Trop Mot). The IgE reactivity of Trop Mot was analyzed in ELISA and compared to that of recombinant tropomyosin from the shrimp Penaeus aztecus (rPen a 1) in ImmunoCAP. MnSOD Mot was weakly recognized by some of the tested sera, suggesting that the IgE binding epitopes of a multimeric globular protein such as MnSOD cannot be fully represented by a motif peptide. In contrast, the motif Trop Mot showed the same IgE reactivity as shrimp full-length tropomyosin, indicating that the major allergenic reactivity of a repetitive structure such as tropomyosin can be covered by a motif peptide. Our results suggest that the motif-generating algorithm may be used for identifying major IgE binding structures of coiled-coil proteins

Preclinical Evaluation of the Antifolate QN254, 5-Chloro- N′6′-(2,5-Dimethoxy-Benzyl)-Quinazoline-2,4,6-Triamine, as an Antimalarial Drug Candidate▿ †

Drug resistance against dihydrofolate reductase (DHFR) inhibitors—such as pyrimethamine (PM)—has now spread to almost all regions where malaria is endemic, rendering antifolate-based malaria treatments highly ineffective. We have previously shown that the di-amino quinazoline QN254 [5-chloro-N′6′-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine] is active against the highly PM-resistant Plasmodium falciparum V1S strain, suggesting that QN254 could be used to treat malaria in regions with a high prevalence of antifolate resistance. Here, we further demonstrate that QN254 is highly active against Plasmodium falciparum clinical isolates, displaying various levels of antifolate drug resistance, and we provide biochemical and structural evidence that QN254 binds and inhibits the function of both the wild-type and the quadruple-mutant (V1S) forms of the DHFR enzyme. In addition, we have assessed QN254 oral bioavailability, efficacy, and safety in vivo. The compound displays favorable pharmacokinetic properties after oral administration in rodents. The drug was remarkably efficacious against Plasmodium berghei and could fully cure infected mice with three daily oral doses of 30 mg/kg. In the course of these efficacy studies, we have uncovered some dose limiting toxicity at higher doses that was confirmed in rats. Thus, despite its relative in vitro selectivity toward the Plasmodium DHFR enzyme, QN254 does not show the adequate therapeutic index to justify its further development as a single agent