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Mutations of the JAK2 gene are frequent aberrations in the aging hematopoietic system and in myeloid neoplasms. While JAK-inhibitors efficiently reduce hyperinflammation induced by the constitutively active mutated JAK2 kinase, the malignant clone and abundance of mutated cells remains rather unaffected. Here, we sought to assess for genetic vulnerabilities of JAK2-mutated clones. We identified lysine-specific demethylase KDM4C as a selective genetic dependency that persists upon JAK-inhibitor treatment. Genetic inactivation of KDM4C in human and murine JAK2-mutated cells resulted in loss of cell competition and reduced proliferation. These findings led to reduced disease penetrance and improved survival in xenograft models of human JAK2-mutated cells. KDM4C deleted cells showed alterations in target histone residue methylation and target gene expression, resulting in induction of cellular senescence. In summary, these data establish KDM4C as a specific dependency and therapeutic target in JAK2-mutated cells that is essential for oncogenic signaling and prevents induction of senescence.

mp3 file (6.8 MB). In the inaugural edition of the Cancer Discovery podcast, Executive Editor Mark Landis talks with Matthew Meyerson about his paper, which describes the identification of the DDR2 kinase as a therapeutic target in squamous cell lung cancer.

XLSX file 75K, This is an excel file containing 9 sheets, one for each of the 9 supplementary tables (S1 to S9) mentioned in the main text

Supplementary Table 1 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer

PDF file 234K, This is a file containing the list of supplementary tables, the list of supplementary figures, as well as the 7 supplementary figures (S1 to S7) and their correspondent legends, mentioned in the main text

Supplementary Figures 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer

We discovered a novel somatic gene fusion, CD74–NRG1, by transcriptome sequencing of 25 lung adenocarcinomas of never smokers. By screening 102 lung adenocarcinomas negative for known oncogenic alterations, we found four additional fusion-positive tumors, all of which were of the invasive mucinous subtype. Mechanistically, CD74–NRG1 leads to extracellular expression of the EGF-like domain of NRG1 III-β3, thereby providing the ligand for ERBB2–ERBB3 receptor complexes. Accordingly, ERBB2 and ERBB3 expression was high in the index case, and expression of phospho-ERBB3 was specifically found in tumors bearing the fusion (P < 0.0001). Ectopic expression of CD74–NRG1 in lung cancer cell lines expressing ERBB2 and ERBB3 activated ERBB3 and the PI3K–AKT pathway, and led to increased colony formation in soft agar. Thus, CD74–NRG1 gene fusions are activating genomic alterations in invasive mucinous adenocarcinomas and may offer a therapeutic opportunity for a lung tumor subtype with, so far, no effective treatment.Significance: CD74–NRG1 fusions may represent a therapeutic opportunity for invasive mucinous lung adenocarcinomas, a tumor with no effective treatment that frequently presents with multifocal unresectable disease. Cancer Discov; 4(4); 415–22. ©2014 AACR.This article is highlighted in the In This Issue feature, p. 377

Supplementary Figure Legends 1-7 from Mutations in the DDR2 Kinase Gene Identify a Novel Therapeutic Target in Squamous Cell Lung Cancer

Magnetosomes represent biogenic, magnetic nanoparticles biosynthesized by magnetotactic bacteria. Subtle biological control on each step of biomineralization generates core–shell nanoparticles of high crystallinity, strong magnetization and uniform shape and size. These features make magnetosomes a promising alternative to chemically synthesized nanoparticles for many applications in the biotechnological and biomedical field, such as their usage as biosensors in medical diagnostics, as drug-delivery agents, or as contrast agents for magnetic imaging techniques. Thereby, the particles are directly applied to mammalian cells or even injected into the body. In the present work, we provide a comprehensive characterization of isolated magnetosomes as potential cytotoxic effects and particle uptake have not been well studied so far. Different cell lines including cancer cells and primary cells are incubated with increasing particle amounts, and effects on cell viability are investigated. Obtained data suggest a concentration-dependent biocompatibility of isolated magnetosomes for all tested cell lines. Furthermore, magnetosome accumulation in endolysosomal structures around the nuclei is observed. Proliferation rates are affected in the presence of increasing particle amounts; however, viability is not affected and doubling times can be restored by reducing the magnetosome concentration. In addition, we evidence magnetosome–cell interactions that are strong enough to allow for magnetic cell sorting. Overall, our study not only assesses the biocompatibility of isolated magnetosomes, but also evaluates effects on cell proliferation and the fate of internalized magnetosomes, thereby providing prerequisites for their future in vivo application as biomedical agents., Treatment of mammalian cells with isolated bacterial magnetosomes indicated biocompatibility. Upon incubation, particles are internalized and located in endolysosomes, thereby magnetizing the cells in amounts sufficient for magnetic separation.

Magnetic hybrid materials are a promising group of substances. Their interaction with matrices is challenging with regard to the underlying physical and chemical mechanisms. But thinking matrices as biological membranes or even structured cell layers they become interesting with regard to potential biomedical applications. Therefore, we established in vitro blood-organ barrier models to study the interaction and processing of superparamagnetic iron oxide nanoparticles (SPIONs) with these cellular structures in the presence of a magnetic field gradient. A one-cell-type–based blood-brain barrier model was used to investigate the attachment and uptake mechanisms of differentially charged magnetic hybrid materials. Inhibition of clathrin-dependent endocytosis and F-actin depolymerization led to a dramatic reduction of cellular uptake. Furthermore, the subsequent transportation of SPIONs through the barrier and the ability to detect these particles was of interest. Negatively charged SPIONs could be detected behind the barrier as well as in a reporter cell line. These observations could be confirmed with a two-cell-type–based blood-placenta barrier model. While positively charged SPIONs heavily interact with the apical cell layer, neutrally charged SPIONs showed a retarded interaction behavior. Behind the blood-placenta barrier, negatively charged SPIONs could be clearly detected. Finally, the transfer of the in vitro blood-placenta model in a microfluidic biochip allows the integration of shear stress into the system. Even without particle accumulation in a magnetic field gradient, the negatively charged SPIONs were detectable behind the barrier. In conclusion, in vitro blood-organ barrier models allow the broad investigation of magnetic hybrid materials with regard to biocompatibility, cell interaction, and transfer through cell layers on their way to biomedical application.

Magnetic nanoparticles (MNPs) are interesting for various applications in medicine. If administered to a biological system like the human body, a so-called biomolecule corona is formed on the surface of the particles, which highly determines the biological fate of the particles. To elucidate whether a preconditioning of the MNPs by incubation with biomolecules influences biocompatibility and bioavailability, the formation of such a corona was investigated in more detail. For this, the influence of particle characteristics, e.g., surface charge, as well as various incubation parameters on the resulting corona was investigated. It was found that the biomolecule corona is formed immediately after bringing together the particles with the biomolecule source. By variation of the biomolecule content of the incubation medium, the size of the corona can be modulated. Regarding the interaction of the nanoparticles with cells, it was shown that the presence of a biomolecule corona reduces the interaction and that a more pronounced biomolecule corona leads to a reduced uptake of the magnetic nanohybrids into the cells. Cell viability tests confirmed biocompatibility of the biomolecule-coated particles. A more pronounced corona promotes a higher cell viability. By using a shell-less hen’s egg model, no or reduced adverse effects of all biomolecule-coated MNP for this in vivo test were found. Resulting from these investigations, we were able to demonstrate that our newly developed nanohybrids significantly reduce in vivo toxicity compared to uncoated MNPs.

In chronic myelogenous leukemia (CML), treatment with tyrosine kinase inhibitors (TKI) is unable to eradicate leukemic stem cells (LSC). Polymethine dye-functionalized nanoparticles can be internalized by specific cell types using transmembrane carrier proteins. In this study we investigated the uptake behavior of various polymethine dyes on leukemia cell lines and searched for carrier proteins that guide dye transport using RNA interference. The results show that the uptake of DY-635 is dependent on organic anion transport protein 1B3 (OATP1B3) in CML cells and immature myeloid precursor cells of CML patients. In contrast to nonspecific poly(lactide-co-glycolic acid) (PLGA) nanoparticle constructs, DY-635-functionalization of nanoparticles led to an uptake in CML cells. Investigation of these nanoparticles on bone marrow of CML patients showed a preferred uptake in LSC. The transcription of OATP1B3 is known to be induced under hypoxic conditions via the hypoxia-inducing factor 1 alpha (HIF1α), thus also in the stem cells niche. Since these cells have the potential to repopulate the bone marrow after CML treatment discontinuation, eliminating them by means of drug-loaded DY-635-functionalized PLGA nanoparticles deployed as a selective delivery system to LSC is highly relevant to the ongoing search for curative treatment options for CML patients., Graphical Abstract, With the finding that DY-635-functionalized nanoparticles are taken up in vitro in an OATP1B3-dependent manner, Ernst et al. identified a possible drug delivery system for CML treatment. This would be an important advance, since TKIs are ineffective in CML stem cells, but their eradication is necessary for curative treatment.

In its recommendations for the protection of people living in long-term contaminated territories after a nuclear accident, the International Commission on Radiological Protection (ICRP) emphasizes the effectiveness of directly involving the affected population and local professionals in the management of the situation, and the responsibility of authorities at both national and local levels to create the conditions and provide the means favouring the involvement and empowerment of the population. In this perspective, ICRP initiated in the fall 2011 a dialogue between representatives of the Fukushima Prefecture, local professionals, local communities and representatives of Belarusian, Norwegian and French organisations to find ways to respond to the challenges of the long-term rehabilitation of the living conditions in the territories affected by the Fukushima nuclear power plant. After a first series of twelve “ICRP Dialogue” meetings between 2011 and 2015 closed by an international workshop, a group of local stakeholders took over and organized a new series of eight “Fukushima Dialogue” meetings between 2016 and 2018. The article gives an overview of the dialogue meetings initiated by ICRP in Japan after the Fukushima nuclear accident.

The excitation function for the $pd\rightarrow$ $d p \pi^{0}$ reaction has been measured by WASA-at-COSY experiment with the aim of searching for $^{3}\hspace{-0.03cm}\mbox{He}$-$\eta$ mesic nuclei. The measurement in the vicinity of $\eta$ meson production was performed using a ramped proton beam. The data analysis and interpretation was carried out with the assumption that the $\eta$-mesic Helium decays via the formation of an intermediate N$^{*}$(1535) resonance. No direct signal of the $\eta$-mesic nucleus is observed in the excitation function. We determine a new improved upper limit for the total cross section for the bound state production and decay in the $pd\rightarrow$ $(^{3}\hspace{-0.03cm}\mbox{He}$-$\eta)_{bound} \rightarrow$ $d p \pi^{0}$ process. It varies between 13 nb to 24 nb for the bound state with width in the range $\Gamma \in (5,50)$ MeV.

Phase shifts and inelasticity parameters for NN scattering in the partial-wave channels $${}^3S_1$$ – $${}^3D_1$$ and $${}^1S_0$$ at energies $$T_\mathrm{lab}$$ from zero to about 1 GeV are described within a unified NN potential model assuming the formation of isoscalar and isovector dibaryon resonances near the $$NN^*(1440)$$ threshold. Evidence for these near-threshold resonances is actually found in the recent WASA experiments on single- and double-pion production in NN collisions. There, the excitation of the Roper resonance $$N^*(1440)$$ exhibits a structure in the energy dependence of the total cross section which corresponds to the formation of dibaryon states with $$I(J^\pi )=0(1^+)$$ and $$1(0^+)$$ at the $$NN^*(1440)$$ threshold. These two S-wave dibaryon resonances may provide new insight into the nature of the strong NN interaction at low and intermediate energies.

Differential cross sections have been extracted from exclusive and kinematically complete high-statistics measurements of quasifree polarized np scattering performed in the energy region of the d*(2380) dibaryon resonance covering the range of beam energies Tn=0.98−1.29 GeV (s=2.32−2.44 GeV). The experiment was carried out with the WASA-at-COSY setup having a polarized deuteron beam impinged on the hydrogen pellet target and utilizing the quasifree process dp→np+pspectator. In this way the np differential cross section σ(Θ) was measured over a large angular range. The obtained angular distributions complement the corresponding analyzing power Ay(Θ) measurements published previously. A SAID partial-wave analysis incorporating the new data strengthens the finding of a resonance pole in the coupled D33-G33 waves.

To investigate whether the classic bystander effect is unique to humans, the effect of bystanders on rat helping was studied. In the presence of rats rendered incompetent to help through pharmacological treatment, rats were less likely to help due to a reduction in reinforcement rather than to a lack of initial interest. Only incompetent helpers of a strain familiar to the helper rat exerted a detrimental effect on helping; rats helped at near control levels in the presence of incompetent helpers from an unfamiliar strain. Duos and trios of potential helper rats helped at superadditive rates, demonstrating that rats act nonindependently with helping facilitated by the presence of competent-to-help bystanders. Furthermore, helping was facilitated in rats that had previously observed other rats' helping and were then tested individually. In sum, the influence of bystanders on helping behavior in rats features characteristics that closely resemble those observed in humans.

Cervical cancer (CC) arises from premalignant cervical intraepithelial neoplasia (CIN) induced by a persistent infection with human papillomaviruses. The multi-stepwise disease progression is driven by genetic and epigenetic alterations. Our previous studies demonstrated a clear downregulation of inter-α-trypsin-inhibitor-heavy chain 5 (ITIH5) at mRNA and protein levels in CC compared to CIN2/3 and normal cervical tissue. Initial in vitro functional analyses revealed a suppressive effect of ITIH5 on relevant mechanisms for cancer progression in conventional two dimensional (2D) cell culture model systems. Based on these studies, we aimed to investigate the functional relevance of ITIH5 in multicellular tumor spheroid (MCTS) models, which resemble in vivo tumors more closely. We successfully established CC cell line-derived MCTS using the hanging-drop technique. ITIH5 was ectopically overexpressed in HeLa and SiHa cells and its functional relevance was investigated under three dimensional (3D) culture conditions. We found that ITIH5 re-expression significantly suppressed tumor spheroid growth and spheroid invasiveness of both HeLa and SiHa spheroids. Immunohistochemical (IHC) analyses revealed a significant reduction in Ki-67 cell proliferation index and CAIX-positive areas indicative for hypoxia and acidification. Furthermore, we observed an increase in cPARP-positive cells suggesting a higher rate of apoptosis upon ITIH5 overexpression. An effect of ITIH5 expression on the susceptibility of cervical MCTS towards cytostatic drug treatment was not observed. Collectively, these data uncover pronounced anti-proliferative effects of ITIH5 under 3D cell culture conditions and provide further functional evidence that the downregulation of ITIH5 expression during cervical carcinogenesis could support cancer development.

It is demonstrated for the first time that the dibaryon resonance d ⁎ ( 2380 ) discovered reliably in the numerous experiments at the WASA@COSY facility (Julich FZ) determines almost completely (when supplemented with the peripheral one-pion exchange) NN scattering phase shifts and inelasticities in the coupled partial-wave channels D 3 3 – G 3 3 not only near the resonance position, but also in a broad energy range from zero up to about 1 GeV.

Hexaquarks constitute a natural extension of complex quark systems, just as tetra- and pentaquarks do. To this end, the current status of in both experiment and theory is reviewed. Recent high-precision measurements in the nucleon-nucleon channel and analyses thereof have established as an indisputable resonance in the long-sought dibaryon channel. Important features of this state are its narrow width and deep binding relative to the threshold. Its decay branchings favor theoretical calculations predicting a compact hexaquark nature of this state. We review the current status of experimental and theoretical studies on as well as new physics aspects it may bring in future. In addition, we review the situation at the and thresholds, where evidence for a number of resonances of presumably molecular nature has been found – similar to the situation in charmed and beauty sectors. Finally, we briefly discuss the situation of dibaryon searches in the flavored quark sectors.

The differential cross section for the 1H(d,pp)n breakup reaction at deuteron beam energy of 340 MeV has been measured with the use of the WASA detector at COSY-Jülich. The set of proton-proton coincidences registered at the Forward Detector has been analyzed on a dense grid of kinematic variables, giving in total around 5600 data points. The cross-section data are compared to theoretical predictions based on the state-of-the-art nucleon-nucleon potentials, combined with a three-nucleon force or the Coulomb interaction or carried out in a relativistic regime.

We report on the search for the rare decay η → π 0 e + e − which is of interest to study C violation in the electromagnetic interaction which would indicate contributions from physics beyond the Standard Model, since the allowed decay via a two-photon intermediate state is strongly suppressed. The experiment has been performed using the WASA-at-COSY installation, located at the COSY accelerator of the Forschungszentrum Julich, Germany. In total 3 × 10 7 events of the reaction p d → 3 He η have been recorded at an excess energy of Q = 59.8 MeV . Based on this data set the C parity violating decay η → π 0 γ ⁎ → π 0 e + e − via a single-photon intermediate state has been searched for, resulting in new upper limits of Γ ( η → π 0 e + e − ) / Γ ( η → π + π − π 0 ) 3.28 × 10 − 5 and Γ ( η → π 0 e + e − ) / Γ ( η → all ) 7.5 × 10 − 6 ( CL = 90 % ), respectively.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms., The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.

Polysaccharide (PS) based nanoparticles (NP) are of great interest for biomedical applications. A key challenge in this regard is the functionalization of these nanomaterials. The aim of the present work was the development of reactive PS-NP that can be coupled with an amino group containing compounds under mild aqueous conditions. A series of cellulose phenyl carbonates (CPC) and xylan phenyl carbonates (XPC) with variable degrees of substitution (DS) was obtained by homogeneous synthesis. The preparation of PS-NP by self-assembling of these hydrophobic derivatives was studied comprehensively. While CPC mostly formed macroscopic aggregates, XPC formed well-defined spherical NP with diameters around 100 to 200 nm that showed a pronounced long-term stability in water against both particle aggregation as well as cleavage of phenyl carbonate moieties. Using an amino group functionalized dye it was demonstrated that the novel XPC-NP are reactive towards amines. A simple coupling procedure was established that enables direct functionalization of the reactive NP in an aqueous dispersion. Finally, it was demonstrated that dye functionalized XPC-NP are non-cytotoxic and can be employed in advanced biomedical applications.

Fe7Pd3 structured thin films were synthesized using GLAD, motivated by the high potential of such structures in magnetically-controlled bioapplications. GLAD was carried out on prestructured gold templates to obtain Fe-Pd structures of several hundred nanometers in width by up to 1.5 μm in length, depending on template and growth parameters. The resulting polycrystalline microstructure was in the body centred cubic (bcc) phase with a composition near Fe7Pd3, determined by energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). Annealing at 900 °C resulted in the appearance of signatures of the face centred tetragonal (fct) martensitic phase within XRD measurements. Therefore, fct structures could be achieved if measures for structural preservation are taken, such as by ultra rapid annealing or lift-off before annealing. The cellular response to the structured films was investigated using human brain microvascular endothelial cells (HBMEC) and revealed consistent cell adhesion, morphologies and proliferation compared to control Fe-Pd and Si substrates. Only trace amounts of palladium and iron were released from the films into the growth medium during culture, regardless of the structures. Overall, this method is highly promising for the development of biocompatible, submicron structured films and shape-anisotropic ferromagnetic micro- and nanostructures, with applicability to a range of other alloys. Keywords: Glancing angle deposition (GLAD), Iron palladium alloy, Fe-Pd submicron structures, Magnetically-responsive material, Shape memory effect

The mechanistic target of rapamycin (mTOR), a protein kinase, is a central regulator of mammalian metabolism and physiology. Protein mTOR complex 1 (mTORC1) functions as a major sensor for the nutrient, energy, and redox state of a cell and is activated by ras homolog enriched in brain (RHEB1), a GTP-binding protein. Increased activation of mTORC1 pathway has been associated with developmental abnormalities, certain form of epilepsy (tuberous sclerosis), and cancer. Clinically, those mTOR-related disorders are treated with the mTOR inhibitor rapamycin and its rapalogs. Because the effects of chronic interference with mTOR signaling in the aged brain are yet unknown, we used a genetic strategy to interfere with mTORC1 signaling selectively by introducing mutations of Rheb1 into the mouse. We created conventional knockout (Rheb1 +/- ) and gene trap (Rheb1 Δ/+ ) mutant mouse lines. Rheb1-insufficient mice with different combinations of mutant alleles were monitored over a time span of 2 years. The mice did not show any behavioral/neurological changes during the first 18 months of age. However, after aging (> 18 months of age), both the Rheb1 +/- and Rheb1 Δ /- hybrid males developed rare stress-induced seizures, whereas Rheb1 +/- and Rheb1 Δ /- females and Rheb1 Δ/+ and Rheb1 Δ/Δ mice of both genders did not show any abnormality. Our findings suggest that chronic intervention with mTORC1 signaling in the aged brain might be associated with major adverse events.

1. Introduction With its proven ability to reduce size (form factor) and save energy (high efficiency) Gallium Nitride (GaN) is now no longer a nice to have, it is a must-have for power conversion. In applications ranging from sub 100 watt to multi kilowatt highly efficient power converters and inverters, GaN HEMTs high switching speed and low efficiency make it a natural choice of Silicon based devices reaching their physical limits of performance. Transphorm has already commercialized JEDEC qualified GaN HEMT power switches manufactured in an automotive grade 6 inch Si CMOS fab [1]. With this strong base and its ability to reduce size, weight and improve miles per gallon, GaN HEMTs are now increasingly being investigated for EV & HEV applications such as on board chargers and other auxiliary power conversion within the automobile under 10 kW. We will review the first ever Automotive (AEC Q101) Qualification for GaN and also discuss results for highly stressed robustness tests, FIT rates & lifetime testing. 2. GaN Products and Qualification Normally off GaN devices (Fig. 1) are achieve through integration of a low voltage Si-MOSFET input device with a high voltage depletion mode GaN device offering the best combination of input gate interface and the most robust high voltage GaN platform [2]. Electrical characteristics of the normally-off GaN power switch are summarized in Table 1 with a Low Rds(on), low gate charge (Qg) and low capacitance (Coss) that enable high efficiency, small form factor power systems. The Ron *Qg or Ron * Coss figure of merit is already better than mature Silicon Superjunction MOSFETs and achieved simultaneously with superior reliability performance. We have successfully passed (on multiple products and generations) the full suite of JEDEC qualification tests [3], as shown in Table 2. 3. Robustness, Long Term Reliability and Lifetime of High Voltage GaN To further establish confidence in long term reliability and operation in the field with low FIT rates, we have extended JEDEC qualification to 3-5x the stresses, for e.g. 5,000 hours of HTRB (5x JEDEC stress) with no degradation in resistance, threshold or leakage (Fig 3). Systematic high voltage off-stage (HVOS) acceleration at over 1100 volts was done to determine intrinsic lifetime (MTTF) of over 100 Million hours and 1% failure of more than 1M hours (Fig 5). Similarly through accelerated high temperature on-state testing of GaN, a high temperature MTTF of over 100 Million hours at 175C was determined. Recently, in March 2017, we completed the first ever successful AEC-Q101 standard qualification of GaN products [4]. These will be discussed in detail at the conference. 4. GaN Products and Qualification The comprehensive suite of data and results with a 3 year manufacturing history on over 3,000 wafers in a high volume commercial 6-inch Wafer fabrication facility unequivocally demonstrate that GaN power switches are now reliable and ready for a wide array of consumer & communication, industrial & renewable energy as well as automotive applications. The next milestones which are now happening include announcement of a variety of end system products (Titanium rated data server power supplies, PV Inverters, Telecom power supplies and Servo motor drives), paving the way for an exciting era in highest efficiency, highest reliability power conversion with GaN. 5. References P. Parikh, et. al., “Commercialization of 600V GaN HEMTs,” 2014 SSDM, Tsukuba, Sep., 2014. Power GaN Devices- Materials, Applications and Reliability, Edited by M. Meneghini et. al., Springer International Publishing, 2017. T. Kikkawa, et al. 600 V JEDEC-Qualified Highly Reliable GaN HEMTs on Si Substrates,” IEEE IEDM, San Francisco, Dec. 2014. APEC 2017, http://www.transphormusa.com/news/transphorm-announces-first-automotive-qualified-gan-fets/ Figure 1

A set of biomedically relevant iron oxide nanoparticles with systematically modified polymer surfaces was investigated regarding their interaction with the first contact partners after systemic administration such as blood cells, blood proteins, and the endothelial blood vessels, to establish structure-activity relationships. All nanoparticles were intensively characterized regarding their physicochemical parameters. Cyto- and hemocompatibility tests showed that (1) the properties of the core material itself were not relevant in short-term incubation studies, and (2) toxicities increased with higher polymer mass, neutral = anionic