INMdok (Leibniz Institute for New Materials)
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Phase diagram studies for the growth of (Mg,Zr):SrGa12O19 crystals
Get PDFBy differential thermal analysis, a concentration field suitable for the growth of Zr, Mg co-doped strontium hexagallate crystals was observed that corresponds well with known experimental results. It was shown that the melting point of doped crystal is ca. 60 K higher than that of undoped crystals. This higher melting points indicate hexagallate phase stabilization by Zr, Mg co-doping and increase the growth window of (Mg,Zr):SrGa12O19, compared to undoped SrGa12O19 that grows from SrO–Ga2O3 melts
Towards hybrid one-pot/one-electrode Pd-NPs-based nanoreactors for modular biocatalysis
Get PDFHere, fundamental aspects affecting template-assisted engineering of oxidase-associated peroxide oxidation co-catalysis of the modeled microanalytical system based on the hybrid palladium nanoparticles (Pd-NPs) with tailored functional properties were studied. By an accurate tuning and validation of the experimental setup, a modular Pd-NPs-doped one-pot/one-electrode amperometric nanobiosensor for advanced multiplex analyte detection was constructed. The specific operational conditions (electrochemical read-out mode, pH, regeneration procedure) of the modular one-pot/one-electrode nanobiosensor allowed a reliable sensing of L-lactate (with linear dynamic range, LDR=500 µM – 2 mM, R2 =0.977), D-glucose (with LDR=200 µM – 50 mM, R2 =0.987), hydrogen peroxide (with LDR=20 µM – 100 mM, R2 =0.998) and glutaraldehyde (with LDR=1 – 100 mM, R2 =0.971). In addition, mechanistic aspects influencing the performance of Pd-NPs-doped one-pot/one-electrode for multiplex analyte sensing were studied in detail. The designed one-pot/one-electrode amperometric nanobiosensor showed a thin layer electrochemical behavior that greatly enhanced electron transfer between the functional hybrid layer and the electrode. Finally, a specific regeneration procedure of the hybrid one-pot/one-electrode and algorithm towards its usage for modular biocatalysis were developed. The reported strategy can readily be considered as a guideline towards the fabrication of commercialized nanobiosensors with tailored properties for advanced modular biocatalysis
High Glucose Enhances Cytotoxic T Lymphocyte-Mediated Cytotoxicity
Get PDFCytotoxic T lymphocytes (CTLs) are key players to eliminate tumorigenic or pathogen-infected cells using lytic granules (LG) and Fas ligand (FasL) pathways. Depletion of glucose leads to severely impaired cytotoxic function of CTLs. However, the impact of excessive glucose on CTL functions still remains largely unknown. Here we used primary human CD8(+) T cells, which were stimulated by CD3/CD28 beads and cultured in medium either containing high glucose (HG, 25 mM) or normal glucose (NG, 5.6 mM). We found that in HG-CTLs, glucose uptake and glycolysis were enhanced, whereas proliferation remained unaltered. Furthermore, CTLs cultured in HG exhibited an enhanced CTL killing efficiency compared to their counterparts in NG. Unexpectedly, expression of cytotoxic proteins (perforin, granzyme A, granzyme B and FasL), LG release, cytokine/cytotoxic protein release and CTL migration remained unchanged in HG-cultured CTLs. Interestingly, additional extracellular Ca2+ diminished HG-enhanced CTL killing function. Our findings suggest that in an environment with excessive glucose, CTLs could eliminate target cells more efficiently, at least for a certain period of time, in a Ca2+-dependent manner
Rings and Chains: Synthesis and Characterization of Polyferrocenylmethylene
Get PDFThe synthesis and characterization of polyferrocenylmethylene (PFM) starting from dilithium 2,2-bis(cyclopentadienide)propane and a Me2C[1]magnesocenophane is reported. Molecular weights of up to Mw = 11 700 g mol–1 featuring a dispersity, Ð, of 1.40 can be achieved. The material is studied by different methods comprising nuclear magnetic resonance (NMR) spectroscopy, matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) mass spectrometry, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) measurements elucidating the molecular structure and thermal properties of these novel polymers. Moreover, cyclic voltammetry (CV) reveals quasi-reversible oxidation and reduction behavior and communication between the iron centers. Also, the crystal structure of a related cyclic hexamer is presented
Colloidal Analysis of Particles Extracted from Microalloyed Steels
Get PDFDifferent colloidal particle characterization methods are examined for their suitability to determine the particle size distribution of particles extracted from steels. Microalloyed steels are dissolved to extract niobium and titanium carbonitride particles that are important for the mechanical properties of these steels. Such particles have sizes ranging from several nanometers to hundreds of nanometers depending on the precipitation stage during the thermomechanically controlled rolling process. The size distribution of the particles is analyzed by dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and hollow fiber flow field-flow fractionation (HF5) and compared to data obtained for reference particles as well as data from electron microscopy, the standard sizing technique used in metallurgy today. AUC and HF5 provide high-quality size distributions, average over large particle numbers that enables statistical analysis, and yield useful insights for alloy design; however, DLS fails due to a lack of resolution. Important aspects in the conversion and comparison of size distributions obtained for broadly distributed particle systems with different measurement principles and the role of surfactants used in sample preparation are discussed
Quantification of EGFR-HER2 Heterodimers in HER2-Overexpressing Breast Cancer Cells Using Liquid-Phase Electron Microscopy
Get PDFCurrently, breast cancer patients are classified uniquely according to the expression level of hormone receptors, and human epidermal growth factor receptor 2 (HER2). This coarse classification is insufficient to capture the phenotypic complexity and heterogeneity of the disease. A methodology was developed for absolute quantification of receptor surface density ρR, and molecular interaction (dimerization), as well as the associated heterogeneities, of HER2 and its family member, the epidermal growth factor receptor (EGFR) in the plasma membrane of HER2 overexpressing breast cancer cells. Quantitative, correlative light microscopy (LM) and liquid-phase electron microscopy (LPEM) were combined with quantum dot (QD) labeling. Single-molecule position data of receptors were obtained from scanning transmission electron microscopy (STEM) images of intact cancer cells. Over 280,000 receptor positions were detected and statistically analyzed. An important finding was the subcellular heterogeneity in heterodimer shares with respect to plasma membrane regions with different dynamic properties. Deriving quantitative information about EGFR and HER2 ρR, as well as their dimer percentages, and the heterogeneities thereof, in single cancer cells, is potentially relevant for early identification of patients with HER2 overexpressing tumors comprising an enhanced share of EGFR dimers, likely increasing the risk for drug resistance, and thus requiring additional targeted therapeutic strategies
Light-Regulated Angiogenesis via a Phototriggerable VEGF Peptidomimetic
Get PDFThe application of growth factor based therapies in regenerative medicine is limited by the high cost, fast degradation kinetics, and the multiple functions of these molecules in the cell, which requires regulated delivery to minimize side effects. Here a photoactivatable peptidomimetic of the vascular endothelial growth factor (VEGF) that allows the light-controlled presentation of angiogenic signals to endothelial cells embedded in hydrogel matrices is presented. A photoresponsive analog of the 15-mer peptidomimetic Ac-KLTWQELYQLKYKGI-NH2 (abbreviated PQK) is prepared by introducing a 3-(4,5-dimethoxy-2-nitrophenyl)-2-butyl (DMNPB) photoremovable protecting group at the Trp4 residue. This modification inhibits the angiogenic potential of the peptide temporally. Light exposure of PQK modified hydrogels provide instructive cues to embedded endothelial cells and promote angiogenesis at the illuminated sites of the 3D culture, with the possibility of spatial control. PQK modified photoresponsive biomaterials offer an attractive approach for the dosed delivery and spatial control of pro-angiogenic factors to support regulated vascular growth by just using light as an external trigger
Perspective on statistical effects in the adhesion of micropatterned surfaces
Get PDFBioinspired micropatterned adhesives have attracted extensive research interest in the past two decades. In modeling the performance of these adhesives, the common assumption has been that the adhesive strength of each sub-contact is identical. Recent experiments, however, have shown that interfacial defects of different characters lead to a distribution of the adhesive strength within a fibrillar array. Based on experimental observations of detachment events, a statistical model for the distribution of the local adhesive strength and the resulting performance of a micropatterned adhesive are presented. This approach constitutes a paradigm shift, providing better understanding of micropatterned adhesives under real conditions. Examples presented include the prediction of unstable detachments in compliant systems. Future directions are discussed, including the extension of the statistical approach to non-uniform loading and rate-dependent effects, the contribution of suction to adhesion and aging of contacts over specific time periods, as well as the necessity for a more in-depth understanding of defect formation considering surface roughness and other imperfections in the system
A New PqsR Inverse Agonist Potentiates Tobramycin Efficacy to Eradicate Pseudomonas aeruginosa Biofilms
Get PDFPseudomonas aeruginosa (PA) infections can be notoriously difficult to treat and are often accompanied by the development of antimicrobial resistance (AMR). Quorum sensing inhibitors (QSI) acting on PqsR (MvfR) – a crucial transcriptional regulator serving major functions in PA virulence – can enhance antibiotic efficacy and eventually prevent the AMR. An integrated drug discovery campaign including design, medicinal chemistry-driven hit-to-lead optimization and in-depth biological profiling of a new QSI generation is reported. The QSI possess excellent activity in inhibiting pyocyanin production and PqsR reporter-gene with IC50 values as low as 200 and 11 × 10−9 m, respectively. Drug metabolism and pharmacokinetics (DMPK) as well as safety pharmacology studies especially highlight the promising translational properties of the lead QSI for pulmonary applications. Moreover, target engagement of the lead QSI is shown in a PA mucoid lung infection mouse model. Beyond that, a significant synergistic effect of a QSI-tobramycin (Tob) combination against PA biofilms using a tailor-made squalene-derived nanoparticle (NP) formulation, which enhance the minimum biofilm eradicating concentration (MBEC) of Tob more than 32-fold is demonstrated. The novel lead QSI and the accompanying NP formulation highlight the potential of adjunctive pathoblocker-mediated therapy against PA infections opening up avenues for preclinical development
Light-sheet scattering microscopy to visualize long-term interactions between cells and extracellular matrix
Get PDFVisualizing interactions between cells and the extracellular matrix (ECM) mesh is important to understand cell behavior and regulatory mechanisms by the extracellular environment. However, long term visualization of three-dimensional (3D) matrix structures remains challenging mainly due to photobleaching or blind spots perpendicular to the imaging plane. Here, we combine label-free light-sheet scattering microcopy (LSSM) and fluorescence microscopy to solve these problems. We verified that LSSM can reliably visualize structures of collagen matrices from different origin including bovine, human and rat tail. The quality and intensity of collagen structure images acquired by LSSM did not decline with time. LSSM offers abundant wavelength choice to visualize matrix structures, maximizing combination possibilities with fluorescently-labelled cells, allowing visualizing of long-term ECM-cell interactions in 3D. Interestingly, we observed ultrathin thread-like structures between cells and matrix using LSSM, which were not observed by normal fluorescence microscopy. Transient local alignment of matrix by cell-applied forces can be observed. In summary, LSSM provides a powerful and robust approach to investigate the complex interplay between cells and ECM.Competing Interest StatementThe authors have declared no competing interest