Patterning of Nanoparticle‐Based Aerogels and Xerogels by Inkjet Printing

Nanoparticle‐based voluminous 3D networks with low densities are a unique class of materials and are commonly known as aerogels. Due to the high surface‐to‐volume ratio, aerogels and xerogels might be suitable materials for applications in different fields, e.g. photocatalysis, catalysis, or sensing. One major difficulty in the handling of nanoparticle‐based aerogels and xerogels is the defined patterning of these structures on different substrates and surfaces. The automated manufacturing of nanoparticle‐based aerogel‐ or xerogel‐coated electrodes can easily be realized via inkjet printing. The main focus of this work is the implementation of the standard nanoparticle‐based gelation process in a commercial inkjet printing system. By simultaneously printing semiconductor nanoparticles and a destabilization agent, a 3D network on a conducting and transparent surface is obtained. First spectro‐electrochemical measurements are recorded to investigate the charge–carrier mobility within these 3D semiconductor‐based xerogel networks.     

Insights into the In Vitro Formation of Apatite from Mg-Stabilized Amorphous Calcium Carbonate

A protein-free formation of bone-like apatite from amorphous precursors through ball-milling is reported. Mg²⁺ ions are crucial to achieve full amorphization of CaCO₃. Mg²⁺ incorporation generates defects which strongly retard a recrystallization of ball-milled Mg-doped amorphous calcium carbonate (BM-aMCC), which promotes the growth of osteoblastic and endothelial cells in simulated body fluid and has no effect on endothelial cell gene expression. Ex situ snapshots of the processes revealed the reaction mechanisms. For low Mg contents (<30%) a two phase system consisting of Mg-doped amorphous calcium carbonate (ACC) and calcite “impurities” was formed. For high (>40%) Mg²⁺ contents, BM-aMCC follows a different crystallization path via magnesian calcite and monohydrocalcite to aragonite. While pure ACC crystallizes rapidly to calcite in aqueous media, Mg-doped ACC forms in the presence of phosphate ions bone-like hydroxycarbonate apatite (dahllite), a carbonate apatite with carbonate substitution in both type A (OH⁻) and type B (PO₄³⁻) sites, which grows on calcite “impurities” via heterogeneous nucleation. This process produces an endotoxin-free material and makes BM-aMCC an excellent “ion storage buffer” that promotes cell growth by stimulating cell viability and metabolism with promising applications in the treatment of bone defects and bone degenerative diseases.     

Metal–Ligand Based Mechanophores Enhance Both Mechanical Robustness and Electronic Performance of Polymer Semiconductors

The backbone of diketopyrrolopyrrole-thiophene-vinylene-thiophene-based polymer semiconductors (PSCs) is modified with pyridine (Py) or bipyridine ligands to complex Fe(II) metal centers, allowing the metal–ligand complexes to act as mechanophores and dynamically crosslink the polymer chains. Mono- and bi-dentate ligands are observed to exhibit different degrees of bond strengths, which subsequently affect the mechanical properties of these Wolf-type-II metallopolymers. The counter ion also plays a crucial role, as it is observed that Py-Fe mechanophores with non-coordinating BPh₄^– counter ions (Py-FeB) exhibit better thin film ductility with lower elastic modulus, as compared to the coordinating chloro ligands (Py-FeC). Interestingly, besides mechanical robustness, the electrical charge carrier mobility can also be enhanced concurrently when incorporating Py-FeB mechanophores in PSCs. This is a unique observation among stretchable PSCs, especially that most reports to date describe a decreased mobility when the stretchability is improved. Next, it is determined that improvements to both mobility and stretchability are correlated to the solid-state molecular ordering and dynamics of coordination bonds under strain, as elucidated via techniques of grazing-incidence X-ray diffraction and X-ray absorption spectroscopy techniques, respectively. This study provides a viable approach to enhance both the mechanical and the electronic performance of polymer-based soft devices.     

DNA Primer Extension with Cyclopropenylated 7‐Deaza‐2′‐deoxyadenosine and Efficient Bioorthogonal Labeling in Vitro and in Living Cells

A deoxyadenosine triphosphate (dATP) analogue for DNA labeling was synthesized with the 1‐methylcyclopropene (1MCP) group at the 7‐position of 7‐deaza‐2′‐deoxyadenosine and applied for primer extension experiments. The real‐time kinetic data reveals that this 1MCP‐modified dATP analogue is incorporated into DNA much faster than that of the similarly 1MCP‐modified deoxyuridine triphosphate (dUTP) analogue. The postsynthetic fluorescent labeling of these oligonucleotides works efficiently according to PAGE analysis, and can be applied for immobilization of a functional antibody on a surface. Site‐specific labeling at two different positions in DNA was achieved and the bioorthogonality of the postsynthetic fluorescent labeling was demonstrated in living HeLa cells.     

Thermal Stress Assessment for Transient Liquid-Phase Bonded Si Chips in High-Power Modules Using Experimental and Numerical Methods

The potential of transient liquid-phase (TLP) bonding for chip packaging applications has been evaluated, focusing on three interlayer arrangements (Ag-Sn-Ag, Ni-Sn-Ni, and Ag-Sn-Ni). Shear tests on TLP-bonded components provided the interlayer-dependent mechanical strength as well as failure mode and position. Critical local stresses, i.e., failure criteria, within the intermetallic compound (IMC) layer were derived by replicating the shear test conditions with finite-element methods. The missing coefficient of thermal expansion for Ag₃Sn IMC was obtained by producing small IMC bulk samples and subjecting them to dilatometric measurements. The experimental results were implemented into a finite-element model of a representative power module architecture to provide first predictions on thermally induced residual stresses that could be classified into fail/safe, as successfully validated by TLP chip bonding experiments. A numerical parameter study then assessed thermal stresses, including failure prediction and design optimization for TLP-bonded Si chips, considering the influence of process temperature, service conditions, TLP interlayer system, and metallization layers within the TLP joint. The presented procedure serves as a guideline to choose an appropriate TLP interlayer system for predefined boundary conditions, or vice versa.     

Human CD22-Transgenic,Primary Murine Lymphoma Challenges Immunotherapies in Organ-Specific Tumor Microenvironments

Targeted immunotherapies have greatly changed treatment of patients with B cell malignancies. To further enhance immunotherapies, research increasingly focuses on the tumor microenvironment (TME), which differs considerably by organ site. However, immunocompetent mouse models of disease to study immunotherapies targeting human molecules within organ-specific TME are surprisingly rare. We developed a myc-driven, primary murine lymphoma model expressing a human-mouse chimeric CD22 (h/mCD22). Stable engraftment of three distinct h/mCD22⁺ lymphoma was established after subcutaneous and systemic injection. However, only systemic lymphoma showed immune infiltration that reflected human disease. In this model, myeloid cells supported lymphoma growth and showed a phenotype of myeloid-derived suppressor cells. The human CD22-targeted immunotoxin Moxetumomab was highly active against h/mCD22⁺ lymphoma and similarly reduced infiltration of bone marrow and spleen of all three models up to 90-fold while efficacy against lymphoma in lymph nodes varied substantially, highlighting relevance of organ-specific TME. As in human aggressive lymphoma, anti-PD-L1 as monotherapy was not efficient. However, anti-PD-L1 enhanced efficacy of Moxetumomab suggesting potential for future clinical application. The novel model system of h/mCD22⁺ lymphoma provides a unique platform to test targeted immunotherapies and may be amenable for other human B cell targets such as CD19 and CD20.     

Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML

This study aimed to characterize different natural killer (NK) cell phenotypes on bone marrow and peripheral blood cells from acute myeloid leukemia (AML) patients and healthy donors (HDs). Our data show that CD56^dimCD16⁻ and CD56^brightCD16⁻ NK cells represent the predominant NK cell subpopulations in AML, while the CD56^dimCD16⁺ NK cells are significantly reduced compared to HDs. Moreover, TIGIT⁺ and PVRIG⁺ cells cluster on the CD56^dimCD16⁺ subset whereas CD39⁺ and CD38⁺ cells do so on CD56^brightCD16⁻ NK cells in AML. Furthermore, functional effects of (co-)blockade of TIGIT and CD39 or A2AR on NK cell functionality were analyzed. These experiments revealed that the single blockade of the TIGIT receptor results in an increased NK-92 cell-mediated killing of AML cells in vitro. Combined targeting of CD39 or A2AR significantly augments the anti-TIGIT-mediated lysis of AML cells. Our data indicate that distinct NK cell subsets in AML exhibit different immunosuppressive patterns (via the TIGIT/PVRIG receptors and the purinergic pathway). In summary, we conclude that TIGIT, CD39, and A2AR constitute relevant inhibitory checkpoints of NK cells in AML patients. A combinatorial blockade synergistically strengthens NK-92 cell-mediated cytotoxicity. As inhibitors of TIGIT, CD39, and A2AR are clinically available, studies on their combined use could be conducted in the near future.     

Heptaplex real-time PCR for the identification and quantification of DNA from beef,pork, chicken,turkey, horse meat,sheep (mutton) and goat

Meat products are often composed of meat from several species. Due to fraud or incorrect manufacturing processes, different proportions of unexpected or undeclared meat may be incorporated. Pork, beef, chicken, turkey, horse meat, sheep (mutton) and goat are the most common types of meat in these products. To measure the fractional proportion of each of the seven meat types simultaneously, a quantitative multiplex PCR has been developed. This system has proven its applicability in the examination of meat compounds with fractional proportions between 2 and 100%. The uncertainty was 32% or better. In a single analytical step, the multiplex PCR identifies and in certain cases quantifies the most probable species of composed meat products. Additionally, this study illustrates that by using dyes with different wavelength shifts, more targets can be distinguished than channels provided for by the Rotorgene 6000^® thermocycler.