Upconversion nanocrystal doped polymer fiber thermometer

In recent years, lanthanide-doped nanothermometers have been mainly used in thin films or dispersed in organic solvents. However, both approaches have disadvantages such as the short interaction lengths of the active material with the pump beam or complicated handling, which can directly affect the achievable temperature resolution. We investigated the usability of a polymer fiber doped with upconversion nanocrystals as a thermometer. The fiber was excited with a wavelength stabilized diode laser at a wavelength of 976 nm. Emission spectra were recorded in a temperature range from 10 to 35◦C and the thermal emission changes were measured. Additionally, the pump power was varied to study the effect of self-induced heating on the thermometer specifications. Our fiber sensor shows a maximal thermal sensitivity of 1.45%/K and the minimal thermal resolution is below 20 mK. These results demonstrate that polymer fibers doped with nanocrystals constitute an attractive alternative to conventional fluorescence thermometers, as they add a long pump interaction length while also being insensitive to strong electrical fields or inert to bio-chemical environments. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Vitamin D Enhances Immune Effector Pathways of NK Cells Thus Providing a Mechanistic Explanation for the Increased Effectiveness of Therapeutic Monoclonal Antibodies

Patients with diffuse large cell lymphoma who have an adequate vitamin D supply derive significantly more benefit from immuno-chemotherapy with rituximab than patients with vitamin D deficiency; this is especially true for female patients. We have already been able to show that vitamin D increases the antibody-dependent cytotoxicity (ADCC) of NK cells in a sex-dependent manner, but it is unclear how vitamin D makes NK cells more efficient. Methods: Healthy individuals with vitamin D deficiency were supplemented with vitamin D to sufficient levels. NK cells were isolated from blood samples before and after vitamin D saturation. For transcriptome analysis, we used the Affymetrix Gene-Chip 2.0™. Gene expression analysis as well as supervised and unsupervised pathway analysis were performed. Results: Among others the “NK cell-associated cytotoxicity pathway” increased after vitamin D substitution. Five IFN-α subtypes (2, 4, 6, 7 and 10) and IFN-κ were more highly expressed and are mainly responsible in these pathways. In contrast, the pathway “interferon-gamma response”, as well as other sets in cytokine production and chemotaxis showed a reduction. Toll-like receptor genes (TLR-8, TLR-7, TLR-2) were downregulated and, therefore, are responsible for the decline of these pathways. The same could be shown for the “ubiquitin-ligase” pathway. Conclusions: Increased expression of several IFN-α subtypes may explain the increased ADCC of NK cells in vitamin D-replenished and otherwise healthy subjects. Other regulators of interferon production and ADCC are compensatory upregulated in compensation, such as Toll-like receptors and those of the ubiquitin ligase, and normalize after vitamin D substitution

Design of Review Systems – A Strategic Instrument to shape Online Reviewing Behavior and Economic Outcomes

As online reviews play a decisive role in consumers’ purchase decisions, e-commerce platforms are using review systems strategically to obtain a competitive advantage. However, the strategic potential can only be leveraged if the review system is designed appropriately. Research on the design of review systems and the effects of design choices has not yet been summarized or synthesized in a review article. We aim to close this gap by providing a scoping review. In our synthesis we posit that the design of review systems moderates the impact of online reviews on economic outcomes and the factors that drive the formation of reviews. After reviewing current research findings, we identify gaps and provide a research agenda covering three key themes: Design features, environments, and devices

Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5~months), DMG-H3 (median OS: 13~months) and HAP (median OS: 8~months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5~months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time

Towards highly efficient polymer fiber laser sources for integrated photonic sensors

Lab-on-a-Chip (LoC) devices combining microfluidic analyte provision with integrated optical analysis are highly desirable for several applications in biological or medical sciences. While the microfluidic approach is already broadly addressed, some work needs to be done regarding the integrated optics, especially provision of highly integrable laser sources. Polymer optical fiber (POF) lasers represent an alignment-free, rugged, and flexible technology platform. Additionally, POFs are intrinsically compatible to polymer microfluidic devices. Home-made Rhodamine B (RB)-doped POFs were characterized with experimental and numerical parameter studies on their lasing potential. High output energies of 1.65 mJ, high slope efficiencies of 56%, and 50%-lifetimes of ≥900 k shots were extracted from RB:POFs. Furthermore, RB:POFs show broad spectral tunability over several tens of nanometers. A route to optimize polymer fiber lasers is revealed, providing functionality for a broad range of LoC devices. Spectral tunability, high efficiencies, and output energies enable a broad field of LoC applications. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Characterization of an HLA-restricted and human cytomegalovirus-specific antibody repertoire with therapeutic potential

With an infection rate of 60–90%, the human cytomegalovirus (HCMV) is very common among adults but normally causes no symptoms. When T cell-mediated immunity is compromised, HCMV reactivation can lead to increased morbidity and mortality. HCMV antigens are processed and presented as peptides on the cell surface via HLA I complexes to the T cell receptor (TCR) of T cells. The generation of antibodies against HCMV peptides presented on HLA complexes (TCR-like antibodies) has been described, but is without therapeutic applications to date due to the polygenic and polymorphic nature of HLA genes. We set out to obtain antibodies specific for HLA/HCMV-peptides, covering the majority of HLA alleles present in European populations. Using phage display technology, we selected 10 Fabs, able to bind to HCMV-peptides presented in the 6 different HLA class I alleles A*0101, A*0201, A*2402, B*0702, B*0801 and B*3501. We demonstrate specific binding of all selected Fabs to HLA-typed lymphoblastoid cell lines (EBV-transformed B cells) and lymphocytes loaded with HCMV-peptides. After infection with HCMV, 4/10 tetramerized Fabs restricted to the alleles HLA-A*0101, HLA-A*0201 and HLA-B*0702 showed binding to infected primary fibroblasts. When linked to the pseudomonas exotoxin A, these Fab antibodies induce highly specific cytotoxicity in HLA matched cell lines loaded with HCMV peptides. TCR-like antibody repertoires therefore represent a promising new treatment modality for viral infections and may also have applications in the treatment of cancers

Decreased demand for olfactory periglomerular cells impacts on neural precursor cell viability in the rostral migratory stream

The subventricular zone (SVZ) provides a constant supply of new neurons to the olfactory bulb (OB). Different studies have investigated the role of olfactory sensory input to neural precursor cell (NPC) turnover in the SVZ but it was not addressed if a reduced demand specifically for periglomerular neurons impacts on NPC-traits in the rostral migratory stream (RMS). We here report that membrane type-1 matrix metalloproteinase (MT1-MMP) deficient mice have reduced complexity of the nasal turbinates, decreased sensory innervation of the OB, reduced numbers of olfactory glomeruli and reduced OB-size without alterations in SVZ neurogenesis. Large parts of the RMS were fully preserved in MT1-MMP-deficient mice, but we detected an increase in cell death-levels and a decrease in SVZ-derived neuroblasts in the distal RMS, as compared to controls. BrdU-tracking experiments showed that homing of NPCs specifically to the glomerular layer was reduced in MT1-MMP-deficient mice in contrast to controls while numbers of tracked cells remained equal in other OB-layers throughout all experimental groups. Altogether, our data show the demand for olfactory interneurons in the glomerular layer modulates cell turnover in the RMS, but has no impact on subventricular neurogenesis