Glass powder doping of nanocrystal-doped fibres: challenges and results

Incorporating new optical materials as nanocrystals into glass fibres for new functionalities has recently become a hot research topic. Our team (funded by the European FET Open project NCLAS) investigates the introduction of nanoscale laser crystallites into the core of optical fibres using the glass powder doping method. Active Y2O3:Pr3+ nanocrystals (NCs) were prepared via different synthesis methods, and structurally and spectroscopically characterized. After modification of technological parameters, the optimised NCs have been proposed as a luminescence centres to embed into germanate and silicate glass hosts. Glasses were analysed in terms of optical (transmission, refractive index matching to NCs) and thermal (thermal stability, viscosity, thermal expansion coefficient) parameters. Crystallisation issues during fibre drawing were particularly investigated. In a first step, glass powder-NCs mixing techniques and fibre preform preparation were developed. It was shown that temperature cycle profiles including dwell time and heating/cooling ramp rates influenced the glass-NCs properties and can lead to glass crystallisation or NCs dissolution. The sintering investigations pointed out the melting temperature limits to preserve active NCs in the glasses. In germanate glasses, Y2O3:Pr3+ dissolution was noticed at 800°C. In the case of the silicate glass compositions these regions vary from 700°C to 1050°C. The results allowed to select optical fibre drawing conditions performed by the powder-in-tube method. Their distribution uniformity is not yet sufficient, requiring further optimisation of the drawing kinetics.The research project funded by the European FET Open project NCLas: NanoCrystals in Fibre Lasers, Grant agreement number: 82916

Structure and luminescence properties of transparent germanate glassceramics co-doped with Ni2+/Er3+ for near-infrared optical fiber application

An investigation of the structural and luminescent properties of the transparent germanate glass-ceramics co-doped with Ni2+/Er3+ for near-infrared optical fiber applications was presented. Modification of germanate glasses with 10–20 ZnO (mol.%) was focused to propose the additional heat treatment process controlled at 650 C to obtain transparent glass-ceramics. The formation of 11 nm ZnGa2O4 nanocrystals was confirmed by the X-ray diffraction (XRD) method. It followed the glass network changes analyzed in detail (MIR—Mid Infrared spectroscopy) with an increasing heating time of precursor glass. The broadband 1000–1650 nm luminescence ( exc = 808 nm) was obtained as a result of Ni2+: 3T2(3F) ! 3A2(3F) octahedral Ni2+ ions and Er3+: 4I13/2 ! 4I15/2 radiative transitions and energy transfer from Ni2+ to Er3+ with the efficiency of 19%. Elaborated glass–nanocrystalline material is a very promising candidate for use as a core of broadband luminescence optical fibers

Investigation of the TeO2/GeO2 Ratio on the Spectroscopic Properties of Eu3+-Doped Oxide Glasses for Optical Fiber Application

This study presented an analysis of the TeO2/GeO2 molar ratio in an oxide glass system. A family of melt-quenched glasses with the range of 0–35 mol% of GeO2 has been characterized by using DSC, Raman, MIR, refractive index, PLE, PL spectra, and time-resolved spectral measurements. The increase in the content of germanium oxide caused an increase in the transition temperature but a decrease in the refractive index. The photoluminescence spectra of europium ions were examined under the excitation of 465 nm, corresponding to 7F0 → 5D2 transition. The PSB (phonon sidebands) analysis was carried out to determine the phonon energy of the glass hosts. It was reported that the red (5D0 → 7F2) to orange (5D0 → 7F1) fluorescence intensity ratio for Eu3+ ions decreased from 4.49 (Te0Ge) to 3.33 (Te15Ge) and showed a constant increase from 4.58 (Te20Ge) to 4.88 (Te35Ge). These optical features were explained in structural studies, especially changes in the coordination of [4]Ge to [6]Ge. The most extended lifetime was reported for the Eu3+ doped glass with the highest content of GeO2. This glass was successfully used for the drawing of optical fiber

SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38-CD123+ and CD34+CD38-CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials

T-Cell Immune Responses Against Env from CRF12_BF and Subtype B HIV-1 Show High Clade-Specificity that Can Be Overridden by Multiclade Immunizations

BACKGROUND: The extreme genetic diversity of the human immunodeficiency virus type 1 (HIV-1) poses a daunting challenge to the generation of an effective AIDS vaccine. In Argentina, the epidemic is characterized by the high prevalence of infections caused by subtype B and BF variants. The aim of this study was to characterize in mice the immunogenic and antigenic properties of the Env protein from CRF12_BF in comparison with clade B, employing prime-boost schemes with the combination of recombinant DNA and vaccinia virus (VV) vectors. METHODOLOGY/PRINCIPAL FINDINGS: As determined by ELISPOT from splenocytes of animals immunized with either EnvBF or EnvB antigens, the majority of the cellular responses to Env were found to be clade-specific. A detailed peptide mapping of the responses reveal that when there is cross-reactivity, there are no amino acid changes in the peptide sequence or were minimal and located at the peptide ends. In those cases, analysis of T cell polifunctionality and affinity indicated no differences with respect to the cellular responses found against the original homologous sequence. Significantly, application of a mixed immunization combining both clades (B and BF) induced a broader cellular response, in which the majority of the peptides targeted after the single clade vaccinations generated a positive response. In this group we could also find significant cellular and humoral responses against the whole gp120 protein from subtype B. CONCLUSIONS/SIGNIFICANCE: This work has characterized for the first time the immunogenic peptides of certain EnvBF regions, involved in T cell responses. It provides evidence that to improve immune responses to HIV there is a need to combine Env antigens from different clades, highlighting the convenience of the inclusion of BF antigens in future vaccines for geographic regions where these HIV variants circulate

Mechanisms Underlining Inflammatory Pain Sensitivity in Mice Selected for High and Low Stress-Induced Analgesia—The Role of Endocannabinoids and Microglia

In this work we strived to determine whether endocannabinoid system activity could account for the differences in acute inflammatory pain sensitivity in mouse lines selected for high (HA) and low (LA) swim-stress-induced analgesia (SSIA). Mice received intraplantar injections of 5% formalin and the intensity of nocifensive behaviours was scored. To assess the contribution of the endocannabinoid system, mice were intraperitoneally (i.p.) injected with rimonabant (0.3–3 mg/kg) prior to formalin. Minocycline (45 and 100 mg/kg, i.p.) was administered to investigate microglial activation. The possible involvement of the endogenous opioid system was investigated with naloxone (1 mg/kg, i.p.). Cannabinoid receptor types 1 and 2 (Cnr1, Cnr2) and opioid receptor subtype (Oprm1, Oprd1, Oprk1) mRNA levels were quantified by qPCR in the structures of the central nociceptive circuit. Levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were measured by liquid chromatography coupled with the mass spectrometry method (LC-MS/MS). In the interphase, higher pain thresholds in the HA mice correlated with increased spinal anandamide and 2-AG release and higher Cnr1 transcription. Downregulation of Oprd1 and Oprm1 mRNA was noted in HA and LA mice, respectively, however no differences in naloxone sensitivity were observed in either line. As opposed to the LA mice, inflammatory pain sensitivity in the HA mice in the tonic phase was attributed to enhanced microglial activation, as evidenced by enhanced Aif1 and Il-1β mRNA levels. To conclude, Cnr1 inhibitory signaling is one mechanism responsible for decreased pain sensitivity in HA mice in the interphase, while increased microglial activation corresponds to decreased pain thresholds in the tonic inflammatory phase

Highly efficient green up-conversion emission from fluoroindate glass nanoparticles functionalized with a biocompatible polymer

Up-conversion nanoparticles have garnered lots of attention due to their ability to transform low energy light (near-infrared) into high-energy (visible) light, enabling their potential use as remote visible light nano-transducers. However, their low efficiency restricts their full potential. To overcome this disadvantage, fluoroindate glasses (InF3) doped at different molar concentrations of Yb3+ and Er3+ were obtained using the melting–quenching technique, reaching the highest green emission at 1.4Yb and 1.75Er (mol%), which corresponds to the 4S3/2 / 4I15/2 (540–552 nm) transition. The particles possess the amorphous nature of the glass and have a high thermostability, as corroborated by thermogravimetric assay. Furthermore, the spectral decay curve analysis showed efficient energy transfer as the rare-earth ions varied. This was corroborated with the absolute quantum yield (QY) obtained (85%) upon excitation at 385 nm with QYEr ¼ 17% and QYYb ¼ 68%. Additionally, InF3–1.4Yb–1.75Er was milled and functionalized using poly(ethylene glycol) to impart biocompatibility, which is essential for biomedical applications. Such functionalization was verified using FTIR, TG/DSC, and XRD