Yb2+-Doped Silicate Glasses as Optical Sensor Materials for Cryogenic Thermometry.

Optical sensors constitute attractive alternatives to resistive probes for the sensing and monitoring of temperature (T). In this work, we investigated, in the range from 2 to 300 K, the thermal behavior of Yb2+ ion photoluminescence (PL) in glass hosts for cryogenic thermometry. To that end, two kinds of Yb2+-doped preforms, with aluminosilicate and aluminophosphosilicate core glasses, were made using the modified chemical vapor deposition (MCVD) technique. The obtained preforms were then elongated, at about 2000 °C, to canes with an Yb2+-doped core of about 500 µm. Under UV excitation and independently of the core composition, all samples of preforms and their corresponding canes presented a wide visible emission band attributed to Yb2+ ions. Furthermore, PL kinetics measurements, recorded at two emission wavelengths (502 and 582 nm) under 355 nm pulsed excitation, showed an increase, at very low T, followed by a decrease in lifetime until room temperature (RT). A modified two-level model was proposed to interpret such a decay time dependence versus T. Based on the fit of lifetime data with this model, the absolute (Sa) and relative (Sr) sensitivities were determined for each sample. For both the preform and its corresponding cane, the aluminophosphosilicate glass composition featured the highest performances in the cryogenic domain, with values exceeding 28.3 µsK-1 and 94.4% K-1 at 30 K for Sa and Sr, respectively. The aluminophosphosilicate preform also exhibited the wider T operating range of 10-300 K. Our results show that Yb2+-doped silicate glasses are promising sensing materials for optical thermometry applications in the cryogenic domain.

Performance Study of a Zirconia-Doped Fiber for Distributed Temperature Sensing by OFDR at 800 °C.

Optical Frequency Domain Reflectometry (OFDR) is used to make temperature distributed sensing measurements along a fiber by exploiting Rayleigh backscattering. This technique presents high spatial and high temperature resolutions on temperature ranges of several hundred of degrees Celsius. With standard telecommunications fibers, measurement errors coming from the correlation between a high temperature Rayleigh trace and the one taken as a reference at room temperature could be present at extremely high temperatures. These correlation errors, due to low backscattering signal amplitude and unstable backscattering signal, induce temperature measurement errors. Thus, for high temperature measurement ranges and at extremely high temperatures (e.g., at 800 °C), a known solution is to use fibers with femtosecond laser inscribed nanograting. These fs-laser-insolated fibers have a high amplitude and thermally stable scattering signal, and they exhibit lower correlation errors. In this article, temperature sensing at 800 °C is reported by using an annealed zirconia-doped optical fiber with an initial 40.5-dB enhanced scattering signal. The zirconia-doped fiber presents initially OFDR losses of 2.8 dB/m and low OFDR signal drift at 800 °C. The ZrO2-doped fiber is an alternative to nanograting-inscribed fiber to make OFDR distributed fiber sensing on several meters with gauge lengths of 1 cm at high temperatures.

Investigation of the Incorporation of Cerium Ions in MCVD-Silica Glass Preforms for Remote Optical Fiber Radiation Dosimetry.

The incorporation of Ce3+ ions in silicate glasses is a crucial issue for luminescence-based sensing applications. In this article, we report on silica glass preforms doped with cerium ions fabricated by modified chemical vapor deposition (MCVD) under different atmospheres in order to favor the Ce3+ oxidation state. Structural analysis and photophysical investigations are performed on the obtained glass rods. The preform fabricated under reducing atmosphere presents the highest photoluminescence (PL) quantum yield (QY). This preform drawn into a 125 µm-optical fiber, with a Ce-doped core diameter of about 40 µm, is characterized to confirm the presence of Ce3+ ions inside this optical fiber core. The fiber is then tested in an all-fibered X-ray dosimeter configuration. We demonstrate that this fiber allows the remote monitoring of the X-ray dose rate (flux) through a radioluminescence (RL) signal generated around 460 nm. The response dependence of RL versus dose rate exhibits a linear behavior over five decades, at least from 330 µGy(SiO2)/s up to 22.6 Gy(SiO2)/s. These results attest the potentialities of the MCVD-made Ce-doped material, obtained under reducing atmosphere, for real-time remote ionizing radiation dosimetry.

Increasing Polarity in Tacrine and Huprine Derivatives: Potent Anticholinesterase Agents for the Treatment of Myasthenia Gravis.

Symptomatic treatment of myasthenia gravis is based on the use of peripherally-acting acetylcholinesterase (AChE) inhibitors that, in some cases, must be discontinued due to the occurrence of a number of side-effects. Thus, new AChE inhibitors are being developed and investigated for their potential use against this disease. Here, we have explored two alternative approaches to get access to peripherally-acting AChE inhibitors as new agents against myasthenia gravis, by structural modification of the brain permeable anti-Alzheimer AChE inhibitors tacrine, 6-chlorotacrine, and huprine Y. Both quaternization upon methylation of the quinoline nitrogen atom, and tethering of a triazole ring, with, in some cases, the additional incorporation of a polyphenol-like moiety, result in more polar compounds with higher inhibitory activity against human AChE (up to 190-fold) and butyrylcholinesterase (up to 40-fold) than pyridostigmine, the standard drug for symptomatic treatment of myasthenia gravis. The novel compounds are furthermore devoid of brain permeability, thereby emerging as interesting leads against myasthenia gravis.

Enantiomeric separation of original heterocyclic organophosphorus compounds in supercritical fluid chromatography.

New and original heterocyclic α-enamido phosphine chiral solutes were prepared: four structurally similar racemates with the chirality center placed on the phosphorus atom, and four other related pairs of enantiomers with chirality borne by the carbon atoms of the phospholane ring. The structural variations were placed on an aliphatic heterocycle (six- or seven-member rings) and on the carbamate function (methyl or t-butyl). Their separation was achieved on a commercial cellulose tris-(3,5-dimethylphenylcarbamate) stationary phase (Lux Cellulose-1, Phenomenex) in supercritical fluid chromatography (SFC). The effects of molecular structure on SFC retention and enantioresolution were studied. Among these eight pairs of enantiomers, some reversal of elution order between similar compounds was observed. The effect of changing the organic solvent (methanol and ethanol) and its proportion (between 5 and 40%) in the mobile phase was investigated. Retention data were collected over the temperature range 0-50 °C, and the results interpreted from thermodynamic aspects.

Discovery of a Potent Dual Inhibitor of Acetylcholinesterase and Butyrylcholinesterase with Antioxidant Activity that Alleviates Alzheimer-like Pathology in Old APP/PS1 Mice.

The combination of the scaffolds of the cholinesterase inhibitor huprine Y and the antioxidant capsaicin results in compounds with nanomolar potencies toward human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that retain or improve the antioxidant properties of capsaicin. Crystal structures of their complexes with AChE and BChE revealed the molecular basis for their high potency. Brain penetration was confirmed by biodistribution studies in C57BL6 mice, with one compound (5i) displaying better brain/plasma ratio than donepezil. Chronic treatment of 10 month-old APP/PS1 mice with 5i (2 mg/kg, i.p., 3 times per week, 4 weeks) rescued learning and memory impairments, as measured by three different behavioral tests, delayed the Alzheimer-like pathology progression, as suggested by a significantly reduced Aß42/Aß40 ratio in the hippocampus, improved basal synaptic efficacy, and significantly reduced hippocampal oxidative stress and neuroinflammation. Compound 5i emerges as an interesting anti-Alzheimer lead with beneficial effects on cognitive symptoms and on some underlying disease mechanisms.

Functional characterization of multifunctional ligands targeting acetylcholinesterase and alpha 7 nicotinic acetylcholine receptor.

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cholinergic dysfunction, provoking memory loss and cognitive dysfunction in elderly patients. The cholinergic hypothesis provided over the years with molecular targets for developing palliative treatments for AD, acting on the cholinergic system, namely, acetylcholinesterase and α7 nicotinic acetylcholine receptor (α7 nAChR). In our synthetic work, we used "click-chemistry" to synthesize two Multi Target Directed Ligands (MTDLs) MB105 and MB118 carrying tacrine and quinuclidine scaffolds which are known for their anticholinesterase and α7 nAChR agonist activities, respectively. Both, MB105 and MB118, inhibit human acetylcholinesterase and human butyrylcholinesterase in the nanomolar range. Electrophysiological recordings on Xenopus laevis oocytes expressing human α7 nAChR showed that MB105 and MB118 acted as partial agonists of the referred nicotinic receptor, albeit, with different potencies despite their similar structure. The different substitution at C-3 on the 2,3-disubstituted quinuclidine scaffold may account for the significantly lower potency of MB118 compared to MB105. Electrophysiological recordings also showed that the tacrine precursor MB320 behaved as a competitive antagonist of human α7 nAChR, in the micromolar range, while the quinuclidine synthetic precursor MB099 acted as a partial agonist. Taken all together, MB105 behaved as a partial agonist of α7 nAChR at concentrations where it completely inhibited human acetylcholinesterase activity paving the way for the design of novel MTDLs for palliative treatment of AD.

Near-infrared emitting lanthanide(iii) complexes as prototypes of optical imaging agents with peptide targeting ability: a methodological approach.

A methodological approach to design prototypes of specific near-infrared emitting imaging agents based on a small molecular compound combining a lanthanide(iii) ion, the cyclen derivative as a coordinating unit and the azo-dye as a sensitizer with a Arg-Gly-Asp cyclopeptide as a targeting moiety, is presented here.

PET and SPECT Radiotracers for Alzheimer's Disease.

The two main pathological hallmarks of Alzheimer's disease (AD) in the brain are senile plaques (SPs) composed of beta-amyloid (Aß) peptides and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein. These hallmarks are associated with a cholinergic deficit. While the process leading to the development of AD is complex and multifactorial, and the etiology of AD is not completely known, it is nowadays clear that AD is a multifaceted illness requiring the combination of synergetic treatment strategies. Because definite diagnosis is achieved by postmortem examination of the brain, new noninvasive diagnostic imaging modalities for AD are in high demand, both to detect and monitor the evolution of this sickness, and evaluate the efficacy of treatments. Positron Emission Tomography (PET) is a nuclear molecular imaging technique that uses radiopharmaceuticals labeled with a positron-emitting isotope (carbon-11, fluorine-18, copper-64, gallium- 68…), to visualize in vivo cellular metabolism with high-spatial resolution and unique sensitivity, while Single-Photon Emission Computed Tomography (SPECT) using radioisotopes such as technetium-99m or iodine-123. Besides being a powerful tool for diagnosis (mostly in oncology with [(18)F]-FDG), PET experiments can provide information about biochemical mechanisms in living tissues or interactions between neurotransmitter and brain receptors. For the past two decades, numerous radiopharmaceuticals have been developed for imaging the lesions observed in AD patients. Tau aggregates and Aß plaques can also be visualized and quantified by mean of specific radioligands. The latter has been the focus of intense research efforts lately, leading to new FDA approved radiopharmaceuticals. This paper aimed at summarizing the recent advances in PET and SPECT imaging of AD pathophysiology.