Design, fabrication and evaluation of chalcogenide glass Luneburg lenses for LiNbO3 integrated optical devices

Optical waveguide Luneburg lenses of arsenic trisulfide glass are described. The lenses are formed by thermal evaporation of As2S3 through suitably placed masks onto the surface of LiNbO3:Ti indiffused waveguides. The lenses are designed for input apertures up to 1 cm and for speeds of f/5 or better. They are designed to focus the TM sub 0 guided mode of a beam of wavelength, external to the guide, of 633 nm. The refractive index of the As2S3 films and the changes induced in the refractive index by exposure to short wavelength light were measured. Some correlation between film thickness and optical properties was noted. The short wavelength photosensitivity was used to shorten the lens focal length from the as deposited value. Lenses of rectangular shape, as viewed from above the guide, as well as conventional circular Luneburg lenses, were made. Measurements made on the lenses include thickness profile, general optical quality, focal length, quality of focal spot, and effect of ultraviolet irradiation on optical properties

Holographic Recording Materials Development

Organic photorefractive materials were evaluated for application in a reversible holographic memory system. Representative indigo and thioindigo derivatives and several stilbene derivatives were studied as well as 15, 16-dialkyldihydropyrene derivatives the following goals were achieved: (1) the successful writing of phase holograms in a thioindigo/polymer gel system, (2) the successful writing and erasing of phase holograms in a variety of indigo/polymer gel and indigo/solid polymer systems, and (3) the identification of indigoid dyes and 15, 16-dialkyldihydropyrene derivatives as materials potentially suitable for utilization in an operational system. Photochemical studies of the stilbene, indigo, thioindigo, and dialkyldihydropyrene derivatives in solution and in a variety of polymer matrix materials were conducted with the goal of optimizing the photorefractive behavior of the chemical system as a whole. The spectroscopic properties required of optimal photorefractive materials were identified, and it was shown that both the indigoid dyes and the dialkyldihydropyrenes closely match the required properties

Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is associated with early memory loss, Alzheimer\u27s disease (AD) neuropathology, inefficient or ineffective neural processing, and increased risk for AD. Unfortunately, treatments aimed at improving clinical symptoms or markers of brain function generally have been of limited value. Physical exercise is often recommended for people diagnosed with MCI, primarily because of its widely reported cognitive benefits in healthy older adults. However, it is unknown if exercise actually benefits brain function during memory retrieval in MCI. Here, we examined the effects of exercise training on semantic memory activation during functional magnetic resonance imaging (fMRI). Seventeen MCI participants and 18 cognitively intact controls, similar in sex, age, education, genetic risk, and medication use, volunteered for a 12-week exercise intervention consisting of supervised treadmill walking at a moderate intensity. Both MCI and control participants significantly increased their cardiorespiratory fitness by approximately 10% on a treadmill exercise test. Before and after the exercise intervention, participants completed an fMRI famous name discrimination task and a neuropsychological battery, Performance on Trial 1 of a list-learning task significantly improved in the MCI participants. Eleven brain regions activated during the semantic memory task showed a significant decrease in activation intensity following the intervention that was similar between groups (p-values ranged 0.048 to 0.0001). These findings suggest exercise may improve neural efficiency during semantic memory retrieval in MCI and cognitively intact older adults, and may lead to improvement in cognitive function. Clinical trials are needed to determine if exercise is effective to delay conversion to AD

Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment

Background: Exercise training has been associated with greater cerebral blood flow (CBF) in cognitively normal older adults (CN). Alterations in CBF, including compensatory perfusion in the prefrontal cortex, may facilitate changes to the brain’s neural infrastructure. Objective: To examine the effects of a 12-week aerobic exercise intervention on resting CBF and cognition in CN and those with mild cognitive impairment (MCI). We hypothesized individuals with MCI (vs. CN) would exhibit greater whole brain CBF at baseline and that exercise would mitigate these differences. We also expected CBF changes to parallel cognitive improvements. Methods: Before and after a 12-week exercise intervention, 18 CN and 17 MCI participants (aged 61–88) underwent aerobic fitness testing, neuropsychological assessment, and an MRI scan. Perfusion-weighted images were collected using a GE 3T MR system. Repeated measures analyses of covariance were used to test within- and between-group differences over time, followed by post-hoc analyses to examine links between CBF changes and cognitive improvement. Results: At baseline, individuals with MCI (vs. CN) exhibited significantly elevated perfusion in the left insula. Twelve weeks of aerobic exercise reversed this discrepancy. Additionally, exercise improved working memory (measured by the Rey Auditory Verbal Learning Test) and verbal fluency (measured by the Controlled Oral Word Association Test) and differentially altered CBF depending on cognitive status. Among those with MCI, decreased CBF in the left insula and anterior cingulate cortex was associated with improved verbal fluency. Conclusions: Exercise training alters CBF and improves cognitive performance in older adults with and without cognitive impairment. Future studies must evaluate the mediating effects of CBF on the association between exercise training and cognition

Evaporated As2S3 Luneburg lenses for LiNbO3:Ti optical waveguides

Luneburg lenses of good quality were formed on high index optical waveguides by evaporation of arsenic trisulfide glass through simple masks. Using only two thin circular aperture masks, lenses with focal spots of a few times the diffraction limited width at f/4 were obtained. These lenses were designed for and tested at both visible (633 nm) and infrared wavelengths. Procedures for the design, fabrication, and testing of lenses of this type are described

Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related functional magnetic resonance imaging during fame discrimination. Significantly greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients, (P=0.03), suggesting PA may enhance memory-related caudate activation in aMCI

Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre (n = 66) and 4 months later (n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant (p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales

An Experiment in Design and Analysis of Real-Time Applications

In the paper some experiences of joining two methodologies, which were originally independently developed in different institutions, with the goal to overcome the possible discrepancies due to the separate design of the hardware and the software part of an embedded real-time application are presented. Based on Multiprocessor PEARL, Specification PEARL has been developed in FERI, Maribor. Hardware and system architecture of an application can be described and gradually refined. Application software can be designed using LACATRE tool, developed at INSA, Lyon. Decisions about the application design taken in each tool have influence to the ones taken in the other, thus allowing for parallel design of both parts. Both designs are subsequently verified and eventually joined for feasibility estimation by co-simulation. The application program is coded using the ObjectPEARL language. The real-time system design cycle is closed by the execution time analysis and measurements upon which it is then considered about further program and/or hardware part reconfiguration. This feature is supported by the specific compiler, which includes the execution time analyser. The article reports on the work that was done in the framework of the PROTEUS project in co-operation of the teams from FERI Maribor, Slovenia, and INSA de Lyon, France

Neuropathological characterisation of a novel TBK1 loss of function mutation associated with amyotrophic lateral sclerosis

Mutations in TANK binding kinase gene (TBK1) have been identified as causative in amyotrophic lateral sclerosis (ALS). Here, we examine the spectrum of TBK1 mutations in a cohort of ALS patients from Northern England, comparing missense and loss of function mutations with clinical phenotype. Analysis of 290 ALS cases identified seven variants, including one novel in-frame deletion (p.Ile85del). In silico analysis and review of the literature suggested that four variants, one nonsense mutation (p.Glu2Ter), two in-frame deletions (p.Ile85del, p.Glu643del) and one missense mutation (p.Gln565Pro) were pathogenic, whilst the remaining three missense mutations were variants of uncertain significance or benign. Post-mortem material was available from the patient with the novel in-frame deletion. Neuropathological examination established this individual had classical ALS pathology, with moderate phosphorylated TDP-43 neuronal and glial cytoplasmic inclusions in the motor cortex, skein-like inclusions in the lower motor neurons and “pre-inclusions” in the medulla. This corresponds to Type B FTLD-TDP pathology and is consistent with previously published literature on TBK1 mutants. In addition to demonstrating no changes in TBK1 staining, we are the first to show there was no differential expression of interferon regulatory factor IRF3, a downstream effector of TBK1 in the innate immunity pathway, in the TBK1-mutant tissue compared to controls. Comparison of clinical and neuropathological data, however, suggests that TBK1-ALS cases show classical ALS pathology but no specific phenotype

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain.

The routine clinical integration of individualized objective markers of disease activity in those diagnosed with the neurodegenerative disorder amyotrophic lateral sclerosis is a key requirement for therapeutic development. A large, multicentre, clinic-based, longitudinal cohort was used to systematically appraise the leading candidate biofluid biomarkers in the stratification and potential therapeutic assessment of those with amyotrophic lateral sclerosis. Incident patients diagnosed with amyotrophic lateral sclerosis (n = 258), other neurological diseases (n = 80) and healthy control participants (n = 101), were recruited and followed at intervals of 3-6 months for up to 30 months. Cerebrospinal fluid neurofilament light chain and chitotriosidase 1 and blood neurofilament light chain, creatine kinase, ferritin, complement C3 and C4 and C-reactive protein were measured. Blood neurofilament light chain, creatine kinase, serum ferritin, C3 and cerebrospinal fluid neurofilament light chain and chitotriosidase 1 were all significantly elevated in amyotrophic lateral sclerosis patients. First-visit plasma neurofilament light chain level was additionally strongly associated with survival (hazard ratio for one standard deviation increase in log10 plasma neurofilament light chain 2.99, 95% confidence interval 1.65-5.41, P = 0.016) and rate of disability progression, independent of other prognostic factors. A small increase in level was noted within the first 12 months after reported symptom onset (slope 0.031 log10 units per month, 95% confidence interval 0.012-0.049, P = 0.006). Modelling the inclusion of plasma neurofilament light chain as a therapeutic trial outcome measure demonstrated that a significant reduction in sample size and earlier detection of disease-slowing is possible, compared with using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. This study provides strong evidence that blood neurofilament light chain levels outperform conventional measures of disease activity at the group level. The application of blood neurofilament light chain has the potential to radically reduce the duration and cost of therapeutic trials. It might also offer a first step towards the goal of more personalized objective disease activity monitoring for those living with amyotrophic lateral sclerosis