Broadband Measurement of Complex Permittivity Using Reflection Method and Coaxial Probes

This paper describes and evaluates a method for determining complex permittivity, and presents results of permittivity measurement of some substances. Complex permittivity of a phantom of biological muscle tissue, of some industrial chemicals and dielectrics is found. A non-destructive and non-invasive method based on reflection coefficient measurement of an open-ended coaxial line attaching the material under test is used. Two coaxial probes are under investigation. Vector measurement of the reflection coefficient on the interface between probes and measured samples is performed with the aid of network analyzer in the frequency range from 300 kHz to 3 GHz. Numerical modeling (FDTD) is compared with measurement. The results indicate that using the coaxial probe with dimensions of N connector the method is suitable in the frequency range approximately from 30 MHz to 1 GHz and using the probe with dimensions of SMA connector in range approximately from 30 MHz to 3 GHz

Improvements and modifications to the NASA microwave signature acquisition system

A user oriented description of the modified and upgraded Microwave Signature Acquisition System is provided. The present configuration of the sensor system and its operating characteristics are documented and a step-by-step operating procedure provides instruction for mounting the antenna truss assembly, readying the system for data acquisition, and for controlling the system during the data collection sequence. The resulting data products are also identified

Delta-9-tetrahydrocannabinol protects against MPP+ toxicity in SH-SY5Y cells by restoring proteins involved in mitochondrial biogenesis

This project was supported through a studentship awarded by the Plymouth University Peninsula Schools of Medicine and Dentistry.Proliferator-activated receptor γ (PPARγ) activation can result in transcription of proteins involved in oxidative stress defence and mitochondrial biogenesis which could rescue mitochondrial dysfunction in Parkinson's disease (PD).The PPARγ agonist pioglitazone is protective in models of PD; however side effects have limited its clinical use. The cannabinoid Δ9-tetrahydrocannabinol (Δ9-THC) may have PPARγ dependent anti-oxidant properties. Here we investigate the effects of Δ9-THC and pioglitazone on mitochondrial biogenesis and oxidative stress. Differentiated SH-SY5Y neuroblastoma cells were exposed to the PD relevant mitochondrial complex 1 inhibitor 1-methyl- 4-phenylpyridinium iodide (MPP+). We found that only Δ9-THC was able to restore mitochondrial content in MPP+ treated SH-SY5Y cells in a PPARγ dependent manner by increasing expression of the PPARγ co-activator 1a (PGC-1a), the mitochondrial transcription factor (TFAM) as well as mitochondrial DNA content. Co-application of Δ9- THC with pioglitazone further increased the neuroprotection against MPP+ toxicity as compared to pioglitazone treatment alone. Furthermore, using lentiviral knock down of the PPARγ receptor we showed that, unlike pioglitazone, Δ9-THC resulted in a PPARγ dependent reduction of MPP+ induced oxidative stress. We therefore suggest that, in contrast to pioglitazone, Δ9-THC mediates neuroprotection via PPARγ-dependent restoration of mitochondrial content which may be beneficial for PD treatment.Publisher PDFPeer reviewe

Dialogue based interfaces for universal access.

Conversation provides an excellent means of communication for almost all people. Consequently, a conversational interface is an excellent mechanism for allowing people to interact with systems. Conversational systems are an active research area, but a wide range of systems can be developed with current technology. More sophisticated interfaces can take considerable effort, but simple interfaces can be developed quite rapidly. This paper gives an introduction to the current state of the art of conversational systems and interfaces. It describes a methodology for developing conversational interfaces and gives an example of an interface for a state benefits web site. The paper discusses how this interface could improve access for a wide range of people, and how further development of this interface would allow a larger range of people to use the system and give them more functionality

Comparison of an enzyme-linked immunosorbent assay (ELISA) to gas chromatography (GC) - measurement of polychlorinated biphenyls (PCBs) in selected US fish extracts

The analysis of PCBs in fish tissues by immunoassay methods was evaluated using fish collected from a US monitoring program, the National Contaminant Biomonitoring Program of the US Department of Interior, Fish and Wildlife Service. Selected composite whole fish samples, which represented widely varying concentrations and sources of PCBs, were extracted and subjected to congener PCB analysis by gas chromatography (GC) and total PCB analysis using an ELISA (ePCBs) calibrated against technical Aroclor 1248. PCB congener patterns in these fishes were different from the patterns found in commercial Aroclors or their combinations as demonstrated by principal component analysis of normalized GC congener data. The sum of the PCB congeners measured by GC (total-PCBs) ranged from 37 to 4600 ng/g (wet weight). Concentrations of PCBs as determined by the ELISA method were positively correlated with total-PCBs and the ePCBs/total-PCBs ratios for individual samples ranged from 1 to 6. Ratios of ePCBs/total- PCBs for dilutions of Aroclors 1242, 1254, and 1260 and for matrix spikes range from 0.6 for 1242 to 2.5 for 1254 and 1260. These results suggest that higher chlorinated PCB congeners have higher anffinity for the anti-PCB antibodies. Partial least squares with latent variable analysis of GC and ELISA data of selected Aroclors and fish samples also support the conclusion that ELISA derived PCB concentrations are dependent on the degree of chlorination. © 1999 Elsevier Science Ltd. All rights reserved

Comparison of an enzyme-linked immunosorbent assay (ELISA) to gas chromatography (GC) - measurement of polychlorinated biphenyls (PCBs) in selected US fish extracts

The analysis of PCBs in fish tissues by immunoassay methods was evaluated using fish collected from a US monitoring program, the National Contaminant Biomonitoring Program of the US Department of Interior, Fish and Wildlife Service. Selected composite whole fish samples, which represented widely varying concentrations and sources of PCBs, were extracted and subjected to congener PCB analysis by gas chromatography (GC) and total PCB analysis using an ELISA (ePCBs) calibrated against technical Aroclor 1248. PCB congener patterns in these fishes were different from the patterns found in commercial Aroclors or their combinations as demonstrated by principal component analysis of normalized GC congener data. The sum of the PCB congeners measured by GC (total-PCBs) ranged from 37 to 4600 ng/g (wet weight). Concentrations of PCBs as determined by the ELISA method were positively correlated with total-PCBs and the ePCBs/total-PCBs ratios for individual samples ranged from 1 to 6. Ratios of ePCBs/total- PCBs for dilutions of Aroclors 1242, 1254, and 1260 and for matrix spikes range from 0.6 for 1242 to 2.5 for 1254 and 1260. These results suggest that higher chlorinated PCB congeners have higher anffinity for the anti-PCB antibodies. Partial least squares with latent variable analysis of GC and ELISA data of selected Aroclors and fish samples also support the conclusion that ELISA derived PCB concentrations are dependent on the degree of chlorination. © 1999 Elsevier Science Ltd. All rights reserved

A systematic review of biomarkers for disease progression in Parkinson's disease

This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124).BACKGROUND: Using surrogate biomarkers for disease progression as endpoints in neuroprotective clinical trials may help differentiate symptomatic effects of potential neuroprotective agents from true disease-modifying effects. A systematic review was undertaken to determine what biomarkers for disease progression in Parkinson's disease (PD) exist. METHODS: MEDLINE and EMBASE (1950-2010) were searched using five search strategies. Abstracts were assessed to identify papers meriting review in full. Studies of participants with idiopathic PD diagnosed by formal criteria or clearly described clinical means were included. We made no restriction on age, disease duration, drug treatment, or study design. We included studies which attempted to draw associations between any tests used to investigate disease progression and any clinical measures of disease progression. The electronic search was validated by hand-searching the two journals from which most included articles came. RESULTS: 183 studies were included: 163 (89%) cross-sectional, 20 (11%) longitudinal. The electronic search strategy had a sensitivity of 71.4% (95% CI 51.1-86.0) and a specificity of 97.1% (95% CI 96.5-97.7). In longitudinal studies median follow-up was 2.0 years (IQR 1.1-3.5). Included studies were generally poor quality--cross-sectional with small numbers of participants, applying excessive inclusion/exclusion criteria, with flawed methodologies and simplistic statistical analyses. CONCLUSION: We found insufficient evidence to recommend the use of any biomarker for disease progression in PD clinical trials, which may simply reflect the poor quality of research in this area. We therefore present a provisional 'roadmap' for conducting future disease progression biomarker studies, and recommend new quality criteria by which future studies may be judged.Publisher PDFPeer reviewe

Standing up in Multiple Sclerosis (SUMS): Protocol for a multi-centre randomised controlled trial evaluating the clinical and cost effectiveness of a home-based self-management standing frame programme in people with progressive multiple sclerosis.

This study is funded by the NIHR Health Technology Assessment Programme (14/176/12), United Kingdom.Background:  Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed ‘Balance Right in MS’ (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls. Our eventual aim is to assess the clinical and cost effectiveness of BRiMS in people with secondary progressive MS by undertaking an appropriately statistically powered, multi-centre, assessor-blinded definitive, randomised controlled trial. This feasibility study will assess the acceptability of the intervention and test the achievability of running such a definitive trial. Methods/design:  This is a pragmatic multi-centre feasibility randomised controlled trial with blinded outcome assessment. Sixty ambulant people with secondary progressive MS who self-report two or more falls in the previous 6 months will be randomly allocated (1:1) to either the BRiMS programme plus usual care or to usual care alone. All participants will be assessed at baseline and followed up at 15 weeks and 27 weeks post-randomisation. The outcomes of this feasibility trial include: • Feasibility outcomes, including trial recruitment, retention and completion • Assessment of the proposed outcome measures for the anticipated definitive trial (including measures of walking, quality of life, falls, balance and activity level) • Measures of adherence to the BRiMS programme • Data to inform the economic evaluation in a future trial • Process evaluation (assessment of treatment fidelity and qualitative evaluation of participant and treating therapist experience) Discussion:  The BRiMS intervention aims to address a key concern for MS service users and providers. However, there are several uncertainties which need to be addressed prior to progressing to a full-scale trial, including acceptability of the BRiMS intervention and practicality of the trial procedures. This feasibility trial will provide important insights to resolve these uncertainties and will enable a protocol to be finalised for use in the definitive trial.Publisher PDFPeer reviewe

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial

\ua9 2022 American Medical Association. All rights reserved.Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P =.006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482

Comb-like pseudopeptides enable very rapid and efficient intracellular trehalose delivery for enhanced cryopreservation of erythrocytes

Cell cryopreservation plays a key role in development of reproducible and cost-effective cell-based therapies. Trehalose accumulated in freezing and desiccation tolerant organisms in nature has been sought as an attractive non-toxic cryoprotectant. Herein, we report a co-incubation method for very rapid and efficient delivery of membrane-impermeable trehalose into ovine erythrocytes through reversible membrane permeabilization using pH-responsive, comb-like pseudopeptides. The pseudopeptidic polymers containing relatively long alkyl side chains were synthesized to mimic membrane-anchoring fusogenic proteins. The intracellular trehalose delivery efficiency was optimized by manipulating the side chain length, degree of substitution and concentration of the pseudopeptides with different hydrophobic alkyl side chains, the pH, temperature and time of incubation, as well as the polymer-to-cell ratio and the concentration of extracellular trehalose. Treatment of erythrocytes with the comb-like pseudopeptides for only 15 min yielded an intracellular trehalose concentration of 177.9 ± 8.6 mM, which resulted in 90.3 ± 0.7% survival after freeze-thaw. The very rapid and efficient delivery was found to be attributed to the reversible, pronounced membrane curvature change as a result of strong membrane insertion of the comb-like pseudopeptides. The pseudopeptides can enable efficient intracellular delivery of not only trehalose for improved cell cryopreservation, but also other membrane-impermeable cargos