Definitive diagnosis of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) relies on postmortem finding of disease-associated alpha-synuclein (αSynD) as misfolded protein aggregates in the central nervous system (CNS). The recent development of the real-time quaking induced conversion (RT-QuIC) assay for ultrasensitive detection of αSynD aggregates has revitalized the diagnostic values of clinically accessible biospecimens, including cerebrospinal fluid (CSF) and peripheral tissues. However, the current αSyn RT-QuIC assay platforms vary widely and are thus challenging to implement and standardize the measurements of αSynD across a wide range of biospecimens and in different laboratories. We have streamlined αSyn RT-QuIC assay based on a second generation assay platform that was assembled entirely with commercial reagents. The streamlined RT-QuIC method consisted of a simplified protocol requiring minimal hands-on time, and allowing for a uniform analysis of αSynD in different types of biospecimens from PD and DLB. Ultrasensitive and specific RT-QuIC detection of αSynD aggregates was achieved in million-fold diluted brain homogenates and in nanoliters of CSF from PD and DLB cases but not from controls. Comparative analysis revealed higher seeding activity of αSynD in DLB than PD in both brain homogenates and CSF. Our assay was further validated with CSF samples of 214 neuropathologically confirmed cases from tissue repositories (88 PD, 58 DLB, and 68 controls), yielding a sensitivity of 98% and a specificity of 100%. Finally, a single RT-QuIC assay protocol was employed uniformly to detect seeding activity of αSynD in PD samples across different types of tissues including the brain, skin, salivary gland, and colon. We anticipate that our streamlined protocol will enable interested laboratories to easily and rapidly implement the αSyn RT-QuIC assay for various clinical specimens from PD and DLB. The utilization of commercial products for all assay components will improve the robustness and standardization of the RT-QuIC assay for diagnostic applications across different sites. Due to ultralow sample consumption, the ultrasensitive RT-QuIC assay will facilitate efficient use and sharing of scarce resources of biospecimens. Our streamlined RT-QuIC assay is suitable to track the distribution of αSynD in CNS and peripheral tissues of affected patients. The ongoing evaluation of RT-QuIC assay of αSynD as a potential biomarker for PD and DLB in clinically accessible biospecimens has broad implications for understanding disease pathogenesis, improving early and differential diagnosis, and monitoring therapeutic efficacies in clinical trials.
Traditional ground-fault arc suppression devices mainly deal with capacitive component of ground current and have weak effect on the active and harmonic ones, which limits the arc suppression performance. The capacitive current detection needed in them suffers from low accuracy and robustness. The commonly-used large-capacity reactive component may bring about overvoltage because of possible resonance with the distributed phase-to-ground capacitance. To solve these problems, an active ground-fault arc suppression device is presented. It employs a topology based on single-phase inverter to inject current into the neutral without any large-capacity reactors, and thus avoids the aforementioned overvoltage. It compensates all the active, reactive and harmonic components of the ground current to reliably extinguish the ground-fault arcs. A dual-loop voltage control method is proposed to realize arc suppression without capacitive current detection. Its time-based feature also brings the benefit of fast response on ground-fault arc suppression. The principle of full current compensation is analyzed, together with the controller design method of the proposed device. Experiment on a prototype was carried out to validate the effectiveness of the device.
The fiscal crisis encountered by state-local governments since 2008 has again made prominent the issue of how to better prepare for and stabilize expenditures during recessions.Does the economic stabilization function of government, and its theory, still hold? Previous studies focus on federal and state levels; only a few look at local governments. This article explores whether localities save and spend across the boom-bust cycle; we intend to identify determinants of local government savings and estimate the impact of savings on stabilizing expenditures. Unlike some early evidence that shows counter-cyclical stabilization properties of local unreserved general fund balance, the empirical results of our study on North Carolina counties do not support the stabilization role by localities. This study carries timely and important implications for state/local policy making and financial operations; it also adds to the literature on the stabilization function of government.
Neutral-to-ground overvoltage may occur in non-effectively grounded power systems because of the distributed parameters asymmetry and resonance between Petersen coil and distributed capacitances. Thus, the constraint of neutral-to-ground voltage is critical for the safety of distribution networks. In this paper, an active grounding system based on single-phase inverter and its control parameter design method is proposed to achieve this objective. Relationship between its output current and neutral-to-ground voltage is derived to explain the principle of neutral-to-ground voltage compensation. Then, a practical current detection method is proposed to specify the reference of compensated current. A current control method consisting of proportional resonant (PR) and proportional integral (PI) with capacitive current feedback is then proposed to guarantee sufficient output current accuracy and stability margin subjecting to large range of load change. The PI method is taken as the comparative method and the performances of both control methods are presented in detail. Experimental results prove the effectiveness and novelty of the proposed grounding system and control method.
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