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Bjorn H Falkenburger – One of the best experts on this subject based on the ideXlab platform.

  • accumulation and clearance of α synuclein Aggregates demonstrated by time lapse imaging
    Journal of Neurochemistry, 2008
    Co-Authors: Felipe Opazo, Antje Krenz, Stephan Heermann, Jorg B Schulz, Bjorn H Falkenburger

    Abstract:

    Aggregates of α-synuclein are the pathological hallmark of sporadic Parkinson’s disease (PD), and mutations in the α-synuclein gene underlie familial forms of the disease. To characterize the formation of α-synuclein Aggregates in living cells, we developed a new strategy to visualize α-synuclein by fluorescence microscopy: α-synuclein was tagged with a six amino acid PDZ binding motif and co-expressed with the corresponding PDZ domain fused to enhanced green fluorescent protein (EGFP). In contrast to the traditional approach of α-synuclein-EGFP fusion proteins, this technique provided several-fold higher sensitivity; this allowed us to compare α-synuclein variants and perform time-lapse imaging. A C-terminally truncated α-synuclein variant showed the highest prevalence of Aggregates and toxicity, consistent with stabilization of the α-synuclein monomer by its C-terminus. Time-lapse imaging illustrated how cells form and accumulate Aggregates of α-synuclein. A substantial number of cells also reduced their Aggregate Load, primarily through formation of an aggresome, which could itself be cleared from the cell. The molecular chaperone Hsp70 not only prevented the formation of Aggregates, but also increased their reduction and clearance, underlining the therapeutic potential of similar strategies. In contrast to earlier assumptions build-up, reduction and clearance of α-synuclein aggregation thus appear a highly dynamic process.

  • Accumulation and clearance of α‐synuclein Aggregates demonstrated by time‐lapse imaging
    Journal of Neurochemistry, 2008
    Co-Authors: Felipe Opazo, Antje Krenz, Stephan Heermann, Jorg B Schulz, Bjorn H Falkenburger

    Abstract:

    Aggregates of α-synuclein are the pathological hallmark of sporadic Parkinson’s disease (PD), and mutations in the α-synuclein gene underlie familial forms of the disease. To characterize the formation of α-synuclein Aggregates in living cells, we developed a new strategy to visualize α-synuclein by fluorescence microscopy: α-synuclein was tagged with a six amino acid PDZ binding motif and co-expressed with the corresponding PDZ domain fused to enhanced green fluorescent protein (EGFP). In contrast to the traditional approach of α-synuclein-EGFP fusion proteins, this technique provided several-fold higher sensitivity; this allowed us to compare α-synuclein variants and perform time-lapse imaging. A C-terminally truncated α-synuclein variant showed the highest prevalence of Aggregates and toxicity, consistent with stabilization of the α-synuclein monomer by its C-terminus. Time-lapse imaging illustrated how cells form and accumulate Aggregates of α-synuclein. A substantial number of cells also reduced their Aggregate Load, primarily through formation of an aggresome, which could itself be cleared from the cell. The molecular chaperone Hsp70 not only prevented the formation of Aggregates, but also increased their reduction and clearance, underlining the therapeutic potential of similar strategies. In contrast to earlier assumptions build-up, reduction and clearance of α-synuclein aggregation thus appear a highly dynamic process.

Felipe Opazo – One of the best experts on this subject based on the ideXlab platform.

  • accumulation and clearance of α synuclein Aggregates demonstrated by time lapse imaging
    Journal of Neurochemistry, 2008
    Co-Authors: Felipe Opazo, Antje Krenz, Stephan Heermann, Jorg B Schulz, Bjorn H Falkenburger

    Abstract:

    Aggregates of α-synuclein are the pathological hallmark of sporadic Parkinson’s disease (PD), and mutations in the α-synuclein gene underlie familial forms of the disease. To characterize the formation of α-synuclein Aggregates in living cells, we developed a new strategy to visualize α-synuclein by fluorescence microscopy: α-synuclein was tagged with a six amino acid PDZ binding motif and co-expressed with the corresponding PDZ domain fused to enhanced green fluorescent protein (EGFP). In contrast to the traditional approach of α-synuclein-EGFP fusion proteins, this technique provided several-fold higher sensitivity; this allowed us to compare α-synuclein variants and perform time-lapse imaging. A C-terminally truncated α-synuclein variant showed the highest prevalence of Aggregates and toxicity, consistent with stabilization of the α-synuclein monomer by its C-terminus. Time-lapse imaging illustrated how cells form and accumulate Aggregates of α-synuclein. A substantial number of cells also reduced their Aggregate Load, primarily through formation of an aggresome, which could itself be cleared from the cell. The molecular chaperone Hsp70 not only prevented the formation of Aggregates, but also increased their reduction and clearance, underlining the therapeutic potential of similar strategies. In contrast to earlier assumptions build-up, reduction and clearance of α-synuclein aggregation thus appear a highly dynamic process.

  • Accumulation and clearance of α‐synuclein Aggregates demonstrated by time‐lapse imaging
    Journal of Neurochemistry, 2008
    Co-Authors: Felipe Opazo, Antje Krenz, Stephan Heermann, Jorg B Schulz, Bjorn H Falkenburger

    Abstract:

    Aggregates of α-synuclein are the pathological hallmark of sporadic Parkinson’s disease (PD), and mutations in the α-synuclein gene underlie familial forms of the disease. To characterize the formation of α-synuclein Aggregates in living cells, we developed a new strategy to visualize α-synuclein by fluorescence microscopy: α-synuclein was tagged with a six amino acid PDZ binding motif and co-expressed with the corresponding PDZ domain fused to enhanced green fluorescent protein (EGFP). In contrast to the traditional approach of α-synuclein-EGFP fusion proteins, this technique provided several-fold higher sensitivity; this allowed us to compare α-synuclein variants and perform time-lapse imaging. A C-terminally truncated α-synuclein variant showed the highest prevalence of Aggregates and toxicity, consistent with stabilization of the α-synuclein monomer by its C-terminus. Time-lapse imaging illustrated how cells form and accumulate Aggregates of α-synuclein. A substantial number of cells also reduced their Aggregate Load, primarily through formation of an aggresome, which could itself be cleared from the cell. The molecular chaperone Hsp70 not only prevented the formation of Aggregates, but also increased their reduction and clearance, underlining the therapeutic potential of similar strategies. In contrast to earlier assumptions build-up, reduction and clearance of α-synuclein aggregation thus appear a highly dynamic process.

Ned Djilali – One of the best experts on this subject based on the ideXlab platform.

  • a new thermostat for real time price demand response cost comfort and energy impacts of discrete time control without deadband
    Applied Energy, 2015
    Co-Authors: Jakob Stoustrup, David P Chassin, P Agathoklis, Ned Djilali

    Abstract:

    Thermostatically controlled electrical Loads can provide valuable energy storage and are prime candidates for fast acting demand response (DR) that can be used to mitigate highly variable renewable power generation and limited availability of ramping resources. When conventional thermostats are retrofitted for real-time price DR control, significant control errors can arise, particularly in the form of dispatch control drift. This paper identifies the underlying causes and presents a new residential thermostat design that enables accurate Aggregate Load control. The new design gives rise to linear time-invariant models of Aggregate Load control and demand response, which facilitate the design of highly accurate Load-based regulation services for electricity interconnections. Detailed simulation and performance studies coupling a residential house and feeder models are presented to show how consumer comfort and cost savings are achieved and how energy use is impacted for cities in three different climatic zones. During peak times, the new thermostat imparts the entire residential Load an energy demand elasticity of about 10–25%. Larger demand elasticities could be achieved by extending the control strategy to other residential thermostatic Loads. The proposed thermostat design can operate in the real-time distribution capacity auction system and can provide all the benefits associated with transactive systems, and in particular facilitate increased integration of renewable resources.

  • Wind integration in self-regulating electric Load distributions
    Energy Systems, 2012
    Co-Authors: Simon Parkinson, Dan Wang, Curran Crawford, Ned Djilali

    Abstract:

    The purpose of this paper is to introduce and assess an alternative method of mitigating short-term wind energy production variability through the control of electric Loads. In particular, co-located populations of electric vehicles and heat pumps are targeted to provide regulation-based ancillary services, as the inherent operational flexibility and autonomous device-level control strategy associated with these Load-types provide an ideal platform to mitigate enhanced variability within the power system. An optimal control strategy capable of simultaneously balancing these grid-side objectives with those typically expected on the demand-side is introduced. End-use digital communication hardware is used to track and control population dynamics through the development of online Aggregate Load models equivalent to conventional dispatchable generation. The viability of the proposed Load control strategy is assessed through model-based simulations that explicitly track end-use functionality of responsive devices within a power systems analysis typically implemented to observe the effects of integrated wind energy systems. Results indicate that there is great potential for the proposed method to displace the need for increased online regulation reserve capacity in systems considering a high penetration of wind energy, thereby allowing conventional generation to operate more efficiently.