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| 2. |
- Fransén, Erik, 1962-, et al.
(författare)
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Mechanism of graded persistent cellular activity of entorhinal cortex layer V neurons
- 2006
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 49:5, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Working memory is an emergent property of neuronal networks, but its cellular basis remains elusive. Recent data show that principal neurons of the entorhinal cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model provides stable plateau firing generated by a nonspecific calcium-sensitive cationic (CAN) current. Sustained firing is insensitive to small variations in Ca2+ concentration in a neutral zone. However, both high and low Ca2+ levels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high levels of calcium, while decreases in rate occur in the presence of low levels of calcium. The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons.
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| 3. |
- de Lemos, Rogerio, et al.
(författare)
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Software Engineering for Self-Adaptive Systems : A Second Research Roadmap
- 2013
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Ingår i: Software Engineering for Self-Adaptive Systems II. - Berlin, Heidelberg : Springer. - 9783642358128 ; , s. 1-32
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The goal of this roadmap paper is to summarize the state-of-the-art and identify research challenges when developing, deploying and managing self-adaptive software systems. Instead of dealing with a wide range of topics associated with the field, we focus on four essential topics of self-adaptation: design space for self-adaptive solutions, software engineering processes for self-adaptive systems, from centralized to decentralized control, and practical run-time verification & validation for self-adaptive systems. For each topic, we present an overview, suggest future directions, and focus on selected challenges. This paper complements and extends a previous roadmap on software engineering for self-adaptive systems published in 2009 covering a different set of topics, and reflecting in part on the previous paper. This roadmap is one of the many results of the Dagstuhl Seminar 10431 on Software Engineering for Self-Adaptive Systems, which took place in October 2010.
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| 4. |
- Kamanzi, Albert, et al.
(författare)
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Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles
- 2021
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 15:12, s. 19244-19255
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development.
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| 5. |
- Tahvildari, Babak, et al.
(författare)
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Switching between on and off states of persistent activity in lateral entorhinal layer III neurons
- 2007
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 17:4, s. 257-263
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Tidskriftsartikel (refereegranskat)abstract
- Persistent neural spiking maintains information during a, working memory task when a stimulus is no longer present. During I retention, this activity needs to be stable to distractors. More importantly, when retention is no longer relevant, cessation of the activity is necessary to enable processing and retention of subsequent information. Here, by means of intracellular recording with sharp microelectrode in in vitro rat brain slices, we demonstrate that single principal layer III neurons of the lateral entorhinal cortex (EC) generate persistent spiking activity with a novel ability to reliably toggle between spiking activity and a silent state. Our data indicates that in the presence of muscarmic receptor activation, persistent activity following an excitatory input may be induced and that a subsequent excitatory input can terminate this activity and cause the neuron to return to a silent state. Moreover, application of inhibitory hyperpolarizing stimuli is neither able to decrease the frequency of the persistent activity nor terminate it. The persistent activity can also be initiated and terminated by synchronized synaptic stimuli of layer II/III of the perirhinal cortex. The neuronal ability to switch On and Off persistent activity may facilitate the concurrent representation of temporally segregated information arriving in the EC and being directed toward the hippocampus.
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