Anaesthetic Preconditioning; The Role of ATP-Sensitive K+ Channels

Stroke in general but especially in the postoperative period is a serious clinical problem that warrants new therapeutic approaches. Here neuroprotective strategies and especially preconditioning have recently emerged as promising. Preconditioning was originally demonstrated in the heart but was subsequently also found in other organs. Classically it describes a phenomenon where short periods of ischaemia render tissues less vulnerable to major infarcts. In addition to ischaemia neuronal preconditioning can be achieved pharmacologically as well as through inhalational anaesthetics or drugs that open ATP-sensitive K+(KATP) channels. However, the mechanisms through which anaesthetics produce protection remain elusive and the use of K+ channel openers is hampered by their inability to cross the blood-brain-barrier. This study was conducted to investigate the effects of inhalational anaesthetics on KATP channels and to explore whether their neuronal preconditioning properties were dependent on KATP channel opening. First, in whole-cell and excised patchclamp experiments the effects of inhalational anaesthetics on recombinant wild type neuronal (Kir6.2/SUR1) KATP and related as well as modified channels were evaluated. Secondly, the KATP channel dependence of anaesthetic preconditioning was tested in neuronal-glial co-cultures. Recombinant KATP channels were activated by xenon, but inhibited by halogenated volatiles. Moreover, it was shown that xenon acted directly on the Kir6.2 pore-forming subunit, reduced the ability of ATP to inhibit the channel and had no effect on the ATP-regulated Kir1.1 channel. Functionally both sevoflurane and xenon preconditioned neurons at clinically used concentrations but only the effect of xenon was dependent on KATP channel activation. Thus this study established xenon as a novel KATP channel opener. It interacts with the pore-forming Kir6.2 rather than the regulatory sulphonylurea receptor subunit and disinhibits the channel from the blocking actions of ATP. As a consequence xenon but not sevoflurane is able to precondition neurons in a KATP channel-dependent manner

Cell death in sepsis: a matter of how, when, and where

Dysregulated cell death in several tissues is intimately involved in the pathogenesis of sepsis and contributes to multiple organ failure. Whether cell death during sepsis occurs by necrosis or apoptosis may depend on the cell type as well as the disease stage and is therefore a matter of intense debate. While lymphocyte apoptosis contributes to immunosuppression in sepsis, recent evidence suggests that necrosis of hepatocytes predominates in septic patients with liver dysfunction and correlates with poor survival. These distinct modes of cell death might have different consequences for the inflammatory response but are also critical for therapeutic interventions and the disease outcome. Understanding the complexity of death processes employing recently available serum biomarkers of cell death could lead to novel therapeutic approaches and assist in the steering of sepsis treatment

Gravitation Physics at BGPL

We report progress on a program of gravitational physics experiments using cryogenic torsion pendula undergoing large-amplitude torsion oscillation. This program includes tests of the gravitational inverse square law and of the weak equivalence principle. Here we describe our ongoing search for inverse-square-law violation at a strength down to $10^{-5}$ of standard gravity. The low-vibration environment provided by the Battelle Gravitation Physics Laboratory (BGPL) is uniquely suited to this study.Comment: To be published in The Proceedings of the Francesco Melchiorri Memorial Conference as a special issue of New Astronomy Review

Mechanisms of Cell Death in Acute Liver Failure

Acute liver failure (ALF) can be the consequence of various etiologies, that might vary between different geographic regions. Most frequent are intoxications with acetaminophen, viral hepatitis, or liver damage of unknown origin. ALF occurs when the extent of hepatocyte death exceeds the regenerative capacity of the liver. The mode of liver cell death that is predominantly induced in ALF, i.e., apoptosis or necrosis, is still controversial and presumably determined by the etiology, duration, and magnitude of liver injury. Severe liver damage involves oxidative stress and depletion of ATP resulting in necrosis. In contrast, maintenance of ATP stores is required for the execution of apoptosis. Recent data suggest that necrosis resulting from severe liver damage is associated with poor outcome of ALF patients. Discrimination between apoptosis and necrosis might be therefore useful for the identification of ALF patients requiring liver transplantation. Identification of the molecular cell death mechanisms remains an important issue not only for early prediction of ALF outcome, but also for therapeutic interventions. In view of the pleiotropic functions of critical mediators of cell death and tissue regeneration, a particular challenge will be to reduce hepatocellular death without inhibiting the regenerative capacity of the liver. Here, we review the molecular mechanisms of hepatocyte injury and the pathways leading to apoptosis and necrosis, which might represent potential diagnostic and therapeutic targets in ALF

Taste Preference Assay for Adult Drosophila

Olfactory and gustatory perception of the environment is vital for animal survival. The most obvious application of these chemosenses is to be able to distinguish good food sources from potentially dangerous food sources. Gustation requires physical contact with a chemical compound which is able to signal through taste receptors that are expressed on the surface of neurons. In insects, these gustatory neurons can be located across the animal's body allowing taste to play an important role in many different behaviors. Insects typically prefer compounds containing sugars, while compounds that are considered bitter tasting are avoided. Given the basic biological importance of taste, there is intense interest in understanding the molecular mechanisms underlying this sensory modality. We describe an adult Drosophila taste assay which reflects the preference of the animals for a given tastant compound. This assay may be applied to animals of any genetic background to examine the taste preference for a desired soluble compound

Simulation meets real-world : deep reinforcement learning on inverted pendulum system

In this thesis, we investigate the differences between the idealized gymnasium cartpole environment and a real cartpole with the aim to train robust agents in the simulation, that perform well in realworld tasks. In this work, we not only consider the classical upright task, but also the so-called swingup. Models for friction and force are implemented and their effectiveness is evaluated on the real cartpole. The robustness of an agent with regards to changing parameters of the cartpole is also examined and possible solutions presented

Finite Element Modeling for the Structural Analysis of Al-Cu Laser Beam Welding

AbstractLaser beam welding of aluminum and copper (Al-Cu) materials is a cost efficient joining technology to produce e.g. connector elements for battery modules. Distortion low connections can be achieved, which have electrical favorable properties. Numerical simulation of the laser beam welding process of Al-Cu dissimilar materials can provide further insight into principal process mechanisms and mechanical response of the joint parts. In this paper a methodology is introduced to investigate the structural behavior of Al-Cu joints in overlap joint with respect to welding distortions and residual stresses. First the material model of the homogeneous base materials are validated. Next, a generic material model approach is used to simulate the structural behavior of heterogeneous Al-Cu connections

Laboratory Tests of Gravitational Physics Using a Cryogenic Torsion Pendulum

Progress and plans are reported for a program of gravitational physics experiments using cryogenic torsion pendula undergoing large amplitude torsional oscillation. The program includes a UC Irvine project to measure the gravitational constant G and joint UC Irvine - U. Washington projects to test the gravitational inverse square law at a range of about 10 cm and to test the weak equivalence principle.Comment: 17 pages, 11 figures, contribution to the 10th Marcel Grossman Conference Proceedings (Rio de Janeiro, July 20 - 26, 2003) - changed wording in first paragraph of section

Neuromorphic Star Tracking Using Monte Carlo Localization

Accurate attitude determination ensures precise payload sensor alignment and optimal solar panel positioning, enhancing data collection and power efficiency while ensuring stable orbit maintenance. The most accurate method of attitude determination is star tracking. Star trackers collect an image of a star field and utilize a catalog of known star positions to calculate the orientation of the system relative to the stars. The errors present in this method of attitude determination tend to be on the order of ten arcseconds or less. Using traditional collection techniques, attitude estimates can be provided at update rates of 1 to 10 Hz and angular velocities are typically limited to a few degrees per second. Neuromorphic cameras, also known as event cameras, detect changes in the input visible signal on a per pixel basis, enabling microsecond temporal resolution and significantly lower data volume. This collection method is also capable of operating with a significantly reduced power usage ( \u3c ~0.1W) and mass ( \u3c 50g) compared to traditional high-speed cameras. These characteristics make neuromorphic cameras ideal candidates for autonomous navigation of small satellites that commonly have stricter size, weight, and power requirements. The application of neuromorphic cameras to autonomous navigation and localization is an active area of research. Many techniques leverage this unique dataset, such as Monte Carlo Localization (MCL). MCL is a probabilistic technique used in robotics and autonomous navigation. It employs random sampling to estimate a system\u27s position and orientation based on a known map and sensor data. Particle filters implement MCL by creating a dynamic model of potential states through a series of particles, which are iteratively updated and reweighted to align with sensor observations and refine the system\u27s state estimate. ExoAnalytic Solutions utilizes a particle filter to process event camera measurements generated by the stars, leveraging MCL to determine the attitude of the satellite. A star catalog is used as the known map that the particle filter compares measurements to. This process streamlines star identification and makes it continuous which saves time compared to traditional approaches like pattern matching algorithms. The high update rate of the neuromorphic star tracker can aid autonomous navigation of small satellites by providing improved stabilization, maneuver/station-keeping efficiency, and maneuverability. In the increasingly crowded space environment, highly accurate and responsive attitude determination technology is critical to ensuring a safe space environment for all operators. This paper presents the results of a MCL particle filter applied to simulated measurements from a neuromorphic star tracker