CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Fluid Dynamics Appearing during Simulated Microgravity Using Random Positioning Machines.

Random Positioning Machines (RPMs) are widely used as tools to simulate microgravity on ground. They consist of two gimbal mounted frames, which constantly rotate biological samples around two perpendicular axes and thus distribute the Earth's gravity vector in all directions over time. In recent years, the RPM is increasingly becoming appreciated as a laboratory instrument also in non-space-related research. For instance, it can be applied for the formation of scaffold-free spheroid cell clusters. The kinematic rotation of the RPM, however, does not only distribute the gravity vector in such a way that it averages to zero, but it also introduces local forces to the cell culture. These forces can be described by rigid body analysis. Although RPMs are commonly used in laboratories, the fluid motion in the cell culture flasks on the RPM and the possible effects of such on cells have not been examined until today; thus, such aspects have been widely neglected. In this study, we used a numerical approach to describe the fluid dynamic characteristic occurring inside a cell culture flask turning on an operating RPM. The simulations showed that the fluid motion within the cell culture flask never reached a steady state or neared a steady state condition. The fluid velocity depends on the rotational velocity of the RPM and is in the order of a few centimeters per second. The highest shear stresses are found along the flask walls; depending of the rotational velocity, they can reach up to a few 100 mPa. The shear stresses in the "bulk volume," however, are always smaller, and their magnitude is in the order of 10 mPa. In conclusion, RPMs are highly appreciated as reliable tools in microgravity research. They have even started to become useful instruments in new research fields of mechanobiology. Depending on the experiment, the fluid dynamic on the RPM cannot be neglected and needs to be taken into consideration. The results presented in this study elucidate the fluid motion and provide insight into the convection and shear stresses that occur inside a cell culture flask during RPM experiments

Simulated Microgravity: Critical Review on the Use of Random Positioning Machines for Mammalian Cell Culture

Random Positioning Machines (RPMs) have been used since many years as a ground-based model to simulate microgravity. In this review we discuss several aspects of the RPM. Recent technological development has expanded the operative range of the RPM substantially. New possibilities of live cell imaging and partial gravity simulations, for example, are of particular interest. For obtaining valuable and reliable results from RPM experiments, the appropriate use of the RPM is of utmost importance. The simulation of microgravity requires that the RPM’s rotation is faster than the biological process under study, but not so fast that undesired side effects appear. It remains a legitimate question, however, whether the RPM can accurately and reliably simulate microgravity conditions comparable to real microgravity in space. We attempt to answer this question by mathematically analyzing the forces working on the samples while they are mounted on the operating RPM and by comparing data obtained under real microgravity in space and simulated microgravity on the RPM. In conclusion and after taking the mentioned constraints into consideration, we are convinced that simulated microgravity experiments on the RPM are a valid alternative for conducting examinations on the influence of the force of gravity in a fast and straightforward approach

Shear stresses in the flask during three periods on the RPM for three different rotational velocities (40, 60 and 90 deg/s).

<p>Both frames rotate with constant and equal velocity, and the flask is placed at the center of rotation. Top: Volume average of the shear stresses in the “bulk volume” over time. The “bulk volume” is 4 mm smaller than the flask and thus has a 2 mm clearance from the flask wall. Middle: Maximum shear stresses in the “bulk volume” over time. Bottom: Maximum shear stresses along the “cultivation surface” (the two largest flask walls).</p

Effects of shear stresses on various cells.

<p>Effects of shear stresses on various cells.</p

Convection on the RPM over three periods for three different rotational velocities (top: 40 deg/s; middle: 60 deg/s; bottom: 90 deg/s).

<p>Both frames rotate with constant and equal velocity, and the flask is placed at the center of rotation. The flask was divided into two compartments, denoted as the “y-positive compartment” (for y ≥ 0) and “y-negative compartment” (for y < 0). A virtual variable was placed in the “y-positive compartment” only. Subsequently, the variable was left to mix by convection, and the average concentration in the two compartments was monitored. The rapid fluid motion leads to thorough mixing within two to three periods (arrows).</p

Shear stresses along the walls during one period on the RPM.

<p>Both frames rotate with constant and equal velocity; the flask is placed at the center of rotation. The rotational velocity is 60 deg/s. The time interval between the illustrations is 1 second (top left: 0 s; top middle: 1 s; top right: 2 s; bottom left: 3 s; bottom middle: 4 s; bottom right: 5 s).</p