GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

Correlation of circular differential optical absorption with geometric chirality in plasmonic meta-atoms

We report a strong correlation between the calculated broadband circular differential optical absorption (CDOA) and the geometric chirality of plasmonic meta-atoms with two-dimensional chirality. We investigate this correlation using three common gold meta-atom geometries: L-shapes, triangles, and nanorod dimers, over a broad range of geometric parameters. We show that this correlation holds for both contiguous plasmonic meta-atoms and non-contiguous structures which support plasmonic coupling effects. A potential application for this correlation is the rapid optimization of plasmonic nanostructure for maximum broadband CDOA

The multiple faces of leukocyte interstitial migration

Spatiotemporal control of leukocyte dynamics within tissues is critical for successful innate and adaptive immune responses. Homeostatic trafficking and coordinated infiltration into and within sites of inflammation and infection rely on signaling in response to extracellular cues that in turn controls a variety of intracellular protein networks regulating leukocyte motility, migration, chemotaxis, positioning, and cell–cell interaction. In contrast to mesenchymal cells, leukocytes migrate in an amoeboid fashion by rapid cycles of actin polymerization and actomyosin contraction, and their migration in tissues is generally referred to as low adhesive and nonproteolytic. The interplay of actin network expansion, contraction, and adhesion shapes the exact mode of amoeboid migration, and in this review, we explore how leukocyte subsets potentially harness the same basic biomechanical mechanisms in a cell-type-specific manner. Most of our detailed understanding of these processes derives from in vitro migration studies in three-dimensional gels and confined spaces that mimic geometrical aspects of physiological tissues. We summarize these in vitro results and then critically compare them to data from intravital imaging of leukocyte interstitial migration in mouse tissues. We outline the technical challenges of obtaining conclusive mechanistic results from intravital studies, discuss leukocyte migration strategies in vivo, and present examples of mode switching during physiological interstitial migration. These findings are also placed in the context of leukocyte migration defects in primary immunodeficiencies. This overview of both in vitro and in vivo studies highlights recent progress in understanding the molecular and biophysical mechanisms that shape robust leukocyte migration responses in physiologically complex and heterogeneous environments

An investigation of the microscale geometry and liquid flow through an isolated foam channel network

Liquid foams represent an extremely diverse and highly functional form of soft matter, whose application is widespread throughout industry. These can range from luxurious and low calorie applications in food and beverages, structural and insulating properties in building and manufacture, right through to dynamic and transport abilities in the petrochemical industry, among others. A common feature of all of these foams is they are required to exhibit longevity, however as foams are thermodynamically unstable systems, this is not always a trivial feat. Foams are highly complex systems, with dynamic processes occurring on the molecular scale that influence properties at the scale of individual bubbles and subsequently at the macroscopic scale of bulk foams. A particular challenge of foam research is to unite these length scale processes, requiring robust theoretical and experimental studies to be made at all size regimes. This PhD thesis is concerned specifically with the microscale process of liquid flow between bubbles, as these liquid channels form the primary network through which liquid ‘drains’ through a foam under the force of gravity; one of the key mechanisms governing foam instability. The initial focus of this PhD thesis was the design and implementation of an experimental technique to isolate and image liquid foam channels formed under controlled liquid flow rates. This was developed with a view to producing highly accurate and reproducible measurements of the channel geometries, which would enable the comparison to theory derived to describe such systems. Measurements of low molecular weight surfactants and higher molecular weight emulsifiers clearly demonstrated three previously unseen geometries of foam channel that could not be described using existing theory. Instead, a new geometric model was developed which was able to account for these differences, relating the bulk and surface properties of the foam channel to its length and the rate of liquid flow passing through it. When used as a fitting parameter, the new model was able to clearly demarcate between the characteristic low and high surface viscosities of the surfactant and emulsifier species respectively. The surface viscosity of the surfactant foam channel interfaces was examined throughout this PhD study, as the values extracted from model fitting were consistently lower than the majority found in literature, but in line with predictions made from hyper-sensitive measurement techniques. Ultimately, it was proposed that these differences could be attributed to a combination of the limited measurement sensitivity of commercial systems, combined with a liquid flow velocity dependence of surfactant concentration at the channel surface. It was suggested that, in the case of low molecular weight surfactants, a surface tension gradient can exist along the length of a foam channel, that is dependent upon the rate of liquid flow, the concentration of surfactant and the rate of surfactant adsorption to the interface. In the case of high liquid flow velocities, it was shown that surface tensions in some channel regions could be almost as high as pure water, despite surfactant concentrations being above the CMC. As such, this could have significant consequences for stability in macroscopic foams where these conditions are present

Payload/orbiter contamination control requirement study

A study was conducted to determine and quantify the expected particulate and molecular on-orbit contaminant environment for selected space shuttle payloads as a result of major shuttle orbiter contamination sources. Individual payload susceptibilities to contamination are reviewed. The risk of payload degradation is identified and preliminary recommendations are provided concerning the limiting factors which may depend on operational activities associated with the payload/orbiter interface or upon independent payload functional activities. A basic computer model of the space shuttle orbiter which includes a representative payload configuration is developed. The major orbiter contamination sources, locations, and flux characteristics based upon available data have been defined and modeled

A systems biology approach to axis formation during early zebrafish embryogenesis: from biophysical measurements to model inference

During early embryogenesis, secreted proteins dictate the body plan of developing individuals. The resulting patterns are thought to be imposed by a graded distribution of molecular signals. To this day, it is not fully understood how signaling gradients are formed, maintained and adjusted to body sizes of differently sized individuals. This dissertation aims to provide new insights into the biophysical underpinnings of signal molecule gradients of early embryonic patterning and propose novel mechanisms that allow for scale-invariant patterning. Two of the most important parameters controlling the range and shape of signaling gradients are the rate at which signaling molecules decay and diffuse. Despite their importance, such biophysical parameters have not been measured or have only been assessed under simplified assumptions or contexts for most developmental systems. In this dissertation I present two assays and specialized software packages that allow the assessment of these parameters in living zebrafish embryos. I then demonstrate how these tools can be used to answer long-standing questions in early embryogenesis, such as how the dorsal-ventral axis is formed. This thesis provides evidence suggesting, in contrast to current hypotheses, that the dorsal-ventral axis is formed by a simple source-sink mechanism. Moreover, I show how to use mathematical modeling equipped with parameters estimated from the biophysical measurements to describe scale-invariant patterning during germ layer patterning in zebrafish development. My model, together with a rigorous multidimensional parameter screen fitted in normal and articially size-reduced embryos, was able to identify a new mechanism that allows for scaling of the germ layers in differently-sized embryos with realistic parameter congurations. In summary, this dissertation outlines how a systems biology approach can play a crucial role to advance the understanding of classical open questions in developmental biology

Mechanics of bacterial cellulose hydrogel

Natural polymer-based hydrogels, like bacterial cellulose (BC) hydrogels, gained a growing interest in the past decade mainly thanks to their good biological properties and similar fibrous structure as real human tissues that make them good potential candidate materials for various applications in a biomedical field. BC hydrogels are produced in a process of primary metabolism of some microorganisms. They were intensively studied with regard to their biological aspects, revealing many potential applications such as a direct implant replacement of some real tissues and an excellent scaffold for in-vitro tissue regeneration; still, its mechanical behaviour under application-relevant conditions has not been well documented. [Continues.