Studying macro- and microvascular responses to major surgery to develop preventive strategies for perioperative complications

Complications occur in up to 70% of patients undergoing surgery and may lead to further morbidity or even mortality. Systemic and local inflammatory processes in small and large blood vessels can cause such complications and therapeutic strategies are required for their prevention or treatment. In this thesis, we focused on understanding and targeting processes that cause inflammation after surgery in large and small blood vessels. We showed that a sharp drop in high-density lipoprotein cholesterol was strongly associated with the occurrence of heart attacks in patients undergoing vascular surgery. Further, we demonstrated smaller plaques in a model of atherosclerosis-prone mice that were lacking the protein Regulator of G Protein Signalling 5, which modulates processes for signal transduction within cells. To elucidate the inflammatory processes in small blood vessels, we generated a model to expose endothelial cells to patient plasma, obtained before and after surgery, under altered blood flow conditions. Furthermore, we identified the protein tyrosine kinases Axl and Fyn as therapeutic targets in microvascular endothelial inflammation induced by the acutely elevated pro-inflammatory mediator Tumour Necrosis Factor . Overall, our aim was to perform studies which can be used to develop strategies to prevent complications after surgery. We used laboratory animal and cell culture models in combination with patient data and materials to improve the current understanding of therapeutic targets for complications after surgery in both large and small blood vessels. While we cannot offer a solution to these problems, we identified multiple possible therapeutic targets that now require further investigations

Studying macro- and microvascular responses to major surgery to develop preventive strategies for perioperative complications

Complications occur in up to 70% of patients undergoing surgery and may lead to further morbidity or even mortality. Systemic and local inflammatory processes in small and large blood vessels can cause such complications and therapeutic strategies are required for their prevention or treatment. In this thesis, we focused on understanding and targeting processes that cause inflammation after surgery in large and small blood vessels. We showed that a sharp drop in high-density lipoprotein cholesterol was strongly associated with the occurrence of heart attacks in patients undergoing vascular surgery. Further, we demonstrated smaller plaques in a model of atherosclerosis-prone mice that were lacking the protein Regulator of G Protein Signalling 5, which modulates processes for signal transduction within cells. To elucidate the inflammatory processes in small blood vessels, we generated a model to expose endothelial cells to patient plasma, obtained before and after surgery, under altered blood flow conditions. Furthermore, we identified the protein tyrosine kinases Axl and Fyn as therapeutic targets in microvascular endothelial inflammation induced by the acutely elevated pro-inflammatory mediator Tumour Necrosis Factor . Overall, our aim was to perform studies which can be used to develop strategies to prevent complications after surgery. We used laboratory animal and cell culture models in combination with patient data and materials to improve the current understanding of therapeutic targets for complications after surgery in both large and small blood vessels. While we cannot offer a solution to these problems, we identified multiple possible therapeutic targets that now require further investigations

Macrophages and cytokines in the early defence against herpes simplex virus

Herpes simplex virus (HSV) type 1 and 2 are old viruses, with a history of evolution shared with humans. Thus, it is generally well-adapted viruses, infecting many of us without doing much harm, and with the capacity to hide in our neurons for life. In rare situations, however, the primary infection becomes generalized or involves the brain. Normally, the primary HSV infection is asymptomatic, and a crucial element in the early restriction of virus replication and thus avoidance of symptoms from the infection is the concerted action of different arms of the innate immune response. An early and light struggle inhibiting some HSV replication will spare the host from the real war against huge amounts of virus later in infection. As far as such a war will jeopardize the life of the host, it will be in both interests, including the virus, to settle the conflict amicably. Some important weapons of the unspecific defence and the early strikes and beginning battle during the first days of a HSV infection are discussed in this review. Generally, macrophages are orchestrating a multitude of anti-herpetic actions during the first hours of the attack. In a first wave of responses, cytokines, primarily type I interferons (IFN) and tumour necrosis factor are produced and exert a direct antiviral effect and activate the macrophages themselves. In the next wave, interleukin (IL)-12 together with the above and other cytokines induce production of IFN-γ in mainly NK cells. Many positive feed-back mechanisms and synergistic interactions intensify these systems and give rise to heavy antiviral weapons such as reactive oxygen species and nitric oxide. This results in the generation of an alliance against the viral enemy. However, these heavy weapons have to be controlled to avoid too much harm to the host. By IL-4 and others, these reactions are hampered, but they are still allowed in foci of HSV replication, thus focusing the activity to only relevant sites. So, no hero does it alone. Rather, an alliance of cytokines, macrophages and other cells seems to play a central role. Implications of this for future treatment modalities are shortly considered

Determining a Function for the Damping Coefficient of a laminated Stack

The design of electrical machines is determined by electrical as well as mechanical requirements. Possible lossesdue to eddy currents in the stator or the rotor are commonly reduced by using stacks of laminated sheet metal. On the other hand, the design of the stator and the rotor has a significant influence on the mechanical properties: Vibrations depend on the stiffness and the damping of the laminated stack. There are different methods to determine the stiffness coefficient of a stack, but it is much more difficult to obtain suitable values for the damping as there are more influencing factors. This paper describes an experimental procedure, which determines the influence of different parameters on the damping of a stack. The stack used during the experiments consists of 200 quadratic steel sheets with a side length of 80 mm and a thickness of 0.5 mm. In accordance with the measurement data, a functional dependance based on three variables is derived. The first one is the surface pressure between the steel sheets, the second one is the frequency of the applied lateral force, and the third one is the displacement between the steel sheets. It is the aim of this investigation to determine the influence of variations of these parameter values on the damping. The forces are applied onto the stack with hydraulic cylinders. The mechanical deformation of the stacked metal sheets is measured by a laser-speckle-based measurement system. This system detects the displacement of single steel sheets. The displacement is measured on two steel sheets, but they are not side by side. The difference between the two measurement points is equal to the displacement of the stack. Through the synchronization of the time signal of the lateral force and the displacement of the stack, a hysteresis loop can be calculated. This hysteresis depends on the lateral force and the displacement of the stack. The area of the hysteresis corresponds to the dissipation energy between the two measurement points on the stack, 140 sheets apart from each other. This area is calculated by numerical integration based on the trapezoidal rule. Through the conservation of energy for this system, it is possible to calculate an effective damping coefficient for the stack. Considering different influencing parameters, a function for the damping coefficient can be identified by the least square method. This function can be used for the parameters in a numerical simulation of an electrical machine

Development and analysis of radial force waves in electrical rotating machines

Vibrations in electrical machines lead to undesired operating conditions and noise. The reasons lie in the design of the machine and the lack of precision in manufacturing. In order to avoid excessive vibrations, complex numerical analyses are carried out. This work deals with the development and analysis of electromechanical excitations in asynchronous machines with a short circuit rotor. The time-dependent electromagnetic forces acting on the stator bore are simulated with the method of finite elements. Subsequently, the force waves with respect to the frequencies and amplitudes are analyzed

Production of exotic atoms at energies available at the CERN Large Hadron Collider

We study in details the space-time dependence of the production of muonic, pionic, and other exotic atoms by the coherent photon exchange between nuclei at the Large Hadron Collider at CERN. We show that a multipole expansion of the electromagnetic interaction yields an useful insight of the bound-free production mechanism which has not been explored in the literature. Predictions for the spatial, temporal, and angular distribution, as well as the total cross sections, for the production of exotic atoms are also included.Comment: 8 pages, 5 figures, version published in the Physical Review

THE INFLUENCE OF TWO DIFFERENT BRACES ON LATERAL PATELLAR DISPLACEMENT – A CADAVERIC STUDY

Patellofemoral pain syndrome (PFPS) often occurs in young and physically active athletes (Taunton et al., 2002, Adirim & Cheng, 2003).It is generally accepted that a cause of PFPS is a malalignment of the patellofemoral joint. Bracing supply is commonly used for the treatment of PFPS. Several studies have shown that patellar bracing and taping improved PFPS (Lun et al., 2005, Warden et al., 2008). Crossley et al. (2009) found a reduced lateral patellar displacement and a decreased mean pain (mean pain was recorded on a 100 mm visual analog scale during single-leg squats) after patellar taping. A more medial displacement of the patella and a decrease in patellofemoral stress could lead to less patellofemoral pain (Powers et al., 2004). A more medial patellar displacement could result in a more centered patella. Therefore, the purpose of this study was to investigate the effect of two different braces on the alignment of the patella

Fault Detection in Offshore Structures: Influence of Sensor Number, Placement and Quality

Within the Space@Sea project floating offshore islands, designed as an assembly of platforms, are used to create space in offshore environments. Offshore structures are exposed to harsh environment conditions. High wind speeds, heavy rainfall, ice and wave forces lead to highly stressed structures. The platforms at the Space@Sea project are connected by ropes and fenders. There exists the risk of a rope failing which is therefore investigated subsequently. To ensure the safety of the structure, the rope parameters are monitored by the Extended Kalman Filter (EKF). For platform arrangements, a large number of sensors is required for accurate fault diagnosis of these ropes, leading to high investment costs. This paper presents a strategy to optimize the number and placement of acceleration sensors attached to the floating platforms. There are also high demands on the sensors due to the harsh offshore conditions. Material deterioration and overloading may lead to decayed sensor performance or sensor defects. Maintenance of offshore sensors is difficult, expensive and often not feasible within a short time. Therefore, sensor measurement deviations must not affect reliable structure fault detection. The influence of defect sensors on the rope fault detection is examined in this study: Types, intensities, number, place of occurrence of defect sensors and the distance between defect sensors and rope faults are varied