Arterial haptoglobin : expression, regulation and function

Several studies have demonstrated that collagen turnover is important during arterial restructuring. However, the precise mediators involved in collagen turnover are still not known. In order to develop specific inhibitors to prevent arterial restructuring, it is essential to get a better understanding of the molecular pathways involved in collagen turnover. In this thesis, we used a subtraction PCR to identify new candidate proteins that are involved in arterial restructuring and to get a better insight in these pathways. One of the identified proteins using subtraction PCR was the acute phase glycoprotein haptoglobin. Haptoglobin was found to be expressed by adventitial fibroblasts, early after flow changes. In vitro assays demonstrated that haptoglobin is a gelatinase inhibitor and important for cell migration. Furthermore, haptoglobin knockout mice demonstrated delayed arterial restructuring after flow changes. As NO plays an important role in flow-induced arterial restructuring, we investigated whether arterial haptoglobin expression was regulated via NO. Inhibition of NO synthesis by a aspecific NOS-inhibitor resulted in decreased arterial haptoglobin expression. This coincided with decreased arterial IL-6 expression, which is a well described regulator of haptoglobin expression in the liver. IL-6 knockout mice were used to confirm a regulatory role of IL-6 in arterial haptoglobin expression. However, haptoglobin expression was normal in IL-6 knockout mice, pointing to back-up mechanisms for the regulation of haptoglobin expression. Previously, sero-epidemiological studies have demonstrated that arthritis and cancer are characterized by increased serum haptoglobin levels. In this thesis, we demonstrated that local expression of haptoglobin is increased in these two pathological tissues that are characterized by enhanced cell migration and matrix turnover. As haptoglobin is present at high concentrations in the serum, the function of local haptoglobin expression is not completely understood. We therefore investigated whether alterations in haptoglobin glycosylation could explain the necessity of local haptoglobin expression. Haptoglobin expression and glycosylation was studied in balloon dilated rabbit arteries. Balloon dilation increased arterial haptoglobin expression within the first two weeks after injury whereas liver haptoglobin expression remained constant. There were no differences in arterial haptoglobin glycosylation patterns after balloon dilation. However, arterial haptoglobin was differentially glycosylated compared to liver haptoglobin and these arterial haptoglobin glycoforms could be detected in the serum. Previously, alterations in serum haptoglobin glycosylation have been associated with the progression and outcome of different diseases. As arterial haptoglobin has a characteristic glycosylation pattern, we investigated whether serum haptoglobin glycosylation patterns could serve as serum marker for atherosclerotic disease. There were, however, no differences were found in total serum haptoglobin levels or serum haptoglobin glycosylation patterns between patients with atherosclerosis and patients with only risk factors. In addition, no relation was found between total serum haptoglobin levels and glycosylation patterns with intima-media thickness in the carotid artery, which is a surrogate measure for the extent of atherosclerosis. These results indicate that serum haptoglobin glycosylation patterns are not suitable to use as serum marker for atherosclerotic diseas

Діалогізм як умова реалізації свободи в іудаїзмі

У статті розглядається проблема співвідношення феномена свободи з такою формою реалізації людської екзистенції, як діалог. Для іудаїзму виявами діалогу на рівні розкриття зв'язку "Я" з "абсолютним Ти" є молитва та пророцтво. Автор доводить, що ці форми діалогу у свій власний спосіб виявляють механізми актуалізації індивідуальної та колективної свободи. Метою свободи виступає повнота розкриття призначення існування людини та людства у світі.In the article examines the problem of comparing the phenomenon of freedom with a form of human realization of existence, such as dialog. For Judaism, prayer and prophecy are the opening to the connection of "I" and the absolute "You". These forms of dialog, in their own way, appear to be mechanisms of the actualization of individual and collective freedom. The goal of this freedom appears to be the full understanding of the purpose of man and humanity in the world

Precise timing when hitting falling balls

People are extremely good at hitting falling balls with a baseball bat. Despite the ball’s constant acceleration, they have been reported to time hits with a standard deviation of only about 7ms. To examine how people achieve such precision, we compared performance when there were no added restrictions, with performance when looking with one eye, when vision was blurred, and when various parts of the ball’s trajectory were hidden from view. We also examined how the size of the ball and varying the height from which it was dropped influenced temporal precision. Temporal precision did not become worse when vision was blurred, when the ball was smaller, or when balls falling from different heights were randomly interleaved. The disadvantage of closing one eye did not exceed expectations from removing one of two independent estimates. Precision was higher for slower balls, but only if the ball being slower meant that one saw it longer before the hit. It was particularly important to see the ball while swinging the bat. Together, these findings suggest that people time their hits so precisely by using the changing elevation throughout the swing to adjust the bat’s movement to that of the ball

Rethinking deindustrialization

Manufacturing in high-income countries is on the decline and Denmark is no exception. Manufacturing employment and the number of firms have been shrinking as a share of the total and in absolute levels. This paper uses a rich linked employer-employee dataset to examine this decline from 1994 to 2007. We propose a different approach to analyze deindustrialization and generate a series of novel stylized facts about the evolution. While most of the decline can be attributed to firm exit and reduced employment at surviving manufacturers, we document that a non-negligible portion is due to firms switching industries, from manufacturing to services. We focus on this last group of firms before, during, and after their sector switch. Overall this is a group of small, highly productive, import intensive firms that grow rapidly in terms of value-added and sales after they switch. By 2007, employment at these former manufacturers equals 8.7 percent of manufacturing employment, accounting for half the decline in manufacturing employment. We focus on the composition of the workforce as firms make their transition. In addition, we identify two types of switchers: one group resembles traditional wholesalers and another group that retains and expands their R&D and technical capabilities. Our findings emphasize that the focus on employment at manufacturing firms overstates the loss in manufacturingrelated capabilities that are actually retained in many firms that switch industries

Atom lithography without laser cooling

Using direct-write atom lithography, Fe nanolines are deposited with a pitch of 186 nm, a full width at half maximum (FWHM) of 50 nm, and a height of up to 6 nm. These values are achieved by relying on geometrical collimation of the atomic beam, thus without using laser collimation techniques. This opens the way for applying direct-write atom lithography to a wide variety of elements.Comment: 7 pages, 11 figure

Similarities between digits’ movements in grasping, touching and pushing

In order to find out whether the movements of single digits are controlled in a special way when grasping, we compared the movements of the digits when grasping an object with their movements in comparable single-digit tasks: pushing or lightly tapping the same object at the same place. The movements of the digits in grasping were very similar to the movements in the single-digit tasks. To determine to what extent the hand transport and grip formation in grasping emerges from a synchronised motion of individual digits, we combined movements of finger and thumb in the single-digit tasks to obtain hypothetical transport and grip components. We found a larger peak grip aperture earlier in the movement for the single-digit tasks. The timing of peak grip aperture depended in the same way on its size for all tasks. Furthermore, the deviations from a straight line of the transport component differed considerably between subjects, but were remarkably similar across tasks. These results support the idea that grasping should be regarded as consisting of moving the digits, rather than transporting the hand and shaping the grip

The latency for correcting a movement depends on the visual attribute that defines the target

Neurons in different cortical visual areas respond to different visual attributes with different latencies. How does this affect the on-line control of our actions? We studied hand movements directed toward targets that could be distinguished from other objects by luminance, size, orientation, color, shape or texture. In some trials, the target changed places with one of the other objects at the onset of the hand’s movement. We determined the latency for correcting the movement of the hand in the direction of the new target location. We show that subjects can correct their movements at short latency for all attributes, but that responses for the attributes color, form and texture (that are relevant for recognizing the object) are 50 ms slower than for the attributes luminance, orientation and size. This dichotomy corresponds to both to the distinction between magno-cellular and parvo-cellular pathways and to a dorsal–ventral distinction. The latency also differed systematically between subjects, independent of their reaction time

Processing of structural neuroimaging data in young children:bridging the gap between current practice and state-of-the-art methods

The structure of the brain is subject to very rapid developmental changes during early childhood. Pediatric studies based on Magnetic Resonance Imaging (MRI) over this age range have recently become more frequent, with the advantage of providing in vivo and non-invasive high-resolution images of the developing brain, toward understanding typical and atypical trajectories. However, it has also been demonstrated that application of currently standard MRI processing methods that have been developed with datasets from adults may not be appropriate for use with pediatric datasets. In this review, we examine the approaches currently used in MRI studies involving young children, including an overview of the rationale for new MRI processing methods that have been designed specifically for pediatric investigations. These methods are mainly related to the use of age-specific or 4D brain atlases, improved methods for quantifying and optimizing image quality, and provision for registration of developmental data obtained with longitudinal designs. The overall goal is to raise awareness of the existence of these methods and the possibilities for implementing them in developmental neuroimaging studies