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

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

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

Does planning a different trajectory influence the choice of grasping points?

We examined whether the movement path is considered when selecting the positions at which the digits will contact the object's surface (grasping points). Subjects grasped objects of different heights but with the same radius at various locations on a table. At some locations, one digit crossed to the side of the object opposite of where it started. In doing so, it moved over a short object whereas it curved around a tall object. This resulted in very different paths for different objects. Importantly, the selection of grasping points was unaffected. That subjects do not appear to consider the path when selecting grasping points suggests that the grasping points are selected before planning the movements towards those points. © 2010 The Author(s)

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

Doppler-free frequency modulation spectroscopy of atomic erbium in a hollow cathode discharge cell

The erbium atomic system is a promising candidate for an atomic Bose-Einstein condensate of atoms with a non-vanishing orbital angular momentum ($L \neq 0$) of the electronic ground state. In this paper we report on the frequency stabilization of a blue external cavity diode laser system on the 400.91 $nm$ laser cooling transition of atomic erbium. Doppler-free saturation spectroscopy is applied within a hollow cathode discharge tube to the corresponding electronic transition of several of the erbium isotopes. Using the technique of frequency modulation spectroscopy, a zero-crossing error signal is produced to lock the diode laser frequency on the atomic erbium resonance. The latter is taken as a reference laser to which a second main laser system, used for laser cooling of atomic erbium, is frequency stabilized

Knee and Hip Joint Kinematics Predict Quadriceps and Hamstrings Neuromuscular Activation Patterns in Drop Jump Landings.

PURPOSE: The purpose was to assess if variation in sagittal plane landing kinematics is associated with variation in neuromuscular activation patterns of the quadriceps-hamstrings muscle groups during drop vertical jumps (DVJ). METHODS: Fifty female athletes performed three DVJ. The relationship between peak knee and hip flexion angles and the amplitude of four EMG vectors was investigated with trajectory-level canonical correlation analyses over the entire time period of the landing phase. EMG vectors consisted of the {vastus medialis(VM),vastus lateralis(VL)}, {vastus medialis(VM),hamstring medialis(HM)}, {hamstring medialis(HM),hamstring lateralis(HL)} and the {vastus lateralis(VL),hamstring lateralis(HL)}. To estimate the contribution of each individual muscle, linear regressions were also conducted using one-dimensional statistical parametric mapping. RESULTS: The peak knee flexion angle was significantly positively associated with the amplitudes of the {VM,HM} and {HM,HL} during the preparatory and initial contact phase and with the {VL,HL} vector during the peak loading phase (p<0.05). Small peak knee flexion angles were significantly associated with higher HM amplitudes during the preparatory and initial contact phase (p<0.001). The amplitudes of the {VM,VL} and {VL,HL} were significantly positively associated with the peak hip flexion angle during the peak loading phase (p<0.05). Small peak hip flexion angles were significantly associated with higher VL amplitudes during the peak loading phase (p = 0.001). Higher external knee abduction and flexion moments were found in participants landing with less flexed knee and hip joints (p<0.001). CONCLUSION: This study demonstrated clear associations between neuromuscular activation patterns and landing kinematics in the sagittal plane during specific parts of the landing. These findings have indicated that an erect landing pattern, characterized by less hip and knee flexion, was significantly associated with an increased medial and posterior neuromuscular activation (dominant hamstrings medialis activity) during the preparatory and initial contact phase and an increased lateral neuromuscular activation (dominant vastus lateralis activity) during the peak loading phase

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PURPOSE: An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. METHODS: Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. RESULTS: Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. CONCLUSION: The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene