Myelofibrosis: molecular and cell biological aspects

A subset of myeloproliferative disorders (MPN) and myelodyplastic syndromes (MDS) evolves to fibrosis of the bone marrow associated with haematopoietic insufficiency. We have been interested in chemokines involved in fibrogenesis within the bone marrow. Besides TGFβ we could identify a number of additional mediators including osteoprotegerin and bone morphogenic proteins. In MPN JAK2 or MPL mutation are not linked to the propensity for bone marrow fibrosis. The hypothesis that an increased intramedullary decay of megakaryocytes undergoing appotosis takes place within the marrow, thus liberating fibrogenic cytokines, could not be confirmed. On the contrary, megakaryocytes in primary fibrosis revealed low expression of proapoptotic genes such as BNIP3. Interestingly, BNIP 3 expression was down regulated in megakaryocytic cell lines kept in hypoxic conditions. Furthermore, expression arrays revealed hypoxia inducible genes to be up-regulated in primary myelofibrosis. Fibrotic MPN are characterized by aberrant proplatelet formation which represent cytoplasmic pseudopodia and normally extend into the sinus. In fibrotic MPN orientation of proplatelet growth appears to be disturbed, which could lead to an aberrant deposition of platelets in the marrow with consecutive liberation of fibrogenic cytokines

Parametric motion control of robotic arms: A biologically based approach using neural networks

A neural network based system is presented which is able to generate point-to-point movements of robotic manipulators. The foundation of this approach is the use of prototypical control torque signals which are defined by a set of parameters. The parameter set is used for scaling and shaping of these prototypical torque signals to effect a desired outcome of the system. This approach is based on neurophysiological findings that the central nervous system stores generalized cognitive representations of movements called synergies, schemas, or motor programs. It has been proposed that these motor programs may be stored as torque-time functions in central pattern generators which can be scaled with appropriate time and magnitude parameters. The central pattern generators use these parameters to generate stereotypical torque-time profiles, which are then sent to the joint actuators. Hence, only a small number of parameters need to be determined for each point-to-point movement instead of the entire torque-time trajectory. This same principle is implemented for controlling the joint torques of robotic manipulators where a neural network is used to identify the relationship between the task requirements and the torque parameters. Movements are specified by the initial robot position in joint coordinates and the desired final end-effector position in Cartesian coordinates. This information is provided to the neural network which calculates six torque parameters for a two-link system. The prototypical torque profiles (one per joint) are then scaled by those parameters. After appropriate training of the network, our parametric control design allowed the reproduction of a trained set of movements with relatively high accuracy, and the production of previously untrained movements with comparable accuracy. We conclude that our approach was successful in discriminating between trained movements and in generalizing to untrained movements

A Recursive Algorithm for Computing Inferences in Imprecise Markov Chains

We present an algorithm that can efficiently compute a broad class of inferences for discrete-time imprecise Markov chains, a generalised type of Markov chains that allows one to take into account partially specified probabilities and other types of model uncertainty. The class of inferences that we consider contains, as special cases, tight lower and upper bounds on expected hitting times, on hitting probabilities and on expectations of functions that are a sum or product of simpler ones. Our algorithm exploits the specific structure that is inherent in all these inferences: they admit a general recursive decomposition. This allows us to achieve a computational complexity that scales linearly in the number of time points on which the inference depends, instead of the exponential scaling that is typical for a naive approach

The distinction between gastric ulceration and carcinoma of the stomach : value of the erythrocyte sedimentation rate and the maximal acid output

CITATION: Bock, O. A. A. & Boyd, I. H. 1973. The distinction between gastric ulceration and carcinoma of the stomach : value of the erythrocyte sedimentation rate and the maximal acid output. South African Medical Journal, 47(29):1259-1260.The original publication is available at http://www.samj.org.zaThe erythrocyte sedimentation rate (ESR) is not a reliable criterion for distinguishing between gastric ulceration and carcinoma of the stomach. If the maximal acid output (MAO) = 0 mEq/h, the lesion is, with few exceptions, a carcinoma. Combining the ESR and MAO did not provide a more reliable criterion for distinguishing between gastric ulcer and carcinoma of the stomach, than when MAO alone is taken into consideration.Publisher’s versio

Age-related differences of the gaze pattern in a realistic pedestrian traffic task

Laboratory studies suggest that the gaze pattern changes in older age, both in seated and in walking persons. Here we investigate the gaze pattern in a more complex and realistic scenario: walking in a virtual-reality shopping precinct. Seventeen young and sixteen older adults walked at their preferred speed on a treadmill driven by their leg movements, thus controlling the presentation of a virtual 3D world on a screen 130 cm ahead. The screen showed a shopping street with stationary and moving objects, and with six pedestrian traffic lights of whom three turned red upon approach. Gaze direction was registered by a video-based system. We found that each glance at a traffic light took longer in older than in young persons, and the sum of all glances at a traffic light was longer as well. In effect, older persons looked at the traffic light equally long throughout all three light phases, while young ones gradually increased their inspection of the traffic light as the green phase went on. The observed change of the gaze pattern in older age could represent a compensatory strategy to facilitate spatial orientation and/or movement preparation, or it could reflect a deficit of gaze disengagement. Future research should disambiguate these alternatives. In any case, the observed change is detrimental for seniors’ sensorimotor performance in everyday scenarios

Thermal acclimation to 4 or 10°C imparts minimal benefit on swimming performance in Atlantic cod ( Gadus morhua L.)

Thermal acclimation is frequently cited as a means by which ectothermic animals improve their Darwinian fitness, i.e. the beneficial acclimation hypothesis. As the critical swimming speed (U crit) test is often used as a proxy measure of fitness, we acclimated Atlantic cod (Gadus morhua) to 4 and 10°C and then assessed their U crit swimming performance at their respective acclimation temperatures and during acute temperature reversal. Because phenotypic differences exist between different populations of cod, we undertook these experiments in two different populations, North Sea cod and North East Arctic cod. Acclimation to 4 or 10°C had a minimal effect on swimming performance or U crit, however test temperature did, with all groups having a 10-17% higher U crit at 10°C. The swimming efficiency was significantly lower in all groups at 4°C arguably due to the compression of the muscle fibre recruitment order. This also led to a reduction in the duration of "kick and glide” swimming at 4°C. No significant differences were seen between the two populations in any of the measured parameters, due possibly to the extended acclimation period. Our data indicate that acclimation imparts little benefit on U crit swimming test in Atlantic cod. Further efforts need to identify the functional consequences of the long-term thermal acclimation proces

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

Impact of anthropogenic ocean acidification on thermal tolerance of the spider crab <i>Hyas araneus</i>

Future scenarios for the oceans project combined developments of CO₂ accumulation and global warming and their impact on marine ecosystems. The synergistic impact of both factors was addressed by studying the effect of elevated CO₂ concentrations on thermal tolerance of the cold-eurythermal spider crab <i>Hyas araneus</i> from the population around Helgoland. Here ambient temperatures characterize the southernmost distribution limit of this species. Animals were exposed to present day normocapnia (380 ppm CO₂), CO₂ levels expected towards 2100 (710 ppm) and beyond (3000 ppm). Heart rate and haemolymph PO₂ (P_eO₂) were measured during progressive short term cooling from 10 to 0&deg;C and during warming from 10 to 25&deg;C. An increase of P_eO₂ occurred during cooling, the highest values being reached at 0&deg;C under all three CO₂ levels. Heart rate increased during warming until a critical temperature (<i>T_c</i>) was reached. The putative <i>T_c</i> under normocapnia was presumably &gt;25&deg;C, from where it fell to 23.5&deg;C under 710 ppm and then 21.1&deg;C under 3000 ppm. At the same time, thermal sensitivity, as seen in the <i>Q₁₀</i> values of heart rate, rose with increasing CO₂ concentration in the warmth. Our results suggest a narrowing of the thermal window of <i>Hyas araneus</i> under moderate increases in CO₂ levels by exacerbation of the heat or cold induced oxygen and capacity limitation of thermal tolerance

Flow into a well by electric and membrane analogy

CER55DFP11.Includes bibliographical references.October, 1955.Proceedings - American Society of Civil Engineers, Engineering Mechanics Division, 1955