Spinal cord injury (SCI) causes delayed secondary biochemical alterations that lead to tissue loss and associated neurological dysfunction. Up-regulation of cell cycle proteins occurs in both neurons ...and glia after SCI and may contribute to these changes. The present study examined the role of cell cycle activation on secondary injury after severe SCI in rat. SCI caused cell cycle protein up-regulation associated with neuronal and oligodendroglial apoptosis, glial scar formation and microglial activation. Treatment with the cell cycle inhibitor flavopiridol reduced cell cycle protein induction and significantly improved functional recovery versus vehicle-treated controls at 21 and 28 days post-injury. Treatment also significantly reduced lesion volume, as measured by MRI and histology, decreased astrocytic reactivity, attenuated neuronal and oligodendroglial apoptosis and reduced the production of factors associated with microglial activation. Thus, flavopiridol treatment improves outcome after SCI by inhibiting cell cycle pathways, resulting in beneficial multifactorial actions on neurons and glia.
Recently developed controllers for robot-assisted gait training allow for the adjustment of assistance for specific subtasks (i.e. specific joints and intervals of the gait cycle that are related to ...common impairments after stroke). However, not much is known about possible interactions between subtasks and a better understanding of this can help to optimize (manual or automatic) assistance tuning in the future. In this study, we assessed the effect of separately assisting three commonly impaired subtasks after stroke: foot clearance (FC, knee flexion/extension during swing), stability during stance (SS, knee flexion/extension during stance) and weight shift (WS, lateral pelvis movement). For each of the assisted subtasks, we determined the influence on the performance of the respective subtask, and possible effects on other subtasks of walking and spatiotemporal gait parameters.
The robotic assistance for the FC, SS and WS subtasks was assessed in nine mildly impaired chronic stroke survivors while walking in the LOPES II gait trainer. Seven trials were performed for each participant in a randomized order: six trials in which either 20% or 80% of assistance was provided for each of the selected subtasks, and one baseline trial where the participant did not receive subtask-specific assistance. The influence of the assistance on performances (errors compared to reference trajectories) for the assisted subtasks and other subtasks of walking as well as spatiotemporal parameters (step length, width and height, swing and stance time) was analyzed.
Performances for the impaired subtasks (FC, SS and WS) improved significantly when assistance was applied for the respective subtask. Although WS performance improved when assisting this subtask, participants were not shifting their weight well towards the paretic leg. On a group level, not many effects on other subtasks and spatiotemporal parameters were found. Still, performance for the leading limb angle subtask improved significantly resulting in a larger step length when applying FC assistance.
FC and SS assistance leads to clear improvements in performance for the respective subtask, while our WS assistance needs further improvement. As effects of the assistance were mainly confined to the assisted subtasks, tuning of FC, SS and WS can be done simultaneously. Our findings suggest that there may be no need for specific, time-intensive tuning protocols (e.g. tuning subtasks after each other) in mildly impaired stroke survivors.
Begemann M, Spengler S, Kanber D, Haake A, Baudis M, Leisten I, Binder G, Markus S, Rupprecht T, Segerer H, Fricke‐Otto S, Mühlenberg R, Siebert R, Buiting K, Eggermann T. Silver‐Russell patients ...showing a broad range of ICR1 and ICR2 hypomethylation in different tissues.
In all known congenital imprinting disorders an association with aberrant methylation or mutations at specific loci was well established. However, several patients with transient neonatal diabetes mellitus (TNDM), Silver‐Russell syndrome (SRS) and Beckwith‐Wiedemann syndrome (BWS) exhibiting multilocus hypomethylation (MLH) have meanwhile been described. Whereas TNDM patients with MLH show clinical symptoms different from carriers with isolated 6q24 aberrations, MLH carriers diagnosed as BWS or SRS present only the syndrome‐specific features. Interestingly, SRS and BWS patients with nearly identical MLH patterns in leukocytes have been identified. We now report on the molecular findings in DNA in three SRS patients with hypomethylation of both 11p15 imprinted control regions (ICRs) in leukocytes. One patient was a monozygotic (MZ) twin, another was a triplet. While the hypomethylation affected both oppositely imprinted 11p15 ICRs in leukocytes, in buccal swab DNA only the ICR1 hypomethylation was visible in two of our patients. In the non‐affected MZ twin of one of these patients, aberrant methylation was also present in leukocytes but neither in buccal swab DNA nor in skin fibroblasts. Despite mutation screening of several factors involved in establishment and maintenance of methylation marks including ZFP57, MBD3, DNMT1 and DNMT3L the molecular clue for the ICR1/ICR2 hypomethylation in our patients remained unclear. Furthermore, the reason for the development of the specific SRS phenotype is not obvious. In conclusion, our data reflect the broad range of epimutations in SRS and illustrate that an extensive molecular and clinical characterization of patients is necessary.
We present resistively detected NMR measurements in induced and modulation-doped electron quantum point contacts, as well as induced hole quantum point contacts. While the magnitude of the resistance ...change and associated NMR peaks in n-type devices is in line with other recent measurements using this technique, the effect in p-type devices is too small to measure. This suggests that the hyperfine coupling between holes and nuclei in this type of device is much smaller than the electron hyperfine coupling, which could have implications in quantum information processing.
We established a real-time PCR assay for the detection and strain identification of Candida species and demonstrated the ability to differentiate between Candida albicans the most common species, and ...also Candida parapsilosis, Candida glabrata, Candida tropicalis and Candida dubliniensis by LightCycler PCR and melting curve analysis. The DNA isolation from cultures and serum was established using the QIAmp Tissue Kit. The sensitivity of the assay was ≥ 2 genome equivalents/assay. It was possible to differentiate all investigated Candida species by melting curve analysis, and no cross-reaction to human DNA or Aspergillus species could be observed. The established real-time PCR assay is a useful tool for the rapid identification of Candida species and a base technology for more complex PCR assays. We carried out initial steps in validation of a PCR assay for the detection and differentiation of medically relevant Candida species. The PCR was improved by generating PCR standards, additional generation of melting curves for species identification and the possibility to investigate different specimens simultaneously.
This paper describes the design and setup of the new AC current transformer calibration system at PTB, which uses enhanced actively compensated current comparators (CCs) for rated primary currents ...from 5 A up to 60 kA and a new current transformer bridge based on the differential method. The bridge makes use of modern high-resolution analog-to-digital converters and makes it possible to connect traditional current transformers (CTs) as well as two-stage CTs with rated secondary currents from 100 mA to 5A. The lower current ranges are integrated to enable a calibration of CTs of the highest available precision for national power standards. The current sensors and the two-channel sampling system of the bridge allow a resolution in the order of 10 -10 , while the estimated Type-B uncertainty of the bridge is in the range of 10 -8 .
Mixed findings have been obtained in prior research with respect to the presence and severity of memory and metamemory deficits in obsessive–compulsive disorder (OCD). We tested the hypothesis that ...experimentally induced increments of subjective responsibility would lead to a disproportionately strong decline of memory confidence and enhanced response latencies in OCD while leaving memory accuracy unaffected. Twenty-eight OCD patients and 28 healthy controls were presented a computerized memory test framed with two different scenarios. In the neutral scenario, the participant was requested to imagine purchasing 15 items from a do-it-yourself store. In the recognition phase, the 15 needed items were presented along with 15 distractor items. The participant was asked to decide whether items were on his or her shopping list or not, graded by subjective confidence. In the responsibility scenario, the general experimental setup was analogous except that the participant now had to envision that he or she was a helper in a region recently struck by an earthquake, dispatched to provide 15 urgently needed goods from a nearby town. In line with prior work by our group, samples did not differ in either condition on memory accuracy in a subsequent recognition task. As hypothesized, OCD participants were less certain in their responses for the high responsibility condition than controls. Whereas patients and controls did not differ in their subjective estimates for memorized items, patients expressed stronger doubt that their earthquake mission was successful. The findings indicate that low memory confidence in OCD may only be elicited in situations where perceived responsibility is high and that patients may share higher performance standards (“good is not good enough”) than controls when perceived responsibility is inflated.
PDF
