266 research outputs found
Standardized loads acting in knee implants
No full textThe loads acting in knee joints must be known for improving joint replacement, surgical procedures, physiotherapy, biomechanical computer simulations, and to advise patients with osteoarthritis or fractures about what activities to avoid. Such data would also allow verification of test standards for knee implants. This work analyzes data from 8 subjects with instrumented knee implants, which allowed measuring the contact forces and moments acting in the joint. The implants were powered inductively and the loads transmitted at radio frequency. The time courses of forces and moments during walking, stair climbing, and 6 more activities were averaged for subjects with I) average body weight and average load levels and II) high body weight and high load levels. During all investigated activities except jogging, the high force levels reached 3,372–4,218N. During slow jogging, they were up to 5,165N. The peak torque around the implant stem during walking was 10.5 Nm, which was higher than during all other activities including jogging. The transverse forces and the moments varied greatly between the subjects, especially during non-cyclic activities. The high load levels measured were mostly above those defined in the wear test ISO 14243. The loads defined in the ISO test standard should be adapted to the levels reported here. The new data will allow realistic investigations and improvements of joint replacement, surgical procedures for tendon repair, treatment of fractures, and others. Computer models of the load conditions in the lower extremities will become more realistic if the new data is used as a gold standard. However, due to the extreme individual variations of some load components, even the reported average load profiles can most likely not explain every failure of an implant or a surgical procedure
A hip implant energy harvester
No full textThis paper presents a kinetic energy harvester designed to be embedded in a hip implant which aims to operate at a low frequency associated with body motion of patients. The prototype is designed based on the constrained volume available in a hip prosthesis and the challenge is to harvest energy from low frequency movements (< 1 Hz) which is an average frequency during free walking of a patient. The concept of magnetic-force-driven energy harvesting is applied to this prototype considering the hip movements during routine activities of patients. The magnetic field within the harvester was simulated using COMSOL. The simulated resonant frequency was around 30 Hz and the voltage induced in a coil was predicted to be 47.8 mV. A prototype of the energy harvester was fabricated and tested. A maximum open circuit voltage of 39.43 mV was obtained and the resonant frequency of 28 Hz was observed. Moreover, the power output of 0.96 ?W was achieved with an optimum resistive load of 250
Realistic loads for testing hip implants
No full textThe aim here was to define realistic load conditions for hip implants, based on in vivo contact force measurements, and to see whether current ISO standards indeed simulate real loads. The load scenarios obtained are based on in vivo hip contact forces measured in 4 patients during different activities and on activity records from 31 patients. The load scenarios can be adapted to various test purposes by applying average or high peak loads, high-impact activities or additional low-impact activities, and by simulating normal or very active patients. The most strenuous activities are walking (average peak forces 1800 N, high peak forces 3900 N), going up stairs (average peak forces 1900 N, high peak forces 4200 N) and stumbling (high peak forces 11,000 N). Torsional moments are 50% higher for going up stairs than for walking. Ten million loading cycles simulate an implantation time of 3.9 years in active patients. The in vitro fatigue properties of cementless implant fixations are exceeded during stumbling. At least for heavyweight and very active subjects, the real load conditions are more critical than those defined by the ISO standards for fatigue tests
Hip contact forces and gait patterns from routine activities
No full textIn vivo loads acting at the hip joint have so far only been measured in few patients and without detailed documentation of gait data. Such information is required to test and improve wear, strength and fixation stability of hip implants. Measurements of hip contact forces with instrumented implants and synchronous analyses of gait patterns and ground reaction forces were performed in four patients during the most frequent activities of daily living. From the individual data sets an average was calculated. The paper focuses on the loading of the femoral implant component but complete data are additionally stored on an associated compact disc. It contains complete gait and hip contact force data as well as calculated muscle activities during walking and stair climbing and the frequencies of daily activities observed in hip patients. The mechanical loading and function of the hip joint and proximal femur is thereby completely documented. The average patient loaded his hip joint with 238% BW (percent of body weight) when walking at about 4 km/h and with slightly less when standing on one leg. This is below the levels previously reported for two other patients (Bergmann et al., Clinical Biomechanics 26 (1993) 969-990). When climbing upstairs the joint contact force is 251% BW which is less than 260% BW when going downstairs. Inwards torsion of the implant is probably critical for the stem fixation. On average it is 23% larger when going upstairs than during normal level walking. The inter- and intra-individual variations during stair climbing are large and the highest torque values are 83% larger than during normal walking. Because the hip joint loading during all other common activities of most hip patients are comparably small (except during stumbling), implants should mainly be tested with loading conditions that mimic walking and stair climbing
The first organocatalytic asymmetric synthesis of 3-substituted isoindolinones
No full textHerein we describe the first asymmetric organocatalytic synthesis of 3-substituted isoindolinones in a convenient aldol-cyclization-rearrangement tandem reaction of malonates with 2-cyanobenzaldehyde. Bifunctional thiourea-cinchona catalysts proved to be particularly effective, giving the title compounds in high yields and moderate to good enantiomeric excesses. Moreover an efficient process of reverse crystallization led to a further enrichment up to >99% ee. © 2012 The Royal Society of Chemistry
Extracellular domains of alpha-neurexins participate in regulating synaptic transmission by selectively affecting N- and P/Q-type Ca2+ channels
No full textNeurexins constitute a large family of highly variable cell-surface molecules that may function in synaptic transmission and/or synapse formation. Each of the three known neurexin genes encodes two major neurexin variants, alpha- and beta-neurexins, that are composed of distinct extracellular domains linked to identical intracellular sequences. Deletions of one, two, or all three alpha-neurexins in mice recently demonstrated their essential role at synapses. In multiple alpha-neurexin knock-outs, neurotransmitter release from excitatory and inhibitory synapses was severely reduced, primarily probably because voltage-dependent Ca2+ channels were impaired. It remained unclear, however, which neurexin variants actually influence exocytosis and Ca2+ channels, which domain of neurexins is required for this function, and which Ca2+-channel subtypes are regulated. Here, we show by electrophysiological recordings that transgenic neurexin 1 alpha rescues the release and Ca2+-current phenotypes, whereas transgenic neurexin 1 beta has no effect, indicating the importance of the extracellular sequences for the function of neurexins. Because neurexin 1 alpha rescued the knock-out phenotype independent of the alpha-neurexin gene deleted, these data are consistent with a redundant function among different alpha-neurexins. In both knock-out and transgenically rescued mice, alpha-neurexins selectively affected the component of neurotransmitter release that depended on activation of N- and P/Q-type Ca2+ channels, but left L-type Ca2+ channels unscathed. Our findings indicate that alpha-neurexins represent organizer molecules in neurotransmission that regulate N- and P/Q-type Ca2+ channels, constituting an essential role at synapses that critically involves the extracellular domains of neurexins
Deletion of α-neurexins does not cause a major impairment of axonal pathfinding or synapse formation
No full textα-Neurexins are synaptic cell-surface molecules that are required for Ca2+-triggered exocytosis. Mice lacking all three α-neurexins show drastically reduced neurotransmitter release at excitatory and inhibitory synapses and die early postnatally. Although previous histological analysis of newborn α-neurexin triple mutants revealed only a moderate reduction in the density of type II synapses in the brainstem, cell culture studies proposed that neurexins are prominently involved in synapse formation. To assess the contribution of α-neurexins to the formation and structural properties of synapses in vivo, we performed a detailed morphological analysis of the brains from surviving adult double knockout mice lacking two of the three α-neurexins. Despite their impaired neurotransmission, we did not observe any gross anatomical defects or changes in the distribution of synaptic proteins in adult mutants. Only mild structural alterations were found: a ?20% reduction of neuropil area in many brain regions, resulting predominantly from shortened distal dendritic branches and fewer spines, as demonstrated by Golgi impregnation of pyramidal neurons. Quantitative electron microscopy revealed ultrastructurally normal type I and II terminals and a ?30% decrease in the density of type II synapses in the neocortex. To exclude errors in pathfinding, we investigated axonal projections in the olfactory bulb of newborn knockouts and did not observe any changes. Therefore, α-neurexins are not essential for the formation of the vast majority of synapses in vivo but rather regulate the function of these synapses. J. Comp. Neurol. 502:261?274, 2007. ? 2007 Wiley-Liss, Inc
Neurexophilin 3 is highly localized in cortical and cerebellar regions and is functionally important for sensorimotor gating and motor coordination
No full textNeurexophilin 3 (Nxph3) is a specific ligand of synaptic alpha-neurexins that are essential for efficient neurotransmitter release. Previous biochemical work demonstrated that Nxph3 interacts with an extracellular domain of alpha-neurexins in a tight complex; however, no information is available on the localization or functional role of Nxph3 in the brain. Here, we generated lacZ reporter gene knock-in mice to investigate the distribution of Nxph3 at the single-cell level and Nxph3 knockout mice to examine its functional importance. Nxph3 expression was restricted mostly to subplate-derived neurons in cortical layer 6b, granule cells in the vestibulocerebellum, and Cajal-Retzius cells during development. Colabeling experiments demonstrated that neurons expressing Nxph3 do not belong to a uniform cell type. Morphological analyses and systematic behavioral testing of knockout mice revealed no anatomical defects but uncovered remarkable functional abnormalities in sensory information processing and motor coordination, evident by increased startle response, reduced prepulse inhibition, and poor rotarod performance. Since Nxph3-deficient mice behaved normally while performing a number of other tasks, our data suggest an important role for Nxph3 as a locally and temporally regulated neuropeptide-like molecule, presumably acting in a complex with alpha-neurexins in select neuronal circuits
α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis
No full textSynapses are specialized intercellular junctions in which cell adhesion molecules connect the presynaptic machinery for neurotransmitter release to the postsynaptic machinery for receptor signalling. Neurotransmitter release requires the presynaptic co-assembly of Ca2+ channels with the secretory apparatus, but little is known about how synaptic components are organized. alpha-Neurexins, a family of > 1,000 presynaptic cell-surface proteins encoded by three genes, link the pre- and postsynaptic compartments of synapses by binding extracellularly to postsynaptic cell adhesion molecules and intracellularly to presynaptic PDZ domain proteins. Using triple-knockout mice, we show that alpha-neurexins are not required for synapse formation, but are essential for Ca2+-triggered neurotransmitter release. Neurotransmitter release is impaired because synaptic Ca2+ channel function is markedly reduced, although the number of cell-surface Ca2+ channels appears normal. These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery
Seminar on adult education in West Germany
No full textLeft to right: Dr Geoff Caldwell, Dr Alfred Pfeil, Dr Volker Otto, Dr Rudi Rohlmann, Dr A. Crombie, Dr Friedrich Baak
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