Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death

Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASICla-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca2+ elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis.

Techniques to improve the shear strength of impacted bone graft: the effect of particle size and washing of the graft.

BACKGROUND: When fresh morselized graft is compacted, as in impaction bone-grafting for revision hip surgery, fat and marrow fluid is either exuded or trapped in the voids between particles. We hypothesized that the presence of incompressible fluid damps and resists compressive forces during impaction and prevents the graft particles from moving into a closer formation, thus reducing the graft strength. In addition, viscous fluid such as fat may act as an interparticle lubricant, thus reducing the interlocking of the particles. METHODS: We performed mechanical shear testing in the laboratory with use of fresh-frozen human femoral-head allografts that had been passed through different orthopaedic bone mills to produce graft of differing particle-size distributions (grading). RESULTS: After compaction of fresh graft, fat and marrow fluid continued to escape on application of normal loads. Washed graft, however, had little lubricating fluid and better contact between the particles, increasing the shear resistance. On mechanical testing, washed graft was significantly (p < 0.001) more resistant to shearing forces than fresh graft was. This feature was consistent for different bone mills that produced graft of different particle-size distributions and shear strengths. CONCLUSIONS: Removal of fat and marrow fluid from milled human allograft by washing the graft allows the production of stronger compacted graft that is more resistant to shear, which is the usual mode of failure. Further research into the optimum grading of particle sizes from bone mills is required.

The role of vibration and drainage in femoral impaction bone grafting.

Vibration is commonly used in civil engineering applications to efficiently compact aggregates. This study examined the effect of vibration and drainage on bone graft compaction and cement penetration in an in vitro femoral impaction bone grafting model with the use of 3-dimensional micro-computed tomographic imaging. Three regions were analyzed. In the middle and proximal femoral regions, there was a significant increase in the proportion of bone grafts with a reciprocal reduction in water and air in the vibration-assisted group (P < .01) as compared with the control group, suggesting tighter graft compaction. Cement volume was also significantly reduced in the middle region in the vibration-assisted group. No difference was observed in the distal region. This study demonstrates the value of vibration and drainage in bone graft compaction, with implications therein for clinical application and outcome.

Techniques to improve the shear strength of impacted bone graft: The effect of particle size and washing of the graft

Background: When fresh morselized graft is compacted, as in impaction bone-grafting for revision hip surgery, fat and marrow fluid is either exuded or trapped in the voids between particles. We hypothesized that the presence of incompressible fluid damps and resists compressive forces during impaction and prevents the graft particles from moving into a closer formation, thus reducing the graft strength. In addition, viscous fluid such as fat may act as an interparticle lubricant, thus reducing the interlocking of the particles. Methods: We performed mechanical shear testing in the laboratory with use of fresh-frozen human femoral-head allografts that had been passed through different orthopaedic bone mills to produce graft of differing particle-size distributions (grading). Results: After compaction of fresh graft, fat and marrow fluid continued to escape on application of normal loads. Washed graft, however, had little lubricating fluid and better contact between the particles, increasing the shear resistance. On mechanical testing, washed graft was significantly (p < 0.001) more resistant to shearing forces than fresh graft was. This feature was consistent for different bone mills that produced graft of different particle-size distributions and shear strengths. Conclusions: Removal of fat and marrow fluid from milled human allograft by washing the graft allows the production of stronger compacted graft that is more resistant to shear, which is the usual mode of failure. Further research into the optimum grading of particle sizes from bone mills is required. Clinical Relevance: Understanding the mechanical properties of milled human allograft is important when impaction grafting is used for mechanical support. A simple means of improving the mechanical strength of graft produced by currently available bone mills, including an intraoperative washing technique, is described.

Orthogonal multipulse modulation for next-generation datacommunication links

Orthogonal multipulse modulation is demonstrated to allow ≈30 Gb/s real-time transmission over multimode fibre using an 850 nm VCSEL. The scheme eases considerably component bandwidth requirements compared with conventional NRZ modulation. © 2011 OSA.

Adaptive BDDC in Three Dimensions

The adaptive BDDC method is extended to the selection of face constraints in three dimensions. A new implementation of the BDDC method is presented based on a global formulation without an explicit coarse problem, with massive parallelism provided by a multifrontal solver. Constraints are implemented by a projection and sparsity of the projected operator is preserved by a generalized change of variables. The effectiveness of the method is illustrated on several engineering problems.

Face-based Selection of Corners in 3D Substructuring

In most recent substructuring methods, a fundamental role is played by the coarse space. For some of these methods (e.g. BDDC and FETI-DP), its definition relies on a 'minimal' set of coarse nodes (sometimes called corners) which assures invertibility of local subdomain problems and also of the global coarse problem. This basic set is typically enhanced by enforcing continuity of functions at some generalized degrees of freedom, such as average values on edges or faces of subdomains. We revisit existing algorithms for selection of corners. The main contribution of this paper consists of proposing a new heuristic algorithm for this purpose. Considering faces as the basic building blocks of the interface, inherent parallelism, and better robustness with respect to disconnected subdomains are among features of the new technique. The advantages of the presented algorithm in comparison to some earlier approaches are demonstrated on three engineering problems of structural analysis solved by the BDDC method.

Energy efficiency, resilience to future climates and long-term sustainability: the role of the built environment.

Just under half of all energy consumption in the UK today takes place indoors, and over a quarter within our homes. The challenges associated with energy security, climate change and sustainable consumption will be overcome or lost in our existing buildings. A background analysis, and the scale of the engineering challenge for the next three to four decades, is described in this paper.

Compliant shell mechanisms.

This paper describes a class of lightweight structures known as compliant shell mechanisms. These are novel reconfigurable solutions for advanced structures, such as morphing shells and deployable membranes. They have local, discrete corrugations, which articulate and deform to achieve dramatic changes in the overall shape of the shell. The unique kinematics are considered by highlighting examples and by performing analysis using established and novel concepts, and favourable predictions of shape compared with laboratory models are demonstrated.

Towards real-time profiling of sprints using wearable pressure sensors

On-body sensor systems for sport are challenging since the sensors must be lightweight and small to avoid discomfort, and yet robust and highly accurate to withstand and capture the fast movements associated with sport. In this work, we detail our experience of building such an on-body system for track athletes. The paper describes the design, implementation and deployment of an on-body sensor system for sprint training sessions. We autonomously profile sprints to derive quantitative metrics to improve training sessions. Inexpensive Force Sensitive Resistors (FSRs) are used to capture foot events that are subsequently analysed and presented back to the coach. We show how to identify periods of sprinting from the FSR data and how to compute metrics such as ground contact time. We evaluate our system using force plates and show that millisecond-level accuracy is achievable when estimating contact times. © 2012 Elsevier B.V. All rights reserved.