Behavioral simulation and synthesis of biological neuron systems using synthesizable VHDL

Neurons are complex biological entities which form the basis of nervous systems. Insight can be gained into neuron behavior through the use of computer models and as a result many such models have been developed. However, there exists a trade-off between biological accuracy and simulation time with the most realistic results requiring extensive computation. To address this issue, a novel approach is described in this paper that allows complex models of real biological systems to be simulated at a speed greater than real time and with excellent accuracy. The approach is based on a specially developed neuron model VHDL library which allows complex neuron systems to be implemented on field programmable gate array (FPGA) hardware. The locomotion system of the nematode Caenorhabditis elegans is used as a case study and the measured results show that the real time FPGA based implementation performs 288 times faster than traditional ModelSim simulations for the same accuracy

A phytolith supported biosphere-hydrosphere predictive model for Southern Ethiopia:Insights into paleoenvironmental changes and human landscape preferences since the last glacial maximum

During the past 25 ka, southern Ethiopia has undergone tremendous climatic changes, from dry and relatively cold during the Last Glacial Maximum (LGM, 25–18 ka) to the African Humid Period (AHP, 15–5 ka), and back to present-day dry conditions. As a contribution to better understand the effects of climate change on vegetation and lakes, we here present a new Predictive Vegetation Model that is linked with a Lake Balance Model and available vegetation-proxy records from southern Ethiopia including a new phytolith record from the Chew Bahir basin. We constructed a detailed paleo-landcover map of southern Ethiopia during the LGM, AHP (with and without influence of the Congo Air Boundary) and the modern-day potential natural landcover. Compared to today, we observe a 15–20% reduction in moisture availability during the LGM with widespread open landscapes and only few remaining forest refugia. We identify 25–40% increased moisture availability during the AHP with prevailing forests in the mid-altitudes and indications that modern anthropogenic landcover change has affected the water balance. In comparison with existing archaeological records, we find that human occupations tend to correspond with open landscapes during the late Pleistocene and Holocene in southern Ethiopia

A microflow cytometer for microsphere-based immunoassays using integrated optics and inertial particle focussing

We present work towards a microflow cytometer for performing multiplex immunoassays using commercially available fluorescently-labelled microspheres. The device consists of a silica chip with integrated GeO2:SiO2 channel waveguides which deliver excitation light orthogonally to an etched flow channel [1], [2]. The rectangular cross section, 2:1 aspect ratio flow channel and flow rate create an inertial focussing effect on the microspheres [3] which ensures they flow through the plane of maximum optical excitation, halfway up the height of the channel, with minimal positional variation. The optical waveguide core is fabricated by magnetron sputtering of GeO2:SiO2 films which are then etched to form channel waveguides by ICP etching. The silica cladding, up to 13.5 µm thick, is deposited by either flame hydrolysis deposition or a combination of magnetron sputtering followed by PECVD. Fluidic channels are etched with ICP etching. Channels with the dimensions of 14.1 µm x 27.5 µm and near vertical sidewalls (91°±4°) have been produced in silica as shown in the cross section in Figure 1A. Figure 1B shows a device with the fluidic channel etched through waveguides clad with PECVD silica. Design parameters were established with PDMS test channels 25.5 µm deep by 12.2 µm wide. Figures 2A and 2B show transmission fluorescence imaging of streaks from multiple 5.6µm diameter microspheres flowing at 0.49 m/s down the fluidic channel. The microspheres are shown to be focused into a tight stream at 15 mm from the channel entrance in Figure 2C, indicating the minimum channel length required for the final devices. Future work will include dual channel quantification of microsphere fluorescence and development of an assay for TNFalpha and later multiplex measurements. Collection of fluorescence with channel waveguides and also characterisation of transmission measurements from flowing microspheres will also be studied

Behavioral simulation and synthesis of biological neuron systems using synthesizable VHDL

Neurons are complex biological entities which form the basis of nervous systems. Insight can be gained into neuron behavior through the use of computer models and as a result many such models have been developed. However, there exists a trade-off between biological accuracy and simulation time with the most realistic results requiring extensive computation. To address this issue, a novel approach is described in this paper that allows complex models of real biological systems to be simulated at a speed greater than real time and with excellent accuracy. The approach is based on a specially developed neuron model VHDL library which allows complex neuron systems to be implemented on field programmable gate array (FPGA) hardware. The locomotion system of the nematode Caenorhabditis elegans is used as a case study and the measured results show that the real time FPGA based implementation performs 288 times faster than traditional ModelSim simulations for the same accuracy

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones

'Wash-out' and inactivation of the Ca current were examined in dialysed, voltage-clamped neurones of Helix aspersa under conditions that isolate the Ca current virtually free of other currents. EGTA or other internal Ca2+ chelators were routinely omitted from the dialysate. The time-dependent loss, or wash-out, of Ca current was slowed by addition to the dialysing solution of agents, such as dibutyryl adenosine 3'-5'-cyclic monophosphate (dibutyryl cyclic AMP), Mg adenosine 5'-triphosphate (ATP) and the catalytic subunit of cyclic-AMP-dependent protein kinase, that promote protein phosphorylation and by EGTA. However, neither the phosphorylation-promoting agents nor internal EGTA prevented wash-out entirely, nor did they significantly restore previously 'washed-out' current. With phosphorylating agents in the dialysing solution, the irreversible development of wash-out was greatly reduced by introduction of leupeptin, an inhibitor of protease activity. Thus, the irreversible component of wash-out appears to result from a Ca-dependent proteolytic process. In the presence of leupeptin alone, Ca current amplitude continued to decline: however, the current could be largely or fully restored with addition of catalytic subunit, dibutyryl cyclic AMP, and Mg ATP to the dialysing solution. Thus, inhibition of proteolysis revealed a reversible component of wash-out that appears to result from dephosphorylation. During perfusion with leupeptin, Mg ATP, dibutyryl cyclic AMP and catalytic subunit the Ca current remained stable for up to several hours without addition of internal Ca2+ buffer. The rate of inactivation of the current that occurs during a depolarizing step showed only a very gradual decline during this time. Under these conditions, perfusion with calcineurin, a Ca-calmodulin-dependent phosphatase, caused a significant increase in the rate of Ca current inactivation. This inactivation was virtually eliminated by introduction of EGTA or by replacement of external Ca2+ with Ba2+, which is consistent with the ion dependency for calmodulin-dependent activation of calcineurin. When ATP in the dialysate was replaced with ATP-gamma-S (adenosine 5'-O-(thiotriphosphate], an analogue that donates a thiophosphate group resistant to hydrolysis, the rate of inactivation slowed. Since Ca-dependent inactivation during step depolarizations is enhanced by conditions that promote dephosphorylation, and Ca current wash-out is slowed by conditions that promote phosphorylation, inactivation and reversible wash-out appear to be related