A mathematical model of adult subventricular neurogenesis

Neurogenesis has been the subject of active research in recent years and many authors have explored the phenomenology of the process, its regulation and its purported purpose. Recent developments in bioluminescent imaging (BLI) allow direct in vivo imaging of neurogenesis, and in order to interpret the experimental results, mathematical models are necessary. This study proposes such a mathematical model that describes adult mammalian neurogenesis occurring in the subventricular zone and the subsequent migration of cells through the rostral migratory stream to the olfactory bulb (OB). This model assumes that a single chemoattractant is responsible for cell migration, secreted both by the OB and in an endocrine fashion by the cells involved in neurogenesis. The solutions to the system of partial differential equations are compared with the physiological rodent process, as previously documented in the literature and quantified through the use of BLI, and a parameter space is described, the corresponding solution to which matches that of the rodent model. A sensitivity analysis shows that this parameter space is stable to perturbation and furthermore that the system as a whole is sloppy. A large number of parameter sets are stochastically generated, and it is found that parameter spaces corresponding to physiologically plausible solutions generally obey constraints similar to the conditions reported in vivo. This further corroborates the model and its underlying assumptions based on the current understanding of the investigated phenomenon. Concomitantly, this leaves room for further quantitative predictions pertinent to the design of future proposed experiments.     

Mixed analogue/digital phase picking algorithm in oversampling burst-mode clock phase alignment

A novel mixed analogue/digital design of a phase picking algorithm in an oversampling clock phase recovery is presented. The proposed approach results in reduced processing time, improved integrability with analogue front-end and low noise generation. Simulations of a 10 Gbit/s burst-mode clock phase alignment circuit in a 0.25 m SiGe BiCMOS process, show a simulated processing delay of only 280 ps.     

OSNR Penalty Imposed by Linear In-Band Crosstalk Caused by Interburst Residual Power in Multipoint-To-Point Networks

We present an analysis of linear in-band crosstalk in high split long reach wavelength/time-division-multiplexing passive optical networks (WDM-TDM PONs). In this letter, a mathematical model is deducted for the first time to calculate optical signal-to-noise ratio penalties due to in-band crosstalk in multipoint-to-point networks. The network performance can be perturbed by in-band crosstalk caused by power leakages from burst-mode optical network units (ONUs) in off-state. Our study results show that the leaked powers in upstream ONU transmitters can have an impact on the achievable split factor of WDM-TDM PONs. Furthermore, the performance limitations caused by aggregated interburst residual power are discussed.     

Morphologic and functional changes in the unilateral 6-hydroxydopamine lesion rat model for Parkinson’s disease discerned with μSPECT and quantitative MRI

Object

In the present study, we aimed to evaluate the impact of neurodegeneration of the nigrostriatal tract in a rodent model of Parkinson’s disease on the different MR contrasts (T₂, T₁, CBF and CBV) measured in the striatum.

Material and methods

Animals were injected with 6-hydroxydopamine (6OHDA) in the substantia nigra resulting in massive loss of nigrostriatal neurons and hence dopamine depletion in the ipsilateral striatum. Using 7T MRI imaging, we have quantified T₂, T₁, CBF and CBV in the striata of 6OHDA and control rats. To validate the lesion size, behavioral testing, dopamine transporter μSPECT and tyrosine hydroxylase staining were performed.

Results

No significant differences were demonstrated in the absolute MRI values between 6OHDA animals and controls; however, 6OHDA animals showed significant striatal asymmetry for all MRI parameters in contrast to controls.

Conclusions

These PD-related asymmetry ratios might be the result of counteracting changes in both intact and affected striatum and allowed us to diagnose PD lesions. As lateralization is known to occur also in PD patients and might be expected in transgenic PD models as well, we propose that MR-derived asymmetry ratios in the striatum might be a useful tool for in vivo phenotyping of animal models of PD.     

BiCMOS variable gain transimpedance amplifier for automotive applications

A new BiCMOS variable gain transimpedance amplifier with a large area integrated photodiode for automotive applications is presented. Through careful control of the input pole position and the frequency response of the core amplifier, the bandwidth of the transimpedance amplifier varies from 112 to 300 MHz when its gain changes from 14.2 kOmega to 400 Omega. The proposed circuit configuration maintains a high voltage across a common anode photodiode, and its bandwidth in highest gain varies from 121 to 102 MHz over a temperature range of -40 to +140degC. Simulation results in a 0.6 mum Si BiCMOS technology are given. The amplifier consumes 16 mW from a 3.3 V supply.     

The FE-BIE technique applied to some 2-D problems relevant toelectromagnetic compatibility: optimal choice of mechanisms to take intoaccount periodicity

A study of mechanisms to account for periodicity when modeling two-dimensional (2-D) structures with a hybrid finite-element boundary integral equation (FE-BIE) method is presented. These techniques are either based on the use of Green's functions or on the application of the Floquet-Bloch theorem as a periodic boundary condition. The described formalism can be used to model very diverse problem geometries as is demonstrated by means of some typical examples. For these configurations, it is shown how an optimal choice can be made between the mechanisms that impose periodicity     

Burst-Mode Electronic Equalization for 10-Gb/s Passive Optical Networks

Using computer simulations, it is shown how burst-mode electronic equalization in the optical line termination of a passive optical network (PON) allows 10 Gb/s in the upstream direction with directly modulated distributed-feedback lasers. This allows achieving 10 Gb/s using cost-effective components at the optical network unit. Fast convergence of the equalizer coefficients is achieved during the preamble of each burst using the recursive least squares algorithm instead of the least mean squares algorithm. With a nine-tap feed-forward equalizer, two-tap decision feedback equalizer, a physical reach of 38 km and a splitting factor of 32 can be achieved in the 1.5-$mu$m window, exceeding requirements for deployed PONs.      

In Vitro Phosphorylation Does not Influence the Aggregation Kinetics of WT α-Synuclein in Contrast to Its Phosphorylation Mutants

The aggregation of alpha-synuclein (α-SYN) into fibrils is characteristic for several neurodegenerative diseases, including Parkinson’s disease (PD). Ninety percent of α-SYN deposited in Lewy Bodies, a pathological hallmark of PD, is phosphorylated on serine129. α-SYN can also be phosphorylated on tyrosine125, which is believed to regulate the membrane binding capacity and thus possibly its normal function. A better understanding of the effect of phosphorylation on the aggregation of α-SYN might shed light on its role in the pathogenesis of PD. In this study we compare the aggregation properties of WT α-SYN with the phospho-dead and phospho-mimic mutants S129A, S129D, Y125F and Y125E and in vitro phosphorylated α-SYN using turbidity, thioflavin T and circular dichroism measurements as well as transmission electron microscopy. We show that the mutants S129A and S129D behave similarly compared to wild type (WT) α-SYN, while the mutants Y125F and Y125E fibrillate significantly slower, although all mutants form fibrillar structures similar to the WT protein. In contrast, in vitro phosphorylation of α-SYN on either S129 or Y125 does not significantly affect the fibrillization kinetics. Moreover, FK506 binding proteins (FKBPs), enzymes with peptidyl-prolyl cis-trans isomerase activity, still accelerate the aggregation of phosphorylated α-SYN in vitro, as was shown previously for WT α-SYN. In conclusion, our results illustrate that phosphorylation mutants can display different aggregation properties compared to the more biologically relevant phosphorylated form of α-SYN.     

Low-frequency reflectivity approximation for two- andthree-dimensional EM absorbers

Large-size electromagnetic absorbers are mainly used in anechoic and semi-anechoic chambers for electromagnetic compatibility testing. Therefore, the determination of the reflectivities in the low-frequency range (30-300 MHz) are of paramount importance in the performance evaluation of the absorber and, finally, in a “dark room” design. We here present a low-frequency approximation of the reflectivity based on a boundary and surface integral equation technique. This approach makes it possible to compare the approximation to the rigorous integral equation approach and to other approximations in the literature. The validity of the new low-frequency approximation is discussed based on reflectivity calculations of representative two- (2-D) and three-dimensional (3-D) absorber structures     

ATP13A2 Regulates Cellular α-Synuclein Multimerization,Membrane Association,and Externalization

ATP13A2, a late endo-/lysosomal polyamine transporter, is implicated in a variety of neurodegenerative diseases, including Parkinson’s disease and Kufor–Rakeb syndrome, an early-onset atypical form of parkinsonism. Loss-of-function mutations in ATP13A2 result in lysosomal deficiency as a consequence of impaired lysosomal export of the polyamines spermine/spermidine. Furthermore, accumulating evidence suggests the involvement of ATP13A2 in regulating the fate of α-synuclein, such as cytoplasmic accumulation and external release. However, no consensus has yet been reached on the mechanisms underlying these effects. Here, we aimed to gain more insight into how ATP13A2 is linked to α-synuclein biology in cell models with modified ATP13A2 activity. We found that loss of ATP13A2 impairs lysosomal membrane integrity and induces α-synuclein multimerization at the membrane, which is enhanced in conditions of oxidative stress or exposure to spermine. In contrast, overexpression of ATP13A2 wildtype (WT) had a protective effect on α-synuclein multimerization, which corresponded with reduced αsyn membrane association and stimulation of the ubiquitin-proteasome system. We also found that ATP13A2 promoted the secretion of α-synuclein through nanovesicles. Interestingly, the catalytically inactive ATP13A2 D508N mutant also affected polyubiquitination and externalization of α-synuclein multimers, suggesting a regulatory function independent of the ATPase and transport activity. In conclusion, our study demonstrates the impact of ATP13A2 on α-synuclein multimerization via polyamine transport dependent and independent functions.