In vivo brain connectivity: optimization of manganese enhanced MRI for neuronal tract tracing

One of the main problems in systems biology is to obtain information on signal processing between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps. Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10 and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection, T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons, respectively) were performed in the brain sections to examine cellular toxicity. All injections produced connectivity maps consistent with the known anterograde projections of SI cortex based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand contra-lateral corticocortical connections were evident in all animal injected with those solutions but not with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1 contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the projection fields. We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and preserves tissue viability, assuring the application of this technique in longitudinal experiments

All Politics is Local: The Renminbi's Prospects as a Future Global Currency

. In this article we describe methods for improving the RWTH German speech recognizer used within the VERBMOBIL project. In particular, we present acceleration methods for the search based on both within-word and across-word phoneme models. We also study incremental methods to reduce the response time of the online speech recognizer. Finally, we present experimental off-line results for the three VERBMOBIL scenarios. We report on word error rates and real-time factors for both speaker independent and speaker dependent recognition. 1 Introduction The goal of the VERBMOBIL project is to develop a speech-to-speech translation system that performs close to real-time. In this system, speech recognition is followed by subsequent VERBMOBIL modules (like syntactic analysis and translation) which depend on the recognition result. Therefore, in this application it is particularly important to keep the recognition time as short as possible. There are VERBMOBIL modules which are capable to work ..

Effective toughness of heterogeneous brittle materials

A heterogeneous brittle material characterized by a random field of local toughness Kc(x) can be represented by an equivalent homogeneous medium of toughness, Keff. Homogenization refers to a process of estimating Keff from the local field Kc(x). An approach based on a perturbative expansion of the stress intensity factor along a rough crack front shows the occurrence of different regimes depending on the correlation length of the local toughness field in the direction of crack propagation. A `"weak pinning" regime takes place for long correlation lengths, where the effective toughness is the average of the local toughness. For shorter correlation lengths, a transition to "strong pinning" occurs leading to a much higher effective toughness, and characterized by a propagation regime consisting in jumps between pinning configurations

Bounds on the strength distribution of unidirectional fiber composites

Failure mechanisms under tensile loading of unidirectional fiber composites comprising of Weibull fibers embedded in a matrix are studied using Monte-Carlo simulations. Two fundamental mechanisms of failure are recognized--stress concentration driven failure and strength driven failure. It is shown that the cumulative distribution function for composite strength predicted by the stress concentration -driven failure and strength-driven failure form apparent upper and lower bounds respectively and also that failure mechanism switches from one to the other as fiber strength variability changes

Fracture model with variable range of interaction

We introduce a fiber bundle model where the interaction among fibers is modeled by an adjustable stress-transfer function which can interpolate between the two limiting cases of load redistribution, the global and the local load sharing schemes. By varying the range of interaction several features of the model are numerically studied and a crossover from mean field to short range behavior is obtained. The properties of the two regimes and the emergence of the crossover in between are explored by numerically studying the dependence of the ultimate strength of the material on the system size, the distribution of avalanches of breakings, and of the cluster sizes of broken fibers. Finally, we analyze the moments of the cluster size distributions to accurately determine the value at which the crossover is observed.Comment: 8 pages, 8 figures. Two columns revtex format. Final version to be published in Phys. Rev.

Feasibility demonstration of back-to-back method for induction traction motors testing

The authors present the feasibility demonstration of energy-saving back-to-back test method implementation for induction traction motors testing. The results of theoretical and physical modeling that support the energy effectiveness and usefulness of the proposed backto-back method are presented in the article. The effectivity ratio of the test circuit has been calculated due to confirm the energy effectiveness and feasibility of the proposed method, and also authors identified a number of advantages of the back-to-back method for high power induction traction motors

Femtosecond x-ray diffraction from an aerosolized beam of protein nanocrystals

We demonstrate near-atomic-resolution Bragg diffraction from aerosolized single granulovirus crystals using an x-ray free-electron laser. The form of the aerosol injector is nearly identical to conventional liquid-microjet nozzles, but the x-ray-scattering background is reduced by several orders of magnitude by the use of helium carrier gas rather than liquid. This approach provides a route to study the weak diffuse or lattice-transform signal arising from small crystals. The high speed of the particles is particularly well suited to upcoming MHz-repetition-rate x-ray free-electron lasers

Gestational Weight Gain and Body Mass Index in Children: Results from Three German Cohort Studies

Previous studies suggested potential priming effects of gestational weight gain (GWG) on offspring's body composition in later life. However, consistency of these effects in normal weight, overweight and obese mothers is less clear. We combined the individual data of three German cohorts and assessed associations of total and excessive GWG (as defined by criteria of the Institute of Medicine) with offspring's mean body mass index (BMI) standard deviation scores (SDS) and overweight at the age of 5-6 years (total: n = 6,254). Quantile regression was used to examine potentially different effects on different parts of the BMI SDS distribution. All models were adjusted for birth weight, maternal age and maternal smoking during pregnancy and stratified by maternal pre-pregnancy weight status. In adjusted models, positive associations of total and excessive GWG with mean BMI SDS and overweight were observed only in children of non- overweight mothers. For example, excessive GWG was associated with a mean increase of 0.08 (95% CI: 0.01, 0.15) units of BMI SDS (0.13 (0.02, 0.24) kg/m(2) of 'real' BMI) in children of normal-weight mothers. The effects of total and excessive GWG on BMI SDS increased for higher- BMI children of normal-weight mothers. Increased GWG is likely to be associated with overweight in offspring of non-overweight mothers

Risk Factors for Obesity: Further Evidence for Stronger Effects on Overweight Children and Adolescents Compared to Normal-Weight Subjects

Background: We recently showed that in preschoolers risk factors for overweight show stronger associations with BMI in children with high BMI values. However, it is unclear whether these findings might also pertain to adolescents. Methods: We extracted data on 3–10 year-old (n = 7,237) and 11–17 year-old (n = 5,986) children from a representative cross-sectional German health survey (KiGGS) conducted between 2003 and 2006 and calculated quantile regression models for each age group. We used z-scores of children's body mass index (BMI) as outcome variable and maternal BMI, maternal smoking in pregnancy, low parental socioeconomic status, exclusive formula-feeding and high TV viewing time as explanatory variables. Results: In both age groups, the estimated effects of all risk factors except formula-feeding on BMI z-score were greatest for children with the highest BMI z-score. The median BMI z-score of 11–17 year-old children with high TV viewing time, for example, was 0.11 [95% CI: 0.03, 0.19] units higher than the median BMI z-score of teenage children with low TV viewing time. This risk factor was associated with an average difference of 0.18 [0.06, 0.30] units at the 90th percentile of BMI z-score and of 0.20 [0.07, 0.33] units at the 97th percentile. Conclusions: We confirmed that risk factors for childhood overweight are associated with greater shifts in the upper parts of the children's BMI distribution than in the middle and lower parts. These findings pertain also to teenagers and might possibly help to explain the secular shift in the upper BMI percentiles in children and adolescents