Morphological paradigms in language processing and language disorders

We present results from two cross‐modal morphological priming experiments investigating regular person and number inflection on finite verbs in German. We found asymmetries in the priming patterns between different affixes that can be predicted from the structure of the paradigm. We also report data from language disorders which indicate that inflectional errors produced by language‐impaired adults and children tend to occur within a given paradigm dimension, rather than randomly across the paradigm. We conclude that morphological paradigms are used by the human language processor and can be systematically affected in language disorders

Identification of a non-purple tartrate-resistant acid phosphatase: an evolutionary link to Ser/Thr protein phosphatases?

BACKGROUND Tartrate-resistant acid phosphatases (TRAcPs), also known as purple acid phosphatases (PAPs), are a family of binuclear metallohydrolases that have been identified in plants, animals and fungi. The human enzyme is a major histochemical marker for the diagnosis of bone-related diseases. TRAcPs can occur as a small form possessing only the ~35 kDa catalytic domain, or a larger ~55 kDa form possessing both a catalytic domain and an additional N-terminal domain of unknown function. Due to its role in bone resorption the 35 kDa TRAcP has become a promising target for the development of anti-osteoporotic chemotherapeutics. FINDINGS A new human gene product encoding a metallohydrolase distantly related to the ~55 kDa plant TRAcP was identified and characterised. The gene product is found in a number of animal species, and is present in all tissues sampled by the RIKEN mouse transcriptome project. Construction of a homology model illustrated that six of the seven metal-coordinating ligands in the active site are identical to that observed in the TRAcP family. However, the tyrosine ligand associated with the charge transfer transition and purple color of TRAcPs is replaced by a histidine. CONCLUSION The gene product identified here may represent an evolutionary link between TRAcPs and Ser/Thr protein phosphatases. Its biological function is currently unknown but is unlikely to be associated with bone metabolism.This work was funded by the Royal Society of Tropical Medicine and Hygiene through a Dennis Burkitt Fellowship to JJM. ARD is supported by the Economic and Social Research Council. JJM is supported by a Wellcome Trust Research Training Fellowship (GR074833MA)

The organophosphate-degrading enzyme from Agrobacterium radiobacter displays mechanistic flexibility for catalysis

The OP (organophosphate)-degrading enzyme from Agrobacterium radiobacter (OpdA) is a binuclear metallohydrolase able to degrade highly toxic OP pesticides and nerve agents into less or non-toxic compounds. In the present study, the effect of metal ion substitutions and site-directed mutations on the catalytic properties of OpdA are investigated. The study shows the importance of both the metal ion composition and a hydrogenbond network that connects the metal ion centre with the substrate-binding pocket using residues Arg254 and Tyr257 in the mechanism and substrate specificity of this enzyme. For theCo(II) derivative of OpdA two protonation equilibria (pKa1 ∼5; pKa2 ∼10) have been identified as relevant for catalysis, and a terminal hydroxide acts as the likely hydrolysis-initiating nucleophile. In contrast, the Zn(II) and Cd(II) derivatives only have one relevant protonation equilibrium (pKa ∼4–5), and theμOHis the proposed nucleophile. The observed mechanistic flexibility may reconcile contrasting reaction models that have been published previously and may be beneficial for the rapid adaptation of OP-degrading enzymes to changing environmental pressures

Proteases in Plasma and Kidney of db/db Mice as Markers of Diabetes-Induced Nephropathy

Db/db mice are overweight, dyslipidemic and develop diabetic complications, relevant for similar complications in human type 2 diabetes. We have used db/db and db/+ control mice to investigate alterations in proteinase expression and activity in circulation and kidneys by SDS-PAGE zymography, electron microscopy, immunohistochemistry, Western blotting, and in situ zymography. Plasma from db/db mice contained larger amounts of serine proteinases compared to db/+ mice. Kidneys from the db/db mice had a significantly larger glomerular surface area and somewhat thicker glomerular basement membranes compared to the db/+ mice. Furthermore, kidney extracts from db/+ mice contained metalloproteinases with Mr of approximately 92000, compatible with MMP-9, not observed in db/db mice. These results indicate that higher levels of serine proteinases in plasma may serve as potential markers for kidney changes in db/db mice, whereas a decrease in MMP-9 in the kidney may be related to the glomerular changes

The motion of small particles in electrostatic travelling waves for transport and separation

Electrostatic travelling waves can be used to transport small particles across a surface. This technology has received particular attention for dust mitigation on solar panels and for manipulating small particles on the Moon as part of in-situ resource utilization processes. Electrostatic travelling wave systems have no moving parts and are particularly well suited to low humidity environments. Here, we analyse the motion of small particles with the aim of exploiting differences in motion and velocity to separate particles by size. We investigate the effects of voltage, frequency, particle size and charge, wavelength and initial conditions on the properties of particle motion, such as particle velocity, levitation height and motion mode. We calculate the electrostatic fields using accurate boundary conditions based on the Fourier expansion method, which shows more detail near the surface of electrodes. We solve the equations of motion using the implicit Runge-Kutta method, and measure the particle charge with a free fall system. We show that the numerical results have a good agreement with the analytical results of a particle moving in a certain mode. We have observed three modes of motion with a high-speed camera, and these results provide guidance for the development of electrostatic travelling wave systems for various applications

Is population structure sufficient to generate area-level inequalities in influenza rates? An examination using agent-based models

Background: In New Haven County, CT (NHC), influenza hospitalization rates have been shown to increase with census tract poverty in multiple influenza seasons. Though multiple factors have been hypothesized to cause these inequalities, including population structure, differential vaccine uptake, and differential access to healthcare, the impact of each in generating observed inequalities remains unknown. We can design interventions targeting factors with the greatest explanatory power if we quantify the proportion of observed inequalities that hypothesized factors are able to generate. Here, we ask if population structure is sufficient to generate the observed area-level inequalities in NHC. To our knowledge, this is the first use of simulation models to examine the causes of differential poverty-related influenza rates. Methods: Using agent-based models with a census-informed, realistic representation of household size, age-structure, population density in NHC census tracts, and contact rates in workplaces, schools, households, and neighborhoods, we measured poverty-related differential influenza attack rates over the course of an epidemic with a 23 % overall clinical attack rate. We examined the role of asthma prevalence rates as well as individual contact rates and infection susceptibility in generating observed area-level influenza inequalities. Results: Simulated attack rates (AR) among adults increased with census tract poverty level (F = 30.5; P < 0.001) in an epidemic caused by a virus similar to A (H1N1) pdm09. We detected a steeper, earlier influenza rate increase in high-poverty census tracts - a finding that we corroborate with a temporal analysis of NHC surveillance data during the 2009 H1N1 pandemic. The ratio of the simulated adult AR in the highest- to lowest-poverty tracts was 33 % of the ratio observed in surveillance data. Increasing individual contact rates in the neighborhood did not increase simulated area-level inequalities. When we modified individual susceptibility such that it was inversely proportional to household income, inequalities in AR between high- and low-poverty census tracts were comparable to those observed in reality. Discussion: To our knowledge, this is the first study to use simulations to probe the causes of observed inequalities in influenza disease patterns. Knowledge of the causes and their relative explanatory power will allow us to design interventions that have the greatest impact on reducing inequalities. Conclusion: Differential exposure due to population structure in our realistic simulation model explains a third of the observed inequality. Differential susceptibility to disease due to prevailing chronic conditions, vaccine uptake, and smoking should be considered in future models in order to quantify the role of additional factors in generating influenza inequalities

A universal framework for Space Resource Utilisation (SRU)

Space Resource Utilisation (SRU) or In Situ Resource Utilisation (ISRU) is the use of natural resources from the Moon, Mars and other bodies for use in situ or elsewhere in the Solar System. The implementation of SRU technologies will provide the breakthrough for humankind to explore further into space. A range of extraction processes to produce usable resources have been proposed, such as oxygen production from lunar regolith, extraction of lunar ice and construction of habitation by 3D printing. Practical and successful implementation of SRU requires that all the stages of the process flowsheet (excavation, beneficiation and extraction) are considered. This requires a complete ‘mine-to-market’ type approach, analogous to that of terrestrial mineral extraction. One of the key challenges is the unique cross-disciplinary nature of SRU; it integrates space systems, robotics, materials handling and beneficiation, and chemical process engineering. This is underpinned by knowledge of the lunar or planetary geology, including mineralogy, physical characteristics, and the variability in local materials. Combining such diverse fields in a coordinated way requires the use of a universal framework. The framework will enable integration of operations and comparison of technologies, and will define a global terminology to be used across all fields. In this paper, a universal SRU flowsheet and terminology are described, and a matrix approach to describing regolith characteristics specifically for SRU is proposed. This is the first time that such an approach has been taken to unify this rapidly-developing sector

Numerical solution of the electric field and dielectrophoresis force of electrostatic traveling wave system

Electrostatic traveling wave (ETW) methods have shown promising performance in dust mitigation of solar panels, particle transport and separation in in situ space resource utilization, cell manipulation, and separation in biology. The ETW field distribution is required to analyze the forces applied to particles and to evaluate ETW design parameters. This study presents the numerical results of the ETW field distribution generated by a parallel electrode array using both the charge simulation method (CSM) and the boundary element method (BEM). A low accumulated error of the CSM is achieved by properly arranging the positions and numbers of contour points and fictitious charges. The BEM can avoid the inconvenience of the charge position required in the CSM. The numerical results show extremely close agreement between the CSM and BEM. For simplification, the method of images is introduced in the implementation of the CSM and BEM. Moreover, analytical formulas are obtained for the integral of Green’s function along boundary elements. For further validation, the results are cross-checked using the finite element method (FEM). It is found that discrepancies occur at the ends of the electrode array. Finally, analyses are provided of the electric field and dielectrophoretic (DEP) components. Emphasis is given to the regions close to the electrode surfaces. These results provide guidance for the fabrication of ETW systems for various applications