Disease-Associated Mutations Prevent GPR56-Collagen III Interaction

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown

Evaluation of land surface models in reproducing satellite derived leaf area index over the high-latitude northern hemisphere. Part II: Earth system models

PublishedJournal ArticleLeaf Area Index (LAI) is a key parameter in the Earth System Models (ESMs) since it strongly affects land-surface boundary conditions and the exchange of matter and energy with the atmosphere. Observations and data products derived from satellite remote sensing are important for the validation and evaluation of ESMs from regional to global scales. Several decades' worth of satellite data products are now available at global scale which represents a unique opportunity to contrast observations against model results. The objective of this study is to assess whether ESMs correctly reproduce the spatial variability of LAI when compared with satellite data and to compare the length of the growing season in the different models with the satellite data. To achieve this goal we analyse outputs from 11 coupled carbon-climate models that are based on the set of new global model simulations planned in support of the IPCC Fifth Assessment Report. We focus on the average LAI and the length of the growing season on Northern Hemisphere over the period 1986-2005. Additionally we compare the results with previous analyses (Part I) of uncoupled land surface models (LSMs) to assess the relative contribution of vegetation and climatic drivers on the correct representation of LAI. Our results show that models tend to overestimate the average values of LAI and have a longer growing season due to the later dormancy. The similarities with the uncoupled models suggest that representing the correct vegetation fraction with the associated parameterizations; is more important in controlling the distribution and value of LAI than the climatic variables. © 2013 by the authors.This work was funded by the European Commission’s 7th Framework Programme under Grant Agreements number 238366 (GREENCYCLESII project) and 282672 (EMBRACE project)

Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704+allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704−allele. In addition, the Pro704+allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups. © 2001 Cancer Research Campaign http://www.bjcancer.co

Tachyonic Inflation in a Warped String Background

We analyze observational constraints on the parameter space of tachyonic inflation with a Gaussian potential and discuss some predictions of this scenario. As was shown by Kofman and Linde, it is extremely problematic to achieve the required range of parameters in conventional string compactifications. We investigate if the situation can be improved in more general compactifications with a warped metric and varying dilaton. The simplest examples are the warped throat geometries that arise in the vicinity of of a large number of space-filling D-branes. We find that the parameter range for inflation can be accommodated in the background of D6-branes wrapping a three-cycle in type IIA. We comment on the requirements that have to be met in order to realize this scenario in an explicit string compactification.Comment: Latex, JHEP class, 20 pages, 4 figures. v2: references added, small error in section 7 corrected, published versio

Detecting Change in the Urban Road Environment Along a Route Based on Traffic Sign and Crossroad Data

Occurrences of traffic signs that belong to certain sign categories and occurrences of crossroads of various topologies are utilized in detecting change in the urban road environment that moves past an ego-car. Three urban environment types, namely downtown, residential and industrial/commercial areas, are considered in the study and changes between these are to be detected. In the preparatory phase, the ego-car is used for traffic sign and crossroads data collection. In the application phase, the ego-car hosts an advanced driver assistance system (ADAS) that captures and analyzes images of the road environment and computes the required input data to the proposed road environment detection (RoED) subsystem. A statistical inference method relying on the minimum description length (MDL) principle was applied to the change detection problem at hand. The above occurrences along a route are seen as a realization of an inhomogeneous marked Poisson process. Page-Hinkley change detectors tuned to empirical data were set to work to detect change in the urban road environment. The process and the quality of the change detection are demonstrated via examples from three urban settlements in Hungary. Document type: Part of book or chapter of boo

Effect of waste materials on acoustical properties of semi-dense asphalt mixtures

Among the urban societal burdens rolling noise generation from tire pavement interaction and urban waste stand apart. Many urban waste materials can be used in pavements with comparable mechanical performance. Noise-related pavement characteristics such as porosity, sound absorption and surface texture, were measured for semi-dense low noise pavement mixtures using urban waste materials namely: recycled concrete aggregates, crumb rubber, polyethylene terephthalate and polyethylene. The results show that the use of these materials is a viable sustainable option for low noise pavements, however that may affect the noise reduction properties. With values around 0.2 at 1000 Hz, the sound absorption of all the mixtures is relatively low and the use of mean profile depth (MPD) alone is not enough to characterize the noise reduction properties. Surface texture was altered in different degrees depending on the waste material used. The results presented can aid in policy pertaining to noise abatement and waste reduction

Non-minimally Coupled Tachyonic Inflation in Warped String Background

We show that the non-minimal coupling of tachyon field to the scalar curvature, as proposed by Piao et al, with the chosen coupling parameter does not produce the effective potential where the tachyon field can roll down from T=0 to large $T$ along the slope of the potential. We find a correct choice of the parameters which ensures this requirement and support slow-roll inflation. However, we find that the cosmological parameter found from the analysis of the theory are not in the range obtained from observations. We then invoke warped compactification and varying dilaton field over the compact manifold, as proposed by Raeymaekers, to show that in such a setup the observed parameter space can be ensured.Comment: minor typos corrected and references adde