Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases.     

A lysosomal enigma CLN5 and its significance in understanding neuronal ceroid lipofuscinosis

Cellular and Molecular Life Sciences - Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations...     

The approximation of long‐memory processes by an ARMA model

A mean square error criterion is proposed in this paper to provide a systematic approach to approximate a long‐memory time series by a short‐memory ARMA(1, 1) process. Analytic expressions are derived to assess the effect of such an approximation. These results are established not only for the pure fractional noise case, but also for a general autoregressive fractional moving average long‐memory time series. Performances of the ARMA(1,1) approximation as compared to using an ARFIMA model are illustrated by both computations and an application to the Nile river series. Results derived in this paper shed light on the forecasting issue of a long‐memory process. Copyright © 2001 John Wiley & Sons, Ltd.     

TiB2和Al3Ti对近共晶Al?12.6Si合金组织、力学性能和断裂行为的影响

A near eutectic Al?12.6Si alloy was developed with 0.0wt%, 2.0wt%, 4.0wt%, and 6.0wt% Al?5Ti?1B master alloy. The microstructural morphology, hardness, tensile strength, elongation, and fracture behaviour of the alloys were studied. The unmodified Al?12.6Si alloy has an irregular needle and plate-like eutectic silicon (E_Si) and coarse polygonal primary silicon (P_Si) particles in the matrix-like α-Al phase. The P_Si, E_Si, and α-Al morphology and volume fraction were changed due to the addition of the Al?5Ti?1B master alloy. The hardness, UTS, and elongation improved due to the microstructural modification. Nano-sized in-situ Al₃Ti particles and ex-situ TiB₂ particles caused the microstructural modification. The fracture images of the developed alloys exhibit a ductile and brittle mode of fracture at the same time. The Al?5Ti?1B modified alloys have a more ductile mode of fracture and more dimples compared to the unmodified alloy.     

Hedgehog signalling in prostate regeneration, neoplasia and metastasis

Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning, is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.