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We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories.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.     

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.

Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.     

A massive reservoir of low-excitation molecular gas at high redshift

Molecular hydrogen (H2) is an important component of galaxies because it fuels star formation and the accretion of gas onto active galactic nuclei (AGN), the two processes that can generate the large infrared luminosities of gas-rich galaxies. Observations of spectral-line emission from the tracer molecule carbon monoxide (CO) are used to probe the properties of this gas. But the lines that have been studied in the local Universe-mostly the lower rotational transitions of J = 1 --> 0 and J = 2 --> 1-have hitherto been unobservable in high-redshift galaxies. Instead, higher transitions have been used, although the densities and temperatures required to excite these higher transitions may not be reached by much of the gas. As a result, past observations may have underestimated the total amount of molecular gas by a substantial amount. Here we report the discovery of large amounts of low-excitation molecular gas around the infrared-luminous quasar APM08279+5255 at redshift z = 3.91, using the two lowest excitation lines of 12 CO (J = 1 --> 0 and J = 2 --> 1). The maps confirm the presence of hot and dense gas near the nucleus, and reveal an extended reservoir of molecular gas with low excitation that is 10 to 100 times more massive than the gas traced by the higher-excitation observations. This raises the possibility that significant amounts of low-excitation molecular gas may exist in the environments of high-redshift (z > 3) galaxies.     

Wavelet Transform and Image Processing

This paper presents systematically a method for image compression/decompression viawavelet transform.It consists of filter,quantization and Huffman coding etc..Different methodshave been compared.Finally,some suggestions for further studies are proposed.In fact,the paper isa summary of our recent research.     

Germline mutations in the ribonuclease L gene in families showing linkage with HPC1.

Although prostate cancer is the most common non-cutaneous malignancy diagnosed in men in the United States, little is known about inherited factors that influence its genetic predisposition. Here we report that germline mutations in the gene encoding 2'-5'-oligoadenylate(2-5A)-dependent RNase L (RNASEL) segregate in prostate cancer families that show linkage to the HPC1 (hereditary prostate cancer 1) region at 1q24-25 (ref. 9). We identified RNASEL by a positional cloning/candidate gene method, and show that a nonsense mutation and a mutation in an initiation codon of RNASEL segregate independently in two HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway and has been suggested to be a candidate tumor suppressor gene. We found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozyogous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway might provide opportunities for developing therapies for those with prostate cancer.     

Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis

Tumour growth requires accompanying expansion of the host vasculature, with tumour progression often correlated with vascular density. Vascular endothelial growth factor (VEGF) is the best-characterized inducer of tumour angiogenesis. We report that VEGF dynamically regulates tumour endothelial expression of Delta-like ligand 4 (Dll4), which was previously shown to be absolutely required for normal embryonic vascular development. To define Dll4 function in tumour angiogenesis, we manipulated this pathway in murine tumour models using several approaches. Here we show that blockade resulted in markedly increased tumour vascularity, associated with enhanced angiogenic sprouting and branching. Paradoxically, this increased vascularity was non-productive-as shown by poor perfusion and increased hypoxia, and most importantly, by decreased tumour growth-even for tumours resistant to anti-VEGF therapy. Thus, VEGF-induced Dll4 acts as a negative regulator of tumour angiogenesis; its blockade results in a striking uncoupling of tumour growth from vessel density, presenting a novel therapeutic approach even for tumours resistant to anti-VEGF therapies.     

Nicolas-Auguste Tissot: a link between cartography and quasiconformal theory

Nicolas-Auguste Tissot (1824–1897) published a series of papers on cartography in which he introduced a tool which became known later on, among geographers, under the name of the Tissot indicatrix. This tool was broadly used during the twentieth century in the theory and in the practical aspects of the drawing of geographical maps. The Tissot indicatrix is a graphical representation of a field of ellipses on a map that describes its distortion. Tissot studied extensively, from a mathematical viewpoint, the distortion of mappings from the sphere onto the Euclidean plane that are used in drawing geographical maps, and more generally he developed a theory for the distortion of mappings between general surfaces. His ideas are at the heart of the work on quasiconformal mappings that was developed several decades after him by Grötzsch, Lavrentieff, Ahlfors and Teichmüller. Grötzsch mentions the work of Tissot, and he uses the terminology related to his name (in particular, Grötzsch uses the Tissot indicatrix). Teichmüller mentions the name of Tissot in a historical section in one of his fundamental papers where he claims that quasiconformal mappings were used by geographers, but without giving any hint about the nature of Tissot’s work. The name of Tissot is missing from all the historical surveys on quasiconformal mappings. In the present paper, we report on this work of Tissot. We shall mention some related works on cartography, on the differential geometry of surfaces, and on the theory of quasiconformal mappings. This will place Tissot’s work in its proper context.     

Historical development of Teichmüller theory

Originally, the expression “Teichmüller theory” referred to the theory that Oswald Teichmüller developed on deformations and on moduli spaces of marked Riemann surfaces. This theory is not an isolated field in mathematics. At different stages of its development, it received strong impetuses from analysis, geometry, and algebraic topology, and it had a major impact on other fields, including low-dimensional topology, algebraic topology, hyperbolic geometry, geometric group theory, representations of discrete groups in Lie groups, symplectic geometry, topological quantum field theory, theoretical physics, and there are certainly others. Of course, the impacts on these various fields are not equally important, but in some cases (namely, low-dimensional topology, algebraic geometry, and physics) the impact was crucial. At the same time, Teichmüller theory established important connections between the fields mentioned. This, in part, is a consequence of the diversity and the richness of the structure that Teichmüller space itself carries. From a more subjective point of view, the result of pondering on these connections and applications demonstrates the unity of mathematics. The aim of this paper is to survey the origin of Teichmüller theory and the development of its early major ideas.     

Fast Implementation of Iterative Reconstruction with Exact Ray-Driven Projector on GPUs

Iterative methods are popular choices in image reconstruction fields due to their capability of recovering object information from incomplete acquisition data.However,the computation process involves frequent uses of forward and backward projections that are computationally expensive.Past research has proved that a forward projector that can produce high quality images is crucial to achieve a good convergence rate.In this paper a high performance iterative reconstruction framework is introduced,where two mo...