A practical miniature long-term bone marrow culture system for investigating early myelodysplasia

A method was devised to grow haemopoietic cells in long-term bone marrow culture (LTBMC) which requires only 1 x 10(6) cells/culture. Such miniature cultures were used to study growth patterns of marrow from patients with myelodysplastic syndromes (MDS). Consistent differences in LTBMC cellularity and cellular composition were noted between MDS and normal marrow. These differences were accentuated by rGM-CSF. The criteria which distinguished between and MDS marrows were: cell count at weeks 1 and 4, % neutrophils and % blasts. In 10 patients with unexplained macrocytosis or pancytopenia miniature LTBMC results clearly segregated into either 'normal' or 'MDS' growth patterns. Miniature LTBMC with rGM-CSF may therefore be a useful diagnostic test for early MDS.

The Paralax Infrastructure: Automatic Parallelization With a Helping Hand

Speeding up sequential programs on multicores is a challenging problem that is in urgent need of a solution. Automatic parallelization of irregular pointer-intensive codes, exempli?ed by the SPECint codes, is a very hard problem. This paper shows that, with a helping hand, such auto-parallelization is possible and fruitful. This paper makes the following contributions: (i) A compiler framework for extracting pipeline-like parallelism from outer program loops is presented. (ii) Using a light-weight programming model based on annotations, the programmer helps the compiler to ?nd thread-level parallelism. Each of the annotations speci?es only a small piece of semantic information that compiler analysis misses, e.g. stating that a variable is dead at a certain program point. The annotations are designed such that correctness is easily veri?ed. Furthermore, we present a tool for suggesting annotations to the programmer. (iii) The methodology is applied to autoparallelize several SPECint benchmarks. For the benchmark with most parallelism (hmmer), we obtain a scalable 7-fold speedup on an AMD quad-core dual processor. The annotations constitute a parallel programming model that relies extensively on a sequential program representation. Hereby, the complexity of debugging is not increased and it does not obscure the source code. These properties could prove valuable to increase the ef?ciency of parallel programming.

FhCaBP4: A Fasciola hepatica calcium binding protein with EF-hand and dynein light chain domains

In trematodes, there is a family of proteins which combine EF-hand-containing domains with dynein light chain (DLC)-like domains. A member of this family from the liver fluke, Fasciola hepatica-FhCaBP4-has been identified and characterised biochemically. FhCaBP4 has an N-terminal domain containing two imperfect EF-hand sequences and a C-terminal dynein light chain-like domain. Molecular modelling predicted that the two domains are joined by a flexible linker. Native gel electrophoresis demonstrated that FhCaBP4 binds to calcium, manganese, barium and strontium ions, but not to magnesium or zinc ions. The hydrophobic, fluorescent probe 8-anilinonaphthalene-1-sulphonate bound more tightly to FhCaBP4 in the presence of calcium ions. This suggests that the protein undergoes a conformational change on ion binding which increases the number of non-polar residues on the surface. FhCaBP4 was protected from limited proteolysis by the calmodulin antagonist W7, but not by trifluoperazine or praziquantel. Protein-protein cross-linking experiments showed that FhCaBP4 underwent calcium ion-dependent dimerisation. Since DLCs are commonly dimeric, it is likely that FhCaBP4 dimerises through this domain. The molecular model reveals that the calcium ion-binding site is located close to a key sequence in the DLC-like domain, suggesting a plausible mechanism for calcium-dependent dimerisation.