A hybrid genetic algorithm for the single machine scheduling problem with sequence-dependent setup times

This paper presents a hybrid approach based on the integration between a genetic algorithm (GA) and concepts from constraint programming, multi-objective evolutionary algorithms and ant colony optimization for solving a scheduling problem. The main contributions are the integration of these concepts in a GA crossover operator. The proposed methodology is applied to a single machine scheduling problem with sequence-dependent setup times for the objective of minimizing the total tardiness. A sensitivity analysis of the hybrid approach is carried out to compare the performance of the GA and the hybrid genetic algorithm (HGA) approaches on different benchmarks from the literature. The numerical experiments demonstrate the HGA efficiency and effectiveness which generates solutions that approach those of the known reference sets and improves several lower bounds.     

High cleavage activity and stability of hammerhead ribozymes with a uniform 2''-amino pyrimidine modification

Induction of a microsomal oleate delta12 (n-6) desaturase which is mainly responsible for an increase in membrane lipid unsaturation at low temperature has been observed in the free-living amoeba Acanthamoeba castellanii. In this study we show that the enzyme can also be regulated by oxygen independently of temperature in batch cultures grown to O2-limitation. Raising the oxygen concentration from below the lower limit of detection (< 0.1 microM) to approximately air-saturation (230 microM), whilst maintaining the growth temperature constant (30 degrees C), increased lipid unsaturation and elevated n-6-desaturase activity 2.3-fold. Addition of the protein synthesis inhibitor, anisomycin, showed that increased desaturase activity was due to new protein synthesis rather than activation of pre-existing enzyme. These observations are important for future studies of the mechanism of temperature adaptation in poikilotherms.     

Inhibition of Stromal PlGF Suppresses the Growth of Prostate Cancer Xenografts

The growth and vascularization of prostate cancer is dependent on interactions between cancer cells and supporting stromal cells. The primary stromal cell type found in prostate tumors is the carcinoma-associated fibroblast, which produces placental growth factor (PlGF). PlGF is a member of the vascular endothelial growth factor (VEGF) family of angiogenic molecules and PlGF mRNA levels increase after androgen deprivation therapy in prostate cancer. In this study, we show that PlGF has a direct dose-dependent proliferative effect on human PC-3 prostate cancer cells in vitro and fibroblast-derived PlGF increases PC-3 proliferation in co-culture. In xenograft tumor models, intratumoral administration of murine PlGF siRNA reduced stromal-derived PlGF expression, reduced tumor burden and decreased the number of Ki-67 positive proliferating cells associated with reduced vascular density. These data show that targeting stromal PlGF expression may represent a therapeutic target for the treatment of prostate cancer.     

Structural Requirements for the Binding of a Peptide to Prohibitins on the Cell Surface of Monocytes/Macrophages

The screening of phage peptide libraries resulted in the identification of a sequence (named NW peptide, NWYLPWLGTNDW) that specifically binds to human monocytes and macrophages. Although the NW peptide can be used for the targeted delivery of therapeutics without knowledge of its receptor(s), the identification of-its binding partners will support future clinical applications-Here, we used the biotinylated NW peptide for cross-linking cell surface receptor(s) on live cells or as bait in pull-down assays with membrane proteins isolated from monocytes or human THP-1 cells differentiated into macrophages. Proteomic analysis of the captured proteins identified cell surface prohibitins (PHB1 and PHB2) and modified albumin as binding partners. Using flow cytometry and pull-down methods, we demonstrated that PHB1 and PHB2 interact directly with the NW peptide. Confocal imaging showed co-localization of the peptide with PHB1 on the surface of monocytes. Single replacement of either tryptophan or leucine with alanine completely inhibited binding, whereas the replacement of asparagine at position 1 or 10 and aspartic acid at position 11 with alanine did not affect the binding of the peptide variants. Neutral amino acid replacement of tryptophan at positions 2, 6, and 12 with tyrosine or phenylalanine also abolished the binding, implying that the indole ring of tryptophan is indispensable for the NW peptide to bind. Overall, the data suggest that membrane-associated prohibitins might be a useful target for the delivery of therapeutics to monocytes/macrophages and that tryptophan and leucine are key residues for peptide binding.     

Antibody epitopes probed by immunoselected phage-display library peptides in members of a family with various rheumatic manifestations

OBJECTIVE: The random peptide combinatorial phage library approach overcomes the problem of lack of structural information about the aetiological agent or the antigen responsible for a given disease. Here, we used such a strategy to gain insight into the aetiology of rheumatoid arthritis (RA). METHODS: We analyzed the reactivity of serum antibodies from a family with various rheumatic manifestations against RA-immunoselected nanopeptides displayed on phage particles. RESULTS AND CONCLUSION: We found that within the same family, there was a difference in antibody reactivity against the peptides tested. The IgG isotype of the peptide reactive antibodies indicated that the observed reactivities were not related to the presence of polyreactive IgM antibodies. Furthermore, it is unlikely that the observed reactivity was due to rheumatoid factors (RF), since two patients who were positive for the immunoselected Pep3 peptide (LSSREPQAR) were RF negative. We also found that the serum of one patient with polyarthralgias also reacted with the same peptide bound by the RA serum, which may suggest the implication of a common aetiological agent in the apparition of this antibody reactivity. Finally, we noted that one patient with Sj?gren's syndrome had antibodies to the RA peptide, which may indicate a potential relationship between these two autoimmune diseases.