A fast single pass edgel extraction routine

An edgel extraction algorithm is presented that requires only a single pass of the image. This algorithm determines the connectivity of all edgels found and also finds all junctions. Thresholding with hysteresis is used within the routine to improve the connectivity of the found edges.     

Methotrexate-resistant form of dihydrofolate reductase protects transgenic murine embryos from teratogenic effects of methotrexate

Methotrexate, a potent inhibitor of the ubiquitously expressed enzyme dihydrofolate reductase, induces limb and facial anomalies that resemble vascular disruptions in their evolution and final outcome. Previous studies suggest that inhibition of dihydrofolate reductase is responsible for methotrexate-induced embryopathy, although specific sites of methotrexate activity have not been well defined. In this report, we show that constitutive expression of a methotrexate-resistant form of dihydrofolate reductase in transgenic embryos and their placentas ameliorates methotrexate teratogenicity. However, expression of the transgene in maternal tissues had no significant protective effect. The results confirm the role of dihydrofolate reductase inhibition in the pathogenesis of methotrexate-induced birth defects and provide a foundation for future studies of targeted transgene expression in select embryonic or placental cell populations.     

Gene therapy for chronic myelogenous leukemia (CML): a retroviral vector that renders hematopoietic progenitors methotrexate-resistant and CML progenitors functionally normal and nontumorigenic in vivo

Chronic myelogenous leukemia (CML) is a malignant disease of the human hematopoietic stem cell caused by the BCR/ABL gene rearrangement. The only curative therapy is allogeneic transplantation. Although autologous transplants may prolong survival, most patients relapse because of disease persisting in the host and in the graft. Continued administration of chemotherapy after transplant could reduce the incidence of relapse provided that the autograft can be protected by transfer of a drug-resistance gene. However, CML autografts will almost certainly contain malignant stem cells that will also be rendered drug-resistant. The presence of the BCR/ABL oncoprotein is necessary and sufficient for malignant transformation seen in CML. We thus hypothesized that transfer of a vector that combines a drug-resistance gene with anti-BCR/ABL antisense (AS) sequences may allow for posttransplant chemotherapy to decrease persistent disease while rendering inadvertently transduced CML stem and progenitor cells functionally normal. We constructed a retroviral vector, LasBD, that combines the methotrexate (MTX)-resistant tyrosine-22 dihydrofolate-reductase (tyr22-DHFR) gene and AS sequences directed at the b3a2 BCR/ABL breakpoint. b3a2 BCR/ABL containing 32D and MO7e cells were transduced with LasBD and selected in MTX for 14 days. Expression of the AS sequences reduced BCR/ABL mRNA and p210(BCR/ABL) protein levels by 6- to 10-fold in most cells. This subsequently led to the restoration of normal function of BCR/ABL cDNA+ cells: they grew significantly slower in the presence of interleukin-3 (IL-3); they underwent apoptotic cell death when cultured without IL-3; and they had restored expression and function of adhesion receptors. These effects were specific, because LasBD-containing AS sequences directed at the b3a2 BCR/ABL breakpoint did not affect p190(BCR/ABL)-containing cells. LasBD also rendered 20% to 30% of primary Ph- and Ph+ CD34(+) cells MTX-resistant and decreased BCR/ABL mRNA levels in MTX resistant Ph+ CD34(+) cells by 10-fold. Expression of the MTX-resistant DHFR gene and the AS sequences has been stable for at least 1 year in vitro and for more than 70 days in vivo. Finally, LasBD decreased tumorigenicity of 32DBCR/ABL cells in vivo by 3 to 4 logs. In conclusion, the tyr22-DHFR gene in the LasBD vector can protect normal hematopoietic cells from MTX-mediated toxicity, whereas the AS sequences in LasBD can suppress expression of the BCR/ABL gene and restore normal function of BCR/ABL cDNA-containing cells. The LasBD vector may therefore prove to be an extremely useful adjunct in autologous transplantation for CML.     

Reducing the negative effects of sales promotions in supply chains using genetic algorithms

This paper considers the detrimental effect of promotions on the supply chain (SC), one of the main causes of the bullwhip effect. A genetic algorithm (GA) is proposed to reduce these negative effects. In order to validate the GA, it is used to determine the optimal ordering policy in an online version of the MIT beer distribution game. Subsequently, the GA is applied in a number of experiments involving deterministic and random demand and lead times combined with sales promotions. It is shown how GAs can be used to dampen the impact of the bullwhip effect and can be used to assist supply managers in predicting reorder quantities along the supply chain.     

High-speed & Low Area Hardware Architectures of the Whirlpool Hash Function

High-speed and low area hardware architectures of the Whirlpool hash function are presented in this paper. A full Look-up Table (LUT) based design is shown to be the fastest method by which to implement the non-linear layer of the algorithm in terms of logic. An unrolled Whirlpool architecture implemented on the Virtex XC4VLX100 device achieves a throughput of 4.9 Gbps. This is faster than a SHA-512 design implemented on the same device and other previously reported hash function architectures. A low area iterative architecture, which utilises 64-bit operations as opposed to full 512-bit operations, is also described. It runs at 430 Mbps and occupies 709 slices on a Virtex X4VLX15. This proves to be one of the smallest 512-bit hash function architectures currently available.

Thermal conductivity measurements of some glass fibre- and carbon fibre-reinforced plastics

Thermal conductivity experiments are reported on unidirectional composites over the temperature range –150 to 130 ° C. Results for R-glass/Fibredux 914 specimens, and for carbon fibre GY-80/Code 69 resin specimens, in directions parallel and perpendicular to the fibre directions have been interpreted using standard theories. Experiments were also made on specimens in which the carbon fibres made angles of 30 °, 45 ° and 60 ° to the temperature gradient. An attempt was made to understand these data using a finite difference model.     

A comparison of local surface geometry estimation methods

The performance of several methods for estimating local surface geometry (the principal frame plus the principal quadric) are examined by applying them to a suite of synthetic and real test data which have been corrupted by various amounts of additive Gaussian noise. Methods considered include finite differences, a facet based approach, and quadric surface fitting. The nonlinear quadric fitting method considered was found to perform the best but has the greatest computational cost. The facet based approach works as well as the other quadric fitting methods and has a much smaller computational cost. Hence it is the recommended method to use in practice.     

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.