A genetic algorithm for the optimisation of assembly sequences

This paper describes a Genetic Algorithm (GA) designed to optimise the Assembly Sequence Planning Problem (ASPP), an extremely diverse, large scale and highly constrained combinatorial problem. The modelling of the ASPP problem, which has to be able to encode any industrial-size product with realistic constraints, and the GA have been designed to accommodate any type of assembly plan and component. A number of specific modelling issues necessary for understanding the manner in which the algorithm works and how it relates to real-life problems, are succinctly presented, as they have to be taken into account/adapted/solved prior to Solving and Optimising (S/O) the problem. The GA has a classical structure but modified genetic operators, to avoid the combinatorial explosion. It works only with feasible assembly sequences and has the ability to search the entire solution space of full-scale, unabridged problems of industrial size. A case study illustrates the application of the proposed GA for a 25-components product.     

A theoretical study of light emission from nanoscale silicon

In comparing our calculated exciton energies with those obtained from pseudopotential calculations (Ref. 27) and from a previous tight binding calculation (Ref. 30), we stated that the differences between the three semi-empirical calculations arise because of different treatment of the nanocrystal surfaces. This appears not to be correct. Subsequent calculations with variable Si-H parameters have shown that the band gap is actually rather insensitive to the actual value of these. Instead, the important feature appears to be the overall quality of the bulk band structure parameterization. References 27 and 30 use more extensive and higher quality empirical parameterizations for bulk Si than the sp³s∗ model used by us. Repeating our time dependent calculations with an improved sp³d⁵ parameterization results in similar values to those of Refs. 27 and 30 for the exciton energies.¹ The agreement of the sp³s∗ values with experimental photoluminescence energies (Fig. 7) cannot, therefore, be regarded as well understood at this time.^1,2     

New unified laws in fatigue: From the Wöhler’s to the Paris’ regime

Generalizations and unification of the celebrated Paris’ and Wöhler’s laws for fatigue crack propagation are derived by applying the recently developed quantized (or finite) fracture mechanics. In particular, three generalized Paris’, Wöhler’s or unified laws are proposed and compared, demonstrating their applicability for predicting the life time of structures containing from small (the Wöhler’s regime) to large (the Paris’ regime) propagating fatigue cracks.     

Mathematical determination of feeding patterns and its consequence on correlational studies

The cell cycle regulatory proteins, which include cyclin-dependent kinases (cdks), cdk inhibitors (CKIs), cyclins, and the pRB, and E2F families of proteins, constitute a network of interacting factors which govern exit from or passage through the mammalian cell cycle. While the proteins within these families have similar structural characteristics, each family member exhibits distinct expression patterns during embryogenesis and distinct biological activities. In order to begin to understand the tissue-specific roles of these interacting factors, we determined the expression pattern and activity of the pRB, E2F, cyclin, cdk, and CKI families of cell cycle regulatory proteins during retinoic acid-induced (neuronal pathway) and DMSO-induced (cardiac muscle pathway) differentiation of the pluripotent murine embryonal carcinoma cell line, P19. We demonstrate here that P19 terminal differentiation causes lineage-specific changes in the expression and activity of distinct members of the E2F, pRB, cyclin, and CKI families. Furthermore, dynamic changes in the activities of these cell cycle regulatory proteins occur through several overlapping mechanisms, culminating in repression of DNA-binding activity by all of the E2F family members as cells terminally differentiate.     

Mechanisms of insulin resistance in experimental hyperinsulinemic dogs

The aim of this work was to identify which proteins in horse dander extracts are allergens and to characterise them. Two-dimensional PAGE showed that horse dander preparations are composed of up to 50 proteins, all having acidic isoelectric points in the pH range 3-4.5. Immunoblots of two-dimensional PAGE were used to compare the reactivity of the proteins with IgE from 23 allergic patients. Patient sera were divided into two main groups recognising either allergens of 18.5 kDa or proteins of 27-29 and 31 kDa. The proteins of 27-29 kDa and 31 kDa were all N-glycosylated and their glycan chains seem to play a role in the binding of IgE from allergic patients. The sugar composition of their carbohydrate moiety was determined and lectin-binding experiments indicated presence of terminal sialic acid linked alpha-(2-->6) to galactose, galactose linked beta-(1-->4) to N-acetylglucosamine, and possibly presence of sialic acid linked alpha-(2-->3) to galactose. The 27-29-kDa glycoproteins had heterogeneous isoelectric points, most probably due to different degrees of sialylation in their oligosaccharide chains. The two 18.5-kDa allergens exhibited slightly different isoelectric points and their N-terminal sequences were identical, showing that they most likely were isoforms of the same protein. Sequence analyses revealed that their N-terminal sequences are similar to proteins belonging to the lipocalin family. We named the two 18.5-kDa proteins Equ c 2.0101 and Equ c 2.0102, according to International Allergen Nomenclature recommendations [King, T. P., Hoffman, D., Lowenstein, H., Marsh, D. G., Platts-Mills, T. A. E. & Thomas, W. (1995) J. Allergy Clin. Immunol. 96, 5-14]. The N-terminal of the allergens of 27-29 kDa were blocked and their sequences were not determined. Their amino acid compositions were determined and comparison with acidic mammalian proteins in the Swiss-Prot database revealed high scores with lipocalin proteins. This suggests that the glycosylated horse dander allergens belong to the lipocalin family, like Equ c 2.0101 and Equ c 2.0102.     

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.     

A globally stable discrete-time controller for current-fed induction motors

In this short paper we present a discrete-time field oriented controller (FOC) for current-fed induction motors which insures global asymptotic speed regulation as well as rotor flux norm tracking. To the best of our knowledge, this is the first time such a result is rigorously established for a controller implemented in discrete-time. To insure global stability a condition on the reference for the rotor flux norm, which is time-varying, is imposed. This condition disappears as the sampling period goes to zero, hence allowing for independent speed regulation and rotor flux norm tracking. One important feature of our scheme is that, compared with the first-difference approximation of the classical indirect FOC, the additional computational burden is negligible. It is also shown that the result can easily be extended to the case of tracking time-varying references in speed or position.     

Mutual Prodrugs of 5-Fluorouracil: From a Classic Chemotherapeutic Agent to Novel Potential Anticancer Drugs

The development of potent antitumor agents with a low toxicological profile against healthy cells is still one of the greatest challenges facing medicinal chemistry. In this context, the “mutual prodrug” approach has emerged as a potential tool to overcome undesirable physicochemical features and mitigate the side effects of approved drugs. Among broad-spectrum chemotherapeutics available for clinical use today, 5-fluorouracil (5-FU) is one of the most representative, also included in the World Health Organization model list of essential medicines. Unfortunately, severe side effects and drug resistance phenomena are still the primary limits and drawbacks in its clinical use. This review describes the progress made over the last ten years in developing 5-FU-based mutual prodrugs to improve the therapeutic profile and achieve targeted delivery to cancer tissues.