Some results characterizing the finite time behaviour of the simulated annealing algorithm

TheSimulated Annealing algorithm is a probabilistic search technique for finding the minimum cost state in a set Ω. The algorithm has been successfully used to obtain near-optimal solutions for problems for which no other effective algorithms exist. For example, problems in integrated circuit layout and in finite impulse response (FIR) filter design have been solved using annealing. In most applications, Ω is finite set, and the annealing algorithm may be modelled as a time-inhomogeneous Markov chain on Ω with transition probabilities that are powers of a time varying parameter ε. It has been shown by several researchers that if ε is driven to 0 sufficiently slowly, then the algorithm will eventually find a minimum cost state in Ω with probability 1. In this paper, we will focus on the finite-time behaviour of the annealing algorithm. In particular, we will summarize some results relating the number of steps taken by the algorithm to the quality of the solutions obtained. These results provide qualitative as well as quantitative information about the status of the annealing algorithm after a finite number of steps. This will be illustrated using some examples.     

A novel 3D mixed finite‐element model for statics of angle‐ply laminates

Analysis of angle‐ply laminates becomes critical and computationally involved because of the presence of extension–shear coupling. A refined three‐dimensional, mixed, 18‐node finite element (FE) model has been developed to analyse angle‐ply laminates under static loading. The minimum potential energy principle has been used for the development of the mixed FE model, where the transverse stress components (τ_xz, τ_yz and σ_z, where z is the thickness direction) have been incorporated as the nodal degrees of freedom, in addition to the three displacement fields. Further, continuity of transverse stress fields through the thickness of the plate and layerwise continuity of displacement fields have been enforced in the formulation. Because all the constitutive and the compatibility conditions have been ensured within the continuum, the present formulation is unique amongst the family of mixed FE models. Results have been obtained for various angle‐ply laminates and compared with analytical and finite‐element solutions, which have been found to be in good agreement with them. Some new results on angle‐ply with clamped–clamped support condition have also been presented to serve as benchmark results. Copyright © 2003 John Wiley & Sons, Ltd.     

Different populations of progesterone receptor-steroid complexes in binding to specific DNA sequences: effects of salts on kinetics and specificity

The endothelium plays an obligatory role in a number of relaxations of isolated arteries. These endothelium-dependent relaxations are due to the release by the endothelial cells of potent vasodilator substances [endothelium-derived relaxing factors (EDRF)]. The best characterized EDRF is nitric oxide (NO). Nitric oxide is formed by the metabolism of L-arginine by the constitutive NO synthase of endothelial cells. In arterial smooth muscle, the relaxations evoked by EDRF are explained best by the stimulation by NO of soluble guanylate cyclase that leads to the accumulation of cyclic GMP. The endothelial cells also release an unidentified substance that causes hyperpolarization of the cell membrane (endothelium-derived hyperpolarizing factor, EDHF). The release of EDRF from the endothelium can be mediated by both pertussis toxin-sensitive (alpha2-adrenergic activation, serotonin, thrombin, aggregating platelets) and insensitive (adenosine diphosphate, bradykinin) G-proteins. In blood vessels from animals with regenerated endothelium, and/or atherosclerosis, there is a selective loss of the pertussis-toxin sensitive mechanism of EDRF-release which favors the occurrence of vasospasm, thrombosis and cellular growth.     

Characterization of two LGR genes homologous to gonadotropin and thyrotropin receptors with extracellular leucine-rich repeats and a G protein-coupled, seven-transmembrane region

The receptors for LH, FSH, and TSH belong to the large G protein-coupled, seven-transmembrane (TM) protein family and are unique in having a large N-terminal extracellular (ecto-) domain containing leucine-rich repeats important for interaction with the glycoprotein ligands. We have identified two new leucine-rich repeat-containing, G protein-coupled receptors and named them as LGR4 and LGR5, respectively. The ectodomains of both receptors contain 17 leucine-rich repeats together with N- and C-terminal flanking cysteine-rich sequences, compared with 9 repeats found in known glycoprotein hormone receptors. The leucine-rich repeats in LGR4 and LGR5 are arrays of 24 amino acids showing similarity to repeats found in the acid labile subunit of the insulin-like growth factor (IGF)/IGF binding protein complexes as well as slit, decorin, and Toll proteins. The TM region and the junction between ectodomain and TM 1 are highly conserved in LGR4, LGR5, and seven other LGRs from sea anemone, fly, nematode, mollusk, and mammal, suggesting their common evolutionary origin. In contrast to the restricted tissue expression of gonadotropin and TSH receptors in gonads and thyroid, respectively, LGR4 is expressed in diverse tissues including ovary, testis, adrenal, placenta, thymus, spinal cord, and thyroid, whereas LGR5 is found in muscle, placenta, spinal cord, and brain. Hybridization analysis of genomic DNA indicated that LGR4 and LGR5 genes are conserved in mammals. Comparison of overall amino acid sequences indicated that LGR4 and LGR5 are closely related to each other but diverge, during evolution, from the homologous receptor found in snail and the mammalian glycoprotein hormone receptors. The identification and characterization of new members of the LGR subfamily of receptor genes not only allow future isolation of their ligands and understanding of their physiological roles but also reveal the evolutionary relationship of G protein-coupled receptors with leucine-rich repeats.     

Successful microsurgical tissue transfer in a patient with postsplenectomy thrombocytosis treated with platelet-phoresis

With the use of platelet-phoresis, two microsurgical free-tissue transfers were successfully undertaken in a patient with postsplenectomy thrombocytosis that had initially caused flap failure. Rapid reduction in the platelet count allowed free-tissue transfer in this patient who required early wound coverage.     

The Baylor College of Medicine experience with gold seed implantation

Advances in imaging technology and implant technique have led to the resurgent interest and practice of brachytherapy for the treatment of prostate cancer. Brachytherapy is a form of radiation treatment in which radioactive sources are placed directly into the tumor; it offers the advantage of maximizing the radiation dose delivered to the tumor while sparing the adjacent normal tissue. Permanent implants have become an important component of radiation delivery. Interstitial gold radioisotope (Au-198) implants for prostate cancer were introduced at Baylor College of Medicine in 1965. The rationale for using Au-198, instead of the two most commonly used radioisotopes, Palladium-103 (Pd-103) and Iodine-125 (I-125), is discussed, and the Baylor implant technique is compared to that used in other centers. Retrospective review divides the patient population into pre-ultrasound versus post-ultrasound eras. Dosimetric calculation and disease control with the Au-198 seed implant for prostatic cancer are reviewed for the two different eras; toxicity is evaluated in the post-ultrasound era only. In the pre-ultrasound era, 510 patients were treated with pelvic lymph node sampling and gold seed insertion of the prostate followed by external beam radiation. In the post-ultrasound era, 54 patients were treated definitively with ultrasound-guided transperineal Au-198 implant followed by external beam irradiation. A small group of 30 patients in the post-ultrasound era were evaluated for the efficacy of Au-198 re-implantation for locally recurrent disease.     

Free radicals and ethanol-induced cytotoxicity in neural crest cells

Associations between ethanol-induced cranial neural crest cell (NCC) damage in mammalian embryos and subsequent malformations as observed in human fetal alcohol syndrome have previously been illustrated. The vulnerability of NCCs to this teratogen may result, at least in part, from their sensitivity to free radical damage. To examine relationships between free radical generation and NCC cytotoxicity, primary culture of mouse NCCs was used. NCC viability was determined in both dose- and time-response studies involving ethanol exposure. After 48 hr of culture, cell viability was significantly diminished at all doses tested (i.e., 50, 100, 150, and 200 mM ethanol). At 100 mM ethanol (a dosage that is teratogenic in vivo and in whole embryo culture), cell viability decreased to approximately 50% of control values over the first 12 hr of culture, and decreased further, to approximately 20% by 48 hr. Using nitroblue tetrazolium as a probe, it was observed that exposure of NCCs to ethanol stimulated the production of superoxide anion radicals. Co-treatment of the ethanol-exposed NCCs with free radical scavengers including 300 units/ml of superoxide dismutase, catalase (500 units/ml), or alpha-tocopherol (300 microM) significantly improved NCC viability. These results suggest that the ethanol-induced NCC injury is mediated, at least in part, through the generation of free radicals. To test this hypothesis further, NCCs were exposed in culture to xanthine/xanthine oxidase. Exogenous free radicals generated by the xanthine/xanthine oxidase system resulted in reduced NCC viability, the severity of which increased in a time and enzyme concentration-related manner. Superoxide dismutase (300 units/ml) and catalase (500 units/ml) significantly reduced the effects of the xanthine/xanthine oxidase-generated free radicals on NCC viability. The similarity between the susceptibility of NCCs to ethanol and their susceptibility to exogenous free radicals in concert with the free radical scavenger-mediated amelioration of ethanol and exogenous free radical-induced NCC death strongly suggest that free radicals play a significant role in ethanol-induced NCC death.     

Protein engineering thrombin for optimal specificity and potency of anticoagulant activity in vivo

Previous alanine scanning mutagenesis of thrombin revealed that substitution of residues W50, K52, E229, and R233 (W60d, K60f, E217, and R221 in chymotrypsinogen numbering) with alanine altered the substrate specificity of thrombin to favor the anticoagulant substrate protein C. Saturation mutagenesis, in which residues W50, K52, E229, and R233 were each substituted with all 19 naturally occurring amino acids, resulted in the identification of a single mutation, E229K, that shifted the substrate specificity of thrombin by 130-fold to favor the activation of the anticoagulant substrate protein C over the procoagulant substrate fibrinogen. E229K thrombin was also less effective in activating platelets (18-fold), was resistant to inhibition by antithrombin III (33-fold and 22-fold in the presence and absence of heparin), and displayed a prolonged half-life in plasma in vitro (26-fold). Thus E229K thrombin displayed an optimal phenotype to function as a potent and specific activator of endogenous protein C and as an anticoagulant in vivo. Upon infusion in Cynomolgus monkeys E229K thrombin caused an anticoagulant effect through the activation of endogenous protein C without coincidentally stimulating fibrinogen clotting and platelet activation as observed with wild-type thrombin. In addition, E229K thrombin displayed enhanced potency in vivo relative to the prototype protein C activator E229A thrombin. This enhanced potency may be attributable to decreased clearance by antithrombin III, the principal physiological inhibitor of thrombin.     

Sexual dimorphism in the tooth crown dimensions of the second deciduous and first permanent molars of Taiwan Chinese

Corticosteroids such as prednisone are commonly prescribed for a variety of illnesses mediated by the immune system. This paper reviews the available literature on mood symptoms during corticosteroid treatment. Few studies have used well-recognized measures of symptoms or clearly defined diagnostic criteria to characterize such mood changes. The limited data available suggest that symptoms of hypomania, mania, depression, and psychosis are common during therapy. Symptoms appear to be dose dependent and generally begin during the first few weeks of treatment. Risk factors for the development of mood instability or psychosis are not known. The similarities of the psychiatric symptoms resulting from corticosteroid treatment to the symptoms of bipolar disorder are discussed.