Cyclooxygenase-2 inhibitors in tumorigenesis (Part II)

The rate-limiting step in arachidonate metabolism is mediated by enzymes known as cyclooxygenases (COXs). These enzymes catalyze the biosynthesis of prostaglandin H2, the precursor of molecules such as prostaglandins, prostacyclin, and thromboxanes. The COX enzyme family consists of the classical COX-1 enzyme, which is constitutively expressed in many tissues, and a second isozyme, i.e., COX-2, which is induced by various stimuli, such as mitogens and cytokines, and is involved in many inflammatory reactions. Because nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, these drugs also cause unwanted side effects, exemplified by gastrointestinal bleeding. Accumulating evidence indicates that NSAIDs can reduce the incidence of colorectal cancers in human and experimental animals and can reduce the number and size of polyps in patients with familial adenomatous polyposis. This Part II (of a two-part review) focuses on the growing clinical and experimental evidence that NSAIDS and COX-2 inhibitors can influence the risk of colon (and possibly of other) cancers.     

Model-based and actual independence for fairness-aware classification

The goal of fairness-aware classification is to categorize data while taking into account potential issues of fairness, discrimination, neutrality, and/or independence. For example, when applying data mining technologies to university admissions, admission criteria must be non-discriminatory and fair with regard to sensitive features, such as gender or race. In this context, such fairness can be formalized as statistical independence between classification results and sensitive features. The main purpose of this paper is to analyze this formal fairness in order to achieve better trade-offs between fairness and prediction accuracy, which is important for applying fairness-aware classifiers in practical use. We focus on a fairness-aware classifier, Calders and Verwer’s two-naive-Bayes (CV2NB) method, which has been shown to be superior to other classifiers in terms of fairness. We hypothesize that this superiority is due to the difference in types of independence. That is, because CV2NB achieves actual independence, rather than satisfying model-based independence like the other classifiers, it can account for model bias and a deterministic decision rule. We empirically validate this hypothesis by modifying two fairness-aware classifiers, a prejudice remover method and a reject option-based classification (ROC) method, so as to satisfy actual independence. The fairness of these two modified methods was drastically improved, showing the importance of maintaining actual independence, rather than model-based independence. We additionally extend an approach adopted in the ROC method so as to make it applicable to classifiers other than those with generative models, such as SVMs.     

Properties and structure of nylon fibers in relation to drawing and aqueous phenol treatments

The changes in nylon 66 fiber structure and properties which take place during drawing and aqueous phenol treatments were studied by means of measurements of length, birefringence, density, moisture regain, x-ray diffraction, stress–strain behavior, and sound velocity. Drawing was found to establish molecular orientation along the fiber axis predominantly in the early stages, whereas the development of lateral order occured primarily after a certain level of orientation had been achieved. Treatments in aqueous phenol solutions caused longitudinal contractions which depended on phenol concentration (1-5%), draw ratio (1-6), and the tension on the fiber during the treatment. The treatments resulted in an increase in the lateral order, decrease in orientation and corresponding changes in mechanical properties. Moisture regain was inversely related with density for the untreated fibers of various draw ratios, but the relationship became complex after treatments in phenol. The data are interpreted in terms of changes in the lateral order distributions, which permits an increase in the fibers' sorptive capacity despite an increase in the mean lateral order.     

Direct Characterization of Grain-Boundary Electrical Activity in Doped (Ba0.6Sr0.4)TiO3 by Combined Imaging of Electron-Beam-Induced Current and Electron-Backscattered Diffraction

Simultaneous measurements of remote electron beam induced current (REBIC) and orientation imaging microscopy (OIM) in a scanning electron microscope (SEM) have been applied to a polycrystalline (Ba_0.6Sr_0.4)TiO₃ with a positive temperature coefficient of resistivity (PTCR) to elucidate a grain-boundary character dependence of the potential barrier formation. The absence of electrical activity in a coherent Σ3 twin boundary is clearly imaged. The resistivity of individual grain boundaries estimated from a resistive contrast image is interpreted in terms of geometrical coherency, which is defined by the degree of coincidence in the reciprocal lattice points.     

Fabrication of Barium Titanate Single Crystals by Solid-State Grain Growth

BaTiO₃ single crystals were prepared by solid-state grain growth. The single crystals were obtained by seeding a poly-crystalline, TiO₂-excess BaTiO₃, which exhibited abnormal grain growth. The condition for single-crystal growth was essentially dependent on the grain growth behavior of the polycrystalline, sintered bodies. The annealing temperature suitable for the single-crystal growth was just below the critical temperature of abnormal grain growth in TiO₂-excess BaTiO₃, which is about 1300°C.     

The modulated structure formed by isothermal ageing in ZrO2-5.2 mol % Y2O3 alloy

The modulated structure produced by isothermal ageing of ZrO₂-5.2 mol % Y₂O₃ alloy was examined mainly by electron microscopy. It was found that the modulated structure was formed at ageing temperatures between 1400 and 1600° C, but not at 1700° C. The structure is developed by spinodal decomposition, which produces compositional fluctuation in the elastically soft 111 direction in cubic zirconia. The hardness increase caused by the development of modulated structure during ageing is larger than the hardening by precipitation of tetragonal phase in the cubic matrix.Graduate Student, Tohoku Univerisy, Sendai, Japan.     

Muscle Fiber Composition Changes after Selective Nerve Innervation

Facial nerve paralysis interferes with mimetic muscle function. To reconstruct natural facial movement, free muscle flaps are transplanted as new muscles. However, it is difficult to maintain resting tonus. A dual innervation technique in which other nerves such as the hypoglossal nerve or contralateral facial nerve are added is often applied. Using 10-week-old rats (n = 10), the masseteric and hypoglossal nerves were cut, and the distal stump of the masseteric nerve and the proximal stump of the hypoglossal nerve were then sutured (suture group). In the other group, the masseteric nerve was cut and cauterized (cut group). Immunohistochemistry and microarray were performed on the extracted masseter muscle. The immunohistochemistry results suggested that the muscles in the suture group obtained oxidative characteristics. The microarray showed the genes involved in mitochondrial function, including Perm1. In summary, our data support the validity of the dualinnervation technique for facial paralysis treatment.     

Size- and invasion-dependent increase in cyclooxygenase 2 levels in human colorectal carcinomas

Nonsteroidal anti-inflammatory drugs reduce the incidence and mortality of colorectal carcinoma. Their chemopreventive effects appear to be due to inhibition of cyclooxygenase (COX)-2. Here, we have studied the relationship between the COX-2 mRNA levels and pathological characteristics in 43 primary colorectal carcinomas. COX-2 levels were significantly higher in tumors with larger sizes and in those with deeper invasions but were not correlated with whether the patients had metastasis or not. These results suggest that larger carcinomas produce more COX-2 to support their own growth and that COX-2 inhibitors may be effective agents of carcinoma growth suppression.