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Background. The authors previously have shown by gas chromatography-mass spectrometry that the hydroxyl radical (.OH) induces alterations in the DNA base structure of the female breast, which are premalignant markers of breast cancer. Fourier transform-infrared (FT-IR) spectroscopy also has a high potential for revealing a broad array of structural changes in DNA that may provide important new insight into breast cancer etiology and prediction. Methods. DNA from normal reduction mammoplasty tissue, invasive ductal carcinoma, and nearby microscopically normal tissue was analyzed by FT-IR spectroscopy. Statistical models based on DNA spectral properties were developed and compared with a statistical model previously used with base modifications. Results. Substantial differences were found in the spectral properties of DNA from women with normal and cancerous breast tissue, indicating an ability to discriminate cancerous tissue from noncancerous tissue with a sensitivity and specificity of 83%. Most importantly, the normal population was divided into subgroups in which a nonrandom progression was identified and a cancerlike DNA phenotype that was highly correlated (r [greater than or equal to] 0.90) with that of the patients with cancer was exhibited in 59% of the women. The spectral data, which also were highly correlated with the base-model data, were used to establish a model for predicting the probability of breast cancer. Consistent with the high cancer reoccurrence rate in the ipsilateral breast, 8 of 10 of the microscopically normal tissue specimens remaining after tumor excision were classified as cancerous using this model. Conclusions. Progressive structural changes in the DNA of the normal female breast, leading to a premalignant cancer-like phenotype in a high proportion of women, are the basis for a new paradigm for understanding the etiology of breast cancer and predicting its occurrence at early stages of oncogenesis. The results also suggest therapeutic strategies for potentially reversing the extent of DNA damage, which may be useful in disease prevention and treatment.

'TECHNOLOGY AUDITS ... GRAPPLING WITH ACCOUNTABILITY' IS MORE THAN THE TITLE OF THIS ARTICLE. THE PHRASE DESCRIBES AN ADVANCE IN THINKING ABOUT HOW EDUCATORS, PARENTS, AND COMMUNITY LEADERS CAN BEGIN […]

Abstract: This paper discusses the concept, application, and usefulness of software design patterns for scientific programming in Fortran 90/95. An example from the discipline of object-oriented design patterns, that of a game based on navigation through a maze, is used to describe how some important patterns can be implemented in Fortran 90/95 and how the progressive introduction of design patterns can usefully restructure Fortran software as it evolves. This example is complemented by a discussion of how design patterns have been used in a real-life simulation of Particle-in-Cell plasma physics. The following patterns are mentioned in this paper: Factory, Strategy, Template, Abstract Factory and Facade. Program summary: Program title: mazev1, mazev2, mazev3 Catalogue identifier: AEAI_v1_0 Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEAI_v1_0.html Program obtainable from: CPC Program Library, Queen''s University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 1958 No. of bytes in distributed program, including test data, etc.: 17 100 Distribution format: tar.gz Programming language: Fortran 95 Computer: PC/Mac Operating system: Unix/Linux/Mac (FreeBSD)/Windows (Cygwin) RAM: These are interactive programs with small (KB) memory requirements Classification: 6.5, 20 Nature of problem: A sequence of programs which demonstrate the use of object oriented design patterns for the restructuring of Fortran 90/95 software. The programs implement a simple maze game similar to that described in [1]. Solution method: Restructuring uses versions of the Template, Strategy and Factory design patterns. Running time: Interactive. References: [[1] ] E. Gamma, R. Helm, R. Johnson, J. Vlissides, Design Patterns: Elements of Reusable Object Oriented Software, Addison-Wesley, 1995, ISBN 0201633612. [Copyright &y& Elsevier]

Likert scaled data, which are frequently collected in studies of interaction in virtual environments, demand specialized statistical tools for analysis. The routine use of statistical methods appropriate for continuous data in this context can lead to significant inferential flaws. Likert scaled data are ordinal rather than interval scaled and need to be analyzed using rank based statistical procedures that are widely available. Likert scores are “lumpy” in the sense that they cluster around a small number of fixed values. This lumpiness is made worse by the tendency for subjects to cluster towards either the middle or the extremes of the scale. We suggest an ad hoc method to deal with such data which can involve a further lumping of the results followed by the application of nonparametric statistics.

The article by Markus [1] discusses the subject of object-oriented (OO) design patterns and describes ways in which three well-known patterns might be implemented in Fortran 90/95. It appears that the idea of object-oriented design patterns in Fortran might just be coming of age and it is a very appropriate subject for discussion in a Forum such as this.We have been developing our own implementations of design patterns in Fortran 90/95 for some time and have one paper under review [2] and another being presented at the 6th Workshop on Parallel/High-Performance Object Oriented Scientific Computing (POOSC) in Nantes, France in July 2006 [3]. Our application area is particle-in-cell simulations in plasma physics, but the results that we have obtained will, we hope, be of interest to Fortran 90/95 programmers in general.Our own starting point with design patterns in Fortran 90/95 stems from the literature on object-based programming in that language [4-10]. Several authors have observed that the obvious unit of encapsulation, the Fortran 90/95 module, can be thought of as an object-based class: it can support a type which defines the stored data together with subprograms which can operate on that data. With some discipline and ingenuity, these authors have shown how to emulate the notions of object construction and destruction, inheritance and polymorphism. These emulations were actually implemented using object composition. For example, one child module might include another parent module in order to simulate inheritance. As Markus correctly points out, most of the famous design patterns are based on object composition and the authors of [4-10] have, frequently, been using design patterns as a way of simulating OO behaviour.Because the subject of OO design patterns in Fortran 90/95 is so fresh, there is ample scope for them to be presented in different ways by different authors. Whilst appreciating the clarity and relevance of Markus' expositions, we would like to make some points of criticism which we believe are important to a further discussion of this topic. The points we make refer to the ideas expressed in the book by Gamma et al. [11] which is considered to be the fundamental exposition of the topic of OO design patterns.

Chlorogenic acid (CGA) is considered to act as an antioxidant. However, the inhibitory effects of CGA on specific radical species are not well understood. Electron spin resonance (ESR) in combination with spin trapping techniques was utilized to detect free radicals. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) was used as a spin trapping reagent while the Fenton reaction was used as a source of hydroxyl radical (·OH). We found that CGA scavenges ·OH in a dose-dependent manner. The kinetic parameters, IC50and Vmax, for CGA scavenging of ·OH were 110 and 1.27 μM/sec, respectively. The rate constant for the scavenging of ·OH by CGA was 7.73 × 109M−1sec−1. Our studies suggest that the antioxidant properties of CGA may involve a direct scavenging effect of CGA on ·OH.

Clinical and laboratory studies have provided evidence of oncostatic activity by the pineal neurohormone melatonin. However, these studies have not elucidated its mechanism of action. The following series of MCF-7 breast tumor cell studies conducted in the absence of exogenous steroid hormones provide evidence for a novel mechanism of oncostatic activity by this endogenous hormone. We observed a 40–60% loss of MCF-7 cells after 20-h treatment with 100 nM melatonin, which confirmed and extended previous reports of its oncostatic potency. Interestingly, there were no observed changes in tritiated thymidine uptake, suggesting a lack of effect on cell cycle/nascent DNA synthesis. Further evidence of a cytocidal effect came from morphologic observations of acute cell death and autophagocytosis accompanied by degenerative changes in mitochondria. Studies of mitochondrial function via standard polarography revealed a significant increase in oxygen consumption in melatonin-treated MCF-7 cells. Enzyme-substrate studies of electron transport chain (complex IV) activity in detergent permeabilized cells demonstrated a concomitant 53% increase (p< 0.01) in cytochrome coxidase activity. Additional studies of succinate dehydrogenase activity (complex II) as determined by reduction of (3-4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide demonstrated a significant increase (p< 0.05) in melatonin-treated cells and further confirmed the accelerated ET activity. Finally, there was a 64% decrease (p< 0.05) in cellular ATP levels in melatonin-treated cells. The G-protein-coupled melatonin receptor antagonist luzindole abrogated the cytotoxic and mitochondrial effects. These studies suggest a receptor-modulated pathway of cytotoxicity in melatonin-treated MCF-7 tumor cells with apparent uncoupling of oxidative phosphorylation.

Japanese medaka (Oryzias latipes) were used to evaluate the carcinogenicity of a complex groundwater that contained 5 U.S. Environmental Protection Agency priority pollutant heavy metals and 13 chlorinated aliphatic hydrocarbons. A test protocol that used 10 mg/L diethylnitrosamine (DEN) prior to groundwater exposure was designed to assess both initiation and promotion. The fish were exposed continuously for 9 mo with 0, 1, 5, or 25% groundwater, by volume, with either West Branch of Canal Creek water (Aberdeen Proving Ground-Edgewood Area, Aberdeen Proving Ground, MD) or dechlorinated tap water as the diluent, while concurrent controls were run in the laboratory. Incidental findings included various neoplasms in the nares, ovary, skeletal muscle, skin, swim bladder, testis, thymus, and thyroid. Factors evaluated during statistical analyses of fish neoplasm prevalence included diluent type, groundwater percentage, fish gender, and DEN initiation. Liver neoplasm prevalence was higher in DEN-initiated fish and was frequently higher in males. Concentrations of up to 25% groundwater, by volume, showed no evidence of being a complete carcinogen and showed no consistent, conclusive evidence of being a promoter.

Chaparral is considered to act as an antioxidant. However, the inhibitory effects of chaparral on specific radical species are not well understood. Using electron paramagnetic resonance (EPR) spectroscopy in combination with spin trapping techniques, we have found that chaparral scavenges superoxide anion radical (O2·-) in a dose-dependent manner. 5,5-dimethyl-lpyrroline-N-oxide (DMPO) was used as a spin trapping agent and the reaction of xanthine and xanthine oxidase as a source of O2·-. The kinetic parameters, IC50and Vmax, for chaparral scavenging of O2·-were found to be 0.899 μg/mL and 8.4 ng/mL/sec, respectively. The rate constant for chaparral scavenging O2·-was found to be 1.22 x 106g-1s-1. Our studies suggest that the antioxidant properties of chaparral may involve a direct scavenging effect of the primary oxygen radical, O2·-.

This study developed a practical method for determining the functional outcome status of patients in an ambulatory setting. Health status of 1,840 primary care patients was compared at three points in time: patient's usual status, status at the initial visit, and status at time of telephone follow-up. Follow-up status was also compared with the physician's expectation, which was estimated at the time of the initial visit. Of the patients, 62% showed improvement, 31% remained at the same level, and 7% deteriorated from the time of their initial clinic visit. Physicians tended to overestimate either the speed or degree with which patients return to their usual functional status; 32% of the patients studied reported themselves as being less well than usual at the time of follow-up.

Software requirements elicitation workshops often make use of a widely used and, on the surface, highly informal, notational medium: the sticky note. Often, in such workshops, facilitators and participants collaborate to construct “diagrams” made up of sticky notes. Methodologies have been developed that prescribe the way that diagram construction can uncover and document software requirements. Because they constitute a collaborative diagrammatic notation, such sticky-note diagrams lend themselves to an evaluation underpinned by theories of visual notation. In this paper we apply an analytic framework, the Patterns of User Experience (PUX), to sticky-note diagrams from two workshop methodologies, “Big Picture Event Storming” (BPES) by Alberto Brandolini and “User Story Mapping” (USM) by Jeff Patton. Our evaluation considers the sticky-note diagrams and the collaborative social processes surrounding them.

The decoration of the interior of hospitals should receive the earnest consideration of the physicians in charge, as the greater sanitary conditions which obtain from the application of thoroughly hygienic coatings are of vital importance in such establishments. I have made a careful study of the characteristics of various paints, and shall endeavor, in this article, to point out the defects and merits of different types of wall-coatings.

IN the absence of any details, apparently Mr. Wilson's simplest plan would be to insulate the hammer and bell of his “small striking clock,” and arrange that a galvanic current should pass through both, when they come in contact by the act of striking: this current of course to be directed to a large electro-magnet, to raise the hammer for striking on his bigger bell. Should the striking of Mr. Wilson's smaller clock be on a gong with a leather-beaked hammer, a separate attachment must be made for contact.