113 research outputs found

    AB INITIO AND CNDO/2 CALCULATION OF FORCE CONSTANTS AND THE PREDICTION OF VIBRATIONAL SPECTRA

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    Part of this work was performed at the University of Texas, Austin, Texas, 78712. Temporary address of Geza Fogarasi: University of Texas, Austin, Texas, 78712.Author Institution: Eotvos L. University, Institut for General and Inorganic ChemistryThe general harmonic valence force fields of benzene and several organic molecules have been calculated by the force method, using moderate size Gaussian lobs basis sets. The theoretical results agree with experiment within 20 percent. The deviations being systematic, a scaling can be made. In typical cases, these scaled values, obtained by combining theory and experiment, can be considered as the most reliable force fields at present. Results obtained on the CNDO level are also presented. The present possibilities of predicting vibrational spectra are discussed

    Differential Activation and Desensitization of Sensory Neurons by Resiniferatoxin

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    Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce45Ca uptake, which suggests the existence of distinct classes of the vanilloid receptor (Acs et al., 1996). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of45Ca uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [3H]RTX binding, contrasting with a ∼10-fold weaker potency and lack of cooperativity to induce45Ca uptake. Likewise, the competitive antagonist capsazepine inhibited RTX-induced desensitization with potency similar to that for inhibition of specific [3H]RTX binding, whereas the potency of capsazepine was ∼10-fold higher for inhibiting RTX-induced45Ca uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and45Ca uptake but showed ∼60-fold selectivity for inhibiting RTX-induced desensitization. The RTX-induced desensitization was not associated with loss of specific [3H]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for45Ca uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked45Ca uptake and depended on external calcium. Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization.</jats:p

    Bone and Joints

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    Interobserver variability by pathologists in the distinction between cellular fibroadenomas and phyllodes tumors

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    Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors.Thomas J. Lawton, Geza Acs, Pedram Argani, Gelareh Farshid, Michael Gilcrease, Neal Goldstein, Frederick Koerner, J. Jordi Rowe, Melinda Sanders, Sejal S. Shah, Carol Reynold

    Gene Expression Profiling in Breast Cancer

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    Background Breast cancer is a heterogeneous group of different tumor subtypes that vary in prognosis and response to therapy. This heterogeneity has spawned an era of molecular assays striving to classify and thus predict outcome, thereby guiding the future in targeted personalized treatment strategies. Methods This article provides an overview of the development and application of molecular assays as applied to breast cancer. Differences in the technology used for these tests as well as scientific evidence supporting the validity of the gene expression profile are discussed. Examples of the clinical applicability of these assays are provided, but these represent only a fraction of the potential uses yet to be discovered. A comparison of the three most commonly used assays is included. Results Molecular assays have provided new genetic approaches to unravel the complexities of clinical specimens relevant to breast cancer treatment planning and assessment of outcome. In particular, on a molecular level specific to the woman's tumor, these assays allow a prediction of outcome (prognosis) in terms of low and high risk for the future development of distant metastatic disease. Additionally, one assay, Oncotype DX (Genomic Health Inc, Redwood City, CA), allows for the prediction of benefit of the addition of chemotherapy to hormone therapy alone. Conclusions While incorporation of molecular assays into the treatment planning strategy of breast cancer continues to be a work in progress, this approach is evolving quickly due to strong scientific evidence to become standard of practice in the near future. The possibilities of these assays in terms of clinical investigation are limitless, but currently their general applicability is limited to less than half of the population of women presenting with breast cancer. </jats:sec

    The Role Weight of Key Factors Determining the (Infrastructure and Traffic) Intensity of Aviation for the Countries of the World

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    The interdependence between air transport and the economic sector can be examined from two directions. Several theoretical and regional studies were published on the economic impact of aviation, which is the fastest growing but the most environmentally harmful among all of the transport subsections. However, out of the many factors that influence the development level / performance of aviation, only the thematization and examination of the relationship with the GDP per capita was carried out for a narrower group of countries. Compared to the past, the author methodologically exceeded previous studies in many respects, since the correlation calculations were carried out on168 countries on 8 hypothetical acting factors and other specific indicators instead of one factor. Furthermore (breaking with the earlier practice), the indicator of passenger traffic per inhabitant was produced not from the data of official statistics (such as ICAO and IATA), which is only related to airlines registered in the given country, but from the complete national airport traffic data that was painstakingly generated by the author. In addition to the global scale, the evaluation of correlation coefficients from a geographical point of view was done according to quantitative categories of hypothetical acting factors and at the same time for every country in the dataset. To illustrate the vast differences among the aviation (infrastructure / traffic) specific indicators, linear scale charts and graphs were made, while the correlation of indicators aggregated by continents was visualized with a logarithmic scaling
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