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To investigate genetic abnormalities in human non-small cell lung carcinomas (NSCLC) associated with pulmonary asbestosis as compared with nou-asbestos linked lung cancers, twenty-nine primary non-small cell lung carcinomas (NSCLC) were examined for genetic abnormalities of p16/CDKN2, p53 and ras genes by single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP) and direct sequencing. Ten specimens were obtained from autopsies in which concurrent pulmonary asbestosis was present, while 19 samples were surgical specimens from asbestosis-free patients. K-ras mutations were detected in 10% each of the cancers from both asbestosis and non-asbestosis cases. p16/CDKN2 deletions or mutations and p53 aberrations were demonstrated in 20% and 10% of tumors from asbestosis cases, whereas, 32% and 21% of the cancers, respectively, from asbestosis-free patients were positive. In conclusion, it is suggested that the enhancement of neoplasia in the lung by asbestos is not dependent on suppression of p16/CDKN2 and p53 or ras activation and therefore, that asbestosis may activate alternate tumorigenic pathways in the development of NSCLC.

Antinuclear factor (ANA) and rheumatoid factor (RF) were determined in 220 employees of an asbestos plant. The relationship of the appearance of the two factors to sex, age, smoking habit, duration of asbestos exposure and asbestos exposure level was studied. In 207 employees who had chest roentgenograms, the relationship of these two factors to pulmonary lesions and pleural lesions was examined. Of the 220 employees, 33 (15%) had ANA and 7 employees (3.2%) had RF. ANA positive rate in the asbestos plant employees was significantly higher than in the control. Factors significantly correlated to their appearance could not be demonstrated. With the progress of pulmonary lesions the ANA positive rate significantly elevated, but ANA positive rate was not significantly correlated with pleural lesions. RF did not show any significant correlation with any of the factors.

Probabilistic model checkers typically provide a list of individual state probabilities on the refutation of a temporal logic formula. For large state spaces, this information is far too detailed to act as useful diagnostic feedback. For quantitative (constrained) reachability problems, sets of paths that carry enough probability mass are more adequate. We recently have shown that in the context of discrete-time probabilistic processes, such sets of smallest size can be efficiently computed by (hop-constrained) $k$-shortest path algorithms. This paper considers the problem of generating counterexamples for continuous-time Markov chains. The key contribution is a set of approximate algorithms for computing small sets of paths that indicate the violation of time-bounded (constrained) reachability probabilities.

Bone is one of the most preferential target organs of cancer metastases. Breast, prostate and lung cancers have a special predilection for colonization in bone. In an animal model in which inoculation of cancer cells into the left cardiac ventricle selectively develops osteolytic bone metastases but rarely forms metastases in non-bone organs, the pattern of breast cancer colonization in bone was studied radiologically and histologically. Colonization of cancer cells in bone was found to initiate and develop along with or at the terminal end of the major arteries running into bone. It should, therefore, be re-recognized that the anatomical vasculature still remains as a critica1 factor which influences cancer colonization in bone in addition to cellular and molecular properties of the bone microenvironment and metastatic cancer cells.

Receptor activator of nuclear factor kappaB (RANK) is a membrane-bound tumor necrosis factor receptor homologue that mediates signals obligatory for osteoclastogenesis as well as osteoclast activation and survival in vivo. The present study was undertaken to evaluate the efficacy of a soluble murine RANK-human immunoglobulin fusion protein (muRANK.Fc) as a bone resorption inhibitor in vitro and in vivo. The in vitro studies demonstrated the ability of muRANK.Fc to inhibit human parathyroid hormone-related protein (PTHrP)-induced resorption in fetal rat long bone cultures. Short-term administration of muRANK.Fc to normal growing mice resulted in a complete disappearance of osteoclasts from metaphyses of long bones associated with a pronounced increase in calcified trabeculae and bone radiodensity. In a model of humoral hypercalcemia of malignancy in which PTHrP secreted by s.c. xenografts of human lung cancer in nude mice induces extensive osteolysis and severe hypercalcemia, daily administration of muRANK.Fc from time of tumor implantation profoundly inhibited osteoclastic bone resorption and prevented hypercalcemia. muRANK.Fc had no effect on tumor production of PTHrP, because there was no significant difference between circulating human PTHrP levels in muRANK.Fc-treated and vehicle-treated tumor-bearing mice. Moreover, even when treatment was initiated after hypercalcemia was established, muRANK.Fc significantly attenuated further increases in blood ionized calcium. These data demonstrate the potent antiresorptive effects of muRANK.Fc in vivo as well as highlight the potential utility of disrupting RANK signaling as a novel therapeutic approach in humoral hypercalcemia of malignancy and possibly multiple myeloma and skeletal metastases associated with osteolysis.

Decoherence is one of the most serious drawback in quantum mechanical applications. We discuss the effects of noise in superconducting devices (Josephson junctions) and suggest a decoherence-control strategy based on the quantum Zeno effect.