Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells

Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.     

Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.     

Experiences with a parallel algorithm for data flow analysis

We have designed a family of parallel data flow analysis algorithms for execution on distributed-memory MIMD machines, based on general-purpose, hybrid algorithms for data flow analysis [Marlowe and Ryder 1990]. We exploit a natural partitioning of the hybrid algorithms and explore a static mapping, dynamic scheduling strategy. Alternative mapping-scheduling choices and refinements of the flow graph condensation used are discussed. Our parallel hybrid algorithm family is illustrated on Reaching Definitions, although parallel algorithms also exist for many interprocedural (e.g., Aliasing) and intraprocedural (e.g., Available Expressions) problems [Marlowe 1989]. We have implemented the parallel hybrid algorithm for Reaching Definitions on an Intel iPSC/2. Our empirical results suggest the practicality of parallel hybrid algorithms.An earlier version of this paper was presented at Supercomputing '90.The research reported here was supported, in part, by the New Jersey Commission on Science and Technology and the CAIP Center's Industrial Members, by Siemens Research Corporation and by National Science Foundation grant CCR-8920078.     

Association between oxygen delivery and consumption in patients undergoing cardiac surgery. Is there supply dependence?

Numerous investigators have suggested that cell glycoconjugates are modified by the development of cancer and the progression of this to a malignant form. Accordingly, in the present work, beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were studied in human thyroid and gastric tumours. Samples were obtained from human gastric mucosa and thyroid gland tumours together with a part of the surrounding normal tissue (control). Enzyme activity was determined spectrophotometrically based on the release of p-nitrophenol from suitable p-nitrophenyl-derivative substrates. Results showed that beta-D-galactosidase, alpha-L-fucosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities were detected in tumour and control samples from thyroid and gastric tissues. The gastric mucosa also showed alpha-L-mannosidase activity. The specific activities of these glycosidases were higher (two- or three-fold) in tumour tissues as compared with their controls. beta-D-galactosidase, beta-N-acetyl-D-glucosaminidase and beta-N-acetyl-D-galactosaminidase activities from thyroid and gastric tumours showed a significant increase in V(max) as compared with their respective controls (P < 0.05 or P < 0.001). Thyroid alpha-L-fucosidase activity showed a statistically and significantly increased affinity (lower K(m)) in tumour samples as compared to normal tissue. In conclusion both gastric and thyroid tumours showed enhanced glycosidase activity as compared with enzyme activity observed in normal tissue. These results are in agreement with the notion of a markedly raised degradation within lysosomes of tumour cells.     

Synthesis and Microstructure of Highly Oriented Lead Titanate Thin Films Prepared by a Sol-Gel Method

Thin films of PbTiO₃ were deposited on fused silica, resistor-grade alumina, and single-crystal (100) MgO by a sol–gel processing method. Whereas the films deposited on silica and alumina substrates were randomly oriented and polycrystalline, highly {100} oriented PbTiO₃ films were grown on the MgO single crystals. The perovskite-type structure was observed with films deposited on the single-crystal MgO and annealed at temperatures as low as 470°C, whereas a pyrochlore-type strcuture was observed with films on fused silica and alumina processed in a similar manner. All films heat-treated at temperatures in excess of 570°C showed significant formation of a second PbTi₃O₇ phase. The films were characterized by electron microscopy and glancing-incidence-angle X-ray diffraction.     

Analysis of nonvolatile material in solvent hexane

The amount and composition of the nonvolatile residue in solvent hexane are important quality criteria. These residue characteristics are particularly significant in the hexane extraction of foods because of the possibility of contaminating edible products. A laboratory evaluation of the residue from a typical hexane was made to find if there was any trace of multi-ring aromatics which might be potential carcinogens. Samples of hexane directly from a refinery and after storage and transportation to two solvent extraction plants were analyzed. All residues were separated by paper chromatography and analyzed by ultraviolet spectrophotometry. In no case, were they found to contain polynuclear aromatic carcinogenic materials. The test method is sensitive to less than 0.01 ppm. In order to verify the accuracy of the test, an analysis was made for the quantitative recovery of a known carcinogen. For this purpose, 0.01 ppm of 3,4 benzpyrene was added to the hexane as an internal standard and the analysis conducted as before. In these tests, the benzpyrene was recovered quantitatively.     

Empirical study of the dynamic behavior of JavaScript objects

Despite the popularity of JavaScript for client‐side web applications, there is a lack of effective software tools supporting JavaScript development and testing. The dynamic characteristics of JavaScript pose software engineering challenges such as program understanding and security. One important feature of JavaScript is that its objects support flexible mechanisms such as property changes at runtime and prototype‐based inheritance, making it difficult to reason about object behavior. We have performed an empirical study on real JavaScript applications to understand the dynamic behavior of JavaScript objects. We present metrics to measure behavior of JavaScript objects during execution (e.g., operations associated with an object, object size, and property type changes). We also investigated the behavioral patterns of observed objects to understand the coding or user interaction practices in JavaScript software. Copyright © 2015 John Wiley & Sons, Ltd.     

Exploring the Interaction between Java's Implicitly Thrown Exceptions and Instruction Scheduling

The frequent occurrence of implicitly thrown exceptions poses one of the challenges present in a Java compiler. Not only do these implicitly thrown exceptions directly affect the performance by requiring explicit checks, they also indirectly impact the performance by restricting code movement in order to satisfy the precise exception model in Java. In particular, instruction scheduling is one transformation that is restricted by implicitly thrown exceptions due to the heavy reliance on reordering instructions to exploit maximum hardware performance. The goal of this study is two-fold: first, investigate the degree to which implicitly thrown exceptions in Java hinder instruction scheduling, and second, find new techniques for allowing more efficient execution of Java programs containing implicitly thrown exceptions. Experimental results show that with aggressive scheduling techniques, such as superblock scheduling, the negative performance impact can be greatly reduced.