CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models

CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice

Mechanistic evaluation of primary human hepatocyte culture using global proteomic analysis reveals a selective dedifferentiation profile

© 2016 The Author(s)The application of primary human hepatocytes following isolation from human tissue is well accepted to be compromised by the process of dedifferentiation. This phenomenon reduces many unique hepatocyte functions, limiting their use in drug disposition and toxicity assessment. The aetiology of dedifferentiation has not been well defined, and further understanding of the process would allow the development of novel strategies for sustaining the hepatocyte phenotype in culture or for improving protocols for maturation of hepatocytes generated from stem cells. We have therefore carried out the first proteomic comparison of primary human hepatocyte differentiation. Cells were cultured for 0, 24, 72 and 168 h as a monolayer in order to permit unrestricted hepatocyte dedifferentiation, so as to reveal the causative signalling pathways and factors in this process, by pathway analysis. A total of 3430 proteins were identified with a false detection rate of <1 %, of which 1117 were quantified at every time point. Increasing numbers of significantly differentially expressed proteins compared with the freshly isolated cells were observed at 24 h (40 proteins), 72 h (118 proteins) and 168 h (272 proteins) (p < 0.05). In particular, cytochromes P450 and mitochondrial proteins underwent major changes, confirmed by functional studies and investigated by pathway analysis. We report the key factors and pathways which underlie the loss of hepatic phenotype in vitro, particularly those driving the large-scale and selective remodelling of the mitochondrial and metabolic proteomes. In summary, these findings expand the current understanding of dedifferentiation should facilitate further development of simple and complex hepatic culture systems

Numerical computation of response time distributions using stochastic reward nets

We consider the numerical computation of response time distributions for closed product form queueing networks using the tagged customer approach. We map this problem on to the computation of the time to absorption distribution of a finite-state continuous time Markov chain. The construction and solution of these Markov chains is carried out using a variation of stochastic Petri nets called stochastic reward nets (SRNs). We examine the effects of changing the service discipline and the service time distribution at a queueing center on the response time distribution. A multiserver queueing network example is also presented. While the tagged customer approach for computing the response time distribution is not new, this paper presents a new approach for computing the response time distributions using SRNs. © 1994 J.C. Baltzer AG, Science Publishers

CORRELATION OF IRON AND MYELOPEROXIDASE LEVELS IN ISCHEMIC HEART DISEASE

Objective: The objective of the study was to estimate, compare, and correlate serum iron and myeloperoxidase (MPO) levels in acute ischemic heart disease (IHD) cases. Methods: Subjects for the study were divided into two groups of 35 acute IHD cases and 35 age and sex matched controls. Serum iron and MPO levels were assayed, and results compared. Statistical analysis: The comparison between two groups was done using the Student’s t-test. Correlation between iron and MPO was established using Pearson’s correlation test. Results: High serum MPO levels and low iron levels were observed in acute IHD cases in comparison to controls. There was no significant correlation between serum iron and MPO in acute IHD cases. Conclusion: High iron levels have a beneficial role, whereas high MPO levels have an inflammatory role in the development of IHD. Determination of serum iron and MPO levels in high-risk subjects may help in taking proper measures to prevent acute IHD

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Not AvailableGenus Jatropha with 172 species having significant economic importance belongs to the family Euphorbiaceae. There are no reports on molecular characterization and phylogenetic relationship among the species of Jatropha. Hence, the present study was undertaken to assess the extent of genetic variability that exist and also to establish phylogenetic relationship among Jatropha curcas, J. glandulifera, J. gossypifolia, J. integerrima, J. multifida, J. podagrica and J. tanjorensis using RAPD and AFLP. The percentage of loci that are polymorphic among the species studied was found to be 97.74% by RAPD and 97.25% by AFLP. The mean percentage of polymorphism (PP) was found to be 68.48 by RAPD and 71.33 by AFLP. The phylogram generated with RAPD and AFLP data showed maximum similarity. With the generated data maximum relatedness was found between J. curcas and J. integerrima this may be the reason for the success of inter hybrid crosses between these two species. Neither RAPD nor AFLP data generated in this study supports the view of J. tanjorensis, a natural interspecific hybrid between J. curcas and J. gossypifolia. The present study concludes that both RAPD and AFLP techniques are comparable in divergence studies of Jatropha species. The markers generated by RAPD and AFLP can be employed efficiently for interspecific hybrids identification, marker assisted selection and genetic resource management.Springe

A simplified method for extraction of high quality genomic DNA from <i>Jatropha curcas</i> for genetic diversity and molecular marker studies

187-192 A simple and efficient protocol for the extraction of high quality genomic DNA from different tissues, including callus generated from leaves of Jatropha curcas has been developed. The important steps in this protocol include (a) use of 3.5 M NaCl in extraction buffer; (b) 2.0 M NaCl (final concentration) during precipitation; (c) Tris saturated phenol in place of phenol:chloroform:isoamyl alcohol at purification phase; (d) 80% ethanol for DNA precipitation, and (e) performing all the steps at RT. The DNA thus extracted from the leaves had 1.81±0.063, OD at A260/280 and the yield was 120 to 140 µg/g of material. The extracted DNA was found suitable for restriction digestion, ligation and PCR amplification. It was also used for DNA fingerprinting techniques, RAPD and AFLP, for development of molecular markers and studies on genetic diversity. </smarttagtype

Towards Pattern-based Reliability Certification of Services

Abstract. On Service-Oriented Architectures (SOAs), the mechanism for run-time discovery and selection of services may conflict with the need to make sure that business process instances satisfy their reliability requirements. In this paper we describe a certification scheme based on machine-readable reliability certificates that will enable run-time negotiation. Service reliability is afforded by means of reliability patterns. Our certificates describe the reliability mechanism implemented by a service and the reliability pattern used to implement such a mechanism. Digital signature is used to associate the reliability claim contained in each certificate with the party (service supplier or accredited third-party) taking responsibility for it.

PRISM: Probabilistic model checking for performance and reliability analysis

Probabilistic model checking is a formal verification technique for the modelling and analysis of stochastic systems. It has proved to be useful for studying a wide range of quantitative properties of models taken from many diffierent application domains. This includes, for example, performance and reliability properties of computer and communication systems. In this paper, we give an overview of the probabilistic model checking tool PRISM, focusing in particular on its support for continuous-time Markov chains and Markov reward models, and how these can be used to analyse performability properties