Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

Deconvolution of infrared spectra using various milk proteins as an example

The theory of deconvolution of infra-red spectra is presented and illustrated using milk protein spectra. The advantage of this method is impressively demonstrated and its relevance for dairy farming shown using a simple example, the cooling of milk.     

Induction of favism-like symptoms in the rat: Effects of vicine and divicine in normal and buthionine sulphoximine-treated rats

Rats were fed an adequate or a deficient diet and offered water or buthionine sulphoximine (BSO) solution for 2 weeks, and then the same diets with vicine for another week in experiment 1. BSO in combination with the deficient diet caused a marked decrease in blood glutathione (GSH) and growth retardation but failed to show any effects resulting from supplementation with vicine. In experiment 2 the rats were given an adequate diet and BSO as before, and injected intravenously with divicine (DV). Here again, BSO depressed rat growth, and so did DV. Each of the insults also caused haematological changes, especially a fall in GSH, but the most severe changes appeared in the group treated with both BSO and DV. A decrease in haematocrit and increases in adrenal and spleen weight were also noted. In experiment 3 the rats were injected with different doses of DV, without pretreatment with BSO. The main effect was a drop in blood GSH and haematocrit, and an increase in adrenal and spleen weights, all of which were dose-related. Administration of the higher doses of DV resulted in a severe cyanosis followed by death within a relatively short period of time.     

Information technology support in the chemical process design life cycle

Information technology has been becoming increasingly important in all areas of engineering during the last few years. Much of the progress achieved in chemical engineering would not have been possible without the enabling methods and tools provided by information technology. This trend will continue in the future but most likely with a considerably wider scope. While individual software tools and services have been in focus until recently, their integration into engineering work processes is an emerging and challenging area of research and development. This contribution attempts to highlight state of the art and future trends in supporting the activities during the life cycle of a chemical process by means of information technology. Emphasis will be largely on the process and plant design process rather than on procurement, manufacturing, and distribution of materials in the supply chain.     

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53.     

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

Gezielte Nutzung biologischer Systeme

Directed exploitation of biological systems . During the past few decades, our knowledge of molecular process responsible for genetics has increased dramatically. Discovery of the giant molecule deoxyribonucleic acid – abbreviated as DNA – as the carrier of genetic information heralded in a development which nowadays permits us to effect directed changes in the genetic material of an organism. Thus we can provide easily cultured microorganisms with genes which were previously located in a completely different genetic environment. This helps us to obtain high yields of proteins or other substances which were formerly very difficult to obtain. Higher organisms such as animals and plants can also undergo modification of their genetic equipment. This adds a new dimension to the breeding of such species. Above all, genetic engineering provides new insights into the enormously complex interplay of molecules which go to make up a living cell. The resulting understanding of life processes on a molecular level permits recognition of malfunction and therapy of the ensuring disease by new drugs. In addition to these positive aspects, genetic engineering provides scope for conducting experiments whose ethical implications demand very earnest consideration.     

Zur kinetik der acrylnitril-polymerisation

The heterogeneous bulk polymerization of acrylonitrile initiated by AIBN has been studied by means of an improved dilatometric technique and a new method of analysis, where the initial reaction rate (v_w)₀ results from the intercept of a straight line in a \documentclass{article}\pagestyle{empty}\begin{document}$ \frac {\ln \left( 1 \hbox{---} {\rm U} \right)} {{\rm e}^{{- 0,5} {\rm k}_{\rm s}{\rm t} \hbox{---} 1}}$\end{document} versus t plot. It has been found that the initial reaction rate is proportional to the square root of the initial catalyst concentration S₀. The ratio of the rate coefficients of propagation and termination\documentclass{article}\pagestyle{empty}\begin{document}$\frac { {\rm k}_{\rm a} } { {\rm k}_{ {\rm w}^{2} } } $\end{document} could be calculated from the slope of a straight line passing through the origin in a plot of (v_w)₀ versus \documentclass{article}\pagestyle{empty}\begin{document}$\sqrt { {\rm S}_{0} }$\end{document} and yielded a value of 280 mol 1^?1.     

Performance and reliability prediction for evolving service-oriented software systems

During software system evolution, software architects intuitively trade off the different architecture alternatives for their extra-functional properties, such as performance, maintainability, reliability, security, and usability. Researchers have proposed numerous model-driven prediction methods based on queuing networks or Petri nets, which claim to be more cost-effective and less error-prone than current practice. Practitioners are reluctant to apply these methods because of the unknown prediction accuracy and work effort. We have applied a novel model-driven prediction method called Q-ImPrESS on a large-scale process control system from ABB consisting of several million lines of code. This paper reports on the achieved performance prediction accuracy and reliability prediction sensitivity analyses as well as the effort in person hours for achieving these results.