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Additional file 1. Additional figures and tables.

The network diameter is an important characteristic parameter of a complex network. Calculation for a large-scale complex network's diameter has been an important subject in the study of complex networks. If the network diameter is calculated directly, the problem mainly exists in efficiency for searching and counting the shortest paths. If the network diameter is calculated indirectly by studying the statistical function about the relationship between the network diameter and parameters affecting the diameter, the problems not only exist in the efficiency of statistic, but also exist in the function which may be not applicable to all kinds of networks. An algorithm for the complex network diameter based on the k order distance matrix is proposed with a matrix multiplication approach, and a mathematical proof for the algorithm correctness is given as well. Furthermore, some relevant propositions and deductions for reducing the complexity of this algorithm are put forward. With a good theoretical basis and a simple calculation process, this algorithm can be used to calculate the diameter of a large-scale complex network with small-world effect more accurately and efficiently. Two cases about the advanced research projects agency (ARPA) network model and the Chinese airline network model are adopted to verify the effect of this algorithm.

In order to evaluate the effect of size and shape of crack defect on steel surface quality and mechanical properties, accurate measurement and characterization should be conducted. Aimed at the high measuring difficulty and low accuracy in the existing manual mode, a new series of characteristic parameters was proposed according to the morphological features of crack defect in steel. Through the quantitative analysis of parameters including linear morphological factor, defect equivalent and defect rate, the automatic measurement and numerical characterization of crack defect were realized. The results show that the above method can completely solve the high measuring difficulty of complex crack defect distributed with blocky inclusion and crack, which provides a reliable basis for the quantitative analysis of steel surface quality.

In consideration of the high tensile strength but low elongation properties of ultra-fine grain microalloyed steels prepared by deformation-induced phase transformation rolling technology, microstructural quantitative analysis was conducted. Results show that the volume ratio of acicular ferrites is mainly influenced by cooling rate, the higher the cooling rate is, the more acicular ferrites are obtained. By increasing the volume ratio of acicular ferrites, the tensile strength increases; On the other hand, the elongation reduces markedly because of the morphological characteristics, needle effect, size factor of acicular ferrites and so on. By adjusting the cooling rate in cooling process, the volume ratio of acicular ferrites can be controlled in the optimum range, so as to improve the comprehensive mechanical properties of steel.

This dissertation describes development of inhibitors targeting two enzymes regarding bacterial RNA polymerase (RNAP) and steroid 11β-hydroxylase (CYP11B1) for wound healing. During our quest for novel bacterial RNAP inhibitors as infective agents, two studies have been launched and involved in artifacts. In one study, compound I-1was identified as a hit compound. Later, an impurity with a structure of polymeric carboxylic acids originating from I-1 was discovered and proven to be responsible for the biological activity. The polymer acted as a negatively charged ligand interacting very efficiently with the protein surface of E. coli RNAP via electrostatic interaction and blocking the DNA channel. In the other study, we focused on CBR703, which was reported to inhibit bacterial RNAP and biofilm formation, considering it to be a good candidate for further optimization. While synthesized derivatives of CBR703 did not result in more active RNAP inhibitors, we observed promising antibacterial activities. These again correlated with a significant cytotoxicity towards mammalian cells. Furthermore, the promising effects on biofilm formation were uncovered to be artifacts. Topical application of CYP11B1 inhibitors to reduce cutaneous cortisol is a novel strategy to promote chronic wound healing. To satisfy this application, inhibitors were developed to possess specific metabolic profile: stable in wound fluid and unstable in liver. The potent inhibitor III-34 (IC50 = 5 nM) was very stable in plasma (t1/2 >> 150 min), which is similar to wound fluid in composition, whereas it was fast metabolized in human liver S9 fraction (t1/2 = 16 min) to avoid impairing adrenal steroidogenesis. It also showed no mutagenic effects and was selective CYP17 and CYP19. Therefore it is a promising candidate for further in vivo evaluation. In der vorliegenden Dissertation wird daher sowohl die Entwicklung von bakteriellen RNA Polymerase (RNAP) httphttp://www.bsz-bw.de/cgi-bin/oswd-suche.pl://www.bsz-bw.de/cgi-bin/oswd-suche.plInhibitoren als auch 11β-hydroxylase (CYP11B1) Inhibitoren für die Wundheilung beschrieben. Während unserer Suche nach neuartigen Hemmstoffen der bakteriellen RNAP zur Behandlung von Infektionskrankheiten sind wir in zwei Studien auf Artefakte gestoßen. In einer der beiden Studien identifizierten wir die Verbindung I-1 als Hit. Später stellte sich jedoch heraus, dass die biologische Aktivität nicht auf der Verbindung selbst beruht, sondern auf eine Verunreinigung mit einem – unter physiologischen Bedingungen negativ geladenen – Polymer. Via elektrostatische Wechselwirkungen und Blockierung des DNA-Kanals interagiert dieses Polymer höchst effizient mit der Proteinoberfläche der E. coli RNAP. In einer weiteren Studie fokussierten wir uns auf die Verbindung CBR703, die in der Literatur als Hemmstoff der RNAP und bakterieller Biofilme beschrieben ist, was sie aus unserer Sicht attraktiv für eine weitere Optimierung machte. Obwohl die von uns synthetisierten Derivate nicht zu aktiveren RNAP-Hemmstoffen führten, beobachteten wir vielversprechende antibakterielle Aktivitäten. Diese korrelierten jedoch mit einer signifikanten Zytotoxizität in Säugerzellen. Zudem klärten wir auf, dass es sich bei den beschriebenen Effekten bezüglich Biofilmhemmung um Artefakte handelt. Die topische Applikation von CYP11B1- Hemmstoffen zur Reduktion der Cortisol-Spiegel in der Haut ist eine neue Strategie zur Förderung der Heilung chronischer Wunden. Um diese Applikation gerecht zu werden, wurden Inhibitoren entwickelt, um durch spezifische metabolische Profil (stabil in Wundflüssigkeit aber instabil in Leber). Der sehr aktive Inhibitor III-34 (IC50 = 5 nM) zeigte dabei eine sehr hohe Stabilität in Plasma (t1/2 >> 150 min), dessen Komponenten ähnlich zu denen der Wundflüssigkeit sind, wohingegen er in humanen Leber-S9-mix schnell metabolisiert wurde (t1/2 = 16 min), was wiederum die Steroidgenese in den Nebennieren weitgehend unbeeinträchtigt lässt. Die Verbindung zeigte keine mutagenen Effekte und keine signifikante Hemmung der Enzyme CYP17 und CYP19. Daher ist sie ein geeigneter Kandidat für weitere Untersuchungen in vivo.

The epidemiological features of lung cancer in Beijing during 1977–1986 were analysed. The data collected showed that lung cancer ncidence and mortality rates ranks first among all other malignant tumor and had been on the increase from year to year. The mortality rate in urban area was higher than that in its suburbs. While the male incidence was higher than that of the female. The sex ratio of the male to female incidence rates was 1.56. The incidence rate rises with age. The lung cancer is one of the lesser prevised cancer and the five-year relative survival rate is 6.5% for both sexes in 1982–1983. The lung cancer mortality rate in Beijing urban area is compared in this report with other countries in the world, and it is found that the female mortality rate of lung cancer in Beijing is among the highest.