Free radicals as potential antitumour agents

The aim of this work was to use extremely low concentrations of free radical generating compounds as a 'catalyst' to trigger endogenous free radical chain reactions in the host and to selectively eliminate neoplastic cells in the host. To test the hypothesis, a number of free radical generating compounds were screened on several malignant cell lines in vitro to select model compounds that were used against tumour models in vivo. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and its derivatives were selected at the model compounds for in vivo experiments in view of their high cytotoxic potency against several malignant cell lines in vitro. The water soluble derivative, 2,2-diphenyl-1-(2', 4'-dinitro-6'-sulphophenyl) hydrazyl (DDSH) given by subcutaneous injections demonstrated significant antitumour activities against the MAC 16 murine colon adenocarcinoma implanted subcutaneously in male NMRI mice at nanomolar concentration range. 40-60% of long term survival of over 60 days was achieved (compared with control survival of 20 days) with total tumour elimination. This compound was also active against both P388 leukaemia in male BDF1 mice and TLX5 lymphoid tumour in male CBA/CA mice at a similar concentration range. However, some of these animals died suddenly after treatment with no evidence of disease present at post mortem. The cause of death was unknown but thought to be related to the treatment. There was significant increase in serum level of malondialdehyde (MDA) following treatment, but did not correlate to the antitumour activities of these compounds. Induction of supcroxide dismutase (SOD), and glutathione peroxidase (GPx) occurred around day 8 after the administration of DDSH. Histological sections of MAC16 tumours showed areas of extensive massive haemorrhagic necrosis and vascular collapse associated with perivascular cell death following the administration of nanomolar concentration of DDSH which was probably compatible with the effects of free radicals. It was concluded that the antitumour activities of these compounds may be related to free radical and cytokine production.

Mechanisms of anticholinesterase-induced myopathy and its prevention

In the introduction a brief outline of the possible mechanisms involved in the process of cellular necrosis with particular emphasis on skeletal muscle necrosis after antiChE is discussed. Ecothiopate (ECO), an antiChE, was shown to produce dose-dependent inhibition of both AChE and BuChE in diaphragm and blood of mice. Inhibition of AChE resulted in dose-dependent influx of calcium at the junctional region with the consequent development of morphological and biochemical alterations. Non-necrotising doses of ECO caused hypercontractions of varying severity, distorted end plate and slight elevation of serum creatine kinase (CK). Necrotising doses of ECO further caused contraction clumps, loss of striations and procion staining with high serum CK. The extent of ECO-induced myopathy depended on entry of extracellular calcium rather than the degree of AChE inhibition. The essential Ca2+ mediated process(es) in ECO-induced myopathy was thought to be the generation of superoxide and superoxide-derived free radicals and/or lipid peroxidation. Mitochondria and xanthine oxidase may be the major contributors to the generation of superoxide. No evidence was found for the depletion of high energy phosphates. ECO-induced myopathy could be successfully prevented by prior administration of pyridostigmine or various antioxidants, the most effective being Vit E or Vit E + N-acetylcysteine. Allopurinol or N-acetylcysteine alone were also effective. However, the use of a wide range of membrane end plate channel blockers or non-quantal release blockers were unsuccessful in the prevention of ECO-induced myopathy.

Micromechanics of agglomerate damage processes

This thesis reports a detailed investigation of the micromechanics of agglomerate behaviour under free-fall impact, double (punch) impact and diametrical compression tests using the simulation software TRUBAL. The software is based on the discrete element method (DEM) which incorporates the Newtonian equations of motion and contact mechanics theory to model the interparticle interactions. Four agglomerates have been used: three dense (differing in interface energy and contact density) and one loose. Although the simulated agglomerates are relatively coarse-grained, the results obtained are in good agreement with laboratory test results reported in the literature. The computer simulation results show that, in all three types of test, the loose agglomerate cannot fracture as it is unable to store sufficient elastic energy. Instead, it becomes flattened for low loading-rates and shattered or crushed at higher loading-rates. In impact tests, the dense agglomerates experience only local damage at low impact velocities. Semi-brittle fracture and fragmentation are produced over a range of higher impact velocities and at very high impact velocities shattering occurs. The dense agglomerates fracture in two or three large fragments in the diametrical compression tests. Local damage at the agglomerate-platen interface always occurs prior to fracture and consists of local bond breakage (microcrack formation) and local dislocations (compaction). The fracture process is dynamic and much more complex than that suggested by continuum fracture mechanics theory. Cracks are always initiated from the contact zones and propagate towards the agglomerate centre. Fracture occurs a short time after the start of unloading when a fracture crack "selection" process takes place. The detailed investigation of the agglomerate damage processes includes an examination of the evolution of the fracture surface. Detailed comparisons of the behaviour of the same agglomerate in all three types of test are presented. The particle size distribution curves of the debris are also examined, for both free-fall and double impact tests.

Deflection of jets discharged into a reservoir with a free surface

Deflections of jets discharged into a reservoir with a free surface are investigated numerically. The jets are known to deflect towards either side of the free surface or the bottom, whose direction is not determined uniquely in some experimental conditions, i.e. there are multiple stable states realizable in the same condition. The origin of the multiple stable states is explored by utilizing homotopy transformations in which the top boundary of the reservoir is transformed from a rigid to a free boundary and also the location of the outlet throat is continuously moved from mid-height to the top. We depicted bifurcation diagrams of the flow compiling the data of numerical simulations, from which we identified the origin as an imperfect pitchfork bifurcation, and obtained an insight into the mechanism for the direction to be determined. The parameter region where such multiple stable states are possible is also delimited. © 2011 The Japan Society of Fluid Mechanics and IOP Publishing Ltd.

Graphene based widely-tunable and singly-polarized pulse generation with random fiber lasers

Pulse generation often requires a stabilized cavity and its corresponding mode structure for initial phase-locking. Contrastingly, modeless cavity-free random lasers provide new possibilities for high quantum efficiency lasing that could potentially be widely tunable spectrally and temporally. Pulse generation in random lasers, however, has remained elusive since the discovery of modeless gain lasing. Here we report coherent pulse generation with modeless random lasers based on the unique polarization selectivity and broadband saturable absorption of monolayer graphene. Simultaneous temporal compression of cavity-free pulses are observed with such a polarization modulation, along with a broadly-tunable pulsewidth across two orders of magnitude down to 900 ps, a broadly-tunable repetition rate across three orders of magnitude up to 3 MHz, and a singly-polarized pulse train at 41 dB extinction ratio, about an order of magnitude larger than conventional pulsed fiber lasers. Moreover, our graphene-based pulse formation also demonstrates robust pulse-to-pulse stability and widewavelength operation due to the cavity-less feature. Such a graphene-based architecture not only provides a tunable pulsed random laser for fiber-optic sensing, speckle-free imaging, and laser-material processing, but also a new way for the non-random CW fiber lasers to generate widely tunable and singly-polarized pulses.

Digital Art and Design

The desire to create unique things and give free rain to one's imagination served as a powerful impetus to the development of digital art and design software. The commoner was the use of computers the wider variety of professional software was developed. Nowadays the creators and computer designers are receiving more and more new and advanced programs that allow their ideas becoming virtual reality. This research paper looks at the history of the development of graphic editors from the simplest to the most modern and advanced. This brief survey includes the history of different graphic editors’ creation, their features and abilities. This paper highlights the two basic branches of graphic editors – these that are in free use and commercial graphic editors design software. The researcher selected the most powerful and influential graphic editors design software brands like Paint.NET and GIMP among free software and commercial Adobe Photoshop. This paper also dwells upon the way digital art transferred from the exclusively professional business into the hobby for ordinary users. This research paper bears implications for those who are interested in features and potentiality of most popular graphic editors design software.

Digitisation Processing and Recognition of Old Greek Manuscipts (the D-SCRIBE Project)

After many years of scholar study, manuscript collections continue to be an important source of novel information for scholars, concerning both the history of earlier times as well as the development of cultural documentation over the centuries. D-SCRIBE project aims to support and facilitate current and future efforts in manuscript digitization and processing. It strives toward the creation of a comprehensive software product, which can assist the content holders in turning an archive of manuscripts into a digital collection using automated methods. In this paper, we focus on the problem of recognizing early Christian Greek manuscripts. We propose a novel digital image binarization scheme for low quality historical documents allowing further content exploitation in an efficient way. Based on the existence of closed cavity regions in the majority of characters and character ligatures in these scripts, we propose a novel, segmentation-free, fast and efficient technique that assists the recognition procedure by tracing and recognizing the most frequently appearing characters or character ligatures.

Modular Digital Watermarking for Image Verification and Secure Data Storage in Web Applications

Our modular approach to data hiding is an innovative concept in the data hiding research field. It enables the creation of modular digital watermarking methods that have extendable features and are designed for use in web applications. The methods consist of two types of modules – a basic module and an application-specific module. The basic module mainly provides features which are connected with the specific image format. As JPEG is a preferred image format on the Internet, we have put a focus on the achievement of a robust and error-free embedding and retrieval of the embedded data in JPEG images. The application-specific modules are adaptable to user requirements in the concrete web application. The experimental results of the modular data watermarking are very promising. They indicate excellent image quality, satisfactory size of the embedded data and perfect robustness against JPEG transformations with prespecified compression ratios. ACM Computing Classification System (1998): C.2.0.

Is pregnancy a teachable moment for diet and physical activity behaviour change? An interpretative phenomenological analysis of the experiences of women during their first pregnancy

OBJECTIVES: Pregnancy may provide a 'teachable moment' for positive health behaviour change, as a time when women are both motivated towards health and in regular contact with health care professionals. This study aimed to investigate whether women's experiences of pregnancy indicate that they would be receptive to behaviour change during this period. DESIGN: Qualitative interview study. METHODS: Using interpretative phenomenological analysis, this study details how seven women made decisions about their physical activity and dietary behaviour during their first pregnancy. RESULTS: Two women had required fertility treatment to conceive. Their behaviour was driven by anxiety and a drive to minimize potential risks to the pregnancy. This included detailed information seeking and strict adherence to diet and physical activity recommendations. However, the majority of women described behaviour change as 'automatic', adopting a new lifestyle immediately upon discovering their pregnancy. Diet and physical activity were influenced by what these women perceived to be normal or acceptable during pregnancy (largely based on observations of others) and internal drivers, including bodily signals and a desire to retain some of their pre-pregnancy self-identity. More reasoned assessments regarding benefits for them and their baby were less prevalent and influential. CONCLUSIONS: Findings suggest that for women who conceived relatively easily, diet and physical activity behaviour during pregnancy is primarily based upon a combination of automatic judgements, physical sensations, and perceptions of what pregnant women are supposed to do. Health professionals and other credible sources appear to exert less influence. As such, pregnancy alone may not create a 'teachable moment'. Statement of contribution What is already known on this subject? Significant life events can be cues to action with relation to health behaviour change. However, much of the empirical research in this area has focused on negative health experiences such as receiving a false-positive screening result and hospitalization, and in relation to unequivocally negative behaviours such as smoking. It is often suggested that pregnancy, as a major life event, is a 'teachable moment' (TM) for lifestyle behaviour change due to an increase in motivation towards health and regular contact with health professionals. However, there is limited evidence for the utility of the TM model in predicting or promoting behaviour change. What does this study add? Two groups of women emerged from our study: the women who had experienced difficulties in conceiving and had received fertility treatment, and those who had conceived without intervention. The former group's experience of pregnancy was characterized by a sense of vulnerability and anxiety over sustaining the pregnancy which influenced every choice they made about their diet and physical activity. For the latter group, decisions about diet and physical activity were made immediately upon discovering their pregnancy, based upon a combination of automatic judgements, physical sensations, and perceptions of what is normal or 'good' for pregnancy. Among women with relatively trouble-free conception and pregnancy experiences, the necessary conditions may not be present to create a 'teachable moment'. This is due to a combination of a reliance on non-reflective decision-making, perception of low risk, and little change in affective response or self-concept.

A családi fészekben élő fiatal felnőttek és fogyasztói döntéseik (In the family nest living young adults and their consumer decisions)

Fiatal felnőttek nagyarányú jelenléte a szülői háztartásokban nemcsak Magyarországon és Európában jellemző, de a fejlett ipari országokban általánosan megfigyelhető jelenség. Az Európai Unióban élő 18–34 év közötti fiatalok 46%-a él együtt legalább egyik szülőjével, a magyar fiatalok esetében hasonló az arány. A fiatalok kitolódó felnőtté válása azt is jelenti, hogy a szülők egyre későbbi időponttól kezdve rendelkeznek szabadabban idejükkel és anyagi forrásaikkal, a fiatal felnőttek döntései pedig részben szüleik részvételével történik. Jelen cikk arra keresi a választ, hogy a szülői fészekben élő vagy a szüleiktől részben függő fiatalok milyen döntési mintákkal rendelkeznek, illetve vásárlási döntéseikben mennyire önállóak. A kérdés vizsgálatát a szülői háztól függő egyetemista fiatalok körében végzett kérdőíves megkérdezés segítségével a szerzők elemezték, és arra is lehetőségük volt, hogy a családtagok által írt rövid esszék segítségével a kérdést több oldalról vizsgálják meg. Eredményeik szerint a szülői háztól függő fiatal felnőttek önálló döntésre képes, sok esetben szakértő fogyasztók, döntéseik önállóságát azonban a termékkategória, a családdal való kapcsolattartás gyakorisága, a családforma és a nemi szerepek is befolyásolják. ____ High ratio of adult children is still living in their parents’ home. This is a significant phenomenon that can be observed in Hungary and throughout Europe, while influences living trends globally. In the EU, 46% of youth between 18-34 years live with at least one of their parents and this same statistic holds true in the case of Hungary. This postponement of adulthood allows parents to enjoy more free time and have higher disposable income from later in life. The young adults, however, in the household make their consumer decisions under parental control. The purpose of this study is to explore the decisionmaking styles of young adults and their independence from their parents in shopping-related decision-making through a literature review and primary study. The survey focused on university students who are dependent on their parental home and short essays were also collected from family members of the target group in order to gain a more complex view on this phenomenon. According to the results the following conclusion can be made: young adults living in their parents’ home are competent consumers with individual decisions, in addition, they are consumer experts within the family in many cases. However, their independent shopping-related decision-making is influenced by product category, frequency of connection to the family home, family form and also sex role orientations.

Essays on durable goods consumption and firm innovation

This dissertation comprises three individual chapters. Chapter Two examines how free riding across neighbors influenced the diffusion of color television sets in rural China. Chapter Three tests for asymmetric information between a firm’s management and other investors concerning its patent output. Chapter Four discusses how knowledge stocks influence a patenting firm’s later diversification. Chapter Two documents the existence of a type of network effects—free riding across neighbors—in the consumption of color television sets in rural China, which reduces the propensity of non-owners to purchase. I construct a model of the timing of the purchase of a durable good in the presence of free riding, and test its key implications using household survey data in rural China. Chapter Three tests for asymmetric information between a firm’s management and other investors about its patent output by examining insider trading patterns and stock price changes in R&D intensive firms. It demonstrates that management has considerable information about its patent output beyond what is known to investors. It also shows that the predictive power of insider trading patterns on patent output comes from purchases rather than sales. Chapter Four discusses two sequential channels through which knowledge stocks may influence a firm’s later diversification. One is that firms with more knowledge are more likely to enter a new industry. The other is that firms’ businesses have a better chance of surviving, conditional on being formed. By examining U.S. public patenting firms in manufacturing sectors for 1984-1996, I find that knowledge stocks predict the likelihood of new industry entry when controlling for firm size. However, this predictive power is weakened when diversification effects are included. On the other hand, a survival study of newly established segments shows that initial knowledge stocks have significant positive effects on segment survival, whereas diversification effects are insignificant.

Synthetic studies of azulenyl and pseudoazulenyl nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (α-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

The civil war of ideas: Ayn Rand, intellectual freedom, and the regulation of thought in the Soviet Union and United States, 1905-1943

The philosopher and novelist Ayn Rand (1905–1982) is an icon of American culture. That culture misunderstands her, however. It perceives her solely as a pure market conservative. In the first forty years of her life, Rand's individualism was intellectual and served as a defense for the free trade of ideas. It originated in the Russian Revolution. In 1926, when Rand left the Soviet Union, she developed her individualism into an American philosophy. Her ideas of the individual in society belonged to a debate where intellectuals intended to abolish the State and free man and woman from its intellectual snares. To present Rand as a freethinker allows me to examine her anticommunism as a reaction against Leninism and to consider the relation of her ideas to Marxism. This approach stresses that Rand, as Marx, opposed the State and argued for the historical importance of a capitalist revolution. For Rand the latter, however, depended on an entrepreneurial class that rejected Protestantism as ideology – which she contended threatened its interests because Christianity had lost its historical significance. This exposes the nature of Rand's intellectual individualism in American society, where the majority on the entire political spectrum still identified with the teachings of Christ. It also reveals the dynamics of her anticommunism. From 1926 to 1943, Rand remodeled American individualism and as she did so, she determined her opposition first to the New Deal liberals and second business conservatives. To these ends, Marxism and Protestantism served Rand's individualism and made her an American icon of the twentieth century.

Three essays on labor liberalization and its effects on world economy

This dissertation consists of three theoretical essays on immigration, international trade and political economy. The first two essays analyze the political economy of immigration in developed countries. The third essay explores new ground on the effects of labor liberalization in developing countries. Trade economists have witnessed remarkable methodological developments in mathematical and game theoretical models during the last seventy years. This dissertation benefits from these advances to analyze economic issues related to immigration. The first essay applies a long run general equilibrium trade model similar to Krugman (1980), and blends it with the median voter ala-Mayer (1984) framework. The second essay uses a short run general equilibrium specific factor trade model similar to Jones (1975) and incorporates it with the median voter model similar to Benhabib (1997). The third essay employs a five stage game theoretical approach similar to Vogel (2007) and solves it by the method of backward induction. The first essay shows that labor liberalization is more likely to come about in societies that have more taste for varieties, and that workers and capital owners could share the same positive stance toward labor liberalization. In a dynamic model, it demonstrates that the median voter is willing to accept fewer immigrants in the first period in order to preserve her domestic political influence in the second period threatened by the naturalization of these immigrants. The second essay shows that the liberalization of labor depends on the host country's stock and distribution of capital, and the number of groups of skilled workers within each country. I demonstrate that the more types of goods both countries produce, the more liberal the host country is toward immigration. The third essay proposes a theory of free movement of goods and labor between two economies with imperfect labor contracts. The heart of my analysis lies in the determinants of talent development where individuals' decisions to emigrate are related to the fixed costs of emigration. Finally, free trade and labor affect income via an indirect effect on individuals' incentives to invest in the skill levels and a direct effect on the prices of goods.

Aplicação do exame da proporcionalidade diante da implantação de empreendimentos eólicos em áreas de preservação permanente

The setting up of wind power enterprises at Permanent Preservation Areas reflects the obvious conflict and necessary convergence between free market and energy security on the one hand, and the promotion of environmental quality on the other. From the perspective of energy sustainability, and in order to achieve development (in its complex meaning, which converges economic, social, environmental and cultural aspects), the harmonization between free market and an ecologically sustainable environment is required. This work aims to identify the link between the protection system of the Permanent Preservation Areas and the current constitutional order, by analyzing the implementation of wind power enterprises in these protected zones focusing on the proportionality aspects. A legal and purposeful research was developed, from a theoretical method, followed by collecting and analyzing both primary and secondary data. From these data, the law, the legal literature and judicial decisions were cross-examined, under the light of the Constitution and guided by the theory of proportionality and related development imperatives. In this context, the present study identified the link between the principles of the economic order, environment and energy law, finding their basis under the Federal Constitution and development. By reproducing this interrelationship and by means of post-crisis institutional reforms, the guiding objectives of the Brazilian electric sector began to corroborate the precepts of development, although issues regarding its sustainability still persist. The appraisal of proportionality indicates that the Permanent Preservation Areas protection system is insufficient to materialize the right to a healthy quality of life upon the implementation of wind projects at Permanent Preservation Areas, albeit seeking the harmonization between free market and environmental protection.