Mass spectrometric analysis of HOCl- and free-radical-induced damage to lipids and proteins

In inflammatory diseases, release of oxidants leads to oxidative damage to biomolecules. HOCl (hypochlorous acid), released by the myeloperoxidase/H2O2/Cl- system, can cause formation of phospholipid chlorohydrins, or alpha-chloro-fatty aldehydes from plasmalogens. It can attack several amino acid residues in proteins, causing post-translational oxidative modifications of proteins, but the formation of 3-chlorotyrosine is one of the most stable markers of HOCl-induced damage. Soft-ionization MS has proved invaluable for detecting the occurrence of oxidative modifications to both phospholipids and proteins, and characterizing the products generated by HOCl-induced attack. For both phospholipids and proteins, the application of advanced mass spectrometric methods such as product or precursor ion scanning and neutral loss analysis can yield information both about the specific nature of the oxidative modification and the biomolecule modified. The ideal is to be able to apply these methods to complex biological or clinical samples, to determine the site-specific modifications of particular cellular components. This is important for understanding disease mechanisms and offers potential for development of novel biomarkers of inflammatory diseases. In the present paper, we review some of the progress that has been made towards this goal.

Intellectual alienation in a fragmented society and universe, as illustrated in the work of Wolfgang Koeppen (1906- )

This text is concerned with the intellectual and social alienation experienced by a twentieth century German writer (1906 - ).·the alienation begins in the context of German society, but this context is later globalised. The thesis first discusses the social and· intellectual origins and the salient features of this alienated stance, before proceeding to a detailed analysis of its recurring symptoms and later intensification in each of the author's main works, chronologically surveyed, supported by reference to minor writings. From the novels of the thirties' showing the burgher-artist conflict, and its symbolic dichotomies, the renunciation of traditional German values, and the ambiguous confrontation with new disruptive socio-political forces, we move to the post-war trilogy (1951-54), with its roots in the German social and political experience of the thirties' onwards. The latter, however, is merely a background for the presentation of a much more comprehensive view of the human condition:- a pessimistic vision of the repetitiveness and incorrigibility of this condition, the possibility of the apocalypse, the bankruptcy and ineffectiveness of European religion and culture, the 'absurd' meaninglessness of history, the intellectual artist's position and role(s) in mass-culture and an abstract, technologised mass-society, the central theme of fragmentation - of the structure of reality, society and personality, the artist's relation to this fragmentation, intensified in the twentieth,century. Style and language are consonant with this world-picture. Many of these features recur in the travel-books (1958-61); diachronic as well as synchronic approaches characterise the presentation of various modes of contemporary society in America, Russia, France and other European countries. Important features of intellectual alienation are:- the changelessness of historical motifs (e.g. tyranny, aggression), the conventions of burgher society, both old and new forms, the qualitative depreciation and standardisation of living, industrialisation and technology in complex, vulnerable and concemtrated urban societies, ambiguities of fragmented pluralism. Reference is made .to other travel-writers.

Vibration analysis of submerged rectangular microplates with distributed mass loading

This paper investigates the vibration characteristics of the coupling system of a microscale fluid-loaded rectangular isotropic plate attached to a uniformly distributed mass. Previous literature has, respectively, studied the changes in the plate vibration induced by an acoustic field or by the attached mass loading. This paper investigates the issue of involving these two types of loading simultaneously. Based on Lamb's assumption of the fluid-loaded structure and the Rayleigh–Ritz energy method, this paper presents an analytical solution for the natural frequencies and mode shapes of the coupling system. Numerical results for microplates with different types of boundary conditions have also been obtained and compared with experimental and numerical results from previous literature. The theoretical model and novel analytical solution are of particular interest in the design of microplate-based biosensing devices.

Analysis of oxidized and chlorinated lipids by mass spectrometry and relevance to signalling

Oxidized and chlorinated phospholipids are generated under inflammatory conditions and are increasingly understood to play important roles in diseases involving oxidative stress. MS is a sensitive and informative technique for monitoring phospholipid oxidation that can provide structural information and simultaneously detect a wide variety of oxidation products, including chain-shortened and -chlorinated phospholipids. MSn technologies involve fragmentation of the compounds to yield diagnostic fragment ions and thus assist in identification. Advanced methods such as neutral loss and precursor ion scanning can facilitate the analysis of specific oxidation products in complex biological samples. This is essential for determining the contributions of different phospholipid oxidation products in disease. While many pro-inflammatory signalling effects of oxPLs (oxidized phospholipids) have been reported, it has more recently become clear that they can also have anti-inflammatory effects in conditions such as infection and endotoxaemia. In contrast with free radical-generated oxPLs, the signalling effects of chlorinated lipids are much less well understood, but they appear to demonstrate mainly pro-inflammatory effects. Specific analysis of oxidized and chlorinated lipids and the determination of their molecular effects are crucial to understanding their role in disease pathology.

Use of narrow mass-window, high-resolution extracted product ion chromatograms for the sensitive and selective identification of protein modifications

Protein modifications, including oxidative modifications, glycosylations, and oxidized lipid-protein adducts, are becoming increasingly important as biomarkers and in understanding disease etiology. There has been a great deal of interest in mapping these on Apo B100 from low density lipoprotein (LDL). We have used extracted ion chromatograms of product ions generated using a very narrow mass window from high-resolution tandem mass spectrometric data collected on a rapid scanning quadrupole time-of-flight (QTOF) instrument, to selectively and sensitively detect modified peptides and identify the site and nature of a number of protein modifications in parallel. We have demonstrated the utility of this method by characterizing for the first time oxidized phospholipid adducts to LDL and human serum albumin and for the detection of glycosylation and kynurenin formation from the oxidation of tryptophan residues in LDL. © 2013 American Chemical Society.

Development of novel mass spectrometry methodology to detect post-translational modifications in oxidative stress and disease

This paper presented at the European Meeting of the Society-for-Free-Radical-Research-Europe 2007, discusses the development of novel mass spectrometry methodology to detect post-translational modifications in oxidative stress and disease.

The unequal segmentation of public preparedness for mass evacuation:a cross-national perspective

This thesis is concerned with understanding how Emergency Management Agencies (EMAs) influence public preparedness for mass evacuation across seven countries. Due to the lack of cross-national research (Tierney et al., 2001), there is a lack of knowledge on EMAs perspectives and approaches to the governance of public preparedness. This thesis seeks to address this gap through cross-national research that explores and contributes towards understanding the governance of public preparedness. The research draws upon the risk communication (Wood et al., 2011; Tierney et al., 2001) social marketing (Marshall et al., 2007; Kotler and Lee, 2008; Ramaprasad, 2005), risk governance (Walker et al., 2010, 2013; Kuhlicke et al., 2011; IRGC, 2005, 2007; Renn et al., 2011; Klinke and Renn, 2012), risk society (Beck, 1992, 1999, 2002) and governmentality (Foucault, 1978, 2003, 2009) literature to explain this governance and how EMAs responsibilize the public for their preparedness. EMAs from seven countries (Belgium, Denmark, Germany, Iceland, Japan, Sweden, the United Kingdom) explain how they prepare their public for mass evacuation in response to different types of risk. A cross-national (Hantrais, 1999) interpretive research approach, using qualitative methods including semi-structured interviews, documents and observation, was used to collect data. The data analysis process (Miles and Huberman, 1999) identified how the concepts of risk, knowledge and responsibility are critical for theorising how EMAs influence public preparedness for mass evacuation. The key findings grounded in these concepts include: - Theoretically, risk is multi-functional in the governance of public preparedness. It regulates behaviour, enables surveillance and acts as a technique of exclusion. - EMAs knowledge and how this influenced their assessment of risk, together with how they share the responsibility for public preparedness across institutions and the public, are key to the governance of public preparedness for mass evacuation. This resulted in a form of public segmentation common to all countries, whereby the public were prepared unequally.  - EMAs use their prior knowledge and assessments of risk to target public preparedness in response to particular known hazards. However, this strategy places the non-targeted public at greater risk in relation to unknown hazards, such as a man-made disaster. - A cross-national conceptual framework of four distinctive governance practices (exclusionary, informing, involving and influencing) are utilised to influence public preparedness. - The uncertainty associated with particular types of risk limits the application of social marketing as a strategy for influencing the public to take responsibility and can potentially increase the risk to the public.

[Review of] Ivo Mijnssen, The Quest for an Ideal Youth in Putin’s Russia I. Back to Our Future! History, Modernity and Patriotism According to Nashi, 2005–2012. Soviet and Post-Soviet Politics and Society, Stuttgart: Ibidem Verlag, 2012, 202pp., e 34.90 p/b

THE YOUTH MOVEMENT NASHI (OURS) WAS FOUNDED IN THE SPRING of 2005 against the backdrop of Ukraine’s ‘Orange Revolution’. Its aim was to stabilise Russia’s political system and take back the streets from opposition demonstrators. Personally loyal to Putin and taking its ideological orientation from Surkov’s concept of ‘sovereign democracy’, Nashi has sought to turn the tide on ‘defeatism’ and develop Russian youth into a patriotic new elite that ‘believes in the future of Russia’ (p. 15). Combining a wealth of empirical detail and the application of insights from discourse theory, Ivo Mijnssen analyses the organisation’s development between 2005 and 2012. His analysis focuses on three key moments—the organisation’s foundation, the apogee of its mobilisation around the Bronze Soldier dispute with Estonia, and the 2010 Seliger youth camp—to help understand Nashi’s organisation, purpose and ideational outlook as well as the limitations and challenges it faces. As such,the book is insightful both for those with an interest in post-Soviet Russian youth culture, and for scholars seeking a rounded understanding of the Kremlin’s initiatives to return a sense of identity and purpose to Russian national life.The first chapter, ‘Background and Context’, outlines the conceptual toolkit provided by Ernesto Laclau and Chantal Mouffe to help make sense of developments on the terrain of identity politics. In their terms, since the collapse of the Soviet Union, Russia has experienced acute dislocation of its identity. With the tangible loss of great power status, Russian realities have become unfixed from a discourse enabling national life to be constructed, albeit inherently contingently, as meaningful. The lack of a Gramscian hegemonic discourse to provide a unifying national idea was securitised as an existential threat demanding special measures. Accordingly, the identification of those who are ‘notUs’ has been a recurrent theme of Nashi’s discourse and activity. With the victory in World War II held up as a foundational moment, a constitutive other is found in the notion of ‘unusual fascists’. This notion includes not just neo-Nazis, but reflects a chain of equivalence that expands to include a range of perceived enemies of Putin’s consolidation project such as oligarchs and pro-Western liberals.The empirical background is provided by the second chapter, ‘Russia’s Youth, the Orange Revolution, and Nashi’, which traces the emergence of Nashi amid the climate of political instability of 2004 and 2005. A particularly note-worthy aspect of Mijnssen’s work is the inclusion of citations from his interviews with Nashicommissars; the youth movement’s cadres. Although relatively few in number, such insider conversations provide insight into the ethos of Nashi’s organisation and the outlook of those who have pledged their involvement. Besides the discussion of Nashi’s manifesto, the reader thus gains insight into the motivations of some participants and behind-the-scenes details of Nashi’s activities in response to the perceived threat of anti-government protests. The third chapter, ‘Nashi’s Bronze Soldier’, charts Nashi’s role in elevating the removal of a World War II monument from downtown Tallinn into an international dispute over the interpretation of history. The events subsequent to this securitisation of memory are charted in detail, concluding that Nashi’s activities were ultimately unsuccessful as their demands received little official support.The fourth chapter, ‘Seliger: The Foundry of Modernisation’, presents a distinctive feature of Mijnssen’s study, namely his ethnographic account as a participant observer in the Youth International Forum at Seliger. In the early years of the camp (2005–2007), Russian participants received extensive training, including master classes in ‘methods of forestalling mass unrest’ (p. 131), and the camp served to foster a sense of group identity and purpose among activists. After 2009 the event was no longer officially run as a Nashi camp, and its role became that of a forum for the exchange of ideas about innovation, although camp spirit remained a central feature. In 2010 the camp welcomed international attendees for the first time. As one of about 700 international participants in that year the author provides a fascinating account based on fieldwork diaries.Despite the polemical nature of the topic, Mijnssen’s analysis remains even-handed, exemplified in his balanced assessment of the Seliger experience. While he details the frustrations and disappointments of the international participants with regard to the unaccustomed strict camp discipline, organisational and communication failures, and the controlled format of many discussions,he does not neglect to note the camp’s successes in generating a gratifying collective dynamic between the participants, even among the international attendees who spent only a week there.In addition to the useful bibliography, the book is back-ended by two appendices, which provide the reader with important Russian-language primary source materials. The first is Nashi’s ‘Unusual Fascism’ (Neobyknovennyi fashizm) brochure, and the second is the booklet entitled ‘Some Uncomfortable Questions to the Russian Authorities’ (Neskol’ko neudobnykh voprosov rossiiskoivlasti) which was provided to the Seliger 2010 instructors to guide them in responding to probing questions from foreign participants. Given that these are not readily publicly available even now, they constitute a useful resource from the historical perspective.