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Enzyme cascade reactions
(2015)
Obesity is a major health problem for many developing and industrial countries. Increasing rates reach almost 50 % of the population in some countries and related metabolic diseases including cardiovascular events and T2DM are challenging the health systems. Adiposity, an increase in body fat mass, is a major hallmark of obesity. Adipose tissue is long known not only to store lipids but also to influence whole-body metabolism including food intake, energy expenditure and insulin sensitivity. Adipocytes can store lipids and thereby protect other tissue from lipotoxic damage. However, if the energy intake is higher than the energy expenditure over a sustained time period, adipose tissue will expand. This can lead to an impaired adipose tissue function resulting in higher levels of plasma lipids, which can affect other tissue like skeletal muscle, finally leading to metabolic complications. Several studies showed beneficial metabolic effects of weight reduction in obese subjects immediately after weight loss. However, weight regain is frequently observed along with potential negative effects on cardiovascular risk factors and a high intra-individual response.
We performed a body weight maintenance study investigating the mechanisms of weight maintenance after intended WR. Therefore we used a low caloric diet followed by a 12-month life-style intervention. Comprehensive phenotyping including fat and muscle biopsies was conducted to investigate hormonal as well as metabolic influences on body weight regulation. In this study, we showed that weight reduction has numerous potentially beneficial effects on metabolic parameters. After 3-month WR subjects showed significant weight and fat mass reduction, lower TG levels as well as higher insulin sensitivity. Using RNA-Seq to analyse whole fat and muscle transcriptome a strong impact of weight reduction on adipose tissue gene expression was observed. Gene expression alterations over weight reduction included several cellular metabolic genes involved in lipid and glucose metabolism as well as insulin signalling and regulatory pathways. These changes were also associated with anthropometric parameters assigning body composition. Our data indicated that weight reduction leads to a decreased expression of several lipid catabolic as well as anabolic genes. Long-term body weight maintenance might be influenced by several parameters including hormones, metabolic intermediates as well as the transcriptional landscape of metabolic active tissues. Our data showed that genes involved in biosynthesis of unsaturated fatty acids might influence the BMI 18-month after a weight reduction phase. This was further supported by analysing metabolic parameters including RQ and FFA levels. We could show that subjects maintaining their lost body weight had a higher RQ and lower FFA levels, indicating increased metabolic flexibility in subjects.
Using this transcriptomic approach we hypothesize that low expression levels of lipid synthetic genes in adipose tissue together with a higher mitochondrial activity in skeletal muscle tissue might be beneficial in terms of body weight maintenance.
Welfare states and policies have changed greatly over the past decades, mostly characterized by retrenchments in terms of government spending or in terms of restricted access to certain benefits. In the area of family policies, however, a lot of countries have simultaneously expanded provisions and transfers for families. Bringing together the macro analysis of policy variation and household income changes on the micro-level, the main research question of the dissertation is to what extent economic consequences following separation and divorce in families with children have changed between the 1980s and the 2000s in Germany and the United States. The second research question of the dissertation regards the differences in dissolution outcomes between married and cohabiting parents in Germany.
The dissertation thus aims to link institutional regulations of welfare states with the actual income situation of families. To achieve this, a research design was developed that has never been used for the analysis of the economic consequences of family dissolution. For this, the two longest running panel datasets, German Socio-economic Panel (GSOEP) and the US American Panel Study of Income Dynamics (PSID), have been used. The analytic strategy applied to estimate the effects of family dissolution on household income is a difference-in-difference design combined with coarsened exact matching (CEM).
To begin with, the dissertation confirmed many findings of previous research, for example regarding the gender differences in family dissolution outcomes. Mothers experience clearly higher relative income losses and consequently higher risks of poverty than fathers. This finding is universal, that is it holds for both countries, for all time periods observed, and for all measures of economic outcome that were employed. Another confirmed finding is the higher level of welfare state intervention in Germany compared to the United States.
The dissertation also revealed a number of novel findings. The results show that the expansion of family policies in Germany over time has not been accompanied by substantially decreasing income losses for mothers. Though income losses have slightly decreased over time, they have become more persistent during the years following family dissolution. The impact of the German welfare state has meanwhile been quite stable.
American mothers’ income losses took place on a slightly lower level than those of German mothers. Only during the 1980s their relative losses were clearly lower than those of German mothers. And also American mothers did not recover as much from their income losses during the 2000s than they used to during the 1980s. For them, the 1996 welfare reform brought a considerable decrease in welfare state support. Accordingly, the results for American mothers can certainly be described as a shift from public to private provision.
The general finding of previous studies that fathers do not have to suffer income losses, or if at all rather moderate ones compared to mothers, can be confirmed. Nevertheless, both German and US American fathers face a deterioration of the economic consequences of family dissolution over time. German fathers’ relative income changes are still positive though they have decreased over time. One reason for this decrease is the increasing loss of partner earnings following union dissolution. Also among American fathers, income gains still prevail in the year of family dissolution. Two years later, however, they have been facing income losses already since the 1980s which have furthermore increased considerably over time.
Zooming in on Germany, family dissolution outcomes by marital status show negligible differences between cohabiting and married mothers in disposable income, but considerable differences in losses of income before taxes and transfers. It is the impact of the welfare state that equalizes the differences in income losses between these two groups of mothers. For married mothers, losses are not as high in the year of event but they have difficulties to recover from these losses. Without the income buffering of the welfare state, married mothers would, three years after family dissolution, remain with relative income losses double as high as for cohabiting mothers.
Compared to mothers, differences between married and cohabiting fathers are visible in changes of income before as well as after taxes and transfers. The welfare state does not alter the difference between the two groups of fathers. With regard to both income concepts, cohabiting fathers fare worse than married fathers. Cohabiting fathers suffer moderate income losses of disposable income while married fathers experience moderate income gains. Accounting for support payments is decisive for fathers’ income changes. If these payments are not deducted from disposable income, both married and cohabiting fathers experience gains in disposable income following family dissolution.
In this contribution, we provide a detailed dynamical analysis of the interfacial hydrogen migration mediated by scanning tunneling microscopy (STM). Contributions from the STM-current and from the non-adiabatic couplings are taken into account using only first principle models. The slight asymmetry of the tunnelling rates with respect to the potential bias sign inferred from experimental observations is reproduced by weighting the contributions of the metal acceptor–donor states for the propagation of the impinging electrons. The quasi-thermal inelastic collision mechanism is treated perturbatively. The influence of hydrogen pre-coverage is also investigated using new potential energy surfaces obtained from periodic density functional theory calculations. Fully quantum dynamical simulations of the system evolution are performed by solving the Pauli master equation, providing insight into the reaction mechanism of STM manipulation of subsurface hydrogens. It is observed that the hydrogen impurity favors resurfacing over occupation of the bulk and subsurface sites whenever possible. The present simulations give strong indication that the experimentally observed protuberances after STM-excitation are due to hydrogen accumulating in the vicinity of the surface.
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C. elegans
(2015)
Overexposure to the essential metal manganese (Mn) can result in an irreversible condition known as manganism that shares similar pathophysiology with Parkinson's disease (PD), including dopaminergic (DAergic) cell loss that leads to motor and cognitive impairments. However, the mechanisms behind this neurotoxicity and its relationship with PD remain unclear. Many genes confer risk for autosomal recessive, early-onset PD, including the parkin/PARK2 gene that encodes for the E3 ubiquitin ligase Parkin. Using Caenorhabditis elegans (C. elegans) as an invertebrate model that conserves the DAergic system, we previously reported significantly increased Mn accumulation in pdr-1/parkin mutants compared to wildtype (WT) animals. For the current study, we hypothesize that this enhanced accumulation is due to alterations in Mn transport in the pdr-1 mutants. While no change in mRNA expression of the major Mn importer proteins (smf-1-3) was found in pdr-1 mutants, significant downregulation in mRNA levels of the putative Mn exporter ferroportin (fpn-1.1) was observed. Using a strain overexpressing fpn-1.1 in worms lacking pdr-1, we show evidence for attenuation of several endpoints of Mn-induced toxicity, including survival, metal accumulation, mitochondrial copy number and DAergic integrity, compared to pdr-1 mutants alone. These changes suggest a novel role of pdr-1 in modulating Mn export through altered transporter expression, and provides further support of metal dyshomeostasis as a component of Parkinsonism pathophysiology.
Wissenschaft, Technik und Medien im Werk Alfred Döblins im Kontext der europäischen Avantgarde
(2015)
Ziel dieser Studie ist es die bislang nur sporadisch untersuchten Wechselverhältnisse zwischen den Kulturbereichen Wissenschaft/Technik und Literatur am herausragenden Beispiel des Oeuvres des Schriftstellers und Arztes Alfred Döblin aufzuspüren. Hierbei scheint seine ärztlich-psychiatrische Laufbahn, die eine breite Grundlage wissenschaftlicher Diskurse anbietet, wie auch seine avantgardistische Literaturpraxis diese gegenseitige Befruchtung gefördert zu haben.
Im Hinblick auf den Forschungsgegenstand und -zweck ist ein kulturwissenschaftlicher Ansatz versucht worden. Dieser vielperspektivische Ansatz, der von der Prämisse eines Wechselspiels aller Kulturbereiche untereinander ausgeht, gestattet eine dem Gegenstand angepasste Verknüpfung von verschiedenen Arbeitsmethoden wie der philologisch-literarhistorischen mit der konstruktivistischen und der komparatistischen. Hierbei ist eine Einbeziehung wissenschafts- und technikphilosophischer Reflexion wie auch eine dementsprechend erweiterte kulturhistorische Kontextualisierung vorgenommen worden.
Die hier vorgelegte Analyse fokussiert auf wissenschaftlich-technische Bezüge sowohl in thematischer Hinsicht als auch in der Textgestaltung der schriftstellerischen Werke Döblins bis 1924. Gleichzeitig wird die diskursgeprägte, sprachliche und literarische Dimension seiner wissenschaftlichen Studien und technischer Texte - wie Krankenakte - hervorgehoben. Dieses erweiterte ‚Oeuvre‘-Konzept gestattet die Analyse der psychiatrischen, klinisch-ärztlichen und biochemischen Schriften Döblins sowie seiner Erzählwerke, seiner vielgestaltigen Publizistik und seiner intermedialen Anregungen aus den neuen audiovisuellen Medien. Dadurch wird eine diskurskritische kulturübergreifende Interdiskursivität wie auch eine ‚Hybridität‘ aller Texte aufgezeigt, die die Grundunterschiede zwischen Textsorten und Gattungsgrenzen relativiert.
The dissertation proposes that the spread of photography and popular cinema in 19th- and 20th-century-India have shaped an aesthetic and affective code integral to the reading and interpretation of Indian English novels, particularly when they address photography and/or cinema film, as in the case of the four corpus texts. In analyzing the nexus between ‘real’ and ‘reel’, the dissertation shows how the texts address the reader as media consumer and virtual image projector. Furthermore, the study discusses the Indian English novel against the backdrop of the cultural and medial transformations of the 20th century to elaborate how these influenced the novel’s aesthetics. Drawing upon reception aesthetics, the author devises the concept of the ‘implied spectator’ to analyze the aesthetic impact of the novels’ images as visual textures.
No God in Sight (2005) by Altaf Tyrewala comprises of a string of 41 interior monologues, loosely connected through their narrators’ random encounters in Mumbai in the year 2000. Although marked by continuous perspective shifts, the text creates a sensation of acute immediacy. Here, the reader is addressed as implied spectator and is sutured into the narrated world like a film spectator ― an effect created through the use of continuity editing as a narrative technique.
Similarly, Ruchir Joshi’s The Last Jet Engine Laugh (2002) coll(oc)ates disparate narrative perspectives and explores photography as an artistic practice, historiographic recorder and epistemological tool. The narrative appears guided by the random viewing of old photographs by the protagonist and primary narrator, the photographer Paresh Bhatt. However, it is the photographic negative and the practice of superimposition that render this string of episodes and different perspectives narratively consequential and cosmologically meaningful. Photography thus marks the perfect symbiosis of autobiography and historiography.
Tabish Khair’s Filming. A Love Story (2007) immerses readers in the cine-aesthetic of 1930s and 40s Bombay film, the era in which the embedded plot is set. Plotline, central scenes and characters evoke the key films of Indian cinema history such as Satyajit Ray’s “Pather Panchali” or Raj Kapoor’s “Awara”. Ultimately, the text written as film dissolves the boundary between fiction and (narrated) reality, reel and real, thereby showing that the images of individual memory are inextricably intertwined with and shaped by collective memory. Ultimately, the reconstruction of the past as and through film(s) conquers trauma and endows the Partition of India as a historic experience of brutal contingency with meaning.
The Bioscope Man (Indrajit Hazra, 2008) is a picaresque narrative set in Calcutta - India’s cultural capital and birthplace of Indian cinema at the beginning of the 20th century. The autodiegetic narrator Abani Chatterjee relates his rise and fall as silent film star, alternating between the modes of tell and show. He is both autodiegetic narrator and spectator or perceiving consciousness, seeing himself in his manifold screen roles. Beyond his film roles however, the narrator remains a void. The marked psychoanalytical symbolism of the text is accentuated by repeated invocations of dark caves and the laterna magica. Here too, ‘reel life’ mirrors and foreshadows real life as Indian and Bengali history again interlace with private history. Abani Chatterjee thus emerges as a quintessentially modern man of no qualities who assumes definitive shape only in the lost reels of the films he starred in.
The final chapter argues that the static images and visual frames forwarded in the texts observe an integral psychological function: Premised upon linear perspective they imply a singular, static subjectivity appealing to the postmodern subject. In the corpus texts, the rise of digital technology in the 1990s thus appears not so much to have displaced older image repertories, practices and media techniques, than it has lent them greater visibility and appeal. Moreover, bricolage and pastiche emerge as cultural techniques which marked modernity from its inception. What the novels thus perpetuate is a media archeology not entirely servant to the poetics of the real. The permeable subject and the notion of the gaze as an active exchange as encapsulated in the concept of darshan - ideas informing all four texts - bespeak the resilience of a mythical universe continually re-instantiated in new technologies and uses. Eventually, the novels convey a sense of subalternity to a substantially Hindu nationalist history and historiography, the centrifugal force of which developed in the twentieth century and continues into the present.
The paper aims at considering characteristics from one field of contemporary visual studies that has for a long time been neglected in academic research: Pictorial signs on Social Network Sites (SNS) are an outstanding class of semiotic resources that is greatly shaped by processes of technological and collective sign production and distribution. A brief examination of the scholarly research on the pragmatics and semiotics of pictorial signs on SNS shows that the heterogeneity of visual signs is often neglected and that it mostly concentrates on one aspect of these pictorial signs: their technological production or their purpose for individual self-disclosure. The paper therefore considers the semiosis of pictorial signs on SNS in a holistic perspective as one the one hand produced by individual and collective meaning making as well as on the other hand a product of technological framing. It therefore develops a techno-semiotic pragmatic account that takes into consideration both processes. Starting from a prominent class of pictorial signs on SNS during Tunisian Revolution, the Tunisian Flag graphics, the paper than shows that communicative and social interaction functions on the graphic interface of SNS (‘like’-function, sharing and commenting option) are not only directly inscribed into the pictorial frame, but also greatly influence the reading of a pictorial sign. The location of images on the SNS’ interface has an impact on its meaning and on the social functions of a pictorial sign, as profile pictures are directly linked to the online identity of the user. Through technological sign processing, the polysemy of the image is reduced. We therefore consider the images on the one hand as individual self-narratives and on the other as instances of SNS’ visual culture that brings out dominant visual codes but also allows social and political movements to spread.
Biological materials, in addition to having remarkable physical properties, can also change shape and volume. These shape and volume changes allow organisms to form new tissue during growth and morphogenesis, as well as to repair and remodel old tissues. In addition shape or volume changes in an existing tissue can lead to useful motion or force generation (actuation) that may even still function in the dead organism, such as in the well known example of the hygroscopic opening or closing behaviour of the pine cone. Both growth and actuation of tissues are mediated, in addition to biochemical factors, by the physical constraints of the surrounding environment and the architecture of the underlying tissue. This habilitation thesis describes biophysical studies carried out over the past years on growth and swelling mediated shape changes in biological systems. These studies use a combination of theoretical and experimental tools to attempt to elucidate the physical mechanisms governing geometry controlled tissue growth and geometry constrained tissue swelling. It is hoped that in addition to helping understand fundamental processes of growth and morphogenesis, ideas stemming from such studies can also be used to design new materials for medicine and robotics.
Traditionally, business process management systems only execute and monitor business process instances based on events that originate from the process engine itself or from connected client applications. However, environmental events may also influence business process execution. Recent research shows how the technological improvements in both areas, business process management and complex event processing, can be combined and harmonized. The series of technical reports included in this collection provides insights in that combination with respect to technical feasibility and improvements based on real-world use cases originating from the EU-funded GET Service project – a project targeting transport optimization and green-house gas reduction in the logistics domain. Each report is complemented by a working prototype.
This collection introduces six use cases from the logistics domain. Multiple transports – each being a single process instance – may be affected by the same events at the same point in time because of (partly) using the same transportation route, transportation vehicle or transportation mode (e.g. containers from multiple process instances on the same ship) such that these instances can be (partly) treated as batch. Thus, the first use case shows the influence of events to process instances processed in a batch. The case of sharing the entire route may be, for instance, due to origin from the same business process (e.g. transport three containers, where each is treated as single process instance because of being transported on three trucks) resulting in multi-instance process executions. The second use case shows how to handle monitoring and progress calculation in this context. Crucial to transportation processes are frequent changes of deadlines. The third use case shows how to deal with such frequent process changes in terms of propagating the changes along and beyond the process scope to identify probable deadline violations. While monitoring transport processes, disruptions may be detected which introduce some delay. Use case four shows how to propagate such delay in a non-linear fashion along the process instance to predict the end time of the instance. Non-linearity is crucial in logistics because of buffer times and missed connection on intermodal transports (a one-hour delay may result in a missed ship which is not going every hour). Finally, use cases five and six show the utilization of location-based process monitoring. Use case five enriches transport processes with real-time route and traffic event information to improve monitoring and planning capabilities. Use case six shows the inclusion of spatio-temporal events on the example of unexpected weather events.