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The full-length translation-regulating add adenine riboswitch (Asw) from Vibrio vulnificus has a more complex conformational space than its isolated aptamer domain. In addition to the predicted apo (apoA) and holo conformation that feature the conserved three-way junctional purine riboswitch aptamer, it adopts a second apo (apoB) conformation with a fundamentally different secondary structure. Here, we characterized the ligand-dependent conformational dynamics of the full-length add Asw by NMR and by single-molecule FRET (smFRET) spectroscopy. Both methods revealed an adenine-induced secondary structure switch from the apoB-form to the apoA-form that involves no tertiary structural interactions between aptamer and expression platform. This strongly suggests that the add Asw triggers translation by capturing the apoA-form secondary structure in the holo state. Intriguingly, NMR indicated a homogenous, docked aptamer kissing loop fold for apoA and holo, while smFRET showed persistent aptamer kissing loop docking dynamics between comparably stable, undocked and docked substates of the apoA and the holo conformation. Unraveling the folding of large junctional riboswitches thus requires the integration of complementary solution structural techniques such as NMR and smFRET.
Biodiversity research heavily relies on recent and older literature, and the data contained therein. Despite great effort, large parts of the literature and the data it holds are still not available in appropriate formats needed for efficient compilation and analysis. As a part of the current funding strategy of the German Research Council (Deutsche Forschungsgemeinschaft, DFG), and resulting from an extensive dialogue with the scientific community in Germany, a "Specialised Information Service" (Fachinformationsdienst, FID) for Biodiversity Research will be established with the objective of making further segments of literature about biodiversity available in up-to-date formats. This project, starting 2017, is conducted by the University Library Johann Christian Senckenberg (Frankfurt/Main, Germany) together with the Senckenberg Gesellschaft für Naturforschung and the Text Technology Lab of the Goethe University (Frankfurt/Main).
The new Specialised Information Service for Biodiversity Research (FID Biodiversitätsforschung) comprises four core elements: (A) A text mining approach which encompasses advanced text technologies and a large body of 20th century literature; (B) the digitisation of selected German biodiversity literature; (C) a platform für Open Access journals; and (D) Acquisition of specialised print literature.
This dissertation provides a comprehensive account of the grammar of relative clause extraposition in English. Based on a systematic review and evaluation of the empirical generalizations and theoretical approaches provided in the literature on generative grammar, it is shown that none of the previous theories is able to account for all the relevant facts. Among the most problematic data are the Principle C and scope effects of relative clause extraposition, cases with obligatory relative clauses, and relative clauses with elliptical NPs as antecedents.
I propose a new analysis of relative clause extraposition within the constraint-based, monostratal grammatical framework of Head-driven Phrase Structure Grammar (HPSG), enhanced with the semantic theory of Lexical Resource Semantics (LRS). Crucially, it is a general analysis of relative clause attachment, since both canonical and extraposed relative clauses are licensed by the same syntactic and semantic constraints. The basic assumption is that a relative clause can be adjoined to any phrase that contains a suitable antecedent of the relative pronoun. The semantic information that licenses the relative clause is introduced by the determiner of the antecedent NP. The techniques of underspecified semantics and the standard semantic representation language used by LRS make it possible to formulate constraints which yield the correct intersective interpretation of the relative clause (arbitrarily distant from its antecedent NP) and at the same time link the scope of the antecedent NP to the adjunction site of the relative clause.
In combination with the revised HPSG binding theory developed in this dissertation, the proposed analysis is able to capture the major properties of relative clause attachment within a unified and internally consistent monostratal constraint-based grammatical framework.
Monetary policy communication is particularly important during unconventional times, because high uncertainty about the economy, the introduction of new policy tools and possible limits to the central bank’s toolkit could hamper the predictability of policy actions. We study how monetary policy communication should and has worked under such circumstances. Our main results relate to announcements of asset purchase programmes and the use of forward guidance. We show that announcements of asset purchase programmes have lowered market uncertainty, particularly when accompanied by a contextual release of implementation details such as the envisaged size of the programme. We also show that forward guidance reduces uncertainty more effectively when it is state‐contingent or when it provides guidance about a long horizon than when it is open‐ended or covers only a short horizon, and that the credibility of forward guidance is strengthened if the central bank also has embarked on an asset purchase programme.
Viewing of ambiguous stimuli can lead to bistable perception alternating between the possible percepts. During continuous presentation of ambiguous stimuli, percept changes occur as single events, whereas during intermittent presentation of ambiguous stimuli, percept changes occur at more or less regular intervals either as single events or bursts. Response patterns can be highly variable and have been reported to show systematic differences between patients with schizophrenia and healthy controls. Existing models of bistable perception often use detailed assumptions and large parameter sets which make parameter estimation challenging. Here we propose a parsimonious stochastic model that provides a link between empirical data analysis of the observed response patterns and detailed models of underlying neuronal processes. Firstly, we use a Hidden Markov Model (HMM) for the times between percept changes, which assumes one single state in continuous presentation and a stable and an unstable state in intermittent presentation. The HMM captures the observed differences between patients with schizophrenia and healthy controls, but remains descriptive. Therefore, we secondly propose a hierarchical Brownian model (HBM), which produces similar response patterns but also provides a relation to potential underlying mechanisms. The main idea is that neuronal activity is described as an activity difference between two competing neuronal populations reflected in Brownian motions with drift. This differential activity generates switching between the two conflicting percepts and between stable and unstable states with similar mechanisms on different neuronal levels. With only a small number of parameters, the HBM can be fitted closely to a high variety of response patterns and captures group differences between healthy controls and patients with schizophrenia. At the same time, it provides a link to mechanistic models of bistable perception, linking the group differences to potential underlying mechanisms.
Background: Although mortality after cardiac surgery has significantly decreased in the last decade, patients still experience clinically relevant postoperative complications. Among others, atrial fibrillation (AF) is a common consequence of cardiac surgery, which is associated with prolonged hospitalization and increased mortality.
Methods: We retrospectively analyzed data from patients who underwent coronary artery bypass grafting, valve surgery or a combination of both at the University Hospital Muenster between April 2014 and July 2015. We evaluated the incidence of new onset and intermittent/permanent AF (patients with pre- and postoperative AF). Furthermore, we investigated the impact of postoperative AF on clinical outcomes and evaluated potential risk factors.
Results: In total, 999 patients were included in the analysis. New onset AF occurred in 24.9% of the patients and the incidence of intermittent/permanent AF was 59.5%. Both types of postoperative AF were associated with prolonged ICU length of stay (median increase approx. 2 days) and duration of mechanical ventilation (median increase 1 h). Additionally, new onset AF patients had a higher rate of dialysis and hospital mortality and more positive fluid balance on the day of surgery and postoperative days 1 and 2. In a multiple logistic regression model, advanced age (odds ratio (OR) = 1.448 per decade increase, p < 0.0001), a combination of CABG and valve surgery (OR = 1.711, p = 0.047), higher C-reactive protein (OR = 1.06 per unit increase, p < 0.0001) and creatinine plasma concentration (OR = 1.287 per unit increase, p = 0.032) significantly predicted new onset AF. Higher Horowitz index values were associated with a reduced risk (OR = 0.996 per unit increase, p = 0.012). In a separate model, higher plasma creatinine concentration (OR = 2.125 per unit increase, p = 0.022) was a significant risk factor for intermittent/permanent AF whereas higher plasma phosphate concentration (OR = 0.522 per unit increase, p = 0.003) indicated reduced occurrence of this arrhythmia.
Conclusions: New onset and intermittent/permanent AF are associated with adverse clinical outcomes of elective cardiac surgery patients. Different risk factors implicated in postoperative AF suggest different mechanisms might be involved in its pathogenesis. Customized clinical management protocols seem to be warranted for a higher success rate of prevention and treatment of postoperative AF.
In Japan, most contemporary readers expect comics, or manga, to be entertaining fiction ('story manga'), magazine-based, and targeted at age- and gender-specific demographics. These narratives eventually reappear in bound book editions ('tankōbon'), after they have proven to be popular to an extent that would warrant print runs of more than 5,000 copies. Due to the central role of magazines as first site of publication since the 1960s, genre specificity has been essential – for editors, readers, and artists alike. While manga's traditional genres have been gender- and age-specific, thematic genres such as SF, horror and comedy, or recently also blog-like essay manga, come to the fore whenever the otherwise prevalent categories forfeit efficacy. But there is one genre which does not comply with these categories, i.e. gakushū manga, educational or instructional comics.
A comic can tell the story of almost anything: a single atom, the entire solar system, the past, future events, dreams and thoughts. All this, and more, can be depicted. When presenting facts, a certain artistic licence can be deployed if, for instance, the author wants to emphasise important details; likewise, aspects he or she deems irrelevant can be left out. Moreover, questions and issues can be laid out that are difficult or even impossible to portray photographically or cinematically. However, when the cartoon strip sets out its version of information, events, objects and people, it can also result in a distortion of reality. The graphic may not always make clear exactly how something looks or the precise way in which something happened. And even where documentary images exist, the comic strip representation of the non-fictional is always coloured by artistic interpretation.
There is no doubt that factual discourse exists in comics – the kind of communication that intends to be understood as a reference to a shared and actual reality. Factual comics are not, however, common. While the formal structure of comics clearly allows for factuality, the historical specificity of its aesthetics seems to introduce a non-binding but plausible 'drift' of the art form, ultimately pulling away from reality and towards fiction. This does not prevent factual comics, but it allows for subversive remnants in their aesthetic make-up. One of these is a 'parasitic imagination', which might be understood in the context of Michel Serres' concepts of the parasite. It opens up cartoonish depictions for tertiary significations beyond the drawing and its ultimate real reference. Rather than avoid this basic vehicle of comic book discourse, the 'challenge to factual comics' must be how to employ them in the service of the intended communication.
Beyond Illustration
(2017)
Sophisticated science reported on in comics. The once unthinkable is here as comics are being leveraged and enthusiastically welcomed into forums that would have been off limits not long ago. It's an exciting time of change. But in this headlong dash forward, I want to offer a pause for consideration, and suggest that we ask, what are the things that comics do uniquely compared to other forms of representation? And from there, let us explore how we can best take advantage of comics' particular affordances to do with comics things only comics can do.
The present volume documents the twofold character of the conference 'Science meets Comics' with the first part focusing on comics as a format for communicating complex topics and the second part addressing food in the age of the Anthropocene as one such example for complex topics. The overall objective of the symposium was to deal with the results and suggestions of the presentations and discussions, to find possible pathways on how to feed the world in the future and to co-produce the final chapter of the scientific comic 'Eating Anthropocene' together with all artists participating in the project. In order to sum up the framing, contents and design process of the comic as well as to highlight its Anthropocene context we below provide a slightly abridged version of the preface of our comic book.
Decreased STARD10 expression is associated with defective insulin secretion in humans and mice
(2017)
Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in β cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, β-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult β cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in β cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the β cell.
Body image dissatisfaction is a serious, global problem that negatively affects life satisfaction. Several claims have been made about the possible psychological benefits of naturist activities, but very little empirical research has investigated these benefits or any plausible explanations for them. In three studies—one large-scale, cross-sectional study (n = 849), and 2 prospective studies (n = 24, n = 100) this research developed and applied knowledge about the possible benefits of naturist activities. It was found that more participation in naturist activities predicted greater life satisfaction—a relationship that was mediated by more positive body image, and higher self-esteem (Study 1). Applying these findings, it was found that participation in actual naturist activities led to an increase in life satisfaction, an effect that was also mediated by improvements in body image and self-esteem (Studies 2 and 3). The potential benefits of naturism are discussed, as well as possible future research, and implications for the use of naturist activities.
In evidence-based weight-loss programs weight regain is common after an initial weight reduction. Eating slowly significantly lowers meal energy intake and hunger ratings. Despite this knowledge, obese individuals do not implement this behaviour. We, thus tested the hypothesis of changing eating behaviour with an intra-oral medical device leading to constant weight reduction in overweight and obesity.
Six obese patients (6 men, age 56 ± 14, BMI 29 ± 2 kg / m2) with increased CVRF profile were included in this prospective study. All patients had been treated for obesity during the last 10 years in a single centre and had at least 3 frustrate evidence-based diets. Patients received a novel non-invasive intra-oral medical device to slow eating time. Further advice included not to count calories, to avoid any other form of diet, to take their time with their meals, and to eat whatever they liked.
This device was used only during meals for the first 4 to 8 weeks for a total of 88 [20–160] hours. Follow-up period was 23 [15–38] months. During this period, patients lost 11% [5–20%] (p<0.001) of their initial weight. At 12 months, all patients had lost >5%, and 67% (4/6) achieved a >10% bodyweight loss. In the course of the study, altered eating patterns were observed. There were no complications with the medical device. Of note, all patients continued to lose weight after the initial intervention period (p<0.001) and none of them had weight regain.
With this medical device, overweight and obese patients with a history of previously frustrating attempts to lose weight achieved a significant and sustained weight loss over two years. These results warrant the ongoing prospective randomised controlled trial to prove concept and mechanism of action.
Background: Kyrgyzstan, where HIV is concentrated in prisons and driven by injection drug use, provides a prison-based methadone maintenance therapy program as well as abstinence-oriented therapeutic community based on the 12-step model called the “Clean Zone.” We aimed to qualitatively assess how prisoners navigate between these treatment options to understand the persistence of the Clean Zone despite a lack of evidence to support its effectiveness in treating opioid use disorders.
Methods: We conducted an analysis of policy documents and over 60 h of participant observation in February 2016, which included focus groups with a convenience sample of 20 therapeutic community staff members, 110 prisoners across three male and one female prisons, and qualitative interviews with two former Clean Zone participants. Field notes containing verbatim quotes from participants were analyzed through iterative reading and discussion to understand how participants generally perceive the program, barriers to entry and retention, and implications for future treatment within prisons.
Results: Our analyses discerned three themes: pride in the mission of the Clean Zone, idealism regarding addiction treatment outcomes against all odds, and the demonization of methadone.
Conclusion: Despite low enrollment and lack of an evidence base, the therapeutic community is buttressed by the strong support of the prison administration and its clients as an “ordered” alternative to what is seen as chaotic life outside of the Clean Zone. The lack of services for Clean Zone patients after release likely contributes to high rates of relapse to drug use. The Clean Zone would benefit from integration of stabilized methadone patients combined with a post-release program.
Background: Only few authors have analyzed the impact of workplace conflicts and the resulting stress on the risk of developing cardiovascular disorders. The goal of this study was to analyze the association between workplace conflicts and cardiovascular disorders in patients treated by German general practitioners.
Methods: Patients with an initial documentation of a workplace conflict experience between 2005 and 2014 were identified in 699 general practitioner practices (index date). We included only those who were between the ages of 18 and 65 years, had a follow-up time of at least 180 days after the index date, and had not been diagnosed with angina pectoris, myocardial infarction, coronary heart diseases, or stroke prior to the documentation of the workplace mobbing. In total, the study population consisted of 7,374 patients who experienced conflicts and 7,374 controls for analysis. The main outcome measure was the incidence of angina pectoris, myocardial infarction, and stroke correlated with workplace conflict experiences.
Results: After a maximum of five years of follow-up, 2.9% of individuals who experienced workplace conflict were affected by cardiovascular diseases, while only 1.4% were affected in the control group (p-value <0.001). Workplace conflict was associated with a 1.63-fold increase in the risk of developing cardiovascular diseases. Finally, the impact of workplace conflict was higher for myocardial infarction (OR=2.03) than for angina pectoris (OR=1.79) and stroke (OR=1.56).
Conclusions: Overall, we found a significant association between workplace conflicts and cardiovascular disorders.
Expression of surfactant protein B is dependent on cell density in H441 lung epithelial cells
(2017)
Background: Expression of surfactant protein (SP)-B, which assures the structural stability of the pulmonary surfactant film, is influenced by various stimuli, including glucocorticoids; however, the role that cell-cell contact plays in SP-B transcription remains unknown. The aim of the current study was to investigate the impact of cell-cell contact on SP-B mRNA and mature SP-B expression in the lung epithelial cell line H441.
Methods: Different quantities of H441 cells per growth area were either left untreated or incubated with dexamethasone. The expression of SP-B, SP-B transcription factors, and tight junction proteins were determined by qPCR and immunoblotting. The influence of cell density on SP-B mRNA stability was investigated using the transcription inhibitor actinomycin D.
Results: SP-B mRNA and mature SP-B expression levels were significantly elevated in untreated and dexamethasone-treated H441 cells with increasing cell density. High cell density as a sole stimulus was found to barely have an impact on SP-B transcription factor and tight junction mRNA levels, while its stimulatory ability on SP-B mRNA expression could be mimicked using SP-B-negative cells. SP-B mRNA stability was significantly increased in high-density cells, but not by dexamethasone alone.
Conclusion: SP-B expression in H441 cells is dependent on cell-cell contact, which increases mRNA stability and thereby potentiates the glucocorticoid-mediated induction of transcription. Loss of cell integrity might contribute to reduced SP-B secretion in damaged lung cells via downregulation of SP-B transcription. Cell density-mediated effects should thus receive greater attention in future cell culture-based research.
In 1983, Brian Henderson published an article that examined various types of narrative structure in film, including flashbacks and flashforwards. After analyzing a whole spectrum of techniques capable of effecting a transition between past and present – blurs, fades, dissolves, and so on – he concluded: "Our discussions indicate that cinema has not (yet) developed the complexity of tense structures found in literary works". His "yet" (in parentheses) was an instance of laudable caution, as very soon – in some ten–fifteen years – the situation would change drastically, and temporal twists would become a trademark of a new genre that has not (yet) acquired a standardized name: "modular narratives", "puzzle films", and "complex films" are among the labels used.
Oncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as "clinical benefit" and "clinical relevance" are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.
In this doctoral thesis the transformation from relativistic hydrodynamics to transport and vice versa is studied. Approximations made by hybrid (hydrodynamics + transport) simulations of relativistic heavy ion collisions are discussed and their reliability is assessed at intermediate collision energies. A new method to simulate heavy ion collisions is suggested, based on the forced thermalization in high-density regions.
Although the Nobel Prize for the discovery of nitric oxide (NO) dates back almost 20 years now, the knowledge about cGMP signaling is still constantly increasing. It looks even so that our understanding of the role of the soluble guanylyl cyclase (sGC) and particulate guanylyl cyclase (pGC) in health and disease is in many aspects at the beginning and far from being understood. This holds even true for the therapeutic impact of innovative drugs acting on both the NO/sGC and the pGC pathways. Since cGMP, as second messenger, is involved in the pathogenesis of numerous diseases within the cardiovascular, pulmonary, renal, and endocrine systems and also plays a role in neuronal, sensory, and tumor processes, drug applications might be quite broad. On the 8th International Conference on cGMP, held in Bamberg, Germany, world leading experts came together to discuss these topics. All aspects of cGMP research from the basic understanding of cGMP signaling to clinical applicability were discussed in depth. In addition, present and future therapeutic applications of cGMP-modulating pharmacotherapy were presented (http://www.cyclicgmp.net/index.html).
Algae as primary producers are highly important in aquatic ecosystems and provide a variety of environmental and anthropogenic services. In small lotic ecosystems in agriculturally influenced landscapes, algae are often the main constituent of the base of the food web and they contribute considerably to biodiversity. Within these small lotic ecosystems, algae are influenced by both natural stressors, such as flow regime and dry-out events, and anthropogenic factors. Agricultural practices especially influence algal communities by introducing plant protection products (PPP) and fertilizers into the water. The impacts of these exposures and how they affect planktonic algae in particular are not yet well studied in small lotic ecosystems. However, the protection of algae as primary producers is of high relevance and was thus included in official biomonitoring programs such as the European Water Framework Directive (WFD) or in risk assessment of e.g. PPPs. Hence, this thesis addresses this knowledge gap and links new information on algal communities in small lotic ecosystems with biomonitoring and risk assessment.
Data was gathered from small ditches and streams in central Germany as well as from laboratory algal assays. A technique to rapidly classify and quantify planktonic and benthic algae based on their photopigment concentration (measured via delayed fluorescence - DF) in ecological and ecotoxicological studies was assessed, both in the laboratory and in the field. This research provides insight into planktonic and benthic algal communities in small streams and ditches in order to improve management and protection strategies in the face of increased agricultural chemical input. ...
Compact stars can be treated as the ultimate laboratories for testing theories of dense matter. They are not only extremely dense objects, but they are known to be associated with strong magnetic fields, fast rotation and, in certain cases, with very high temperatures. Here, we present several different approaches to model numerically the signatures and properties of these stars, namely:
•The effects of strong magnetic fields on hybrid stars by using a fully general relativistic approach. We solved the coupled Maxwell-Einstein equations in a self-consistent way, taking into consideration the anisotropy of the energy-momentum tensor due purely to the magnetic field, magnetic field effects on equation of state and the interaction between matter and the magnetic field (magnetization). We showed that the effects of the magnetization and the magnetic field on the equation of state for matter do not play an important role on global properties of neutron stars (only the pure magnetic _eld contribution does). In addition, the magnetic field breaks the spherical symmetry of stars, inducing major changes in the populated degrees of freedom inside these objects and, potentially, converting a hybrid star into a hadronic star over time.
•The effects of magnetic fields and rotation on the structure and composition of proto-neutron stars. We found that the magnetic field not only deforms these stars, but also significantly alters the number of trapped neutrinos in the stellar interior, together with the strangeness content and temperature in each evolution stage from a hot proto-neutron star to a cold neutron star.
•The influence of the quark-hadron phase transitions in neutron stars. In particular, previous calculations have shown that fast rotating neutron stars, when subjected to a quark-hadron phase transition in their interiors, could give rise to the backbending phenomenon characterized by a spin-up era. In this work, we obtained the interesting backbending phenomenon for fast spinning neutron stars. More importantly, we showed that a magnetic field, which is assumed to be axisymmetric and poloidal, can also be enhanced due to the phase transition from normal hadronic matter to quark matter on highly magnetized neutron stars. Therefore, in parallel to the spin-up era, classes of neutron stars endowed with strong magnetic fields may go through a `magnetic-up era' in their lives.
•Finally, we were also able to calculate super-heavy white dwarfs in the presence of strong magnetic fields. White dwarfs are the progenitors of supernova Type Ia explosions and they are widely used as candles to show that the Universe is expanding and accelerating. However, observations of ultraluminous supernovae have suggested that the progenitor of such an explosion should be a white dwarf with mass above the well-known Chandrasekhar limit ~ 1.4 M. In corroboration with other works, but by using a fully general relativistic framework, we obtained also strongly magnetized white dwarfs with masses M ~ 2:0 M.
In thesis I investigate the possibility that at the smallest length scale (Planck scale) the very notion of "dimension" needs to be revisited. Due to "quantum effects" spacetime might become very turbulent at these scales and properties like those of "fractals" emerge, including a "scale dependent dimension". It seems that this "spontaneous dimensional reduction" and the appearance of a minimal physical length are very general effects that most approaches to quantum gravity share. Main emphasis is given to the"spectral dimension" and its calculation for strings and p-branes.
The first principle lattice QCD methods allow to calculate the thermodynamic observables at finite temperature and imaginary chemical potential. These can be compared to the predictions of various phenomenological models. We argue that Fourier coefficients with respect to imaginary baryochemical potential are sensitive to modeling of baryonic interactions. As a first application of this sensitivity, we consider the hadron resonance gas (HRG) model with repulsive baryonic interactions, which are modeled by means of the excluded volume correction. The Fourier coefficients of the imaginary part of the netbaryon density at imaginary baryochemical potential – corresponding to the fugacity or virial expansion at real chemical potential – are calculated within this model, and compared with the Nt = 12 lattice data. The lattice QCD behavior of the first four Fourier coefficients up to T 185 MeV is described fairly well by an interacting HRG with a single baryon–baryon eigenvolume interaction parameter b 1 fm3, while the available lattice data on the difference χB 2 − χB 4 of baryon number susceptibilities is reproduced up to T 175 MeV.
We study the correlation between the distributions of the net-charge, net-kaon, net-baryon and net-proton number at hadronization and after the final hadronic decoupling by simulating ultra relativistic heavy ion collisions with the hybrid version of the ultrarelativistic quantum molecular dynamics (UrQMD) model. We find that due to the hadronic rescattering these distributions are not strongly correlated. The calculated change of the correlation, during the hadronic expansion stage, does not support the recent paradigm, namely that the measured final moments of the experimentally observed distributions do give directly the values of those distributions at earlier times, when the system had been closer to the QCD crossover.
The CRISPR/Cas9 prokaryotic adaptive immune system and its swift repurposing for genome editing enables modification of any prespecified genomic sequence with unprecedented accuracy and efficiency, including targeted gene repair. We used the CRISPR/Cas9 system for targeted repair of patient-specific point mutations in the Cytochrome b-245 heavy chain gene (CYBB), whose inactivation causes chronic granulomatous disease (XCGD)—a life-threatening immunodeficiency disorder characterized by the inability of neutrophils and macrophages to produce microbicidal reactive oxygen species (ROS). We show that frameshift mutations can be effectively repaired in hematopoietic cells by non-integrating lentiviral vectors carrying RNA-guided Cas9 endonucleases (RGNs). Because about 25% of most inherited blood disorders are caused by frameshift mutations, our results suggest that up to a quarter of all patients suffering from monogenic blood disorders could benefit from gene therapy employing personalized, donor template-free RGNs.
Riboswitches are an important class of regulatory RNA elements that respond to cellular metabolite concentrations to regulate gene expression in a highly selective manner. 2’-deoxyguanosine-sensing (2’dG) riboswitches represent a unique riboswitch subclass only found in the bacterium Mesoplasma florum and are closely related to adenine- and guanine-sensing riboswitches. The I-A type 2’dG-sensing riboswitch represses the expression of ribonucleotide reductase genes at high cellular concentrations of 2’dG as a result of premature transcription termination.
Increasing evidence within the last decade suggests that transcriptional regulation by riboswitches is controlled kinetically and emphasizes the importance of co-transcriptional folding.2–4 Addition of single nucleotides to nascent transcripts causes a continuous shift in structural equilibrium, where refolding rates are competing with the rate of transcription.5,6
For transcriptional riboswitches, both ligand binding and structural rearrangements within the expression platform are precisely coordinated in time with the rate of transcription. The current thesis investigates the mechanistic details of transcriptional riboswitch regulation using the I-A 2’dG-sensing riboswitch as an example for a riboswitch that acts under kinetic control.
We report on the results on the dynamical modelling of cluster formation with the new combined PHSD+FRIGA model at Nuclotron and NICA energies. The FRIGA clusterization algorithm, which can be applied to the transport models, is based on the simulated annealing technique to obtain the most bound configuration of fragments and nucleons. The PHSD+FRIGA model is able to predict isotope yields as well as hypernucleus production. Based on present predictions of the combined model we study the possibility to detect such clusters and hypernuclei in the BM@N and MPD/NICA detectors.
In Britain in the late 1880s, two pop cultural icons had an extraordinary meeting: one, Ally Sloper, the fictional star of comic books and stage productions and the other Jack the Ripper, the real-life serial killer who was instantly fictionalised on page and stage as the bogeyman of the moment. The aim here is to explore the way in which this dynamic developed, with a focus on a single issue of 'Ally Sloper’s Half-Holiday' (October 20, 1888), which appeared at the point in time when it was first realised that the killings were being done by a lone individual, and when panic was at its peak. What was at stake politically in the comic’s reaction? What can it tell us about Victorian attitudes to fear, death, and poverty? About the status of women? Finally, about law and order, and the social contract that existed between citizen and police?
Monsters are no rarity in the history of U. S.-American comics, but in Ken Dahl's eponymous small press comic they assume a articular function: His morphing monsters tell a story about how being a carrier of the herpes virus leads to incessant worry and social isolation. Dahl's narrative exposes the instability of the body's boundaries, and that of the distinction between illness and health. This chapter reads Monsters through traditions and theorizations of the Monstrous and Grotesque, as well as cultural histories of medicine that have shed light on discourses of contagion and (in-)visibility of illness. It is the idiosyncrasies of the comics medium and its history, and those of Dahl's stylistic choices, that enable a particularly tangible representation of social and personal illness experience.
In this article I read Jaime Cortez's graphic novel 'Sexile' as an intervention into linear narratives of crossing such as the "victim-rescuing narrative" (Shaksari) or the "transsexual narrative" (Bhanji). 'Sexile' celebrates the resourcefulness and creativity with which the denizens of the borderlands craft homes in the no-man’s land between departures and impossible arrivals. I argue that it is both the story that Sexile (re)tells as well as the format of the graphic novel that make 'Sexile' a life-affirming, useful, and challenging monument to life in the borderlands of national and gendered belonging.
Knowledge for justice : critical perspectives from southern african-nordic research partnerships
(2017)
With the adoption of the United Nations Sustainable Development Goals (SDGs) and the Paris Agreement, the purpose of development is being redefined in both social and environmental terms. Despite pushback from conservative forces, change is accelerating in many sectors. To drive this transformation in ways that bring about social, environmental and economic justice at a local, national, regional and global levels, new knowledge and strong cross-regional networks capable of foregrounding different realities, needs and agendas will be essential. In fact, the power of knowledge matters today in ways that humanity has probably never experienced before, placing an emphasis on the roles of research, academics and universities. In this collection, an international diverse collection of scholars from the southern African and Nordic regions critically review the SDGs in relation to their own areas of expertise, while placing the process of knowledge production in the spotlight. In Part I, the contributors provide a sober assessment of the obstacles that neo-liberal hegemony presents to substantive transformation. In Part Two, lessons learned from NorthSouth research collaborations and academic exchanges are assessed in terms of their potential to offer real alternatives. In Part III, a set of case studies supply clear and nuanced analyses of the scale of the challenges faced in ensuring that no one is left behind. This accessible and absorbing collection will be of interest to anyone interested in NorthSouth research networks and in the contemporary debates on the role of knowledge production. The Southern AfricanNordic Centre (SANORD) is a network of higher education institutions that stretches across Denmark, Finland, Iceland, Norway, Sweden, Botswana, Namibia, Malawi, South Africa, Zambia and Zimbabwe. Universities in the southern African and Nordic regions that are not yet members are encouraged to join.
Insects, the new food?
(2017)
In many parts of the world it is common to eat insects while in the western world it is regarded as a bizarre habit, even evoking disgust. Is this justified? What if insects were nutritionally similar to our common meat products and have proven to be delicious in blind tests? Insects have an environmental impact which is much less than our common production animals, so why not eat it? If these questions can be answered affirmatively, then the question is: Can we persuade the western consumers to take this psychological barrier? There has been a tremendous interest during the last five years to promote insects as food. There are now close to 200 start-up companies listed. Also, in the scientific world the interest is growing exponentially, testified by the number of articles on edible insects that have appeared during the last 15 years (83 from 2011 to 2015 against 9 from 2001 to 20051). These articles deal with harvesting from nature, environmental benefits, nutritional value, food safety, processing, and consumer attitudes. I will give a short overview of the developments in these different areas.
This is a brief in the bEUcitizen policy brief series. The bEUcitizen project - funded by the European Union - set out to identify, investigate, discuss, and ameliorate the barriers to the active use of rights (and knowledge of duties, the concomitant to rights, in so far as there are any) by European citizens. The project aimed to provide a comparative overview and classification of the various barriers to the exercise of the rights and obligations of European Union citizens in the member states. Simultaneously, the project analysed whether and how such barriers can be overcome and the future opportunities and challenges the European Union and its member states face to further develop the idea and reality of European Union citizenship.
Drawing on research conducted during the project, this policy brief discusses the problems preventing European Union citizens from becoming active political citizens. European citizenship as active political citizenship has been underdeveloped from the start and is currently under strong pressure. Over time, European Union citizens seem to have lost enthusiasm for the European political process: Voter turnout in European Parliament elections decreased from 61,99% in 1979 to 42,61% in 2014. Attempts to transform elections for the European Parliament into a meaningful decision about the policies and the personnel of European institutions have been ineffective so far in two ways: On the one hand, they did not raise more interest in European affairs; on the other hand, and even more problematically, the "Spitzenkandidaten"-experiment was overshadowed by the power struggle between national leaders and the European Parliament.
Although similar tendencies towards decreasing voter turnout can be observed in national elections, the trend of fading popular support is particularly alarming at the European Union level. It threatens to undermine the legitimacy and functionality of the European Union, thus jeopardizing the entire integration process. Institutions without support cannot last. The European Union provokes a rather negative political reaction among its citizens and populist activism is challenging its policies and the integration process more broadly. The Brexit decision expresses this problem in an ideal-typical form: Europe-friendly citizens do not use their right to vote while anti-European activism brings citizens to the ballot box. Concerned with this passivity as well as with the activism mobilised by anti-European populism, Europe-friendly observers and actors see a major opportunity for the European Union to strengthen the European Parliament as the core institution of a European representative democracy.
In recent years, Ontological Security Theory (OST) has been established as a new theory in the field of International Relations. The theory seeks to explain state behavior, and offers a new perspective on the security dilemma and the persistence of conflicts. It has proven itself helpful in explaining seemingly irrational state behavior such as an aggressive foreign policy by weak states or the provision of humanitarian aid by powerful nations. OST further allows scholars to analyze norm-violating behavior of states, for instance the use of torture at the hands of Americans in the War on Terror. If you have not engaged with the theory before, you might want to learn about its core arguments as well as its potential and limitations in the following. For those who know the theory well, let me show you how the theory was key to gaining new insights in my research.
Not unlike the recent report Filling the ranks on the recruitment problems of the British Army shows for the UK, the German armed forces (Bundeswehr) struggle badly to meet their recruitment goals and to fulfill the “Trendwende Personal” (the turnaround in the personnel strength) as proclaimed by the German Defence Minister Ursula von der Leyen. Last year the recruitment department of the Bundeswehr tried a new way of targeting especially young people on YouTube. With a series of 59 episodes called Die Rekruten (The Recruits) YouTube users followed a couple of German Navy recruits through their basic training at the German Navy Technical School.
The series was widely criticised for not showing the serious implications of military service. Two weeks ago, the new series MALI on the deployment of German forces with the United Nations mission MINUSMA in Mali started as a sequel. But does the new series give a realistic impression of the challenges and risks of being a German soldier today and why should this be a requirement for a YouTube series?
In the Global South, private corporations and development aid programs are widely implementing information and communication technology (ICT). Stakeholders export infrastructure (including satellites, drones, and white spaces technology) as well as mobile and internet services (mobile money services, zero-rating), following the proclaimed goal to close the global digital divide. They particularly target under-connected regions in Africa, as Africa shows the lowest levels of internet connectivity (cf. International Telecommunications Union 2017). According to companies and development aid programs, these digitalization efforts in the Global South are key to development and security. However, an ethical perspective points to concerns about the practice of digitalization in the Global South. One central concern is that certain values are inscribed in ICT, and that they may be indirectly implemented through technology in the importing countries. Thus, the export of ICT by Western companies and development aid programs to the Global South may have a "neo-colonial" character. This raises ethical questions about global justice...
In October 2015, the Cluster of Excellence 'Image Knowledge Gestaltung. An Interdisciplinary Laboratory' at Humboldt Universität zu Berlin staged a symposium entitled Science meets Comics. Academics from various disciplines converged along with artists from all over the world in order to discuss the future of global nutrition – and the medium of the comic strip as a communication tool for the complex issues in this field. The open two-day symposium was followed by a closed, three-day workshop wherein the artists and cluster members took up the issues raised at the symposium and worked on possible directions for the future.
Human-induced environmental change represents one of the major challenges of current and future generations. To evaluate the anthropogenic impacts on the biosphere, the concept of Planetary Boundaries was developed, indicating that in case of four out of nine environmental indicators a transgression of corresponding boundaries has already taken place: Biodiversity loss, climate change, land-system change, and biogeochemical flows. Further, paleoclimate research has shown that the earth´s environment has been relatively stable for the last 12,000 years. Researchers assume that this, in geological terms, very short period – called Holocene – is now already again replaced by a new geological era: the Anthropocene, due to the tremendous impacts humans had on earth.
Our daily food consumption is slowly but surely turning into the largest environmental threat. The agricultural sector consumes 70% of the water used by humankind. The production of meat consumes enormous amounts of water compared to plants. Innovations in the area of food production are lately summarized as AgTech, agricultural technology. This encompasses all sorts of areas, ranging from drone-controlled tractors to printed hamburgers. Specifically the challenge of making use of the limited areas available in cities and maximizing crop yields has seen a recent boom in novel approaches – and quite a bit of investor finance.
Ruth Preser's essay 'Things I Learned from the "Book of Ruth": Diasporic Reading of Queer Conversions' performs a queer appropriation of history. The "Book of Ruth" is a biblical narrative that opens with two women, Naomi the Israelite, a bereaved woman who wishes to return from Moab to Judea, and her no-longer-daughter-in-law Ruth the Moabite, who pledges to follow Naomi, turning away from her gods and people. This laconic tale of nomadic intimacies and speech-acts of pledges and conversions has become an iconic narrative and a seminal text in Judaism, and it has also been appropriated by contemporary feminist and lesbian readings. Indeed, since it is not fully narrated but rather full of gaps, voids, and 'ghostly matters', the "Book of Ruth" provides apt ground and a malleable vessel for contemporary appropriation by stories seeking incarnation beyond linear or teleological constraints. In Preser's 'palimpsest reading', the biblical tale continues to communicate a story of successful assimilation of the poor and the foreign, and of a 'home-coming', but it is troubled by displacement, unresolved diasporic longing, and an acute and continuous sense of vulnerability. Thinking with Avery Gordon's modality of haunting, Preser's reading aims to understand contemporary forms of dispossession and their impact, especially when their oppressive nature is denied. It reflects on what kind of theory might emerge by remobilizing the category of 'home' through its de-constitution, through movement rather than destination, through disintegration rather than determination. Troubled by questions of race, nomadism, gender, and sexuality, in an era when (some) bodies may traverse national, sexual, and class borders, Preser's investigation asks what happens to bodies that continuously signify precarity and loss.
During the transition from early-modern societies to the nation states of the 19th and 20th centuries, the formation of the territorial state performed an important function. The combining of dominions to form a geographical and political unit could occur through the annexation of the weaker territory by the stronger one, but it could also occur with the mutual agreement of the political decision-makers of both territories. In the case of a union, a distinction emerged very early on between a real union and a personal union (or union of crowns). While in a real union agreements under international law were equally binding for both partners, the personal union assumed a special status, in which the person of the ruler was the only connection between the two states. However, this strictly legal definition only applied to the political institutions. Below the state level, there were forms of transfer that could give a personal union a special, transnational character. Academic opinion remains divided on the extent to which these connections, which are referred to using the term "composite statehood", constitute a Europe-wide development.
The centerpiece of all neuronal processes is the synaptic transmission. It consists of a complex series of events. Two key elements are the binding of synaptic vesicles (SV) to the presynaptic membrane and the subsequent fusion of the two membranes. SV are neurotransmitter-filled membranous spheres with many integral and peripheral proteins. The synaptic SNARE complex consists of three interacting proteins, which energize and regulate the fusion of the SV membrane with the presynaptic membrane. Both processes are closely orchestrated to ensure a specific release of neurotransmitter. Already many experiments have been performed, such as genetic screens and proteome analysis of SV, to determine the functions of the various proteins involved. Nevertheless, the functions of the identified proteins are still not fully elucidated. The aim of this thesis was initially applying a tandem affinity purification (TAP) of SV to identify unknown interaction partner of SV and to determine their role. This was supposed to be performed in the model organism Caenorhabditis elegans (C. elegans). The underlying mechanisms are conserved throughout the phylogentic tree and identified interaction partners will help to understand the processes in the mammalian brain. Although there is no neuron-rich tissue in C. elegans as in other model organisms, the diverse genetic methods allows a rapid creation of modified organisms and a prompt determination of the function of identified proteins. The integral SV protein synaptogyrin has been fused to a TAP-tag. The TAP-tag consists of a ProteinA, a TEV protease cleavage site and a calmodulin binding peptide (CBP). Both affinity purification steps are performed sequentially and allow a highly specific native purification of proteins and their interaction partners. Due to technical difficulties the purification strategy was modified several times during the course of this thesis and then finally abandoned for a more promising project, the SNARE complex purification. In conclusion, one of the reasons was the necessary lack of detergent.
The amended aim of this thesis has been the TAP of solubilized SNARE complex to identify unknown interaction partner and to determine their role. In order to increase the specificity of the purification, in terms of formed complexes, the two SNARE subunits, synaptobrevin (SNB-1 in C. elegans) and syntaxin (UNC-64 in C. elegans), were separately fused to the different affinity tags. As the modifications of the proteins could impair their function and lead to false interaction partners, their functionality was tested. For this purpose, the corresponding fusion constructs were expressed in strains with mutated snb¬1 and unc-64. Non-functional synaptic proteins display an altered course of paralysis in an aldicarb assay. The fusion proteins which were expressed in their respective mutant strains displayed a near to wild-type (WT) behavior in contrast to the naive mutant strains. Multiple TAP demonstrated SNB-1 signals in Western blot analysis and complex sets of proteins in the final elution step in a silver staining of SDS-PAGEs. These samples were sent with negative control (WT purification) for MS analysis to various cooperation partners. 119 proteins were identified which appeared only in data sets with SNARE proteins and not in WT samples. If proteins were detected in ≥ 2 SNARE positive MS analysis and had known neural functions or homologies to neuronal proteins in other species, they were selected for further analysis. These candidates were knocked down by RNAi and tested for synaptic function in a following aldicarb assay. The treatment with their specific RNAi resulted for mca-3 in a strong resistance, while frm-2, snap-29, ekl-6, klb-8, mdh-2, pfk-2, piki-1 and vamp-8 resulted in hypersensitivity. The most responsive genes frm-2, snap-29 and mca-3 were examined, whether they displayed a co-localization together with synaptobrevin in promoter fusion constructs or functional fusion constructs. In fluorescence microscopy images only MCA-3::YFP demonstrated neuronal expression.
In order to substantiate the synaptic nature and functionality of the MCA-3::YFP a swimming assay was performed. Here, fusion construct expressing strains, which contained mutated mca-3, were compared with untreated mutant strains and WT strains according to their behavior. In this swimming assay a partial restoration of WT behavior was shown in the MCA-3::YFP expressing mutant strains. Based on these data, we discovered with MCA 3 a new interaction partner of the SNARE complex. MCA-3 is a plasma membrane Ca2+-ATPase and was initially seen only in their role in the endocytosis. Its new putative role is the reduction of Ca2+ concentration at the bound SNARE complex. Since an interaction of syntaxin with Ca2+ channels has been demonstrated, it would be comprehensible to reduce the local concentration of Ca2+ to a minimum by tethering Ca2+ transporters to the SNARE complex.