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Tumor-associated macrophages, angiogenesis, and tumor cell migration in oral squamous cell carcinoma
(2017)
Objective: To investigate the relationship between tumor-associated macrophages (TAMs), neovascularization, and tumor cell migration in oral squamous cell carcinoma (OSCC) of an African subpopulation.
Materials and Methods: Twenty OSCC paraffin blocks underwent immunohistochemistry to TAM1 (CCR7), TAM2 (CD206), Twist, E-cadherin, N-cadherin, and CD34. The relative percentage of CCR7 + and CD206 + cells to overall immune cell population was calculated for three high power fields and an average was taken. TAM-related microvessel density (MVD) was determined as the mean of the three recorded values. Cases that had no CD34 + vessels adjacent to the TAMs region were regarded as having an MVD score of 0.
Results: Ten cases (50%) expressed greater CCR7 activity than CD206, seven cases (35%) expressed approximately equal activity of CCR7 and CD206, while three cases (15%) expressed greater activity of CD206 than CCR7. Twist expression was strong in some cases with strong N-cadherin and weak E-cadherin, but the expression of Twist was not consistently high in all cases that expressed strong N-cadherin and weak E-cadherin.
Conclusions: TAMs distribution suggested antitumor activity and the potential for tumor metastasis was only partly due to Twist-mediated epithelial–mesenchymal transition.
BACKGROUND: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements.
RESULTS: The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF).
CONCLUSION: Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1.
Prioritization of introduction pathways is seen as an important component of the management of biological invasions. We address whether established alien plants, mammals, freshwater fish and terrestrial invertebrates with known ecological impacts are associated with particular introduction pathways (release, escape, contaminant, stowaway, corridor and unaided). We used the information from the European alien species database DAISIE (www.europe-aliens.org) supplemented by the EASIN catalogue (European Alien Species Information Network), and expert knowledge. Plants introduced by the pathways release, corridor and unaided were disproportionately more likely to have ecological impacts than those introduced as contaminants. In contrast, impacts were not associated with particular introduction pathways for invertebrates, mammals or fish. Thus, while for plants management strategies should be targeted towards the appropriate pathways, for animals, management should focus on reducing the total number of taxa introduced, targeting those pathways responsible for high numbers of introductions. However, regardless of taxonomic group, having multiple introduction pathways increases the likelihood of the species having an ecological impact. This may simply reflect that species introduced by multiple pathways have high propagule pressure and so have a high probability of establishment. Clearly, patterns of invasion are determined by many interacting factors and management strategies should reflect this complexity.
To study the implications of highly space-demanding organic moieties on the properties of self-assembled monolayers (SAMs), triptycyl thiolates and selenolates with and without methylene spacers on Au(111) surfaces were comprehensively studied using ultra-high vacuum infrared reflection absorption spectroscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy and thermal desorption spectroscopy. Due to packing effects, the molecules in all monolayers are substantially tilted. In the presence of a methylene spacer the tilt is slightly less pronounced. The selenolate monolayers exhibit smaller defect densities and therefore are more densely packed than their thiolate analogues. The Se–Au binding energy in the investigated SAMs was found to be higher than the S–Au binding energy.
While many programs are available to edit phylogenetic trees, associating pictures with branch tips in an efficient and automatic way is not an available option. Here, we present TreePics, a standalone software that uses a web browser to visualize phylogenetic trees in Newick format and that associates pictures (typically, pictures of the voucher specimens) to the tip of each branch. Pictures are visualized as thumbnails and can be enlarged by a mouse rollover. Further, several pictures are can be selected and displayed in a separate window for visual comparison. TreePics works either online or in a full standalone version, where it can display trees with several thousands of pictures (depending on the memory available). We argue that TreePics can be particularly useful in a preliminary stage of research, such as to quickly detect conflicts between a DNA-based phylogenetic tree and morphological variation, that may be due to contamination that needs to be removed prior to final analyses, or the presence of species complexes.
We study exchangeable coalescent trees and the evolving genealogical trees in models for neutral haploid populations.
We show that every exchangeable infinite coalescent tree can be obtained as the genealogical tree of iid samples from a random marked metric measure space when the marks are added to the metric distances. We apply this representation to generalize the tree-valued Fleming-Viot process to include the case with dust in which the genealogical trees have isolated leaves.
Using the Donnelly-Kurtz lookdown approach, we describe all individuals ever alive in the population model by a random complete and separable metric space, the lookdown space, which we endow with a family of sampling measures. This yields a pathwise construction of tree-valued Fleming-Viot processes. In the case of coming down from infinity, we also read off a process whose state space is endowed with the Gromov-Hausdorff-Prohorov topology. This process has additional jumps at the extinction times of parts of the population.
In the case with only binary reproduction events, we construct the lookdown space also from the Aldous continuum random tree by removing the root and the highest leaf, and by deforming the metric in a way that corresponds to the time change that relates the Fleming-Viot process with a Dawson-Watanabe process. The sampling measures on the lookdown space are then image measures of the normalized local time measures.
We also show invariance principles for Markov chains that describe the evolving genealogy in Cannings models. For such Markov chains with values in the space of distance matrix distributions, we show convergence to tree-valued Fleming-Viot processes under the conditions of Möhle and Sagitov for the convergence of the genealogy at a fixed time to a coalescent with simultaneous multiple mergers. For the convergence of Markov chains with values in the space of marked metric measure spaces, an additional assumption is needed in the case with dust.
Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis
(2017)
Background: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.
Aim: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.
Methods: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.
Results: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.
Conclusions: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.
A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.
The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany.
This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.
We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.
O intuito deste trabalho é destacar a importância do escrito juvenil Traumland para a formação do poeta Georg Trakl, por meio de uma leitura cerrada do texto. Sob a forma de uma lembrança do narrador, esse breve relato apresenta uma experiência de iniciação ou perda da inocência oriunda da percepção do mal no mundo, concentrado na figura de uma prima doente, Maria. O conflito entre o anseio romântico (Sehnsucht) pleno de expectativas e entusiasmo e essa realidade aterradora, vivenciado como uma quebra no sentimento (Stimmung) de harmonia cósmica, impulsiona uma transformação no sentimento e na visão de mundo do protagonista, que metaforicamente pode ser lida como a transição de uma poética puramente romântica para uma poética mais sintonizada com as exigências do século XX, especialmente no sentido da dimensão reconhecida ao mal irremediável, que não pode ser completamente romantizado.
Background: Posttraumatic Stress Disorder (PTSD) related to childhood sexual abuse (CSA) is often associated with a wide range of trauma-related aversive emotions such as fear, disgust, sadness, shame, guilt, and anger. Intense experience of aversive emotions in particular has been linked to higher psychopathology in trauma survivors. Most established psychosocial treatments aim to reduce avoidance of trauma-related memories and associated emotions. Interventions based on Dialectical Behavior Therapy (DBT) also foster radical acceptance of the traumatic event.
Methods: This study compares individual ratings of trauma-related emotions and radical acceptance between the start and the end of DBT for PTSD (DBT-PTSD) related to CSA. We expected a decrease in trauma-related emotions and an increase in acceptance. In addition, we tested whether therapy response according to the Clinician Administered PTSD-Scale (CAPS) for the DSM-IV was associated with changes in trauma-related emotions and acceptance. The data was collected within a randomized controlled trial testing the efficacy of DBT-PTSD, and a subsample of 23 women was included in this secondary data analysis.
Results: In a multilevel model, shame, guilt, disgust, distress, and fear decreased significantly from the start to the end of the therapy whereas radical acceptance increased. Therapy response measured with the CAPS was associated with change in trauma-related emotions.
Conclusions: Trauma-related emotions and radical acceptance showed significant changes from the start to the end of DBT-PTSD. Future studies with larger sample sizes and control group designs are needed to test whether these changes are due to the treatment.
Trial registration: ClinicalTrials.gov, number NCT00481000
Telemonitoring devices can be used to screen consumers' characteristics and mitigate information asymmetries that lead to adverse selection in insurance markets. However, some consumers value their privacy and dislike sharing private information with insurers. In the second-best efficient Wilson-Miyazaki-Spence framework, we allow for consumers to reveal their risk type for an individual subjective cost and show analytically how this affects insurance market equilibria as well as utilitarian social welfare. Our analysis shows that the choice of information disclosure with respect to revelation of their risk type can substitute deductibles for consumers whose transparency aversion is sufficiently low. This can lead to a Pareto improvement of social welfare and a Pareto efficient market allocation. However, if all consumers are offered cross-subsidizing contracts, the introduction of a transparency contract decreases or even eliminates cross-subsidies. Given the prior existence of a WMS equilibrium, utility is shifted from individuals who do not reveal their private information to those who choose to reveal. Our analysis provides a theoretical foundation for the discussion on consumer protection in the context of digitalization. It shows that new technologies bring new ways to challenge crosssubsidization in insurance markets and stresses the negative externalities that digitalization has on consumers who are not willing to take part in this development.
One of the fundamental challenges in deconstructing, rethinking and remaking the world from a Pan African vantage point is that some captives have tended to delight in the warmth of the [imperial] predator's mouth. In other words, some captives forget that the imperial predator's mouth gets warm because empire is eating and heating up from prey on the continent. (De-)Militarisation, Transnational Land Grabs and Restitution in an Age of the New Scramble for Africa: A Pan African Socio-Legal Perspective is a book that knocks on key aspects relating to land, militarisation, a PostAfrican World Order and a chaotic Post-God World Order, which require critical scholarly and policy attention in the quest to free Africa from centuries-old imperial depredations. The book carefully navigates the imperial entrapments which are designed to focus African attention only on decolonising African minds without also engaging in the [imperially more unsettling] decolonisation of African materialities.
Des critiques et écrivains de nouvelles ont défendu l'idée que la brieveté et un unique moment de clarté sont les éléments essentiels du format court typique de la nouvelle. Cependant, la nouvelle postcoloniale est plurielle, polyphonique et versatile, et elle a tendance à s'appuyer sur le désaccord culturel, social, et linguistique. Ce chapitre examine la traduction et l'échec de celle-ci dans l'oeuvre de deux nouvellistes prolifiques qui viennent des deux différentes traditions postcoloniales : Nadine Gordimer et Anita Desai. La prémisse de mon argument est que les nouvelles de ces écrivains ont pour la plupart lieu dans des espaces périphériques, par exemple des villages et des avant-postes. Elles dramatisent une forme de processus postcolonial de désengagement des centres de pouvoir en explorant et en remettant en question des hiérarchies discursives. Cette renégociation implique la présence de perspectives multiples et de subjectivités plurielles, de même qu'elle insiste sur des traductions problématiques et des malentendus surgissant en leur sein. Par l'étude de textes de Gordimer et Desai, ce chapitre considère plusieurs formes de malentendus – fausses représentations, mécompréhension, traductions erronées et obstructions linguistiques – qui ses présentent dans deux nouvelles. Il ressort de cette analyse que les malentendus sont susceptibles de devenir les instruments de l'expression d'une résistance dans les sites hégémoniques de la langue et du pouvoir.
Languages in general have various possibilities to express one and the same propositional content. One of these possibilities is grammatical variation. This thesis is concerned with the variation of the linear word order in a clause and the effects triggered by word order alternations. Although sharing the same propositional content, different word order variants can carry different functions; word order variation can be used to achieve certain stylistic effects. The dissertation looks at functional and stylistic preferences of English regarding variation from the canonical word order in (1).
(1) [Ernie]S [sits]V [on the table]O. (SVO)
The variation under consideration is locative inversion (LOCI), exemplified in (2).
(2) On the table sits Ernie.
As any variation from the canonical word order is said to strongly depend on the grammatical system of the language a sentence is realized in, the perspective is extended to the word order equivalent of the sentence above in German (3). The goal is to highlight possible differences/similarities between English and German with respect to one specific word order variant in a declarative main clause.
(3) Auf dem Tisch liegt ein Brief.
On the table lies a letter
‘On the table lies a letter’.
As the variation from the canonical word order is not expected to be coincidental in both languages, the features that favor the pattern under consideration are examined. This is done through a statistical analysis by employing two comparable corpora, the BNC for English and the TÜPP D/Z for German. The central questions for the thesis therefore are: What are the functions of the inverted constructions in English and German, what features favor their use in the respective languages, and how are they realized syntactically?
One finding is that German uses the syntactic pattern PP-V-NP for very similar reasons this pattern is used for in English. There seems to be a general tendency to order shorter before longer constituents. The syntactic pattern under consideration fulfills similar discourse functions in both languages. Both languages show similar preferences, they are driven by similar factors when having to decide on whether to stay with the canonical order or to prepose (respectively invert) the canonically postverbal PP.
In diesem Beitrag wird ein Aufzeichnungsbuch aus der Großstadt, der Prosaband "Die Kurve" (1920) von Elisabeth Janstein (1891-1944), einer bis heute ziemlich unbekannten Autorin aus dem Umfeld des sogenannten Prager Kreises, mit dem für die Gattung vorbildhaften "Spleen de Paris" von Charles Baudelaire (1869) und einigen motivverwandten, teils auch auf Baudelaire beziehbaren Texten von Rilke in Verbindung gebracht. Als weiterer Bezugspunkt dient das Tagebuch der Russin Maria Bashkirtseff (1898). Auf die Großstadtthematik lassen sich dabei verschiedene Aspekte der Antithese von Zentrum und Peripherie projizieren, die anscheinend transkulturell verbreitet sind: die Gegensätze von moderner Zivilisation und einfachem Leben; Armut und Reichtum; Drogen, Künstlertum und Alltagsleben.
Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process.
Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed.
Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition.
Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.
Trial registration: number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).
Transition path sampling is a powerful tool in the study of rare events. Shooting trial trajectories from configurations along existing transition paths proved particularly efficient in the sampling of reactive trajectories. However, most shooting attempts tend not to result in transition paths, in particular in cases where the transition dynamics has diffusive character. To overcome the resulting efficiency problem, we developed an algorithm for “shooting from the top.” We first define a shooting range through which all paths have to pass and then shoot off trial trajectories only from within this range. For a well chosen shooting range, nearly every shot is successful, resulting in an accepted transition path. To deal with multiple mechanisms, weighted shooting ranges can be used. To cope with the problem of unsuitably placed shooting ranges, we developed an algorithm that iteratively improves the location of the shooting range. The transition path sampling procedure is illustrated for models of diffusive and Langevin dynamics. The method should be particularly useful in cases where the transition paths are long so that only relatively few shots are possible, yet reasonable order parameters are known.
Die durchgeführte Studie befasste sich mit der Fragestellung, wie transidente Menschen in verschiedenen italienischen und rumänischen gesellschaftlichen Diskursen dargestellt werden und welche Aussagen anhand der in den Textauszügen enthaltenen sprachlichen Phänomene über die Situation und Lebensrealität von transidenten Menschen in Italien und Rumänien getroffen werden können.
Hierzu wurde in der vorliegenden Arbeit zunächst eine theoretische Grundlage geschaffen, die einerseits die Zusammenhänge im Themenbereich Diskurs und Diskriminierung beleuchtete und andererseits jene zwischen Gendertheorie, queeren communities und Lebensrealitäten im Kontext von Transidentität. Ebenso wurde im Zuge dessen eine präzise Definition des Begriffs Transidentität erarbeitet.
In der anschließenden Analyse wurden Auszüge aus diagnostischen Standardwerken der Psychologie, Gesetzestexten, medialen Fremddarstellungen transidenter Menschen und Eigendarstellungen transidenter Menschen in sozialen Netzwerken auf Inhalt, Präsentation, Lexikon und Syntax untersucht. Hierbei sollten Hinweise auf die Darstellungen transidenter Menschen in den folgenden vier gesellschaftlichen Diskursen gesucht werden: erstens der Diskurs über die medizinisch-psychologische Versorgung transidenter Menschen sowie darin enthaltene Pathologisierung; zweitens gesetzliche Regelungen sowie darin enthaltener Schutz vor Gewalttaten und Diskriminierung; drittens Gesellschaft sowie Teilhabe und Diskriminierung innerhalb dieser; und zuletzt Selbstverständnis im Kontext von aktivistischen Diskursen.
Üniversiteler bilginin üretildiği yerlerdir. Bu bilgiler paylaşıldıkça anlam kazanırlar. Küresel dünyada üniversitelerden beklenen, bu bilgi paylaşımının yoğun olmasıdır. Yabancı dil bilmek bu aşamada oldukça önemlidir. Akademisyenlerin bu bilgi ağına katılım etkinliği, yabancı dili sözlü ve yazılı etkin kullanabilmesine bağlıdır. Bu çalışmanın amacı, öğretim üyelerinin yabancı dil seviyelerinin demografik değişkenlere göre ölçülmesi ve yabancı dil kullanım amaçlarının betimlenmesidir. Çalışmaya 2015 yılında Trakya Üniversitesi'nde çalışan 269 öğretim üyesi katkı sağlamıştır. Öğretim üyelerinin yabancı dil seviyeleri 'Diller için Avrupa Ortak Öneriler Çerçevesi - Ortak Öneri Düzeyleri Genel Basamaklar Kümesi - A1, A2, B1, B2, C1 ve C2' aracılığı ile ölçülmüştür. Yabancı dil kullanım amaçları ise güvenilirlik oranı % 95 olan bir ölçme aracı ile ölçülmüştür. Betimsel bir yaklaşımla yürütülen çalışmada veriler yüzdelik olarak hesaplanmıştır. Verilerin analizi çalışmaya katılan öğretim üyelerinin yaklaşık üçte birinin B1 (%30,1) ve B2 (%30,1) seviyelerinde olduğunu göstermiştir. Ayrıca yabancı dili kullanma amaçları (akademik, eğitim-öğretim ve kişisel) arasında alımlamaya ve üretime yönelik becerilerde farklılıklar tespit edilmiştir.
Biological invasions are occurring frequently and with great impact to agricultural production and other ecosystem services. In response to this, the Australian Weed Risk Assessment (AWRA) was created to assess the potential 'weediness' of plants based on answers to questions related to biogeography, undesirable attributes, and biology or ecology. This basic model has been expanded and adapted for use on other taxa, often without adequate validation. Since invasive insect crop pests are a major economic cost to agricultural production, there is interest in using an expanded model for insects. Here, we review traits related to invasiveness of insects based on a systematic review of the literature. We then compare the identified invasive traits of insects with those identified for plants in the AWRA. Using insects as a case study, we illustrate that although there is some overlap in invasive traits, there are many unique traits related to invasion for both insects and plants. For insects, these traits relate largely to social behaviour. This lack of congruence may also be the case for other taxa. To increase predictive power, a taxon-specific risk assessment tool and deliberate verification are required.
The concept of the "comprehensive approach" has become a paradigm for international state engagement in the field of fostering sustainable peace in crisis-ridden countries. This approach stipulates joint actions of different governmental institutions. The ministry of defence, providing interventionist armed forces; the ministry of interior, providing police personal; the ministry of foreign affairs, providing crisis aid and the ministry of economic cooperation and development define the core actors on the highest level, whilst the implementation of this approach is left to the various, highly heterogeneous employees of the ministries and their sub-contractors...
Sustainable Development Goals (SDGs) comprise of 17 goals and 169 targets. All SDGs are interlinked to produce synergetic eff ects and emphasize health in all policies. Among the 17 Goals, Goal 3 has a central focus on health, which is underpinned by 13 targets. Th e other 16 goals are also directly or indirectly related to health and will contribute to achieving the associated targets for Goal 3. Th e ambitious SDG agenda and their progress can be tracked by measuring numerous goals, targets, and indicators. The main objective of this paper is to provide an overview about how health- related SDGs and their targets and indicators are being tracked in the national context of Nepal. Adequate investment in research for knowledge generation, capacity building and innovation, and continous research communication among policy makers, researchers and external development partners will contribute to tracking the progress of SDGs in Nepal.
Studies investigating the prevalence, cause, and consequence of multiple sclerosis (MS) fatigue typically use single measures that implicitly assume symptom-stability over time, neglecting information about if, when, and why severity fluctuates. We aimed to examine the extent of moment-to-moment and day-to-day variability in fatigue in relapsing-remitting MS and healthy individuals, and identify daily life determinants of fluctuations. Over 4 weekdays, 76 participants (38 relapsing-remitting MS; 38 controls) recruited from multiple sites provided real-time self-reports six times daily (n = 1661 observations analyzed) measuring fatigue severity, stressors, mood, and physical exertion, and daily self-reports of sleep quality. Fatigue fluctuations were evident in both groups. Fatigue was highest in relapsing-remitting MS, typically peaking in late-afternoon. In controls, fatigue started lower and increased steadily until bedtime. Real-time stressors and negative mood were associated with increased fatigue, and positive mood with decreased fatigue in both groups. Increased fatigue was related to physical exertion in relapsing-remitting MS, and poorer sleep quality in controls. In relapsing-remitting MS, fatigue fluctuates substantially over time. Many daily life determinants of fluctuations are similar in relapsing-remitting MS and healthy individuals (stressors, mood) but physical exertion seems more relevant in relapsing-remitting MS and sleep quality most relevant in healthy individuals.
A great challenge in life sciences remains the site-specific modification of proteins with minimal perturbation for in vitro as well as in vivo studies. Therefore, different chemoselective reactions and semi-synthetic techniques such as native chemical ligation or intein-mediated protein splicing have been established. They enable a site-specific incorporation of chemical reporters into proteins, such as organic fluorophores or unnatural amino acids. In this PhD Thesis, protein trans-splicing was guided by minimal high-affinity interaction pairs to trace proteins in mammalian cells. In addition, the temporal modulation of cellular processes by photo-cleavable viral immune evasins was achieved.
Protein trans-splicing mediated by split inteins is a powerful technique for site-specific and 'traceless' protein modifications. Despite recent developments there is still an urgent need for ultra-small high-affinity intein tags for in vitro and in vivo approaches. So far, only a very few in-cell applications of protein trans-splicing are reported, all limited to C-terminal protein modifications. Here, a strategy for covalent N-terminal intein-mediated protein labeling at sub-nanomolar probe concentrations was developed. Combined with the minimalistic Ni-trisNTA/His-tag interaction pair, the affinity between the intein fragments was increased 50-fold (KD ~ 10 nM). Site-specific and efficient 'traceless' protein modification by high-affinity trans-splicing is demonstrated at nanomolar concentrations in mammalian cells.
High background originating from non-reacted, 'always-on' fluorescent probes still is a crucial issue in life sciences. Covalent labeling approaches with simultaneous activation of fluorescence are advantageous to increase sensitivity and to reduce background signal. Therefore, high-affinity protein trans-splicing was combined with fluorophore/quencher pairs for online detection of covalent N-terminal protein labeling in cellular environments. Substantial fluorescence enhancement at nanomolar probe concentrations was achieved. This ultra-small fluorogenic high-affinity split intein system is an unprecedented example for real-time monitoring of the trans-splicing reaction in cell-like environments as well as for protein labeling with fluorogenic probes at nanomolar concentrations.
To extend the field of chemical immunology and to address spatiotemporal aspects in adaptive immune response, new tools to control antigen processing are required. Therefore, synthetic photo-conditional viral immune evasins were designed to modulate antigen processing on demand. By using light, the time and dose controlled antigen translocation by the transporter associated with antigen processing (TAP) was triggered with response in the second regime. Peptide delivery and loading by the peptide-loading complex (PLC) was rendered inactive, whereas blocking was abolished in a light-controlled fashion to inactivate the synthetic viral immune evasin ICP47 along with simultaneous activation of the antigen presentation pathway. Lightresponsive peptide translocation by the TAP complex was assayed in vitro by utilizing microsomes isolated from professional antigen presenting B-cell lymphomas (Raji). To extend these studies, suppression and photo-controlled rescue of antigen presentation was examined at single-cell resolution in human primary immune cells.
Native chemical ligation interconnects peptide chemistry with recombinantly expressed proteins. This technique was applied to generate the semi-synthetic full-length ICP47. Although this approach was realized, the low product yield was not sufficient for further functional studies. Therefore, full-length ICP47 was consecutively generated by utilizing a full synthetic four-fragment ligation approach. However, this synthetic viral immune evasin was not able to block peptide translocation in a robust way.
Robinia pseudoacacia L. (black locust) is a North American tree, considered controversial because of the conflict between multiple uses by humans and negative environmental impacts, which have resulted in it being listed among the most invasive species in Europe. The current management of Robinia stands in Central Europe varies locally according to national legislation, preferring either socio-economic benefits or biodiversity impacts. We collected field data from our target region of Czechia, reviewed research articles including local grey literature mostly from Central and Southern Europe, unpublished results of local projects and inquired relevant specialists. Because Robinia grows in habitats ranging from urban to forest to natural grassland, neither unrestricted cultivation nor large-scale eradication is applicable as a universal practice. In this paper we suggest a complex management strategy for Robinia stands that takes into account habitat, this species’ local ability to spread, as well as economic, cultural and biodiversity aspects. We categorized Robinia stands growing in Europe into eight groups and proposed stratified approach to the management based on decisions that reflect local context. Depending on that, the management includes (i) establishment of new plantations, (ii) maintenance or utilization of existing stands, (iii) tolerance
and (iv) conversion to original vegetation. Our complex management strategy will provide a comprehensive guideline for the management of alien trees in Europe.
The study of lattice gauge theories with Monte Carlo simulations is hindered by the infamous sign problem that appears under certain circumstances, in particular at non-zero chemical potential. So far, there is no universal method to overcome this problem. However, recent years brought a new class of non-perturbative Hamiltonian techniques named tensor networks, where the sign problem is absent. In previous work, we have demonstrated that this approach, in particular matrix product states in 1+1 dimensions, can be used to perform precise calculations in a lattice gauge theory, the massless and massive Schwinger model. We have computed the mass spectrum of this theory, its thermal properties and real-time dynamics. In this work, we review these results and we extend our calculations to the case of two flavours and non-zero chemical potential. We are able to reliably reproduce known analytical results for this model, thus demonstrating that tensor networks can tackle the sign problem of a lattice gauge theory at finite density
The properties of matter at finite baryon densities play an important role for the astrophysics of compact stars as well as for heavy ion collisions or the description of nuclear matter. Because of the sign problem of the quark determinant, lattice QCD cannot be simulated by standard Monte Carlo at finite baryon densities. I review alternative attempts to treat dense QCD with an effective lattice theory derived by analytic strong coupling and hopping expansions, which close to the continuum is valid for heavy quarks only, but shows all qualitative features of nuclear physics emerging from QCD. In particular, the nuclear liquid gas transition and an equation of state for baryons can be calculated directly from QCD. A second effective theory based on strong coupling methods permits studies of the phase diagram in the chiral limit on coarse lattices.
The special set of papers entitled “DNA Library of Life” constitutes an outcome of the project “Bibliothèque du vivant” (BdV), which aims to promote the molecular taxonomy of eukaryotes by offering research teams the possibility to produce and manage a molecular library linked with specimens deposited in natural history museums. The project was funded by three French institutions (the CNRS, INRA and MNHN), and provided access to the sequencing power offered by the Genoscope for 105 teams between 2011 and 2013. It was subsequently supported by the CNRS through the “Groupement de Recherche Génomique Environnementale”. The scientific objectives of this programme were threefold: 1) species delimitation among species complexes; 2) phylogenetic reconstruction (including phylogenomics); and 3) metabarcoding and improving NGS methods for systematic purposes. Within the present collection, 19 papers contribute to these objectives across a large taxonomic range and a worldwide geographic coverage. These papers propose taxonomic novelties (22 new species and 3 new genera) in both animal and plant taxa.
Land surface and hydrologic models (LSMs/HMs) are used at diverse spatial resolutions ranging from catchment-scale (1–10 km) to global-scale (over 50 km) applications. Applying the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the chosen resolution, i.e., fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent hydrologic parameter fields. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB, and WaterGAP models demonstrate the pitfalls of deficient parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge's 1982 statement on the unsolved problem of parameterization in these models remains true. Based on a review of existing parameter regionalization techniques, we postulate that the multiscale parameter regionalization (MPR) technique offers a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. Herein, we develop a general model protocol to describe how MPR can be applied to a particular model and present an example application using the PCR-GLOBWB model. Finally, we discuss potential advantages and limitations of MPR in obtaining the seamless prediction of hydrological fluxes and states across spatial scales.
Land surface and hydrologic models (LSM/HM) are used at diverse spatial resolutions ranging from 1-10 km in catchment-scale applications to over 50 km in global-scale applications. Application of the same model structure at different spatial scales requires that the model estimates similar fluxes independent of the model resolution and fulfills a flux-matching condition across scales. An analysis of state-of-the-art LSMs and HMs reveals that most do not have consistent and realistic parameter fields for land surface geophysical properties. Multiple experiments with the mHM, Noah-MP, PCR-GLOBWB and WaterGAP models are conducted to demonstrate the pitfalls of poor parameterization practices currently used in most operational models, which are insufficient to satisfy the flux-matching condition. These examples demonstrate that J. Dooge’s 1982 statement on the unsolved problem of parameterization in these models remains true. We provide a short review of existing parameter regionalization techniques and discuss a method for obtaining seamless hydrological predictions of water fluxes and states across multiple spatial resolutions. The multiscale parameter regionalization (MPR) technique is a practical and robust method that provides consistent (seamless) parameter and flux fields across scales. A general model protocol is presented to describe how MPR can be applied to a specific model, with an example of this application using the PCR-GLOBWB model. Applying MPR to PCR-GLOBWB substantially improves the flux-matching condition. Estimation of evapotranspiration without MPR at 5 arcmin and 30 arcmin spatial resolutions for the Rhine river basin results in a difference of approximately 29%. Applying MPR reduce this difference to 9%. For total soil water, the differences without and with MPR are 25% and 7%, respectively.
It has been noted (Perkins, 2009; Zwaan, 1999; Zwaan & Radvansky, 1998) that causality, character, location, and time are the four main aspects of narrative discourse, even if not attended to by listeners or readers in equal ways. For example, character is highly ranked, and the locational/spatial components have often been underestimated for English narratives (see Perkins, 2009, for a review). Relative to the ranking, there is no inherent reason why character needs to be highly ranked, and locational/spatial information is in fact important in English narrative discourse (Perkins, 2009). I instead suggest that there are linguistic and cultural factors in the ranking of these aspects of discourse. Specifically, I suggest that causality is (probably) the highest ranked component, in languages that have a ranking, with the other three elements being linked to causality more or less strongly, depending on linguistic and cultural factors; it is possible that some languages do not rank narrative elements or that some elements are ranked as highly as others. In English, the strongest link is between causality and character. However, this is not universal.
In a survey of fifty-eight languages from thirty language families, including an in-depth study of Hobongan, an Austronesian language spoken by approximately two thousand people on the island of Borneo that I am in the process of describing, it is found that there is a great deal of cross-linguistic variation, to the extent that it is possible that each logically possible combination of narrative elements is present in the world’s languages.
The object of this study is one of the most ambitious projects of twentieth-century art history: Aby Warburg's 'Atlas Mnemosyne', conceived in the summer of 1926 – when the first mention of a 'Bilderatlas', or "atlas of images", occurs in his journal – and truncated three years later, unfinished, by his sudden death in October 1929. Mnemosyne consisted in a series of large black panels, about 170x140 cm., on which were attached black-and-white photographs of paintings, sculptures, book pages, stamps, newspaper clippings, tarot cards, coins, and other types of images. Warburg kept changing the order of the panels and the position of the images until the very end, and three main versions of the Atlas have been recorded: one from 1928 (the "1-43 version", with 682 images); one from the early months of 1929, with 71 panels and 1050 images; and the one Warburg was working on at the time of his death, also known as the "1-79 version", with 63 panels and 971 images (which is the one we will examine). But Warburg was planning to have more panels – possibly many more – and there is no doubt that Mnemosyne is a dramatically unfinished and controversial object of study.
El texto se propone exponer críticamente algunos contenidos fundamentales del concepto de totalidad y su importancia para el pensamiento dialéctico. Partiendo de una crítica de la concepción hegeliana de totalidad, busca sin embargo defender este concepto, aunque reconstruido desde un giro materialista a partir de la filosofía desarrollada por Theodor W. Adorno. El concepto de totalidad cambiaría su significado y función a partir de la crítica materialista, pasando de la idea de un todo determinado y definitivo, a un criterio epistemológico y normativo para oponerse con efectividad a la imposición de una totalidad social.
Tortonian teleost otoliths from northern Italy: taxonomic synthesis and stratigraphic significance
(2017)
The Tortonian fish otoliths of northern Italy have been studied for more than a century and represent one of the best known otolith-based teleost faunas in the Miocene of the Mediterranean Basin. Yet with the growing knowledge on Recent otoliths, an updated taxonomic overview of this fauna is needed. Moreover, new material from hemipelagic Tortonian marls sampled at nine localities is described herein, revealing 109 taxa of which 88 are recognised at species level. Four of these are new: Coryphaenoides biobtusus sp. nov., “Merluccius” rattazzii sp. nov., Neobythites auriculatus sp. nov. and Lesueurigobius stironensis sp. nov. The compilation of previously studied and newly acquired material revealed a total of 118 nominal Tortonian species. At generic level, the fauna is characterised by many modern forms; more than 90% can be assigned to present day genera. At species level, however, more than half of the represented taxa are extinct. Based on the fossil otolith record, the Tortonian fauna of the Mediterranean is most similar to that of the Langhian (Badenian) of the Central Paratethys by sharing many extinct Miocene species, but it is also very close to that of the Pliocene Mediterranean, by sharing many modern Atlantic-Mediterranean forms. The Tortonian fauna is further characterised by many species that are apparently confined to the upper Miocene, resulting in a unique combination of its taxonomic composition.
Bevor ich mich im Folgenden von Spinoza ausgehend der Frage des 'mischpat ivri' zuwende und die Frage stelle, welche Rolle die Idee der Torah als Staatsrecht im modernen Israel spielt, möchte ich kurz in Erinnerung rufen, was wir historisch über die Torah im Alten Israel und aus dem antiken bzw. spätantiken Judentum wissen. Ich beginne also bei Spinoza, gehe dann kurz in die tiefere Vergangenheit und wende mich dann der zionistischen und israelischen Beschäftigung mit dem hebräischen Recht zu. Der Bezug auf die Torah als Staatsrecht bewegt sich sowohl im Fall der Staatstheorie der Frühen Neuzeit als auch im Fall des 'mischpat ivri' auf der dreifachen Grenze von Religionsquelle, Gelehrtentradition und Politik bzw. Entwürfen der Gesellschaftsgestaltung. Ohne das hier weiter theoretisch reflektieren zu können, gehören diese Beobachtungen meines Erachtens in den Bereich der hier verhandelten Fragen um das Verhältnis von Religion und Kulturwissenschaft.
This paper analyses the bail-in tool under the BRRD and predicts that it will not reach its policy objective. To make this argument, this paper first describes the policy rationale that calls for mandatory PSI. From this analysis the key features for an effective bail-in tool can be derived. These insights serve as the background to make the case that the European resolution framework is likely ineffective in establishing adequate market discipline through risk-reflecting prices for bank capital. The main reason for this lies in the avoidable embeddedness of the BRRD’s bail-in tool in the much broader resolution process which entails ample discretion of the authorities also in forcing private sector involvement. Finally, this paper synthesized the prior analysis by putting forward an alternative regulatory approach that seeks to disentangle private sector involvement as a precondition for effective bank-resolution as much as possible form the resolution process as such.
This paper analyzes the bail-in tool under the Bank Recovery and Resolution Directive (BRRD) and predicts that it will not reach its policy objective. To make this argument, this paper first describes the policy rationale that calls for mandatory private sector involvement (PSI). From this analysis, the key features for an effective bail-in tool can be derived.
These insights serve as the background to make the case that the European resolution framework is likely ineffective in establishing adequate market discipline through risk-reflecting prices for bank capital. The main reason for this lies in the avoidable embeddedness of the BRRD’s bail-in tool in the much broader resolution process, which entails ample discretion of the authorities also in forcing private sector involvement. Moreover, the idea that nearly all positions on the liability side of a bank’s balance sheet should be subjected to bail-in is misguided. Instead, a concentration of PSI in instruments that fall under the minimum requirements for own funds and eligible liabilities (MREL) is preferable.
Finally, this paper synthesized the prior analysis by putting forward an alternative regulatory approach that seeks to disentangle private sector involvement as a precondition for effective bank-resolution as much as possible form the resolution process as such.
Mara Kollien beschäftigt sich im Beitrag "Tod und Sterben in der zeitgenössischen Filmkomödie" buchstäblich mit dem Unerfahrbarem, dem Tod als Gegenstand der zeitgenössischen Filmkomödie. Vor dem Hintergrund kultureller Zugangs- und Umgangsweisen mit dem Tod identifiziert die Autorin den humoresken Umgang mit dem Verdrängten als Möglichkeit einer distanzierten Annäherung.
To imitate all that is hidden. The place of mimesis in Adorno’s theory of musical performance
(2017)
The article examines the use of the concept of mimesis in Adorno’s notes towards a theory of musical performance. In trying to idiosyncratically define the latter as “reproduction”, Adorno relied on a framework elaborating on concepts introduced by Arnold Schoenberg, Hugo Riemann and Walter Benjamin – a framework that the article discusses insofar as it deals with the problem of mimesis. Specific attention is devoted to the relation between Benjamin’s essays on language and translation and Adorno’s theory of notation, that soon became the crucial aspect of his theory of reproduction. Given the shortcomings of Adorno’s theory, which in the end did not achieve its goals, the article proposes to capitalize on his terminology while at the same time rethinking his framework in the light of recent musicological paradigms for the study of musical performance. On the whole, the article shows that it was Adorno’s philosophical assumptions – in particular the theses of music’s non-intentionality and of its non-similarity to language – that prevented him from convincingly theorizing musical performance, and suggests an alternative framework for future research.
The neutron capture cross section of several key unstable isotopes acting as branching points in the s-process are crucial for stellar nucleosynthesis studies, but they are very challenging to measure due to the difficult production of sufficient sample material, the high activity of the resulting samples, and the actual (n,γ) measurement, for which high neutron fluxes and effective background rejection capabilities are required. As part of a new program to measure some of these important branching points, radioactive targets of 147Pm and 171Tm have been produced by irradiation of stable isotopes at the ILL high flux reactor. Neutron capture on 146Nd and 170Er at the reactor was followed by beta decay and the resulting matrix was purified via radiochemical separation at PSI. The radioactive targets have been used for time-of-flight measurements at the CERN n_TOF facility using the 19 and 185 m beam lines during 2014 and 2015. The capture cascades were detected using a set of four C6D6 scintillators, allowing to observe the associated neutron capture resonances. The results presented in this work are the first ever determination of the resonance capture cross section of 147Pm and 171Tm. Activation experiments on the same 147Pm and 171Tm targets with a high-intensity 30 keV quasi-Maxwellian flux of neutrons will be performed using the SARAF accelerator and the Liquid-Lithium Target (LiLiT) in order to extract the corresponding Maxwellian Average Cross Section (MACS). The status of these experiments and preliminary results will be presented and discussed as well.
Neurogenesis of hippocampal granule cells (GCs) persists throughout mammalian life and is important for learning and memory. How newborn GCs differentiate and mature into an existing circuit during this time period is not yet fully understood. We established a method to visualize postnatally generated GCs in organotypic entorhino-hippocampal slice cultures (OTCs) using retroviral (RV) GFP-labeling and performed time-lapse imaging to study their morphological development in vitro. Using anterograde tracing we could, furthermore, demonstrate that the postnatally generated GCs in OTCs, similar to adult born GCs, grow into an existing entorhino-dentate circuitry. RV-labeled GCs were identified and individual cells were followed for up to four weeks post injection. Postnatally born GCs exhibited highly dynamic structural changes, including dendritic growth spurts but also retraction of dendrites and phases of dendritic stabilization. In contrast, older, presumably prenatally born GCs labeled with an adeno-associated virus (AAV), were far less dynamic. We propose that the high degree of structural flexibility seen in our preparations is necessary for the integration of newborn granule cells into an already existing neuronal circuit of the dentate gyrus in which they have to compete for entorhinal input with cells generated and integrated earlier.
Three new species of Kynotus from the Central Highlands of Madagascar (Clitellata, Megadrili)
(2017)
The earthworm fauna of Madagascar is scarcely known. A recently launched exploration of the soil fauna (“Global Change and Soil Macrofauna Diversity in Madagascar”) resulted in the discovery of six new earthworm species belonging to the Malagasy endemic family Kynotidae. The success of the collecting campaign carried out between 2008 and 2011 inspired a new exploration of the earthworm fauna across the Central Highland Region of the island in the spring of 2015. During this expedition, two new species of Kynotus, K. ankisiranus sp. nov. and K. voimmanus sp. nov., were discovered. Barcoding of the recently collected species of Kynotus revealed that the unpigmented worms referred previously to K. alaotranus Michaelsen, 1897 also represented a new, still undescribed species, K. blancharti sp. nov.