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Die HBO-Serie The Wire erzählt eine Geschichte von Kriminalität, Polizeiarbeit und Politik in Baltimore. Eine ihrer Stärken liegt darin, wie sie die Ambivalenz des sozialen und politischen Lebens nachzeichnet. Eine zentrale Rolle spielt dabei allgegenwärtige Korruption. Ihre Ambivalenz bricht sich nicht zuletzt in der Darstellung der Figur des State Senator Clay Davis.
Limb loss is a devastating disability and while current treatments provide aesthetic and functional restoration, they are associated with complications and risks. The optimal solution would be to harness the body's regenerative capabilities to regrow new limbs. Several methods have been tried to regrow limbs in mammals, but none have succeeded. One such attempt, in the early 1970s, used electrical stimulation and demonstrated partial limb regeneration. Several researchers reproduced these findings, applying low voltage DC electrical stimulation to the stumps of amputated rat forelimbs reporting "blastema, and new bone, bone marrow, cartilage, nerve, skin, muscle and epiphyseal plate formation". In spite of these encouraging results this research was discontinued. Recently there has been renewed interest in studying electrical stimulation, primarily at a cellular and subcellular level, and studies have demonstrated changes in stem cell behavior with increased proliferation, differentiation, matrix formation and migration, all important in tissue regeneration. We applied electrical stimulation, in vivo, to the stumps of amputated rat limbs and observed significant new bone, cartilage and vessel formation and prevention of neuroma formation. These findings demonstrate that electricity stimulates tissue regeneration and form the basis for further research leading to possible new treatments for regenerating limbs.
Promove-se uma recuperação do debate endógeno estabelecido entre alguns pensadores da Escola de Frankfurt, sobretudo no que se refere às diferentes perspectivas de análise sobre as relações entre ação e estrutura social, bem como as distintas percepções acerca das racionalidades (prática ou comunicativa) que organizam a conexão entre os indivíduos e a sociedade. Verifica-se o modo como os autores ligados à teoria crítica compreenderam as relações entre esferas subjetivas e estruturais em termos de possibilidades de emancipação social e de exercício de práticas deliberativas. Nessa perspectiva, considera-se uma cisão teórica estabelecida no interior da própria escola, cuja expressão se dá a partir das diferenças epistemológicas existentes entre o núcleo central do pensamento frankfurtiano e um conjunto de autores periféricos. Os trabalhos produzidos por esse núcleo “marginal”, bem como seu posterior refinamento na obra de Habermas, apresentam alternativas teóricas de caráter relacional que contrapõem a visão estrutural e cética presente nos trabalhos de Horkheimer, Adorno e Marcuse. É justamente na recuperação dessas fronteiras endógenas que se pretende ponderar as possíveis contribuições do pensamento frankfurtiano para uma perspectiva crítica da sociedade contemporânea.
Although much is known about the critical importance of active verbal rehearsal for successful recall, knowledge about the mechanisms of rehearsal and their respective development in children is very limited. To be able to rehearse several items together, these items have to be available, or, if presented and rehearsed previously, retrieved from memory. Therefore, joint rehearsal of several items may itself be considered recall. Accordingly, by analyzing free recall, one cannot only gain insight into how recall and rehearsal unfold, but also into how principles that govern children’s recall govern children’s rehearsal. Over a period of three and a half years (beginning at grade 3) 54 children were longitudinally assessed seven times on several overt rehearsal free recall trials. A first set of analyses on recall revealed significant age-related increases in the primacy effect and an age-invariant recency effect. In the middle portion of the list, wave-shaped recall characteristics emerged and increased with age, indicating grouping of the list into subsequences. In a second set of analyses, overt rehearsal behavior was decomposed into distinct rehearsal sets. Analyses of these sets revealed that the distribution of rehearsals within each set resembled the serial position curves with one- or two-item primacy and recency effects and wave-shaped rehearsal patterns in between. In addition, rehearsal behavior throughout the list was characterized by a decreasing tendency to begin rehearsal sets with the first list item. This result parallels the phenomenon of beginning recall with the first item on short lists and with the last item on longer lists.
Background: Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown.
Methods: We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine.
Results: Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. Conclusions: The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.
Synesthesia is a phenomenon in which additional perceptual experiences are elicited by sensory stimuli or cognitive concepts. Synesthetes possess a unique type of phenomenal experiences not directly triggered by sensory stimulation. Therefore, for better understanding of consciousness it is relevant to identify the mental and physiological processes that subserve synesthetic experience. In the present work we suggest several reasons why synesthesia has merit for research on consciousness. We first review the research on the dynamic and rapidly growing field of the studies of synesthesia. We particularly draw attention to the role of semantics in synesthesia, which is important for establishing synesthetic associations in the brain. We then propose that the interplay between semantics and sensory input in synesthesia can be helpful for the study of the neural correlates of consciousness, especially when making use of ambiguous stimuli for inducing synesthesia. Finally, synesthesia-related alterations of brain networks and functional connectivity can be of merit for the study of consciousness.
African trypanosomes cause a parasitic disease known as sleeping sickness. Mitochondrial transcript maturation in these organisms requires a RNA editing reaction that is characterized by the insertion and deletion of U-nucleotides into otherwise non-functional mRNAs. Editing represents an ideal target for a parasite-specific therapeutic intervention since the reaction cycle is absent in the infected host. In addition, editing relies on a macromolecular protein complex, the editosome, that only exists in the parasite. Therefore, all attempts to search for editing interfering compounds have been focused on molecules that bind to proteins of the editing machinery. However, in analogy to other RNA-driven biochemical pathways it should be possible to stall the reaction by targeting its substrate RNAs. Here we demonstrate inhibition of editing by specific aminoglycosides. The molecules bind into the major groove of the gRNA/pre-mRNA editing substrates thereby causing a stabilization of the RNA molecules through charge compensation and an increase in stacking. The data shed light on mechanistic details of the editing process and identify critical parameters for the development of new trypanocidal compounds.
This thesis covers the analysis of radix sort, radix select and the path length of digital trees under a stochastic input assumption known as the Markov model.
The main results are asymptotic expansions of mean and variance as well as a central limit theorem for the complexity of radix sort and the path length of tries, PATRICIA tries and digital search trees.
Concerning radix select, a variety of different models for ranks are discussed including a law of large numbers for the worst case behavior, a limit theorem for the grand averages model and the first order asymptotic of the average complexity in the quantile model.
Some of the results are achieved by moment transfer techniques, the limit laws are based on a novel use of the contraction method suited for systems of stochastic recurrences.
Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.
In der Großregion Saarland-Lothringen-Luxemburg-Rheinland-Pfalz-Wallonie-Deutsch-sprachige Gemeinschaft Belgiens ist ein rasanter demografischer Wandel zu erwarten, die Altersstruktur der Bevölkerung wird sich erheblich verändern. Die Zahl der über 80-jährigen, hochaltrigen Einwohnerinnen und Einwohner in der Großregion wird bis zum Jahr 2030 voraussichtlich um 29,4% steigen. Im Jahr 2013 lebten 626.065 Menschen im Alter von über 80 Jahren in der Großregion, im Jahr 2030 werden es 812.657 sein. Besonders stark dürfte der Anstieg der hochaltrigen Bevölkerung in der DG Belgien (+44,4%) und in Luxemburg (+36,2%) ausfallen. Da mit einer älter werdenden Bevölkerung auch die Zahl der Personen steigt, die auf professionelle Pflege angewiesen sind, steht die Großregion vor folgender Herausforderung: Mit einer ausreichenden Zahl an Pflegekräften muss die pflegerische Versorgung für den erhöhten Bedarf sichergestellt werden. Dafür ist eine Bedarfsanalyse für die kommenden Jahre notwendig.
This study examines the urban heat island (UHI) of Brussels, for both current (2000–2009) and projected future (2060–2069) climate conditions, by employing very high resolution (250 m) modelling experiments, using the urban boundary layer climate model UrbClim. Meteorological parameters that are related to the intensity of the UHI are identified and it is investigated how these parameters and the magnitude of the UHI evolve for two plausible trajectories for future climate conditions. UHI intensity is found to be strongly correlated to the inversion strength in the lowest 100 m of the atmosphere. The results for the future scenarios indicate that the magnitude of the UHI is expected to decrease slightly due to global warming. This can be attributed to the increased incoming longwave radiation, caused by higher air temperature and humidity values. The presence of the UHI also has a significant impact on the frequency of extreme temperature events in the city area, both in present and future climates, and exacerbates the impact of climate change on the urban population as the amount of heat wave days in the city increases twice as fast as in the rural surroundings.
Background: Emerging evidence indicates that mesenchymal stromal cells (MSCs) isolated from different tissue sources may be used in vivo as tissue restorative agents. To date, there is no evidence, however, on migration and proliferation ("wound healing") potential of different subsets of MSCs. The main goal of this study was therefore to compare the in vitro "wound healing" capacity of MSCs generated from positively selected CD271+ bone marrow mononuclear cells (CD271-MSCs) and MSCs generated by plastic adherence (PA-MSCs).
Methods: The in vitro model of wound healing (CytoSelect™ 24-Well Wound Healing Assay) was used in order to compare the migration and proliferation potential of CD271-MSCs and PA-MSCs of passage 2 and 4 cultured in presence or absence of growth factors or cytokines.
Results: CD271-MSCs of both passages when compared to PA-MSCs demonstrated a significantly higher potential to close the wound 12 and 24 h after initiation of the wound healing assay (P < 0.003 and P < 0.002, respectively). Noteworthy, the migration capacity of PA-MSCs of second passage was significantly improved after stimulation with FGF-2 (P < 0.02), PDGF-BB (P < 0.006), MCP-1 (P < 0.002) and IL-6 (P < 0.03), whereas only TGF-β enhanced significantly migration process of PA-MSCs of P4 12 h after the treatment (P < 0.02). Interestingly, treatment of CD271-MSCs of both passages with growth factors or cytokines did not affect their migratory potential.
Conclusions: Our in vitro data provide the first evidence that CD271-MSCs are significantly more potent in "wound healing" than their counterparts PA-MSCs.
Type 1 Diabetes (T1D) is an autoimmune disorder in which the own immune system attacks the insulin producing _-cells in the pancreas. Therapy of T1D with anti-CD3 antibodies (aCD3) leads to a blockade of the autoimmune process in animal models and patients resulting in reduced insulin need. Unfortunately, this effect is only temporal and the insulin need increases after a few years. In the first approach, I aimed at a blockade of the cellular re-entry into the islets of Langerhans after aCD3 treatment by neutralising the key chemokine CXCL10, which is important for the T cell migration. In the second approach I tried to block the transmigration of leukocytes trough the endothelial layer into inflamed tissue with an anti-JAM-C antibody (aJAM-C) after aCD3 treatment.
I used the well-established RIP-LCMV-GP mouse model of T1D. As target autoantigen in the _-cells, such mice express the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP). These mice develop T1D within 10 to 14 days only after LCMV-infection. In the combination therapy (CT) I treated diabetic RIP-LCMV-GP mice with 3 5g aCD3 per mouse (3 injections in 3 days) followed by administration of a neutralising anti-CXCL10 (CT) or aJAM-C (CT-J) monoclonal antibody (8 injections of 100 5g per mouse over 2.5 weeks).
CT reverted T1D in RIP-LCMV-GP mice significantly (CT: 67 % reversion; control: 16 % reversion) and with superior efficacy to monotherapies with aCD3 (38 % reversion) and aCXCL10 (36 % reversion).
The CD8 T cells in the spleen have fully regenerated at day 31 after infection. However, the frequency of islet antigen (GP)-specific CD8 T-cells was significantly reduced by 73 % in the spleen after CT compared to isotype control treated mice. In contrast, in aCD3 treated mice the T cells were only reduced by 56 % of the frequency of isotype control treated mice. Flow cytometry and immunohistological examinations demonstrated a marked reduction of CD8 T cells in the pancreas of CT treated mice. Importantly, the number of GP-specific CD8 T cells was reduced dramatically by 78 % in the pancreas of CT treated mice, whereas aCD3 treatment led to a less pronounced reduction of the GP-specific CD8 T cell number (23 %). This reduction of infiltration was long lasting since in the pancreas of CT treated mice the _-cells produce insulin and there were almost no infiltrating T cells present at day 182 post-infection. aCD3 treated mice also showed many insulin producing cells after 182 days post-infection. Nevertheless, their pancreas displayed also some infiltrates around the islets.
In order to confirm my data I treated non-obese diabetic (NOD) mice with CT. In contrast to RIP-LCMV-GP mice, NOD mice develop spontaneous T1D within 15 to 30 weeks after birth, due to a mutation in the CTLA-4 gene. Strikingly CT cured 55 % of diabetic NOD mice, whereas only 30 % showed T1D reversion with aCD3 alone and none reverted after isotype control administration.
The impact of CT on GP-specific T cells (Teff) was stronger in the RIP LCMV-GP than in the NOD model. In contrast, regulatory T cells (Tregs) were induced predominantly in NOD mice rather than in RIP-LCMV-GP mice. However, looking at the Treg/Teff ratio and compared to isotype control antibody treated mice, I found a significant 4-fold increase in the pancreas of CT treated RIP LCMV-GP mice and a 17-fold increase in the PDLN of CT treated NOD mice. In addition, a tendency for an increase in Treg/Teff ratio was obtained in the spleen of CT-treated RIP LCMV-GP as well as NOD mice compared to aCD3 and isotype control antibody treated mice.
In the second combination therapy with neutralising aJAM-C, CT-J (51 % reversion) slightly improved the aCD3 therapy (41 % reversion). However, there was no significant difference between CT-J and aCD3 administration in terms of total CD8 and GP-specific CD8 T cells.
JAM-C also interacts with the integrin receptor macrophage-1 antigen (MAC-1), which is among others expressed by neutrophils. Accordingly, JAM-C could be involved in neutrophil transmigration to the pancreas. Indeed, I found a significant reduction for the infiltrating neutrophils into the pancreas of mice after CT-J compared to aCD3 monotherapy.
In summary the addition of aJAM-C to aCD3 monotherapy showed a small improvement, which was associated with a reduced neutrophil migration into the pancreas. However, JAM C seemed to play only a minor role in T1D development and some other adhesion molecules might be more important. Nevertheless, the combination of aCD3 and aCXCL10 resulted in a significant and long lasting reduction of aggressive T cells in the pancreas in two independent mouse models. Furthermore a protective immune balance was obtained. Since both antibodies are available for as well as tested in humans and the therapy is only for a short period of time after disease onset, this combination therapy might kick-start a novel therapy for T1D.
The increasing number of casting shows and talent contests in the media over the past years suggests a public interest in rating the quality of vocal performances. In many of these formats, laymen alongside music experts act as judges. Whereas experts' judgments are considered objective and reliable when it comes to evaluating singing voice, little is known about laymen's ability to evaluate peers. On the one hand, layman listeners–who by definition did not have any formal training or regular musical practice–are known to have internalized the musical rules on which singing accuracy is based. On the other hand, layman listeners' judgment of their own vocal skills is highly inaccurate. Also, when compared with that of music experts, their level of competence in pitch perception has proven limited. The present study investigates laypersons' ability to objectively evaluate melodies performed by untrained singers. For this purpose, laymen listeners were asked to judge sung melodies. The results were compared with those of music experts who had performed the same task in a previous study. Interestingly, the findings show a high objectivity and reliability in layman listeners. Whereas both the laymen's and experts' definition of pitch accuracy overlap, differences regarding the musical criteria employed in the rating task were evident. The findings suggest that the effect of expertise is circumscribed and limited and supports the view that laypersons make trustworthy judges when evaluating the pitch accuracy of untrained singers.
Currently, the structure of the X(3872) meson is unknown. Different competing models of the exotic state X(3872) exist, including the possibilities that this state is either a mesonic molecule with dominating D0D¯ ∗0 + c.c. composition, a tetraquark, or a -gluon hybrid state. It is expected that the X(3872) state is rather strongly coupled to the channel and, therefore, can be produced in and collisions at PANDA. We propose to test the hypothetical molecular structure of by studying the D or D¯⁎ stripping reactions on a nuclear residue.
El artículo, después de haber tratado la cuestión del tiranicidio en Tomás de Aquino y en Bartolo de Sassoferrato, muestra cómo Francisco de Vitoria, consciente de las soluciones que ofrecen los autores anteriores a él, afronta el argumento de forma innovadora, aunque en línea con la tradición anterior. En la base de la solución que propone Vitoria, se encuentra, en efecto, la afirmación de un derecho a la auto-defensa, entendido como derecho natural inalienable que reside en los individuos y en las comunidades; un derecho que siempre lo pueden ejercer los súbditos en relación con un gobernante que se convierte en tirano. Vitoria expresa de este modo el principio de resistencia a la autoridad injusta e ilegal en los términos de un derecho subjetivo, el de la auto-defensa, pero, al mismo tiempo, señala los límites afirmando la necesidad de cada individuo de respetar y someterse a un orden de justicia objetivo. De aquí su prohibición a un particular de matar a un hombre, aunque sea un tirano, sin un justo procedimiento jurídico. Así pues, el artículo muestra, a través del debate sobre la licitud del tiranicidio cómo en la obra de Vitoria se encuentra una teoría sólida de la soberanía juntamente con la afirmación tenaz de derechos naturales individuales. En efecto, Vitoria retoma, por una parte, una tradición de pensamiento para la que la formación de las sociedades políticas era la consecuencia de la sociabilidad natural de los hombres; y por otra, desarrollaba una teoría coherente de los derechos subjetivos a partir de la necesidad misma de los individuos de asociarse los unos con los otros para los fines de una vida éticamente justa y gratificante.
Cancer is characterized by a remarkable intertumoral, intratumoral, and cellular heterogeneity that might be explained by the cancer stem cell (CSC) and/or the clonal evolution models. CSCs have the ability to generate all different cells of a tumor and to reinitiate the disease after remission. In the clonal evolution model, a consecutive accumulation of mutations starting in a single cell results in competitive growth of subclones with divergent fitness in either a linear or a branching succession. Acute lymphoblastic leukemia (ALL) is a highly malignant cancer of the lymphoid system in the bone marrow with a dismal prognosis after relapse. However, stabile phenotypes and functional data of CSCs in ALL, the so-called leukemia-initiating cells (LICs), are highly controversial and the question remains whether there is evidence for their existence. This review discusses the concepts of CSCs and clonal evolution in respect to LICs mainly in B-ALL and sheds light onto the technical controversies in LIC isolation and evaluation. These aspects are important for the development of strategies to eradicate cells with LIC capacity. Common properties of LICs within different subclones need to be defined for future ALL diagnostics, treatment, and disease monitoring to improve the patients’ outcome in ALL.
The success stories of design-oriented companies like Apple, Audi or Nike have put design on the agenda in many marketing departments. Consumers cannot elude the effect of aesthetics and therefore design is a major factor for business success. Typically consumers choose the product with the best design, all other aspects being equal. Only when the interplay of product characteristics, brand and design is carefully coordinated can successful products be created. This requires an integrated approach to design, one which is applied right at the beginning of the value chain. Product development, marketing and design need to work in close cooperation, communicate well and frequently, and collect feedback from the market. Superior aesthetics are always important but should be a top priority in cases where efficiency-oriented Asian competitors are able to offer functionally similar products at much lower prices.
This thesis develops a conceptual framework for a better understanding of the impact of slow-onset climate and environmental changes on human migration in developing countries. Its regional focus is on the West African Sahel, where the majority of the population depends on agriculture and thus is highly vulnerable to environmental changes. Migration from fragile environments is predominantly considered one of several household strategies to adapt to and minimise the risk of environmental stress. Based on qualitative and quantitative data from two selected rural study areas, Bandiagara in Mali and Linguère in Senegal, this thesis analyses the drivers of migration from the two areas.
The findings illustrate that, even though people highly depend on the natural environment, migration motives are manifold and that migration often is not a household strategy to cope with environmental changes. Although environmental conditions shape migration in the region and the migrants’ support is crucial for most households, environmental stress plays a relatively small role as a driver of migration - at least in Mali, where it is considerably less important than in Senegal. On the contrary, migration is often driven by better opportunities elsewhere rather than by livelihood stressors in the home area. Particularly the migration of young people is often an individual rather than a household decision and influenced by individual aspirations, such as aspirations for consumer goods or a better future, rather than by environmental stress.
This thesis claims that research should consider people’s capabilities to migrate or to stay as well as their individual aspirations and preferences - in addition to the household’s needs and the opportunities elsewhere. This is important in order to explain why some people stay in and others migrate from an area affected by environmental stress, though living under similar conditions. Depending on people’s capabilities to choose freely between staying and migrating and their preferences and aspirations for one or the other activity, people can either be “voluntary migrants”, “voluntary non-migrants”, “forced migrants” or “trapped people”.
Moreover, it is important to consider social trends and transformation processes in the analysis of the linkages between environment change and migration. Higher education levels and aspirations to a “modern” lifestyle among young people, for instance, might decrease the impact of environmental factors on migration, despite worsening environmental conditions.
CLOUD COMPUTING PROMISES ENHANCED FLEXIBILITY AND SUBSTANTIAL ECONOMIC
BENEFITS THROUGH THE ON-DEMAND LEASE OF IT RESOURCES. THESE TWO ASPECTS ARE STRONGLY INFLUENCED BY THE PRICING OF CLOUD RESOURCES. BASED ON A SAMPLE OF 48 INFRASTRUCTURE PROVIDERS, WE EXAMINE CURRENT PRICING SCHEMES IN THE CLOUD MARKET FROM A USER PERSPECTIVE.
This paper explores how banks adjust their risk-based capital ratios and asset allocations following an exogenous shock to their asset quality caused by Hurricane Katrina in 2005. We find that independent banks based in the disaster areas increase their risk-based capital ratios after the hurricane, while those part of a bank holding company do not. The effect on independent banks mainly comes from the subgroup of high-capitalized banks. These banks increase their holdings in government securities and reduce loans to non-financial firms. Hence, banks that become more stable achieve this at the cost of reduced lending.
Macroautophagy requires membrane trafficking and remodelling to form the autophagosome and deliver its contents to lysosomes for degradation. We have previously identified the TBC domain‐containing protein, TBC1D14, as a negative regulator of autophagy that controls delivery of membranes from RAB11‐positive recycling endosomes to forming autophagosomes. In this study, we identify the TRAPP complex, a multi‐subunit tethering complex and GEF for RAB1, as an interactor of TBC1D14. TBC1D14 binds to the TRAPP complex via an N‐terminal 103 amino acid region, and overexpression of this region inhibits both autophagy and secretory traffic. TRAPPC8, the mammalian orthologue of a yeast autophagy‐specific TRAPP subunit, forms part of a mammalian TRAPPIII‐like complex and both this complex and TBC1D14 are needed for RAB1 activation. TRAPPC8 modulates autophagy and secretory trafficking and is required for TBC1D14 to bind TRAPPIII. Importantly, TBC1D14 and TRAPPIII regulate ATG9 trafficking independently of ULK1. We propose a model whereby TBC1D14 and TRAPPIII regulate a constitutive trafficking step from peripheral recycling endosomes to the early Golgi, maintaining the cycling pool of ATG9 required for initiation of autophagy.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4-H2O) system, and the ternary system involving ammonia (H2SO4-H2O-NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a Chemical Ionization Mass Spectrometer (CIMS). From these measurements dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) mass spectrometry.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4–H2O) system and the ternary system involving ammonia (H2SO4–H2O–NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a chemical ionization mass spectrometer (CIMS). From these measurements, dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248 K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using chemical ionization–atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometry.
Aerosolteilchen agieren als Kondensationskeime für Wolkentröpfchen (engl. Cloud Condensation Nuclei, CCN) oder Eiskristalle und sind deswegen für die Wolken- und Niederschlagsbildung entscheidend. Sowohl die Aerosolpartikel als auch die Wolken können Sonnenlicht effizient streuen, wodurch ein kühlender Effekt auf das Klima ausgeübt wird. Einige der Teilchen, wie z. B. aufgewirbelter Staub oder Seesalz, werden direkt in die Atmosphäre injiziert; der größte Anteil der Teilchen und etwa die Hälfte der CCN werden allerdings durch die Kondensation gasförmiger Substanzen gebildet. Dieser Prozess wird als Nukleation oder Partikelneubildung (engl. New Particle Formation, NPF) bezeichnet. Trotz intensiver Forschung ist die NPF noch nicht vollständig verstanden, was an der Komplexität der chemischen Abläufe in der Atmosphäre und an der Schwierigkeit liegt, die relevanten Substanzen bei extrem geringen Mischungsverhältnissen (etwa ein Molekül oder Cluster per 1012 bis 1015 Moleküle) zu identifizieren und zu quantifizieren. Neben der Frage nach den bei der Nukleation beteiligten Substanzen ist außerdem noch unklar, ob Ionen-induzierte Nukleation ein wichtiger Prozess für das Klima ist. Das CLOUD-Projekt (Cosmics Leaving OUtdoor Droplets) am CERN soll diesen Fragen nachgehen, indem dort die Partikelbildung in einem Kammer-Experiment unter extrem gut kontrollierten Bedingungen simuliert wird. Die chemischen Systeme, die in dieser Schrift diskutiert werden, umfassen das binäre (H2SO4-H2O), das ternäre Ammoniak (H2SO4-H2O-NH3) und das ternäre Dimethylamin (H2SO4-H2O-(CH3)2NH)-System.
Einige der wesentlichen Ergebnisse von Experimenten an der CLOUD-Kammer werden diskutiert. Diese zeigen, dass das binäre und das ternäre Ammoniak System die atmosphärische Nukleation bei niedrigen Temperaturen erklären können, wohingegen das ternäre Dimethylamin System prinzipiell in der Lage ist, die hohen bodennahen Nukleationsraten bei atmosphärisch relevanten Schwefelsäure-Konzentrationen zu beschreiben. Des Weiteren werden zwei für Nukleationsstudien wesentliche Messmethoden vorgestellt. Das Chemical Ionization Mass Spectrometer (CIMS) wird zur Messung von gasförmiger Schwefelsäure verwendet, da H2SO4 vermutlich die wichtigste Substanz bei der atmosphärischen Nukleation ist. Das Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) Massenspektrometer misst Schwefelsäure und neutrale Cluster. Beide Geräte wurden für den Einsatz bei CLOUD optimiert und instrumentelle Entwicklungen wurden in Bezug auf die Ionenquelle vorgenommen, die eine Korona-Entladung verwendet. Außerdem wurden eine Kalibrationseinheit zur Bereitstellung definierter Schwefelsäure-Konzentrationen entwickelt und das CI-APi-TOF aufgebaut. In Bezug auf das ternäre Dimethylamin System werden Nukleationsraten und die ersten Messungen von gro en nukleierenden neutralen Clustern präsentiert. Monomer- und Dimer-Konzentrationen der Schwefelsäure, die mit dem CIMS bei tiefen Temperaturen gemessen wurden, dienten der Ableitung der thermodynamischen Eigenschaften bei der Dimer-Bildung im binären und ternären Ammoniak System. Um möglichst exakte Nukleationsraten zu bestimmen, wurde eine neue Methode entwickelt, die es erlaubt, den Effekt der Selbst-Koagulation bei der Nukleation miteinzubeziehen.
Die zusammengefassten Studien tragen signifikant zum Verständnis der Partikelneubildung bei.
Teil VIII unserer Serie zum “Islamischen Staat”: "Blogforum 'Kalifat des Terrors: Interdisziplinäre Perspektiven auf den Islamischen Staat".
Die Kurden feiern in diesen Tagen den Sieg über den Islamischen Staat in Kobane. Die Hauptstadt des Distrikts Ain al-Arab im Gouvernement Aleppo in Syrien liegt nahe der syrisch-türkischen Grenze. Seit Anfang 2014 ist Ain al-Arab Zentrum eines der drei selbstverwalteten Kantone Rojavas. Diese Kantone stehen unter der Kontrolle der kurdischen “Partei der Demokratischen Union” (PYD) und ihrer Verbündeten. Die PYD ist eine Schwesterpartei der PKK, sie erkennt Abdullah Öcalan als ideologischen Führer an...
»In der Praxis läuft nicht alles so glatt, wie man es sich vorstellt …« : »Starker Start« als Tutor
(2015)
Bei den Baustrukturen der Pyramiden des Alten Reiches sind sehr große Unterschiede erkennbar, weist doch jede ein individuelles Inneres auf. Während die Cheops- Pyramide über ein sehr komplexes Kammersystem verfügt, das während des Baus sicherlich größere Komplikationen und damit auch einen höheren Zeitaufwand verursachte, ist bereits unter Chefren eine weitaus weniger komplexe Innenstruktur gewählt worden. In dessen Pyramide befindet sich die Sargkammer in Bodenhöhe, bei Mykerinos sind alle Kammern gänzlich unterhalb des Bodenniveaus. Diese Änderung der Bauweise resultierte sicher aus den Erfahrungen und Problemen beim Bau der Cheopspyramide. Diese ist über einem natürlichen Steinkern unbekannter Größe errichtet, wodurch sehr viel Baumaterial gespart werden konnte. Die Pyramiden der 5. und 6. Dynastie zeichnen sich wiederum durch eine gänzlich andere Bauweise als die der 4. Dynastie aus und sind weitaus kleiner konzipiert. Sehr selten sind Hinweise auf die zeitlichen Abläufe eines Pyramidenbaues zu finden, wie sie z.B. im Verlauf der Grabungen des Deutschen Archäologischen Institutes unter R. Stadelmann an der Roten Pyramide zutage kamen...
Bei dem vorliegenden Werk handelt es sich um die erste längere Monographie zu der Königin Teje überhaupt, wenn auch z.B. ihr Portraitkopf in Berlin des Öfteren in kürzerer Form Beachtung fand. Teje war die Große königliche Gemahlin von Amenophis III., Pharao der 18. Dynastie des Neuen Reiches, sowie die Mutter des Königs Echnaton und Schwiegermutter Nofretetes. Bei ihren Eltern handelt es sich um Juja und Tuja, deren Grab in Theben (KV46) bei der Auffindung 1905 noch mit zahlreichen Objekten versehen war, die heute im Ägyptischen Museum Kairo ausgestellt sind. So wurde z.B. neben den äußeren, mit Schlittenkufen versehenen Sarkophagen, Särgen, Kanopenkästen und vergoldeten Totenmasken einer der überaus wenigen heute vollständig erhaltenen Streitwagen aus pharaonischer Zeit in ihrem Grab gefunden...
Il saggio indaga le connessioni tra l’abolizione della prostituzione legalizzata e i processi di democratizzazione in Germania e Italia, a partire dalla storia dei diritti umani nella sua interazione con il sistema politico. Le fonti principali sono i dibattiti parlamentari e le leggi che portarono alla chiusura dei bordelli e all’abolizione del sistema di sorveglianza nel 1927 in Germania e nel 1958 in Italia. I dibattiti sulla prostituzione pongono anche la questione dell’uguaglianza e della giustizia di genere. In particolare, il problema della regolamentazione della prostituzione, la cui efficienza viene verificata da un numero sempre maggiore di ricercatori nel corso del XX secolo, dispiega fattori di politica sanitaria, di diritti umani e di morale, aspetti di politica sociale e di sicurezza, mettendo in discussione non solo la gerarchia tra i generi, ma anche quella tra gli strati sociali.
Over the last decade, the prospect of improving or maintaining cognitive functioning has provoked a steadily increasing number of cognitive training studies. Central target populations are individuals at risk for a disadvantageous development, such as older adults exhibiting cognitive decline or children with learning impairments. They rely on cognitive resources to meet the challenges of an independent life in old age or requirements at school.
To support daily cognitive functioning, training outcomes need to generalize to other cognitive abilities. Such transfer effects are, however, highly discussed. For example, recent meta-analyses on working memory training differed in the conclusion on the presence (Au et al., 2015; Karbach and Verhaeghen, 2014) or absence of transfer effects (Melby-Lervåg and Hulme, 2013). Usually training-specific design factors such as type, intensity, duration, and feedback routines are discussed as reasons for such inconsistent findings. However, even individuals participating in exactly the same training regime highly differ in their training outcomes. We argue that it is time to study the individual development during trainings to understand these differential outcomes. It is time to have a closer look at the intraindividual training data.
Die vorliegende Dissertation zeigt, dass globale Kohärenz in Lebenserzählungen erst in der Adoleszenz entsteht und sich im Erwachsenenalter weiter entwickelt. Außerdem konnte gezeigt werden, dass die fragmentarische Nutzung der Lebensgeschichte in Form autobiographischen Urteilens in Zeiten tiefgreifender Lebensveränderungen zum Erhalt der Selbst-Kontinuität beiträgt.
Die Arbeit mit Rechnungen bietet den Vorteil, dass es sich dabei fast immer um Originalquellen handelt. Rechnungen wurden üblicherweise nicht in Kompilationen aufgenommen oder nicht in Urkunden inseriert. Wenn sie abgeschrieben wurden, geschah das höchstens im Zuge des Abrechnungsprozesses und nicht, wie etwa bei Chroniken, um für ihre weitere Verbreitung zu sorgen. Unter den schriftlichen Quellen kommen die Rechnungen damit wohl der Definition eines Überrestes am nächsten: Sie wurden für die Mit-, nicht die Nachwelt erstellt. Das bringt allerdings den Nachteil mit sich, dass wir selten genau wissen, zu welchem Zweck eine Rechnung eigentlich verfertigt wurde. Keine Arenga klärt den Forscher über die Vorgeschichte und den Zusammenhang der Niederschrift auf. Erklärende Dokumente sind fast nie überliefert. Die Menschen, die Rechnungen erstellten und mit ihnen arbeiteten, lernten das durch und bei ihrer Arbeit, eventuell unter mündlicher Anleitung. ...
The planned Facility for Antiproton and Ion Research (FAIR) at GSI has to cope with a wide range of beam intensities in its high-energy beam transport systems and in the storage rings. To meet the requirements of a non-intercepting intensity measurement down to nA range, it is planned to install a number of Cryogenic Current Comparator (CCC) units at different locations in the FAIR beamlines. In this work, the first CCC system for intensity measurement of heavy ion beams, which was developed at GSI, was re-commissioned and upgraded to be used as a 'GSI - CCC prototype' for extensive optimization and development of an improved CCC for FAIR. After installation of a new SQUID sensor and related electronics, as well as implementation of improved data acquisition components, successful beam current measurements were performed at a SIS18 extraction line. The measured intensity values were compared with those of a Secondary Electron Monitor (SEM). Furthermore, the spill-structure of a slowly extracted beam was measured and analyzed, investigating its improvement due to bunching during the slow-extraction process. Due to the extreme sensitivity of the superconducting sensor, the determined intensity values as well as the adjustment of the system for optimal performance are strongly influenced by the numerous noise sources of the accelerators environment. For this reason, detailed studies of different effects caused by noise have been carried out, which are presented together with proposals to reduce them. Similarly, studies were performed to increase the dynamic range and overcome slew rate limitations, the results of which are illustrated and discussed as well. By combining the various optimizations and characterizations of the GSI CCC prototype with the experiences made during beam operation, criteria for a more efficient CCC System could be worked out, which are presented in this work. The details of this new design are worked out with respect to the corresponding boundary conditions at FAIR. Larger beam tube diameters, higher radiation resistivity and UHV requirements are of particular importance for the cryostat. At the same time these parameters affect the CCC superconducting magnetic shielding, which again has significant influence on the current resolution of the system. In order to investigate the influence of the geometry of the superconducting magnetic shield on different magnetic field components and to optimize the attenuation, FEM simulations have been performed. Based on the results of these calculations, modifications of the shield geometry for optimum damping behavior are proposed and discussed in the thesis.
This work proposes to employ the (bursty) GLO model from Bingmer et. al (2011) to model the occurrence of tropical cyclones. We develop a Bayesian framework to estimate the parameters of the model and, particularly, employ a Markov chain Monte Carlo algorithm. This also allows us to develop a forecasting framework for future events.
Moreover, we assess the default probability of an insurance company that is exposed to claims that occur according to a GLO process and show that the model is able to substantially improve actuarial risk management if events occur in oscillatory bursts.
Euro crash risk
(2015)
"Mehr Licht!", um die "Seele" der Natur zu erfassen – das verband die Impressionisten mit der vorangegangenen Künstlergeneration um Camille Corot. Claude Monet und seine Kollegen suchten die Wälder und Parks auf, um Licht, Atmosphäre und Farbigkeit in ihrer Malerei festzuhalten. Dabei reagierten sie eher intuitiv auf die in jener Zeit intensiv erforschten optischen Gesetzmäßigkeiten.
n this paper we compute the optimal tax and education policy transition in an economy where progressive taxes provide social insurance against idiosyncratic wage risk, but distort the education decision of households. Optimally chosen tertiary education subsidies mitigate these distortions. We highlight the importance of two different channels through which academic talent is transmitted across generations (persistence of innate ability vs. the impact of parental education) for the optimal design of these policies and model different forms of labor as imperfect substitutes, thereby generating general equilibrium feedback effects from policies to relative wages of skilled and unskilled workers. We show that subsidizing higher education has important redistributive benefits, by shrinking the college wage premium in general equilibrium. We also argue that a full characterization of the transition path is crucial for policy evaluation. We find that optimal education policies are always characterized by generous tuition subsidies, but the optimal degree of income tax progressivity depends crucially on whether transitional costs of policies are explicitly taken into account and how strongly the college premium responds to policy changes in general equilibrium.
Peter Oestmann unterscheidet in seiner Intervention drei Arten der Rechtsgeschichtsschreibung, die er Normen-, Wissenschafts- und Praxisgeschichte nennt. Als bekennender Vertreter der letzten Kategorie setzt er sich für deren Emanzipation von der rechtsdogmatischen "Normenkontrolle" ein. Er bezeichnet es als "unfair, wenn Vertreter der Normengeschichte erwarten, diejenigen, die sich mit der Rechtspraxis beschäftigen, müssten im gleichen Maße die Rechtsliteratur und normative Quellen in ihre Untersuchungen einbeziehen wie andere Rechtshistoriker auch" (8). Zugleich bricht er eine Lanze für die "erheblich unjuristischere" Rechtsgeschichte der Praxis (ebd.). Wir pflichten diesem Anliegen vorbehaltlos bei. Zugleich beobachten wir, dass Oestmanns Kritik an Grundlagen des rechtshistorischen Selbstverständnisses rührt, die zur Diskussion zu stellen im deutschsprachigen Raum erfahrungsgemäß schwer fällt. Auch bleibt Oestmann zu oft in den Kategorien des von ihm Kritisierten befangen. Unsere Replik setzt sich mit den historischen Ursachen dieses strukturellen Unbehagens in der Rechtsgeschichte auseinander.