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A number of recent studies regress a "narratively" identified measure of a macroeconomic shock directly on an outcome variable. In this note, we argue that this approach can be viewed as the reduced-form regression of an instrumental variable approach in which the narrative time series is used as an instrument for an endogenous series of interest. This motivates evaluating the validity of narrative measures through the lens of a randomized experiment. We apply our framework to four recently constructed narrative measures of tax shocks by Romer and Romer (2010), Cloyne (2013), and Mertens and Ravn (2012). All of them turn out to be weak instruments for observable measures of taxes. After correcting for weak instruments, we find that using any of the considered narrative tax measures as an instrument for cyclically adjusted tax revenues yields tax multiplier estimates that are indistinguishable from zero. We conclude that the literature currently understates the uncertainty associated with quantifying the tax multiplier.
The Time Projection Chamber (TPC), a large gaseous detector, is the main particle identification device of the ALICE experiment at the CERN LHC. The desired performance of the TPC defines the requirements for the gas mixture used in the detector. The active volume was filled with either Ne-CO2 (90-10) or Ne-CO2-N2 (90-10-5) during the first LHC running period. For LHC Run 2 the gas mixture is changed to Ar-CO2. Calculations of relevant gas properties are performed for Ar-based gas mixtures and compared to Ne-based gas mixtures to identify the most suitable Ar mixture. The drift velocity of ions in Ar is lower than in Ne. The closing time of the gating grid has to be adjusted accordingly to avoid drift field distortions due to back-drifting ions. The drift times of ions in the TPC readout chambers are calculated for the respective gas mixtures to determine the time to collect all ions from the amplification region. For LHC Run 3 the TPC readout chambers will be upgraded. The Multiwire Proportional Chambers (MWPCs) will be replaced by readout chambers based on Gas Electron Multipliers (GEMs) which are operated in continuous mode. As a consequence an ion backflow of the order of 1% causes significant space-charge distortions in the TPC drift volume. Similar distortions are expected in data taken specifically for the study of space-charge effects at the end of Run 1. The gating grid of the MWPCs is operated in the open state allowing the ions from the amplification region to enter the drift volume. The magnitude of the distortions in this data is measured and compared to the expectations for the TPC upgrade and results from current simulations.
RUCAM (Roussel Uclaf Causality Assessment Method) or its previous synonym CIOMS (Council for International Organizations of Medical Sciences) is a well established tool in common use to quantitatively assess causality in cases of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI). Historical background and the original work confirm the use of RUCAM as single term for future cases, dismissing now the term CIOMS for reasons of simplicity and clarity. RUCAM represents a structured, standardized, validated, and hepatotoxicity specific diagnostic approach that attributes scores to individual key items, providing final quantitative gradings of causality for each suspect drug/herb in a case report. Experts from Europe and the United States had previously established in consensus meetings the first criteria of RUCAM to meet the requirements of clinicians and practitioners in care for their patients with suspected DILI and HILI. RUCAM was completed by additional criteria and validated, assisting to establish the timely diagnosis with a high degree of certainty. In many countries and for more than two decades, physicians, regulatory agencies, case report authors, and pharmaceutical companies successfully applied RUCAM for suspected DILI and HILI. Their practical experience, emerging new data on DILI and HILI characteristics, and few ambiguous questions in domains such alcohol use and exclusions of non-drug causes led to the present update of RUCAM. The aim was to reduce interobserver and intraobserver variability, to provide accurately defined, objective core elements, and to simplify the handling of the items. We now present the update of the well accepted original RUCAM scale and recommend its use for clinical, regulatory, publication, and expert purposes to validly establish causality in cases of suspected DILI and HILI, facilitating a straightforward application and an internationally harmonized approach of causality assessment as a common basic tool.
A three-dimensional gridded climatology of carbon monoxide (CO) has been developed by trajectory mapping of global MOZAIC-IAGOS in situ measurements from commercial aircraft data. CO measurements made during aircraft ascent and descent, comprising nearly 41 200 profiles at 148 airports worldwide from December 2001 to December 2012 are used. Forward and backward trajectories are calculated from meteorological reanalysis data in order to map the CO measurements to other locations, and so to fill in the spatial domain. This domain-filling technique employs 15 800 000 calculated trajectories to map otherwise sparse MOZAIC-IAGOS data into a quasi-global field. The resulting trajectory-mapped CO dataset is archived monthly from 2001–2012 on a grid of 5° longitude × 5° latitude × 1 km altitude, from the surface to 14 km altitude.
The mapping product has been carefully evaluated, by comparing maps constructed using only forward trajectories and using only backward trajectories. The two methods show similar global CO distribution patterns. The magnitude of their differences is most commonly 10 % or less, and found to be less than 30 % for almost all cases. The trajectory-mapped CO dataset has also been validated by comparison profiles for individual airports with those produced by the mapping method when data from that site are excluded. While there are larger differences below 2 km, the two methods agree very well between 2 and 10 km with the magnitude of biases within 20 %.
Maps are also compared with Version 6 data from the Measurements Of Pollution In The Troposphere (MOPITT) satellite instrument. While agreement is good in the lowermost troposphere, the MOPITT CO profile shows negative biases of ∼ 20 % between 500 and 300 hPa. These upper troposphere biases are not related to the
mapping procedure, as almost identical differences are found with the original in situ MOZAIC-IAGOS data. The total CO trajectory-mapped MOZAIC-IAGOS climatology column agrees with the MOPITT CO total column within ±5 %, which is consistent with previous reports.
The maps clearly show major regional CO sources such as biomass burning in the central and southern Africa and anthropogenic emissions in eastern China. The dataset shows the seasonal CO cycle over different latitude bands and altitude ranges that are representative of the regions as well as long-term trends over latitude bands. We observe a decline in CO over the Northern Hemisphere extratropics and the tropics consistent with that reported by previous studies.
Similar maps have been made using the concurrent O3 measurements by MOZAICIAGOS, as the global variation of O3–CO correlations can be a useful tool for the evaluation of ozone sources and transport in chemical transport models. We anticipate use of the trajectory-mapped MOZAIC-IAGOS CO dataset as an a priori climatology for satellite retrieval, and for air quality model validation and initialization.
Models propose an auditory-motor mapping via a left-hemispheric dorsal speech-processing stream, yet its detailed contributions to speech perception and production are unclear. Using fMRI-navigated repetitive transcranial magnetic stimulation (rTMS), we virtually lesioned left dorsal stream components in healthy human subjects and probed the consequences on speech-related facilitation of articulatory motor cortex (M1) excitability, as indexed by increases in motor-evoked potential (MEP) amplitude of a lip muscle, and on speech processing performance in phonological tests. Speech-related MEP facilitation was disrupted by rTMS of the posterior superior temporal sulcus (pSTS), the sylvian parieto-temporal region (SPT), and by double-knock-out but not individual lesioning of pars opercularis of the inferior frontal gyrus (pIFG) and the dorsal premotor cortex (dPMC), and not by rTMS of the ventral speech-processing stream or an occipital control site. RTMS of the dorsal stream but not of the ventral stream or the occipital control site caused deficits specifically in the processing of fast transients of the acoustic speech signal. Performance of syllable and pseudoword repetition correlated with speech-related MEP facilitation, and this relation was abolished with rTMS of pSTS, SPT, and pIFG. Findings provide direct evidence that auditory-motor mapping in the left dorsal stream causes reliable and specific speech-related MEP facilitation in left articulatory M1. The left dorsal stream targets the articulatory M1 through pSTS and SPT constituting essential posterior input regions and parallel via frontal pathways through pIFG and dPMC. Finally, engagement of the left dorsal stream is necessary for processing of fast transients in the auditory signal.
BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study).
OBJECTIVE: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab.
METHODS: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16.
RESULTS: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies.
LIMITATIONS: The study was not placebo-controlled and of short-term duration.
CONCLUSIONS: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.
The CARIBIC (Civil Aircraft for the Regular Investigation of the Atmosphere Based on an Instrument Container) passenger aircraft observatory performed in situ measurements at 10–12 km altitude in the South Asian summer monsoon anticyclone between June and September 2008. These measurements enable us to investigate this atmospheric region, which so far has mostly been observed from satellites, using the broad suite of trace gases and aerosols measured by CARIBIC. Elevated levels of a range of atmospheric pollutants were recorded e.g. carbon monoxide, total reactive nitrogen oxides, aerosol particles and several volatile organic compounds. The measurements provide detailed information about the chemical composition of air in different parts of the monsoon anticyclone, particularly of ozone precursors. While covering a range of 3500 km inside the monsoon anticyclone, CARIBIC observations show remarkable consistency, i.e. with regular latitudinal patterns of trace gases during the entire monsoon period. Trajectory calculations indicate that these air masses originated mainly from South Asia and Mainland Southeast Asia.
Using the CARIBIC trace gas and aerosol measurements in combination with the Lagrangian particle dispersion model FLEXPART we investigated the characteristics of monsoon outflow and the chemical evolution of air masses during transport. Estimated photochemical ages of the air were found to agree well with transport times from a source region east of 95 ° E. The photochemical ages of the air in the southern part of the monsoon anticyclone were consistently younger (less than 7 days) and the air masses mostly in an ozone forming chemical regime. In its northern part the air masses were older (up to 13 days) and had unclear ozone formation or destruction potential. Based on analysis of forward trajectories several receptor regions were identified. In addition to predominantly westward transport, we found evidence for efficient transport (within 10 days) to the Pacific and North America, particularly during June and September, and also of cross-tropopause exchange, which was strongest during June and July. Westward transport to Africa and further to the Mediterranean was the main pathway during July.
During CNS development and adult neurogenesis, immature neurons travel from the germinal zones towards their final destination using cellular substrates for their migration. Classically, radial glia and neuronal axons have been shown to act as physical scaffolds to support neuroblast locomotion in processes known as gliophilic and neurophilic migration, respectively (Hatten, 1999; Marin and Rubenstein, 2003; Rakic, 2003). In adulthood, long distance neuronal migration occurs in a glial-independent manner since radial glia cells differentiate into astrocytes after birth. A series of studies highlight a novel mode of neuronal migration that uses blood vessels as scaffolds, the so-called vasophilic migration. This migration mode allows neuroblast navigation in physiological and also pathological conditions, such as neuronal precursor migration after ischemic stroke or cerebral invasion of glioma tumor cells. Here we review the current knowledge about how vessels pave the path for migrating neurons and how trophic factors derived by glio-vascular structures guide neuronal migration both during physiological as well as pathological processes
An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1–47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1–21.0 % and CTM v2: 15.0–32.3 %; CVs at 25 IU/ml: RealTime 17.6–34.9 % and CTM v2 28.2–54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR.
No. And not only for the reason you think. In a world with multiple inefficiencies the single policy tool the central bank has control over will not undo all inefficiencies; this is well understood. We argue that the world is better characterized by multiple inefficiencies and multiple policy makers with various objectives. Asking the policy question only in terms of optimal monetary policy effectively turns the central bank into the residual claimant of all policy and gives the other policymakers a free hand in pursuing their own goals. This further worsens the tradeoffs faced by the central bank. The optimal monetary policy literature and the optimal simple rules often labeled flexible inflation targeting assign all of the cyclical policymaking duties to central banks. This distorts the policy discussion and narrows the policy choices to a suboptimal set. We highlight this issue and call for a broader thinking of optimal policies.
The practical aim of this work is twofold. Firstly, it is to construct a theory of language based on historical-materialist premises, i.e. a theory which stresses the sociality and historicity of language, and finds in them the fundamental characteristics which make language one of the central phenomena of human life. Such a theory is inherently counterposed to the dominant theories and philosophies of language in the last century, be they Saussurean, idealistic, structuralist, psychologistic or Chomskyan etc. It also rejects vulgar materialistic accounts of language, where language is seen merely as a “reflection” of the economic base of society, as well as the version proposed in Stalin’s short pamphlet, Marxism and Linguistics, which sees language merely as a means of communication, regardless of society or class, therefore neutralised and consequently branded irrelevant for Marxist theory. In short, the first aim would be showing what language is not and what it cannot be by showing what it is.
The second aim is related to Marxist theory in general. Following the presuppositions of this work, a Marxist account of language proves to be an immensely important field of research for Marxism. The reasons are fairly simple, if one is willing to accept them: language is a certain type of social practice, it is related to the way people act, which also means that it is interconnected with consciousness, i.e. to the way people think and to the content of their thought. Language is ideological and political; it is an element of class rule and class struggle. Thus, understanding language should be of utmost importance for any socialist revolutionary project, as ideological struggle is central not only to a revolutionary period, but, perhaps even more, to a period where revolution is not even in sight. I do not wish to derogate other Marxist fields of research, but, on the contrary, to simply insist on their equal importance. Ideological phenomena should not be a secondary or inferior object of research to strictly economic phenomena, or vice-versa. In reality, those phenomena form a dialectic unity; only if theory follows suit, can a pregnant Marxist philosophy be formed.
It has been claimed and widely assumed that caseless direct objects in Turkish exhibit a sort of syntactic incorporation, and only their cased counterparts are true syntactic arguments (Kornfilt 1997; Knecht 1986; Nilsson 1986; Öztürk 2005 among others). Cased and caseless objects are thus widely taken as derivationally related, crystallized in Kelepir's (2001) proposal that objects pick up overt accusative as they move out of the VP. In this paper, I would like to revisit both the empirical evidence and the interpretation leading to these claims and propose revisions.
I first show that not all caseless objects are the same. Mostly drawing on Aydemir (2004), I argue that bare caseless objects and those with indefinite expressions have differences that would be very unusual if they were both incorporated. However, adopting Öztürk (2005) and against Aydemir (2004), neither of the cases can be analyzed as head incorporation.
I then turn to the cased vs. caseless distinction and argue that cased and caseless objects are not that different after all. Based on data with strictly controlled information structure, I arrive at a different generalization than most of the earlier reports and claim that caseless objects are morphosyntactically as moveable as their cased counterparts.
Hence, I propose to replace the notion of incorporation in the literature of Turkish syntax with the notion of weak case (de Hoop 1992) and conclude by a discussion of the domain of syntactic analysis in this primarily semantic phenomenon.
Savings accounts are owned by most households, but little is known about the performance of households’ investments. We create a unique dataset by matching information on individual savings accounts from the DNB Household Survey with market data on account-specific interest rates and characteristics. We document considerable heterogeneity in returns across households, which can be partly explained by financial sophistication. A one-standard deviation increase in financial literacy is associated with a 13% increase compared to the median interest rate. We isolate the usage of modern technology (online accounts) as one channel through which financial literacy has a positive association with returns.
Abstract: The current Ebola outbreak poses a threat to individual and global public health. Although the disease has been of interest to the scientific community since 1976, an effective vaccination approach is still lacking. This fact questions past global public health strategies, which have not foreseen the possible impact of this infectious disease. To quantify the global research activity in this field, a scientometric investigation was conducted. We analyzed the research output of countries, individual institutions and their collaborative networks. The resulting research architecture indicated that American and European countries played a leading role regarding output activity, citations and multi- and bilateral cooperations. When related to population numbers, African countries, which usually do not dominate the global research in other medical fields, were among the most prolific nations. We conclude that the field of Ebola research is constantly progressing, and the research landscape is influenced by economical and infrastructural factors as well as historical relations between countries and outbreak events.
Author Summary: For the first time in the history of the disease, the Ebola virus left its local setting and affected people not only in isolated rural areas, but reached larger towns and cities leading to worldwide repercussions. This development prompted a joint global response to this health threat. This encompassed not only immediate relief efforts, but also an up search in global research work. In this study, the scientific output in Ebola research available in one of the mayor medical search platforms was characterized. We studied among others the origin of research, the collaboration between countries and the research topics. Partly, the obtained data was weighted against economic parameters. We attained a detailed map of the research activities from the discovery of Ebola in 1976 up to today. Our research provides the first overview of the worldwide Ebola research output. It might help stakeholders in Ebola research to better plan investigations with a global perspective.
Thought structures of modelling task solutions and their connection to the level of difficulty
(2015)
Although efforts have been made to integrate the concept of mathematical modelling in school, among others PISA and TIMSS revealed weaknesses of not only German students in the field of mathematical modelling. There may be various reasons starting from educational policy via curricular issues to practical instructional concerns. Studies show that mathematical modelling has not been arrived yet in everyday school class (Blum &BorromeoFerri, 2009, p. 47). Thus, the proportion of mathematical modelling in everyday school classes is low (Jordan et al., 2006). When focusing on the teachers’ point of view there are difficulties which may contribute to avoid modelling tasks in class. The development of reasonable modelling tasks, estimating the task space, valuating the task difficulty and assessing the student solutions are difficulties which occur to an increasing degree compared to ordinary mathematics tasks.The project MokiMaS (transl.: modeling competency in math classes of secondary education) aims at providing inter-year modelling tasks, whose task space and level of difficulty is known, together with an evaluation scheme. In particular a theory based method has been developed to determine the level of difficulty of modelling tasks on the basis of thought structures, representing the cognitive load of solution approaches. The current question is whether this method leads to a realistic rating. To go further into that question an evaluation scheme has been developed which is guided by the daily assessment work of teachers, to investigate the relation of task difficulty and student performance.
Tibnīn was an important small Crusader fief and a fortified castle. It was vital for the Kingdom of Jerusalem, because it included fertile agricultural lands, was a tax collection centre, and because it controlled the Damascus-to-Tyre commercial route. Additionally, its castle played defensive and offensive role in the north of the Kingdom of Jerusalem and upper Galilee, and its rulers of Tibnīn played a major role in forming the history of the Latin East. When the Crusaders invaded the Levant at the end of the eleventh century, it was given rise to new demographic, cultural, socio-economic, and architectural features. The present Paper aims at removing some of the mystery concerning the fief of Tibnīn and its castle in the Latin East. This paper thus is a study of the demographic structure of Tibnīn and discusses the socio-economic role of Tibnīn in the Latin east. Moreover, the role of Tibnīn in influencing the relations between Muslims and the Crusaders in the Levant and the architecture of the castle of Tibnīn and its importance in the age of the Crusade will be examined.
In order to investigate the diversity of the western honeybee, Apis mellifera L., in West and Central Africa, a total of 204 colonies were sampled from 44 localities in four countries – Nigeria, Niger, Cameroon and Chad. 86 of these colonies, from 23 localities, were subjected to full morphometric analysis. In a principal component analysis (PCA) of the morphometric data, the colonies formed a single cluster. It also revealed that overall size of the body was the most important source of variation between the colonies. A hierarchical structure analysis, followed by a stepwise discriminant analysis, classified the colonies into three distinct morphoclusters; however, these clusters were not geographically demarcated. In another PCA carried out with the samples under investigation and reference samples of A. m. adansonii, A. m. jemenitica and A. m. scutellata, the colonies under investigation again formed one cluster which lying over and extended beyond the clusters of the reference subspecies. This is suggestive of a wider variation in size in the bees under investigation. In a stepwise DA, 94.2% of cross-validated grouped cases were correctly classified and the distances between group centroids were highly significant (p < 0.0005) according to F-statistic. 61 and 22 of the 83 colonies under investigation were assigned to A. m. jemenitica and A. m. adansonii, respectively. Mitochondrial DNA analysis was carried out on 148 colonies from 39 localities. Four mitochondrial haplotypes, previously reported from Africa and belonging to the African mitochondrial lineage, A, were detected: A1 (n = 62), A4 (n = 70), A4' (n = 15) and A14 (n = 1). The overall haplotype diversity was low (h = 0.478 ± S. E. 0.057). A chi-square test for association was conducted between haplotypes and type of vegetation, latitude, longitude, altitude, temperature and rainfall, severally. There was a statistically significant association between haplotype and each of the six variables and the association was strong with latitude, moderate with vegetation and rainfall and weak with the remaining variables. The neighbour-joining, maximum likelihood and maximum parsimony trees, obtained from sequence variation of the cytochrome b gene of mitochondrial DNA, showed that the samples, from the current study, unambiguously clustered with the reference sequences of A. m. scutellata from Kenya, but without showing further subdivision within this sub-Saharan cluster. 133 workers (one per colony) collected from 38 localities were subjected to microsatellite analysis. A total of 292 different alleles were recorded for the 15 microsatellite loci used. All microsatellite loci were polymorphic and the number of different alleles per locus ranged between 10, in locus At163, and 31, in locus A029. Heterozygosity (or gene diversity) was high in all loci. The unbiased expected heterozygosity, which is a better expression of gene diversity, was 0.861 ± S.E. 0.017. The overall FST value, which is a good estimate of genetic differentiation of populations, was very low: 0.007 ± S.E. 0.001 (0.001 - 0.014). AMOVA and Bayesian assignment showed no differentiation of the investigated populations. Based on morphometric analysis, the results of this study present the honeybees of western Africa as a single entity with an internal variation which lacks a geographical demarcation. Consequently the results do not support the splitting of the honeybees of the region into the two subspecies, A. m. adansonii and A. m. jemenitica, as reported in the literature. More morphometric, molecular, physiological and behavioural studies are required to confirm the taxonomic status of the honeybees of the region. Meanwhile, the use of A. m. adansonii, as the sole sub-specific name for the honeybees of West and Central Africa, is recommended.
In the last couple of years the research on natural products concerning ecological questions has gained more and more interest. Especially natural products play an important role for the maintenance of symbiotic relationships.
Here we present the application of the “overlap extension PCR-yeast homologous recombination“(ExRec) to simplify the availability of natural products. We successfully cloned a 45 kb gene cluster and characterized two new peptides ambactin and xenolindicin from Xenorhabdus – the latter derived from a silent gene cluster. ExRec is a very efficient cloning technique and resembles a powerful method regarding the assembly of large gene clusters as well as the cloning from metagenomic libraries or RNA pools.
In addition, we discovered bacterial pyrrolizidine alkaloids from Xenorhabdus, referred to as pyrrolizixenamides. The gene cluster consisted of a NRPS and a hydroxylase encoding gene. Surprisingly, this gene cluster and its variations (type A to D) can be found throughout the bacterial kingdom which might indicate an essential function. While these substances are mainly known to play a role in the defense mechanism of plants, the function of the identified pyrrolizixenamides from Xenorhabdus yet remains unsolved.
Moreover, we firstly identified a phosphopantetheinyl transferase (PPTase) from the lichenized fungus of Evernia prunastri. The gene eppA encoding a Sfp-type PPTase was heterologously expressed in Escherichia coli and Saccharomyces cerevisiae and functional characterized by indigoidine production and complementation of lys5, respectively. All represented results contribute to the elucidation of natural products and thereby to their role in nature with special regard to symbiotic associations.
Photosynthesis is one of the most vital processes that takes place on Earth. Due to its global significance related to food, energy and material production, photosynthesis research is one of the leading scientific fields in the contemporary world. Particular interest in photosynthesis research is focused on diatoms and as one of the major players of marine phytoplankton, diatoms have a huge impact on global photosynthesis.
Diatoms originated from a secondary endosymbiosis that took place between a putative photosynthetic red algal ancestor and a heterotrophic eukaryote. Secondary endosymbiosis resulted in the formation of chloroplasts with four membranes. Centric diatoms (e.g. Thalassiosira pseudonana or Cyclotella meneghiniana) usually possess many small chloroplasts, while pennates (e.g. Phaeodactylum tricornutum) have several larger ones, or even only one which can occupy half of the cell volume...
In the title compound, C20H24N2O4, both peptide bonds adopt a trans configuration with respect to the —N—H and —C=O groups. The dihedral angle between the aromatic rings is 53.58 (4)°. The molecular conformation is stabilized by an intramolecular N—H⋯O hydrogen bond. The crystal packing is characterized by zigzag chains of N—H⋯O hydrogen-bonded molecules running along the b-axis direction.
Heavy-ion collisions at ultra-relativistic energies allow access to the Quark-Gluon Plasma, the deconfined phase of the strong interaction, a state which is believed to have existed fractions of seconds after the big bang. Two-particle correlations at small relative momenta, and particularly their dependence on pair transverse mass, are distinctly sensitive to the reaction dynamics of the fireball created in heavy-ion collisions.
Being the heaviest system to extract a size of the particle emitting source, proton-lambda correlations extend the studied range in pair transverse mass and are therefore well suited to explore the dynamical behavior of the matter created in Pb-Pb collisions at the Large Hadron Collider. The centrality dependence of the extracted source radii affirms the expectations of a larger source for more central collisions. Source radii were attained over a span of more than 0.9 GeV/c2 in mean pair transverse mass with a source radius extracted for a mean transverse mass as high as 2.18 GeV/c2. The source radii decrease with increasing pair transverse mass, as expected in a hydrodynamical picture. The comparison with radii obtained from other particle species exhibits the clear breaking of an elsewhere proposed scaling behavior of source radii with mean pair transverse mass for all particle species.
Gamma-gamma correlations possibly allow to look past the barrier of kinetic freeze-out. Additionally, they bear the potential to solve the puzzling observation in heavy-ion collisions of an excess of photons with a large temperature-like inverse slope parameter on the one hand and an elliptic flow coefficient of photons comparable to the one of hadrons on the other hand. A striking signal in the two-photon correlation function is observed; however it seems likely to not be of quantum statistical origin. A path for further studies is laid out.
Measurements of the transverse momentum (pt) spectra of K0 s and Λ(Λ̄) in Pb–Pb and pp collisions at √sNN = 2.76TeV with the ALICE detector at the LHC at CERN up to pt = 20GeV/c and pt = 16GeV/c, respectively, are presented in this thesis. In addition, the particle rapidity densities at mid-rapidity and nuclear modification factors of K0 s and Λ(Λ̄) are shown and discussed. The analysis was performed using the Pb–Pb data set from 2010 and the pp data set from 2011. For the identification of K0 s and Λ(Λ̄), the on-the-fly V0 finder was employed on tracking information from the TPC and ITS detectors. The Λ and Λ̄ spectra were feed-down corrected using the measured published Ξ− spectra as input.
Regarding the rapidity density at mid-rapidity, a suppression of the strange particle production in pp as compared to Pb–Pb collisions is observed at all centralities, whereas the production per pion rapidity density stays constant as a function of dNch/dη including both systems. Furthermore, the relative increase of the individual particle species in pp and AA collisions is compatible for non- and single-strange particles when going from RHIC (√sNN = 0.2TeV) to LHC energies. On the other hand, in case of multi-strange baryons, a stronger increase in the particle production in pp is seen. The Λ̄ and Λ production in Pb–Pb and pp collisions was found to be equal. Concerning the nuclear modification factors, at lower pt (pt <5GeV/c), an enhancement of the RAA of Λ with respect to that of K0 s and charged hadrons is observed. This baryon-to-meson enhancement appearing in central Pb–Pb collisions at RHIC and LHC is currently explained by the interplay of the radial flow and recombination as the dominant particle production mechanism in this pt sector. The effect of radial flow is thus also seen in the low and intermediate pt region of RAA, where a mass hierarchy is discovered among the baryons and mesons, respectively, with the heaviest particle being least suppressed. When comparing the results from RHIC and LHC, the RCP is found to be similar at low-to-intermediate pt, while a significantly smaller RAA of K0 s and Λ in central and peripheral events at the LHC is observed in this pt region as compared to the RHIC results. This can be attributed to the larger radial flow in AA collisions and to the harder spectra at the LHC. At high pt (pt > 8GeV/c), a strong suppression in central Pb–Pb collisions with respect to pp collisions is found for K0 s and Λ(Λ̄). A significant high-pt suppression of these hadrons is also observed in the ratio of central-to-peripheral collisions. The nuclear modification of K0 s and Λ(Λ̄) is compatible with the modification of charged hadrons at
high pt. The calculations with the transport model BAMPS agree with these results suggesting a similar energy loss for all light quarks, i.e. u, d and s. Moreover, a compatible suppression for c-quarks appears in the ALICE measurements via the D meson RAA as well as in the BAMPS calculations, which hints to a flavour-independent suppression if light- and c-quarks are regarded. Within this consideration, no indication for a medium-modified fragmentation is found yet.
To summarize, for the particle production in Pb–Pb collisions at the LHC relative to pp neither at lower pt (rapidity density) nor at higher pt (nuclear modification factor) a significant difference of K0 s and Λ(Λ̄) carrying strangeness to hadrons made of u- and d-quarks was found.
Understanding land cover degradation patterns and the effects of geomorphological units on phytodiversity is important for guiding management decisions and restoration strategies in the Sahelian vulnerables zones. This paper describes land cover degradation by combining Landsat TM image analysis and field data measurements in the Gourouol catchment of the Sahelian zone of Burkina Faso. Erdas Imagine 9.2 and Arc-GIS.10 were applied. The change patterns were obtained by superposing land cover maps for 1992 and 2010. The field data were collected by the mean of inventories according to the Braun-Blanquet phytosociological relevés methods. Plot sizes were 50 m x 20 m for woody species and 10 m x 10 m for herbaceous species. Six land cover types were identified and mapped: cultivated lands, bared lands, lowlands, which all spatially increased; and shrub-steppes, grasslands and water bodies, which all spatially decreased. The dynamic patterns based on the geomorphological units were non-degraded lowlands, stable sand dunes and degraded glacis. High plant diversity was found in lowlands, whereas low diversity occurred in glacis. A significant dissimilarity was observed between communities. The Shannon diversity indices in plant communities were approximately close to ln(species richness). The Pielou indices were close to 1, indicating a species fairly good distribution. Our results showed a variation of land cover over time and the effects of geomorphological units on phytodiversity. Furthermore, this variation helps oppose land degradation in the Sahel.
The Asian bush mosquito (Aedes japonicus japonicus, Theobald 1901) is an invasive culicid species which originates in Asia but is nowadays present in northern America and Europe. It is a competent vector for several human disease pathogens. In addition to the public health threat, this invasive species may also be an ecological threat for native container-breeding mosquitoes which share a similar larval habitat. Therefore, it is of importance to gain knowledge on ecological and eco-toxicological features of the Asian bush mosquito. However, optimal laboratory feeding conditions have not yet been established. Standardized feeding methods will be needed in assessing the impact of insecticides or competitional strength of this species. To fill this gap, we performed experiments on food quality and quantity for Ae. j. japonicus larvae. We found out that the commercial fish food TetraMin (Tetra, Melle, Germany) in a dose of 10 mg per larva is the most suitable food tested. We also suggest a protocol with a feeding sequence of seven portions for all larval stages of this species.
This paper investigates whether a fiscal stimulus implies a different impact for flexible and rigid labour markets. The analysis is done for 11 advanced OECD economies. Using quarterly data from 1999 to 2013, I estimate a panel threshold structural VAR model in which regime switches are determined by OECD’s employment protection legislation index. My empirical results indicate significant differences between rigid and flexible labour markets regarding the impact of the fiscal stimulus on output and unemployment. While the impulse response of real GDP to a government spending shock is positive and more effective in flexible labour markets, it has less impact in the rigid ones. Moreover, it is found that a fiscal stimulus leads to higher overall unemployment in highly regulated countries.
Recent STAR data for the directed flow of protons, antiprotons and charged pions obtained within the beam energy scan program are analyzed within the Parton-Hadron-String-Dynamics (PHSD/HSD) transport models. Both versions of the kinetic approach are used to clarify the role of partonic degrees of freedom. The PHSD results, simulating a partonic phase and its coexistence with a hadronic one, are roughly consistent with the STAR data. Generally, the semi-qualitative agreement between the measured data and model results supports the idea of a crossover type of quark-hadron transition which softens the nuclear EoS but shows no indication of a first-order phase transition. Furthermore, the directed flow of kaons and antikaons is evaluated in the PHSD/HSD approachesfrom √sNN ≈ 3 - 200 GeV which shows a high sensitivity to hadronic potentials in the FAIR/NICA energy regime √sNN ≤ 8 GeV.
Within this thesis, the mechanical integration of the Micro Vertex Detector (MVD) of the Compressed Baryonic Matter (CBM) experiment is developed. The CBM experiment, which is being set up at the future FAIR facility, aims to investigate the phase diagram of strongly interacting matter in the regime of high net-baryon densities and moderate temperatures. Heavy-ion collisions at beam energies in the range of 2 to 45 AGeV, complemented by results from elementary reactions, will allow access to these conditions. The experiments conducted at LHC (CERN, Switzerland) and at RHIC (BNL, USA = does not apply within the Beam Energy Scan program) so far focus on the investigation of the phase diagram in the regime of high temperatures and vanishing net-baryon densities. The high beam intensities provided by FAIR will enable CBM to focus its experimental program on systematical studies of rare particles. Among other particle species, open charm-carrying particles are one of the most promising observables to investigate the medium created in heavy-ion collisions since their charm quarks are exposed to the medium and traverse its whole evolution. The fact that the decay particles of these rare observables are also produced abundantly in direct processes in heavy-ion collisions results in a huge combinatorial background which attributes specific requirements to the detector systems. The call for a high interaction rate leads to a cutting-edge detector system which provides an excellent spatial resolution, thin detector stations and the capability to cope with the induced radiation as well as the high rate of traversing particles and the resulting track density. The required demands are to be implemented by the MVD which will be equipped with four planar stations positioned at 50, 100, 150 and 200 mm downstream the target. The geometrical acceptance, which has to be covered with charge-sensitive material, is defined according to the requirements of CBM in the polar angle range of [2.5°; 25°]. The MVD stations have to contribute as little as possible to the overall material budget. The expected beam intensity and the vicinity close to the target require silicon detectors that provide a hardness against non-ionizing radiation of more than 10^13 n_eq/cm² and against ionizing radiation of more than 1 Mrad. In addition, the read-out time of the sensors has to be as short as possible to avoid potential ambiguities in the particle tracking caused by the pile-up of hits having emerged from different collisions. For the time being, Monolithic Active Pixel Sensors (MAPS) offer the optimal choice of technology required to address the physics program of CBM with respect to the spectroscopy of open charm and di-electrons. The geometrical properties of these sensors define the layout of the detector. To limit the multiple scattering of the produced particles inside the geometrical acceptance, the sensors and the MVD have to operate in a moderate vacuum. The sensors are thinned down to a thickness of 50 µm and, to achieve a maximum polar angle coverage, they are glued onto both sides of dedicated thin carriers. These carriers, which are made of highly thermally conductive materials such as CVD diamond or encapsulated TPG, allow efficient extraction of the power produced in the sensors. This enables their operation at temperatures well below 0 °C as suggested by corresponding radiation hardness studies. Dedicated actively cooled aluminum-based heat sinks are positioned outside of the acceptance to dissipate the heat produced by the sensors and the front-end electronics. The design of the MVD, including the realistic thicknesses of the integrated materials, has been developed and refined in the context of this thesis. It has been transformed into a unique software model which is used to simulate and further optimize the mechanical and thermal properties of the MVD, as well as in sophisticated physics simulations. The model allowed evaluation of the material budget of each individual MVD station in its geometrical acceptance. The calculated averaged material budget values stay well below the material budget target values demanded by the physics cases. The thermal management of the MVD has been simulated on the level of a quadrant of each MVD station – four identically constructed quadrants are forming an MVD station – taking into account material properties of the sensors, the glue and the sensor carrier. The temperature gradients across the pixels of a given sensor area in the direction of the rows and columns were found to be in an acceptable range of below 5 K. A temperature difference between the thermal interface area and the maximum sensor temperature of dT = 5 K on the first and a value of dT = 40 K on the fourth MVD station has been thermally simulated assuming a sensor power dissipation of 0.35 W/cm², highlighting the need to optimize the thermal interface between the involved materials as well as the power dissipation of the sensors. The feasibility of several key aspects required for the construction phase of the MVD has been investigated within the MVD Prototype project. The construction of the MVD Prototype allowed evaluation, testing and validation of the handling and the double-sided integration of ultra-thin sensors – the required working steps for their integration have been specified, evaluated and successfully established – as well as their operation in the laboratory and during a concluding in-beam test using high-energetic pions provided by the CERN-SPS. The thermal characterization of the MVD Prototype during its operation – in a temperature range from [5 °C; 25 °C], not in vacuum – confirmed the corresponding thermal simulations conducted during its design phase and substantiated the results of the thermal simulations for the design of the MVD. The aim of a material budget value of only x/X_0 ~ 0.3% for the MVD Prototype has been accomplished. Analyzing the in-beam data, the nominal sensor performance parameters were successfully reproduced, demonstrating that the proposed integration process does not impair the sensors’ performance. Moreover, no evidence of potential impact on the sensors’ performance arising from mechanical weaknesses of the MVD Prototype mechanics has been found within the analyzed data. Based on the MVD Prototype and the simulations of the material budget as well as the thermal management, this thesis evaluated the work packages, procedures and quality assurance parameters needed to set up the starting version of the MVD and addressed open questions as well as critical procedures to be studied prior to the production phase of the detector, emphasizing the evaluation of the cooling concept in vacuum and the integration of sensors in ladder structures on both sides of the quadrants of the MVD stations.
Termites are important ecosystem engineers of the savanna biome, with the large mounds of fungus-cultivating termites being sources of habitat heterogeneity and structural complexity in African savanna landscapes. Studies from different localities throughout Africa have shown that termite mounds have a strong influence of diversity and composition of plant communities. However, most research has been conducted only at the local scale, and integrating knowledge across Africa is hampered by different methodology of studies and differing environmental context. Little is known about the variation in vegetation composition on termite mounds compared to the surrounding savanna at the regional scale and at the landscape scale, and the main determinants of plant communities on mounds are yet to be ascertained.
This thesis aimes at better understanding the influence of termite mounds on vegetation compared to the surrounding savanna across spatial scales. Three research projects analyse vegetation data and soil data from paired mound and savanna plots in West Africa. The first project examines the influence of termite-induced heterogeneity on plant diversity and vegetation composition at a regional scale, following a bioclimatic gradient from the Sahel of Burkina Faso to the Sudanian vegetation zone in North Benin. The second Project analysed variation of vegetation on and off mounds at the landscape scale in Pendjari National Park, North Benin. The third is a monitoring study over the course of two years, exploring dynamics of juvenile woody plant communities on mounds and in the surrounding savanna at a local scale. The thesis thus provides the first comparative quantitative analysis across scales of mound and savanna vegetation and the drivers of the mound–savanna difference in vegetation.
Synthesizing across scales, its results confirm that termite mounds strongly contribute to savanna plant diversity, even though mounds are not generally more species rich than the surrounding savanna. Variation in mound vegetation is much higher along climatic and soil gradients than previously acknowledged. Mound vegetation differs from the surrounding savanna in the whole study area and in each sampled savanna type, with the strongest differences occurring at the most humid study sites. A large proportion of the differences between mound and savanna vegetation is explained by clay enrichment and related soil factors, such as cation concentrations. Plants on mounds thus benefit from favourable soil conditions, including higher fertility and higher water availability, which is also mirrored by the higher abundance and basal area of juvenile woody plants found on mounds. The variation in mound vegetation between study sites across scales results in part from local differences in soil composition and from climatic differences that influence the regional distribution of species. Different sets of characteristic mound species are identified in each project. Specific plant families and traits like succulency, lianescence, and adaptations to zoochory are found to be overrepresented in mound communities.
In addition to the findings in this thesis, remaining parts of the variation in mound vegetation between study sites could likely be explained by investigating further factors. Specifically, mound vegetation depends on habitat context, which includes available species pools, spatial distribution of mounds, biotic interactions with dispersers and herbivores, fire, and also anthropogenic influence. The high proportion of species with adaptations to zoochory found on mounds, for example, indicates that animal dispersers should be of particular importance for vegetation on termite mounds. Herbivory and fire regime, which are known to contribute to the diversity and community composition of the mound–savanna system, also show strong local variation, not least because of anthropogenic influence.
In conclusion, termite mounds play a crucial role in maintaining heterogeneity and plant diversity in the savanna across scales. Ecosystem services provided by termites, especially considering long-term effects on soil fertility and ecosystem resilience, are most likely undervalued. Mounds should be considered in management plans from local to regional, transnational scales as a matter of course, accompanied by further research on the role of termite mounds in savanna ecology on a longer temporal scale. The research presented here thus provides a basis for future studies on termite mound vegetation that should specifically consider the biotic and abiotic context of the mound–savanna system.
Das natürlich vorkommende Polyphenol Resveratrol (3,4‘,5-(E)-Trihydroxystilben) ist eine potente chemopräventive Substanz, die in vielen verschiedenen Krebszelllinien wirksam ist. Außerdem verfügt sie über anti-inflammatorische, anti-oxidative und pro-apoptotische Wirkungen. Da Resveratrol auch in Tiermodellen des Typ-2-Diabetes und der nicht-alkoholischen Fettlebererkrankung gute Effekte gezeigt hat, wird in Erwägung gezogen es zur Prävention und Behandlung von metabolischen Erkrankungen einzusetzen. Allerdings liegen, aufgrund von schneller Metabolisierung und geringer Bioverfügbarkeit, die wirksamen Konzentrationen im mikromolaren Bereich. Eine geeignete Strategie, um die anti-tumorale Wirkung und die Bioverfügbarkeit von Resveratrol zu verbessern, scheint die Methylierung der freien Hydroxylgruppen zu sein. Allerdings liefern einige Studien Hinweise darauf, dass diese strukturelle Modifikation der Stilbengrundstruktur zu einer Veränderung des antiproliferativen Wirkmechanismus der methylierten Substanzen führt. Daher führten wir im ersten Teil dieser Arbeit genauere Untersuchungen durch, um die Veränderungen der biologischen Wirkung, die durch die Methylierung der freien Hydroxylgruppen von (E)- und (Z)-Resveratrol verursacht werden, zu charakterisieren. Einen Schwerpunkt bildete die Bestimmung der metabolischen Effekte der methylierten Substanzen. Dabei sollte aufgeklärt werden, ob die Analoga noch immer in der Lage sind bekannte Resveratrol-Targets, wie AMPK, SIRT1 und Phosphodiesterasen, zu modulieren. Zunächst bestätigten wir, dass die methylierten Resveratrolanaloga ST911 (3,4‘,5-Z)-Trimethoxystilben) und ST912 (3,4‘,5-(E)-Trimethoxystilben) einen starken antiproliferativen Effekt auf verschiedene Krebszelllinien ausüben. Wie bereits zuvor beschrieben, konnten wir beobachten, dass ST911 und ST912 das Wachstum von Tumorzellen stärker beeinflussen, als die hydroxylierten Substanzen (E)- und (Z)-Resveratrol. Dies, in Verbindung mit einer vernachlässigbaren zytotoxischen Wirkung und einer deutlich geringeren antiproliferativen Wirkung auf Primärzellen, legt nahe, dass ST911 als potentielles neues Chemotherapeutikum weiter untersucht werden sollte. Zudem zeigten ST911 und ST912 signifikante pro-apoptotische Wirkungen in CaCo-2-Zellen. Auch Resveratrol konnte in diesen Zellen Apoptose auslösen, allerdings erst nach Behandlung mit deutlich höheren Konzentrationen, verglichen mit ST911 und ST912. Eine genauere Charakterisierung der antitumoralen Wirkung von ST911 in HT-29-Zellen zeigte, dass ST911 die Polymerisation von Tubulin zu Mikrotubuli beeinflusst und einen Arrest des Zellzyklus in der Mitose-Phase auslöst. Im Gegensatz dazu führt Resveratrol zu einem Zellzyklus-Arrest in der S-Phase und beeinflusst die Tubulinpolymerisation nicht. Diese Beobachtungen verstärkten die Annahme, dass ST911 ein Mitosehemmer ist und betonten noch einmal die mechanistischen Unterschiede zwischen Resveratrol und den methylierten Analoga. Interessanterweise konnte ST911 die hepatische Fettakkumulation in einem in-vitro-Steatosemodell nicht beeinflussen, während eine Behandlung mit Resveratrol zu einer signifikanten Reduktion der intrahepatischen Triglyzeride führte. Dieses Experiment lässt vermuten, dass die stärkere antiproliferative Wirkung von ST911, keine erhöhte Aktivität in metabolischen Krankheitsmodellen nach sich zieht. Die beobachteten Unterschiede im Steatosemodell führten zu der Frage, ob die methylierten Analoga noch immer in der Lage sind die gleichen metabolischen Targetgene zu modulieren, die in der Literatur für Resveratrol beschrieben sind. Vor kurzem wurden Phosphodiesterasen (PDEs) als direkte Targets von Resveratrol identifiziert. Die Inhibition von PDEs durch Resveratrol führt zu einem Anstieg der intrazellulären cAMP-Konzentration. Diese wiederum aktiviert die bekannten Resveratrol-Targetgene AMPK und SIRT1. Unsere Experimente zeigten, dass ST911 und ST912 keinen Einfluss auf die intrazelluläre cAMP-Konzentration haben. Zusätzlich konnten wir keine AMPK- oder SIRT1-abhängigen Veränderungen der Genexpression beobachten. Dies ist ein Hinweis darauf, dass die Substanzen ihre zellulären Effekte vermutlich nicht über eine Modulation von PDEs, AMPK oder SIRT1 vermitteln. Zusammenfassend liefert der erste Teil der Arbeit Beweise dafür, dass ST911 keine positiven Effekte in metabolischen Krankheitsmodellen ausübt. Dies liegt vermutlich in einem Aktivitätsverlust gegenüber den metabolischen Targetgenen von Resveratrol begründet. Des Weiteren unterstützen unsere Ergebnisse frühere Arbeiten, die zeigen konnten, dass ST911 an Tubulin bindet und die Polymerisation zu Mikrotubuli verhindert. Weiterhin bestätigen unsere Daten, dass die Methylierung von Resveratrol zu einer grundlegenden Veränderung des Wirkmechanismus dieser Substanzen führt, die von einem kompletten Verlust der metabolischen Aktivität begleitet wird. Dies sollte bei zukünftigen Leitstrukturoptimierungen mit Resveratrol berücksichtigt werden. Im ersten Teil dieser Arbeit konnte außerdem gezeigt werden, dass Resveratrol die Gentranskription des nukleären Rezeptors SHP (aus dem Englischen: small heterodimer partner) stark induziert. Der Mechanismus dieser Induktion scheint von der Aktivität von AMPK und SIRT1 abhängig zu sein. Diese Ergebnisse konnten unser Verständnis der vielseitigen biologischen Wirkungen von Resveratrol erweitern. Dennoch sollte die Relevanz der SHP-Induktion für die Effekte von Resveratrol auf metabolische Krankheiten und Tumorwachstum noch weiter untersucht werden. Während der Experimente für den ersten Teil der Arbeit stellten wir fest, dass der AMPK-Inhibitor Compound C (CC) in der Lage war, die wachstumshemmende Wirkung von ST911 signifikant zu reduzieren. Die Untersuchung dieses sogenannten „Rescue-Effektes“ wird durch die Tatsache bestärkt, dass eine steigende Anzahl von Tumoren resistent gegenüber Chemotherapeutika ist. Außerdem fehlen spezifische Antidota für akute Intoxikationen mit Mitosehemmern. Daher zielten die folgenden Experimente darauf ab den Rescue-Effekt näher zu charakterisieren und die zugrundeliegenden Wirkmechanismen aufzuklären. Zunächst zeigten Knockdown-Experimente, dass der Rescue-Effekt unabhängig von der AMPK-inhibierenden Wirkung von CC vermittelt wird. Da CC ein ATP-kompetitiver Inhibitor der AMPK ist und zuvor bereits gezeigt wurde, dass es auch eine große Zahl anderer Kinasen inhibieren kann, vermuteten wir, dass der Rescue-Effekt mit diesen Off-Target-Effekten von CC zusammenhängt. Als nächstes testeten wir, ob die wachstumshemmenden Effekte von anderen Mitosehemmern auch durch CC aufgehoben werden können. Wir wählten verschiedene etablierte Substanzen, die dafür bekannt sind mit Mikrotubuli zu interagieren: Colchicin, das Vinca-Alkaloid Vinblastin, Disorazol A und das aus Taxus-Arten isolierte Paclitaxel. Die ersten drei dieser Substanzen haben eine depolymerisierende Wirkung auf die Mikrotubuli, während Paclitaxel zu einer stärkeren Polymerisierung führt. Zudem binden diese Substanzen an drei verschiedenen Bindestellen am Tubulin. Interessanterweise zeigten unsere Versuche, dass CC die antiproliferative Wirkung aller getesteten Mitosehemmer auf HT-29-Zellen, unabhängig von der Bindestelle, abschwächen kann. Des Weiteren konnte CC die Wirkung der pro-apoptotischen Substanz Staurosporin nicht reduzieren. Diese Ergebnisse weisen darauf hin, dass eher die tubulinbindenden, als die pro-apoptotischen Eigenschaften, von ST911 für den Rescue-Effekt verantwortlich sind. Um zu untersuchen, ob der Rescue-Effekt mit einer kompetitiven Bindung von CC und Mitosehemmern an Mikrotubuli erklärt werden kann, führten wir eine Immunfluoreszenzfärbung von ?-Tubulin durch. Wir konnten beobachten, dass die Tubulinpolymerisation und die Funktion des Spindelapparates in Zellen, die mit Mitosehemmern behandelt wurden, deutlich eingeschränkt waren. Außerdem stellten wir fest, dass CC nicht in der Lage ist die Zerstörung des Tubulingerüstes durch die Mitosehemmer zu verhindern. Eine Einzelbehandlung mit CC hatte keine Wirkung auf die Polymerisation des Tubulin zu Mikrotubuli. Insgesamt legen diese Daten nahe, dass CC nicht direkt an Mikrotubuli binden kann, um mit den Mitosehemmern um eine Bindung zu kompetitieren. Um diese Hypothese zu stärken, führten wir, in Kooperation mit Dr. Jennifer Herrmann (Helmholtz Institut für Pharmazeutische Forschung, Saarbrücken) SPR-Experimente mit Chips durch, auf denen Tubulin immobilisiert wurde. Die Messungen zeigten, das CC nicht in der Lage war gebundenes Disorazol A von der Bindestelle am Tubulin zu verdrängen. Dies zeigte nun deutlich, dass der Rescue-Effekt nicht auf einer Kompetition von CC und Mitosehemmern um Tubulinbindestellen beruht. Zellzyklusanalysen zeigten, dass die kombinierte Behandlung mit ST911 und CC zu einer Abschwächung des durch ST911 verursachten G2/M-Arrestes führt. Da wir zuvor bereits eine Beeinflussung der direkten Targets von CC und Mitosehemmern, AMPK oder Tubulin, ausgeschlossen hatten, schlussfolgerten wir, dass CC vermutlich mit anderen zellulären Signalwegen interagiert, die zu den beschriebenen Veränderungen des Zellwachstums und der Zellzyklusprogression führen. Eine Literaturrecherche ergab, dass ein erhöhter intrazellulärer Polyaminspiegel, die Aktivierung des PI3K/Akt-Signalweges oder eine erhöhte Aktivität des Transkriptionsfaktors c-Myc zu einer Abschwächung eines G2/M-Arrestes führen können. Daher fokussierten wir die weiteren Experimente auf die Untersuchung einer möglichen Beteiligung dieser Targets an der Vermittlung des Rescue-Effektes. Wir zeigten, dass CC die Expression der Spermidin/Spermin-N1-Acetyltransferase (SSAT) erhöhen kann. Die SSAT ist ein Enzym, das an der Biosynthese der Polyamine beteiligt ist. Zusätzlich beobachteten wir, dass die Behandlung mit CC nach 4 h zu einer Erhöhung von phosphoryliertem und damit aktiviertem Akt (pAkt) führt. Die zusätzliche Behandlung mit Wortmannin, einer Substanz, welche die Phosphorylierung von Akt hemmen kann, führte zu einer Abschwächung des Rescue-Effektes. Insgesamt weisen diese Ergebnisse darauf hin, dass eine Aktivierung von Akt-Signalwegen und ein Einfluss auf die Polyaminbiosynthese, zumindest teilweise, mit dem Rescue-Effekt zusammenhängen können. Die Überexpression von c-Myc, einem Transkriptionsfaktor, der eng mit dem Akt-Signalweg und der Biosynthese von Polyaminen zusammenhängt, ist oft mit einer erhöhten Zellproliferation verbunden. Wir untersuchten die zellulären Proteinmengen von c-Myc mittels Western Blot und entdeckten, dass nach der Behandlung mit Mitosehemmern zusätzliche Banden für c-Myc auf den Blots auftauchten. Diese Ergebnisse geben einen Hinweis auf eine posttranslationale Modifikation von c-Myc nach der Behandlung mit Mitosehemmern. Durch Kombination mit CC wurden die zusätzlichen Banden abgeschwächt und die Gesamtmenge an c-Myc-Protein nahm nach längeren Inkubationszeiten rapide ab. Dies legt nahe, dass die posttranslationale Modifikation von c-Myc zum Abbau des Proteins führt und, dass CC dies abschwächen kann. Verschiedene Arbeiten zeigten bereits, dass c-Myc phosphoryliert wird und nach Konjugation mit Ubiquitin vom Proteasom abgebaut wird. Daher überprüften wir, ob eine Inhibition des Proteasoms mit MG-132 zu einem ähnlichen Rescue-Effekt führt wie mit CC. Tatsächlich führte die Behandlung mit ST911 in Kombination mit MG-132 zu einer Zunahme der Zellproliferation, wie sie vorher bereits für CC beobachtet wurde. Dies bestärkte die Theorie, dass der proteasomale Abbau von c-Myc eine Rolle beim Rescue-Effekt spielen kann. Als nächstes untersuchten wir die Phosphorylierungen von c-Myc am Ser62 und Thr58. Diese Phosphorylierungen spielen eine wichtige Rolle beim Abbau von c-Myc, indem Sie das Protein für die Konjugation mit Ubiquitin markieren. Die densitometrische Auswertung der Western Blots ergab, dass die Behandlung mit ST911 initial zu einem Anstieg von phospho-c-Myc führt, dem eine schnelle Abnahme zu späteren Zeitpunkten folgt. Außerdem konnte gezeigt werden, dass dieser Anstieg von phospho-c-Myc durch Kombination mit CC reduziert wurde. Dies unterstützt die Hypothese, dass ST911 den proteasomalen Abbau von c-Myc begünstigt und CC dies verhindern kann. Dies ist eine mögliche Erklärung für die erhöhte Zellproliferation, die für die durch CC „geretteten“ Zellen beobachtet wurde. Allerdings konnte das direkte Target, das für die Vermittlung des Rescue-Effektes durch CC verantwortlich ist, bisher nicht identifiziert werden. DYRKs (aus dem Englischen: Dual-specificity tyrosine-phosphorylation-regulated kinases) sind wichtige Regulatoren von Proteinstabilität und –abbau während der Zellzyklusprogression. Vor kurzem wurde gezeigt, dass DYRK1A und DYRK2 c-Myc am Ser62 phosphorylieren können und es dadurch für den proteasomalen Abbau markieren. Interessanterweise wurde CC bereits in einer früheren Publikation als potenter Inhibitor verschiedener DYRKs beschrieben. Allerdings wurde die Hemmung der DYRKs durch CC in diesem Artikel nur in einer einzelnen Konzentration getestet. Daher bestimmten wir in einem in-vitro-Kinaseassay in Kooperation mit Dr. Matthias Engel (Universität des Saarlandes, Saarbrücken) die IC50-Werte für CC gegenüber DYRK1A, DYRK1B und DYRK2. Unsere Ergebnisse zeigten deutlich, dass CC ein bevorzugter Inhibitor von DYRK1A und DYRK1B (IC50-Wert von etwa 1 µM) ist, aber auch DYRK2 hemmen kann (IC50-Wert von etwa 5 µM). Da sich die vermutete Bindestelle von CC in der stark konservierten Kinasedomäne befindet, ist eine unspezifische Inhibition verschiedener DYRKs nicht überraschend. Genexpressionsanalysen zeigten, dass HT-29 und HepG2 vergleichbare Mengen an DYRK1A exprimieren, während DYRK1B und DYRK2 deutlich weniger in HepG2 vorhanden sind. Vorige Experimente hatten gezeigt, dass HepG2 weniger sensitiv für ST911 und den durch CC vermittelten Rescue-Effekt waren. Wir schlussfolgerten, dass die unterschiedliche Expression der DYRK-Formen eine mögliche Erklärung für diese Unterschiede sein könnte. Daher entschieden wir uns für eine nähere Untersuchung von DRK1B und DYRK2. Experimente mit verschiedenen Inhibitoren der DYRKs zeigten, dass diese Substanzen, ähnlich wie CC, in der Lage waren die antiproliferative Wirkung von ST911 abzuschwächen. Diese Ergebnisse wurden in nachfolgenden Knockdown-Experimenten bestätigt. Dies legt nahe, dass die DYRKs zumindest teilweise für die Vermittlung des Rescue-Effektes verantwortlich sind. Zusammenfassend man kann sagen, dass der Rescue-Effekt vermutlich mit der Biosynthese von Polyaminen, dem Akt-Signalweg und dem proteasomalen Abbau von c-Myc zusammenhängt. Des Weiteren scheint die direkte Inhibition von DYRKs durch CC ein vielversprechender Ansatz für die Erklärung des Effektes zu sein. Allerdings konnte in keinem der Experimente eine kompletten Aufhebung des Rescue-Effektes durch CC gezeigt werden. Daher gehen wir davon aus, dass verschiedene Targets in die Vermittlung des Rescue-Effektes involviert sind. Dies ist höchstwahrscheinlich auf eine unspezifische, ATP-kompetitive Hemmung verschiedener Kinasen durch CC zurückzuführen. Nichtsdestotrotz, sind eine nähere Untersuchung von DYRKs im Rahmen der Therapieresistenz von Tumoren und eine genauere Aufklärung der am Rescue-Effekt beteiligten Signalwege eine interessantes Feld für weitere Untersuchungen.
In addition to infectious viral particles, hepatitis B virus-replicating cells secrete high amounts of SVPs, which are ssembled by HBsAg in the shape of spheres and filaments but lack any capsid and genome. Filaments are characterized by a much higher amount of the surface protein LHBs as compared to spheres. Spheres are
released via the constitutive secretory pathway, while viral particles are ESCRT-dependently released via MVBs. The interaction of virions with the ESCRT machinery is mediated by α-taxilin that connects the PreS1 domain of LHBs with the ESCRT-component tsg101. Since viral particles and filaments contain a significant amount of LHBs, it is unclear whether filaments are secreted as spheres or released like viral particles. To study the release pathways of HBV filaments in the absence of viral particles, A core-deficient
HBV mutant (1.2×HBVΔCore) was generated by site-directed mutagenesis based on wt1.2x HBV. The start codon of core protein was mutated into stop codon, which was confirmed by DNA sequencing. Data from HBsAg ELISA, Western blot, immunofluorescence microscopy and immunoelectron microscopy showed that the lack of core protein did neither affect the production nor the secretion of HBV SVPs. The intracellular distribution of
LHBs and SHBs showed no difference between wtHBV and the core-deficient mutant expressing cells. Therefore, this system is suitable to investigate the release pathway of HBV filaments in the absence of viral particles. Confocal microscopy analysis of cells cotransfected core-deficient mutants with peYFPRab7 as marker for the endosomal/MVB pathway or with pGalT-eGFP as marker for the trans Golgi apparatus showed that YFP-Rab7, but not GalT-GFP, partially colocalized with LHBs. Furthermore, LHBs could be found in dilated MVBs by immune electron microscopy of ultrathin sections. This was confirmed by isolation of MVBs by cell fractionation using discontinuous sucrose gradient ultracentrifugation and percoll-based linear gradient ultracentrifugation, indicating that filaments enter MVBs in the absence of virion formation. Moreover, inhibition of MVB biogenesis by the small molecular inhibitor U18666A significantly abolished the release of filaments in a dose-dependent manner, but no inhibition could be observed in the production. In contrast, no inhibition on the secretion and production of spheres could be
detected. Inhibition of ESCRT-functionality by coexpression of transdominant negative mutants (Vps4A, Vps4B, CHMP3) abolished the release of filaments while secretion of spheres was not affected. These data indicate that in contrast Abstract 73 to spheres while are secreted via the secretory pathway, filaments are released via ESCRT/MVB pathway like infectious viral particles.
After the mass-vaccination campaign during the influenza A (H1N1) 2009 pandemic, a significant increase in narcolepsy incidence was observed initially in Scandinavia, later in other European countries and recently also in Canada. Narcolepsy is a sleep disease caused by the loss of hypocretin-producing cells in the hypothalamus. Almost all narcolepsy patients carry the HLA-DQB1*0602 allele, giving a link to an autoimmune-mediated process.
Most of the observed narcolepsy cases were correlated to the vaccination with Pandemrix, the most frequently used vaccine in the EU, and a slight connection to Arepanrix was also detected, which was distributed in Canada. Both vaccines were adjuvanted with AS03, suggesting a possible link between AS03 and narcolepsy. No narcolepsy cases were detected with MF59-adjuvanted or non-adjuvanted influenza vaccines. Recent studies reported differences between Pandemrix and Arepanrix and suggested the vaccine rather than the adjuvant as a suspect for narcolepsy development following vaccination. In addition, in China an increase of narcolepsy cases was reported to occur in absence of vaccination. Possible factors and potential additive effects that may have triggered narcolepsy after the pandemic vaccination are being reviewed in this paper.
Disturbances in lipid metabolism are responsible for many chronic disorders, such as type 2 diabetes and atherosclerosis. Regulation of lipid metabolism occurs by activated transcription factors peroxisome proliferator-activated receptor δ (PPARδ) and liver X receptor α (LXRα) mediating transcription of different target genes involved in regulation of fatty acid uptake and oxidation or cellular cholesterol homeostasis. This is especially relevant for the macrophages, since pathways regulated by PPARδ and LXRα affect foam cell formation, a process driving the progression of atherosclerotic lesion. AMP-activated protein kinase (AMPK) plays a central role in energy homeostasis in every type of eukaryotic cell, but its role in human macrophages, particularly with regard to lipid metabolism, is not precisely defined yet. Thus, I investigated the impact of AMPK activity on PPARδ and LXRα and the expression of their target genes involved in fatty acid oxidation (FAO) and cholesterol metabolism.
As PPARδ has been described as a potential target for prevention and treatment of several disorders and AMPK as interesting drug target for diabetes and metabolic syndrome, the aim of the first part of my studies was to investigate their interaction in primary human macrophages. Completing the first challenge successfully, I was able to establish a lentiviral transduction system for constitutively active AMPK (consisting of a truncated catalytic AMPKα1 subunit bearing an activating T198D mutation) in primary human macrophages.
Using genome-wide microarray analysis of gene expression, I demonstrate FAO as the strongest affected pathway during combined AMPKα1 overexpression and PPARδ activation.
The most influenced genes were validated by quantitative PCR as well as by Western analysis. I found that AMPK increases the expression of FAO-associated genes targeted by PPARδ. Corroborating the results obtained using AMPKα1 overexpression, PPARδ target gene expression was increased not only by PPARδ agonist GW501516, but also by pharmacological allosteric AMPK activator A-769662. Additional enhancement of target gene mRNA expression was achieved upon co-activation of PPARδ and AMPK. Silencing PPARδ expression increased basal expression of target genes, confirming the repressive nature of ligand-free PPARδ, abolishing the increased target gene expression upon AMPK or PPARδ activation. Measurements of triglyceride contents of human macrophages incubated with VLDL following PPARδ activation demonstrated a reduction of intracellular triglyceride accumulation in cells, which may reflect the enhancement of fat catabolism.
In the second part of my studies, I concentrated on the regulation of cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) expression by AMPK. ABCA1 facilitates
cholesterol efflux from macrophages thus, preventing atherosclerosis progression. For the first time, AMPK implication in the regulation of the ABCA1 pathway could be presented. Both AMPK overexpression and activation lead to significantly increased ABCA1 expression, whereas AMPKα1 knock-down strongly reduced this effect. Besides, I was able to prove an enhanced activity of ABCA1 during AMPK activation in human THP-1 macrophages by measuring cholesterol efflux into apolipoprotein AI-containing medium.
Previous findings showed regulation of ABCA1 by LXRα. I confirmed these results by silencing experiments indicating an essential role of LXRα in ABCA1 regulation pathway.
Here, ABCA1 mRNA as well as protein expression were positively mediated by LXRα. LXRα activation elevated ABCA1 levels, whereas its silencing down-regulated this effect.
Interestingly, ABCA1 was found to be regulated only by LXRα and not through LXRα. At the same time, knock-down of PPARδ, -γ or -δ, which may be also involved in the regulation of LXR/ABCA1 axis, did not influence the activation of ABCA1 expression by an AMPK activator. To confirm that LXRE on Abca1 promoter is essential for ABCA1 regulation, I performed luciferase reporter assay using constructs based on Abca1 promoter with or without LXRE mutation. Mutation of LXRE abolished reporter activity, whereas AMPK activation increased luciferase activity of wild-type LXRE construct. Furthermore, I demonstrate AMPK-dependent LXRα binding to the LXRE site of Abca1 promoter using the method of chromatin immunoprecipitation. AMPK activation significantly increased, whereas silencing of AMPK significantly attenuated LXRα binding, indicating AMPK as one of the most important regulators of ABCA1 expression.
In summary, I provided an evidence for AMPK involvement into lipid and cholesterol metabolism in human macrophages showing the regulation of PPARδ and LXRα target genes. The understanding of AMPK and PPARδ interaction allows the development of new approaches for treatment of metabolic syndrome and related diseases. Increased FAO during the activation of both proteins may exhibit better therapeutic benefit. On the other hand, I have shown the impact of AMPK activation on ABCA1 via LXRα up-regulation leading to increased cholesterol efflux in human macrophages for the first time. These findings thus may impact future improving of anti-atherosclerosis therapies.
Tiphallus torreon n. sp., the fi rst rhachodesmid milliped from Coahuila, Mexico, displays an iridescent turquoise pigmentation with patterned white paranotal markings and a truncated, subapical projection from the broad, non-descript gonopodal acropodite. Four genera – Strongylodesmus Saussure, Mexidesmus Loomis, and Ceuthauxus and Tiphallus, both by Chamberlin – contain forms exhibiting this general condition, but the last is the only one whose type species does. Synthetic treatments are essential to advance familial knowledge beyond the descriptive stage, and revising these four taxa would constitute a meaningful initial study. Rhachodesmidae extend from northern Nuevo León, Mexico, ca. 77 km (48 mi) from the Rio Grande, to central Costa Rica; Glomeridae (Glomerida), Platydesmidae (Platydesmida), and Stemmiulidae (Stemmiulida) show similar distributions whereas Allopocockiidae (Spirobolida) and Rhysodesmus Cook (Polydesmida: Xystodesmidae) traverse the river and occupy southernmost Texas. Tridontomidae, the other component of Rhachodesmoidea, occupies a small enclave in Alta Verapaz, Guatemala. Rhachodesmidae/oidea do not occur in Panama and are initially recorded from Belize; localities are needed from Honduras.
The fauna of Panama is species-rich due to its location and topography, and the resulting diversity of microclimates and habitats. The last summary of information about the caddisfly fauna (Insecta: Trichoptera) of Panama in 1992 noted 168 taxa in 13 families and 39 genera. Since then, and through 2014,
a large number of publications, based on work by a dedicated cadre of individuals, have recorded a net gain of 78 species and six genera. In 2015, 17 new species to science and 38 new country records were added, including one new family and two new genera for the country; and, two species were removed. Thus, 299 species of caddisflies are now known from the Republic of Panama and are distributed among 14 families
and 47 genera. Given the higher diversity in neighboring Costa Rica (>500 species), we feel certain that there are many more species yet to be discovered.
The frequency of intensional and non-first-order definable operators in natural languages constitutes a challenge for automated reasoning with the kind of logical translations that are deemed adequate by formal semanticists. Whereas linguists employ expressive higher-order logics in their theories of meaning, the most successful logical reasoning strategies with natural language to date rely on sophisticated first-order theorem provers and model builders. In order to bridge the fundamental mathematical gap between linguistic theory and computational practice, we present a general translation from a higher-order logic frequently employed in the linguistics literature, two-sorted Type Theory, to first-order logic under Henkin semantics. We investigate alternative formulations of the translation, discuss their properties, and evaluate the availability of linguistically relevant inferences with standard theorem provers in a test suite of inference problems stated in English. The results of the experiment indicate that translation from higher-order logic to first-order logic under Henkin semantics is a promising strategy for automated reasoning with natural languages.
"Je suis Charlie" was used over 619.000 times in the two days that have followed the attack of the editorial team of Charlie Hebdo (Le Progrès, The Huffington Post) and has regularly been taken up in both written and spoken form since. In this paper, we argue that the structure of this sentence actually clashes with its meaning. More specifically, whereas its word order and default rightmost sentence stress are compatible either with an all-focus reading or a narrow focusing of Charlie, the context of use of this sentence as well as the solidarity/empathy message it intends to communicate suggest that its subject is narrowly focused. We will propose that two strategies have emerged to solve this conflict: (i) various alternative forms have appeared that allow proper subject focusing and (ii) speakers have reinterpreted the structure so as to pragmatically retrieve the (additive) focused nature of the subject.
Increasing bike traffic in many European countries is a sign of a shift in planning paradigms towards more sustainable mobility cultures. It is also the result of 20 to 30 years of evolution and refinement in the training of urban and transport planners. Capacity development is therefore key when it comes to changing mobility cultures. Nevertheless, the day-to-day work of transport planners still focuses mostly on motorised traffic and the tasks of creating a smooth traffic flow, improving accessibility, and maintaining infrastructure. Cycling plays only a minor role, with efforts often still concentrated on the building of cycle lanes. The broader strategic goal of how to make urban mobility culture more sustainable – and within this the need to focus on cycling as an everyday mode of transport – is often neglected. Direct regulation is not possible when it comes to mobility cultures. Instead they represent a community-wide (communication) process that calls for a new planning paradigm: Besides the political will to establish a sustainable urban mobility culture, emphasis must also be placed on skills and training for urban and transport planners.
Even though the microevolution of plant hosts and pathogens has been intensely studied, knowledge regarding macro-evolutionary patterns is limited. Having the highest species diversity and host-specificity among Oomycetes, downy mildews are a useful a model for investigating long-term host-pathogen coevolution. We show that phylogenies of Bremia and Asteraceae are significantly congruent. The accepted hypothesis is that pathogens have diverged contemporarily with their hosts. But maximum clade age estimation and sequence divergence comparison reveal that congruence is not due to long-term coevolution but rather due to host-shift driven speciation (pseudo-cospeciation). This pattern results from parasite radiation in related hosts, long after radiation and speciation of the hosts. As large host shifts free pathogens from hosts with effector triggered immunity subsequent radiation and diversification in related hosts with similar innate immunity may follow, resulting in a pattern mimicking true co-divergence, which is probably limited to the terminal nodes in many pathogen groups.
In this paper we assemble an annual data set on broad and narrow money, prices, real economic activity and interest rates in Ireland from a variety of sources for the period 1933-2012. We discuss in detail how the data set is constructed and what assumptions we have made to do so. Furthermore, we estimate a simple SVAR model to provide some empirical evidence on the behaviour of these time series. Money supply shocks appear to be the most important drivers of both money and prices. Interest rate shocks, which capture monetary policy, play an important role driving output and, of course, interest rates. The GDP shocks, which raise prices, seem of less importance.
Since the 1970s, the overarching view in the literature has been that a Phillips curve relationship did not exist in Ireland prior to the 1979 exchange rate break with Sterling. It was argued that, as a small open economy, prices were determined externally. To test this relationship, we study the determination of inflation between 1926 and 2012, a longer sample period than any previously used. We find that the difference between unemployment and the NAIRU is a significant determinant of inflation both in the full sample and in the subsamples spanning the periods before and after the Sterling parity link.
Expectations of Sterling returning to Gold have been disregarded in empirical work on the US dollar – Sterling exchange rate in the early 1920s. We incorporate such considerations in a PPP model of the exchange rate, letting the probability of a return to gold follow a logistic function. We draw several conclusions: (i) the PPP model works well from spring 1919 to spring 1925; (ii) wholesale prices outperform consumer prices; (iii) allowing for a return to gold leads to a higher speed of adjustment of the exchange rate to PPP; (iv) interest rate differentials and the relative monetary base are crucial determinants of the expected return to gold; (v) the probability of a return to Gold peaked at about 72% in late 1924 and but fell to about 60% in early 1925; and (vi) our preferred model does not support the Keynes’ view that Sterling was overvalued after the return to gold.
Writing the history of archaeology has become increasingly diverse in recent years due to developments in the historiography of the sciences and the humanities. A move away from hagiography and presentations of scientific processes as an inevitable progression has been requested in this context. Historians of archaeology have begun to utilize approved and new historiographical concepts to trace how archaeological knowledge has been acquired as well as to reflect on the historical conditions and contexts in which knowledge has been generated. This volume seeks to contribute to this trend. By linking theories and models with case studies from the nineteenth and twentieth century, the authors illuminate implications of communication on archaeological knowledge and scrutinize routines of early archaeological practices. The usefulness of different approaches such as narratological concepts or the concepts of habitus is thus considered.
Mimuloria Chamberlin 1928 is revived from synonymy under Nannaria Chamberlin 1918a for Nannariini (Polydesmida: Xystodesmidae) with simple but apically ornamented gonopodal acropodites that arch or lean mediad and cross body midlines and opposing acropodites in situ. It encompasses two assemblages based primarily on the nature of the ornamentations, the castanea and dilatata species groups. The former includes three established species [M. castanea (McNeill 1887) M. missouriensis Chamberlin 1928 and M. davidcauseyi (Causey 1950a)], and the latter contains two new ones (M. dilatata [M. d. dilatata, M. d. sigmoidea], and M.
rhysodesmoides). Castanaria Causey 1950b is returned to synonymy under Mimuloria, and C. depalmai Causey 1950b is placed under M. castanea, thereby constituting a new synonymy. The fi rst illustrations of the holotype gonopods of Fontaria oblonga C. L. Koch 1847 and N. minor Chamberlin 1918a unequivocally establish their identities, and the convoluted nomenclatural tangle involving Oenomaea Hoffman 1964 and O. pulchella (Bollman 1889a) is detailed. Whether in Oenomaea or a new genus, separate generic status seems appropriate for Nannariini with subterminal solenomeres; N. morrisoni Hoffman 1948 and its potential synonym N. shenandoa Hoffman 1949 may also belong here. Initial tribal localities are reported from Alabama, South Carolina, and coastal Virginia and Maryland, and “O. pulchella” occurs in northern Alabama north/west of the Tennessee River; M. castanea is newly recorded from Missouri and Tennessee. A horizontally subtriangular distribution in the eastern and midwestern states is projected for Nannariini, which even occur on South Bass Island, Ohio, in Lake Erie, and may thus inhabit
nearby Pelee Island, Ontario, Canada.
Pandirodesmus rutherfordi, n. sp., represented by 18 individuals including eight adult males, occurs in secondary forests near Charlotteville and Speyside, Tobago, Trinidad and Tobago. Along with the type and second species, P. disparipes Silvestri, from Guyana and known only from females, the segmental legs of P. rutherfordi alternate between long (anterior pairs) and short (posterior ones), spiracular openings are on straw-like tubules, and ozopores are located on paramedian metatergal spines. These features appear to be adaptations for biotopes of loose sand, detritus, or frass, and 17 specimens, including the six juveniles, exhibit coatings of “sand grains” that are loosely cemented together and to the smooth, translucent, grayish-white exoskeleton. The tubules and spines elevate the spiracles and ozopores above the coating, thereby ensuring that they remain open and functional.
The coating, which provides camoufl age and lends strength and rigidity to the poorly sclerotized exoskeleton, is a subuniform “pavement” that covers the entire animal except the labrum/clypeus, tarsal and antennal apices, prozonae, paraprocts, and the gonopods in males. Ramose/dendritic setae, particularly on narrowly rounded podo-/antennomeres, trap “sand grains,” and the ozopore secretions apparently constitute the “glue” that cements the coating, as evidenced circumstantially by layers of “sand” between the spines on the anterior metaterga, where they are physically closest. The alternating segmental leg lengths, in part due to differing ventrolateral and ventromedial origins, appear to be an adaptation for lateral/sideways motion in which the long (anterior) legs extend laterally and pull the body to the level of the short (posterior) ones, which continue the motion while the anterior legs extend to begin the next stroke. The opposing legs perform the complementary pushing motion a fraction after the long legs initiate the pulling stroke and hence are slightly and purposefully out of sync. An adult male paratype lacks the coating, probably because it had just molted and lacked time to amass it; the juvenile female paratype of P. disparipes also is “naked,” as was, according to Silvestri, the now lost adult female holotype. Until fresh material is collected, coatings cannot be confi rmed for P. disparipes even though it shares the anatomical modifi cations that seem adaptions for such. The minute, triramous gonotelopodites of P. rutherfordi are unlike any known for a chelodesmid, so the current generic placement, in a monotypic tribe in the nominate chelodesmid subfamily, is retained. With species in both South America and the southern Antilles, Pandirodesmus/ini had to exist on both the “proto-Antillean” terrane and the adjoining part of Pangaean Gondwana before the former rifted in the Cretaceous/Paleocene, ~66 million years ago, and P. rutherfordi is a remnant of the former population that became isolated on present-day Tobago when the terrane fragmented. Affi nity between Guyanan and southern Antillean platyrhacid millipeds (Polydesmida: Leptodesmidea) suggest that Pandirodesmus/ini may occur sporadically as far north in the island chain as St. Lucia.
The aim of this paper is to analyze the concept of body developed by Luhmann's systems theory. Privileged places where one can look for the body will be the interpenetration between human beings and the concept of socialization. Another fundamental problem is the relationship between semantics and body, although the most explicit presence of the body in this theory comes with the concept of symbiotic mechanisms or symbols. The last place where this enquiry will look for a bodily reference are emotions, which were highly ignored by Luhmann. Alternative approaches explored in the paper are treating the body as a structure, as a medium or as an internal environment.
In the initial stage of relativistic heavy-ion collisions, strong magnetic fields appear due to the large velocity of the colliding charges. The evolution of these fields appears as a novel and intriguing feature in the fluid-dynamical description of heavy-ion collisions. In this work, we study analytically the one-dimensional, longitudinally boost-invariant motion of an ideal fluid in the presence of a transverse magnetic field. Interestingly, we find that, in the limit of ideal magnetohydrodynamics, i.e., for infinite conductivity, and irrespective of the strength of the initial magnetization, the decay of the fluid energy density e with proper time τ is the same as for the time-honoured “Bjorken flow” without magnetic field. Furthermore, when the magnetic field is assumed to decay , where a is an arbitrary number, two classes of analytic solutions can be found depending on whether a is larger or smaller than one. In summary, the analytic solutions presented here highlight that the Bjorken flow is far more general than formerly thought. These solutions can serve both to gain insight on the dynamics of heavy-ion collisions in the presence of strong magnetic fields and as testbeds for numerical codes.
The Treaty of Maastricht imposed the strict obligation on the European Union (EU) to establish an economic and monetary union, now Article 3(4) TEU. This economic and monetary union is, however, not designed as a separate entity but as an integral part of the EU. The single currency was to become the currency of the EU and to be the legal tender in all Member States unless an exemption was explicitly granted in the primary law of the EU, as in the case of the UK and Denmark. The newly admitted Member States are obliged to introduce the euro as their currency as soon as they fulfil the admission criteria. Technically, this has been achieved by transferring the exclusive competence for the monetary policy of the Member States whose currency is the euro on the EU, Article 3(1)(c) TFEU and by bestowing the euro with the quality of legal tender, the only legal tender in the EU, Article 128(1) sentence 3 TFEU.
The paper traces the developments from the formation of the European Economic and Monetary Union to this date. It discusses the fact that the primary mandate of the European System of Central Banks (ESCB) is confined to safeguarding price stability and does not include general economic policy. Finally, the paper contributes to the discussion on whether the primary law of the European Union would support a eurozone exit. The Treaty of Maastricht imposed the strict obligation on the European Union (EU) to establish an economic and monetary union, now Article 3(4) TEU. This economic and monetary union is, however, not designed as a separate entity but as an integral part of the EU. The single currency was to become the currency of the EU and to be the legal tender in all Member States unless an exemption was explicitly granted in the primary law of the EU, as in the case of the UK and Denmark. The newly admitted Member States are obliged to introduce the euro as their currency as soon as they fulfil the admission criteria. Technically, this has been achieved by transferring the exclusive competence for the monetary policy of the Member States whose currency is the euro on the EU, Article 3(1)(c) TFEU and by bestowing the euro with the quality of legal tender, the only legal tender in the EU, Article 128(1) sentence 3 TFEU.
In its meeting on 6 September 2012, the Governing Council of the ECB took decisions on a number of technical features regarding the Eurosystem’s outright transactions in secondary sovereign bond markets (OMT). This decision was challenged in the German Federal Constitutional Court (GFCC) by a number of constitutional complaints and other petitions. In its seminal judgment of 14 January 2014, the German court expressed serious doubts on the compatibility of the ECB’s decision with the European Union law.
It admitted the complaints and petitions even though actual purchases had not been executed and the control of acts of an organ of the EU in principle is not the task of the GFCC. As justification for this procedure the court resorted to its judicature on a reserved “ultra vires” control and the defense of the “constitutional identiy” of Germany. In the end, however, the court referred the case pursuant to Article 267 TFEU to the European Court of Justice (ECJ) for preliminary rulings on several questions of EU law. In substance, the German court assessed OMT as an act of economic policy which is not covered by the competences of the ECB. Furthermore, it judged OMT as a – by EU primary law – prohibited monetary financing of sovereign debt. The defense of the ECB (disruption of monetary policy transmission mechanism) was dismissed without closer scrutiny as being “irrelevant”. Finally the court opened, however, a way for a compromise by an interpretation of OMT in conformity with EU law under preconditions, specified in detail.
Procedure and findings of this judgment were harshly criticized by many economists but also by the majority of legal scholars. This criticism is largely convincing in view of the admissibility of the complaints. Even if the “ultra vires” control is in conformity with prior decisions of court it is in this judgment expanded further without compelling reasons. It is also questionable whether the standing of the complaining parties had to be accepted and whether the referral to the ECJ was indicated. The arguments of the court are, however, conclusive in respect of the transgression of competences by the ECB and – to somewhat lesser extent – in respect of the monetary debt financing. The dismissal of the defense as “irrelevant” is absolutey persuasive.
Tracheomalacia or tracheobronchomalacia (TM or TBM) is a common problem especially for elderly patients often unfit for surgical techniques. Several surgical or minimally invasive techniques have already been described. Stenting is one option but in general long-time stenting is accompanied by a high complication rate. Stent removal is more difficult in case of self-expandable nitinol stents or metallic stents in general in comparison to silicone stents. The main disadvantage of silicone stents in comparison to uncovered metallic stents is migration and plugging. We compared the operation time and in particular the duration of a sufficient Dumon stent fixation with different techniques in a patient with severe posttracheotomy TM and strongly reduced mobility of the vocal cords due to Parkinson’s disease. The combined approach with simultaneous Dumon stenting and endoluminal transtracheal externalized suture under cone-beam computer tomography guidance with the Berci needle was by far the fastest approach compared to a (not performed) surgical intervention, or even purely endoluminal suturing through the rigid bronchoscope. The duration of the endoluminal transtracheal externalized suture was between 5 minutes and 9 minutes with the Berci needle; the pure endoluminal approach needed 51 minutes. The alternative of tracheobronchoplasty was refused by the patient. In general, 180 minutes for this surgical approach is calculated. The costs of the different approaches are supposed to vary widely due to the fact that in Germany 1 minute in an operation room costs on average approximately 50–60€ inclusive of taxes. In our own hospital (tertiary level), it is nearly 30€ per minute in an operation room for a surgical approach. Calculating an additional 15 minutes for patient preparation and transfer to wake-up room, therefore a total duration inside the investigation room of 30 minutes, the cost per flexible bronchoscopy is per minute on average less than 6€. Although the Dumon stenting requires a set-up with more expensive anesthesiology accompaniment, which takes longer than a flexible investigation estimated at 1 hour in an operation room, still without calculation of the costs of the materials and specialized staff that the surgical approach would consume at least 3,000€ more than a minimally invasive approach performed with the Berci needle. This difference is due to the longer time of the surgical intervention which is calculated at approximately 180 minutes in comparison to the achieved non-surgical approach of 60 minutes in the operation suite.
Reading is not only "cold" information processing, but involves affective and aesthetic processes that go far beyond what current models of word recognition, sentence processing, or text comprehension can explain. To investigate such "hot" reading processes, standardized instruments that quantify both psycholinguistic and emotional variables at the sublexical, lexical, inter-, and supralexical levels (e.g., phonological iconicity, word valence, arousal-span, or passage suspense) are necessary. One such instrument, the Berlin Affective Word List (BAWL) has been used in over 50 published studies demonstrating effects of lexical emotional variables on all relevant processing levels (experiential, behavioral, neuronal). In this paper, we first present new data from several BAWL studies. Together, these studies examine various views on affective effects in reading arising from dimensional (e.g., valence) and discrete emotion features (e.g., happiness), or embodied cognition features like smelling. Second, we extend our investigation of the complex issue of affective word processing to words characterized by a mixture of affects. These words entail positive and negative valence, and/or features making them beautiful or ugly. Finally, we discuss tentative neurocognitive models of affective word processing in the light of the present results, raising new issues for future studies.
Different highly effective interferon-free treatment options for chronic hepatitis C virus (HCV) infection are currently available. Pre-existence of resistance associated variants (RAVs) to direct antiviral agents (DAAs) reduces sustained virologic response (SVR) rates by 3–53% in hepatitis C virus (HCV) genotype 1 infected patients depending on different predictors and the DAA regimen used. Frequencies of single and combined resistance to NS3, NS5A and NS5B inhibitors and consequences for the applicability of different treatment regimens are unknown. Parallel population based sequencing of HCV NS3, NS5A and NS5B genes in 312 treatment-naïve Caucasian HCV genotype 1 infected patients showed the presence of major resistant variants in 20.5% (NS3), 11.9% (NS5A), and 22.1% (NS5B) with important differences for HCV subtypes. In NS3, Q80K was observed in 34.7% and 2.1% of subtype 1a and 1b patients, respectively while other RAVs to second generation protease inhibitors were detected rarely (1.4%). Within NS5A RAVs were observed in 7.1% of subtype 1a and 17.6% in subtype 1b infected patients. RAVs to non-nucleoside NS5B inhibitors were observed in 3.5% and 44.4% of subtype 1a and 1b patients, respectively. Considering all three DAA targets all subtype 1a and 98.6% of subtype 1b infected patients were wildtype for at least one interferon free DAA regimen currently available. In conclusion, baseline resistance testing allows the selection of at least one RAVs-free treatment option for nearly all patients enabling a potentially cost- and efficacy-optimized treatment of chronic hepatitis C.
We model education as an investment in human capital that, like other investments, is appropriately evaluated in a framework that accounts for risk as well as return. In contrast to dominant wage-premia approach to calculating the returns to education, but which implicitly ignores risk, we evaluate the returns by treating the value of human capital as the price of a non-tradable risky asset. We do so using a lifecycle framework that incorporates risk preferences and earnings risk, as well as a progressive income tax and social insurance system. Our baseline estimate is that a college degree provides a $440K dollar increase in annual certainty-equivalent consumption. Although significantly smaller than traditional estimates of the value of education, these returns are still large enough to offset both the direct and indirect cost of college education for a large range of plausible preference parameters. Importantly, however, we find that accounting for risk reverses the finding from the education wage-premia literature regarding the trends in the returns to education. In particular, we find that the risk-adjusted gains from college completion actually decreased rather than increased in the recent period. Overall, our results show the importance of earnings risks in assessing the value of education.
This paper studies a two-country production economy with complete and frictionless financial markets and international trade of final goods in which competition in R&D leads to endogenous new firm creation and economic growth. Current monopolists ("incumbents") and potential new firms ("entrants") compete in developing patents domestically. I find that this induces negative spillover in consumption, i.e. home country's consumption decreases in response to positive productivity shocks in the foreign country. Second, there is positive spillover in R&D expenditures, i.e. home country's R&D expenditures increase in response to positive foreign productivity shocks, which is consistent with empirical evidence on international technology diffusion. Furthermore, the stylized fact in international macroeconomics that the cross-country correlation of consumption growth is significantly lower than the one of output growth is explained by the model. Fourth, net exports are negatively correlated with output as in the data. Fifth, the model matches the high comovement of the risk-free rates and stock returns across countries. Finally, the model produces a positive value premium.
The role of social groups in making historical events succeed takes shape according to two important factors: Their ability to change and the kind of their contribution to the development of that change in a way or another. The role of social groups especially emerges at times of revolutions and their subsequent changes on the political, socioeconomic and even intellectual levels. The most active and capable group to achieve change is the group of youth and students. In the revolutionary movements in Latin America, for instance, students prominently contributed to the fall down of long-lasting totalitarian dictatorships such in Chile, Brazil and Argentina. In the Arab uprisings in 2010-2011, students‘ roles varied from one country to another based on three axes of context, networks and contentious practices. This article expands on the role of Egyptian student movement in thriving for change despite the intensified restrictions by the state and how it continued its protest under repressive circumstances as a political actor...
The aim of this study was to identify sex-dependent expression of renal transporter mRNA in lean and obese Zucker spontaneously hypertensive fatty (ZSF1) rats and to investigate the interaction of the most altered transporter, organic anion transporter 2 (Oat2), with diabetes-relevant metabolites and drugs. Higher incidence of glomerulosclerosis, tubulointerstitial fibrosis, and protein casts in Bowman’s space and tubular lumen was detected by PAS staining in obese male compared to female ZSF1 rats. Real-time PCR on RNA isolated from kidney cortex revealed that Sglt1-2, Oat1-3, and Oct1 were higher expressed in kidneys of lean females. Oct2 and Mrp2 were higher expressed in obese males. Renal mRNA levels of transporters were reduced with diabetic nephropathy in females and the expression of transcription factors Hnf1β and Hnf4α in both sexes. The highest difference between lean and obese ZSF1 rats was found for Oat2. Therefore, we have tested the interaction of human OAT2 with various substances using tritium-labeled cGMP. Human OAT2 showed no interaction with diabetes-related metabolites, diabetic drugs, and ACE-inhibitors. However, OAT2-dependent uptake of cGMP was inhibited by furosemide. The strongly decreased expression of Oat2 and other transporters in female diabetic ZSF1 rats could possibly impair renal drug excretion, for example, of furosemide.
This paper undertakes a quantitative investigation of the effects of anticipated inflation on the distribution of household wealth and welfare. Consumer Finance Data on household financial wealth suggests that about a third of the US population holds all its financial assets in transaction accounts. The remaining two-third of the US population holds most of their financial assets outside transaction accounts. To account for this evidence, I introduce a portfolio choice in a standard incomplete markets model with heterogeneous agents. I calibrate the model economy to SCF 2010 US data and use this environment to study the distributive effects of changes in anticipated inflation. An increase in anticipated inflation leads households to reshuffle their portfolio towards real assets. This crowding-in of supply for real assets lowers equilibrium interest rates and thereby redistributes wealth from creditors to borrowers. Because borrowers have a higher marginal utility, this redistribution improves aggregate welfare. First, this paper shows that inflation acts not only a regressive consumption tax as in Erosa and Ventura (2002), but also as a progressive tax. Second, this paper shows that the welfare cost of inflation are even lower than the estimates computed by Lucas (2000) and Ireland (2009). Finally, this paper offers insights into why deflationary environments should be avoided.
Political rationality as a theory is important in its own right. Government leaders must calculate political costs such as the resources needed to generate support for a policy, the implications of a policy decision for re-election, and the possibility of provoking hostility for decisions not well received. Bounded rationality approach has yielded an enhanced understanding of how government organizations may produce unexpected or even unpredicted policy or program results. With public organizations not operating under full rationality conditions, administrators aspiring toward rationality may nonetheless find their goals undermined by a variety of forces, such as informational uncertainties and non-rational elements of organisational decision-making...
Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
Indigenous knowledge is the dynamic information base of a society, facilitating communication and decision-making. It is the cornerstone of many modern-day innovations in science and technology. It is also a ready and valuable resource for sustainable and resilient livelihoods, and attracts increasing public interest due to its applications in bio-technology, health, bioprospecting, pharmaceuticals, agriculture, food preparation, mathematics and astronomy. INDIGENOUS KNOWLEDGE OF NAMIBIA is a fascinating compendium aimed at a wide readership of academics and students, government officials, policy makers, and development partners. The 17 chapters examine the indigenous knowledge of medicinal plants for treating HIV/AIDS, malaria, cancer, and other microbial infections of humans and livestock; indigenous foods; coping and response strategies in dealing with human-wildlife conflicts, floods, gender, climate change and the management of natural resources. A new rationalisation of adolescent customary and initiation ceremonies is recommended in response to the HIV/AIDS pandemic; and a case study of the San people of Namibia speaks to the challenges of harmonising modern education with that of indigenous people.
Re-Viewing Resistance in Namibian History brings together the work of experienced academics and a new wave of young Namibian historians - architects of the past - who are working on a range of public history and heritage projects, from late nineteenth century resistance to the use of songs, from the role of gender in SWAPO's camps to memorialisation, and from international solidarity to aspects of the history of Kavango and Caprivi. In a culturally and politically diverse democracy such as Namibia, there are bound to be different perspectives on the past, and history will be as plural as the history-tellers. The chapters in this book reflect this diversity, and combine to create a remarkable collection of divergent voices, providing alternative perspectives on the past. Re-Viewing Resistance in Namibian History writes 'forgotten' people into history; provides a reading of the past that reflects the tensions and competing identities that pervaded 'the struggle'; and deals with 'heritage that hurts'.
This edited volume is about the rekindled investment in the figure of the first president Julius K. Nyerere in contemporary Tanzania. It explores how Nyerere is remembered by Tanzanians from different levels of society, in what ways and for what purposes. Looking into what Nyerere means and stands for today, it provides insight into the media, the political arena, poetry, the education sector, or street-corner talks. The main argument of this book is that Nyerere has become a widely shared political metaphor used to debate and contest conceptions of the Tanzanian nation and Tanzanian-ness. The state-citizens relationship, the moral standards for the exercise of power, and the contours of national sentiment are under scrutiny when the figure of Nyerere is mobilized today. The contributions gathered here come from a generation of budding or renowned scholars in varied disciplines - history, anthropology and political science. Drawing upon materials collected through extensive fieldwork and archival research, they all critically engage the existing literature about Tanzania and prevailing political narratives to explore how nationhood is (re)imagined in Tanzania today through assent and contest.
This is a commemorative volume devoted to the late Professor Willfried F. Feuser, a literary icon and a comparatist of no mean repute. Though German by origin, Professor Feuser showed great concern to the Africanist agenda of self-realisation, and therefore devoted the greatest part of his productive academic life to the cultural revival and socio-economic emancipation of Africa and the Diaspora through his scholarly publications. This book contains 20 essays on a wide range of issues in literary criticism.
The Last Of The Virgins
(2015)
Evelyn Ndangeh, a pretty Cameroonian teenager brought up in a strict Christian home, vows to preserve her maidenhood until she gets married to a man she truly loves. While in Our Lady of Lourdes College Mankon, she is approached by Lesley Njapa a student of Cameroon Protestant College Bali, after a student of CCAST Bambili. Evelyn turns him down only to find later that she can't stay alone without a man who must be none other than Lesley. Evelyn begins frantic moves to entice Lesley but on meeting him it seems too late though she gets close to his heart. Tragedy strikes when Lesley is involved in a motor accident. Evelyn arrives Bamenda general hospital wailing and settles beside Lesley to console and comfort him in his agony. Anxiety builds up to a crescendo and a medical team is mobilised to save Lesley's life.
According to Fossungu, we need healthy competition for progress. Competition that is not geared toward progress is negative competition. No competition or the absence of self-help is negative competition. With factories competing healthily, consumers have a variety of quality goods and services from which to choose. The entire community benefits when people in any grouping are competing positively; thus making the rules of competition graphical. The central focus of this book is the extent to which Canadian regulations apply without discrimination to all of Canada and to everyone, individuals and corporations alike. A swift answer is affirmative. But is that really it? The book is also about voluntary slavery, which is worse than forced enslavement. Drawing on Ignorance Theory, the book argues that the worst thing that can happen to anyone is to be ignorant of one's ignorance. He who does not know what he does not know will never know. Voluntary African slaves generally employ 'One Has No Choice' (On n'a pas le choix) to cloak their having chosen not to secure their rights. Fossungu demonstrates why he considers this an escapist way of shying away from doing the normal thing, thus giving the dictator or oppressor reason to dictate and oppress with impunity. This is Fossungu at his provocative and controversial best.
One Eternal Sleep
(2015)
In this volume Bill F. Ndi portrays life, death, and dying as one great adventure through which one would explore the limitless bounds of Life. At its best, the collection echoes the words of anthropologist Francis B. Nyamnjoh when he underlines that, 'one is only dead to particular context as a way of making oneself alive to prospective new contexts.' Ndi in this collection invites the reader to learn the art of living through the art of dying and accepting death.
Issue Two of Women in Islam includes investigations of social issues, profiles of inspiring women, book and film reviews, poetry, and opinion pieces. The theme of the dossier, The Female Body: A Contested Land, focuses on womens bodies, including articles on FGM, sexual harassment, and how art can challenge repressive social norms. Another section focuses on masculinity and the ways men can support women in the struggle for equality. Other highlights include profiles of Somali singer and politician Saado Ali Warsame, an analysis of Sudans discriminatory legal system, and a portrait of a Muslim society in Sumatra where religion and matriarchal traditions coexist.
Contemporary Oral Literature Fieldwork is based on rich research experience dating back to the 1990s. The book is written against the backdrop of Africa's confusion with regard to the place of oral literature in the face of the rest of the world, where oral literature exists in conjunction with new literary forms. Wasamba argues that the oral and the written literatures are complementary literary forms. Throughout the work, the author underscores the universal dimension of oral literature as he demonstrates its particular attributes.
This publication addresses the extent to which social work curricula in Kenya prepares graduates to handle issues of poverty and social development, the specific knowledge and skills that they are equipped with an existing gaps therein. In addition, the challenges that confront the training and practice of social workers and what needs to be done to ensure that there is an enabling environment for social work education and practice in the country have also been addressed. The publication, which is the outcome of a study on the promotion of professional social work towards social development and poverty reduction in East Africa, analyses the role that professional social work plays in the efforts to reduce poverty, enhance social development and realise the Millennium Development Goals (MDGs) in Kenya. Consequently, emphasis has been laid on the status of professional social work education and practice in preparing social workers to address issues of poverty and MDGs in the country. Cross cutting gender issues that impact on social work education and practice which in turn affect the efforts to address poverty in Kenya have also been analysed. Given that the time span for MDGs was to end in 2015, the authors envisage that the lessons learnt through this study, and the gains made with regard to MDGs should not end in the set time span but rather, that social work educators and practitioners, together with other stakeholders in policy formulation and implementation, still have more to of in making sure that these gains are consolidated into social work training and practice, with additional efforts being made towards sustainable poverty reduction efforts in Kenya.
When voters enthusiastically turn up to cast their vote during general elections, they expect that their action would meaningfully change their lives. But in most of Africa, even when elections are held on a regular basis, voters are quite often disappointed by the performance of their leaders who use the new positions as an opportunity to loot public resources and consolidate power. It is almost as if elections are of minimal value to the populace. Notwithstanding this trend, when they are free and fair, general elections can be transformative. They can bring into the political arena men and women of integrity committed to service and account-ability. Inspired by the determination to have inclusive governance and the advancement of democracy, Kenya's 2013 General Election: Stakes, Practices and Outcomes asks important questions related to political participation, coalition building, politics of identity, the international criminal court, electoral systems and institutions, and the judiciary. The papers are written by mainly Kenyan academics and civil society actors who examine the drivers of the 20?3 general elections and the sources of the mandate to lead.This book is part of publications by Twaweza Communications on democratic practice and accountable governance in Kenya.
Bites of Insanity
(2015)
In this collection of poems Nsah Mala casts a critical compassionate gaze at the predicaments in the lives of present day Cameroonians. The poet lambasts power abuse in Cameroon and Africa. He decries the lost glory of traditional values sacrificed at the altar of ingratiation and materialism. Insalubrities are condemned, ignorance and its ramifications satirised, and wanton destruction of the environment indicted. With a fascinating richness of imagery, Mala conveys the disillusionment, bitterness and traumas of ordinary Cameroonians - young and old - debased with impunity by the lethal and sterile grip on power of the high and might. The moral depravity and human frailties mused about in this exceptionally compelling collection have no room in Mala's paradise of Cameroon.
Unmasking Social Science Imperialism : Globalization Theory As A Phase Of Academic Colonialism
(2015)
Contemporary social science is a product of the capitalist world-system and Eurocentrism is constitutive of the geoculture of this system characterized by the parochiality of its universalism, assumptions about the superiority of Western civilization and imposition as the sole theory of global progress. The creation of these structures of knowledge, specifically the institutionalization of the social sciences, is a phenomenon that is inextricably linked to the very formation and maturation of Europe's capitalist world system or imperialism. There is therefore nothing that is natural, logical, or accidental about the institutionalization of the social sciences. These Europeanized structures of knowledge are imposed ways of producing knowledge of the world. This Eurocentrism of social science has justifiably come under increasingly vigorous scrutiny, especially in the period since 1945 with the formal decolonization of Africa, Asia, and much of the Caribbean. This book forcefully argues that if social science is to make any progress in the twenty-first century, it must overcome its Eurocentric heritage that has distorted social analyses and its capacity to deal with the problems of the contemporary world and embrace other non-Western funds of knowledge production.
Between Rhetoric and Reality : The State and Use of Indigenous Knowledge in Post-Colonial Africa
(2015)
Since time immemorial, indigenous peoples around the world have developed knowledge systems to ensure their continued survival in their respective territories. These knowledge systems have always been dynamic such that they could meet new challenges. Yet, since the so-called enlightenment period, these knowledges have been supplanted by the Western enlightenment science or colonial science hegemony and arrogance such that in many cases they were relegated to the periphery. Some Euro-centric scholars even viewed indigenous knowledge as superstitious, irrational and anti-development. This erroneous view has, since the colonial period, spread like veld fire to the extent of being internalised by some political elites and Euro-centric academics of Africa and elsewhere. However, for some time now, the potential role that indigenous peoples and their knowledge can play in addressing some of the global problems haunting humanity across the world is increasingly emerging as part of international discourse. This book presents an interesting and insightful discourse on the state and role that indigenous knowledge can play in addressing a tapestry of problems of the world and the challenges connected with the application of indigenous knowledge in enlightenment science-dominated contexts. The book is not only useful to academics and students in the fields of indigenous studies and anthropology, but also those in other fields such as environmental science, social and political ecology, development studies, policy studies, economic history, and African studies.
Blot On The Landscape
(2015)
This Book is the outcome of a long project begun thirty years ago. It is a book on the makings of pan-Africanism through the predicaments of being black in a world dominated by being white. The book is a tribute and celebration of the efforts of the African-American and African-Caribbean Diaspora who took the initiative and the audacity to fight and liberate themselves from the shackles of slavery. It is also a celebration of those Africans who in their own way carried the torch of inspiration and resilience to save and reconstruct the Free Humanism of Africa. As a story of the rise from the shackles of slavery and poverty to the summit of Victors of their Renaissance Identity and Self-Determination as a People, the book is the story of African refusal to celebrate victimhood. The book also situates women as central actors in the Pan-African project, which is often presented as an exclusively masculine endeavour. It introduces a balanced gender approach and diagnosis of the Women actors of Pan-Africanism which was very much lacking. The problem of balkanisation of Africa on post-colonial affiliations and colonial linguistic lines has taken its toll on Africa's building of its common identity and personality. The result is that Africans are more remote to each other in their pigeon-hole-nation-states which put more restrictions for African inter-mobility, coupled by education and cultural affiliations, the communication and transportation and trading networks which are still tied more to their colonial masters than among themselves. This book looks into the problem of the new wave of Pan-Africanism and what strategies that can be proposed for a more participatory Pan-Africanism inspired by the everyday realities of African masses at home and in the diaspora. This book is the first book of its kind that gives a comprehensive and multidimensional coverage of Pan-Africanism. It is a very timely and vital compendium.
Questions surrounding democracy, governance, and development especially in the view of Africa have provoked acrimonious debates in the past few years. It remains a perennial question why some decades after political independence in Africa the continent continues experiencing bad governance, lagging behind socioeconomically, and its democracy questionable. We admit that a plethora of theories and reasons, including iniquitous and malicious ones, have been conjured in an attempt to explain and answer the questions as to why Africa seems to be lagging behind other continents in issues pertaining to good governance, democracy and socio-economic development. Yet, none of the theories and reasons proffered so far seems to have provided enduring solutions to Africas diverse complex problems and predicaments. This book dissects and critically examines the matrix of Africas multifaceted problems on governance, democracy and development in an attempt to proffer enduring solutions to the continents long-standing political and socio-economic dilemmas and setbacks.
This book makes a rare contribution towards the preservation and promotion of ukhaliro wa bene Malawi (Malawian culture) that is fast waning. This dilution of culture was put in motion by the British colonial masters and got exacerbated with the inception of democratic governance in 1994. There is need for concerted efforts amongst various practitioners and stakeholders, led by the government itself, if the situation is to be put under control. Otherwise, sooner or later, it will simply be remote history that long time ago, there was a unique culture in Malawi. The book is a collection of twenty short stories that generally promote such themes as nkharo yiwemi (good behaviour); uheni wa chigolo na sanje (the bad side of selfishness and jealousy); kulimbikira pa vinthu (hard working spirit); and uheni wa mitala (the folly of polygamy), among others. The strength of the book lies in the fact that there is room for the reader to draw their own lessons based on their understanding of a particular story, in addition to the lesson already highlighted there-in. The book is a must read for all, young and old, especially those interested in understanding the societal values, not only about Malawi, but of Africa as a whole.
'In Who's Afraid of Mongo Wa Swolenka? a book launch is planned which, from information given to His Royal Excellency Gbadarango Binyambutu Buthablaisi, by a traitorous intellectual seeking preferment; and by his security agents, is a campaign led by disgruntled writers and intellectuals of Nubialand for the return of their exiled colleague and international award winner, Professor Mongo Wa Swolenka. How the celebrated leader of Nubialand and master of gunocratic politics responds to the prevailing circumstances is the nerve centre of dialogue, action and morality in the play.' - John Nkemngong Nkengasong, Writer and critic, University of Yaounde I, Cameroon
Africa Reunite or Perish
(2015)
Africa Reunite or Perish is a daring and timely book that explores the essence and nefariousness of neocolonialism in a purportedly independent Africa. The book shows how Africa spends billions of dollars in pseudo threats among African countries due to colonially-entrenched fear and war mongering. The book is emphatic on deconstruction and decolonisation as a categorical imperative for the reunification of Africa beyond the narrow confines of current nation states. Mhango takes a diagnostic-cum-prognostic approach in discussing Africa's predicaments, and in identifying and proposing solutions to problems confronting Africans. The book ascertains Africa's untapped potentials by proving how Africa can live without the infamy of excruciating dependency and beggarliness. It makes a compelling case for African unity beyond the tokenism of officialdom. It prescribes a truly pan-African driven reunification of Africa as the only means of reclaiming the glory she used to enjoy before she was savagely partitioned.
100 years since the end of German colonial rule in Namibia, the relationship between the former colonial power and the Namibian communities who were affected by its brutal colonial policies remains problematic, and interpretations of the past are still contested. This book examines the ongoing debates, conflicts and confrontations over the past. It scrutinises the consequences of German colonial rule, its impact on the descendants of victims of the 190408 genocide, Germanys historical responsibility, and ways in which post-colonial reconciliation might be achieved.
Milestones in Green Transition and Climate Compatible Development in Eastern and Southern Africa
(2015)
It is widely recognised that climate change poses significant serious threats to sustained economic growth and agricultural development, poverty reduction, food security and political stability globally. Nowhere are these challenges more marked than in Africa where two-thirds of all available land is classified either as desert or dry land, in relation to which the Intergovernmental Panel on Climate Change (IPCC) (2013) has classified the continent as the most vulnerable to climate change variability. This anthology is a product of a call from OSSREA to collate evidence based researches in a book in a bid to assess how far countries in eastern and southern Africa are implementing the UNFCCC, Rio+20, Agenda 21 and other global and Africa-wide decisions concerning the need to address climate change. This will contribute to post-2015 development agenda for sustainable development goals (SDGs), in which climate change and disaster risk reduction will be priority areas of focus. We hope this book will serve as a valuable tool for experts, advisers and policymakers in pursing effective green growth policies and practices and achieving climate compatible development and in doing so inspire readers to choose a more sustainable pathway for humanity. It will also help in looking at climate change as both a challenge and opportunity for development. Further, this book aims at stimulating more research in climate compatible development and climate financing which have put most countries at crossroads.
The Rwandan justice system know as Gacaca, originally preserved by word of mouth was revived, documented, tested and used successfully to handle millions of legal cases in the aftermath of the Rwandan genocide against the Tutsi. This monograph begins by depicting the general picture of customary law and ponders on the practical challenges in the production of the modern Gacaca law in three versions: Kinyarwanda, French and English. The author demonstrates that translation involves language use and transfer, as well as communication within a cultural setting. The book amply demonstrates that linguistic, textual, contextual and cultural cues in translation should not be downplayed. It also shows that the cultural turn in translation has transformed and re-conceptualised the translation theory to integrate non-western thought about translation discipline since time immemorial. A major theme within the book is that teranslation as a mediating form between cultures and contexts should not overlook cultural differences because language is a marker of identity.
Kenya, Uganda and Tanzania have minorities from the Indian sub-continent amongst their population. The East African Indians mostly reside in the main cities, particularly Nairobi, Dar es Salaam, Zanzibar, Mombasa, Kampala; they can also be found in smaller urban centres and in the remotest of rural townships. They play a leading social and economic role as they work in business, manufacturing and the service industry, and make up a large proportion of the liberal professions. They are divided into multiple socio-religions communities, but united in a mutual feeling of meta-cultural identity. This book aims at painting a broad picture of the communities of Indian origin in East Africa, striving to include changes that have occurred since the end of the 1980s. The different contributions explore questions of race and citizenship, national loyalties and cosmopolitan identities, local attachment and transnational networks. Drawing upon anthropology, history, sociology and demography, Indian Africa depicts a multifaceted population and analyses how the past and the present shape their sense of belonging, their relations with others, their professional and political engagement. This book is a must-read for contemporary researchers, students, policy practitioners as well as the general reader.
The volume constitutes Klaus Fiedler's crowning contribution to scholarship. Essays in the first half of the book focus on Malawian Christianity and how contrasting Powers, Gospel and Secular, engage each other, creating social, political and cultural conflict in the process. In the second half, Fiedler examines general missiological themes. These essays provide a broader missiological background, offering a theoretical framework necessary for appreciating the essays in the first half. He concludes with a chapter that reviews selected seminal books on themes under study. Throughout the volume Fiedler applies the 'restorationist revival theory' he constructed in The Story of Faith Missions, an earlier 1994 work putting emphasis on non classical missions and churches, not systematically covered in earlier scholarship. This volume, the first of its kind on Malawian Christianity, will long remain an indispensable text for those interested in Missiology and Malawian Christianity.