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Reciprocal exchanges can be understood as the updating of an initial belief about a partner. This initial level of trust is essential when it comes to establishing cooperation with an unknown partner, as cooperation cannot arise without a minimum of trust not justified by previous successful exchanges with this partner. Here we demonstrate the existence of a representation of the initial trust level before an exchange with a partner has occurred. Specifically, we can predict the Investor’s initial investment—i.e. his initial level of trust toward the unknown trustee in Round 1 of a standard 10-round Trust Game—from resting-state functional connectivity data acquired several minutes before the start of the Trust Game. Resting-state functional connectivity is, however, not significantly associated with the level of trust in later rounds, potentially mirroring the updating of the initial belief about the partner. Our results shed light on how the initial level of trust is represented. In particular, we show that a person’s initial level of trust is, at least in part, determined by brain electrical activity acquired well before the beginning of an exchange.
How to abolish cyberwar
(2014)
Part III of our series "Cyberpeace: Dimensionen eines Gegenentwurfs" on cyberpeace: Cyberwar is like a discursive plague. After years and years of writing texts about it and against it, the concept is still scary, still spreading, still harmful. Its power is such that it is not simply being used in discourse – but is in fact forcing its specific discursive structures and rules on us. In short, we may keep questioning this concept, but we will never get rid of it...
In ‘Strafe für fremde Schuld’ Harald Maihold uncovered how a doctrine of surrogate punishment in the legal treatises of the Salamanca school gradually gave way to the principle of guilt. This meant that punishment eventually could only be inflicted upon a culprit and no longer upon an innocent. We will use René Girard’s philosophy of (the disruption of) scapegoat mechanisms and sacrifice to develop a coherent interpretation not only of how this institution of surrogate punishment functioned, how it selected its victims and the way it was legitimated, but also of the theology that formed its background. We argue that most of what surrogate punishment is about can be grasped in two words: sacrificial logic. The elimination of surrogation from criminal law would then correspond to the rejection of this logic, an evolution which could be interpreted as a desacralisation or secularisation of criminal law under the influence of the upcoming principle of guilt.
How special are they? - Targeting systemic risk by regulating shadow banking : (October 5, 2014)
(2014)
This essay argues that at least some of the financial stability concerns associated with shadow banking can be addressed by an approach to financial regulation that imports its functional foundations more vigorously into the interpretation and implementation of existing rules. It shows that the general policy goals of prudential banking regulation remain constant over time despite dramatic transformations in the financial and technological landscape. Moreover, these overarching policy goals also legitimize intervention in the shadow banking sector. On these grounds, this essay encourages a more normative construction of available rules that potentially limits both the scope for regulatory arbitrage and the need for ever more rapid updates and a constant increase in the complexity of the regulatory framework. By tying the regulatory treatment of financial innovation closely to existing prudential rules and their underlying policy rationales, the proposed approach potentially ends the socially wasteful race between hare and tortoise that signifies the relation between regulators and a highly dynamic industry. In doing so it does not generally hamper market participants’ efficient discoveries where disintermediation proves socially beneficial. Instead, it only weeds-out rent-seeking circumventions of existing rules and standards.
How special are they? - Targeting systemic risk by regulating shadow banking : (October 5, 2014)
(2014)
This essay argues that at least some of the financial stability concerns associated with shadow banking can be addressed by an approach to financial regulation that imports its functional foundations more vigorously into the interpretation and implementation of existing rules. It shows that the general policy goals of prudential banking regulation remain constant over time despite dramatic transformations in the financial and technological landscape. Moreover, these overarching policy goals also legitimize intervention in the shadow banking sector. On these grounds, this essay encourages a more normative construction of available rules that potentially limits both the scope for regulatory arbitrage and the need for ever more rapid updates and a constant increase in the complexity of the regulatory framework. By tying the regulatory treatment of financial innovation closely to existing prudential rules and their underlying policy rationales, the proposed approach potentially ends the socially wasteful race between hare and tortoise that signifies the relation between regulators and a highly dynamic industry. In doing so it does not generally hamper market participants’ efficient discoveries where disintermediation proves socially beneficial. Instead, it only weeds-out rent-seeking circumventions of existing rules and standards.
Before the 2007–09 crisis, standard risk measurement methods substantially underestimated the threat to the financial system. One reason was that these methods didn’t account for how closely commercial banks, investment banks, hedge funds, and insurance companies were linked. As financial conditions worsened in one type of institution, the effects spread to others. A new method that more accurately accounts for these spillover effects suggests that hedge funds may have been central in generating systemic risk during the crisis.
How much additional tax revenue can the government generate by increasing labor income taxes? In this paper we provide a quantitative answer to this question, and study the importance of the progressivity of the tax schedule for the ability of the government to generate tax revenues. We develop a rich overlapping generations model featuring an explicit family structure, extensive and intensive margins of labor supply, endogenous accumulation of labor market experience as well as standard intertemporal consumption-savings choices in the presence of uninsurable idiosyncratic labor productivity risk. We calibrate the model to US macro, micro and tax data and characterize the labor income tax Laffer curve under the current choice of the progressivity of the labor income tax code as well as when varying progressivity. We find that more progressive labor income taxes significantly reduce tax revenues. For the US, converting to a flat tax code raises the peak of the Laffer curve by 6%, whereas converting to a tax system with progressivity similar to Denmark would lower the peak by 7%. We also show that, relative to a representative agent economy tax revenues are less sensitive to the progressivity of the tax code in our economy. This finding is due to the fact that labor supply of two earner households is less elastic (along the intensive margin) and the endogenous accumulation of labor market experience makes labor supply of females less elastic (around the extensive margin) to changes in tax progressivity.
Rising powers are fundamentally shifting the relations of power in the global economic and political landscape. International political theory, however, has so far failed to evaluate this nascent multipolarity. This article fills this lacuna by synthesizing empirical and normative modes of inquiry. It examines the transformation of sovereignty exercised by emerging democracies and focuses especially on the case of Brazil. The paper shows that – in stark contrast to emerging democracies' foreign policy rhetoric – the "softening" of sovereignty, which means that emerging powers gain as well as lose certain aspects of sovereignty, has become the norm. The paper explores this softening of sovereignty from the perspective of global justice by assessing it on the basis of globalist, statist, and internationalist conceptions of global justice. We find that the emergent multipolarity contributes in various ways to the realization of the distinct socioeconomic and political criteria of these three conceptions of global justice. However, we also point out that the transformation of sovereignty generates particular problems for the realization of all three conceptions.
This paper studies the geometry and the thermodynamics of a holographic screen in the framework of the ultraviolet self-complete quantum gravity. To achieve this goal we construct a new static, neutral, nonrotating black hole metric, whose outer (event) horizon coincides with the surface of the screen. The spacetime admits an extremal configuration corresponding to the minimal holographic screen and having both mass and radius equalling the Planck units. We identify this object as the spacetime fundamental building block, whose interior is physically unaccessible and cannot be probed even during the Hawking evaporation terminal phase. In agreement with the holographic principle, relevant processes take place on the screen surface. The area quantization leads to a discrete mass spectrum. An analysis of the entropy shows that the minimal holographic screen can store only one byte of information, while in the thermodynamic limit the area law is corrected by a logarithmic term.
This study describes the Holocene sedimentary lagoonal deposition history, including event sedimentation and benthic foraminiferal analyzes, from about 10 kyrs BP until today. This is the first study describing the sedimentation of a Maldivian atoll lagoon in such detail. Thirty-nine sediment cores have been recovered from the deep Rasdhoo Atoll lagoon of the Maldives (4°N/73°W). Seventeen sediment cores were opened, described, and 296 sediment samples have been collected and analyzed. Different methods have been used to evaluate the coarse- and fine-grained carbonate components and a total of fifty-eight samples have been dated radiometrically by Beta Analytic Inc., Miami, Florida. In general, the Rasdhoo Atoll lagoon sediments can be divided into (1) a Late Pleistocene soil, (2) an early Holocene peat layer composed of mangrove deposits which mark the beginning inundation of the atoll lagoon by the rising Holocene sea-level at 10,320 ± 100 yrs BP, and (3) carbonate sediments starting to fill up the lagoon 7850 ± 140 yrs BP until today. The transition from peat to carbonate is characterized by a considerable hiatus. Six different carbonate sediment facies are classified by statistical analyses, listed in decreasing abundance:
(1) mollusk-coral-algal floatstone to rudstone (30%)
(2) mollusk-coral-red algae rudstone (23%)
(3) mollusk-coral-algal wackestone to floatstone (23%)
(4) mollusk-coral wackestone (13%)
(5) mollusk-coral mudstone to wackestone (9%)
(6) mollusk mudstone (2%)
Based on grain-sizes in combination with coral identification, the facies represent both lagoonal background sedimentation (mostly fine-grained sediments (matrix >50%)) and event sedimentation (coarse-grained sediment layers composing reefal components).
Six coarser grained layers in muddy background sediments of the Rasdhoo Atoll lagoon were interpreted as Holocene tsunami events, based on the increase of allochthonous skeletal material with shallow-water reef affinity such as fragments of shallow-water coral species, coralline red algae, and reef-dwelling foraminifera in these layers, as well as AMS dating:
• Event 1: 420 - 890 yrs BP (655 yrs BP)
• Event 2: 890 - 1560 yrs BP (1225 yrs BP)
• Event 3: 2040 - 2340 yrs BP (2190 yrs BP)
• Event 4: 2420 - 3380 yrs BP (2900 yrs BP)
• Event 5: 3890 - 4330 yrs BP (4110 yrs BP)
• Event 6: 5480 - 5760 yrs BP (5620 yrs BP)
Five of the six layers may be correlated to previously published tsunami events at adjacent coastal research sites. The mid-late Holocene atoll lagoon archive is incomplete though based on the assumption that major earthquakes at the Indonesian subduction zone generated more than six major tsunamis during the past 6.5 kyrs.
According to Gischler (2006), the sediments of the Rasdhoo Atoll lagoon can be divided into two areas: (1) a central to marginal deep lagoon with a lateral west-to-east gradient of sediment facies distribution, visible in sections <4 kyrs BP with sedimentary facies of mudstone to wackestone in the western part (e.g., cores 16, 18, and 34) and coarse-grained coral and algal-rich sediments in the eastern part of the lagoon (e.g., cores 30 and 31). (2) A northern enclosed and shallow area between the sand apron and the sand spit accumulating “sandy” sediments of wackestone facies (cores 2, 19, 25, and 26).
Comparing the sediment accumulation data of the lagoon with two reconstructed local sea-level curves, three different sequence-stratigraphical systems tracts are visible: (1) a lowstand systems tract (LST) >10 kyrs BP. Pleistocene brownish soil superposing subaerially exposed Pleistocene reef limestone. (2) A transgressive systems tract (TST) 10-6.5 kyrs BP. A peat layer marks the beginning of the inundation, and the carbonate sedimentation starts with very low sedimentation rates of 0.02 m/kyr. (3) A highstand systems tract (HST) 6.5-0 kyrs BP, further divided into three stages (6.5-3, 3-1, 1-0 kyrs BP). The sea-level rise slowed down, sedimentation rates are increasing continuously up to a maximum of 1.4 m/kyr, the sand spit developed some 4 kyrs BP, the lagoonal circulation got restricted, and the lateral west-to-east gradient of grain-size accumulation started. From 1-0 kyrs BP the sedimentation rates slowed down to modern mean sedimentation rates of 0.6 m/kyr.
Two cores, one core from the center of the lagoon (core 16) and one core from the northern margin of the lagoon (core 19), have been analyzed on diversity and assemblages of benthic foraminifera in high-resolution. The transitions of Ammonia spp. to a more even and diverse fauna marks a significant environmental change at 7.0 kyrs BP in core 16 (onset of a stable environment in the deep lagoon after the sea-level rise slowed down at HST stage 1) and at 4.0 kyrs BP in core 19. A continuing environmental change after 1.4 kyrs BP in core 16 caused the fauna to become more even, a recovery of diversity and a permanent decline of foraminiferal accumulation rate. The changes in the faunas at 4.0 kyrs BP and at 1.4 kyrs BP could be explained with the sand spit formation in the northwestern and western lagoon. The sand spit has apparently acted as an obstacle in lagoonal circulation and might have caused unstable environmental conditions due to a more rapid circulation at the shallow marine site of core 19 and a slowdown of bottom water circulation in the main lagoon (core 16) leading to higher residence times and to lower oxygen and higher nutrient concentrations.
This publication is the result of a baseline study of the state of the higher education systems in the five Portuguese speaking countries in Africa (PALOP): Angola, Cape Verde, Guinea-Bissau, Mozambique and Sao Tome and Principe. The project was undertaken by an African international expert in the field of higher education studies and was fully sponsored and supported by the Association for the Development of Education in Africa (ADEA). The report offers a historical overview of the development of higher education in PALOP from colonial times to the present. The main objective of this baseline study is to map the landscape and dynamics of change in the higher education systems of PALOP countries. It focuses on describing the latest developments of trends of expansion, financing, governance and policy reforms closely linked to the development of higher education systems in these countries. Furthermore, the study will facilitate an informed debate and the dissemination of knowledge on the role of higher education for development in Africa.
Background: In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance.
Methods: In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4.
Results: A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%.
Conclusion: In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher.
In this paper we argue that very high marginal labor income tax rates are an effective tool for social insurance even when households have preferences with high labor supply elasticity, make dynamic savings decisions, and policies have general equilibrium effects. To make this point we construct a large scale Overlapping Generations Model with uninsurable labor productivity risk, show that it has a wealth distribution that matches the data well, and then use it to characterize fiscal policies that achieve a desired degree of redistribution in society. We find that marginal tax rates on the top 1% of the earnings distribution of close to 90% are optimal. We document that this result is robust to plausible variation in the labor supply elasticity and holds regardless of whether social welfare is measured at the steady state only or includes transitional generations.
Species distributed across vast continental areas and across major biomes provide unique model systems for studies of biotic diversification, yet also constitute daunting financial, logistic and political challenges for data collection across such regions. The tree frog Dendropsophus minutus (Anura: Hylidae) is a nominal species, continentally distributed in South America, that may represent a complex of multiple species, each with a more limited distribution. To understand the spatial pattern of molecular diversity throughout the range of this species complex, we obtained DNA sequence data from two mitochondrial genes, cytochrome oxidase I (COI) and the 16S rhibosomal gene (16S) for 407 samples of D. minutus and closely related species distributed across eleven countries, effectively comprising the entire range of the group. We performed phylogenetic and spatially explicit phylogeographic analyses to assess the genetic structure of lineages and infer ancestral areas. We found 43 statistically supported, deep mitochondrial lineages, several of which may represent currently unrecognized distinct species. One major clade, containing 25 divergent lineages, includes samples from the type locality of D. minutus. We defined that clade as the D. minutus complex. The remaining lineages together with the D. minutus complex constitute the D. minutus species group. Historical analyses support an Amazonian origin for the D. minutus species group with a subsequent dispersal to eastern Brazil where the D. minutus complex originated. According to our dataset, a total of eight mtDNA lineages have ranges >100,000 km2. One of them occupies an area of almost one million km2 encompassing multiple biomes. Our results, at a spatial scale and resolution unprecedented for a Neotropical vertebrate, confirm that widespread amphibian species occur in lowland South America, yet at the same time a large proportion of cryptic diversity still remains to be discovered.
High lipoprotein expression and potent activation of host Toll-like receptor-2 (TLR2) are characteristic features of the staphylococcal species. Expression of TLR2 in the host is important for clearance of Staphylococcus aureus infection and host survival. Thus, we hypothesized that bacterial regulation of its intrinsic TLR2-stimulatory capacity could represent a means for immune evasion or host adaptation. We, therefore, compared clinical S. aureus isolates in regards to their TLR2 activation potential and assessed the bacterial factors that modulate TLR2-mediated recognition. S. aureus isolates displayed considerable variability in TLR2-activity with low to absent TLR2-activity in 64% of the isolates tested (68/106). Notably, strain-specific TLR2-activity was independent of the strain origin, e.g. no differences were found between strains isolated from respiratory specimen from cystic fibrosis patients or those isolated from invasive disease specimen. TLR2-activity correlated with protein A expression but not with the agr status. Capsule expression and small colony variant formation had a negative impact on TLR2-activity but any disruption of cell wall integrity enhanced TLR2 activation. Altogether, heterogeneity in host TLR2-activity reflects differences in metabolic activity and cell wall synthesis and/or remodeling.
Background: Targeted therapies have improved therapeutic options of treating renal cell carcinoma (RCC). However, drug response is temporary due to resistance development.
Methods: Functional and molecular changes in RCC Caki-1 cells, after acquired resistance to the mammalian target of rapamycin (mTOR)-inhibitor everolimus (Cakires), were investigated with and without additional application of the histone deacetylase (HDAC)-inhibitor valproic acid (VPA). Cell growth was evaluated by MTT assay, cell cycle progression and apoptosis by flow cytometry. Target molecules of everolimus and VPA, apoptotic and cell cycle regulating proteins were investigated by western blotting. siRNA blockade was performed to evaluate the functional relevance of the proteins.
Results: Everolimus resistance was accompanied by significant increases in the percentage of G2/M-phase cells and in the IC50. Akt and p70S6K, targets of everolimus, were activated in Cakires compared to drug sensitive cells. The most prominent change in Cakires cells was an increase in the cell cycle activating proteins cdk2 and cyclin A. Knock-down of cdk2 and cyclin A caused significant growth inhibition in the Cakires cells. The HDAC-inhibitor, VPA, counteracted everolimus resistance in Cakires, evidenced by a significant decrease in tumor growth and cdk2/cyclin A.
Conclusion: It is concluded that non-response to everolimus is characterized by increased cdk2/cyclin A, driving RCC cells into the G2/M-phase. VPA hinders everolimus non-response by diminishing cdk2/cyclin A. Therefore, treatment with HDAC-inhibitors might be an option for patients with advanced renal cell carcinoma and acquired everolimus resistance.
Halting biological invasions in Europe : from data to decisions ; a message from NEOBIOTA 2012
(2014)
The NEOBIOTA conferences initiated by the European Group on Biological Invasions represents a forum for exchange of ideas and discussion of topics related to biological invasions as well as an interface between science, application and policies (Kowarik and Starfinger 2009). The 7th NEOBIOTA conference (http://neobiota2012.blogspot.com.es/), held in Pontevedra (Spain) from 12–14 September 2012, brought together 288 participants (ecologists, conservationists, representatives of governmental agencies and stake-holders), from 24 European countries and 9 non-European ones (namely, Australia, Brazil, Canada, Chile, Colombia, New Zealand, South Africa, United States and Venezuela).
Halophilic archaea cultivated from surface sterilized middle-late Eocene rock salt are polyploid
(2014)
Live bacteria and archaea have been isolated from several rock salt deposits of up to hundreds of millions of years of age from all around the world. A key factor affecting their longevity is the ability to keep their genomic DNA intact, for which efficient repair mechanisms are needed. Polyploid microbes are known to have an increased resistance towards mutations and DNA damage, and it has been suggested that microbes from deeply buried rock salt would carry several copies of their genomes. Here, cultivable halophilic microbes were isolated from a surface sterilized middle-late Eocene (38–41 million years ago) rock salt sample, drilled from the depth of 800 m at Yunying salt mine, China. Eight unique isolates were obtained, which represented two haloarchaeal genera, Halobacterium and Halolamina. We used real-time PCR to show that our isolates are polyploid, with genome copy numbers of 11–14 genomes per cell in exponential growth phase. The ploidy level was slightly downregulated in stationary growth phase, but the cells still had an average genome copy number of 6–8. The polyploidy of halophilic archaea living in ancient rock salt might be a factor explaining how these organisms are able to overcome the challenge of prolonged survival during their entombment.
It was long assumed that translation initiation in prokaryotes generally occurs via the so-called Shine Dalgarno (SD) mechanism. Recently, it became clear that translation initiation in prokaryotes is more heterogeneous. In the haloarchaeon Haloferax volcanii, the majority of transcripts is leaderless and most transcripts with a 5′-UTR lack a SD motif. Nevertheless, a bioinformatic analysis predicted that 20–30% of all genes are preceded by a SD motif in haloarchaea. To analyze the importance of the SD mechanism for translation initiation in haloarchaea experimentally the monocistronic sod gene was chosen, which contains a 5′-UTR with an extensive SD motif of seven nucleotides and a length of 19 nt, the average length of 5′UTRs in this organism. A translational fusion of part of the sod gene with the dhfr reporter gene was constructed. A mutant series was generated that matched the SD motif from zero to eight positions, respectively. Surprisingly, there was no correlation between the base pairing ability between transcripts and 16S rRNA and translational efficiency in vivo under several different growth conditions. Furthermore, complete replacement of the SD motif by three unrelated sequences did not reduce translational efficiency. The results indicate that H. volcanii does not make use of the SD mechanism for translation initiation in 5′-UTRs. A genome analysis revealed that while the number of SD motifs in 5′-UTRs is rare, their fraction within open reading frames is high. Possible biological functions for intragenic SD motifs are discussed, including re-initiation of translation at distal genes in operons.
The simultaneous description of the hadronic yields, pion, kaon and proton spectra, elliptic flows and femtoscopy scales in hydrokinetic model of A+A collisions is presented at different centralities for the top RHIC and LHC energies. The hydrokinetic model is used in its hybrid version that allows one to switch correctly to the UrQMD cascade at the isochronic hypersurface which separates the cascade stage and decaying hydrodynamic one. The results are compared with pure hybrid model where hydrodynamics and hadronic cascade are matching just at the non-space-like hypersurface of chemical freeze-out. The initial conditions are based on both Glauber- and KLN- Monte-Carlo simulations and results are compared. It seems that the observables, especially femtoscopy data, prefer the Glauber initial conditions. The modification of the particle number ratios caused, in particular, by the particle annihilations at the afterburn stage is analyzed.
In many markets, design is one of the key factors in determining a product’s success. The present research offers insights into the role of design for the success of cars, and offers procedures to measure the quality of the designs objectively. The authors show that visual design plays a major role in a product’s success in the automobile market. In the study, two visual design aspects were already sufficient to significantly improve traditional sales forecasting models for cars. Visual prototypicality and visual complexity both had a positive impact on sales, and designs that were perceived as both prototypical and complex were the ones that displayed the best results. Most design evaluation used to be based on subjective measures, but the researcher applied a new, objective procedure to measure prototypicality and complexity. While the latter was detected by the disk space needed by the compressed image file, the new approach for measuring prototypicality was even more sophisticated. It relied on the technique of image morphing. Morphing is a technique that allows the construction of a visual synthesis – or average picture – from a number of individual pictures. Once a car morph is developed, one can determine the visual similarity of different car models to the morph in order to obtain its prototypicality. In principle, this procedure can be automated completely, and including a large number of versions is possible. These measures therefore seem suitable for supporting design decision processes in practice.
In Growing up with Tanzania. Karim Hirji, a renowned Professor of Medical Statistics and Fellow of the Tanzania Academy of Science, presents a multi-faceted, evocative portrait of his joyous but conflicted passage to adulthood during colonial and early-Uhuru Tanzania. His smooth style engages the reader with absorbing true tales, cultural currents, critical commentary and progressive possibilities. By vibrantly contrasting the hope-filled sixties with the cynical modern era, he also lays bare the paradoxes of personal life and society, past and present.
We study the dispersion of debt maturities across time, which we call "granularity of corporate debt,'' using a model in which a firm's inability to roll over expiring debt causes inefficiencies, such as costly asset sales or underinvestment. Since multiple small asset sales are less costly than a single large one, firms diversify debt rollovers across maturity dates. We construct granularity measures using data on corporate bond issuers for the 1991-2012 period and establish a number of novel findings. First, there is substantial variation in granularity in that we observe both very concentrated and highly dispersed maturity structures. Second, observed variation in granularity supports the model's predictions, i.e. maturities are more dispersed for larger and more mature firms, for firms with better investment oppo
God was African
(2014)
When Kendem, a varsity instructor, returns to his native Lewoh countryside where he spent his childhood, he is seeking relief from the complexity of human civilization after attending the Fulbright Institute in the United States. Instead, he is confronted with two seething issues: how to reveal to his sick and troubled mother the situation in which he finds his elder brother, the successor of Mbe Tanju-Ngong's household, who travelled to the United States many years before and had never returned and the dispute over Fuo Beyano's funeral which is tearing the land apart, whether the deceased village chief, should be given a Christian burial or he should, according to the age-old tradition of Lewoh people, go through a ritual to enable him return and continue ruling his people.
Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride. To address the role of GlnA2 in the biosynthesis of the osmolytes glutamate and glutamine, a deletion mutant (ΔglnA2) was generated and characterized in detail. We compared the pool of compatible solutes and performed transcriptional analyses of the principal genes controlling the solute production in the wild type strain and the deletion mutant. These measurements did not confirm the hypothesized role of GlnA2 in the osmolyte production. Most likely the presence of another, yet to be identified enzyme has the main contribution in the measured activity in crude extracts and probably determines the total chloride-modulated profile. The role of GlnA2 remains to be elucidated.
The exposure to tobacco smoke during pregnancy is considered to be amongst the most harmful avoidable risk factors. In this scientometric and gender study scientific data on smoking and pregnancy was analyzed using a variety of objective scientometric methods like the number of scientific contributions, the number of citations and the modified h-index in combination with gender-specific investigations. Covering a time period from 1900 to 2012, publishing activities of 27,955 authors, institutions and countries, reception within the international scientific community and its reactions were analyzed and interpreted. Out of 10,043 publications the highest number of scientific works were published in the USA (35.5%), followed by the UK (9.9%) and Canada (5.3%). These nations also achieve the highest modified h-indices of 128, 79 and 62 and the highest citation rates of 41.4%, 8.6% and 5.3%, respectively. Out of 12,596 scientists 6,935 are female (55.1%), however they account for no more than 49.7% of publications (12,470) and 42.8% of citations (172,733). The highest percentage of female experts about smoking and pregnancy is found in Australasia (60.7%), while the lowest is found in Asia (41.9%). The findings of the study indicate an increase in gender equality as well as in quantity and quality of international scientific research about smoking and pregnancy in the future.
Treatment with inhibitors of the receptor tyrosine kinase FLT3 are currently studied as promising therapies in acute myeloid leukemia (AML). However, only a subset of patients benefit from these treatments and the presence of activating mutations within FLT3 can predict response to a certain extent only. ...
The long-run consumption risk (LRR) model is a promising approach to resolve prominent asset pricing puzzles. The simulated method of moments (SMM) provides a natural framework to estimate its deep parameters, but caveats concern model solubility and weak identification. We propose a two-step estimation strategy that combines GMM and SMM, and for which we elicit informative macroeconomic and financial moment matches from the LRR model structure. In particular, we exploit the persistent serial correlation of consumption and dividend growth and the equilibrium conditions for market return and risk-free rate, as well as the model-implied predictability of the risk-free rate. We match analytical moments when possible and simulated moments when necessary and determine the crucial factors required for both identification and reasonable estimation precision. A simulation study – the first in the context of long-run risk modeling – delineates the pitfalls associated with SMM estimation of a non-linear dynamic asset pricing model. Our study provides a blueprint for successful estimation of the LRR model.
Girl on the Edge: A Memoir
(2014)
Ruth was four years old when her father was arrested for high treason and her world was turned upside-down. She grew up in constant fear of Special Branch policemen knocking on the door to arrest her mother or father, prominent South African communist. Ruth learned how to keep her mouth shut, to look out for microphones in the walls and to beware of friends who could betray her trust. At fourteen, Ruth left South Africa, clutching her teddy bear in one hand and her drawings in the other. A plan to England carried her into exile, a new world where she struggled to reconstruct a life fractured by fear. With an artist's eye for detail and colour, Ruth recalls her life with unflinching honesty: the Treason Trial; her struggle to conform; Friern Barnet Asylum for the 'hopeless insane'; LSD, protests, and free love in London, art school and motherhood; communes and camping- all steps in a journey that finally brought her home to South Africa on the brink of change. Heart- wrenchingly sad one minute, bursting with life and vigour the next, seamed throughout by strength and courage, girl on the edge allows us to look deep into one woman's life and travel with her to the brink and back again.
Two new species and one subspecies of Pharnaciini, belonging to two different genera, are described from Vietnam: one species and subspecies of Phryganistria Stål, 1875 and one species of Phobaeticus Brunner von Wattenwyl, 1907. Two species currently attributed to the genus Ramulus Saussure, 1862, Ramulus magnus (Brunner von Wattenwyl, 1907) and R. chinensis (Brunner von Wattenwyl, 1907), are transferred to Baculonistria Hennemann & Conle, 2008 comb. nov. Phobaeticus longicornis Bi & Wang, 1998 and Phobaeticus yuexiensis Chen & He, 1993 represent the male and female of Baculonistria magnus (Brunner von Wattenwyl, 1907) syn. nov. A lectotype is designated for Baculonistria chinensis (Brunner von Wattenwyl, 1907). The genus Baculonistria now contains three species. Nearchus bachmaensis Ta & Hoang, 2004 is transferred to Phryganistria and the new combination Phryganistria bachmaensis (Ta & Hoang, 2004) comb. nov. is proposed. The species is redescribed and the authors’ attribution corrected, the egg is described and figured for the first time.
Phryganistria tamdaoensis sp. nov. is described and figured from both sexes and the egg. Females of P. tamdaoensis sp. nov. are easily recognised by the conspicuously enlarged lanceolate cerci, a character previously unknown in this tribe. The distribution range of Phryganistria heusii heusii (Hennemann & Conle, 1997) is extended to Tam Dao National Park. A new subspecies Phryganistria heusii yentuensis subsp. nov. is described from Tay Yen Tu Nature Reserve from adult males and females and the eggs. Males can easily be distinguished from the nominal subspecies by their colouration. This huge subspecies represents the second longest insect recorded to date. A key to the species of the genus Phryganistria is provided. Phobaeticus trui sp. nov. is described from central Vietnam. It is the first species of Phobaeticus recorded from Vietnam. Adults of both sexes are illustrated.
Freshwater ecosystems are increasingly impacted by alien invasive species which have the potential to alter various ecological interactions like predator-prey and host-parasite relationships. Here, we simultaneously examined predator-prey interactions and parasitization patterns of the highly invasive round goby (Neogobius melanostomus) in the rivers Rhine and Main in Germany. A total of 350 N. melanostomus were sampled between June and October 2011. Gut content analysis revealed a broad prey spectrum, partly reflecting temporal and local differences in prey availability. For the major food type (amphipods), species compositions were determined. Amphipod fauna consisted entirely of non-native species and was dominated by Dikerogammarus villosus in the Main and Echinogammarus trichiatus in the Rhine. However, the availability of amphipod species in the field did not reflect their relative abundance in gut contents of N. melanostomus. Only two metazoan parasites, the nematode Raphidascaris acus and the acanthocephalan Pomphorhynchus sp., were isolated from N. melanostomus in all months, whereas unionid glochidia were only detected in June and October in fish from the Main. To analyse infection pathways, we examined 17,356 amphipods and found Pomphorhynchus sp. larvae only in D. villosus in the river Rhine at a prevalence of 0.15%. Dikerogammarus villosus represented the most important amphipod prey for N. melanostomus in both rivers but parasite intensities differed between rivers, suggesting that final hosts (large predatory fishes) may influence host-parasite dynamics of N. melanostomus in its introduced range.
In this article, I review select institutional and analytical traditions of Legal History in 20th century Germany, in order to put forth some recommendations for the future development of our discipline. A careful examination of the evolution of Legal History in Germany in the last twenty-five years, in particular, reveals radical transformations in the research framework: Within the study of law, there has been a shift in the internal reference points for Legal History. While the discipline is opening up to new understandings of law and to its neighboring disciplines, its institutional position at the law departments has become precarious. Research funding is being allocated in new ways and the German academic system is witnessing ever more internal differentiation. Internationally, German contributions and analytic traditions are receiving less attention and are being marginalized as new regions enter into a global dialogue on law and its history. The German tradition of research in Legal History had for long been setting benchmarks internationally; now it has to reflect upon and react to new global knowledge systems that have emerged in light of the digital revolution and the transnationalization of legal and academic systems. If legal historians in Germany accept the challenge these changing conditions pose, thrilling new intellectual and also institutional opportunities emerge. Especially the transnationalization of law and the need for a transnational legal scholarship offers fascinating perspectives for Legal History.
This is the first English edition of Tamara Mcheidze's monograph on the spiders of Georgia (Mcheidze 1997; in alternative transliteration: Mkheidze 1997), containing taxonomic, faunistic and ecological information on 362 spider species recorded by T. Mcheidze in Georgia between the 1920s and 1992. The English edition resembles the original text, with a preface, taxonomic comments and a part with supplementary information on the locations, a location map and an index provided by the editor.
The ladybeetle Anovia sp. (Coleoptera: Coccinellidae: Noviini), known as an important natural enemy of the Colombian fluted scale, Crypticeria muticicatrices Kondo and Gullan (Hemiptera: Coccoidea: Monophlebidae) is here identified as A. punica Gordon, 1972, and reported for the first time from Peru. Here we provide information and illustrations of the great variation in color and dorsal patterns of A. punica found in Colombia and Peru.
Ultraviolet-B (UVB)-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24), chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5), the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022). In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.
Symbiotic nitrogen fixation (SNF) in root nodules of grain legumes such as chickpea is a highly complex process that drastically affects the gene expression patterns of both the prokaryotic as well as eukaryotic interacting cells. A successfully established symbiotic relationship requires mutual signaling mechanisms and a continuous adaptation of the metabolism of the involved cells to varying environmental conditions. Although some of these processes are well understood today many of the molecular mechanisms underlying SNF, especially in chickpea, remain unclear. Here, we reannotated our previously published transcriptome data generated by deepSuperSAGE (Serial Analysis of Gene Expression) to the recently published draft genome of chickpea to assess the root- and nodule-specific transcriptomes of the eukaryotic host cells. The identified gene expression patterns comprise up to 71 significantly differentially expressed genes and the expression of twenty of these was validated by quantitative real-time PCR with the tissues from five independent biological replicates. Many of the differentially expressed transcripts were found to encode proteins implicated in sugar metabolism, antioxidant defense as well as biotic and abiotic stress responses of the host cells, and some of them were already known to contribute to SNF in other legumes. The differentially expressed genes identified in this study represent candidates that can be used for further characterization of the complex molecular mechanisms underlying SNF in chickpea.
Lichens are present in most land ecosystems, frequently occupying habitats where few other organisms are able to survive. Their contribution to the ecosystems in terms of biomass and ground cover increases with latitude and altitude, being, together with bryophytes, the most conspicuous component of alpine and polar landscapes. Whereas some polar lichens have reduced distributions and are restricted to high latitudes, most of them have very wide distributional ranges, which oven extend over several climatic regions. Many of them are common to Polar Regions of both hemispheres, a distributional pattern that has been denominated as bipolar, antitropical or amphitropical. Bipolar distributions are not exclusive to lichens, but common to many groups of organisms. The bipolar element in lichens is exceptional as it includes a large number of species, while in most other land organisms it includes genera or families but very seldom species.
In this dissertation I use the bipolar lichen Cetraria aculeata to give a first insight into the phylogeography of this biogeographic element in lichens. I discuss how and when the disjunct distribution of C. aculeata came to be, and try to partial out the roles that historical and ecological processes played in shaping its distribution.
Sampling was designed to cover a wide geographic extension. The main e"ort was made to collect in boreal, temperate and tropical mountain ranges in North and South America, as well to include Mediterranean populations in which specimens with deviant morphologies are observed.
I found that Cetraria aculeata forms a genetically congruent taxon. Although whether it should include C. muricata remains unsolved, I excluded all specimens identified as the latter from our analyses. Thee populations of both algal and fungal symbionts have a strong geographic structure. The study of the lichen fungus suggested that the species originated in the Eurasian continent and later expanded to acquire its current distribution during the Pleistocene. The results showed that all American populations originated from an ancestral population, more similar to the extant Arctic populations than to the Mediterranean ones.
The comparison between the structure of fungal and algal populations showed a high degree of coherence between them. However, the similarity in photobiont use between Arctic and Antarctic populations suggests that photobiont use responds not only to a history of codispersal in vegetative propagula, but it is also a result of a selective process related to climate. Since this climatic pattern of similarity is also found in the community of Alphaproteobacteria associated with C. aculeata, we concluded that lichens might be able to accommodate or to respond to different environmental conditions by selectively associating with different symbiotic partners.
Lastly, we found the Mediterranean populations of C. aculeata to be genetically differentiated in algal and fungal symbionts from the rest of the populations. While we found no grounds to believe that the overgrown morphs encountered in the region are due to the association with different algal lineages, I believe that a switch in photobiont use might be responsible for the pattern of genetic isolation encountered. Furthermore, I suggest that the Mediterranean and bipolar C. aculeata could be two different species, since both are ecologically, genetically and at least in part morphologically divergent.
The haloarchaeon Haloferax volcanii was shown to contain 145 intergenic and 45 antisense sRNAs. In a comprehensive approach to unravel various biological roles of haloarchaeal sRNAs in vivo, 27 sRNA genes were selected and deletion mutants were generated. The phenotypes of these mutants were compared to that of the parent strain under ten different conditions, i.e. growth on four different carbon sources, growth at three different salt concentrations, and application of four different stress conditions. In addition, cell morphologies in exponential and stationary phase were observed. Furthermore, swarming of 17 mutants was analyzed. 24 of the 27 mutants exhibited a difference from the parent strain under at least one condition, revealing that haloarchaeal sRNAs are involved in metabolic regulation, growth under extreme conditions, regulation of morphology and behavior, and stress adaptation. Notably, 7 deletion mutants showed a gain of function phenotype, which has not yet been described for any other prokaryotic sRNA gene deletion mutant. Comparison of the transcriptomes of one sRNA gene deletion mutant and the parent strain led to the identification of differentially expressed genes. Genes for flagellins and chemotaxis were up-regulated in the mutant, in accordance with its gain of function swarming phenotype. While the deletion mutant analysis underscored that haloarchaeal sRNAs are involved in many biological functions, the degree of conservation is extremely low. Only 3 of the 27 genes are conserved in more than 10 haloarchaeal species. 22 of the 27 genes are confined to H. volcanii, indicating a fast evolution of haloarchaeal sRNA genes.
Generating functionals may guide the evolution of a dynamical system and constitute a possible route for handling the complexity of neural networks as relevant for computational intelligence.We propose and explore a new objective function, which allows to obtain plasticity rules for the afferent synaptic weights. The adaption rules are Hebbian, self-limiting, and result from the minimization of the Fisher information with respect to the synaptic flux. We perform a series of simulations examining the behavior of the new learning rules in various circumstances.The vector of synaptic weights aligns with the principal direction of input activities, whenever one is present. A linear discrimination is performed when there are two or more principal directions; directions having bimodal firing-rate distributions, being characterized by a negative excess kurtosis, are preferred. We find robust performance and full homeostatic adaption of the synaptic weights results as a by-product of the synaptic flux minimization. This self-limiting behavior allows for stable online learning for arbitrary durations.The neuron acquires new information when the statistics of input activities is changed at a certain point of the simulation, showing however, a distinct resilience to unlearn previously acquired knowledge. Learning is fast when starting with randomly drawn synaptic weights and substantially slower when the synaptic weights are already fully adapted.
The Generalized Uncertainty Principle (GUP) arises from Quantum Gravity thought experiments and contains a minimal lenght. In this thesis I calculate Schwarzschild Black Holes that are modified by the GUP. These Black Holes have the property, that their temperature does not diverge for small masses, although they still posses a curvature singularity. I calculate analytically that in more than 3+1 dimensions the temperature diverges again.
Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
Smut fungi are well-suited to investigate the ecology and evolution of plant pathogens, as they are strictly biotrophic, yet cultivable on media. Here we report the genome sequence of Melanopsichium pennsylvanicum, closely related to Ustilago maydis and other Poaceae-infecting smuts, but parasitic to a dicot plant. To explore the evolutionary patterns resulting from host adaptation after this huge host jump, the genome of M. pennsylvanicum was sequenced and compared to the genomes of Ustilago maydis, Sporisorium reilianum, and Ustilago hordei. While all four genomes had a similar completeness in CEGMA analyses, gene absence was highest in M. pennsylvanicum, and most pronounced in putative secreted proteins, which are often considered as effector candidates. In contrast, the amount of private genes was similar among the species, highlighting that gene loss rather than gene gain is the hallmark of adaptation after the host jump to the dicot host. Our analyses revealed a trend of putative effectors to be next to another putative effector, but the majority of these are not in clusters and thus the focus on pathogenicity clusters might not be appropriate for all smut genomes. Positive selection studies revealed that M. pennsylvanicum has the highest number and proportion of genes under positive selection. In general, putative effectors showed a higher proportion of positively selected genes than non-effector candidates. The 248 putative secreted effectors found in all four smut genomes might constitute a core set needed for pathogenicity, while those 92 that are found in all grass-parasitic smuts, but have no ortholog in M. pennsylvanicum might constitute a set of effectors important for successful colonization of grass hosts.
Gender Issues in African Literature examines the ways in which some protagonists of African fictions are made to counter and challenge intertwined Western discourses on gender, employment, sexuality, and health. Here the conflict between Tradition and Modernity is argues from the favourite premise of male supremacist ideology showing how women have -unlearned- these false concepts to build a sustained feminist movement and (re)learn the value of sisterhood. There is a bold attempt to reread Achebe as a consistent in urging women to fight the seemingly oppressive structures that have traditionally discriminated against them, and to disregard their diversity and embrace their unity. A chapter of Feminist Re-writing disagrees with the attempt to equate theory with political activism and presents Feminist literature as more than a verbal assertion that points to Feminist aesthetics and politics. The use of the trauma theory and testimonio literature to explore traumatisation of female characters and its impact for Zimbabwean civil society is a useful addition to these gender studies in African literature.
One of the major issues this book examines is what the African experience and identity have contributed to the debate on citizenship in the era of globalisation. This volume presents case studies of different African contexts, illustrating the gendered aspects of citizenship as experienced by African men and women. Citizenship carries manifold gendered aspects and given the distinct gender roles and responsibilities, globalisation affects citizenship in different way. It further examines new forms of citizenship emerging from the current era dominated by a neoliberal focus. This book is not exclusive in terms of theorisation but its focus on African contexts, with an in-depth analysis taking into consideration local culture and practices and their implications for citizenship, provides a good foundation for further scholarly work on gender and citizenship in Africa.
Background: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study.
Patients and methods: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0–2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks + 1-week rest followed by once 3-weeks + 1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were prospectively stained for sorafenib targets and potential biomarkers. Serum samples (first two cycles) were measured for vascular endothelial growth factors (VEGFs), vascular endothelial growth factor receptor 2 (VEGFR-2) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay (ELISA).
Results: Gemcitabine plus sorafenib was generally well tolerated. Four and three patients achieved partial responses in the sorafenib and placebo groups, respectively. There was no difference in the primary end-point, median progression-free survival (PFS) for gemcitabine plus sorafenib versus gemcitabine plus placebo (3.0 versus 4.9 months, P = 0.859), and no difference for median overall survival (OS) (8.4 versus 11.2 months, P = 0.775). Patients with liver metastasis after resection of primary BTC survived longer with sorafenib (P = 0.019) compared to placebo. Patients who developed hand-foot syndrome (HFS) showed longer PFS and OS than patients without HFS. Two sorafenib targets, VEGFR-2 and c-kit, were not expressed in BTC samples. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage. Absence of PDGFRβ expression correlated with longer PFS.
Conclusion: The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients. Biomarker subgroup analysis suggested that some patients might benefit from combined treatment.
The neutron sensitivity of the C6D6 detector setup used at n_TOF facility for capture measurements has been studied by means of detailed GEANT4 simulations. A realistic software replica of the entire n_TOF experimental hall, including the neutron beam line, sample, detector supports and the walls of the experimental area has been implemented in the simulations. The simulations have been analyzed in the same manner as experimental data, in particular by applying the Pulse Height Weighting Technique. The simulations have been validated against a measurement of the neutron background performed with a natC sample, showing an excellent agreement above 1 keV. At lower energies, an additional component in the measured natC yield has been discovered, which prevents the use of natC data for neutron background estimates at neutron energies below a few hundred eV. The origin and time structure of the neutron background have been derived from the simulations. Examples of the neutron background for two different samples are demonstrating the important role of accurate simulations of the neutron background in capture cross-section measurements.
We present results for calculating fusion cross-sections using a new microscopic approach based on a time-dependent density-constrained DFT calculations. The theory is implemented by using densities and other information obtained from TDDFT time-evolution of the nuclear system as a constraint on the density for DFT calculations.
A population of 700 Blandfordia cunninghamii Lindl. (family Blandfordiaceae) plants in the Blue Mountains, 100 km west of Sydney, New South Wales was monitored over a period of seven years, during which a part of the population area was burnt in a Hazard Reduction Burn (HRB). The survey measured flowering of Blandfordia cunninghamii in both the burnt and unburnt areas. In part of the unburnt area flowering (in December) was strongly correlated with previous September rainfall, but in another unburnt area there was no flowering at all over the seven years. An enhanced flowering response after fire was found in the burnt area and the diminution of this enhanced response in subsequent years was found to be logarithmic (taking into account potential rainfall effects). No recruitment of juvenile plants after fire was observed. 87% of seeds of Blandfordia cunninghamii were found to be germinable. Slow juvenile growth of Blandfordia cunninghamii in the field was measured over seven years. Seed was collected for two major seedbanks, the NSW Plantbank at the Australian Botanic Garden, Mt Annan and the Millennium Seedbank at Kew in the United Kingdom.
Introduction: Electrical impedance tomography (EIT) is an emerging clinical tool for monitoring ventilation distribution in mechanically ventilated patients, for which many image reconstruction algorithms have been suggested. We propose an experimental framework to assess such algorithms with respect to their ability to correctly represent well-defined physiological changes. We defined a set of clinically relevant ventilation conditions and induced them experimentally in 8 pigs by controlling three ventilator settings (tidal volume, positive end-expiratory pressure and the fraction of inspired oxygen). In this way, large and discrete shifts in global and regional lung air content were elicited.
Methods: We use the framework to compare twelve 2D EIT reconstruction algorithms, including backprojection (the original and still most frequently used algorithm), GREIT (a more recent consensus algorithm for lung imaging), truncated singular value decomposition (TSVD), several variants of the one-step Gauss-Newton approach and two iterative algorithms. We consider the effects of using a 3D finite element model, assuming non-uniform background conductivity, noise modeling, reconstructing for electrode movement, total variation (TV) reconstruction, robust error norms, smoothing priors, and using difference vs. normalized difference data.
Results and Conclusions: Our results indicate that, while variation in appearance of images reconstructed from the same data is not negligible, clinically relevant parameters do not vary considerably among the advanced algorithms. Among the analysed algorithms, several advanced algorithms perform well, while some others are significantly worse. Given its vintage and ad-hoc formulation backprojection works surprisingly well, supporting the validity of previous studies in lung EIT.
HIV neutralizing antibodies (nAbs) represent an important tool in view of prophylactic and therapeutic applications for HIV-1 infection. Patients chronically infected by HIV-1 represent a valuable source for nAbs. HIV controllers, including long-term non-progressors (LTNP) and elite controllers (EC), represent an interesting subgroup in this regard, as here nAbs can develop over time in a rather healthy immune system and in the absence of any therapeutic selection pressure. In this study, we characterized two particular antibodies that were selected as scFv antibody fragments from a phage immune library generated from an LTNP with HIV neutralizing antibodies in his plasma. The phage library was screened on recombinant soluble gp140 envelope (Env) proteins. Sequencing the selected peptide inserts revealed two major classes of antibody sequences. Binding analysis of the corresponding scFv-Fc derivatives to various trimeric and monomeric Env constructs as well as to peptide arrays showed that one class, represented by monoclonal antibody (mAb) A2, specifically recognizes an epitope localized in the pocket binding domain of the C heptad repeat (CHR) in the ectodomain of gp41, but only in the trimeric context. Thus, this antibody represents an interesting tool for trimer identification. MAb A7, representing the second class, binds to structural elements of the third variable loop V3 and neutralizes tier 1 and tier 2 HIV-1 isolates of different subtypes with matching critical amino acids in the linear epitope sequence. In conclusion, HIV controllers are a valuable source for the selection of functionally interesting antibodies that can be selected on soluble gp140 proteins with properties from the native envelope spike.
Our focus is the identification, characterisation and functional analysis of different MLL fusions. In general, MLL fusion proteins are encoded by large cDNA cassettes that are difficult to transduce into haematopoietic stem cells. This is due to the size limitations of the packaging process of those vector-encoded RNAs into retro- or lentiviral particles. Here, we present our efforts in establishing a universal vector system to analyse different MLL fusions. The universal cloning system was embedded into the backbone of the Sleeping Beauty transposable element. This transposon has no size limitation and displays no integration preference, thereby avoiding the integration into active genes or their promoter regions. We utilised this novel system to test different MLL fusion alleles (MLL-NEBL, NEBL-MLL, MLL-LASP1, LASP1-MLL, MLL-MAML2, MAML2-MLL, MLL-SMAP1 and SMAP1-MLL) in appropriate cell lines. Stable cell lines were analysed for their growth behaviour, focus formation and colony formation capacity and ectopic Hoxa gene transcription. Our results show that only 1/4 tested direct MLL fusions, but 3/4 tested reciprocal MLL fusions exhibit oncogenic functions. From these pilot experiments, we conclude that a systematic analysis of more MLL fusions will result in a more differentiated picture about the oncogenic capacity of distinct MLL fusions.
Computational analyses of functions of gene sets obtained in microarray analyses or by topical database searches are increasingly important in biology. To understand their functions, the sets are usually mapped to Gene Ontology knowledge bases by means of over-representation analysis (ORA). Its result represents the specific knowledge of the functionality of the gene set. However, the specific ontology typically consists of many terms and relationships, hindering the understanding of the ‘main story’. We developed a methodology to identify a comprehensibly small number of GO terms as “headlines” of the specific ontology allowing to understand all central aspects of the roles of the involved genes. The Functional Abstraction method finds a set of headlines that is specific enough to cover all details of a specific ontology and is abstract enough for human comprehension. This method exceeds the classical approaches at ORA abstraction and by focusing on information rather than decorrelation of GO terms, it directly targets human comprehension. Functional abstraction provides, with a maximum of certainty, information value, coverage and conciseness, a representation of the biological functions in a gene set plays a role. This is the necessary means to interpret complex Gene Ontology results thus strengthening the role of functional genomics in biomarker and drug discovery.
Alzheimer’s disease (AD) is a common, age associated neurodegenerative disease that manifests as progressive dementia and is characterized by accumulation of the amyloid beta (Aβ) peptide which is a processing product of a transmembrane protein termed Alzheimer Amyloid Precursor Protein (APP). The Aβ peptide is generated by a sequential proteolytic processing of APP by two distinct proteases that are termed β- and γ-secretase. The β-secretase, also called BACE-1 or memapsin 2, belongs to the family of aspartyl proteases. BACE-1 evidently cleaves APP in an acidic endosomal compartment after endocytosis of APP, thereby facilitating Aβ peptide generation.
Sorting of transmembrane proteins is generally controlled by sorting signals in the cytoplasmic domains of the cargo proteins. The short cytoplasmic tail of BACE-1 with 23 amino acids contains a sorting signal of the acidic cluster, di-leucine (ACDL) type. The two Leu residues in this determinant are important for the clathrin mediated endocytosis of BACE-1, whereas the acidic residues together with the Leu are required for the endosomal sorting and recycling of BACE-1 back to the plasma membrane. The ACDL motif binds to the members of the GGA (Golgi-localized γ ear-containg ARF- binding proteins) family (GGA1-GGA3) that are involved in the sorting of BACE-1.
One of the major aims of this study was to address the role of flotillins in the intracellular sorting of BACE-1. This study shows that flotillin-1 directly binds to the di-leucine motif in the cytoplasmic tail of BACE-1, whereas flotillin-2 only shows an association mediated by flotillin-1. Flotillin-1 competes with GGA2 for the binding to BACE-1 tail, and thus influences the endosomal sorting of BACE-1. Importantly, depletion of flotillins results in an altered localization of the wildtype BACE-1, whereas the plasma membrane resident Leu to Ala (LLAA) mutant is not affected. Flotillin knockdown results in an accumulation of BACE-1, implicating reduced degradation and enhanced stability of this protease. Thus, flotillins appear to be important for the cellular targeting of BACE-1 and also influence the amyloidogenic processing of APP, as demonstrated by an increase in the amyloidogenic C-99 processing fragments.
When flotillin depleted cells were subjected to apoptotic stresses including Aβ25-35 synthetic peptide (inducer of the extrinsic apoptosis pathway) or several chemotherapeutic agents (staurosporine, brefeldin A, doxorubicin, carboplatin and paclitaxel: intrinsic apoptosis pathway) and cytotoxicity was determined, various apoptotic markers were activated in flotillin depleted cells. Caspase-3 and GGA3 are well accepted apoptosis markers and an enhanced caspase-3 cleavage was detected upon STS induced apoptosis in SH-SY5Y, HeLa, and HaCaT cell lines and increased GGA3 cleavage was observed in MCF7 cell line.
One of the major reasons for the apoptotic sensitivity in the absence of flotillins was a PI3K/Akt signaling defect. Neuroblastoma cells depleted of flotillins showed diminished levels of total Akt, phospho-Akt and phospho-ERK upon STS induced apoptosis. Since PI3K/Akt was the primary survival pathway affected upon STS induced apoptosis, ectopic expression of Akt in neuroblastoma cell line reduced caspase-3 cleavage and retarded apoptosis.
The direct downstream target of Akt is FOXO3a, whose localization was investigated in flotillin depleted cells. A major proportion of FOXO3a was localized in the nucleus of flotillin knockdown cells, implicating that FOXOs are active in these cells and subsequently trigger the transcription of death genes. Strikingly, an essential anti-apoptotic molecule and a major cancer target, Mcl-1, was inherently downregulated in flotillin knockdown cells. Mcl-1 is a chief member of the Bcl-2 family as it plays a pivotal role in cell survival and it is a critical protein in cancer therapeutics as suppression of Mcl-1 protein can curtail the survival and growth of tumorous cells.
Neuroblastoma cells were rescued from undergoing permanent damage due to STS induced apoptosis by overexpression of anti-apoptotic Bcl-2. Phorbol esters are well known PKC activators, and pre-treatment of neuroblastoma cells with phorbol esters along with staurosporine reduced caspase-3 cleavage.
These results demonstrate that absence of flotillins can sensitize cellular systems to apoptosis induction. The two main characteristics of cancer cells include resistance to apoptosis and unresponsiveness to chemotherapeutic agents. It is a well established fact that impaired apoptosis is central to tumour development. This study implicates that the downregulation of flotillin function can trigger cellular susceptibility and enhances apoptosis in response to conventional chemotherapeutic agents. Therefore, flotillins can serve as vital regulators in providing a more rational approach in molecular-targeted therapies for receding cancer growth and survival.
Social impact bonds are a special type of bond whose purpose is to provide long term funds to projects with a social impact. Especially in the UK and in the US these bonds are increasingly being used to raise funds to finance government projects. Their return depends on the social improvements achieved. Especially in times of crisis, governments lack funds to prevent the social consequences of recessions. Faia argues that the European Union should develop an equivalent to the British Social Finance Ltd. to finance projects for social improvement.
Cryo-electron tomography (CET) is a unique technique to visualize biological objects under near-to-native conditions at near-atomic resolution. CET provides three-dimensional (3D) snapshots of the cellular proteome, in which the spatial relations between macromolecular complexes in their near native cellular context can be explored. Due to the limitation of the electron dose applicable on biological samples, the achievable resolution of a tomogram is restricted to a few nanometers, higher resolution can be achieved by averaging of structures occurring in multiples. For this purpose, computational techniques such as template matching, sub-tomogram averaging and classification are essential for a meaningful processing of CET data.
This thesis introduces the techniques of template matching and sub-tomogram averaging and their applications on real biological data sets. Subsequently, the problem of reference bias, which restricts the applicability of those techniques, is addressed. Two methods that estimate the reference bias in Fourier and real space are demonstrated. The real space method, which we have named the “M-free” score, provides a reliable estimation of the reference bias, which gives access to the reliability of the template matching or sub-tomogram averaging process. Thus, the “M-free” score makes those approaches more applicable to structural biology. Furthermore, a classification algorithm based on Neural Networks (NN) called “KerDenSOM3D” is introduced, which is implemented in 3D and compensates for the missing-wedge. This approach helps extracting different structural states of macromolecular complexes or increasing the class purity of data sets by eliminating outliers. A comprehensive comparison with other classification methods shows superior performance of KerDenSOM3D.
The birth of a new nation is an exciting time. Mick Bond spent the years 1962-73 as a District Officer and a District Commissioner, actively participating in the demise of the colonial regime and then as a civil servant in independent Zambia. This detailed account of his life and work includes the daily routine of a colonial officer, his personal experiences of the 1964 Lumpa conflict and his involvement in the elections of 1962, 1964, and 1968.
We discuss recent applications of the partonic perturbative QCD based cascade model BAMPS with focus on heavy-ion phenomenology in the hard and soft momentum range. First, the elliptic flow and suppression of charm and bottom quarks are studied at LHC energies. Thereafter, we compare in a detailed study the standard Gunion-Bertsch approximation of the matrix elements for inelastic processes to the exact results in leading order perturbative QCD. Since a disagreement is found, we propose an improved Gunion-Bertsch matrix element, which agrees with the exact result in all phase space regions.
This book is about home. With Malawi as its focus, it seeks to understand ideas about home as expressed through poetry written by Malawians in English. Although African Literatures are studied those of Malawi have not received agreeable attention. This book surveys poetry by five Malawian writers - Felix Mnthali, Frank Chipasula, Jack Mapanje, Lupenga Mphande, and Steve Chimombo. The discussion negotiates scribed experience of exile, engendered by Dr. Banda's regime, and shows that the selected poets effectively converse with a sense of home, reflecting on its transformations in their work. Interrogating the strict definitions of home, the argument highlights that far from home-less exiles in fact clarify the sense of what 'home' is. The manoeuvre is one of thinking towards an unboundaried 'home'. This book will be of value not only to readers interested in the cultures of Africa but to all those with an interest in worldwide literary phenomena, and ideas therein of home and exile.
German underwent a typological change from a syllable language in Old High German towards a word language today (Szczepaniak 2007). Proper names followed this development until the last century (cf. Christel, Gertrud, Klaus, Wolfgang). Some of the most popular German first names from 2010, however, such as Mia, Lea, Leon, Noah, show completely different structures compared to common nouns. In sharp contrast to common nouns, first names dispose of CV-structures, full vowels in unstressed syllables and different accent positions. Thus, there must have been a deep-rooted onomastic change. The most frequent baby names of 1945 were still in harmony with the usual word structures. This article shows that the decrease of transgenerational transmission of first names led to a departure fom native phonological structures. The following factors are analyzed: the number of syllables; accent position; and the number of consonant clusters, hiatuses, schwa and unstressed full vowels. It will be demonstrated that the phonological distance between first names (particularly female names) and common nouns has increased over time and that there is an increasing tendency for names to contain syllable language structures. Thus, a typological difference developed between these two nominal classes. The reason behind this change can be found in the individualizing function of proper names and social individualization over time.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is caused by mutations in the CLN3 gene, which encodes for a putative lysosomal transmembrane protein with thus far undescribed structure and function. Here we investigate the membrane topology of human CLN3 protein with a combination of advanced molecular cloning, spectroscopy, and in silico computation. Using the transposomics cloning method we first created a library of human CLN3 cDNA clones either with a randomly inserted eGFP, a myc-tag, or both. The functionality of the clones was evaluated by assessing their ability to revert a previously reported lysosomal phenotype in immortalized cerebellar granular cells derived from Cln3Δex7/8 mice (CbCln3Δex7/8). The double-tagged clones were expressed in HeLa cells, and FRET was measured between the donor eGFP and an acceptor DyLight547 coupled to a monoclonal α-myc antibody to assess their relative membrane orientation. The data were used together with previously reported experimental data to compile a constrained membrane topology model for hCLN3 using TOPCONS consensus membrane prediction algorithm. Our model with six transmembrane domains and cytosolic N- and C-termini largely agrees with those previously suggested but differs in terms of the transmembrane domain positions as well as in the size of the luminal loops. This finding improves understanding the function of the native hCLN3 protein.
Global warming, changes in the hydrological cycle and enhanced marine primary productivity all have been invoked to have contributed to the occurrence of widespread ocean anoxia during the Cenomanian-Turonian Oceanic Anoxic Event (OAE2; ~ 94 Ma), but disentangling these factors on a regional scale has remained problematic. We generated palynological and organic geochemical records that allow the separation of these forcing factors in a core spanning the OAE2 from Wunstorf, Lower Saxony Basin (LSB; North Gemany), which exhibits cyclic black shale–marl alternations related to the orbital precession cycle.
Despite the widely varying depositional conditions complicating the interpretation of the obtained records, TEX86H indicates that sea-surface temperature (SST) evolution in the LSB during OAE2 resembles that of previously studied sites throughout the proto-North Atlantic. Cooling during the so-called Plenus Cold Event interrupted black shale deposition during the early stages of OAE2. However, TEX86 does not vary significantly across marl–black shale alternations, suggesting that temperature variations did not force the formation of the cyclic black shale horizons. Relative (i.e., with respect to marine palynomorphs) and absolute abundances of pollen and spores are elevated during phases of black shale deposition, indicative of enhanced precipitation and run-off. High abundances of cysts from inferred heterotrophic and euryhaline dinoflagellates supports high run-off, which likely introduced additional nutrients to the epicontinental shelf resulting in elevated marine primary productivity.
We conclude that orbitally-forced enhanced precipitation and run-off, in tandem with elevated marine primary productivity, were critical in cyclic black shale formation on the northwest European epicontinental shelf and potentially for other OAE2 sections in the proto-Atlantic and Western Interior Seaway at similar latitudes as well.
Freiburg School of Law and Economics, Freiburg (Lehrstuhl-)Tradition and the Genesis of Norms
(2014)
The paper analyzes the parallels and differences between the Freiburg School of Law and Economics represented by the works of Eucken (and Röpke) and the Freiburg (Lehrstuhl-)Tradition represented by the works of Hayek and Vanberg. The parallels are illustrated by making use of the constitutional economics concepts Ordnungspolitik (i.e., order of rules/choices over rules) as well as freedom of privileges and discrimination. The differences, which have received surprisingly little attention, include the following aspects: 1. philosophy of science and epistemology, 2. genesis of norms, and 3. political philosophy. The paper tackles these issues in three steps. The second chapter presents Vanberg’s constitutional economics theory with special emphasis on the concepts of citizen sovereignty and normative individualism. The third chapter reviews the ordoliberal concepts of science and the state which are – to a certain degree – elitist and expertocratic, that is, they rely to a considerable degree on intellectual experts (in particular, scientists) being part of the societal elite. The fourth chapter differentiates two kinds of genesis of norms: an evolutionary one and an elitist-expertocratic one allowing for a differentiation between Eucken’s and Röpke’s Ordoliberalism on the on the hand and Vanberg’s Hayekian -- and Buchanan-style constitutional economics approach on the other hand. The paper ends with a summary of the main findings.
Freeze-out radii extracted from three-pion cumulants in pp, p–Pb and Pb–Pb collisions at the LHC
(2014)
In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose–Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e.g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p–Pb and Pb–Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p–Pb collisions are found to be 5–15% larger than those in pp, while those in Pb–Pb are 35–55% larger than those in p–Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p–Pb as compared to pp collisions at similar multiplicity.
Kokori: The Struggle for June 12 is the candid account of Chief Frank Kokori, former General Secretary of The Nigeria Union of Petroleum and Natural Gas Workers (NUPENG). It details the roles he and other individuals played in the quest to revalidate the June 12, 1993 presidential election, which was annulled by Gen. Ibrahim Babangida. The book details, in depth, the events before, during and after the election, up until the incarceration of Chief Kokori as well as the political fall-out which followed.
Francisco Suárez (1548-1617) and Rodrigo Arriaga (1592-1667) on the state of innocence and community
(2014)
Recent scholarship on late-scholastic thought has stressed a Jesuit discontinuity from Thomism. While Aquinas’ Aristotelian thesis located the political sphere in the state of innocence, Jesuit thought on community formation is said to have referred to ‘fallen’ and ‘pure’ nature. In this piece, I trace one particular narrative: In the hypothetical, lasting state of innocence (if original sin had not occurred), Aquinas identified the political community, but not the institution of the sacraments. Two celebrated Jesuit scholastics, Francisco Suárez and Rodrigo Arriaga, challenged the latter claim and defended the naturalness of spiritual alongside temporal power. This effectively allowed them to connect ‘nature’ to ‘utility’ and ‘necessity’ without tying their claims to the supernatural teleology. To them, the state of innocence remained relevant for politics, albeit in a way that challenged the Thomist account.
Four taxa belonging to the complex of species around Achnanthidium minutissimum were found during the ongoing taxonomic revision of the Antarctic freshwater and limno-terrestrial diatom flora. Two taxa were previously described as Achnanthidium lailae and A. sieminskae. Two others were formerly identified as A. minutissimum but detailed light and scanning electron microscopical observations revealed sufficient morphological differences compared to the type of A. minutissimum, to justify their separation and description as new taxa: Achnanthidium indistinctum and A. maritimo-antarcticum. The morphology and ecology of all four taxa are discussed comparing the species with morphologically similar taxa. The biogeographical consequences of the splitting of the former A. minutissimum complex in the Antarctic Region are discussed.
n a contribution prepared for the Athens Symposium on “Banking Union, Monetary Policy and Economic Growth”, Otmar Issing describes forward guidance by central banks as the culmination of the idea of guiding expectations by pure communication. In practice, he argues, forward guidance has proved a misguided idea. What is presented as state of the art monetary policy is an example of pretence of knowledge. Forward guidance tries to give the impression of a kind of rule-based monetary policy. De facto, however, it is an overambitious discretionary approach which, to be successful, would need much more (or rather better) information than is currently available. In Issing's view, communication must be clear and honest about the limits of monetary policy in a world of uncertainty.
Invasions by non-native species are a threat to biodiversity because invaders can impact native populations, communities and entire ecosystems. To manage this threat, it is necessary to have a strong mechanistic understanding of how non-native species affect local species and communities. We reviewed 259 published papers (1972–2012) that described field experiments quantifying the impact of aquatic nonnative species, to examine whether various types of study biases are limiting this understanding. Our review revealed that invasion impacts had been experimentally quantified for 101 aquatic non-native species, in all major freshwater and marine habitats, on all continents except Antarctica and for most higher taxonomic groupings. Over one-quarter (26%) of studies included tests for impacts on local biodiversity. However, despite this extensive research effort, certain taxa, habitats and regions remain poorly studied. For example, of the over one hundred species examined in previous studies, only one was a marine fish and only six were herbivores. Furthermore, over half (53%) of the studies were from the USA and two-thirds (66%) were from experiments conducted in temperate latitudes. By contrast, only 3% of studies were from Africa and <2% from high latitudes. We also found that one-fifth (20%) of studies were conducted in estuaries, but only 1% from coral reefs. Finally, we note that the standard procedure of pooling or not reporting non-significant treatments and responses is likely to limit future synthetic advancement by biasing meta-analysis and severely limiting our ability to identify non-native species with none or negligible ecological impacts. In conclusion, a future focus on poorly-studied taxa, habitats and regions, and enhanced reporting of results, should improve our understanding and management of impacts associated with aquatic non-native species.
In the article the state of forming of communicative competence of future lawyers in higher education of Ukraine and Germany is analyzed. There is made the comparative description of preparation of the students of law faculty with an accent on forming of communicative competence on the example of the University of modern knowledge (Ukraine) and Frankfort university is named after Goethe (Germany).
It is drawn the conclusion, that the structure of professional preparation of future lawyers is folded educational and cognitive, research constituents, and also productive practice. A main place is taken to conception of communicative preparation of the future lawyers, the essence of it consists in integration of the special courses of the special and professional disciplines, in continuous perfection of skills of the verbal and writing broadcasting, receptions of analytical mental work, that need knowledge. It is also outlined the aim of productive practice of future lawyers in Ukraine that begins from the second course: the forming of professional abilities and skills of acceptance of independent decisions; the education of necessity systematic to proceed the knowledge, to promote a legal culture and professional legal consciousness; to teach to apply knowledge in practical activity. In Germany the practice for future lawyers begins from the first course and lasts two years in legal establishments (from civil cases, court from criminal cases or office of public prosecutor, administrative and managerial establishments, advocacy). The sign line of studies is an active collaboration with the faculties of law of the foreign states. All these factors assist the forming of communicative competence of lawyers.
Tumor development usually follows predictable paths where tumor cells acquire common characteristics and features known as the hallmarks of cancer. Recently, additional characteristics have been added to these hallmarks since solid tumors are composed of a very heterogeneous population of transformed, formerly normal tissue cells and stromal cells, e.g. immune cells and fibroblasts. Compelling evidence suggests that stromal cells and tumor cells maintain a symbiotic relationship to build up the tumor microenvironment and to fuel tumor growth. In cancer therapies, common features of tumors such as unrestricted cell growth, suppression of immunological responses, and the ability to form new blood vessels (angiogenesis) have emerged as the main targets of interest. The lipid mediator prostaglandin E2 (PGE2) is known to promote all these features and thus, is connected to cancer progression in general. Its synthesis is triggered in response to stress factors or during inflammation. Inducible PGE2 production relies on the enzymes cyclooxygenase 2 (COX-2) and microsomal prostanglandin E synthase 1 (mPGES-1), which are simultaneously expressed in response to a variety of different stimuli and are functionally coupled. Inhibition of COX-2 with non-steroidal antiinflammatory drugs (NSAIDs) for cancer treatment is, however, limited by cardiovascular risks, since selective COX-2 inhibition disrupts the prostacyclin/thromboxane balance. Therefore targeting mPGES-1 downstream of COX-2 for PGE2 inhibition was evaluated in this work in different steps of carcinogenesis. Knockdown of mPGES-1 in DU145 prostate cancer cells revealed that the mPGES-1 status did not affect growth of monolayer tumor cells, but significantly impaired 3D growth of multi-cellular tumor spheroids (MCTS). Spheroid formation induced COX-2 in DU145 and other prostate cancer spheroids. High levels of PGE2 were detected in supernatants of DU145 MCTS as opposed to monolayer DU145 cells. Pharmacological inhibition of COX-2 and mPGES-1 confirmed the pivotal role of PGE2 for DU145 MCTS growth. Besides promoting spheroid growth, MCTS-derived PGE2 also inhibited cytotoxic T lymphocyte (CTL) activation. When investigating the mechanisms of COX-2 induction during spheroid formation, the typical tumor microenvironmental factors such as glucose deprivation, hypoxia or tumor cell apoptosis failed to enhance COX-2. Interestingly, when interfering with apoptosis in DU145 spheroids, the pan-caspase inhibitor Z-VAD-FMK triggered a Summary 12 shift towards necrosis, thus enhancing COX-2 expression. Coculturing viable DU145 monolayer cells with isolated heat-shocked-treated necrotic DU145 cells, but not with necrotic cell supernatants, induced COX-2 and PGE2, confirming the impact of necrosis for MCTS growth and CTL inhibition. As mentioned, in vivo tumors are very heterogenous mixtures of tumor cells and stromal cells e.g. immune cells. Hence, the interaction of the immune system with tumors was investigated in further experiments. When coculturing MCF-7 breast cancer spheroids with human peripheral blood mononuclear cells (PBMCs), only low levels of PGE2 were detected, since MCF-7 cells did not upregulate COX-2 during spheroid formation and did not induce PGE2 production by PBMCs. Under inflammatory conditions, by adding the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) to cocultures, PGE2 production was triggered, spheroid sizes were reduced, and numbers of high levels of granzyme B expressing (GrBhi) CTLs were increased, while CD80 expression by tumor-associated phagocytes was also elevated. Inhibition of CD80 but not CD86 diminished numbers of GrBhi CTLs and attenuated spheroid lysis. To determine the role of ctivation-induced PGE2 production, use of the COX-2 inhibitor celecoxib and the experimental mPGES-1 inhibitor C3 further increased CD80 expression. Addition of PGE2, the prostaglandin E2 (EP2) receptor agonist butaprost, and the phosphodiesterase 4 (PDE4) inhibitor rolipram reduced LPS/C3-triggered CD80 expression, confirming the impact of COX- 2/mPGES-1-derived PGE2 on shaping phagocyte phenotypes in an EP2/cAMP-dependent manner. In a spontaneous breast cancer model (MMTV-PyMT), mPGES-1-deficiency significantly delayed tumor growth in mice, confirming an overall protumorigenic role of mPGES-1 in breast cancer development in vivo. However in tumors of mPGES-1-/- mice, tumor-infiltrating phagocytes expressed low levels of CD80 similar to their wildtype counterparts. These data suggest that the immunosuppressive microenvironment does not allow for immunostimulatory effects by mPGES-1 inhibition without an activating stimulus. Evidences in this study recommend the application of mPGES-1 inhibitors for treating cancer diseases, since mPGES-1 promotes tumor growth in multiple steps of carcinogenesis, ranging from well-characterized effects of tumor cell growth to immune suppression of CTL activity and phagocyte polarization. Regarding the latter, blunting PGE2 during immune activation may limit the tumor-favoring features of inflammation and improve the efficiency of TLR4 based immune therapies.
A selection of duplicates from the collection of Michel Edmond de Selys Longchamps was found at the Übersee-Museum Bremen/Germany (UMB). Selys determined a lot of Odonata in the UMB collection and sent 80 European and 76 exotic species to Bremen on 23 April, 1875. According to the labels 121 specimens could be assigned to this shipment and eleven specimens must have been sent to UMB in later years. This collection includes two paralectotypes (Progomphus gracilis Hagen inSelys, 1853;Palaemnema nathalia Selys, 1886) and seven syntypes (Rhinocypha trifasciata Selys, 1853; Dysphaea dimidiata limbata Selys, 1859; Argia sordida Hagen inSelys, 1865; Oxyagrion dissidens Selys, 1876; Oxyagrion haematinum Selys, 1876; Oxyagrion pavi-dum Hagen in Selys, 1876; Telagrion longum Selys, 1876). In addition, a male specimen of Euphaea tricolor subcostalis Selys, 1873 might also belong to the original syntype series. Altogether three specimens with labeled nomina nuda(Diplax catharina Selys, Diplax fausta Selys, Dythemis bilineata Hagen) and two labeled with manuscript names (Diplax marcellina Selys, Perithemis ovate Bates) are in this collection.
The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future, due to global climate change. Dynamic Global Vegetation Models (DGVMs) are very useful to understand vegetation dynamics under present climate, and to predict its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modelling. Model outcomes, obtained including different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. Through these comparisons, and by drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need an improved representation in the DGVMs. The first mechanism includes water limitation to tree growth, and tree-grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass-fire feedback, which maintains both forest and savanna occurrences in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant savanna trees, and fire-resistant and shade-intolerant forest trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.
Climate is frequently used to predict the outcome of species introductions based on the results from species distribution models (SDMs). However, despite the widespread use of SDMs for pre- and post-border risk assessments, data that can be used to validate predictions is often not available until after an invasion has occurred. Here we explore the potential for using historical forestry trials to assess the performance of climate-based SDMs. SDMs were parameterized based on the native range distribution of 36 Australian acacias, and predictions were compared against both the results of 150 years of government forestry trials, and current invasive distribution in southern Africa using true skill statistic, sensitivity and specificity. Classification tree analysis was used to evaluate why some Australian acacias failed in trials while others were successful. Predicted suitability was significantly related to the invaded range (sensitivity = 0.87) and success in forestry trials (sensitivity = 0.80), but forestry trial failures were under-predicted (specificity = 0.35). Notably, for forestry trials, the success in trials was greater for species invasive somewhere in the world. SDM predictions also indicate a considerable invasion potential of eight species that are currently naturalized but not yet widespread. Forestry trial data clearly provides a useful additional source of data to validate and refine SDMs in the context of risk assessment. Our study identified the climatic factors required for successful invasion of acacias, and accentuates the importance of integration of status elsewhere for risk assessment.
Focus on quantum efficiency
(2014)
Technologies which convert light into energy, and vice versa, rely on complex, microscopic transport processes in the condensed phase, which obey the laws of quantum mechanics, but hitherto lack systematic analysis and modeling. Given our much improved understanding of multicomponent, disordered, highly structured, open quantum systems, this ‘focus on’ collection collects cuttingedge research on theoretical and experimental aspects of quantum transport in truly complex systems as defined, e.g., by the macromolecular functional complexes at the heart of photosynthesis, by organic quantum wires, or even photovoltaic devices. To what extent microscopic quantum coherence effects can (be made to) impact on macroscopic transport behavior is an equally challenging and controversial question, and this "focus on" collection provides a setting for the present state of affairs, as well as for the "quantum opportunities" on the horizon.
FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces.
As part of a wider study of floodplain vegetation along the River Murray, we carried out a field survey in 1987–1988 involving collection of floristic and vegetation condition data from 335 sample plots (each 400 m2 in area), between Hume Dam and Lake Alexandrina (including the Edward-Wakool anabranch system). The floodplain vegetation is dominated by just two tree species, River Red Gum (Eucalyptus camaldulensis) and Black Box (Eucalyptus largiflorens), but the composition of the understorey shows much greater variation, both along the river and across the floodplain. A total of 499 plant species, subspecies and varieties were recorded from the survey plots, of which 316 (63%) were native and 183 (37%) were exotic. From analysis of the floristic data we identified 37 vegetation communities, not including the vegetation of permanent wetlands and cleared areas; 21 communities were distinguished in the River Red Gum zone, 12 communities in the Black Box zone, and 4 communities on rises within the floodplain. The main floristic division among the River Red Gum communities was between Riverine Plain/ Headwaters Zone communities of the upper Murray, and Mallee Zone communities of the lower Murray. Among the Black Box communities, the main floristic division was between inner floodplain communities and outer floodplain communities, with a further division between South Australian communities and New South Wales/Victorian communities. Major factors influencing the floristic patterns included flooding frequency/duration and soil salinity.
Eucalypt health declined steadily downstream and was poorest in the lower reaches of the river below the Darling Junction, where 60% of the trees were healthy, 18% unhealthy (at least 40% of the canopy dead) and 22% dead. By comparison, at the upper end of the river, above Tocumwal, 84% of the trees were healthy, 14% unhealthy and only 2% dead. Overall, the condition of Black Box trees (44% unhealthy or dead) was worse than the condition of River Red Gum trees (29% unhealthy or dead). Eucaypt regeneration was also poorest below the Darling Junction, with regenerants present in 77% of plots upstream of the Darling but only 35% of plots downstream. The findings of poor tree health and sparse regeneration below the Darling coincide with the most heavily regulated part of the Murray, where the reduction in flooding due to upstream storages and water extraction, mainly for irrigation, has been greatest. Black Box regeneration was much sparser overall than River Red Gum regeneration (regenerants present in 69% of River Red Gum plots but only 29% of Black Box plots). The poor condition of the Black Box trees, coupled with their poor regeneration, suggests that the long-term future of this species along the Murray, particularly below the Darling Junction, is tenuous, even though it is a dominant component of the vegetation.
The integrity of floodplain vegetation along the Murray has been severely compromised by weed invasion. Weeds were common throughout the survey area, but were most prevalent in the climatically wetter sections of the river, at both the downstream and upstream ends (below Mannum and above Tocumwal). The median number of exotic species per plot equalled or exceeded the number of native species in these sections of the river, whereas native species outnumbered exotic species in the other river sections. Communities of the River Red Gum zone and the rises were generally weedier than those of the Black Box zone. Exotic species strongly influenced the community classification. They were the dominant overstorey species in two communities (Salix species – willows) and outnumbered native species in the understorey of another eight communities. At the lower end of the river, below Mannum, the River Red Gums that originally fringed the river had been mostly replaced by dense thickets of the exotic Weeping Willow, Salix babylonica.
Other factors that have impacted on the floodplain vegetation at the plant community level have been river regulation and soil salinisation. Stabilization of water levels in the lower Murray by construction of a series of weirs and barrages has favoured the spread of some communities at the expense of others. The favoured communities, which are characterised by stands of Common Reed, Phragmites australis, along the water’s edge, appear to be artefacts of river regulation. Salinisation has resulted in death of eucalypts and replacement of eucalypt communities by shrub communities dominated by samphires, Tecticornia species. The samphire community characteristic of the most saline sites is one of the most species-poor communities on the Murray floodplain.
Logging along the Murray in New South Wales and Victoria has resulted in extensive replacement of old growth River Red Gum forests and woodlands by more even-aged stands of straight young trees. Following the recent conversion of many areas of State Forest along the Murray in both New South Wales and Victoria to National Park or Regional Park, and thus the cessation of logging in these areas, they should now revert gradually to mature forest and woodland.
This study is the first to describe broad scale floristic patterns in the floodplain vegetation of the Murray covering most of the length of the river. It also provides data on the vegetation condition in the 1980s, and provides a benchmark of conditions before the prolonged Millenium Drought in south-eastern Australia from 1997 to 2010. More recent surveys of vegetation condition have reported a severe decline in tree health during the drought. The results from our 1987–88 survey are important because they show that the deteriorating condition of the vegetation was already evident in the 1980s and although exacerbated by the subsequent drought, it is not just a consequence of that drought. The results are consistent with the conclusion that the primary cause of the decline has been river regulation and water extraction for irrigation. The rate of deterioration has increased rapidly since the 1980s because of the drought. There has been some improvement since the breaking of the drought, but the poor condition of the River Murray floodplain vegetation, an Australian icon, remains a major conservation and management issue. The impacts of climate change – higher temperatures and reduced rainfall – have compounded the problem and will continue to do so at an increasing rate. The results of the study support listing of the floodplain vegetation of the lower reaches of the river as a critically endangered ecological community.
Five new species of Cerambycidae (Coleoptera) from Peru and Bolivia, and two new records for Peru
(2014)
The following four new species of Cerambycidae are described from Bolivia: Chrysoprasis imitatrix (Heteropsini); Carneades vigneaulti (Colobotheini); Colobothea larriveei (Colobotheini); Colobothea boliviana (Colobotheini). Esthlogena (Pseudotaxia) bella (Pteropliini) is described from Peru. A key to species of Carneades Bates, 1869 is provided. The other new species are included in previously published keys. Additionally, two new country records are reported for the fauna of Peru.
The present paper describes five new species of candonid ostracods in two genera: Pseudocandona agostinhoi sp. nov., P. cillisi sp. nov., P. claudinae sp. nov., Candobrasilopsis elongata sp. nov. and C. acutis sp. nov. The three species of Pseudocandona belong to the caribbeana-group in this genus. With the two new species of Candobrasilopsis, this genus now comprises four species.
Candobrasilopsis elongata sp. nov. is the most common of the five new species described here, while C. acutis sp. nov. and P. claudinae sp. nov. are known from one locality only, which is furthermore the same for both species: a small streamlet entering the Paraná River. With the description of the present five species, the number of species known from the Paraná River alluvial valley, including the Taquaruçu lakes, now amounts to 49.
US data and new stockholding data from fifteen European countries and China exhibit a common pattern: stockholding shares increase in household income and wealth. Yet, there is a multitude of numbers to match through models. Using a single utility function across households (parsimony), we suggest a strategy for fitting stockholding numbers, while replicating that saving rates increase in wealth, too. The key is introducing subsistence consumption to an Epstein-Zin-Weil utility function, creating endogenous risk-aversion differences across rich and poor. A closed-form solution for the model with insurable labor-income risk serves as calibration guide for numerical simulations with uninsurable labor-income risk.
Recent advances in understanding the mechanisms of nonsmall cell lung cancer (NSCLC) has led to the development of targeted treatments, including the reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib, and the irreversible ErbB family blocker afatinib. Several important activating EGFR mutations have now been identified, which correlate strongly with response to treatment with these agents. Multiple randomised controlled trials have confirmed the association between the presence of activating EGFR mutations and objective response to gefitinib, erlotinib and afatinib, thus demonstrating their superiority over platinum-based chemotherapy as first-line treatment for NSCLC patients with EGFR mutation-positive tumours, and resulting in approval of these agents for use in this setting. It can be tempting to compare outcome data across multiple clinical trials and agents; however, substantial differences in methodology between studies, including investigator versus independent assessment and differences in patient eligibility, makes such comparisons fraught with difficulty. This critical review provides an overview of the evolution of the methodology used in eight phase III trials investigating first-line targeted treatment of NSCLC, identifies key differences in methodology and reporting, and critically assesses how these differences should be taken into account when interpreting the findings from such trials.