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The first study of ϕ-meson production in p–Pb collisions at forward and backward rapidity, at a nucleon–nucleon centre-of-mass energy √sNN=5.02 TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions — where y stands for the rapidity in the nucleon–nucleon centre-of-mass — the integrated luminosity amounting to 5.01±0.19 nb−1 and 5.81±0.20 nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward–backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT=3–4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at √s=2.76 TeV, which is used to determine a reference for the p–Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4, for a 78±3 nb−1 integrated luminosity sample.
The first study of ϕ-meson production in p-Pb collisions at forward and backward rapidity, at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02~TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass, the integrated luminosity amounting to 5.01±0.19~nb−1 and 5.81±0.20~nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4 for a 78±3~nb−1 integrated luminosity sample.
The first study of ϕ-meson production in p-Pb collisions at forward and backward rapidity, at a nucleon-nucleon centre-of-mass energy sNN−−−√=5.02~TeV, has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass, the integrated luminosity amounting to 5.01±0.19~nb−1 and 5.81±0.20~nb−1, respectively, for the two data samples. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward ratio for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a ratio ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4 for a 78±3~nb−1 integrated luminosity sample.
An invariant differential cross section measurement of inclusive π0 and η meson production at mid-rapidity in pp collisions at s√=8 TeV was carried out by the ALICE experiment at the LHC. The spectra of neutral mesons π0 and η were measured in transverse momentum ranges of 0.3<pT<35 GeV/c and 0.5<pT<35 GeV/c, respectively. Next-to-leading order perturbative QCD calculations using fragmentation functions DSS14 for π0 and AESSS for η overestimate the cross sections of both neutral mesons, but agree with the measured η/π0 ratio within uncertainties. The results are also compared with PYTHIA~8.2 predictions for which the Monash~2013 tune yields the best agreement with the measured neutral meson spectra. The measurements confirm a universal behavior of the η/π0 ratio seen for NA27, PHENIX and ALICE data for pp collisions from s√=27.5 GeV to s√=8 TeV within experimental uncertainties. A relation between the π0 and η production cross sections for pp collisions at s√=8 TeV is given by mT scaling for pT>3.5 GeV/c. However, a deviation from this empirical scaling law is observed for transverse momenta below pT<3.5 GeV/c in the η/π0 ratio with a significance of 6.2σ.
The pT-differential production cross section of prompt Λ+c charmed baryons was measured with the ALICE detector at the Large Hadron Collider (LHC) in pp collisions at s√=7 TeV and in p-Pb collisions at sNN−−−√=5.02 TeV at midrapidity. The Λ+c and Λ¯¯¯¯−c were reconstructed in the hadronic decay modes Λ+c→pK−π+, Λ+c→pK0S and in the semileptonic channel Λ+c→e+νeΛ (and charge conjugates). The measured values of the Λ+c/D0 ratio, which is sensitive to the c-quark hadronisation mechanism, and in particular to the production of baryons, are presented and are larger than those measured previously in different colliding systems, centre-of-mass energies, rapidity and pT intervals, where the Λ+c production process may differ. The results are compared with the expectations obtained from perturbative Quantum Chromodynamics calculations and Monte Carlo event generators. Neither perturbative QCD calculations nor Monte Carlo models reproduce the data, indicating that the fragmentation of heavy-flavour baryons is not well understood. The first measurement at the LHC of the Λ+c nuclear modification factor, RpPb, is also presented. The RpPb is found to be consistent with unity and with that of D mesons within the uncertainties, and consistent with a theoretical calculation that includes cold nuclear matter effects and a calculation that includes charm quark interactions with a deconfined medium.
In April and May 2012 data on Au+Au collisions at beam energies of Ekin = 1.23A GeV were recorded with the High Acceptance Di-Electron Spectrometer, which is located at the GSI Helmholtz Center for Heavy Ion Research in Darmstadt, Germany. At this beam energy all hadrons containing strangeness are produced below their elementary production threshold. The required energy is not available in binary NN collisions but must be provided by the system e.g. through multi-particle interactions or medium effects like a modified in-medium potential (e.g. KN/ΛN potential). Thus, a high sensitivity to these medium effects is expected in the investigated system.
The baryon-dominated systems created in relativistic heavy-ion collisions (HIC) at SIS18 energies reach densities of about 2-3 times ground state density p0 and may be similar to the properties of matter expected in the inner core of neutron stars. It is in particular the behavior of hadrons containing strangeness, i.e. kaons and hyperons, and their potentials in the dense medium which may have severe implications on astrophysical objects and processes. As ab-initio calculations of quantum chromodynamics (QCD) cannot be performed rigorously on the lattice at finite baryo-chemical potentials due to the fermion sign problem, effective descriptions have to be used in order to model properties of dense systems and the involved particles. The only way to access the in-medium potential of strange hadrons above nuclear ground state density p0 is by comparing data from relativistic HIC to such effective microscopic models. Up to now, not much data on neutral kaons and Λ hyperons are available from heavy collision systems close to their NN production threshold. These two electromagnetically uncharged strange hadrons are in particular well suited to study their potential in a dense nucleon-dominated environment as their kinematic spectra are not affected by Coulomb interactions.
Poetry is fragments of music thrown into the air. The primary job and aim of a poet is to create these musical notes, to play these musical notes, and the wind will take these fragment notes, sounds, musics into the ears of listeners. Zimbolicious Poetry Anthology, Volume 2 is one of those winds among many others. As we all are aware of, when the wind travels it has no boundaries, it collects, it deposits, it mixes things up; you never know where that leaf you see the wind carrying will eventually be deposited, is there another wind, another element that is going to move that leaf to another place... We firmly believe it is a good wind. It will be able to push our poetry making in Zimbabwe into other frontiers. Zimbolicious Poetry Anthology, Volume 2 continues from where we left off with the first Zimbolicious Poetry Anthology we created in 2016. In this Volume 2, we have 77 poems from 30 poets and translators, which include among others; experienced poets, academic poets, street poets, emergent poets, beginning poets, all telling stories associated with what all these poets refer to as home, that is, Zimbabwe. It is an ongoing debate on what is Zimbabwe, what we want our Zimbabwe to be socially, culturally, politically, thus we allowed every opinion space in this anthology, whether us editors agree with them or not. We have poets tackling issues to do with poetry, writing in general, art, place, identity, tradition, struggle, culture, gender, collective understanding, religion, individual, human rights and love, among others.
Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase “RET”, several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like. Our results report high-level insect cell expression of post-translationally modified and dimerized zebrafish RET and its binding partners. We also found that zebrafish GFRα1 and GDNF are comparably active as mammalian cell-produced ones. We also report the first measurements of the affinity of the complex to RET in solution: at least for zebrafish, the Kd for GFRα1-GDNF binding RET is 5.9 μM. Surprisingly, we also found that zebrafish GDNF as well as zebrafish GFRα1 robustly activated human RET signaling and promoted the survival of cultured mouse dopaminergic neurons with comparable efficiency to mammalian GDNF, unlike E. coli-produced human proteins. These results contradict previous studies suggesting that mammalian GFRα1 and GDNF cannot bind and activate non-mammalian RET and vice versa.
A new species belonging to the crustacean class Remipedia is described from an anchialine cave system on the island of Cozumel (Mexico), and is illustrated and compared morphologically and molecularly (CO1 and 16S) with closely related taxa. Xibalbanus cozumelensis sp. nov., the first remipede described from Cozumel, is morphologically similar to Xibalbanus tulumensis (Yager, 1987) from the Yucatán Peninsula, but the two species are genetically separate from each other (about 10% in CO1). A phylogenetic (Bayesian) analysis of Yucatán remipede populations based on CO1 and 16S placed them in a monophyletic Xibalbanus (in Xibalbanidae fam. nov.), with X. cozumelensis as most closely related to X. tulumensis. The Yucatán Peninsula and Cozumel have been separate since approx. early Cenozoic (~65 Ma), which suggests allopatric speciation for X. cozumelensis sp. nov. and X. tulumensis. However, the comparatively low genetic divergence between the two species may indicate that there has been gene flow between ‘mainland’ Yucatán and Cozumel long after the geological separation of the two landmasses, e.g., in cave systems under the sea bed, either continuously or sporadically, for example during the Last Glacial Maximum when the sea level was about 120 m lower than today.
This poetry anthology offers a feast and face of poetry as it currently is in Uganda. It is all encompassing and presents a variety of writers ranging from seasoned voices to new ones of great promise. The voices are adventurous, reflective, provocative and even sassy. The poets explore with passion diverse themes from the private to the public realm reassuring the reader that poetry is about everything and is perhaps everything. The pages of this anthology pulsate with rhythmic variations that give unexpected pleasure and provoke the reader to be exceptionally alert. This is a welcome and priceless addition to Uganda Poetry Anthology 2000.
We test two hypotheses, based on sexual selection theory, about gender differences in costly social interactions. Differential selectivity states that women invest less than men in interactions with new individuals. Differential opportunism states that women’s investment in social interactions is less responsive to information about the interaction’s payoffs. The hypotheses imply that women’s social networks are more stable and path dependent and composed of a greater proportion of strong relative to weak links. During their introductory week, we let new university students play an experimental trust game, first with one anonymous partner, then with the same and a new partner. Consistent with our hypotheses, we find that women invest less than men in new partners and that their investments are only half as responsive to information about the likely returns to the investment. Moreover, subsequent formation of students’ real social networks is consistent with the experimental results: being randomly assigned to the same introductory group has a much larger positive effect on women’s likelihood of reporting a subsequent friendship.
In 1905, the managing editor of the Jewish Encyclopedia, Isidore Singer (1859–1939), published an article in the journal Ost und West from a "bird’s eye perspective on the development of American Jewry in the last 250 years." In this historical overview, Singer eventually attested that Jewish scholarship in America had an "absolute dependency on the European motherland." This judgment was based on his disapproving view of the two American rabbinical seminaries that existed at that time. According to Singer, there were still no scholars at the Hebrew Union College (HUC) in Cincinnati of the "already American[-born] generation of Israel." In fact, Singer’s observation was appropriate because it applied to the Jewish Theological Seminary of America (JTSA) in New York as much as to the HUC.3 Despite the history of Jewish settlement in America, around 1900 there was still no native Jewish scholarship in America. The scene was dominated by scholars educated in Europe, who often came with broken English and a strict academic sense of mission. In 1903, Kaufmann Kohler (1843–1926), born in Bavaria and trained at German universities, was chosen as the president of HUC. And a year earlier, Solomon Schechter (1847–1915) had been called to the JTSA in New York as its new president. ...
Background: Correct species identification of blow flies is a crucial step for understanding their biology, which can be used not only for designing fly control programs, but also to determine the minimum time since death. Identification techniques are usually based on morphological and molecular characters. However, the use of classical morphology requires experienced entomologists for correct identification; while molecular techniques rely on a sound laboratory expertise and remain ambiguous for certain taxa. Landmark-based geometric morphometric analysis of insect wings has been extensively applied in species identification. However, few wing morphometric analyses of blow fly species have been published.
Methods: We applied a landmark-based geometric morphometric analysis of wings for species identification of 12 medically and forensically important blow fly species of Thailand. Nineteen landmarks of each right wing of 372 specimens were digitised. Variation in wing size and wing shape was analysed and evaluated for allometric effects. The latter confirmed the influence of size on the shape differences between species and sexes. Wing shape variation among genera and species were analysed using canonical variates analysis followed by a cross-validation test.
Results: Wing size was not suitable for species discrimination, whereas wing shape can be a useful tool to separate taxa on both, genus and species level depending on the analysed taxa. It appeared to be highly reliable, especially for classifying Chrysomya species, but less robust for a species discrimination in the genera Lucilia and Hemipyrellia. Allometry did not affect species separation but had an impact on sexual shape dimorphism.
Conclusions: A landmark-based geometric morphometric analysis of wings is a useful additional method for species discrimination. It is a simple, reliable and inexpensive method, but it can be time-consuming locating the landmarks for a large scale study and requires non-damaged wings for analysis.
Ebola virus (EBOV) infection causes a high death toll, killing a high proportion of EBOV-infected patients within 7 days. Comprehensive data on EBOV infection are fragmented, hampering efforts in developing therapeutics and vaccines against EBOV. Under this circumstance, mathematical models become valuable resources to explore potential controlling strategies. In this paper, we employed experimental data of EBOV-infected nonhuman primates (NHPs) to construct a mathematical framework for determining windows of opportunity for treatment and vaccination. Considering a prophylactic vaccine based on recombinant vesicular stomatitis virus expressing the EBOV glycoprotein (rVSV-EBOV), vaccination could be protective if a subject is vaccinated during a period from one week to four months before infection. For the case of a therapeutic vaccine based on monoclonal antibodies (mAbs), a single dose might resolve the invasive EBOV replication even if it was administrated as late as four days after infection. Our mathematical models can be used as building blocks for evaluating therapeutic and vaccine modalities as well as for evaluating public health intervention strategies in outbreaks. Future laborator experiments will help to validate and refine the estimates of the windows of opportunity proposed here.
Why MREL won’t help much
(2017)
The bail-in tool as implemented in the European bank resolution framework suffers from severe shortcomings. To some extent, the regulatory framework can remedy the impediments to the desirable incentive effect of private sector involvement (PSI) that emanate from a lack of predictability of outcomes, if it compels banks to issue a sufficiently sized minimum of high-quality, easy to bail-in (subordinated) liabilities. Yet, even the limited improvements any prescription of bail-in capital can offer for PSI’s operational effectiveness seem compromised in important respects.
The main problem, echoing the general concerns voiced against the European bail-in regime, is that the specifications for minimum requirements for own funds and eligible liabilities (MREL) are also highly detailed and discretionary and thus alleviate the predicament of investors in bail-in debt, at best, only insufficiently. Quite importantly, given the character of typical MREL instruments as non-runnable long-term debt, even if investors are able to gauge the relevant risk of PSI in a bank’s failure correctly at the time of purchase, subsequent adjustment of MREL-prescriptions by competent or resolution authorities potentially change the risk profile of the pertinent instruments. Therefore, original pricing decisions may prove inadequate and so may market discipline that follows from them.
The pending European legislation aims at an implementation of the already complex specifications of the Financial Stability Board (FSB) for Total Loss Absorbing Capacity (TLAC) by very detailed and case specific amendments to both the regulatory capital and the resolution regime with an exorbitant emphasis on proportionality and technical fine-tuning. What gets lost in this approach, however, is the key policy objective of enhanced market discipline through predictable PSI: it is hardly conceivable that the pricing of MREL-instruments reflects an accurate risk-assessment of investors because of the many discretionary choices a multitude of agencies are supposed to make and revisit in the administration of the new regime. To prove this conclusion, this chapter looks in more detail at the regulatory objectives of the BRRD’s prescriptions for MREL and their implementation in the prospectively amended European supervisory and resolution framework.
The bail-in tool as implemented in the European bank resolution framework suffers from severe shortcomings. To some extent, the regulatory framework can remedy the impediments to the desirable incentive effect of private sector involvement (PSI) that emanate from a lack of predictability of outcomes, if it compels banks to issue a sufficiently sized minimum of high-quality, easy to bail-in (subordinated) liabilities. Yet, even the limited improvements any prescription of bail-in capital can offer for PSI’s operational effectiveness seem compromised in important respects.
The main problem, echoing the general concerns voiced against the European bail-in regime, is that the specifications for minimum requirements for own funds and eligible liabilities (MREL) are also highly detailed and discretionary and thus alleviate the predicament of investors in bail-in debt, at best, only insufficiently. Quite importantly, given the character of typical MREL instruments as non-runnable long-term debt, even if investors are able to gauge the relevant risk of PSI in a bank’s failure correctly at the time of purchase, subsequent adjustment of MREL-prescriptions by competent or resolution authorities potentially change the risk profile of the pertinent instruments. Therefore, original pricing decisions may prove inadequate and so may market discipline that follows from them.
The pending European legislation aims at an implementation of the already complex specifications of the Financial Stability Board (FSB) for Total Loss Absorbing Capacity (TLAC) by very detailed and case specific amendments to both the regulatory capital and the resolution regime with an exorbitant emphasis on proportionality and technical fine-tuning. What gets lost in this approach, however, is the key policy objective of enhanced market discipline through predictable PSI: it is hardly conceivable that the pricing of MREL-instruments reflects an accurate risk-assessment of investors because of the many discretionary choices a multitude of agencies are supposed to make and revisit in the administration of the new regime. To prove this conclusion, this chapter looks in more detail at the regulatory objectives of the BRRD’s prescriptions for MREL and their implementation in the prospectively amended European supervisory and resolution framework.
Current theories of schizophrenia (ScZ) posit that the symptoms and cognitive dysfunctions arise from a dysconnection syndrome. However, studies that have examined this hypothesis with physiological data at realistic time scales are so far scarce. The current study employed a state-of-the-art approach using Magnetoencephalography (MEG) to test alterations in large-scale phase synchronization in a sample of n = 16 chronic ScZ patients, 10 males and n = 19 healthy participants, 10 males, during a perceptual closure task. We identified large-scale networks from source reconstructed MEG data using data-driven analyses of neuronal synchronization. Oscillation amplitudes and interareal phase-synchronization in the 3–120 Hz frequency range were estimated for 400 cortical parcels and correlated with clinical symptoms and neuropsychological scores. ScZ patients were characterized by a reduction in γ-band (30–120 Hz) oscillation amplitudes that was accompanied by a pronounced deficit in large-scale synchronization at γ-band frequencies. Synchronization was reduced within visual regions as well as between visual and frontal cortex and the reduction of synchronization correlated with elevated clinical disorganization. Accordingly, these data highlight that ScZ is associated with a profound disruption of transient synchronization, providing critical support for the notion that core aspect of the pathophysiology arises from an impairment in coordination of distributed neural activity.
Whiteout: animal traces in Werner Herzog’s Grizzly man and encounters at the end of the world
(2017)
Literary animal studies are confronted with a systematic question: How can writing, as a human-made sign system, represent the nonhuman animal as an autonomous agent without falling back into the pitfalls of anthropomorphism? Against the backdrop of this problem, this paper asks how the medium of film allows for a different representation of the animal and analyzes two of Werner Herzog’s later documentary films. Although the depiction of animals and landscapes has always played a significant part in Herzog’s films, critical assessments of his work—including those of Herzog himself—tended to view the role of nature imagery as purely allegorical: it expresses the inner nature, the inner landscapes of the film’s human protagonists. This paper tries to open up a different view. It argues that both Grizzly Man and Encounters at the End of the World develop an aesthetic that depicts nonhuman nature as an autonomous and lively presence. In the close proximity amongst camera, human, and nonhuman agents, a clear distinction between nature and culture is increasingly blurred.
Several millions frogs captured in the wild in Indonesia are sold for food yearly in French supermarkets, as deep frozen frog legs. They are commercialized as Rana macrodon, but up to 15 lookalike species might also be concerned by this trade. From December 2012 to May 2013, we bought 209 specimens of deep frozen frog legs, and identified them through a barcoding approach based on the 16S gene. Our results show that 206 out of the 209 specimens belong to Fejervarya cancrivora, two to Limnonectes macrodon and one to F. moodiei. Thus only 0.96 % of the frogs were correctly identified. Unless misclassification was intentional, it seems that Indonesian frog leg exporters are not able to discriminate between the species. The quasi absence of L. macrodon in our samples might be an indication of its rarity, confirming that its natural populations are declining rapidly, in agreement with its “vulnerable” status according to the IUCN Red List. Our results show that the genetic and morphological diversity of the frogs in trade is much higher than the genetic and morphological diversity measured so far by scientific studies. These results underline the need for large scale studies to assess the status of wild populations.
When is a crisis a crisis?
(2017)
The marketing materials of remote eye-trackers suggest that data quality is invariant to the position and orientation of the participant as long as the eyes of the participant are within the eye-tracker’s headbox, the area where tracking is possible. As such, remote eye-trackers are marketed as allowing the reliable recording of gaze from participant groups that cannot be restrained, such as infants, schoolchildren and patients with muscular or brain disorders. Practical experience and previous research, however, tells us that eye-tracking data quality, e.g. the accuracy of the recorded gaze position and the amount of data loss, deteriorates (compared to well-trained participants in chinrests) when the participant is unrestrained and assumes a non-optimal pose in front of the eye-tracker. How then can researchers working with unrestrained participants choose an eye-tracker? Here we investigated the performance of five popular remote eye-trackers from EyeTribe, SMI, SR Research, and Tobii in a series of tasks where participants took on non-optimal poses. We report that the tested systems varied in the amount of data loss and systematic offsets observed during our tasks. The EyeLink and EyeTribe in particular had large problems. Furthermore, the Tobii eye-trackers reported data for two eyes when only one eye was visible to the eye-tracker. This study provides practical insight into how popular remote eye-trackers perform when recording from unrestrained participants. It furthermore provides a testing method for evaluating whether a tracker is suitable for studying a certain target population, and that manufacturers can use during the development of new eye-trackers.
Most event studies rely on cumulative abnormal returns, measured as percentage changes in stock prices, as their dependent variable. Stock price reflects the value of the operating business plus non-operating assets minus debt. Yet, many events, in particular in marketing, only influence the value of the operating business, but not non-operating assets and debt. For these cases, the authors argue that the cumulative abnormal return on the operating business, defined as the ratio between the cumulative abnormal return on stock price and the firm-specific leverage effect, is a more appropriate dependent variable. Ignoring the differences in firm-specific leverage effects inflates the impact of observations pertaining to firms with large debt and deflates those pertaining to firms with large non-operating assets. Observations of firms with high debt receive several times the weight attributed to firms with low debt. A simulation study and the reanalysis of three previously published marketing event studies shows that ignoring the firm-specific leverage effects influences an event study's results in unpredictable ways.
Background: Treatment of asthma does not always comply with asthma guidelines (AG). This may be rooted in direct or indirect resistance on the doctors’ and/or patients’ side or be caused by the healthcare system. To assess whether patients’ concepts and attitudes are really an implementation barrier for AG, we analysed the patients’ perspective of a “good asthma therapy” and contrasted their wishes with current recommendations.
Methods: Using a qualitative exploratory design, topic centred focus group (FG) discussions were performed until theoretical saturation was reached. Inclusion criteria were an asthma diagnosis and age above 18. FG sessions were recorded audio-visually and analysed via a mapping technique and content analysis performed according to Mayring (supported by MAXQDA®). Participants’ speech times and the proportion of time devoted to different themes were calculated using the Videograph System® and related to the content analysis.
Results: Thirteen men and 24 women aged between 20 and 77 from rural and urban areas attended five FG. Some patients had been recently diagnosed with asthma, others years previously or in childhood. The following topics were addressed: (a) concern about or rejection of therapy components, particularly corticosteroids, which sometimes resulted in autonomous uncommunicated medication changes, (b) lack of time or money for optimal treatment, (c) insufficient involvement in therapy choices and (d) a desire for greater empowerment, (e) suboptimal communication between healthcare professionals and (f) difficulties with recommendations conflicting with daily life. Primarily, (g) participants wanted more time with doctors to discuss difficulties and (h) all aspects of living with an impairing condition.
Conclusions: We identified some important patient driven barriers to implementing AG recommendations. In order to advance AG implementation and improve asthma treatment, the patients’ perspective needs to be considered before drafting new versions of AG. These issues should be addressed at the planning stage.
Trial registration: DRKS00000562 (German Clinical Trials Registry).
What is the magnetic field distribution for the equation of state of magnetized neutron stars?
(2017)
In this Letter, we report a realistic calculation of the magnetic field profile for the equation of state inside strongly magnetized neutron stars. Unlike previous estimates, which are widely used in the literature, we find that magnetic fields increase relatively slowly with increasing baryon chemical potential (or baryon density) of magnetized matter. More precisely, the increase is polynomial instead of exponential, as previously assumed. Through the analysis of several different realistic models for the microscopic description of stellar matter (including hadronic, hybrid and quark models) combined with general relativistic solutions endowed with a poloidal magnetic field obtained by solving Einstein–Maxwell's field equations in a self-consistent way, we generate a phenomenological fit for the magnetic field distribution in the stellar polar direction to be used as input in microscopic calculations.
Far-right parties gained considerable support in many European countries in recent years. Austria comes within a whisker of becoming the first country in the history of the European Union to elect a far-right president, Horbert Hofer, the candidate from the Freedom Party. Similarly, in France, Marie Le Pen is expected to be Front National’s (FN) candidate in the 2017 presidential election and probably to make it to the second round of voting...
Much of today’s conflicts and challenges, globally and locally, can be in part attributed to or are influenced by the hegemony of Western over non-Western cultures and politics. Long-standing and still reproduced Western dominance and power are directed at the protection of own interests, thereby re-creating power imbalances, inequalities and practices of exclusion...
This book is a biography based on a qualitative ethnographic study of adaptation to climate by Mr Zephaniah Phiri Maseko, an award-winning smallholder farmer from Zvishavane, rural Zimbabwe. Ethnographic data provides insight and lessons of Mr Phiri Maseko and other farmers' practices for rethinking existing strategies for adaptation to climate change. The concept of adaptation is probed in relationship to the closely related concepts of vulnerability, resilience and innovation. This study also explores the concept of conviviality and argues that Mr Phiri Maseko's adaptation to climate hinges on mediating barriers between local and exogenous knowledge systems. The book argues that Mr Phiri Maseko offered tangible adaptive climate strategies through his innovations that 'marry water and soil so that it won't elope and run-off but raise a family' on his plot. His agricultural practices are anchored on the Shona concept of' hurudza'(an exceptionally productive farmer). This book explores the concept and practices of 'uhurudza,'to suggest that the latter-day 'hurudza' (commercial farmer)'as embodied by Mr Phiri Maseko offers an important set of resources for the development of climate adaptation strategies in the region. This study of smallholder farmers' adoption of innovations to climate highlights the 'complex interplay' of multiple factors that act as barriers to uptake. Such interplay of multiple stressors increases the vulnerability of smallholders. The study concludes by arguing that in as much as the skewed colonial land policy impoverished the smallholder farmers, Mr Phiri Maseko nonetheless redefined himself as a latter-day 'hurudza and thus breaks free from the poverty cycle by conjuring ingenious ways of reducing vulnerability to climate. The book does not suggest that Mr Phiri Maseko's innovations offer a silver bullet solution to the insecure rural livelihoods of smallholder farmers; nevertheless, they are a source of hope in an environment of uncertainty. His steely tenacity in the face of a multi-stressor environment is to be treasured.
Filippo Trentin's essay 'Warburg's Ghost: On Literary Atlases and the "Anatopic" Shift of a Cartographic Object' analyses the atlas as a method of assemblage in literary theory. It takes issue with the use of cartography advocated by proponents of a 'spatial turn' within literary studies, including Malcolm Bradbury's "Atlas of Literature", Franco Moretti's "Atlas of European Literature", and Sergio Luzzatto and Gabriele Pedullà's "Atlante della letteratura italiana". While these atlases claim to dismantle the normative canon of historicism and to offer a different way of gathering knowledge, Trentin argues that they often risk reproducing analogous positivistic, hierarchical, and colonizing assumptions. Showing a totalizing attitude embedded in modern atlases and in the 'cartographic reason' emerging from the sixteenth century onwards, the essay proposes a speculative and heuristic use of the term 'anatopy' that aims to capture the disorienting potentialities that are intrinsic to non-cartographic explorations of space. In particular, it interprets Aby Warburg's "Bilderatlas Mnemosyne" as an 'anatopic' object that keeps troubling any purely cartographic use of the atlas. In Trentin's reading, by theorizing an anti-foundational (and anti-identitarian) method of knowledge organization based on the morphological affect between disparate images and objects, Warburg's project leads to the profanation of the atlas as a topographical machine and, with its recurrences, intervals, and voids, destitutes its traditional apparatus of power. This disparate and anti-holistic aesthetic disposition challenges the solid foundations of the constructions of historicism and cartographic reason. It breaks up the technical explanation of cause and effect and substitutes it with a 'danced causality', which Trentin relates to Leo Bersani's idea of 'aesthetic subject' and the possibility of moving beyond an immobile and filial principle of identity formation towards a virtual and impersonal one that is located beyond the 'ego', as well as beyond the rigid borders of cartographic reason and the linearity of positivistic historicism.
Walter Greiner: in memoriam
(2017)
Walter Greiner (29 October 1935 - 6 October 2016) was a German theoretical physicist. His scientific research interests include the thematic areas of atomic physics, heavy ion physics, nuclear physics, elementary particle physics (particularly quantum electrodynamics and quantum chromodynamics). He is most known in Germany for his series of books in theoretical physics, but he is also well known around the world. Greiner was born on October 29, 1935, in Neuenbau, Sonnenberg, Germany. He studied physics at the University of Frankfurt (Goethe University in Frankfurt Am Main), receiving in this institution a BSci in physics and a Master’s degree in 1960 with a thesis on plasma-reactors, and a PhD in 1961 at the University of Freiburg under Hans Marshal, with a thesis on the nuclear polarization in μμ-mesic atoms. During the period of 1962 to 1964 he was assistant professor at the University of Maryland, followed by a position as research associate at the University of Freiburg, in 1964. Starting in 1965, he became a full professor at the Institute for Theoretical Physics at Goethe University until 2003. Greiner has been a visiting professor to many universities and laboratories, including Florida State University, the University of Virginia, the University of California, the University of Melbourne, Vanderbilt University, Yale University, Oak Ridge National Laboratory and Los Alamos National Laboratory. In 2003, with Wolf Singer, he was the founding Director of the Frankfurt Institute for Advanced Studies (FIAS), and gave lectures and seminars in elementary particle physics. He died on October 6, 2016 at the age of 80.
Walter Greiner was an excellent teacher, researcher, friend. And he was a great supporter of the series of events known by the acronyms IWARA - International Workshop on Astronomy and Relativistic Astrophysics, STARS - Caribbean Symposium on Cosmology, Gravitation, Nuclear and Astroparticle Physics, and SMFNS - International Symposium on Strong Electromagnetic Fields and Neutron Stars. Walter Greiner left us. But his memory will remain always alive among us who have had the privilege of knowing him and enjoy his wisdom and joy of living.
Walking, Falling
(2017)
Walking, Falling is Kelwyn Soles seventh collection of poetry. It extends and deepens themes that emerged in his earlier books: love and human relationships; the exposing of false and clichéd perspectives in our socio-political life; our relationship as South Africans to land and landscape. Rustum Kozain has written about his work: Whether the theme is the end of a relationship or the murder of immigrants, there is the calm look of analysis, a voice, like a conscience, that threatens to disturb the readers complacency, but a voice simultaneously gentle with empathy and sincerity.
The W and Z boson production was measured via the muonic decay channel in proton-lead collisions at sNN−−−√=5.02 TeV at the Large Hadron Collider with the ALICE detector. The measurement covers backward (−4.46<ycms<−2.96) and forward (2.03<ycms<3.53) rapidity regions, corresponding to Pb-going and p-going directions, respectively. The Z-boson production cross section, with dimuon invariant mass of 60<mμμ<120 GeV/c2 and muon transverse momentum (pμT) larger than 20 GeV/c, is measured. The production cross section and charge asymmetry of muons from W-boson decays with pμT>10 GeV/c are determined. The results are compared to theoretical calculations both with and without including the nuclear modification of the parton distribution functions. The W-boson production is also studied as a function of the collision centrality: the cross section of muons from W-boson decays is found to scale with the average number of binary nucleon-nucleon collisions within uncertainties.
The W and Z boson production was measured via the muonic decay channel in proton-lead collisions at sNN−−−√=5.02 TeV at the Large Hadron Collider with the ALICE detector. The measurement covers backward (−4.46<ycms<−2.96) and forward (2.03<ycms<3.53) rapidity regions, corresponding to Pb-going and p-going directions, respectively. The Z-boson production cross section, with dimuon invariant mass of 60<mμμ<120 GeV/c2 and muon transverse momentum (pμT) larger than 20 GeV/c, is measured. The production cross section and charge asymmetry of muons from W-boson decays with pμT>10 GeV/c are determined. The results are compared to theoretical calculations both with and without including the nuclear modification of the parton distribution functions. The W-boson production is also studied as a function of the collision centrality: the cross section of muons from W-boson decays is found to scale with the average number of binary nucleon-nucleon collisions within uncertainties.
We extend the classical ”martingale-plus-noise” model for high-frequency prices by an error correction mechanism originating from prevailing mispricing. The speed of price reversal is a natural measure for informational efficiency. The strength of the price reversal relative to the signal-to-noise ratio determines the signs of the return serial correlation and the bias in standard realized variance estimates. We derive the model’s properties and locally estimate it based on mid-quote returns of the NASDAQ 100 constituents. There is evidence of mildly persistent local regimes of positive and negative serial correlation, arising from lagged feedback effects and sluggish price adjustments. The model performance is decidedly superior to existing stylized microstructure models. Finally, we document intraday periodicities in the speed of price reversion and noise-to-signal ratios.
Systemic lupus erythematosus (SLE) is a chronic disease characterized by progressive tissue damage. In recent decades, novel treatments have greatly extended the life span of SLE patients. This creates a high demand for identifying the overarching symptoms associated with SLE and developing therapies that improve their life quality under chronic care. We hypothesized that SLE patients would present dysphonic symptoms. Given that voice disorders can reduce life quality, identifying a potential SLE-related dysphonia could be relevant for the appraisal and management of this disease. We measured objective vocal parameters and perceived vocal quality with the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched healthy controls. SLE patients also filled a questionnaire reporting perceived vocal deficits. SLE patients had significantly lower vocal intensity and harmonics to noise ratio, as well as increased jitter and shimmer. All subjective parameters of the GRBAS scale were significantly abnormal in SLE patients. Additionally, the vast majority of SLE patients (29/36) reported at least one perceived vocal deficit, with the most prevalent deficits being vocal fatigue (19/36) and hoarseness (17/36). Self-reported voice deficits were highly correlated with altered GRBAS scores. Additionally, tissue damage scores in different organ systems correlated with dysphonic symptoms, suggesting that some features of SLE-related dysphonia are due to tissue damage. Our results show that a large fraction of SLE patients suffers from perceivable dysphonia and may benefit from voice therapy in order to improve quality of life.
Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed. Once per week, patients received either 20 drops of Vigantol oil, corresponding to a daily dose of 1904 IU/d vitamin D (verum: n = 31), or a placebo oil consisting of medium chain triglycerides (placebo: n = 28). Blood samples were taken from all of the participants at three different time points: 1) at the beginning of the study (baseline), 2) after 6 months supplementation, and 3) after an additional 6 months of follow-up. Plasma sphingolipids were measured by high-performance liquid chromatography tandem mass spectrometry. At baseline and 6 months follow-up, no significant differences in plasma sphingolipid species were detected between the placebo and verum groups. After 6 months, vitamin D supplementation significantly enhanced plasma C18dihydroceramide (dhCer; N-stearoyl-sphinganine (d18:0/18:0)) and C18ceramide (Cer; N-stearoyl-sphingosine (d18:1/18:0)) levels were observed in the verum group compared to the placebo group. This was accompanied by significantly higher 25-hydroxyvitamin D3 (25(OH)D3) blood levels in patients receiving vitamin D compared to the placebo group. Taken together, vitamin D supplementation induced changes of the C18 chain-length-specific dhCer and Cer plasma levels in patients with T2D. The regulation of sphingolipid signaling by vitamin D may thus unravel a novel mechanism by which vitamin D can influence glucose utilization and insulin action. Whether this acts favorably or unfavorably for the progression of T2D needs to be clarified.
Visualization of cytosolic ribosomes on the surface of mitochondria by electron cryo‐tomography
(2017)
We employed electron cryo‐tomography to visualize cytosolic ribosomes on the surface of mitochondria. Translation‐arrested ribosomes reveal the clustered organization of the TOM complex, corroborating earlier reports of localized translation. Ribosomes are shown to interact specifically with the TOM complex, and nascent chain binding is crucial for ribosome recruitment and stabilization. Ribosomes are bound to the membrane in discrete clusters, often in the vicinity of the crista junctions. This interaction highlights how protein synthesis may be coupled with transport. Our work provides unique insights into the spatial organization of cytosolic ribosomes on mitochondria.
Yves R. Simon (1903-1961), one of the greatest contemporary philosophers, gives a modern formulation for many classical philosophical concepts such as authority, the common good, and natural law. These topics have received extensive attention from scholars. Simon also discusses the nature of human virtue, moral and intellectual, but this topic has been less studied until now. The idea of virtue, and in our case virtue in political life, runs through Simon's works. Through a close study of Simon's works and the relevant secondary literature, this book explores Simon's definition of virtue in order to highlight its originality, and show how he weaves the need for it into the fabric of three facets of political life, namely, the common good, the virtue of the ruler and the ruled, and the law. These ideas are important for the ruler-ship of any country and especially of developing nations which are populated by sit-tight dictators. Philosophy can be dry and abstract, yet in this case we deal with one of its more practical manifestations.
EMITTERS OF MUTUAL FUNDS AND OTHER FINANCIAL PRODUCTS LACK INFORMATION ABOUT THEIR CUSTOMERS. THEY MOSTLY OPERATE WITH A PRODUCT-CENTRIC MARKE TING CONCEPT. WITH INFORMATION ABOUT CUSTOMERS, THEY COULD SHIFT TOWARDS A MORE CUSTOMER-CENTRIC STRATEGY. HOWEVER, SUCH A STRATEGY DEMANDS INFOR MATION THAT IS HARDLY AVAILABLE. VIRTUAL PORTFOLIOS CAN BRIDGE THIS GAP AND PROVIDE EMITTERS OF FINANCIAL PRODUCTS WITH KNOWLEDGE ABOUT THEIR CUSTOMERS AND THEIR COMPETITORS. THIS ARTICLE ILLUSTRATES THE INSIGHTS THAT VIRTUAL PORTFOLIOS CAN PROVIDE TO EMITTERS OF A MUTUAL FUND.
The venture capital industry holds relevance for entrepreneurs looking for money to finance an innovative project, investors seeking to make money by investing in entrepreneurial firms and governments trying to promote innovation and entrepreneurship. Venture capital investment could facilitate innovation and thus a better economy.
Venture capital has enabled the U.S. to support its entrepreneurial talent by turning ideas into world-famous products and services, building companies from mere business plans to mature and powerful organizations. Three of the five largest U.S. public companies by market capitalization – Apple, Google and Microsoft – received most of their early external funding from venture capital. Having its ups and downs, venture capital investment in the U.S. expanded from virtually zero in the mid-1970s to $8 billion in 1995 and $49.3 billion in 2014. Venture backed companies have been a prime driver of economic growth in the U.S.Across the pacific, venture capital investment in China has grown out of the transition from a centrally planned economy to a free market economy over the past three decades, becoming an important pillar supporting China’s innovation system. In 2015, a total of 2,824 venture capital investment deals provided an aggregate investment of $36.9 billion. Venture capital has long been a hot topic in China’s capital market, particularly since the government decided to boost “mass entrepreneurship and innovation” in 2014.
In the U.S., most venture capital firms are organized as limited partnerships, with the venture capitalists being general partners and the investors limited partners. Studies have shown that investors choose to invest through venture funds as an intermediary rather than placing their investments directly with the entrepreneurs; because of the high risk nature of the entrepreneur’s business, it is hard for them to get bank loans or direct equity investments. Conflicts may also arise, however, between the venture capitalists acting as agents and the investors as principals.5 This agency problem maybe particularly severe, since venture capital provides money for businesses with high potential and high risk, although the limited partnership has certain merits and is still most commonly chosen as the business form for venture capital funds.6 At the same time, the fact that general partners have total control of the partnership business necessitates that the agency problem is addressed by legal rules, contracts and other mechanisms.
Meanwhile, despite the rapid growth of venture capital investments in China, little attention has been paid to the organizational form of venture capital funds. In contrast to the U.S., most Chinese venture funds have been structured as corporations. One may argue that it was due to legislative reasons: that the limited partnership was not recognized by Chinese law when venture capital first appeared in China. However, after adopted a chapter was adopted in the Partnership Enterprise Law (PEL) governing limited partnerships in 2007, most of the venture funds abided by their choice, while those opting for the limited partnership have encountered difficulties: the limited partners are having trouble trusting the general partners with their money and are therefore interfering with the operation of the partnership business, which may lead to dissolution of the partnership.
This thesis applies transaction cost theory to explain the benefits and costs of choosing the limited partnership as a business form in the special context of venture capital investments, showing that the potential agency conflict between the general partners and the limited partners have been mitigated by legal and other mechanismsin the United States, and that the U.S. investors could therefore exploit the merit of the limited partnership form in venture capital financing. In China, investors have different answers to the agency problem. Similarly to the situation in the U.S., Chinese partners also employ contract terms to deal with agency problems, and the legislators enact laws that aim at regulating the limited partnership form; some legislation was even transplanted from the U.S., such as that part of the PEL which governs limited partnerships. It seems, then, that similar mechanisms that deal with agency problems also exist in China. However, given the unique history of the development of China’s innovation system and venture capital market, the effectiveness of these constraints is questionable. Chinese venture capital investors have therefore characteristically behaved differently to U.S. investors. Rather than relying on these questionable mechanisms, Chinese investors as well as the Chinese government have developed different approaches to addressing these agency problems.
Transitional between the Pannonian Basin and the Eastern Carpathians the Transcarpathian Ukraine (Transcarpathia) has a diverse geology including Quaternary sediments, volcanites, limestones and flysch, and its climate at low altitudes is relatively warm and humid. We conducted a field survey in June 2016 focusing on mesophilous forest vegetation along a transect covering almost the whole lowaltitudinal part of Transcarpathia. We recorded 54 relevés in the field and further digitized 22 relevés from literature. Using classification analysis, we distinguished three clusters of oak-hornbeam forests (alliance Carpinion betuli; 1–3) and three clusters of scree and ravine forests (alliance Tilio platyphylli-Acerion; 4–6): (1) Slightly wet Pannonian oak-hornbeam forests occurring in the lowland part of the region (Circaeo-Carpinetum); (2) Mesophilous oak-hornbeam forests (Carici pilosae-Carpinetum); (3) Xero-mesophilous oak-hornbeam forests (a drier subtype of the Carici pilosae-Carpinetum and the association Primulo veris-Carpinetum); (4) Mesophilous scree forests (Phyllitido-Aceretum); (5) Forests of steep slopes (Aceri-Tilietum) and transitions to mesophilous oak-hornbeam forests (Carici pilosae-Carpinetum); (6) Cool and wet scree and ravine forests (Arunco dioici-Aceretum pseudoplatani). Using indirect ordination analysis, three environmental variables (altitude, heat load index and slope) were identified as factors of significant influence on the species composition. These factors well distinguish oak-hornbeam forests from scree and ravine forests.
Savannas provide essential ecosystem services for human well-being in West Africa. Thus, ecosystem change not only directly affects biodiversity but also human livelihoods. Human land use considerably shaped these savanna ecosystems for millennia, particularly agriculture, livestock grazing, logging and the collection of non-timber forest products (NTFPs). NTFPs are wild plant products and comprise all organic matter from herbaceous plants, shrubs, and trees (excluding timber). Current increasing land use pressure through fast demographic changes is widely esteemed as a severe threat for savanna biodiversity and the socio-economy of rural communities. In consideration of the pivotal role of NTFP species for biodiversity and livelihoods, it is important to evaluate the effect of increasing land use change on savanna vegetation and on its provisioning service for human well-being. Thus, the major aim of this thesis is to investigate the impacts of land use intensification on vegetation composition, diversity and function and its consequences for provisioning ecosystem services (NTFPs) and human well-being in a West African savanna.
The research for this study was conducted in the North Sudanian vegetation zone of south-eastern Burkina Faso, where population growth exceeds the nationwide trend. Generally, Burkina Faso belongs to the worldwide poorest countries, where nearly one quarter of the population suffers from malnutrition (FAO 2014). The integration of NTFPs and particularly wild food species into rural household economies is, thus, an important measure in the national combat against poverty and food insecurity (FAO 2014). Against this background, I focus on vegetation changes, the economic importance of NTFPs as well as the decrease and substitution of wild food species in this study.
Vegetation resurveys of different vegetation types since the early 1990s showed that land use change led to more pronounced changes in the herbaceous than in the woody vegetation layer. Most woody vegetation types stayed stable in species composition and richness, even though some highly useful tree species (Vitellaria paradoxa, Parkia biglobosa) declined in some woody vegetation types. In contrast, in most herbaceous vegetation types species richness increased and species composition considerably changed. This change might be explained by a general ruderalisation process through a pronounced increase of wide-ranging herbaceous species. However, in spite of a general species increase in the herbaceous layer, a decrease of preferred herbaceous fodder species was found. Thus, the decline of useful species in both layers is alarming. Herbaceous vegetation types also showed more pronounced changes in plant functional trait characteristics in comparison to woody vegetation types. However, an increase of smaller plant species and species with a high diaspore terminal velocity (VTerm) was found in both vegetation layers. Since these two trait responses are generally related to grazing and browsing, the strong increase of livestock herds is likely to be responsible for the detected vegetation changes.
In addition to the vegetation study, interviews showed that all useful food species were widely considered to decline. The two economically most important tree species, the shea tree (Vitellaria paradoxa) and the locust bean tree (Parkia biglobosa) that contribute with 70% to wild food income, were considered among the most declining species of all cited wild food species. On this matter, local perceptions of species decline and results from field observations are in accordance. However, a wide range of cited substitutes indicated a great knowledge on alternative plant species in the area. Most wild food species are, however, substituted by other highly valued wild food species. Although our results suggest that rural communities are able to cope with the decrease or absence of wild food species, growing decline of one species would concurrently increase the pressure on other native food species. Therefore, the need to counteract the decrease of highly useful wild food species should be of high priority in management measures. In general, I showed that NTFPs are an essential component in rural households, since it contributed with 45 % to total household income. Significant differences in NTFP dependency between the two investigated villages and across the three main ethnic groups were detected, reflecting different traditional uses and harvesting practices. In general, it was shown that poorer households depend more on NTFP income than wealthier households. Against the background of this study, management strategies for agroforestry systems and poverty alleviation should consider local differences, and ethnicity-dependent NTFP-use patterns.
Overall, the combination of field studies on temporal and functional vegetation change with socio-economic and ethno-botanic interviews increases the knowledge on qualitative and quantitative vegetation changes and on the consequences for rural populations. This thesis gives a thorough insight into decreasing trends of economically valued plant species and thus gives evidence on the consequences of vegetation changes for ecosystem services of West African savanna ecosystems. Further, different NTFP-dependencies and use preferences according to socio-economic and cultural variables, such as ethnicity, present a valuable basis for specific decision-making and should be considered in management plans.
Seit 12 Jahren werden von Mitgliedern der Eurasian Dry Grassland Group (EDGG) und deren Vorgängerorganisationen Grasland-Sonderteile in Tuexenia herausgegeben. Der diesjährige Sonderteil enthält fünf Artikel, die das Grasland verschiedener mitteleuropäischer Länder mit unterschiedlichen Zielen untersuchen. Der erste Artikel untersucht Auswirkungen von Weide und Mahd auf die Diversität des Graslands in Deutschland in Abhängigkeit von verschiedenen Umweltfaktoren, der zweite die Auswirkung kleiner Büsche auf den Artenreichtum von Gefäßpflanzen in beweideten Wiesensteppen in Ungarn. Der dritte Artikel fragt, ob sich ungarische Sandtrockenrasen mit Festuca vaginata von solchen mit F. pseudovaginata in ihrer Vegetation und ihren Standortsbedingungen unterscheiden; die letztere war erst kürzlich beschrieben worden. Der vierte Artikel modelliert Auswirkungen des Klimawandels auf geschützte Graslandbestände in Serbien und deren Arten während schließlich der fünfte Artikel die Initiative einer neuen Datenbank des deutschen Graslands (GrassVeg.DE) vorstellt und dazu aufruft, sich daran zu beteiligen. Insgesamt haben zu diesem 12. Grasland-Sonderteil 41 Autoren aus fünf Ländern (Dänemark, Deutschland, Italien, Schweiz, Serbien und Ungarn) beigetragen.
We present a method that enables the identification and analysis of conformational Markovian transition states from atomistic or coarse-grained molecular dynamics (MD) trajectories. Our algorithm is presented by using both analytical models and examples from MD simulations of the benchmark system helix-forming peptide Ala5, and of larger, biomedically important systems: the 15-lipoxygenase-2 enzyme (15-LOX-2), the epidermal growth factor receptor (EGFR) protein, and the Mga2 fungal transcription factor. The analysis of 15-LOX-2 uses data generated exclusively from biased umbrella sampling simulations carried out at the hybrid ab initio density functional theory (DFT) quantum mechanics/molecular mechanics (QM/MM) level of theory. In all cases, our method automatically identifies the corresponding transition states and metastable conformations in a variationally optimal way, with the input of a set of relevant coordinates, by accurately reproducing the intrinsic slowest relaxation rate of each system. Our approach offers a general yet easy-to-implement analysis method that provides unique insight into the molecular mechanism and the rare but crucial (i.e., rate-limiting) transition states occurring along conformational transition paths in complex dynamical systems such as molecular trajectories.
Background: In oldest-old patients (>80), few trials showed efficacy of treating hypertension and they included mostly the healthiest elderly. The resulting lack of knowledge has led to inconsistent guidelines, mainly based on systolic blood pressure (SBP), cardiovascular disease (CVD) but not on frailty despite the high prevalence in oldest-old. This may lead to variation how General Practitioners (GPs) treat hypertension. Our aim was to investigate treatment variation of GPs in oldest-olds across countries and to identify the role of frailty in that decision.
Methods: Using a survey, we compared treatment decisions in cases of oldest-old varying in SBP, CVD, and frailty. GPs were asked if they would start antihypertensive treatment in each case. In 2016, we invited GPs in Europe, Brazil, Israel, and New Zealand. We compared the percentage of cases that would be treated per countries. A logistic mixed-effects model was used to derive odds ratio (OR) for frailty with 95% confidence intervals (CI), adjusted for SBP, CVD, and GP characteristics (sex, location and prevalence of oldest-old per GP office, and years of experience). The mixed-effects model was used to account for the multiple assessments per GP.
Results: The 29 countries yielded 2543 participating GPs: 52% were female, 51% located in a city, 71% reported a high prevalence of oldest-old in their offices, 38% and had >20 years of experience. Across countries, considerable variation was found in the decision to start antihypertensive treatment in the oldest-old ranging from 34 to 88%. In 24/29 (83%) countries, frailty was associated with GPs’ decision not to start treatment even after adjustment for SBP, CVD, and GP characteristics (OR 0.53, 95%CI 0.48–0.59; ORs per country 0.11–1.78).
Conclusions: Across countries, we found considerable variation in starting antihypertensive medication in oldest-old. The frail oldest-old had an odds ratio of 0.53 of receiving antihypertensive treatment. Future hypertension trials should also include frail patients to acquire evidence on the efficacy of antihypertensive treatment in oldest-old patients with frailty, with the aim to get evidence-based data for clinical decision-making.
Central European temperate forests are – with the exception of floodplain forests – relatively little invaded by alien plants. However, despite substantial recent progress, there is still a lack of using vege-tation plot data for analyzing spatio-temporal patterns of alien tree species invasions.
We calculated relevé-based metrics of tree species’ ecological preferences using 19,413 phytosociological forest relevés of the Austrian vegetation database. We focused on the five most widely distributed alien trees, i.e. two archaeophytes (Castanea sativa, Juglans regia) and three neophytes (Acer negundo, Ailanthus altissima, Robinia pseudoacacia). For each of these species we analyzed the mean cover in the tree layer and the occurrence in the herb and shrub layers in relevés colonized by adult trees as a measure for persistence. Further, we evaluated the intergenerational ecological plasticity (= the ability of young trees to grow under different site conditions than adults) for the tree species, and the mean relevé indicator values for light, nutrients, moisture and hemeroby. We then compared these alien and native tree species metrics.
We found that A. altissima and R. pseudoacacia build up high mean cover values in invaded forests, but this was not the case for the other alien trees. Thus, both species strongly affected forest communities of invaded sites. Similarly, the two species were common in the lower vegetation layers indicating recruitment under the canopy of adult conspecifics; this was facilitated by their ability to produce root suckers. Highest values of inter-generational ecological plasticity occurred in native pioneer trees and species of softwood floodplain forests, while alien trees had moderately high (A. negundo, A. altissima, J. regia) to low values (C. sativa, R. pseudoacacia). With the exception of C. sativa, all alien species showed high mean Ellenberg indicator values for light and nutrients, and were more common in sites with high hemeroby and high mean Ellenberg indicator values for temperature. Distinct from the ecological preferences of alien trees, and thus rarely invaded, were montane beech forests, coniferous mountain forests and forests at extremely dry sites, as well as swamp and bog forests dominated by willows and ash.
We conclude that relevé-based metrics of the behavior of alien tree species allow new insights into the spatio-temporal dynamics of invasion of woody species in forests. Future work should expand this approach, e.g., by considering the role of life history traits and actual site conditions.
HADES is a fixed target experiment using SIS18 heavy-ion beams. It investigates the microscopic properties of matter formed in heavy-ion, proton and pion - induced reactions in the 1-3.5 GeV/u energy regime. In 2014 HADES used a secondary pion beam produced by interaction between high-intensity nitrogen primary beam and a beryllium target. In these conditions beam losses, generated by slow extraction and beam transport to the experimental area, led to activation of the beam line elements and triggered radiation alarms. The primary beam intensity had to be reduced and the beam optics modified in order to keep radiation levels within the allowed limits. Similar beam conditions are requested by HADES experiment for upcoming run in 2018 and in the following years. Therefore, a number of measures have been proposed to improve beam transmission and quality. These measures are: additional shielding, additional beam instrumentation, modification of beam optics and increase of vacuum chambers' apertures in critical locations. The optics study and preliminary results of FLUKA simulations for optimization of location of loss detectors are presented.
Results are presented of a brief odonatological examination of the Abrau and Taman' Peninsulas at the northwesternmost Caucasian Black Sea coast in Krasnodarskiy Kray, Russia, on July 2026, 2017. Twenty three species have been observed at the former peninsula and five at the latter. The Odonata records at the Abrau Peninsula are summarised, to include 34 species.
The Odonata fauna of flat marshy areas of the Gulf of Siam coast in Koh Kong Province of Cambodia, containing 55 species, is considered. The published data of 2010- 2013 and new data of 2014 and 2016 on the surroundings of Koh Kong town are compiled and the first data on the area of large swampy Melaleuca forests at Andoung Tuek village are presented as well as some occasional photographic records. Gynacantha bayadera, Lyriothemis mortoni and Pornothemis serrata were for the first time recorded for Cambodia. Mortonagrion falcatum was found unexpectedly abundant at Andoung Tuek.
In shelled molluscs, assigning valid species names to independent evolutionary lineages can be a difficult task. Most original descriptions are based on empty shells and the high levels of variation in shape, color and pattern in some groups can make the shell a poor proxy for species-level identification. The deep-sea gastropod turbinid genus Bolma is one such example, where species-level identification based on shell characters alone is challenging. Here, we show that in Bolma both traditional and molecular taxonomic treatments are associated with a number of pitfalls that can lead to biased inferences about species diversity. Challenges derive from the few phylogenetically informative characters of shells, insufficient information provided in original descriptions and sampling artefacts, which at the molecular level in spatially fragmented organisms can blur distinctions between genetically divergent populations and separate species. Based on a comprehensive dataset combining molecular, morphological and distributional data, this study identified several cases of shell-morphological plasticity and convergence. Results also suggest that what was thought to be a set of distinct, range-restricted species corresponds instead to a smaller number of more widespread species. Overall, using an appropriate sampling design, including type localities, allowed us to assign available names to evolutionarily significant units.
Unparticle Casimir effect
(2017)
In this paper we present the un-Casimir effect, namely the study of the Casimir energy in the presence of an unparticle component in addition to the electromagnetic field contribution. The distinctive feature of the un-Casimir effect is a fractalization of metallic plates. This result emerges through a new dependence of the Casimir energy on the plate separation that scales with a continuous power controlled by the unparticle dimension. As long as the perfect conductor approximation is valid, we find bounds on the unparticle scale that are independent of the effective coupling constant between the scale invariant sector and ordinary matter. We find regions of the parameter space such that for plate distances around 5 μm and larger the un-Casimir bound wins over the other bounds.
Dendrites form predominantly binary trees that are exquisitely embedded in the networks of the brain. While neuronal computation is known to depend on the morphology of dendrites, their underlying topological blueprint remains unknown. Here, we used a centripetal branch ordering scheme originally developed to describe river networks—the Horton-Strahler order (SO)–to examine hierarchical relationships of branching statistics in reconstructed and model dendritic trees. We report on a number of universal topological relationships with SO that are true for all binary trees and distinguish those from SO-sorted metric measures that appear to be cell type-specific. The latter are therefore potential new candidates for categorising dendritic tree structures. Interestingly, we find a faithful correlation of branch diameters with centripetal branch orders, indicating a possible functional importance of SO for dendritic morphology and growth. Also, simulated local voltage responses to synaptic inputs are strongly correlated with SO. In summary, our study identifies important SO-dependent measures in dendritic morphology that are relevant for neural function while at the same time it describes other relationships that are universal for all dendrites.
This paper analyzes the relationship between monetary policy and financial stability in the Banking Union. There is no uniform global model regarding the relationship between monetary policy-making on the one hand, and prudential supervision on the other. Before the crisis, EU Member States followed different approaches, some of them uniting monetary and supervisory functions in one institution, others assigning them to different, neatly separated institutions. The financial crisis has underlined that monetary policy and prudential supervision deeply affect each other, especially in case of systemic events. Even in normal times, monetary and supervisory decisions might conflict with each other. After the crisis, some jurisdictions have moved towards a more holistic approach under which monetary policy takes supervisory considerations into account, while supervisory decisions pay due regard to monetary policy.
The Banking Union puts prudential supervision in the hands of the European Central Bank (ECB), the institution responsible for monetary policy. Nevertheless, at its establishment there was the political understanding that the ECB should follow a policy of meticulous separation in the discharge of its different functions. This raises the question whether the ECB may pursue a holistic approach to monetary policy and supervisory decision-making, respectively. On the basis of a purposive reading of the monetary policy mandate and the SSM Regulation, the paper answers this question in the affirmative. Effective monetary policy (or supervision) requires financial stability (or smooth monetary policy transmission). Moreover, without a holistic approach, the SSM Regulation is more likely to provoke the adoption of mutually defeating decisions by the Governing Board. The reputation of the ECB would suffer considerably under such a situation – in a field where reputation is of paramount importance for effective policy.
As any meticulous separation between monetary and supervisory functions turns out to be infeasible, the paper explores the reasons. Parting from Katharina Pistor’s legal theory of finance, which puts the emphasis on exogenous factors to explain the (non)enforcement of legal rules, the paper suggests a legal instability theorem which focuses on endogenous reasons, such as law’s indeterminacy, contextuality, and responsiveness to democratic deliberation. This raises the question whether the holistic approach would be democratically legitimate under the current framework of the ESCB. The idea of technocratic legitimacy that exempts the ECB from representative structures is effectively called into question by the legal instability theorem. This does not imply that the independence of the ECB should be given up, as there are no viable alternatives to protect monetary policy against the time inconsistency problem. Rather, any solution might benefit from recognizing the ECB in its mixed technocratic and political shape as a centerpiece of European integration and improving.
The diagnosis that we are living in a world risk society formulated by Ulrich Beck 20 years ago (Beck, Kölner Z Soziol Sozialpsychol 36:119–147, 1996) has lost nothing of its power, especially against the background of the Anthropocene debate. “Global risks” have been identified which are caused by human activities, technology, and modernization processes. Microplastics are a by-product of exactly these modernization processes, being distributed globally by physical processes like ocean currents, and causing effects far from their place of origin. In recent years, the topic has gained great prominence, as microplastics have been discovered nearly everywhere in the environment, raising questions about the impacts on food for human consumption. But are microplastics really a new phenomenon or rather a symptom of an old problem? And exactly what risks are involved? It seems that the phenomenon has accelerated political action—the USA has passed the Microbead-Free Waters Act 2015—and industries have pledged to fade out the use of microbeads in their cosmetic products. At first sight, is it a success for environmentalists and the protection of our planet?
This chapter deals with these questions by adopting a social-ecological perspective, discussing microplastics as a global risk. Taking four main characteristics of global risks, we develop four arguments to discuss (a) the everyday production of risk by societies, (b) scientific risk evaluation of microplastics, (c) social responses, and (d) problems of risk management. To illustrate these four issues, we draw on different aspects of the current scientific and public debate. In doing so, we contribute to a comprehensive understanding of the social-ecological implications of microplastics.
Effective market discipline incentivizes financial institutions to limit their risk-taking behavior, making it a key element for financial regulation. However, without adequate incentives to monitor and control the risk-taking behavior of financial institutions market discipline erodes. As a consequence, bailing out financial institutions, as happened unprecedentedly during the recent financial crisis, may impose indirect costs to financial stability if bailout expectations of investors change. Analyzing US data covering the period between 2004 and 2014, Hett und Schmidt (2017) find that market participants adjusted their bailout expectations in response to government interventions, undermining market discipline mechanisms. Given these findings, policymakers need to take into account the potential effects on market discipline when deciding about public support to troubled financial institutions in the future. Considering the parallelism of events and public responses during the financial crisis as well as the recent developments of Italian banks, these results not only concern the US, but also have important implications for European financial markets and policy makers.
In view of the resilience of Africa's underdevelopment, what do Africans make of their determined aspirations for development? The continent of Africa has constantly drawn global attention, most especially for both human and natural evils. Underdevelopment, it appears, is one of the most eminent threatening evils. It has plunged and promises to maintain the majority of Africa in abject poverty, insecurity, and vulnerability. What perpetuates the ghost and gory of underdevelopment in Africa, despite a proliferation of development rhetoric and initiatives? How do ordinary Africans react to repeated talk and claims of development with little evidence of transformation for the better in their material circumstances? This book interrogates the tenacity of underdevelopment amid calls for Africa to rise from its slumber and reclaim its position in global affairs as the mother continent of humankind. It contributes to the ongoing debates on why Africa remains trapped in the clutch of underdevelopment many decades after the purported end of colonialism. The book comes at a critical time in human history; a time when the talk on Africa's [under-]development is louder due to the ravages of economic downturns and dysfunctional conflicts. It poses a challenge to development practitioners, civil society activists, statesmen, economists, political scientists and theorists to rethink and reconsider their role as technocrats, experts and ambassadors of positive change in Africa and the world beyond.
The cryptic assassin bug subfamily Physoderinae is characterized by a distinctly uneven species and genus-level diversity across continents, but the lack of a phylogeny has so far precluded investigations into the biogeographic history of the group. Endemic Madagascan Physoderinae (11 of the 15 genera) exhibit broad morphological diversity, but the large (38 spp.) and seemingly uniform genus Physoderes is widely distributed across the Oriental and Australasian regions. The three remaining genera are small or even monotypic and restricted to the Neotropical (Cryptophysoderes, Leptophysoderes) and Afrotropical (Porcelloderes) regions. To investigate relationships among Physoderinae, with emphasis on the monophyly of the Madagascan fauna and the monophyly of Physoderes, we conducted a cladistic analysis based on 57 morphological characters and complete genus-level taxon sampling. We found that the Madagascan fauna is not monophyletic, indicating that the island was colonized more than once, although the great majority of Madagascan taxa are part of a single clade. Overall relationships are recovered as Afrotropical Porcelloderes + [(Neotropical Cryptophysoderes, Leptophysoderes) + (Madagascan, Oriental and Australasian taxa)]. Physoderes is shown to be polyphyletic and 3 new genera, Breviphysoderes gen. nov., Macrophysoderes gen. nov. and Nanophysoderes gen. nov., are erected to accommodate new species and several species previously classified as Physoderes. A taxonomic revision of Physoderes and allied genera is conducted. Diagnoses, updated distribution ranges, habitus and genitalic images, and identification keys are provided. A total of 17 synonymies are given, and 15 new species and 3 new genera are described, focusing on the diversity of Physoderinae in the Oriental and Australasian regions. The new species are Breviphysoderes fulvopicta gen. et sp. nov., B. tenebrosa gen. et sp. nov., Macrophysoderes cirripilosa gen. et sp. nov., M. elongata gen. et sp. nov., M. finisterre gen. et sp. nov., M. grandis gen. et sp. nov., Paraphysoderes popeye sp. nov., Physoderes anamalaiensis sp. nov., P. brevipennis sp. nov., P. minime sp. nov., P. muluensis sp. nov., P. mysorensis sp. nov., P. nigripennis sp. nov., P. ractepilosa sp. nov. and P. tricolor sp. nov.
A new species of Autostichidae, Eraina beechei nov. sp., is described from specimens collected in the Andean mountains of Ñuble, Biobío. Diagnostic characters for the species are presented; photographs of adults, illustrations of male and female genitalia, and a key for identifi cation of Eraina species are provided.
Ufocandona hannaleeae gen. et sp. nov. (Crustacea, Ostracoda) from an artesian well in Texas, USA
(2017)
We describe a new genus, Ufocandona gen. nov. with its type species Ufocandona hannaleeae gen. et sp. nov., from an artesian well in San Marcos, Texas, USA. The new genus has diagnostic characteristics that distinguish it from other genera in Candonidae, including the asymmetric shape of the valves, the smooth central area on the external surface of the valves, the hexagonal ornamentations around the marginal ends of the carapace, the dense spines on the marginal edges of the right valve and the dorsal prolongation and tubercles seen from inside the ventral edges of the left valve. Additional differences in the soft body parts of the male and female (e.g., claw-like uropod, shape of hemipenis, long Y aesthetascs, two short or reduced exopods on antenna, reduced numbers of setae and segments on other extremities) distinguish the new genus from others in the family. The discovery of this species from a deep artesian well contributes important information to our understanding of groundwater species diversity in a biologically diverse aquifer where the ostracod fauna has been unstudied.
Rho GTPases control fundamental cellular processes and Cdc42 is a well-studied member of the family that controls filopodia formation and cell migration. Although the regulation of Cdc42 activity by nucleotide binding is well documented, the mechanisms driving its proteostasis are not clear. Here, we demonstrate that the highly conserved, RING domain containing E3 ubiquitin ligase XIAP controls the protein stability of Cdc42. XIAP binds to Cdc42 and directly conjugates poly ubiquitin chains to the Lysine 166 of Cdc42 targeting it for proteasomal degradation. Depletion of XIAP led to an increased protein stability and activity of Cdc42 in normal and tumor cells. Consistently, loss of XIAP enhances filopodia formation in a Cdc42-dependent manner and this phenomenon phenocopies EGF stimulation. Further, XIAP depletion promotes lung colonization of tumor cells in mice in a Cdc42-dependent manner. These observations shed molecular insights into ubiquitin-dependent regulation of Cdc42 and that of actin cytoskeleton.
Ubiquitination is a widespread post-translational modification that controls multiple steps in autophagy, a major lysosome-mediated intracellular degradation pathway. A variety of ubiquitin chains are attached as selective labels on protein aggregates and dysfunctional organelles, thus promoting their autophagy-dependent degradation. Moreover, ubiquitin modification of autophagy regulatory components is essential to positively or negatively regulate autophagy flux in both non-selective and selective pathways. We review the current findings that elucidate the components, timing, and kinetics of the multivalent role of ubiquitin signals in control of amplitude and selectivity of autophagy pathways as well as their impact on the development of human diseases.
Cytokine regulation of high-output nitric oxide (NO) derived from inducible NO synthase (iNOS) is critically involved in inflammation biology and host defense. Herein, we set out to characterize the role of type I interferon (IFN) as potential regulator of hepatic iNOS in vitro and in vivo. In this regard, we identified in murine Hepa1-6 hepatoma cells a potent synergism between pro-inflammatory interleukin-β/tumor necrosis factor-α and immunoregulatory IFNβ as detected by analysis of iNOS expression and nitrite release. Upregulation of iNOS by IFNβ coincided with enhanced binding of signal transducer and activator of transcription-1 to a regulatory region at the murine iNOS promoter known to support target gene expression in response to this signaling pathway. Synergistic iNOS induction under the influence of IFNβ was confirmed in alternate murine Hepa56.1D hepatoma cells and primary hepatocytes. To assess iNOS regulation by type I IFN in vivo, murine acetaminophen (APAP)-induced sterile liver inflammation was investigated. In this model of acute liver injury, excessive necroinflammation drives iNOS expression in diverse liver cell types, among others hepatocytes. Herein, we demonstrate impaired iNOS expression in type I IFN receptor-deficient mice which associated with diminished APAP-induced liver damage. Data presented indicate a vital role of type I IFN within the inflamed liver for fine-tuning pathological processes such as overt iNOS expression.
We propose that resilience effectively helps people cope with stress, thus predominantly reducing the negative. However, we argue that individuals’ social identification has the potential to contribute to their well-being, thus fostering the positive. A two-wave survey study of 180 students shows that resilience is more strongly (negatively) associated with ill-health (i.e. stress and depression), whereas social identification is more strongly (positively) related to well-being (i.e. satisfaction and work engagement). We believe that it is necessary to see these two routes to improving people’s health as complementary, both in future research and for therapy and interventions.
Two new species of the Rhyacophila nigrocephala species group, R. voluta sp. nov. and R. linguiformis sp. nov., are described, diagnosed and illustrated. Rhyacophila voluta sp. nov. is similar to R. pentagona Malicky & Sun, 2002 in male genitalia, but can be diagnosed by the inferior appendages of the same length as the complex of preanal appendages and dorsal lobe of segment IX, fused base of the basal segments of inferior appendages, and slightly incised distal margin of apical segment of inferior appendage. Rhyacophila linguiformis sp. nov. is similar to R. rima Sun & Yang, 1995 and R. esorima Mey, 1996 in male genitalia, but can be diagnosed by the progressively narrowed complex of preanal appendages and the dorsal lobe of segment X, the short anal sclerites, and the small gap between the upper and lower lobes of apical segment of inferior appendages. An updated checklist of 23 species recorded from China is presented.
Two new species of hangingflies, Terrobittacus rostratus sp. nov. and Terrobittacus angustus sp. nov., are described and illustrated from Yunnan, southwestern China, increasing the species number of Terrobittacus Tan & Hua, 2009 to six. Terrobittacus rostratus sp. nov. differs from its congeners by wings devoid of markings and epandrial appendages slightly longer than half the length of the gonocoxites. Terrobittacus angustus sp. nov. can be recognized by wing markings along R5 distally. A key to species of the genus is updated to include the two new species.
Samples from deep benthic areas in the Bransfield Strait, Antarctica, revealed the presence of two new species of Colletteidae: Filitanais elongatus sp. nov. and Macrinella lavradoae sp. nov. Filitanais elongatus sp. nov. resembles F. moskalevi in its habitus; it can, however, be distinguished by characters such as the pleonites and pleotelson with lateral margins parallel and the uropod exopod being longer than half of the first endopod article. Macrinella lavradoae sp. nov. differs from the other species of Macrinella in the shape of the uropod and the pleotelson, with the uropod exopod shorter than the first article of the endopod, the uropod about as long as the pleotelson and the pleotelson with a rounded tip. The number of species of Tanaidacea recorded from Antarctica increases to 162, while the colletteids are now represented by 16 species. Moreover, the diagnosis of the genus Filitanais is herein modified.
Two new genera and species of tiger beetles from Baltic amber (Coleoptera: Carabidae: Cicindelinae)
(2017)
Two fossil tiger beetle species (Coleoptera, Carabidae, Cicindelinae) are described from Eocene Baltic amber using light microscopic and X-ray microscopic techniques. Both species are considered representatives of the subtribe Iresina Rivalier, 1971 due to the shared combination of character states: glabrous head, six labral and four suborbital setae, and glabrous pronotum. Palaeopronyssiformia groehni Wiesner, Will, and Schmidt, new genus, new species, is characterized by a glabrous and furrowed head with six labral setae, large eyes, presence of two supraorbital setae on each side, mandibles with two teeth of the incisor region, and a glabrous and furrowed pronotum. Palaeoiresina cassolai Wiesner, Will, and Schmidt, new genus, new species, is characterized by a unicolored, undentated labrum, mandibles with two teeth of the incisor region, glabrous head with six labral setae, two clypeal setae, two supraorbital setae on each side, and a glabrous pronotum, mesepisternum, mesepimeron, and metepisternum. The species described here represent the only known tiger beetle fossils preserved in Baltic amber.
Background: The Hawking–Perry–Strominger (HPS) work states a new controversial idea about the black hole (BH) information paradox , where BHs maximally entropize and encode information in their event horizon area , with no “hair” thought to reveal information outside but angular momentum, mass, and electric charge only in a unique quantum gravity (QG) vacuum state. New conservation laws of gravitation and electromagnetism , appear to generate different QG vacua, preserving more information in soft photon/graviton hair implants. We find that BH photon hair implants can encode orbital angular momentum (OAM) and vorticity of the electromagnetic (EM) field. Methods: Numerical simulations are used to plot an EM field with OAM emitted by a set of dipolar currents together with the soft photon field they induce. The analytical results confirm that the soft photon hair implant carries OAM and vorticity. Results: a set of charges and currents generating real EM fields with precise values of OAM induce a “curly”, twisted, soft-hair implant on the BH with vorticity and OAM increased by one unit with respect to the initial real field. Conclusions: Soft photon implants can be spatially shaped ad hoc, encoding structured and densely organized information on the event horizon
Twelve + one contains interviews with 13 poets from Johannesburg who span a wide range with respect to age, gender, colour and class. Mike Alfred, who has contributed to journals for many years and has published several individual collections of his own work, provides an intimate opportunity for poets to tell both their biographical stories, describe their artistic aims and processes as well compiling a selection of poems which best represent their themes and styles. The result grants the reader a fascinating insight into a key cross-section of South African poets.
Die Arbeit beschäftigt sich mit der Herstellung sowie der strukturellen und magnetischen Charakterisierung von zwei Materialklassen von kupferbasierten zweidimensionalen Quanten-Spin-Systemen: Quadratische Gitter von Dimeren sowie geometrisch frustrierte Kagomé Gitter. In beiden Systemen werden Substitutionen vorgestellt die zu verbesserten Eigenschaften führen.
Tumor-associated macrophages, angiogenesis, and tumor cell migration in oral squamous cell carcinoma
(2017)
Objective: To investigate the relationship between tumor-associated macrophages (TAMs), neovascularization, and tumor cell migration in oral squamous cell carcinoma (OSCC) of an African subpopulation.
Materials and Methods: Twenty OSCC paraffin blocks underwent immunohistochemistry to TAM1 (CCR7), TAM2 (CD206), Twist, E-cadherin, N-cadherin, and CD34. The relative percentage of CCR7 + and CD206 + cells to overall immune cell population was calculated for three high power fields and an average was taken. TAM-related microvessel density (MVD) was determined as the mean of the three recorded values. Cases that had no CD34 + vessels adjacent to the TAMs region were regarded as having an MVD score of 0.
Results: Ten cases (50%) expressed greater CCR7 activity than CD206, seven cases (35%) expressed approximately equal activity of CCR7 and CD206, while three cases (15%) expressed greater activity of CD206 than CCR7. Twist expression was strong in some cases with strong N-cadherin and weak E-cadherin, but the expression of Twist was not consistently high in all cases that expressed strong N-cadherin and weak E-cadherin.
Conclusions: TAMs distribution suggested antitumor activity and the potential for tumor metastasis was only partly due to Twist-mediated epithelial–mesenchymal transition.
BACKGROUND: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements.
RESULTS: The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF).
CONCLUSION: Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1.
Prioritization of introduction pathways is seen as an important component of the management of biological invasions. We address whether established alien plants, mammals, freshwater fish and terrestrial invertebrates with known ecological impacts are associated with particular introduction pathways (release, escape, contaminant, stowaway, corridor and unaided). We used the information from the European alien species database DAISIE (www.europe-aliens.org) supplemented by the EASIN catalogue (European Alien Species Information Network), and expert knowledge. Plants introduced by the pathways release, corridor and unaided were disproportionately more likely to have ecological impacts than those introduced as contaminants. In contrast, impacts were not associated with particular introduction pathways for invertebrates, mammals or fish. Thus, while for plants management strategies should be targeted towards the appropriate pathways, for animals, management should focus on reducing the total number of taxa introduced, targeting those pathways responsible for high numbers of introductions. However, regardless of taxonomic group, having multiple introduction pathways increases the likelihood of the species having an ecological impact. This may simply reflect that species introduced by multiple pathways have high propagule pressure and so have a high probability of establishment. Clearly, patterns of invasion are determined by many interacting factors and management strategies should reflect this complexity.
To study the implications of highly space-demanding organic moieties on the properties of self-assembled monolayers (SAMs), triptycyl thiolates and selenolates with and without methylene spacers on Au(111) surfaces were comprehensively studied using ultra-high vacuum infrared reflection absorption spectroscopy, X-ray photoelectron spectroscopy, near-edge X-ray absorption fine structure spectroscopy and thermal desorption spectroscopy. Due to packing effects, the molecules in all monolayers are substantially tilted. In the presence of a methylene spacer the tilt is slightly less pronounced. The selenolate monolayers exhibit smaller defect densities and therefore are more densely packed than their thiolate analogues. The Se–Au binding energy in the investigated SAMs was found to be higher than the S–Au binding energy.
While many programs are available to edit phylogenetic trees, associating pictures with branch tips in an efficient and automatic way is not an available option. Here, we present TreePics, a standalone software that uses a web browser to visualize phylogenetic trees in Newick format and that associates pictures (typically, pictures of the voucher specimens) to the tip of each branch. Pictures are visualized as thumbnails and can be enlarged by a mouse rollover. Further, several pictures are can be selected and displayed in a separate window for visual comparison. TreePics works either online or in a full standalone version, where it can display trees with several thousands of pictures (depending on the memory available). We argue that TreePics can be particularly useful in a preliminary stage of research, such as to quickly detect conflicts between a DNA-based phylogenetic tree and morphological variation, that may be due to contamination that needs to be removed prior to final analyses, or the presence of species complexes.
We study exchangeable coalescent trees and the evolving genealogical trees in models for neutral haploid populations.
We show that every exchangeable infinite coalescent tree can be obtained as the genealogical tree of iid samples from a random marked metric measure space when the marks are added to the metric distances. We apply this representation to generalize the tree-valued Fleming-Viot process to include the case with dust in which the genealogical trees have isolated leaves.
Using the Donnelly-Kurtz lookdown approach, we describe all individuals ever alive in the population model by a random complete and separable metric space, the lookdown space, which we endow with a family of sampling measures. This yields a pathwise construction of tree-valued Fleming-Viot processes. In the case of coming down from infinity, we also read off a process whose state space is endowed with the Gromov-Hausdorff-Prohorov topology. This process has additional jumps at the extinction times of parts of the population.
In the case with only binary reproduction events, we construct the lookdown space also from the Aldous continuum random tree by removing the root and the highest leaf, and by deforming the metric in a way that corresponds to the time change that relates the Fleming-Viot process with a Dawson-Watanabe process. The sampling measures on the lookdown space are then image measures of the normalized local time measures.
We also show invariance principles for Markov chains that describe the evolving genealogy in Cannings models. For such Markov chains with values in the space of distance matrix distributions, we show convergence to tree-valued Fleming-Viot processes under the conditions of Möhle and Sagitov for the convergence of the genealogy at a fixed time to a coalescent with simultaneous multiple mergers. For the convergence of Markov chains with values in the space of marked metric measure spaces, an additional assumption is needed in the case with dust.
Treatment of refractory ascites with an automated low-flow ascites pump in patients with cirrhosis
(2017)
Background: Refractory ascites (RA) is a frequent complication of cirrhosis, requiring large volume paracentesis or placement of a transjugular intrahepatic portosystemic shunt (TIPSS). The automated low-flow ascites pump (alfapump, Sequana Medical AG, Zurich, Switzerland) is an innovative treatment option for patients with RA.
Aim: To assess safety and efficacy of this treatment in patients with a contraindication to TIPSS.
Methods: Fifty-six patients (43 males; mean age 62 years) from centres in Germany, Switzerland, UK and Spain were included and followed for up to 24 months. Complications, device deficiencies, paracentesis frequency and patient survival were recorded.
Results: At the time of this analysis, 3 patients completed the 24-month observation period, monitoring of 3 was ongoing, 9 underwent liver transplantation, 17 patients were withdrawn due to serious adverse events and 23 patients died. Most frequently observed technical complication was blocking of the peritoneal catheter. Twenty-three pump-related reinterventions (17 patients) and 12 pump exchanges (11 patients) were required during follow-up. The pump system was explanted in 48% of patients (in 17 patients due to serious adverse events, in 9 at the time of liver transplantation and in 1 due to recovery from RA). Median frequency of paracentesis dropped from 2.17 to 0.17 per month.
Conclusions: The alfapump can expand therapeutic options for cirrhotic patients with RA. Continuous drainage of ascites in a closed loop automated system led to significant reduction in paracentesis frequency. Technical and procedural improvements are required to reduce the rate of adverse events and reinterventions.
A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.
The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany.
This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.
We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.
Background: Posttraumatic Stress Disorder (PTSD) related to childhood sexual abuse (CSA) is often associated with a wide range of trauma-related aversive emotions such as fear, disgust, sadness, shame, guilt, and anger. Intense experience of aversive emotions in particular has been linked to higher psychopathology in trauma survivors. Most established psychosocial treatments aim to reduce avoidance of trauma-related memories and associated emotions. Interventions based on Dialectical Behavior Therapy (DBT) also foster radical acceptance of the traumatic event.
Methods: This study compares individual ratings of trauma-related emotions and radical acceptance between the start and the end of DBT for PTSD (DBT-PTSD) related to CSA. We expected a decrease in trauma-related emotions and an increase in acceptance. In addition, we tested whether therapy response according to the Clinician Administered PTSD-Scale (CAPS) for the DSM-IV was associated with changes in trauma-related emotions and acceptance. The data was collected within a randomized controlled trial testing the efficacy of DBT-PTSD, and a subsample of 23 women was included in this secondary data analysis.
Results: In a multilevel model, shame, guilt, disgust, distress, and fear decreased significantly from the start to the end of the therapy whereas radical acceptance increased. Therapy response measured with the CAPS was associated with change in trauma-related emotions.
Conclusions: Trauma-related emotions and radical acceptance showed significant changes from the start to the end of DBT-PTSD. Future studies with larger sample sizes and control group designs are needed to test whether these changes are due to the treatment.
Trial registration: ClinicalTrials.gov, number NCT00481000
Telemonitoring devices can be used to screen consumers' characteristics and mitigate information asymmetries that lead to adverse selection in insurance markets. However, some consumers value their privacy and dislike sharing private information with insurers. In the second-best efficient Wilson-Miyazaki-Spence framework, we allow for consumers to reveal their risk type for an individual subjective cost and show analytically how this affects insurance market equilibria as well as utilitarian social welfare. Our analysis shows that the choice of information disclosure with respect to revelation of their risk type can substitute deductibles for consumers whose transparency aversion is sufficiently low. This can lead to a Pareto improvement of social welfare and a Pareto efficient market allocation. However, if all consumers are offered cross-subsidizing contracts, the introduction of a transparency contract decreases or even eliminates cross-subsidies. Given the prior existence of a WMS equilibrium, utility is shifted from individuals who do not reveal their private information to those who choose to reveal. Our analysis provides a theoretical foundation for the discussion on consumer protection in the context of digitalization. It shows that new technologies bring new ways to challenge crosssubsidization in insurance markets and stresses the negative externalities that digitalization has on consumers who are not willing to take part in this development.
One of the fundamental challenges in deconstructing, rethinking and remaking the world from a Pan African vantage point is that some captives have tended to delight in the warmth of the [imperial] predator's mouth. In other words, some captives forget that the imperial predator's mouth gets warm because empire is eating and heating up from prey on the continent. (De-)Militarisation, Transnational Land Grabs and Restitution in an Age of the New Scramble for Africa: A Pan African Socio-Legal Perspective is a book that knocks on key aspects relating to land, militarisation, a PostAfrican World Order and a chaotic Post-God World Order, which require critical scholarly and policy attention in the quest to free Africa from centuries-old imperial depredations. The book carefully navigates the imperial entrapments which are designed to focus African attention only on decolonising African minds without also engaging in the [imperially more unsettling] decolonisation of African materialities.
Des critiques et écrivains de nouvelles ont défendu l'idée que la brieveté et un unique moment de clarté sont les éléments essentiels du format court typique de la nouvelle. Cependant, la nouvelle postcoloniale est plurielle, polyphonique et versatile, et elle a tendance à s'appuyer sur le désaccord culturel, social, et linguistique. Ce chapitre examine la traduction et l'échec de celle-ci dans l'oeuvre de deux nouvellistes prolifiques qui viennent des deux différentes traditions postcoloniales : Nadine Gordimer et Anita Desai. La prémisse de mon argument est que les nouvelles de ces écrivains ont pour la plupart lieu dans des espaces périphériques, par exemple des villages et des avant-postes. Elles dramatisent une forme de processus postcolonial de désengagement des centres de pouvoir en explorant et en remettant en question des hiérarchies discursives. Cette renégociation implique la présence de perspectives multiples et de subjectivités plurielles, de même qu'elle insiste sur des traductions problématiques et des malentendus surgissant en leur sein. Par l'étude de textes de Gordimer et Desai, ce chapitre considère plusieurs formes de malentendus – fausses représentations, mécompréhension, traductions erronées et obstructions linguistiques – qui ses présentent dans deux nouvelles. Il ressort de cette analyse que les malentendus sont susceptibles de devenir les instruments de l'expression d'une résistance dans les sites hégémoniques de la langue et du pouvoir.
Languages in general have various possibilities to express one and the same propositional content. One of these possibilities is grammatical variation. This thesis is concerned with the variation of the linear word order in a clause and the effects triggered by word order alternations. Although sharing the same propositional content, different word order variants can carry different functions; word order variation can be used to achieve certain stylistic effects. The dissertation looks at functional and stylistic preferences of English regarding variation from the canonical word order in (1).
(1) [Ernie]S [sits]V [on the table]O. (SVO)
The variation under consideration is locative inversion (LOCI), exemplified in (2).
(2) On the table sits Ernie.
As any variation from the canonical word order is said to strongly depend on the grammatical system of the language a sentence is realized in, the perspective is extended to the word order equivalent of the sentence above in German (3). The goal is to highlight possible differences/similarities between English and German with respect to one specific word order variant in a declarative main clause.
(3) Auf dem Tisch liegt ein Brief.
On the table lies a letter
‘On the table lies a letter’.
As the variation from the canonical word order is not expected to be coincidental in both languages, the features that favor the pattern under consideration are examined. This is done through a statistical analysis by employing two comparable corpora, the BNC for English and the TÜPP D/Z for German. The central questions for the thesis therefore are: What are the functions of the inverted constructions in English and German, what features favor their use in the respective languages, and how are they realized syntactically?
One finding is that German uses the syntactic pattern PP-V-NP for very similar reasons this pattern is used for in English. There seems to be a general tendency to order shorter before longer constituents. The syntactic pattern under consideration fulfills similar discourse functions in both languages. Both languages show similar preferences, they are driven by similar factors when having to decide on whether to stay with the canonical order or to prepose (respectively invert) the canonically postverbal PP.
Objectives: It is known that transition, as a shift of care, marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Still, the transition process of adolescents and young adults living with a kidney transplant in Germany is not well defined. The present research aims to assess transition-relevant structures for this group of young people. Special attention is paid to the timing of the process.
Setting: In an observational study, we visited 21 departments of paediatric nephrology in Germany. Participants were doctors (n=19), nurses (n=14) and psychosocial staff (n=16) who were responsible for transition in the relevant centres. Structural elements were surveyed using a short questionnaire. The experiential viewpoint was collected by interviews which were transcribedverbatim before thematic analysis was performed.
Results: This study highlights that professionals working within paediatric nephrology in Germany are well aware of the importance of successful transition. Key elements of transitional care are well understood and mutually agreed on. Nonetheless, implementation within daily routine seems challenging, and the absence of written, structured procedures may hamper successful transition.
Conclusions: While professionals aim for an individual timing of transfer based on medical, social, emotional and structural aspects, rigid regulations on transfer age as given by the relevant health authorities add on to the challenge.
Trial registration: number ISRCTN Registry no 22988897; results (phase I) and pre-results (phase II).
Transition path sampling is a powerful tool in the study of rare events. Shooting trial trajectories from configurations along existing transition paths proved particularly efficient in the sampling of reactive trajectories. However, most shooting attempts tend not to result in transition paths, in particular in cases where the transition dynamics has diffusive character. To overcome the resulting efficiency problem, we developed an algorithm for “shooting from the top.” We first define a shooting range through which all paths have to pass and then shoot off trial trajectories only from within this range. For a well chosen shooting range, nearly every shot is successful, resulting in an accepted transition path. To deal with multiple mechanisms, weighted shooting ranges can be used. To cope with the problem of unsuitably placed shooting ranges, we developed an algorithm that iteratively improves the location of the shooting range. The transition path sampling procedure is illustrated for models of diffusive and Langevin dynamics. The method should be particularly useful in cases where the transition paths are long so that only relatively few shots are possible, yet reasonable order parameters are known.
Biological invasions are occurring frequently and with great impact to agricultural production and other ecosystem services. In response to this, the Australian Weed Risk Assessment (AWRA) was created to assess the potential 'weediness' of plants based on answers to questions related to biogeography, undesirable attributes, and biology or ecology. This basic model has been expanded and adapted for use on other taxa, often without adequate validation. Since invasive insect crop pests are a major economic cost to agricultural production, there is interest in using an expanded model for insects. Here, we review traits related to invasiveness of insects based on a systematic review of the literature. We then compare the identified invasive traits of insects with those identified for plants in the AWRA. Using insects as a case study, we illustrate that although there is some overlap in invasive traits, there are many unique traits related to invasion for both insects and plants. For insects, these traits relate largely to social behaviour. This lack of congruence may also be the case for other taxa. To increase predictive power, a taxon-specific risk assessment tool and deliberate verification are required.
The concept of the "comprehensive approach" has become a paradigm for international state engagement in the field of fostering sustainable peace in crisis-ridden countries. This approach stipulates joint actions of different governmental institutions. The ministry of defence, providing interventionist armed forces; the ministry of interior, providing police personal; the ministry of foreign affairs, providing crisis aid and the ministry of economic cooperation and development define the core actors on the highest level, whilst the implementation of this approach is left to the various, highly heterogeneous employees of the ministries and their sub-contractors...
Sustainable Development Goals (SDGs) comprise of 17 goals and 169 targets. All SDGs are interlinked to produce synergetic eff ects and emphasize health in all policies. Among the 17 Goals, Goal 3 has a central focus on health, which is underpinned by 13 targets. Th e other 16 goals are also directly or indirectly related to health and will contribute to achieving the associated targets for Goal 3. Th e ambitious SDG agenda and their progress can be tracked by measuring numerous goals, targets, and indicators. The main objective of this paper is to provide an overview about how health- related SDGs and their targets and indicators are being tracked in the national context of Nepal. Adequate investment in research for knowledge generation, capacity building and innovation, and continous research communication among policy makers, researchers and external development partners will contribute to tracking the progress of SDGs in Nepal.
Studies investigating the prevalence, cause, and consequence of multiple sclerosis (MS) fatigue typically use single measures that implicitly assume symptom-stability over time, neglecting information about if, when, and why severity fluctuates. We aimed to examine the extent of moment-to-moment and day-to-day variability in fatigue in relapsing-remitting MS and healthy individuals, and identify daily life determinants of fluctuations. Over 4 weekdays, 76 participants (38 relapsing-remitting MS; 38 controls) recruited from multiple sites provided real-time self-reports six times daily (n = 1661 observations analyzed) measuring fatigue severity, stressors, mood, and physical exertion, and daily self-reports of sleep quality. Fatigue fluctuations were evident in both groups. Fatigue was highest in relapsing-remitting MS, typically peaking in late-afternoon. In controls, fatigue started lower and increased steadily until bedtime. Real-time stressors and negative mood were associated with increased fatigue, and positive mood with decreased fatigue in both groups. Increased fatigue was related to physical exertion in relapsing-remitting MS, and poorer sleep quality in controls. In relapsing-remitting MS, fatigue fluctuates substantially over time. Many daily life determinants of fluctuations are similar in relapsing-remitting MS and healthy individuals (stressors, mood) but physical exertion seems more relevant in relapsing-remitting MS and sleep quality most relevant in healthy individuals.
A great challenge in life sciences remains the site-specific modification of proteins with minimal perturbation for in vitro as well as in vivo studies. Therefore, different chemoselective reactions and semi-synthetic techniques such as native chemical ligation or intein-mediated protein splicing have been established. They enable a site-specific incorporation of chemical reporters into proteins, such as organic fluorophores or unnatural amino acids. In this PhD Thesis, protein trans-splicing was guided by minimal high-affinity interaction pairs to trace proteins in mammalian cells. In addition, the temporal modulation of cellular processes by photo-cleavable viral immune evasins was achieved.
Protein trans-splicing mediated by split inteins is a powerful technique for site-specific and 'traceless' protein modifications. Despite recent developments there is still an urgent need for ultra-small high-affinity intein tags for in vitro and in vivo approaches. So far, only a very few in-cell applications of protein trans-splicing are reported, all limited to C-terminal protein modifications. Here, a strategy for covalent N-terminal intein-mediated protein labeling at sub-nanomolar probe concentrations was developed. Combined with the minimalistic Ni-trisNTA/His-tag interaction pair, the affinity between the intein fragments was increased 50-fold (KD ~ 10 nM). Site-specific and efficient 'traceless' protein modification by high-affinity trans-splicing is demonstrated at nanomolar concentrations in mammalian cells.
High background originating from non-reacted, 'always-on' fluorescent probes still is a crucial issue in life sciences. Covalent labeling approaches with simultaneous activation of fluorescence are advantageous to increase sensitivity and to reduce background signal. Therefore, high-affinity protein trans-splicing was combined with fluorophore/quencher pairs for online detection of covalent N-terminal protein labeling in cellular environments. Substantial fluorescence enhancement at nanomolar probe concentrations was achieved. This ultra-small fluorogenic high-affinity split intein system is an unprecedented example for real-time monitoring of the trans-splicing reaction in cell-like environments as well as for protein labeling with fluorogenic probes at nanomolar concentrations.
To extend the field of chemical immunology and to address spatiotemporal aspects in adaptive immune response, new tools to control antigen processing are required. Therefore, synthetic photo-conditional viral immune evasins were designed to modulate antigen processing on demand. By using light, the time and dose controlled antigen translocation by the transporter associated with antigen processing (TAP) was triggered with response in the second regime. Peptide delivery and loading by the peptide-loading complex (PLC) was rendered inactive, whereas blocking was abolished in a light-controlled fashion to inactivate the synthetic viral immune evasin ICP47 along with simultaneous activation of the antigen presentation pathway. Lightresponsive peptide translocation by the TAP complex was assayed in vitro by utilizing microsomes isolated from professional antigen presenting B-cell lymphomas (Raji). To extend these studies, suppression and photo-controlled rescue of antigen presentation was examined at single-cell resolution in human primary immune cells.
Native chemical ligation interconnects peptide chemistry with recombinantly expressed proteins. This technique was applied to generate the semi-synthetic full-length ICP47. Although this approach was realized, the low product yield was not sufficient for further functional studies. Therefore, full-length ICP47 was consecutively generated by utilizing a full synthetic four-fragment ligation approach. However, this synthetic viral immune evasin was not able to block peptide translocation in a robust way.