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Electromagnetic calorimeter (ECAL) is being developed to complement dilepton spectrometer HADES. ECAL will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 AGeV on the beam of future accelerator SIS100@FAIR. We will report results of the last beam test with quasi-monoenergetic photons carried out in MAMI facility at Johannes Gutenberg Universität Mainz.
The quark gluon plasma produced in heavy ion collisions behaves like an almost ideal fluid described by viscous hydrodynamics with a number of transport coefficients. The second order coefficient κ is related to a Euclidean correlator of the energy-momentum tensor at vanishing frequency and low momentum. This allows for a lattice determination without maximum entropy methods or modelling, but the required lattice sizes represent a formidable challenge. We calculate κ in leading order lattice perturbation theory and simulations on 1203 × 6, 8 lattices with a < 0.1 fm. In the temperature range 2Tc − 10Tc we find κ = 0.36(15)T2. The error covers both a suitably rescaled AdS/CFT prediction as well as, remarkably, the result of leading order perturbation theory. This suggests that appropriate noise reduction methods on the lattice and NLO perturbative calculations could provide an accurate QCD prediction in the near future.
With its broad spectrum of cults and coexisting religions Graeco-Roman antiquity seems, at first glance, to be the embodiment of religious freedom. Yet, a closer analysis shows that a concept of tolerance or the idea of religious freedom did not exist. Political institutions could easily suppress religious practices that were regarded as offensive. Fighting against the oppression of Christians appears to have increased under the influence of oecumenical paganism during the reign of the Severans. In this time, the Christian thinkerTertullian discovered and articulated the concept of religious freedom. However, he did not do so emphatically and the concept was not very successful in antiquity. With the Christianization of the Roman Empire it disappeared soon, although its rediscovery in later epochs contributed heavily to the formation of the European norm of religious freedom.
We demonstrate high-density labelling of cellular DNA and RNA using click chemistry and perform confocal and super-resolution microscopy. We visualize the crescent and ring-like structure of densely packed RNA in nucleoli. We further demonstrate click chemistry with unnatural amino acids for super-resolution imaging of outer-membrane proteins of E. coli.
Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved.
Data structures and advanced models of computation on big data : report from Dagstuhl seminar 14091
(2014)
This report documents the program and the outcomes of Dagstuhl Seminar 14091 "Data Structures and Advanced Models of Computation on Big Data". In today's computing environment vast amounts of data are processed, exchanged and analyzed. The manner in which information is stored profoundly influences the efficiency of these operations over the data. In spite of the maturity of the field many data structuring problems are still open, while new ones arise due to technological advances.
The seminar covered both recent advances in the "classical" data structuring topics as well as new models of computation adapted to modern architectures, scientific studies that reveal the need for such models, applications where large data sets play a central role, modern computing platforms for very large data, and new data structures for large data in modern architectures.
The extended abstracts included in this report contain both recent state of the art advances and lay the foundation for new directions within data structures research.
Purpose: To evaluate the effect of chronic liver disease (CLD) in a multivariate analysis of associated risk factors in patients with hepatocellular carcinoma (HCC) using transarterial chemoembolization (TACE). Materials and methods: A total of 145 patients with HCC (99 men, 46 women; mean age: 63 years ±8.1; age range: 46-84 years) underwent 598 TACE procedures. The presence of CLD, number and location of lesions, tumor size, Child-Pugh score, vascularity, portal involvement and alpha fetoprotein value were analyzed using the multivariate regression model. Cox regression was used for survival analysis. Results: The median survival time was 26.7 months, and 78.6% of all treated lesions showed tumor responses. The presence of CLD (OR 2.12, P=0.004), Child-Pugh score B (OR 2.24, P=0.002), alpha fetoprotein >100ng/dl (OR 1.18, P<0.001), multinodularity (≥3 lesions) (OR 4.41, P=0.003), lesion size >5cm (OR 4.12, P=0.002) and hypervascularity (OR 7.94, P=0.003) were significant effective factors for a local response when analyzed using a multivariate logistic model. Multivariate survival analysis using Cox's regression model during the median follow-up period of 25 months (range: 1-42 months) demonstrated a significant difference in survival rates (P values <0.05). No significant difference in responses was noted for males, locations of lesions and portal involvements statistically. Conclusion: The presence of chronic liver disease as well as associated risk factors including Child-Pugh score B, alpha fetoprotein 100ng/dl, multinodularity (≥3 lesions), lesion size >5cm and hypervascularity statistically led to a significant effect in tumor response in HCC patients treated with TACE. Patient gender, location of lesion and involvement of portal vein showed no significant difference in response.
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
We present an approach for combining high resolution MRI-based myelin mapping with functional information from electroencephalography (EEG) or magnetoencephalography (MEG). The main contribution to the primary currents detectable with EEG and MEG comes from ionic currents in the apical dendrites of cortical pyramidal cells, aligned perpendicularly to the local cortical surface. We provide evidence from an in-vivo experiment that the variation in MRI-based myeloarchitecture measures across the cortex predicts the variation of the current density over individuals and thus is of functional relevance. Equivalent current dipole locations and moments due to pitch onset evoked response fields (ERFs) were estimated by means of a variational Bayesian algorithm. The myeloarchitecture was estimated indirectly from individual high resolution quantitative multi-parameter maps (MPMs) acquired at 800 μm isotropic resolution. Myelin estimates across cortical areas correlated positively with dipole magnitude. This correlation was spatially specific: regions of interest in the auditory cortex provided significantly better models than those covering whole hemispheres. Based on the MPM data we identified the auditory cortical area TE1.2 as the most likely origin of the pitch ERFs measured by MEG. We can now proceed to exploit the higher spatial resolution of quantitative MPMs to identify the cortical origin of M/EEG signals, inform M/EEG source reconstruction and explore structure–function relationships at a fine structural level in the living human brain.
he aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups (n=15). Fifteen specimens (group 1) were glazed and 15 specimens (group 2) were veneered with feldspathic ceramic and then glazed. Prior to grinding, maximum roughness depth (Rmax) values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 µm, 10 µm, and 7.5 µm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmax values were determined. Differences between groups were examined using one-way analysis of variance (ANOVA). The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing. It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces.
The U-turn is a classical three-dimensional RNA folding motif first identified in the anticodon and T-loops of tRNAs. It also occurs frequently as a building block in other functional RNA structures in many different sequence and structural contexts. U-turns induce sharp changes in the direction of the RNA backbone and often conform to the 3-nt consensus sequence 5'-UNR-3' (N = any nucleotide, R = purine). The canonical U-turn motif is stabilized by a hydrogen bond between the N3 imino group of the U residue and the 3' phosphate group of the R residue as well as a hydrogen bond between the 2'-hydroxyl group of the uridine and the N7 nitrogen of the R residue. Here, we demonstrate that a protonated cytidine can functionally and structurally replace the uridine at the first position of the canonical U-turn motif in the apical loop of the neomycin riboswitch. Using NMR spectroscopy, we directly show that the N3 imino group of the protonated cytidine forms a hydrogen bond with the backbone phosphate 3' from the third nucleotide of the U-turn analogously to the imino group of the uridine in the canonical motif. In addition, we compare the stability of the hydrogen bonds in the mutant U-turn motif to the wild type and describe the NMR signature of the C+-phosphate interaction. Our results have implications for the prediction of RNA structural motifs and suggest simple approaches for the experimental identification of hydrogen bonds between protonated C-imino groups and the phosphate backbone.
A consistent muscle activation strategy underlies crawling and swimming in Caenorhabditis elegans
(2014)
Although undulatory swimming is observed in many organisms, the neuromuscular basis for undulatory movement patterns is not well understood. To better understand the basis for the generation of these movement patterns, we studied muscle activity in the nematode Caenorhabditis elegans. Caenorhabditis elegans exhibits a range of locomotion patterns: in low viscosity fluids the undulation has a wavelength longer than the body and propagates rapidly, while in high viscosity fluids or on agar media the undulatory waves are shorter and slower. Theoretical treatment of observed behaviour has suggested a large change in force–posture relationships at different viscosities, but analysis of bend propagation suggests that short-range proprioceptive feedback is used to control and generate body bends. How muscles could be activated in a way consistent with both these results is unclear. We therefore combined automated worm tracking with calcium imaging to determine muscle activation strategy in a variety of external substrates. Remarkably, we observed that across locomotion patterns spanning a threefold change in wavelength, peak muscle activation occurs approximately 45° (1/8th of a cycle) ahead of peak midline curvature. Although the location of peak force is predicted to vary widely, the activation pattern is consistent with required force in a model incorporating putative length- and velocity-dependence of muscle strength. Furthermore, a linear combination of local curvature and velocity can match the pattern of activation. This suggests that proprioception can enable the worm to swim effectively while working within the limitations of muscle biomechanics and neural control.
This article focuses on the opportunities and challenges of implementing an extensive reading project in an English as a foreign language classroom in Germany. Studies such as PISA have shown that comparatively poor German and foreign language reading skills are still a prevalent issue in German society today. Consequently, the question of how these poor results can be improved is of utmost importance. Reading motivation is often described as the ‘driving force of reading’. Research has shown that if reading motivation and reading for pleasure are supported, interest in reading in a foreign language can be created, which may in turn have a positive impact on the other influential factors in reading and related skills. Dörnyei’s framework of L2 motivation sums up the current thinking on reading motivation. With its constituents ‘language’, ‘learner’, and ‘learning situation’, it shows the aspects to be taken into consideration when it comes to the improvement of motivation. Within this theoretical framework, an ER project was conducted at a grammar school (Gymnasium) in Frankfurt/Main, Germany. On the basis of the gathered data, gained from questionnaires, worksheets and the transcript of a focus group discussion, six main categories could be identified. They point to the development of a positive attitude towards reading among the students and the potential of graphic novels as a motivating factor. It was also confirmed that a successful application of reading strategies led to increased motivation. Generally, the project showed that reading is still an issue amongst many teenagers and that an ER project can affect learners, their motivation and related language skills in a positive way.
Aim: The cytokine receptor tumor necrosis factor receptor superfamily member 9 (TNFRSF9) is mainly considered to be a co-stimulatory activation marker in hematopoietic cells. Several preclinical models have shown a dramatic beneficial effect of treatment approaches targeting TNFRSF9 with agonistic antibodies. However, preliminary clinical phase I/II studies were stopped after the occurrence of several severe deleterious side effects. In a previous study, it was demonstrated that TNFRSF9 was strongly expressed by reactive astrocytes in primary central nervous system (CNS) tumors, but was largely absent from tumor or inflammatory cells. The aim of the present study was to address the cellular source of TNFRSF9 expression in the setting of human melanoma brain metastasis, a highly immunogenic tumor with a prominent tropism to the CNS.
Methods: Melanoma brain metastasis was analyzed in a cohort of 78 patients by immunohistochemistry for TNFRSF9 and its expression was correlated with clinicopathological parameters including sex, age, survival, tumor size, number of tumor spots, and BRAF V600E expression status.
Results: Tumor necrosis factor receptor superfamily member 9 was frequently expressed independently on both melanoma and endothelial cells. In addition, TNFRSF9 was also present on smooth muscle cells of larger vessels and on a subset of lymphomonocytic tumor infiltrates. No association between TNFRSF9 expression and patient survival or other clinicopathological parameters was seen. Of note, several cases showed a gradual increase in TNFRSF9 expression on tumor cells with increasing distance from blood vessels, an observation that might be linked to hypoxia-driven TNFRSF9 expression in tumor cells.
Conclusion: The findings indicate that the cellular source of TNFRSF9 in melanoma brain metastasis largely exceeds the lymphomonocytic pool, and therefore further careful (re-) assessment of potential TNFRSF9 functions in cell types other than hematopoietic cells is needed. Furthermore, the hypothesis of hypoxia-driven TNFRSF9 expression in brain metastasis melanoma cells requires further functional testing.
Speolepta leptogaster (Winnertz, 1863) is frequently occurring in European subterranean environments. As for most cave animals, studies addressing non-anatomical aspects are sparse. Here we present the first molecular study on S. leptogaster. We investigated the demographic structure (i.e. COI locus) of 69 specimens from 36 underground populations in Hesse (Central German Uplands) to get first insights into the species’ dispersal ability.
In total, 14 haplotypes were revealed. Haplotype diversity was relatively high, whereas nucleotide diversity was low. Furthermore, a significant but low pattern of isolation-by-distance and (a) past population expansion event(s) were detected.
Our genetic results suggest a (good) active dispersal ability for Speolepta leptogaster. The occurrence of several surface records of adult specimens corroborates this hypothesis. We discuss the developmental stages of S. leptogaster in the context of the ecological classification system and regard the species as a eutroglophile. Evidence has been found to distinguish two larval types. A reconstructed life-cycle of the species is provided.
Does the rotten child spoil his companion? : spatial peer effects among children in rural India
(2014)
This paper identifies the effect of neighborhood peer groups on childhood skill acquisition using observational data. We incorporate spatial peer interaction, defined as a child's nearest geographical neighbors, into a production function of child cognitive development in Andhra Pradesh, India. Our peer group definition takes the form of networks, whose structure allows us to identify endogenous peer effects and contextual effects separately. We exploit variation over time to avoid confounding correlated with social effects. Our results suggest that spatial peer and neighborhood effects are strongly positively associated with a child's cognitive skill formation. Further, we explore the effect of peer groups in helping to provide insurance against the negative impact of idiosyncratic shocks to child learning. We find that the data reject full risk-sharing, but cannot rule out the existence of partial risk-sharing on behalf of peers. We show that peer effects are robust to different specifications of peer interactions and investigate the sensitivity of our estimates to potential misspecification of the network structure using Monte Carlo experiments.
Research in the field of Digital Humanities, also known as Humanities Computing, has seen a steady increase over the past years. Situated at the intersection of computing science and the humanities, present efforts focus on making resources such as texts, images, musical pieces and other semiotic artifacts digitally available, searchable and analysable. To this end, computational tools enabling textual search, visual analytics, data mining, statistics and natural language processing are harnessed to support the humanities researcher. The processing of large data sets with appropriate software opens up novel and fruitful approaches to questions in the traditional humanities. This report summarizes the Dagstuhl seminar 14301 on “Computational Humanities - bridging the gap between Computer Science and Digital Humanities”.
1998 ACM Subject Classification I.2.7 Natural Language Processing, J.5 Arts and Humanities
Benjamin's early reception in the United States can be broken into eight phases: 1) a few notices of his work in the 1930s; 2) the appearance of two major works, without translation, in the 'Zeitschrift für Sozialforschung', when it was published in New York and mimeographed in Los Angeles; 3) several reports of his suicide along with the death of other Jewish and left-wing writers who fell victim to Nazi terror; 4) scattered use of his work in the late 1940s and 1950s; 5) a growing realization in the early 1960s that American literary and cultural criticism was missing something of significance by neglecting Benjamin's work; 6) the appearance in the 1960s of competing portraits of Benjamin by four of his surviving friends, including Hannah Arendt, who edited and introduced the first collection of his writings in English; 7) an uncanny repetition of the earlier neglect, as a significant number of Benjamin's texts are published in Great Britain during the 1970s and early 1980s but remain unavailable in the States; 8) the beginning of a sustained critical engagement with Benjamin in the late 1970s.
At the forefront of those who tenaciously pondered this issue are, I would claim, Walter Benjamin and Ludwig Wittgenstein. Benjamin and Wittgenstein both are philosophers of language who tried to establish in unique ways the doctrine of resemblance respectively: "Lehre vom Ähnlichen" and "[Lehre der] Familienähnlichkeit." What they see and find in language are not communication and mutual understanding but instead one of the weirdest phenomena in/of the world, viz., resemblance (likeness) in/of language. This phenomenon, I would insist, indicates the correlation of appearing and disappearing, of differentiating and integrating, and of dividing and imparting of language as such. For Benjamin and Wittgenstein, to sum up, language is a paradigmatic paradoxical site of (dis)appearance, differentiating integrity, and divisive imparting. For this reason, it is worthwhile to pin down where their thoughts on language converge and where they diverge.
To explicate what distinguishes pain, Benjamin elaborates: "Of all corporeal feelings, pain alone is like a navigable river which never dries up and which leads man down to the sea. [...] Pain [...] is a link between worlds. This is why organic pleasure is intermittent, whereas pain can be permanent. This comparison of pleasure and pain explains why the cause of pain is irrelevant for the understanding of man's nature, whereas the source of his greatest pleasure is extremely important. For every pain, even the most trivial one, can lead upward to the highest religious suffering, whereas pleasure is not capable of any enhancement, and owes any nobility it possesses to the grace of its birth - that is to say, its source. (SW I, 397)" In these important lines, pain's unique strength is linked not to its origin (this is reserved for pleasure), but rather to the way that its strenuous flow throughout the suffering body has the power to lead it to infinite heights. In contrast to pleasure, which is forever seeking out its sources, pain manifests itself most consummately when it is intensified; it fulfills itself most deeply by gradually reenforcing its own fortitude. To make sense of pain, therefore, we must understand the nature of its 'movement': and in Benjamin's metaphor of the "navigable river" - its flow. In what follows, I develop Benjamin's idea of the nature of pain as manifested in the internal law of its ,ow in two other of Benjamin's texts: 'Berlin Childhood Around 1900' (1934) and 'Thought Figures' (1933).
One of the cruxes of Walter Benjamin’s work is the tension between an indebting and an expiating "memoria", i. e. the afflicting and the salvific insistence of history within the present moment. On the one hand, memory inscribes itself onto spaces and bodies in the violent and painful fashion of Kafka's "Penal Colony" apparatus. On the other hand, it can, in the form of rememoration ('Eingedenken'), sublate these very inscriptions. This sublation usually involves some form of redemptive, timely (re-)verbalization, but Benjamin’s conception of it varies. To gain a better insight into this inherent, varying tension, the article will take a closer look at the connection between pain, memory and law-positing violence in some Benjaminian texts, occasionally relating them to the historical background of his discussion.
Walter Benjamin had a revealing fascination with the legend of a Chinese artist who entered his painting and disappeared in it. In his writings this character becomes an emblematic figure that enables the philosopher to discuss the nature of representation in its various infections (in games and in painting, in theater and in cinema); to explore the status of the image and of the threshold that simultaneously separates and connects image and reality; to analyse the different bodily (i. e. "aesthetic") attitudes of the beholder in his/her close or distant relationship to the image; to investigate the manifold implications of empathy ('Einfühlung ') toward the figurative world; and finally, to approach a peculiar kind of dialectics, namely the "Chinese". My paper aims at considering such varied aspects in Benjamin's interpretation of the Chinese painter, understanding it as a true "dialectical image" that in its 'non-coincidentia oppositorum' provokes not only significant hermeneutic oscillations, but even a radical inversion of its fundamental meaning.
If we take Benjamin's definitions to their logical conclusion, then the monad and the reproduced copy are set unequivocally into binary opposition, as we, the masses capable and most needful of action, are implicitly denied the potential for liberation through aesthetic experience. This denial could not have been his long-term intention. When we take into account the breadth of his writings in response to Fascism, and we look at the artistic movements, Dada in particular, that Benjamin defines as 'politicizing art,' it seems as though we risk too narrow a reading of Benjamin's theories by assuming the aura can be, or must be, done away with. Rather, I would argue that this moment of auratic interaction is crucial to effectively politicizing art at all. Mechanically-produced art, in order to function politically, must allow its audience the space necessary to step back, awaken their 'Geistesgegenwart', and take action 'before' the present moment is finished and past. The elimination of aura - as per Benjamin’s own definitions of aura - neuters the interaction this awakening requires. While Benjamin provides the framework and asks the right questions, when determining what will allow his definitions to realize their aims most fully, I submit that he draws his line in the wrong place.
The flourishing of literature and thought during the age of Goethe may have inspired German nationalism in the 1930s, but Walter Benjamin identified other values in the period worth defending. 'Deutsche Menschen' is a short collection of edited letters by well-known German authors which Benjamin published in 1936 under the pseudonym Detlef Holz in order to hide his Jewish identity. In his inscription to Scholem's copy of the book, Benjamin wrote, "May you, Gerhard, find a chamber in this ark - which I built when the Fascist flood started to rise - for the memories of your youth," and in his sister’s copy Benjamin wrote, "This ark, built after a Jewish model, for Dora - From Walter." This essay considers what Benjamin may have meant by those inscriptions. Looking beyond discussions of "German," "Jewish," and even "German-Jewish" identity, this essay explores Benjamin's descriptions of his letter collection, asking how he conceptualized and framed it at first and how it may have changed between 1931 and 1936. The categories of tradition and agency will be my focus, which I will develop in the context of Benjamin's other writings and his particular interests in quotation and materialism. &e formation and reception of 'Deutsche Menschen' reveal a complex, ambitious project that combines many of Benjamin's ideas and goals.
Two alternative hypotheses – referred to as opportunity- and stigma-based behavior – suggest that the magnitude of the link between unemployment and crime also depends on preexisting local crime levels. In order to analyze conjectured nonlinearities between both variables, we use quantile regressions applied to German district panel data. While both conventional OLS and quantile regressions confirm the positive link between unemployment and crime for property crimes, results for assault differ with respect to the method of estimation. Whereas conventional mean regressions do not show any significant effect (which would confirm the usual result found for violent crimes in the literature), quantile regression reveals that size and importance of the relationship are conditional on the crime rate. The partial effect is significantly positive for moderately low and median quantiles of local assault rates.
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Heterogenous subtypes of breast cancer need to be analyzed separately. Pooling of datasets can provide reasonable sample sizes but dataset bias is an important concern. We assembled a combined dataset of 579 Affymetrix microarrays from triple negative breast cancer (TNBC) in Gene Expression Omnibus (GEO) series GSE31519. We developed a method for selecting comparable datasets and to control for the amount of dataset bias of individual probesets.
"I Am a Hottentot" : africanist mimicry and green xenophilia in Hans Paasche and Karen Blixen
(2014)
Claims that industrialized western countries must reform their environmental practices have often been made with reference to less-developed non-western societies living in greater "harmony" or "balance" with the natural world. Examples of what I call green xenophilia (from the Greek "xenos", meaning strange, unknown or foreign, and "philia", meaning love or attraction), are myriad, wide-ranging and culturally dispersed. They range from the appearance of the iconic "crying Indian" in anti-pollution TV and newspaper spots in the months leading up to the first Earth Day on April 22 1970 to numerous environmentalist individuals' and groups' use of the fabricated "Chief Seattle's Speech" as an authoritative touchstone of ecological consciousness, and from the British Schumacher College's endorsement of India as a source of simplicity, holism, humility, vegetarianism etc. to leading deep ecologists' advocacy of East Asian religions (especially Buddhism, Jainism and Taoism) as "biocentric" alternatives to "anthropocentric" Christianity (Rolston 1987; Dunaway 2008; Krupat 2011; Corrywright 2010). Invocations of non-western cultures, identities and worldviews have proved potent heuristic devices, enabling greens both to critique the status quo and to gesture (however schematically) towards the possibility of alternatives. Pervasive media-borne ideas and images like "the Green Tibet" (Huber 1997) and "the ecological Indian" (Krech 1999) have given environmentalist ideas about the good life physical incarnation, making them seem less remote and abstract. Yet the prevalence of xenophile dis course has also made environmentalism vulnerable to recurrent accusations of romantic primitivism, orientalism and exoticism, as western greens have sometimes (though not always) appeared to buttress traditional socio-cultural norms in the very act of challenging them (Guha 1989; Lohmann 1993; Bartholomeusz 1998). What is gained and what is risked when western greens speak about, with, for or as "the other"? In this essay I engage with two early-twentieth-century North European writers, the German Hans Paasche (1881-1921) and the Dane Karen Blixen (1885-1962), whose works bring this question to the forefront. Critical of European industrialization, and awkwardly positioned vis-a-vis their upper-class social milieus, Paasche and Blixen wrote as self-made "Africans", testing the limits between colonialism, anti-colonialism and emergent forms of environmentalism and green" lifestyle reform. More precisely, Paasche in "Die Forschungsreise des Afrikaners Lukanga Kukara ins Innerste Deutschland" ("The African Lukanga Mukara's Research Joumey into the Innermost of Germany" (1912-1913) and Blixen in "Out of Africa" (1937) deploy the ambiguous form of mimicry that Susan Gubar labels "racechange", impersonating or appropriating culturally other voices and perspectives on animals, food, physical embodiment and human-natural relations (Gubar 1997). Paasche and Blixen, I argue, used their considerable intercultural insight to construct images of Africa that they hoped would stand in redemptive contrast to the humanly and environmentally ruinous beliefs and practices of European modernity. I am interested in the acts of ethnic and textual self-alienation that these writers perform because they highlight the discursive, ethical and political ambiguities of green xenophilia - ambiguities that can be explored from different positions within the developing field of ecocritical studies.
The present article analyzes a prominent yet relatively understudied contact space among Native American, New Zealand Maori, and aboriginal Taiwanese literatures: the struggle of indigenous peoples to negotiate optimal relationships between themselves and the natural world, particularly in light of capitalist modernity and globalization. Many indigenous narratives draw sharp distinctions between native peoples and outsiders, predictably portraying the former as protectors and the latter as destroyers of both nature and indigenous local cultures. The Native American Chickasaw writer Linda Hogan's (1947-) novel 'People of the Whale' (2008), the Maori writer Patricia Grace's (1937-) novel 'Patiki' (1986), and the aboriginal Taiwanese writer Topas Tamapima's short story "Zuihou de lieren" are no exception. But these texts also problematize notions of the so-called "ecological native." They do so most conspicuously by revealing the ambiguous relationships those peoples believed closest to nature have with the nonhuman world, that is to say their environmental ambiguity ('ecoambiguity') (Thornber 2012).
Ecocriticism started out in the early 1990s in the framework of American literary studies - in the Anglo sense that equates "America" with the "United States." In fact, the new field's first professional organization, the Association for the Study of Literature and the Environment, was founded as an offshoot of academic interest focused on a particular region of the United States, in the backroom of a casino in Reno, Nevada, during the 1992 annual convention of the Western Literature Association. During its first decade, the bulk of ecocritical attention focused on American literature as shaped by Thoreau and British literature as shaped by Wordsworth - a limited but powerful concentration on nature writing in the genres of poetry, nonfiction prose, and the noveI, with particular attention to Native American literature. By the turn of the millennium, in a story that has by now been told repeatedly, interest in the literature-environment nexus had grown and diversified enough that ecocriticism almost literally exploded into a much broader research area encompassing multiple historical periods (from the Middle Ages to postmodernism), genres (from poetry to the graphic novel and narrative film), and regions: the Caribbean, Latin America, East Asia, and Western Europe all emerged as new areas of ecocritical exploration. New encounters between postcolonial theory and ecocritical analysis proved particularly productive for both fields: linking historical exploration and political ecology with literary analysis, the emergent "poco-eco" matrix opened new perspectives on the connections and disjunctures between imperialism, ecological crisis, and conservation. Over the last few years, the concept of "Environmental Humanities" has increasingly co me to accompany and to superimpose itself as an umbrella term on ecocriticism and comparable research areas in neighboring disciplines: environmental history, environmental anthropology, environmental philosophy, cultural geography, and political ecology. Driven by the impulse to connect environmental research across the humanities, to justify humanistic research at institutions often prone to cut first in the humanities, and to bring the knowledge generated through humanistic research into the public sphere, environmentally oriented scholars have used the term "Environmental Humanities" as a shorthand for what they hope will be a new vision of their discipline. As of this writing, the concept remains somewhat more aspirational than real. While ecocritics and environmental philosophers have long collaborated in Australia, and environmental historians and ecocritics sometimes collaborate in the United States, the disciplines that make up the Environmental Humanities have to date largely pursued their own disciplinary trajectories. But there are signs that the tide may have begun to turn. Various universities and research organizations have started programs in the field. The Swedish environmental historian Sverker Sörlin published a brief outline of the new interdisciplinary matrix in the journal 'BioScience' in 2012, and a longer manifesto followed from the editorial collective of the newly established journal 'Environmental Humanities' at Macquarie University in Australia (Rose et al. 2012). Another journal focusing on the environmental humanities began publication in early 2014 from the University of Oregon under the title 'Resilience'.
Background and Purpose. Leukocyte migration into alveolar space plays a critical role in pulmonary inflammation resulting in lung injury. Acute ethanol (EtOH) exposure exerts anti-inflammatory effects. The clinical use of EtOH is critical due to its side effects. Here, we compared effects of EtOH and ethyl pyruvate (EtP) on neutrophil adhesion and activation of cultured alveolar epithelial cells (A549). Experimental Approach. Time course and dose-dependent release of interleukin- (IL-) 6 and IL-8 from A549 were measured after pretreatment of A549 with EtP (2.5–10 mM), sodium pyruvate (NaP, 10 mM), or EtOH (85–170 mM), and subsequent lipopolysaccharide or IL-1beta stimulation. Neutrophil adhesion to pretreated and stimulated A549 monolayers and CD54 surface expression were determined. Key Results. Treating A549 with EtOH or EtP reduced substantially the cytokine-induced release of IL-8 and IL-6. EtOH and EtP (but not NaP) reduced the adhesion of neutrophils to monolayers in a dose- and time-dependent fashion. CD54 expression on A549 decreased after EtOH or EtP treatment before IL-1beta stimulation. Conclusions and Implications. EtP reduces secretory and adhesive potential of lung epithelial cells under inflammatory conditions. These findings suggest EtP as a potential treatment alternative that mimics the anti-inflammatory effects of EtOH in early inflammatory response in lungs.
Malignant gliomas are intrinsic brain tumors with a dismal prognosis. They are well-adapted to hypoxic conditions and poorly immunogenic. NKG2D is one of the major activating receptors of natural killer (NK) cells and binds to several ligands (NKG2DL).
Here we evaluated the impact of miRNA on the expression of NKG2DL in glioma cells including stem-like glioma cells. Three of the candidate miRNA predicted to target NKG2DL were expressed in various glioma cell lines as well as in glioblastomas in vivo: miR-20a, miR-93 and miR-106b. LNA inhibitor-mediated miRNA silencing up-regulated cell surface NKG2DL expression, which translated into increased susceptibility to NK cell-mediated lysis. This effect was reversed by neutralizing NKG2D antibodies, confirming that enhanced lysis upon miRNA silencing was mediated through the NKG2D system. Hypoxia, a hallmark of glioblastomas in vivo, down-regulated the expression of NKG2DL on glioma cells, associated with reduced susceptibility to NK cell-mediated lysis. This process, however, was not mediated through any of the examined miRNA. Accordingly, both hypoxia and the expression of miRNA targeting NKG2DL may contribute to the immune evasion of glioma cells at the level of the NKG2D recognition pathway. Targeting miRNA may therefore represent a novel approach to increase the immunogenicity of glioblastoma.
The Cueva del Azufre in Tabasco, Mexico, is a nutrient-rich cave and its inhabitants need to cope with high levels of dissolved hydrogen sulfide and extreme hypoxia. One of the successful colonizers of this cave is the poeciliid fish Poecilia mexicana, which has received considerable attention as a model organism to examine evolutionary adaptations to extreme environmental conditions. Nonetheless, basic ecological data on the endemic cave molly population are still missing; here we aim to provide data on population densities, size class compositions and use of different microhabitats. We found high overall densities in the cave and highest densities at the middle part of the cave with more than 200 individuals per square meter. These sites have lower H2S concentrations compared to the inner parts where most large sulfide sources are located, but they are annually exposed to a religious harvesting ceremony of local Zoque people called La Pesca. We found a marked shift in size/age compositions towards an overabundance of smaller, juvenile fish at those sites. We discuss these findings in relation to several environmental gradients within the cave (i.e., differences in toxicity and lighting conditions), but we also tentatively argue that the annual fish harvest during a religious ceremony (La Pesca) locally diminishes competition (and possibly, cannibalism by large adults), which is followed by a phase of overcompensation of fish densities.
The Future of the Noosphere
(2014)
In this article, a Koselleckian approach to the issue of time will be employed. In Koselleck's view, modernity has been characterized by a multiplicity of synchronous times, or as Helge Jordheim puts it, by "multiple temporalities". By temporality, Koselleck means something different than epochs or periodizations. More precisely, Jordheim asserts, Koselleck uses this term to reach for experiences of time, such as "progress, decadence, acceleration, or delay, the 'not yet' and the 'no longer', the 'earlier' or 'later than', the 'too early' and the 'too late', situation and the duration". Especially pertinent for this article is Koselleck's category of a horizon of expectations (Erwartungshorizont), understood as perceived prospects for the future. In both the noosphere and the Anthropocene discussion, the notion of an Age of Man seems to merge different timescales into one another, or, as stated by one of the most prominent scientists in the early debate, "The division of historical and geological time is levelled out for us". This article examines the temporality implied in the noosphere concept in order to formulate a specific question regarding the Anthropocene. The article is thus intended to contribute to the on-going examination of the Anthropocene concept by way of historicising its temporality.
For more than two decades, the National Planning Office for Philosophy and Social Sciences (NPOPSS) has been managing official funding of social science research in China under the orbit of the Communist Party of China’s (CPC) propaganda system. By focusing on “Major Projects”, the most prestigious and well-funded program initiated by the NPOPSS in 2004, this contribution outlines the political and institutional ramifications of this line of official funding and attempts to identify larger shifts during the past decade in the “ideologics” of official social science research funding – the changing ideological circumscriptions of research agendas in the more narrow sense of echoing party theory and rhetoric and – in the broader sense – of adapting to an increasingly dominant official discourse of cultural and national self-assertion. To conclude, this article offers reflections on the potential repercussions of these shifts for international academic collaboration.
In order to achieve climate change mitigation, long-term decisions are required that must be reconciled with other societal goals that draw on the same resources. For example, ensuring food security for a growing population may require an expansion of crop land, thereby reducing natural carbon sinks or the area available for bio-energy production. Here, we show that current impact-model uncertainties pose an important challenge to long-term mitigation planning and propose a new risk-assessment and decision framework that accounts for competing interests.
Based on cross-sectorally consistent simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) we discuss potential gains and limitations of additional irrigation and trade-offs of the expansion of agricultural land as two possible response measures to climate change and growing food demand. We describe an illustrative example in which the combination of both measures may close the supply demand gap while leading to a loss of approximately half of all natural carbon sinks.
We highlight current limitations of available simulations and additional steps required for a comprehensive risk assessment.
Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing.
BACKGROUND: Acetogenic bacteria are able to use CO2 as terminal electron acceptor of an anaerobic respiration, thereby producing acetate with electrons coming from H2. Due to this feature, acetogens came into focus as platforms to produce biocommodities from waste gases such as H2+CO2 and/or CO. A prerequisite for metabolic engineering is a detailed understanding of the mechanisms of ATP synthesis and electron-transfer reactions to ensure redox homeostasis. Acetogenesis involves the reduction of CO2 to acetate via soluble enzymes and is coupled to energy conservation by a chemiosmotic mechanism. The membrane-bound module, acting as an ion pump, was of special interest for decades and recently, an Rnf complex was shown to couple electron flow from reduced ferredoxin to NAD+ with the export of Na+ in Acetobacterium woodii. However, not all acetogens have rnf genes in their genome. In order to gain further insights into energy conservation of non-Rnf-containing, thermophilic acetogens, we sequenced the genome of Thermoanaerobacter kivui.
RESULTS: The genome of Thermoanaerobacter kivui comprises 2.9 Mbp with a G+C content of 35% and 2,378 protein encoding orfs. Neither autotrophic growth nor acetate formation from H2+CO2 was dependent on Na+ and acetate formation was inhibited by a protonophore, indicating that H+ is used as coupling ion for primary bioenergetics. This is consistent with the finding that the c subunit of the F1FO ATP synthase does not have the conserved Na+ binding motif. A search for potential H+-translocating, membrane-bound protein complexes revealed genes potentially encoding two different proton-reducing, energy-conserving hydrogenases (Ech).
CONCLUSIONS: The thermophilic acetogen T. kivui does not use Na+ but H+ for chemiosmotic ATP synthesis. It does not contain cytochromes and the electrochemical proton gradient is most likely established by an energy-conserving hydrogenase (Ech). Its thermophilic nature and the efficient conversion of H2+CO2 make T. kivui an interesting acetogen to be used for the production of biocommodities in industrial micobiology. Furthermore, our experimental data as well as the increasing number of sequenced genomes of acetogenic bacteria supported the new classification of acetogens into two groups: Rnf- and Ech-containing acetogens.
Biodiversity is unevenly distributed on Earth and hotspots of biodiversity are often associated with areas that have undergone orogenic activity during recent geological history (i.e. tens of millions of years). Understanding the underlying processes that have driven the accumulation of species in some areas and not in others may help guide prioritization in conservation and may facilitate forecasts on ecosystem services under future climate conditions. Consequently, the study of the origin and evolution of biodiversity in mountain systems has motivated growing scientific interest. Despite an increasing number of studies, the origin and evolution of diversity hotspots associated with the Qinghai-Tibetan Plateau (QTP) remains poorly understood. We review literature related to the diversification of organisms linked to the uplift of the QTP. To promote hypothesis-based research, we provide a geological and palaeoclimatic scenario for the region of the QTP and argue that further studies would benefit from providing a complete set of complementary analyses (molecular dating, biogeographic, and diversification rates analyses) to test for a link between organismic diversification and past geological and climatic changes in this region. In general, we found that the contribution of biological interchange between the QTP and other hotspots of biodiversity has not been sufficiently studied to date. Finally, we suggest that the biological consequences of the uplift of the QTP would be best understood using a meta-analysis approach, encompassing studies on a variety of organisms (plants and animals) from diverse habitats (forests, meadows, rivers), and thermal belts (montane, subalpine, alpine, nival). Since the species diversity in the QTP region is better documented for some organismic groups than for others, we suggest that baseline taxonomic work should be promoted.
The LPJ-GUESS dynamic vegetation model uniquely combines an individual- and patch-based representation of vegetation dynamics with ecosystem biogeochemical cycling from regional to global scales. We present an updated version that includes plant and soil N dynamics, analysing the implications of accounting for C–N interactions on predictions and performance of the model. Stand structural dynamics and allometric scaling of tree growth suggested by global databases of forest stand structure and development were well reproduced by the model in comparison to an earlier multi-model study. Accounting for N cycle dynamics improved the goodness of fit for broadleaved forests. N limitation associated with low N-mineralisation rates reduces productivity of cold-climate and dry-climate ecosystems relative to mesic temperate and tropical ecosystems. In a model experiment emulating free-air CO2 enrichment (FACE) treatment for forests globally, N limitation associated with low N-mineralisation rates of colder soils reduces CO2 enhancement of net primary production (NPP) for boreal forests, while some temperate and tropical forests exhibit increased NPP enhancement. Under a business-as-usual future climate and emissions scenario, ecosystem C storage globally was projected to increase by ca. 10%; additional N requirements to match this increasing ecosystem C were within the high N supply limit estimated on stoichiometric grounds in an earlier study. Our results highlight the importance of accounting for C–N interactions in studies of global terrestrial N cycling, and as a basis for understanding mechanisms on local scales and in different regional contexts.
Strong seasonal variability of hygric and thermal soil conditions are a defining environmental feature in Northern Australia. However, how such changes affect the soil–atmosphere exchange of nitrous oxide (N2O), nitric oxide (NO) and dinitrogen (N2) is still 5 not well explored. By incubating intact soil cores from four sites (3 savanna, 1 pasture) under controlled soil temperatures (ST) and soil moisture (SM) we investigated the release of the trace gas fluxes of N2O, NO and carbon dioxide (CO2). Furthermore, the release of N2 due to denitrification was measured using the helium gas flow soil core technique. Under dry pre-incubation conditions NO and N2O emission were very low (< 7.0± 5.0 μgNO-Nm−2 h−1; < 0.0± 1.4 μgN2O-Nm−2 h−1) or in case of N2O, even a net soil uptake was observed. Substantial NO (max: 306.5 μgNm−2 h−1) and relatively small N2O pulse emissions (max: 5.8±5.0 μgNm−2 h−1) were recorded following soil wetting, but these pulses were short-lived, lasting only up to 3 days. The total atmospheric loss of nitrogen was dominated by N2 emissions (82.4–99.3% of total N lost), although NO emissions contributed almost 43.2% at 50% SM and 30 °C ST. N2O emissions were systematically higher for 3 of 12 sample locations, which indicates substantial spatial variability at site level, but on average soils acted as weak N2O sources or even sinks. Emissions were controlled by SM and ST for N2O and CO2, ST and pH for NO, and SM and pH for N2.
Strong seasonal variability of hygric and thermal soil conditions are a defining environmental feature in northern Australia. However, how such changes affect the soil–atmosphere exchange of nitrous oxide (N2O), nitric oxide (NO) and dinitrogen (N2) is still not well explored. By incubating intact soil cores from four sites (three savanna, one pasture) under controlled soil temperatures (ST) and soil moisture (SM) we investigated the release of the trace gas fluxes of N2O, NO and carbon dioxide (CO2). Furthermore, the release of N2 due to denitrification was measured using the helium gas flow soil core technique. Under dry pre-incubation conditions NO and N2O emissions were very low (<7.0 ± 5.0 μg NO-N m−2 h−1; <0.0 ± 1.4 μg N2O-N m−2 h−1) or in the case of N2O, even a net soil uptake was observed. Substantial NO (max: 306.5 μg N m−2 h−1) and relatively small N2O pulse emissions (max: 5.8 ± 5.0 μg N m−2 h−1) were recorded following soil wetting, but these pulses were short lived, lasting only up to 3 days. The total atmospheric loss of nitrogen was generally dominated by N2 emissions (82.4–99.3% of total N lost), although NO emissions contributed almost 43.2% to the total atmospheric nitrogen loss at 50% SM and 30 °C ST incubation settings (the contribution of N2 at these soil conditions was only 53.2%). N2O emissions were systematically higher for 3 of 12 sample locations, which indicates substantial spatial variability at site level, but on average soils acted as weak N2O sources or even sinks. By using a conservative upscale approach we estimate total annual emissions from savanna soils to average 0.12 kg N ha−1 yr−1 (N2O), 0.68 kg N ha−1 yr−1 (NO) and 6.65 kg N ha−1 yr−1 (N2). The analysis of long-term SM and ST records makes it clear that extreme soil saturation that can lead to high N2O and N2 emissions only occurs a few days per year and thus has little impact on the annual total. The potential contribution of nitrogen released due to pulse events compared to the total annual emissions was found to be of importance for NO emissions (contribution to total: 5–22%), but not for N2O emissions. Our results indicate that the total gaseous release of nitrogen from these soils is low and clearly dominated by loss in the form of inert nitrogen. Effects of seasonally varying soil temperature and moisture were detected, but were found to be low due to the small amounts of available nitrogen in the soils (total nitrogen <0.1%).
Questions about how human-environment-relations can be conceptualized in a non-dualistic way have been intensively discussed throughout the last decades. The majority of the established realist and constructivist perspectives aim at explaining a given situation by analytically dissecting it. Unfortunately, such an interactionist perspective systematically reproduces the dualistic division between humans, environment and nature.
In contrast, this paper offers a transactive perspective origin in classical pragmatism and discusses its meta-theoretical consequences for human-environment-research. A transactionist perspective interprets the world as a flow of unique and entangled events. Instead of ontologically separating humans and environment, it advocates to look at their relations as being part of a "connatural world". Such a point of view raises new ethical and political questions for geographical human-environment research, argues for a renaissance of ideographic methodologies and hints to a fruitful unity of geographical inquiry.
The prediction of climate on time scales of years to decades is attracting the interest of both climate researchers and stakeholders. The German Ministry for Education and Research (BMBF) has launched a major research programme on decadal climate prediction called MiKlip (Mittelfristige Klimaprognosen, Decadal Climate Prediction) in order to investigate the prediction potential of global and regional climate models (RCMs). In this paper we describe a regional predictive hindcast ensemble, its validation, and the added value of regional downscaling. Global predictions are obtained from an ensemble of simulations by the MPI-ESM-LR model (baseline 0 runs), which were downscaled for Europe using the COSMO-CLM regional model. Decadal hindcasts were produced for the 5 decades starting in 1961 until 2001. Observations were taken from the E-OBS data set. To identify decadal variability and predictability, we removed the long-term mean, as well as the long-term linear trend from the data. We split the resulting anomaly time series into two parts, the first including lead times of 1–5 years, reflecting the skill which originates mainly from the initialisation, and the second including lead times from 6–10 years, which are more related to the representation of low frequency climate variability and the effects of external forcing. We investigated temperature averages and precipitation sums for the summer and winter half-year. Skill assessment was based on correlation coefficient and reliability. We found that regional downscaling preserves, but mostly does not improve the skill and the reliability of the global predictions for summer half-year temperature anomalies. In contrast, regionalisation improves global decadal predictions of half-year precipitation sums in most parts of Europe. The added value results from an increased predictive skill on grid-point basis together with an improvement of the ensemble spread, i.e. the reliability.
In old and heavily weathered soils, the availability of P might be so small that the primary production of plants is limited. However, plants have evolved several mechanisms to actively take up P from the soil or mine it to overcome this limitation. These mechanisms involve the active uptake of P mediated by mycorrhiza, biotic de-occlusion through root clusters, and the biotic enhancement of weathering through root exudation. The objective of this paper is to investigate how and where these processes contribute to alleviate P limitation on primary productivity. To do so, we propose a process-based model accounting for the major processes of the carbon, water, and P cycles including chemical weathering at the global scale. Implementing P limitation on biomass synthesis allows the assessment of the efficiencies of biomass production across different ecosystems. We use simulation experiments to assess the relative importance of the different uptake mechanisms to alleviate P limitation on biomass production. We find that active P uptake is an essential mechanism for sustaining P availability on long timescales, whereas biotic de-occlusion might serve as a buffer on timescales shorter than 10 000 yr. Although active P uptake is essential for reducing P losses by leaching, humid lowland soils reach P limitation after around 100 000 yr of soil evolution. Given the generalized modelling framework, our model results compare reasonably with observed or independently estimated patterns and ranges of P concentrations in soils and vegetation. Furthermore, our simulations suggest that P limitation might be an important driver of biomass production efficiency (the fraction of the gross primary productivity used for biomass growth), and that vegetation on old soils has a smaller biomass production rate when P becomes limiting. With this study, we provide a theoretical basis for investigating the responses of terrestrial ecosystems to P availability linking geological and ecological timescales under different environmental settings.
Introduction
(2014)
BACKGROUND: Micro-RNAs (miRNA) are attributed to the systems biological role of a regulatory mechanism of the expression of protein coding genes. Research has identified miRNAs dysregulations in several but distinct pathophysiological processes, which hints at distinct systems-biology functions of miRNAs. The present analysis approached the role of miRNAs from a genomics perspective and assessed the biological roles of 2954 genes and 788 human miRNAs, which can be considered to interact, based on empirical evidence and computational predictions of miRNA versus gene interactions.
RESULTS: From a genomics perspective, the biological processes in which the genes that are influenced by miRNAs are involved comprise of six major topics comprising biological regulation, cellular metabolism, information processing, development, gene expression and tissue homeostasis. The usage of this knowledge as a guidance for further research is sketched for two genetically defined functional areas: cell death and gene expression. Results suggest that the latter points to a fundamental role of miRNAs consisting of hyper-regulation of gene expression, i.e., the control of the expression of such genes which control specifically the expression of genes.
CONCLUSIONS: Laboratory research identified contributions of miRNA regulation to several distinct biological processes. The present analysis transferred this knowledge to a systems-biology level. A comprehensible and precise description of the biological processes in which the genes that are influenced by miRNAs are notably involved could be made. This knowledge can be employed to guide future research concerning the biological role of miRNA (dys-) regulations. The analysis also suggests that miRNAs especially control the expression of genes that control the expression of genes.
Recently a considerable amount of effort has been put into quantifying how interactions of the carbon and nitrogen cycle affect future terrestrial carbon sinks. Dynamic vegetation models, representing the nitrogen cycle with varying degree of complexity, have shown diverging constraints of nitrogen dynamics on future carbon sequestration. In this study, we use LPJ-GUESS, a dynamic vegetation model employing a detailed individual- and patch-based representation of vegetation dynamics, to evaluate how population dynamics and resource competition between plant functional types, combined with nitrogen dynamics, have influenced the terrestrial carbon storage in the past and to investigate how terrestrial carbon and nitrogen dynamics might change in the future (1850 to 2100; one representative "business-as-usual" climate scenario). Single-factor model experiments of CO2 fertilisation and climate change show generally similar directions of the responses of C–N interactions, compared to the C-only version of the model as documented in previous studies using other global models. Under an RCP 8.5 scenario, nitrogen limitation suppresses potential CO2 fertilisation, reducing the cumulative net ecosystem carbon uptake between 1850 and 2100 by 61%, and soil warming-induced increase in nitrogen mineralisation reduces terrestrial carbon loss by 31%. When environmental changes are considered conjointly, carbon sequestration is limited by nitrogen dynamics up to the present. However, during the 21st century, nitrogen dynamics induce a net increase in carbon sequestration, resulting in an overall larger carbon uptake of 17% over the full period. This contrasts with previous results with other global models that have shown an 8 to 37% decrease in carbon uptake relative to modern baseline conditions. Implications for the plausibility of earlier projections of future terrestrial C dynamics based on C-only models are discussed.
Cryptochrome 1a, located in the UV/violet-sensitive cones in the avian retina, is discussed as receptor molecule for the magnetic compass of birds. Our previous immunohistochemical studies of chicken retinae with an antiserum that labelled only activated cryptochrome 1a had shown activation of cryptochrome 1a under 373 nm UV, 424 nm blue, 502 nm turquoise and 565 nm green light. Green light, however, does not allow the first step of photoreduction of oxidized cryptochromes to the semiquinone. As the chickens had been kept under ‘white’ light before, we suggested that there was a supply of the semiquinone present at the beginning of the exposure to green light, which could be further reduced and then re-oxidized. To test this hypothesis, we exposed chickens to various wavelengths (1) for 30 min after being kept in daylight, (2) for 30 min after a 30 min pre-exposure to total darkness, and (3) for 1 h after being kept in daylight. In the first case, we found activated cryptochrome 1a under UV, blue, turquoise and green light; in the second two cases we found activated cryptochrome 1a only under UV to turquoise light, where the complete redox cycle of cryptochrome can run, but not under green light. This observation is in agreement with the hypothesis that activated cryptochrome 1a is found as long as there is some of the semiquinone left, but not when the supply is depleted. It supports the idea that the crucial radical pair for magnetoreception is generated during re-oxidation.
It is common practice to use a 30-year period to derive climatological values, as recommended by the World Meteorological Organization. However this convention relies on important assumptions, of which the validity can be examined by deriving the uncertainty inherent to using a limited time-period for deriving climatological values. In this study a new method, aiming at deriving this uncertainty, has been developed with an application to precipitation for a station in Europe (Westdorpe) and one in Africa (Gulu). The weather generator framework is used to produce synthetic daily precipitation time-series that can also be regarded as alternative climate realizations. The framework consists of an improved Markov model, which shows good performance in reproducing the 5-day precipitation variability. The sub-seasonal, seasonal and the inter-annual signals are introduced in the weather generator framework by including covariates. These covariates are derived from an empirical mode decomposition analysis with an improved stability and significance assessment. Introducing covariates was found to substantially improve the monthly precipitation variability for Gulu. From the weather generator, 1,000 synthetic time-series were produced. The divergence between these time-series demonstrates an uncertainty, inherent to using a 30-year period for mean precipitation, of 11 % for Westdorpe and 15 % for Gulu. The uncertainty for precipitation 10-year return levels was found to be 37 % for both sites.
Endoscopic retrograde cholangiopancreatography (ERCP) offers an effective interventional option for treating symptomatic chronic pancreatitis. Endoscopic pancreatic sphincterotomy is performed to facilitated endoscopic treatment. Pancreatic duct strictures can be treated by inserting plastic stents, and a 10 Fr endoprosthesis is adequate in many cases. Before stent insertion, hydrostatic balloon dilation is needed in some cases. Pancreatic stones can be removed with a dormia basket, but combining ERCP and extracorporeal shockwave lithotripsy (ESWL) is often most effective.
Standard and advanced endoscopic treatment approaches are delineated in this article and include stricture dilation with a Soehendra retriever, cSEMS placement and multi-stenting.
Most available knowledge on fungal arginine metabolism is derived from studies on Saccharomyces cerevisiae, in which arginine catabolism is initiated by releasing urea via the arginase reaction. Orthologues of the S. cerevisiae genes encoding the first three enzymes in the arginase pathway were cloned from Kluyveromyces lactis and shown to functionally complement the corresponding deletion in S. cerevisiae. Surprisingly, deletion of the single K. lactis arginase gene KlCAR1 did not completely abolish growth on arginine as nitrogen source. Growth rate of the deletion mutant strongly increased during serial transfer in shake-flask cultures. A combination of RNAseq-based transcriptome analysis and 13C-15N-based flux analysis was used to elucidate the arginase-independent pathway. Isotopic 13C15N-enrichment in γ-aminobutyrate revealed succinate as the entry point in the TCA cycle of the alternative pathway. Transcript analysis combined with enzyme activity measurements indicated increased expression in the Klcar1Δ mutant of a guanidinobutyrase (EC.3.5.3.7), a key enzyme in a new pathway for arginine degradation. Expression of the K. lactis KLLA0F27995g (renamed KlGBU1) encoding guanidinobutyrase enabled S. cerevisiae to use guanidinobutyrate as sole nitrogen source and its deletion in K. lactis almost completely abolish growth on this nitrogen source. Phylogenetic analysis suggests that this enzyme activity is widespread in fungi.
The first cultural influences come out in Dobruja together with the appearance of the first German colonists, beginning from 1840 till 1891. The colonization process develops itself in three stages and colonies in places like Tulcea, Malcoci, Almagea, Ciucurova, Cogealac, Tariverde, M. Kogălniceanu and others set up as a result. The German population has created an original culture, an ethnic and spiritual communication being deeply set up, but at the same time a communication struck by the specific conditions imposed by the history of this south-eastern European area. On the other side, the Turkish invasion of Dobruja started earlier, in 1388, when it was actually defeated by Mircea cel Bătrân. In 1393 the Turks succeeded in taking Dobruja and Silistra, but in 1404 Micea cel Bătrân re-conquered the greatest part of these regions. Many Turkish and Tartars moved into Dobruja during the long period of Ottoman rule. The 19th century ethnographic maps show a mainly Turkish population in the area of modern day Dobruja, Tartars and Turks in the southern part of Dobruja and Romanians dominating the north of Dobruja. The paper aims at presenting aspects regarding these two different identities and cultures which are to be found in Dobruja, as well as their integration process within the Romanian Dobrujan modern society.
BACKGROUND: Recent findings support the idea that interleukin (IL)-22 serum levels are related to disease severity in end-stage liver disease. Existing scoring systems--Model for End-Stage Liver Disease (MELD), Survival Outcomes Following Liver Transplantation (SOFT) and Pre-allocation-SOFT (P-SOFT)--are well-established in appraising survival rates with or without liver transplantation. We tested the hypothesis that IL-22 serum levels at transplantation date correlate with survival and potentially have value as a predictive factor for survival.
MATERIAL AND METHODS: MELD, SOFT, and P-SOFT scores were calculated to estimate post-transplantation survival. Serum levels of IL-22, IL-6, IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were collected prior to transplantation in 41 patients. Outcomes were assessed at 3 months, 1 year, and 3 years after transplantation.
RESULTS: IL-22 significantly correlated with MELD, P-SOFT, and SOFT scores (Rs 0.35, 0.63, 0.56 respectively, p<0.05) and with the discrimination in post-transplantation survival. IL-6 showed a heterogeneous pattern (Rs 0.40, 0.63, 0.57, respectively, p<0.05); CRP and PCT did not correlate. We therefore added IL-22 serum values to existing scoring systems in a generalized linear model (GLM), resulting in a significantly improved outcome prediction in 58% of the cases for both the P-SOFT (p<0.01) and SOFT scores (p<0.001).
CONCLUSIONS: Further studies are needed to address the concept that IL-22 serum values at the time of transplantation provide valuable information about survival rates following orthotopic liver transplantation.
Caspase-2 represents the most conserved member of the caspase family, which exhibits features of both initiator and effector caspases. Using ribonucleoprotein (RNP)-immunoprecipitation assay, we identified the proapoptotic caspase-2L encoding mRNA as a novel target of the ubiquitous RNA-binding protein HuR in DLD-1 colon carcinoma cells. Unexpectedly, crosslinking-RNP and RNA probe pull-down experiments revealed that HuR binds exclusively to the caspase-2-5' untranslated region (UTR) despite that the 3' UTR of the mRNA bears several adenylate- and uridylate-rich elements representing the prototypical HuR binding sites. By using RNAi-mediated loss-of-function approach, we observed that HuR regulates the mRNA and in turn the protein levels of caspase-2 in a negative manner. Silencing of HuR did not affect the stability of caspase-2 mRNA but resulted in an increased redistribution of caspase-2 transcripts from RNP particles to translational active polysomes implicating that HuR exerts a direct repressive effect on caspase-2 translation. Consistently, in vitro translation of a luciferase reporter gene under the control of an upstream caspase-2-5'UTR was strongly impaired after the addition of recombinant HuR, whereas translation of caspase-2 coding region without the 5'UTR is not affected by HuR confirming the functional role of the caspase-2-5'UTR. Functionally, an elevation in caspase-2 level by HuR knockdown correlated with an increased sensitivity of cells to apoptosis induced by staurosporine- and pore-forming toxins as implicated by their significant accumulation in the sub G1 phase and an increase in caspase-2, -3 and poly ADP-ribose polymerase cleavage, respectively. Importantly, HuR knockdown cells remained insensitive toward STS-induced apoptosis if cells were additionally transfected with caspase-2-specific siRNAs. Collectively, our findings support the hypothesis that HuR by acting as an endogenous inhibitor of caspase-2-driven apoptosis may essentially contribute to the antiapoptotic program of adenocarcinoma cells by HuR.
This article reviews the most recent results concerning second harmonic generation (SHG) experiments of non-phase matchable and phase matchable powder samples at high pressures and explains the pressure dependence of the intensity of the SHG signal by correlating it to the ratio between the average coherence length and the average particle size. The examples discussed here include pressure-induced structural changes in quartz, ZnO, ice VII and KIO3. It is shown that the second harmonic generation technique is a unique tool for the detection of pressure-induced structural phase transitions. It is laboratory based and allows fast measurements. It is complementary to X-ray diffraction and provides additional information about the presence of an inversion center for unknown or controversially discussed structures at high pressure.
BACKGROUND: Transient episodes of ischemia in a remote organ or tissue (remote ischemic preconditioning, RIPC) can attenuate myocardial injury. Myocardial damage is associated with tissue remodeling and the matrix metalloproteinases 2 and 9 (MMP-2/9) are crucially involved in these events. Here we investigated the effects of RIPC on the activities of heart tissue MMP-2/9 and their correlation with serum concentrations of cardiac troponin T (cTnT), a marker for myocardial damage.
METHODS: In cardiosurgical patients with cardiopulmonary bypass (CPB) RIPC was induced by four 5 minute cycles of upper limb ischemia/reperfusion. Cardiac tissue was obtained before as well as after CPB and serum cTnT concentrations were measured. Tissue derived from control patients (N = 17) with high cTnT concentrations (≥0.32 ng/ml) and RIPC patients (N = 18) with low cTnT (≤0.32 ng/ml) was subjected to gelatin zymography to quantify MMP-2/9 activities.
RESULTS: In cardiac biopsies obtained before CPB, activities of MMP-2/9 were attenuated in the RIPC group (MMP-2: Control, 1.13 ± 0.13 a.u.; RIPC, 0.71 ± 0.12 a.u.; P < 0.05. MMP-9: Control, 1.50 ± 0.16 a.u.; RIPC, 0.87 ± 0.14 a.u.; P < 0.01), while activities of the pro-MMPs were not altered (P > 0.05). In cardiac biopsies taken after CPB activities of pro- and active MMP-2/9 were not different between the groups (P > 0.05). Spearman's rank tests showed that MMP-2/9 activities in cardiac tissue obtained before CPB were positively correlated with postoperative cTnT serum levels (MMP-2, P = 0.016; MMP-9, P = 0.015).
CONCLUSIONS: Activities of MMP-2/9 in cardiac tissue obtained before CPB are attenuated by RIPC and are positively correlated with serum concentrations of cTnT. MMPs may represent potential targets for RIPC mediated cardioprotection.
TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00877305.
The question of whether most gliomas are infected with human cytomegalovirus (HCMV) has been under dispute for more than 10 years. We recently reported our failure to detect HCMV in gliomas in Neuro-Oncology.1 Our article was accompanied by 2 related editorials,2,3 one of which boldly criticized our approach.3 Instead of fighting a petty, ivory tower dispute, we would like to lobby for a serious collaborative approach to providing conclusive evidence on the presence of HCMV in glioma (and other cancers). Since we developed the concept of oncomodulation (ie, that HCMV …
Telecommunications companies traditionally offer several tariffs from which their customers can choose the tariff that best suits their preferences. Yet, customers sometimes make choices that are not optimal for them because they do not minimize their bill for a certain usage amount. We show in this paper that companies should be very concerned about choices in which customers pick tariffs that are too small for them because they lead to a significant increase in customers churn. In contrast, this is not the case if customers choose tariffs that are too big for them. The reason is that in particular flat-rates provide customers with the additional benefit that they guarantee a constant bill amount that consumption can be enjoyed more freely because all costs are already accounted for.
In a recent article of major importance (2013), Tijmen Pronk has treated the accentuation of l-participles of the type neslъ in western South Slavic. Pronk points out correctly that Dybo’s law did not shift the accent onto final jers, e.g. in *kòņь, *bòbъ, and that the short vowel was preserved in Slovak osem < *òsmь, oheň < *ògņь, mohol < *mòglъ. Contrary to what Pronk claims, Slovene nę́sǝlis the phonetic reflex of *néslъ < *neslъ̀, Slovak niesol. The Slovene doublets (v)ǫ̑gǝl < *ǫ̀glь and (v)ózǝl < *ǫ̀zlъ suggest an earlier paradigm with vǫ̑- < ǫ̑- in the nom.sg. form and ó- < *ǫ̀- in the oblique cases. The vowel of ógǝnj < *ògņь also stems from the oblique cases. The expected neo-circumflex in the nom.sg. form is actually attested in rę̑bǝr < *rèbrь beside rę́bǝr with the reflex of Stang’s law from the oblique cases. There is no reason to assume that the accent was not retracted at an early stage in *neslъ̀, nor is there any reason to assume that Dybo’s law shifted the accent to the final jer in *dòbrъ and *sèdmь, as Pronk claims.
Although it is a generally acknowledged fact that Neo-Latin consists of a set of linguistic varieties, there is a short supply of research into its linguistic diversification, especially in non-literary texts. One of the characteristical text classes within Neo-Latin tradition are canonical visitations, a special type of ecclesiastical administrative texts, produced extensively after the Council of Trent in all parts of Europe that had Roman Catholic hierarchical structures. The present paper analyses the language of three canonical visitations written in 18th century Diocese of Senj and Modruš (Krbava) and tries to recognise linguistic peculiarities that could prove to be distinguishing properties for canonical visitations and similar texts.
Croatian negative indefinite expressions, or the so-called ni-words, are complex forms made by adding the prefix ni- to simple forms of indefinite pronouns. The Croatian standard norm prescribes that in prepositional phrases involving negative idefinite pronouns (the so-called ni-pronouns), the negative element ni should be separated from the pronoun and put in front of the preposition. However, in everyday communication one may often notice the use of the word order P + negative indefinite pronoun, and this word order has also made its way into newspapers and other media. This paper attempts to determine whether there is a significant difference in meaning between the order ni + P + indefinite pronoun and the order P + negative indefinite pronoun to account for such a change in language. We also analyze the frequency of use of these two different word orders in the Croatian National Corpus, examining eleven most frequent prepositions and six simple indefinite pronouns.
Obligatory control refers to the relation of obligatory coreference between one of the arguments in the matrix clause and an unexpressed argument of the subordinate infinitive. This paper provides examples of subject and object control in Croatian that reveal significant differences between these two constructions. Subject control is understood as a purely syntactic relation, while the analysis of object control requires the introduction of semantic macroroles. The two constructions are therefore based on different basic principles, which results in various asymmetries with regard to restrictions on possible syntactic realizations. Moreover, the limitations on scope interpretation of temporal adverbs resulting from word order changes in object control constructions suggest that the two verbs in object control might form a tighter unit than those in subject control constructions.
The paper considers the interdependence between word order, congruence and formal cases – the means which, together with lexical meaning and formal class markers, explicate the concrete syntactic relations in a sentence. There are languages (including the Slavic ones) in whose structure congruence is very important. They may or may not possess formal cases. Even if they have no formal cases their word order is relatively free due to the compensatory role of congruence, which is often, but not always, able to eliminate potential ambiguity in the sentence, assisted to a certain extent by animacy, definiteness, pronoun duplicates of the objects and extra-linguistic knowledge (and Modern Bulgarian is good enough to illustrate this). At the same time, even in congruence languages with formal cases there are strict word order rules. In both kinds of congruence languages the violation of these rules can make a sentence utterly unintelligible (the last is exemplified by a couple of lines from Spanish and Ukrainian poetry).
The article gives an overview of the most important linguistic publications on the Burgenland Croatian dialects so far and concludes that our picture of these dialects is still far from complete. Two examples are given of unsolved questions that illustrate why a more complete picture than we have at the moment is necessary. The author wishes to point out that good quality linguistic fieldwork in this region deserves higher priority than it is given now, especially since the dialects are dying out so fast.
The article analyzes the accentuation of western South Slavic l-participles of verbal stems ending in an occlusive that are formed by adding the formant *-l- directly to the stem, e.g. *nes-lъ, Croatian nȅsao, Slovene nesel. Data from Slovene, Čakavian, Kajkavian and Štokavian dialects are compared and discussed against the background of late Proto-Slavic and early dialectal accentual and phonological changes. The operation of accentological changes such as Dybo’s law, Stang’s law and the rise of the neocircumflex, as well as the reduction of weak jers caused alternations in tone, vowel-length and position of the ictus. These alterations could be analogically eliminated or extended at different times and in different areas during the linguistic history of western South Slavic, thus causing the rise of some of the earliest isoglosses in the area in which western South Slavic is spoken.
Background & Aims: Simeprevir is an oral, once-daily inhibitor of hepatitis c virus (HCV) protease NS3/4A. We investigated the safety and efficacy of simeprevir with peg-interferon α-2a and ribavirin (PR) in a randomized, double-blind, placebo-controlled, phase 3 trial of patients with HCV genotype 1 infection who relapsed after previous interferon-based therapy.
Methods: Patients were assigned randomly (2:1) to groups given simeprevir (150 mg, once daily) and PR (n = 260) or placebo and PR (n = 133) for 12 weeks. Patients then were given PR alone for 12 or 36 weeks (simeprevir group, based on response-guided therapy criteria) or 36 weeks (placebo group).
Results: Simeprevir and PR was significantly superior to placebo and PR; rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were 79.2% vs 36.1%, respectively (43.8% difference; 95% confidence interval, 34.6–53.0; P < .001). Among patients given simeprevir, 92.7% met the response-guided therapy criteria and were eligible to complete PR at week 24; of these, 83.0% achieved SVR12. HCV RNA was undetectable at week 4 in 77.2% of patients given simeprevir and 3.1% given placebo. On-treatment failure and relapse rates were lower among patients given simeprevir and PR than those given placebo and PR (3.1% vs 27.1%, and 18.5% vs 48.4%, respectively). Patients given simeprevir did not have adverse events beyond those that occurred in patients given PR alone. Most adverse events were grades 1/2; the prevalence of anemia and rash was similar in both groups. Patients in both groups reported similar severity of fatigue and functional impairments during the study, but duration was reduced among patients given simeprevir.
Conclusions: In a phase 3 trial of patients who had relapsed after interferon-based therapy, the addition of simeprevir to PR was generally well tolerated, with an SVR12 rate of 79.2%. Most patients (92.7%) receiving simeprevir were able to shorten therapy to 24 weeks. ClinicalTrials.gov number: NCT01281839.
In many markets, design is one of the key factors in determining a product’s success. The present research offers insights into the role of design for the success of cars, and offers procedures to measure the quality of the designs objectively. The authors show that visual design plays a major role in a product’s success in the automobile market. In the study, two visual design aspects were already sufficient to significantly improve traditional sales forecasting models for cars. Visual prototypicality and visual complexity both had a positive impact on sales, and designs that were perceived as both prototypical and complex were the ones that displayed the best results. Most design evaluation used to be based on subjective measures, but the researcher applied a new, objective procedure to measure prototypicality and complexity. While the latter was detected by the disk space needed by the compressed image file, the new approach for measuring prototypicality was even more sophisticated. It relied on the technique of image morphing. Morphing is a technique that allows the construction of a visual synthesis – or average picture – from a number of individual pictures. Once a car morph is developed, one can determine the visual similarity of different car models to the morph in order to obtain its prototypicality. In principle, this procedure can be automated completely, and including a large number of versions is possible. These measures therefore seem suitable for supporting design decision processes in practice.
OBJECTIVES: Outcome of aortic valve replacement may be influenced by the choice of bioprosthesis. Pericardial heart valves are described to have a favourable haemodynamic profile compared with porcine valves, although the clinical notability of this finding is still controversially debated. Herein, we compared the long-term results of two commonly implanted bioprosthesis at a single centre.
METHODS: All consecutive patients undergoing isolated aortic valve replacement with either a Carpentier-Edwards Magna pericardial prosthesis or a Medtronic Mosaic porcine prosthesis between 2002 and 2008 were analysed regarding preoperative characteristics, short- and long-term survival, valve-related complications and echocardiographic findings.
RESULTS: The Medtronic Mosaic was implanted in 163 patients and the Carpentier-Edwards Magna in 295 patients. The sizes of implanted valves were 22.4 ± 1.5 mm for the Mosaic and 21.8 ± 1.8 mm for the Magna (P = 0.001). The long-term survival rate was 76 and 56% after 5 and 10 years for the Medtronic Mosaic, which was comparable with the Carpentier-Edwards Magna (77 and 57%; P = 0.92). Overall long-term survival was comparable with an age- and sex-matched Austrian general population for both groups. Valve-related adverse events were similar between groups. The postoperative mean transvalvular gradient was significantly increased in the Mosaic group (24 ± 9 mmHg vs 17 ± 7 mmHg; P < 0.001).
CONCLUSIONS: Both types of aortic bioprostheses offer excellent results after isolated aortic valve replacement. Despite relevant differences in gradients, long-term survival was comparable with the expected normal survival for both bioprostheses. Patients with a porcine heart valve had a higher postoperative transvalvular gradient.
The paper is aimed at contributing to an empirically grounded understanding of the psychosocial dynamics that underlie the relation between heteronormative images of masculinity, internalized heterosexism and health behavior of gay men in the global North. It is based on a qualitative interview study that focuses on the consequences of the internalization of dominant images of masculinity for the identity constructions of gay men and their HIV-related sexual risk behavior in Germany. In the paper it will be argued that 1) the tension between the authoritative image of masculinity that is determined by heteronormative discourses one the one hand and the gendered self-image that is shaped and threatened by connotations of a non-masculine homosexuality on the other constitutes a decisive issue of gay identity constructions, 2) a higher sexual risk behavior can be understood as a possible consequence of the internalization of masculine images and its impact on the self-esteem, if the self-image does not match the male ideal, and 3) this may include a paradoxical desire for the imagined masculinity that is experienced as violent with regard to one’s own psychodynamics. Finally, perspectives on gay masculinities that may transgress dominant heteronormative modes of subjectification are discussed.
CD4+CD25+ regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of the CD4 molecule that is not recognized by other anti-CD4 mAbs. We found that, due to this special epitope binding, BT-061 induces a unique phosphorylation of T-cell receptor complex-associated signaling molecules. This is sufficient to activate the function of Tregs without activating effector T cells. Furthermore, BT-061 does not induce the release of pro-inflammatory cytokines. These results demonstrate that BT-061 stimulation via the CD4 receptor is able to induce T-cell receptor-independent activation of Tregs. Selective activation of Tregs via CD4 is a promising approach for the treatment of autoimmune diseases where insufficient Treg activity has been described. Clinical investigation of this new approach is currently ongoing.
Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage.
Generating functionals may guide the evolution of a dynamical system and constitute a possible route for handling the complexity of neural networks as relevant for computational intelligence.We propose and explore a new objective function, which allows to obtain plasticity rules for the afferent synaptic weights. The adaption rules are Hebbian, self-limiting, and result from the minimization of the Fisher information with respect to the synaptic flux. We perform a series of simulations examining the behavior of the new learning rules in various circumstances.The vector of synaptic weights aligns with the principal direction of input activities, whenever one is present. A linear discrimination is performed when there are two or more principal directions; directions having bimodal firing-rate distributions, being characterized by a negative excess kurtosis, are preferred. We find robust performance and full homeostatic adaption of the synaptic weights results as a by-product of the synaptic flux minimization. This self-limiting behavior allows for stable online learning for arbitrary durations.The neuron acquires new information when the statistics of input activities is changed at a certain point of the simulation, showing however, a distinct resilience to unlearn previously acquired knowledge. Learning is fast when starting with randomly drawn synaptic weights and substantially slower when the synaptic weights are already fully adapted.
Polo-like kinase 1 regulates the stability of the mitotic centromere-associated kinesin in mitosis
(2014)
Proper bi-orientation of chromosomes is critical for the accurate segregation of chromosomes in mitosis. A key regulator of this process is MCAK, the mitotic centromere-associated kinesin. During mitosis the activity and localization of MCAK are regulated by mitotic key kinases including Plk1 and Aurora B. We show here that S621 in the MCAK’s C-terminal domain is the major phosphorylation site for Plk1. This phosphorylation regulates MCAK’s stability and facilitates its recognition by the ubiquitin/proteasome dependent APC/CCdc20 pathway leading to its D-box dependent degradation in mitosis. While phosphorylation of S621 does not directly affect its microtubule depolymerising activity, loss of Plk1 phosphorylation on S621 indirectly enhances its depolymerization activity in vivo by stabilizing MCAK, leading to an increased level of protein. Interfering with phosphorylation at S621 causes spindle formation defects and chromosome misalignments. Therefore, this study suggests a new mechanism by which Plk1 regulates MCAK: by regulating its degradation and hence controlling its turnover in mitosis.
Objective: To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy.
Materials and methods: For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival.
Results: In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p = 0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (p < 0.01) but not with distant metastases.
Conclusions: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.
Late stage cancer is often associated with reduced immune recognition and a highly immunosuppressive tumor microenvironment. The presence of tumor infiltrating lymphocytes (TILs) and specific gene-signatures prior to treatment are linked to good prognosis, while the opposite is true for extensive immunosuppression. The use of adenoviruses as cancer vaccines is a form of active immunotherapy to initialise a tumor-specific immune response that targets the patient’s unique tumor antigen repertoire. We report a case of a 68-year-old male with asbestos-related malignant pleural mesothelioma who was treated in a Phase I study with a granulocyte-macrophage colony‑stimulating factor (GM-CSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in prominent infiltration of CD8C lymphocytes to tumor, marked induction of systemic antitumor CD8C T-cells and induction of Th1- type polarization in the tumor. These results indicate that ONCOS-102 treatment sensitizes tumors to other immunotherapies by inducing a T-cell positive phenotype to an initially T-cell negative tumor.
Response to Kriticos et al.
(2014)
Various aspects of uncertainty have become topical in pest risk modelling discussions. A recent contribution to the literature sought to explore the effect of taxonomic uncertainty on modelled pest risk. The case study involved a high profile plant pathogen Puccinia psidii, which causes a major disease of plants within the Myrtaceae family. Consequently, the results and recommendations may attract a wide range of interest in the biosecurity and pest risk modelling communities. We found the study by Elith et al. (2013) included a number of methodological issues that limit some of the specific and general conclusions reached in the paper. We discuss these issues and the ensuing implications for biosecurity management. We also draw attention to the need for pest risk modellers and biosecurity managers to find ways to communicate more effectively. We urge modellers and managers alike to develop a better understanding of the challenges and limitations of modelling species potential distributions across novel climates, and to be able to appreciate the meanings and limitations of models framed in different ways.
This dataset represents a registry of species that are not native but recorded to live in the wild of at least one of the four countries that comprise the Two Seas Area, i.e. Great Britain, France, Belgium and the Netherlands. For each of the 6,661 species, subspecies and hybrids listed, we provide detailed information on its status in each country, taxonomic affiliation and environment inhabited. The data were collected by review of 36 web- and print-based sources over an eight-month period. Further systematic scanning of three of the most relevant scientific journals, i.e. Neobiota, Aquatic Invasions and BioInvasions Records, recovered 19 additional relevant publications from which information was included in the registry. As a result, the registry will serve as a basis for developing effective, cross-boundary strategies to manage and control non-native species, which can have severe ecological and economic impacts. The registry can further be used as a general reference for both scientists and practitioners, as well as a tool to assess reliability and comprehensiveness of other well-known databases such as the DAISIE portal.
The article reviews distribution records of Deroceras invadens (previously called D. panormitanum and D. caruanae), adding significant unpublished records from the authors’ own collecting, museum samples, and interceptions on goods arriving in the U.S.A. By 1940 D. invadens had already arrived in Britain, Denmark, California, Australia and probably New Zealand; it has turned up in many further places since, including remote oceanic islands, but scarcely around the eastern Mediterranean (Egypt and Crete are the exceptions), nor in Asia. Throughout much of the Americas its presence seems to have been previously overlooked, probably often being mistaken for D. laeve. New national records include Mexico, Costa Rica, and Ecuador, with evidence from interceptions of its presence in Panama, Peru, and Kenya. The range appears limited by cold winters and dry summers; this would explain why its intrusion into eastern Europe and southern Spain has been rather slow and incomplete. At a finer geographic scale, the occurrence of the congener D. reticulatum provides a convenient comparison to control for sampling effort; D. invadens is often about half as frequently encountered and sometimes predominates. Deroceras invadens is most commonly found in synanthropic habitats, particularly gardens and under rubbish, but also in greenhouses, and sometimes arable land and pasture. It may spread into natural habitats, as in Britain, South Africa,
Australia and Tenerife. Many identifications have been checked in the light of recent taxonomic revision, revealing that the sibling species D. panormitanum s.s. has spread much less extensively. A number of published or online records, especially in Australia, have turned out to be misidentifications of D. laeve.
Non-neuronal acetylcholine plays a substantial role in the human skin by influencing adhesion, migration, proliferation and differentiation of keratinocytes. These processes are regulated by the Mitogen-Activated Protein (MAP) kinase cascade. Here we show that in HaCaT keratinocytes all five muscarinic receptor subtypes are expressed, but M1 and M3 are the subtypes involved in mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to activation of the MAP kinase extracellular signal regulated kinase, together with the protein kinase Akt. The activation is fully dependent on the transactivation of the epidermal growth factor receptor (EGFR), which even appears to be the sole pathway for the muscarinic receptors to facilitate MAP kinase activation in HaCaT cells. The transactivation pathway involves a triple-membrane-passing process, based on activation of matrix metalloproteases, and extracellular ligand release; whereas phosphatidylinositol 3-kinase, Src family kinases or protein kinase C do not appear to be involved in MAP kinase activation. Furthermore, phosphorylation, ubiquitination and endocytosis of the EGF receptor after cholinergic transactivation are different from that induced by a direct stimulation with EGF, suggesting that ligands other than EGF itself mediate the cholinergic transactivation.
It has become increasingly apparent over the last decades that cooking pottery played a considerable role as a trade commodity in ancient times, yet relatively little research has yet been done on this topic for its own sake. By taking a closer look at the cooking pottery found in Priene, a small city in southern Ionia re-founded in the middle of the 4th century BCE, we want to trace some of the broader developments within the cooking wares that were used over a period of roughly 300 years. The aim is not only to outline the general shapes that were in use over this period of time, but also to register if and how these shapes correlate with the different fabrics observed in Priene so far.
The title compound, [Li2(C25H23BN4OP)2], features a centrosymmetric dimeric complex. The four-memberered Li2O2 ring is exactly planar due to symmetry. The Li atom is four-coordinated by two O atoms and by two N atoms of two different pyrazole rings. The dihedral angle between two pyrazole rings bonded to the same B atom is 45.66 (9)°. The B—N—N—Li—N—N metalla ring adopts a boat conformation. The crystal packing is stabilized by van der Waals interactions only.
The structure of the title compound, C8H16N4, which consists of four fused seven-membered rings, has been redetermined at 173 K. This redetermination corrects the orientation of two H atoms, which were located at unrealistic positions in the original room-temperature study [Murray-Rust (1974[Murray-Rust, P. (1974). J. Chem. Soc. Perkin Trans. 2, pp. 1136-1141.]). J. Chem. Soc. Perkin Trans. 2, pp. 1136–1141]. The complete molecule is generated by -42m symmetry, with one quarter of a molecule [one N atom (site symmetry m), two C atoms (one with site symmetry m and the other with site symmetry 2) and two H atoms] in the asymmetric unit. No directional interactions beyond van der Waals contacts are apparent in the crystal structure.
In the title compound, C40H76Si, the Si atom is located on a special position of site symmetry -4. Thus, there is just a quarter of a molecule in the asymmetric unit. The C=C double bonds exhibit a trans configuration. The Si atom and the tert-butyl group are located on the same side of the plane formed by the C=C double bond and its four substituents. The crystal packing shows no short contacts between the molecules and despite the low crystal density (0.980 Mg m−3), there are no significant voids in the structure.
In the title compound, C19H24N2O2, a di-Mannich base derived from 2-methylphenol and 1,3,6,8-tetraazatricyclo[4.4.1.13,8]dodecane, the imidazolidine ring adopts a twist conformation, with a twist about the ring N—C bond [C—N—C—C torsion angle = −44.34 (14)°]. The two 2-hydroxy-3-methylbenzyl groups are located in trans positions with respect to the imidazolidine fragment. The structure displays two intramolecular O—H⋯N hydrogen bonds, which each form an S(6) ring motif. In the crystal, the molecules are linked by weak C—H⋯O interactions with a bifurcated acceptor, forming a three-dimensional network.
In the title solvate, C14H12N2O·0.5C6H6, the complete benzene molecule is generated by a crystallographic inversion centre. The dihedral angle between the planes of the benzimidazole moiety and the phenol substituent is 75.28 (3)°. In the crystal, O—H⋯N hydrogen bonds link the molecules into parallel chains propagating along [100]. The molecules are further connected by C—H⋯π interactions.
Background: The invasive eel parasite Anguillicoloides crassus (syn. Anguillicola crassus) is considered one of the major causes for the decline of the European eel (Anguilla anguilla) panmictic population. It impairs the swim bladder function and reduces swimming performance of its host. The life cycle of this parasite involves different intermediate and paratenic hosts. Despite an efficient immune system of the paratenic fish hosts acting against infections with A. crassus, levels of parasitized eels remain high in European river systems. Recently, the round goby Neogobius melanostomus (Gobiidae) has become dominant in many rivers in Europe and is still spreading at a rapid pace. This highly invasive species might potentially act as an important, so far neglected paratenic fish host for A. crassus.
Methods: Based on own observations and earlier single sightings of A. crassus in N. melanostomus, 60 fresh individuals of N. melanostomus were caught in the Rhine River and examined to assess the infection levels with metazoan parasites, especially A. crassus. Glycerin preparations were used for parasite identification.
Results: The parasite most frequently found in N. melanostomus was the acanthocephalan Pomphorhynchus sp. (subadult stage) which occurred mainly encysted in the mesenteries and liver. Every third gobiid (P = 31.7%) was infected by A. crassus larvae (L3) which exclusively occurred inside the acanthocephalan cysts. No intact or degenerated larvae of A. crassus were detected elsewhere in the goby, neither in the body cavity and mesenteries nor in other organs. Affected cysts contained the acanthocephalan larvae and 1-12 (mI =3) living A. crassus larvae. Additionally, encysted larvae of the nematode Raphidascaris acus were detected in the gobies, but only in the body cavity and not inside the acanthocephalan cysts.
Conclusions: Based on our observations, we suggest that A. crassus might actively bypass the immune response of N. melanostomus by invading the cysts of acanthocephalan parasites of the genus Pomphorhynchus using them as "Trojan horses". Providing that eels prey on the highly abundant round goby and that the latter transfers viable infective larvae of A. crassus, the new paratenic host might have a strong impact on the epidemiology of A. crassus.
The late physicist Carl Sagan, whom I quote in the first part of my title, skillfully phrased the common sense view on evidence in the mature sciences. In linguistics, however, evidence has become a controversial issue, especially so when it comes to the investigation of less well studied languages. In this paper, I argue that Sagan's principle should be applied to linguistics. The growing accessibility of a wide array of experimental techniques and computational tools to analyze such data makes it feasible to back up extraordinary claims with evidence from a variety of sources. At the same time, it is in many cases possible to agree on what constitutes an ordinary claim and focus the extra effort on extraordinary claims. For non-controversial claims no more than the minimum effort to establish the claim and properly document the evidence is necessary.
Mapping is an important tool for the management of plant invasions. If landscapes are mapped in an appropriate way, results can help managers decide when and where to prioritize their efforts. We mapped vegetation with the aim of providing key information for managers on the extent, density and rates of spread of multiple invasive species across the landscape. Our case study focused on an area of Galapagos National Park that is faced with the challenge of managing multiple plant invasions. We used satellite imagery to produce a spatially explicit database of plant species densities in the canopy, finding that 92% of the humid highlands had some degree of invasion and 41% of the canopy was comprised of invasive plants. We also calculated the rate of spread of eight invasive species using known introduction dates, finding that species with the most limited dispersal ability had the slowest spread rates while those able to disperse long distances had a range of spread rates. Our results on spread rate fall at the lower end of the range of published spread rates of invasive plants. This is probably because most studies are based on the entire geographic extent, whereas our estimates took plant density into account. A spatial database of plant species densities, such as the one developed in our case study, can be used by managers to decide where to apply management actions and thereby help curtail the spread of current plant invasions. For example, it can be used to identify sites containing several invasive plant species, to find the density of a particular species across the landscape or to locate where native species make up the majority of the canopy. Similar databases could be developed elsewhere to help inform the management of multiple plant invasions over the landscape.
The deregulation of Polo-like kinase 1 is inversely linked to the prognosis of patients with diverse human tumors. Targeting Polo-like kinase 1 has been widely considered as one of the most promising strategies for molecular anticancer therapy. While the preclinical results are encouraging, the clinical outcomes are rather less inspiring by showing limited anticancer activity. It is thus of importance to identify molecules and mechanisms responsible for the sensitivity of Polo-like kinase 1 inhibition. We have recently shown that p21Cip1/CDKN1A is involved in the regulation of mitosis and its loss prolongs the mitotic duration accompanied by defects in chromosome segregation and cytokinesis in various tumor cells. In the present study, we demonstrate that p21 affects the efficacy of Polo-like kinase 1 inhibitors, especially Poloxin, a specific inhibitor of the unique Polo-box domain. Intriguingly, upon treatment with Polo-like kinase 1 inhibitors, p21 is increased in the cytoplasm, associated with anti-apoptosis, DNA repair and cell survival. By contrast, deficiency of p21 renders tumor cells more susceptible to Polo-like kinase 1 inhibition by showing a pronounced mitotic arrest, DNA damage and apoptosis. Furthermore, long-term treatment with Plk1 inhibitors induced fiercely the senescent state of tumor cells with functional p21. We suggest that the p21 status may be a useful biomarker for predicting the efficacy of Plk1 inhibition.
The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.
Predominant polarity in bipolar disorder and validation of the polarity index in a German sample
(2014)
Background: A large number of patients with bipolar disorder (BD) can be characterized by predominant polarity (PP), which has important implications for relapse prevention. Recently, Popovic et al. (EUR NEUROPSYCHOPHARM 22(5): 339¿346, 2012) proposed the Polarity Index (PI) as a helpful tool in the maintenance treatment of BD. As a numeric expression, it reflects the efficacy of drugs used in treatment of BD. In the present retrospective study, we aimed to validate this Index in a large and well characterized German bipolar sample.
Methods: We investigated 336 bipolar patients (BP) according to their PP and calculated the PI for each patient in order to prove if maintenance treatment differs according to their PP. Furthermore, we analysed whether PP is associated with demographic and clinical characteristics of BP.
Results: In our sample, 63.9% of patients fulfilled criteria of PP: 169 patients were classified as depressive predominant polarity (DPP), 46 patients as manic predominant polarity (MPP). The two groups differed significantly in their drug regime: Patients with DPP were more often medicated with lamotrigine and antidepressants, patients with MPP were more often treated with lithium, valproate, carbamazepine and first generation antipsychotics. However, patients with DPP and MPP did not differ significantly with respect to the PI, although they received evidence-based and guideline-driven treatment.
Conclusion: The reason for this negative finding might well be that for several drugs, which were used frequently, no PI value is available. Nevertheless we suggest PP as an important concept in the planning of BD maintenance treatment.
Background: In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable locoregional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Our primary goal was to assess the long-term outcome of patients with durable response to trastuzumab.
Methods: 268 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and non-progressive disease for at least 2 years under trastuzumab treatment were documented retrospectively or prospectively in the HER-OS registry, an online documentation tool, between December 2006 and September 2010 by 71 German oncology centers. The study end point was time to tumor progression.
Results: Overall, 47.1% of patients (95% confidence interval (CI): 39.9–54.1%) remained in remission for more than 5 years, while the median time to progression was 4.5 years (95% CI: 4.0–6.6 years). Lower age (<50 years) and good performance status (ECOG 0) at time of trastuzumab treatment initiation as well as complete remission after initial trastuzumab treatment were associated with longer time to progression. Interruption of trastuzumab therapy correlated with shorter time to progression.
Conclusions: HER2-positive patients, who initially respond to palliative treatment with trastuzumab, can achieve a long-term tumor remission of several years.
Oscillations play a critical role in cognitive phenomena and have been observed in many brain regions. Experimental evidence indicates that classes of neurons exhibit properties that could promote oscillations, such as subthreshold resonance and electrical gap junctions. Typically, these two properties are studied separately but it is not clear which is the dominant determinant of global network rhythms. Our aim is to provide an analytical understanding of how these two effects destabilize the fluctuation-driven state, in which neurons fire irregularly, and lead to an emergence of global synchronous oscillations. Here we show how the oscillation frequency is shaped by single neuron resonance, electrical and chemical synapses.The presence of both gap junctions and subthreshold resonance are necessary for the emergence of oscillations. Our results are in agreement with several experimental observations such as network responses to oscillatory inputs and offer a much-needed conceptual link connecting a collection of disparate effects observed in networks.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
This study investigates the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of H3K9Ac and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5-related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-α general control of amino acid synthesis (GCN5a), determining a relative decrease in total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.