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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.
D2.1. provides further elaboration of the original research design and informs about ideas for the final Volume II of bEUcitizen. It is closely connected to task 1 of work package 2: specifying various concrete tasks for the different work packages and formulating overarching questions suitable to provide substantive cohesion and integration of the overall project. The elaboration of 10 crosscutting topics (to become chapters in the “horizontal” book, D2.3.) is a first step towards this goal. Discussing these cross-cutting topics is supposed to feed, infuse and inspire the work done in the different work packages and to build cross-cutting connections between them. Themes 1-10 merge into a valuable overview of the multi-faceted research on (EU) citizenship. They access the main issues of EU-citizenship and citizenship in general from different angles and different disciplines. Taken together these contributions help to identify barriers towards EU citizenship and ways to overcome them. Each Theme formulates questions how it might feed and be fed by further information and findings in the other work packages.
D2.1. is mainly meant for internal use. Its functions are firstly to inform about preliminary ideas, eventual contributions to planned final results and secondly to make out some more of less specific guiding questions that connect the work done by the single researchers in every different work package to the project as a whole. This task implies a normative yardstick, a clear picture of what would be a "good" EU citizenship practice. Elaborating on such a normative yardstick is a meta-topic that cuts across the range of cross-cutting topics presented in this working paper.
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
Ultrafast protein dynamics are of great interest for understanding the molecular basis of biochemical function. One method to study structural changes with highest time-resolution starting in the femtosecond regime is 2D-IR spectroscopy. However its application to investigate protein dynamics both with high temporal and spatial resolution is currently limited to few biological systems with intrinsic chromophores. Spectral congestion, the contribution of many similar oscillators to the same signals, makes it difficult to draw conclusions about local structural dynamics in most other proteins.
The aim of this thesis is to extend the application of 2D-IR spectroscopy to a wider range of proteins by introducing unnatural amino acids (UAAs) with azide or nitrile groups as site-specific vibrational probes, which absorb in the free spectral window between 1800 to 3000 cm-1 by using methods from chemical biology.
In a comparative experimental study using FTIR and 2D-IR spectroscopy of single amino acids azidohomoalanine (Aha), a methionine analogue, was identified as preferred label. To demonstrate the application potential of UAAs as site-specific probes, Aha was then incorporated into different positions in a small globular protein. By using both FTIR and ultrafast 2D-IR it was shown, that indeed the local microenvironment as well as conformational fluctuations on picosecond timescale could be monitored with high spatial information. The azide moiety shows a shift of its absorption frequency depending on the polarity of its surrounding. Using this approach, different subensembles for the protein conformations with more polar and less polar environment around the vibrational probe can be distinguished.
A second major application of site-specific labels is the study of vibrational energy transfer processes (VET), predicted to be relevant for allosteric communication in protein domains such as the PDZ domain. VET can be tracked with high spatial resolution using time-resolved IR spectroscopy by exciting a localized vibrational mode and probing separate modes in a two-colour 2D-IR experiment. To extend this kind of experiment to proteins, a specific donor-acceptor pair of two UAAs was introduced. It uses an azulene moiety as donor that can be excited in the visible range but deposits the excess energy by internal conversion into the vibrational modes of the ground state. In small peptides this VET pair was applied successfully, showing a distance-dependent energy transfer induced signal for VET through covalent bonds. These findings bare great promise for the direct observation of vibrational energy flow in proteins in real-time.
Overall this thesis is the basis for extending the usability of 2D-IR spectroscopy to study structural dynamics in a wide range of proteins systems both with high temporal and spatial resolution.
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.