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This work presents an effective model for strongly interacting matter and the QCD equation of state (EoS). The model includes both hadron and quark degrees of freedom and takes into account the transition of chiral symmetry restoration as well as the deconfinement phase transition. At low temperatures T and baryonic densities ρB a hadron resonance gas is described using a SU(3)-flavor sigma-omega model and a quark phase is introduced in analogy to PNJL models for higher T and ρB. In this way, the correct asymptotic degrees of freedom are used in a wide range of T and ρB. Here, results of this model concerning the chiral and deconfinement phase transitions and thermodynamic model properties are presented. Large hadron resonance multiplicities in the transition region emphasize the importance of heavy-mass resonance states in this region and their impact on the chiral transition behavior. The resulting phase diagram of QCD matter at small chemical potentials is in line with latest lattice QCD and thermal model results.
Spinodal crumbling
(2013)
Extending a previously developed two-phase equation of state, we simulate head-on relativistic lead-lead collisions with fluid dynamics, augmented with a finite-range term, and study the effects of the phase structure on the evolution of the baryon density. For collision energies that bring the bulk of the system into the mechanically unstable spinodal region of the phase diagram, the density irregularities are being amplified significantly. We also present results for the associated clump size distribution.
We analyze hadrochemical freeze-out in central Pb+Pb collisions at CERN SPS and LHC energies. Employing the UrQMD hybrid transport model we study the effects of the final hadron/resonance expansion phase on the hadron multiplicities established at hadronization. The bulk meson yields freeze out directly at hadronization whereas the baryon-antibaryon sector is subject to significant alterations, due to annihilation and regeneration processes. We quantify the latter changes by survival factors for each species which are applied to modify the statistical model predictions for the data. The modified SM analysis recovers the hadronization points, which coincide with the recent lattice QCD predictions of the parton-hadron transition line at finite baryochemical potential.
Recent results on baryon production in relativistic heavy ion collisions show that a revision of the chemical freeze-out conditions is necessary. Particularly, there is evidence that chemical freezeout does not occur at full chemical equilibrium. We present a method to reconstruct original hadronization conditions and show that the newly found points in the T − µB plane are in very good agreement with extrapolations of the lattice QCD critical line.
This novel kind of neutron beam facility will provide 1 ns short neutron pulses with an approximately thermal energy distribution around 30 keV. The pulse repetition rate will be up to 250 kHz, the total proton number per pulse will be up to 6×1010 in the final stage, starting with a p – source current of 200 mA. A second target station will allow n – activation experiments by cw beam operation. An intense 2 MeV proton beam will drive a neutron source by the 7 Li (p,n) 7 Be reaction. The facility is under construction at the physics experimental hall of the J.W. Goethe – University. The 1m thick concrete tunnel was installed in 2009. In 2011 all rf amplifiers will be delivered and installed. Successful 200 mA proton source experiments in 2010 at a test stand will be followed by experiments on the 120 kV FRANZ terminal in 2011. The 250 kHz, 100 ns chopper in front of the rf linac is under construction, while the 2 MeV bunch compressor design was finished and the technical design of all components has started. The main accelerator cavity is under construction. First 2 MeV beam tests are expected for end of 2012.
Over-allotment arrangements are nowadays part of almost any initial public offering. The underwriting banks borrow stocks from the previous shareholders to issue more than the initially announced number of shares. This is combined with the option to cover this short position at the issue price. We present empirical evidence on the value of these arrangements to the underwriters of initial public offerings on the Neuer Markt. The over-allotment arrangement is regarded as a portfolio of a long call option and a short position in a forward contract on the stock, which is different from other approaches presented in the literature.
Given the economically substantial values for these option- like claims we try to identify benefits to previous shareholders or new investors when the company is using this instrument in the process of going public. Although we carefully control for potential endogeneity problems, we find virtually no evidence for a reduction in underpricing for firms using over-allotment arrangements. Furthermore, we do not find evidence for more pronounced price stabilization activities or better aftermarket performance for firms granting an over-allotment arrangement to the underwriting banks.
EFM Classification: 230, 410
The aim of this paper is to give a unified account of the way that German demonstrative pronouns (henceforth: D-pronouns) like der, die and das behave (a) in sentences where they receive a coreferential interpretation, and (b) in sentences where they receive a covarying interpretation because they are in some way dependent on a quantificational expression – either via direct binding or indirectly, because the value they receive varies with the value that is assigned to the variable bound by an indefinite determiner.
Aims: We have provided evidence in former studies that cytokines (IL-8, TNF alpha, LBP, TGFß) measured in blood correlate negatively with lung function in deltaF508 homozygous patients. GAP junction proteins might be of importance for the influx of blood cells into the lung. Our aim was to assess the relationship between connexin genotypes and cytokines (IL-8, TNF-alpha, LBP, TGFß) in induced sputum and serum, and lung disease.
Methods: 36 patients homozygous for deltaF508 (median age 18 y, m/f 16/20, FEV1(%) 77) were examined. Sequence analysis was performed for genes encoding GAP junction protein alpha 1 (GJA1/connexin 43) and gap junction protein alpha 4 (GJA4/connexin 37). Cytokines were assessed in serum and induced sputum (IS) by chemiluminescence (DPC Biermann, Bad Homburg, Germany) as well as leukocyte counts.
Results: DNA analysis was performed in 35 patients. Whereas GJA1 showed only one rare heterozygous synonymous SNP (rs138386744) in one patient, four common SNPs were detected in GJA4. Two were synonymous changes, but the third variant (rs41266431) predicts an amino acid substitution (GTA → valine, ATA → isoleucine) as well as the fourth SNP (rs1764391: CCC→proline, TCC→serine). For rs41266431 patients with homozygosity for the G variant had higher IL-8 levels (median: 13.3/8.0 pg/ml, p=0.07) in serum as well as leukocytes in sputum (median: 2050/421 /µl p=0.041) than those showing heterozygosity (G/A). In individuals > 30 years lung function (FEV1 41.3/84.83 % predicted, p=0.07) was worse.
Conclusion: SNP rs41266431 seems a promising candidate for further investigations, suggesting GJA4 a potential disease modifying gene.
Rating agencies state that they take a rating action only when it is unlikely to be reversed shortly afterwards. Based on a formal representation of the rating process, I show that such a policy provides a good explanation for the puzzling empirical evidence: Rating changes occur relatively seldom, exhibit serial dependence, and lag changes in the issuers’ default risk. In terms of informational losses, avoiding rating reversals can be more harmful than monitoring credit quality only twice per year.
Evaluating the quality of credit portfolio risk models is an important issue for both banks and regulators. Lopez and Saidenberg (2000) suggest cross-sectional resampling techniques in order to make efficient use of available data. We show that their proposal disregards cross-sectional dependence in resampled portfolios, which renders standard statistical inference invalid. We proceed by suggesting the Berkowitz (1999) procedure, which relies on standard likelihood ratio tests performed on transformed default data. We simulate the power of this approach in various settings including one in which the test is extended to incorporate cross-sectional information. To compare the predictive ability of alternative models, we propose to use either Bonferroni bounds or the likelihood-ratio of the two models. Monte Carlo simulations show that a default history of ten years can be sufficient to resolve uncertainties currently present in credit risk modeling.
Modeling the effects of neuronal morphology on dendritic chloride diffusion and GABAergic inhibition
(2014)
Poster presentation at the Twenty Third Annual Computational Neuroscience Meeting: CNS*2014 Québec City, Canada. 26-31 July 2014.
Gamma-aminobutyric acid receptors (GABAARs) are ligand-gated chloride (Cl−) channels which mediate the majority of inhibitory neurotransmission in the CNS. Spatiotemporal changes of intracellular Cl− concentration alter the concentration gradient for Cl− across the neuronal membrane and thus affect the current flow through GABAARs and the efficacy of GABAergic inhibition. However, the impact of complex neuronal morphology on Cl− diffusion and the redistribution of intracellular Cl− is not well understood. Recently, computational models for Cl− diffusion and GABAAR-mediated inhibition in realistic neuronal morphologies became available [1-3]. Here we have used computational models of morphologically complex dendrites to test the effects of spines on Cl− diffusion. In all dendritic morphologies tested, spines slowed down longitudinal Cl− diffusion along dendrites and decreased the amount and spatial spread of synaptically evoked Cl− changes. Spine densities of 2-10 spines/µm decreased the longitudinal diffusion coefficient of Cl− to 80-30% of its value in smooth dendrites, respectively. These results suggest that spines are able to limit short-term ionic plasticity [4] at dendritic GABAergic synapses.
Poster presentation at The Twenty Third Annual Computational Neuroscience Meeting: CNS*2014 Québec City, Canada. 26-31 July 2014: We study random strongly heterogeneous recurrent networks of firing rate neurons, introducing the notion of cohorts: groups of co-active neurons, who compete for firing with one another and whose presence depends sensitively on the structure of the input. The identities of neurons recruited to and dropped from an active cohort changes smoothly with varying input features. We search for network parameter regimes in which the activation of cohorts is robust yet easily switchable by the external input and which exhibit large repertoires of different cohorts. We apply these networks to model the emergence of orientation and direction selectivity in visual cortex. We feed these random networks with a set of harmonic inputs that vary across neurons only in their temporal phase, mimicking the feedforward drive due to a moving grating stimulus. The relationship between the phases that carries the information about the orientation of the stimulus determines which cohort of neurons is activated. As a result the individual neurons acquire non-monotonic orientation tuning curves which are characterized by high orientation and direction selectivity. This mechanism of emergence for direction selectivity differs from the classical motion detector scheme, which is based on the nonlinear summation of the time-shifted inputs. In our model these two mechanisms coexist in the same network, but can be distinguished by their different frequency and contrast dependences. In general, the mechanism we are studying here converts temporal phase sequence into population activity and could therefore be used to extract and represent also various other relevant stimulus features.
Poster presentation at 1st International Workshop on Odor Spaces.
Mice are exceptional in their ability to capture their chemical environment, mapping the olfactory world into a basic sensory representation with over one thousand different types of chemical sensors, that is, olfactory sensory neurons (OSNs). OSNs of each type converge in the olfactory bulb onto exclusive distinct physiological areas called glomeruli. The glomeruli constitute the first relay station of olfactory stimulus representation in the mouse brain. Thus, the stimulus induced glomerular input pattern spatially embodies an important part of the sensory representation in the olfactory bulb. Still, topographic organization principles (chemotopy, tunotopy) are under debate. One reason might be that investigation are, due to experimental limitations, only performed on stimuli sets in the size of one hundred odors. But this represents only a tiny snapshot of the vast amount of molecules in the olfactory world and topographic relationships might be disguised in the incomplete representation of molecular receptive ranges (MRR). Therefore we investigated the problem with the MOR18-2 glomerulus as point of reference: First we determined it's MRR. Then, based on a measurement set covering this MRR, we elucidated the topographic embedding. It shows that MOR18-2 is embedded in a hierarchy of patchy tunotopic domains.
Poster presentation: 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
Significant progress has been made over the last decade towards realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells, and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also continuously expanding cytotoxic cell lines such as NK-92 are being considered for adoptive cancer immunotherapy. High cytotoxicity of NK-92 has previously been shown against malignant cells of hematologic origin in preclinical studies, and general safety of infusion of NK-92 cells has been established in phase I clinical trials. To enhance their therapeutic utility, we genetically modified NK-92 cells to express chimeric antigen receptors (CAR) specific for tumor-associated surface antigens. Such CAR were composed of a tumor-specific scFv antibody fragment fused via hinge and transmembrane domains to intracellular signaling moieties such as CD3 zeta chain, or composite fusion molecules also containing a costimulatory protein domain in addition to CD3 zeta. For development towards clinical applications, here a codon-optimized second generation CAR was constructed that consists of an ErbB2-specific scFv antibody domain fused via a linker to a composite CD28-CD3 zeta signaling domain. GMP-compliant protocols for vector production, lentiviral transduction and expansion of a genetically modified NK-92 single cell clone (NK-92/5.28.z) were established. Functional analysis of NK-92/5.28.z cells revealed high and stable CAR expression, selective cytotoxicity against ErbB2-expressing but otherwise NK-resistant tumor cells of different origins in vitro, as well as homing to ErbB2-expressing tumors in vivo. Furthermore, antigen specificity and selective cytotoxicity of these cells were retained in vivo, resulting in antitumoral activity against subcutaneous and intracranial glioblastoma xenografts in NSG mice. Ongoing work now focuses on the development of these cells for adoptive immunotherapy of ErbB2-positive glioblastoma.
poster presentation at the 31st International Symposium on Lattice Field Theory LATTICE 2013:
We explore and compare three mixed action setups with Wilson twisted mass sea quarks and different valence quark actions: (1) Wilson twisted mass, (2) Wilson twisted mass + clover and (3) Wilson + clover. Our main goal is to reduce lattice discretization errors in mesonic spectral quantities, in particular to reduce twisted mass parity and isospin breaking.
AKUE is developed by the e-learning centre of the University of Frankfurt, studiumdigitale, and is a procedure to assure high quality levels of e-learning course design and digital media production. The name AKUE stands for the German words for analysis, concept, implementation and evaluation and describes the four phases of the process. Background of AKUE is the fact, that costs and benefits of e-learning courses are difficult to be quantified. Therefore so called procedure (or process) models are applied in order to improve the quality and effectiveness of e-learning courses. This paper presents the process and steps of AKUE and gives examples for its application.
In: conference proceedings, edulearn 2010, Barcelona 5.-7.7.2010.
In order to design and tutor online and blended learning courses, trainers and teachers need to obtain appropriate qualification. In this paper different competency models for online teaching which developed in Germany 2005 – 2008 will be addressed as well as different settings to qualify teachers and trainers appropriately. Finally the results of an evaluation of two different training settings will be presented in order to compare an in house versus a transorganisational training program.
The paper presents a study which was based on the hypothesis that wikis that are initiated bottom up by students might be used more deliberately than wikis which are introduced top down by teachers. Therefore it examines the specific effects observed in nine different wiki projects at the university of Frankfurt ranging from student wiki projects up to wikis used in seminars and as information tool for institutions.
Since 2007 the concept of open online courses came up leading to many discussions of this new format in blog posts and articles especially in the US and Canada. 2011, the first German open online course was started addressing the Future of Learning.
The article discusses the concept of open online courses, the experiences with the first German course, and gives some perspectives on further developments which partly were implemented in a new course that was just started in 2012.
Diffusion of e-learning as an innovation and economic aspects of e-learning support structures
(2012)
Meanwhile, many universities and educational institutions have implemented an e-learning center or some similar, often smaller institutional units in order to support the usage of new media in teaching and learning processes [1]. This paper addresses questions around the installation of such e-learning support structures at different levels of an institution and also looks at the diffusion of e-learning as an innovation in educational institutions.
This volume contains the abstracts of all oral and poster presentations of the international scientific conference „Sustainable Consumption – Towards Action and Impact“ held in Hamburg (Germany) on November 6th-8th 2011. This unique conference aims to promote a comprehensive academic discourse on issues concerning sustainable consumption and brings together scholars from a wide range of academic disciplines.
In modern societies, private consumption is a multifaceted and ambivalent phenomenon: it is a ubiquitous social practice and an economic driving force, yet at the same time, its consequences are in conflict with important social and environmental sustainability goals. Finding paths towards “sustainable consumption” has therefore become a major political issue. In order to properly understand the challenge of “sustainable consumption”, identify unsustainable patterns of consumption and bring forward the necessary innovations, a collaborative effort of researchers from different disciplines is needed.
Oral presentation: 23rd World Congress of the World Society of Cardio-Thoracic Surgeons. Split, Croatia. 12-15 September 2013.
Background: In the past, questions have been raised, whether an open flexible annuloplasty band can reliably prevent recurrent mitral valve regurgitation. The purpose of this study was to evaluate the durability of mitral valve repair at midterm, using the Cosgrove-Edwards annuloplasty band in a homogenic patient cohort.
Methods: From January 2004 to December 2007, 157 consecutive patients with degenerative mitral valve disease were included in the study. All had quadrangular resection of a P2 prolapse and annuloplasty with a Cosgrove-Edwards annuloplasty band. Clinical and echocardiography follow-up was complete.
Results: There was no intraoperative or 30 day mortality. After a mean follow-up of 5.0 ± 1.9 years, survival was 94.3%. At midterm, freedom from reoperations was 98.9%, freedom from thromboembolism was 97.5% and freedom from endocarditis was 99.4%. Echocardiography follow-up showed recurrent mitral valve regurgitation higher than grade 2 in two patients. Mean ejection fraction was 60.3 ± 10.2%, left atrial diameter was 42 ± 7 mm, mean gradient was 3.2 ± 1.4 mmHg, effective orifice area was 3.3 ± 1.3cm², mitral leaflet coaptation length was 7.5 ± 1.9 mm and mitral leaflet tethering height was 6.2 ± 2.3 mm.
Conclusion: Mitral valve repair using the Cosgrove annuloplasty band for degenerative mitral valve disease provides an effective and durable form of reconstruction.
Oral presentation: 23rd World Congress of the World Society of Cardio-Thoracic Surgeons. Split, Croatia. 12-15 September 2013.
Background: Partial upper sternotomy (PUS) is established less invasive approach for single and double valve surgery. Reports of aortic surgery performed through PUS are rare.
Methods: The records of 52 patients undergoing primary elective surgery on the proximal aorta through PUS between 2005 and 2011 were reviewed. Patients mean age was 57 years, 35% were in NYHA Class III or IV, 59% had recent cardiac decompensation, and 17% had pulmonary hypertension. The PUS was taken down to the 4th left intercostal space in 44 patients (85%).
Results: No conversion to full sternotomy was necessary. The aortic cross-clamp, cardiopulmonary bypass and operative times averaged 136 ± 20 min., 186 ± 36 min. and 327 ± 83 min., respectively. In eight patients, the right axillary artery was cannulated for establishing cardiopulmonary bypass; the others were cannulated centrally. All patients except one received a procedure on the ascending aorta, either replacement in 30 (58%) or reduction aortoplasty in 21 (40%). Aortic root replacement was additionally performed in 31 patients (60%), including David in 20 (38%) and Ross procedure in 6 (11.5%). The aortic arch was replaced either partially in 5 (10%) or totally in 3 (6%) patients, in moderate hypothermia employing antegrade cerebral perfusion. Additional procedures, included mitral valve repair in 15 (29%) patients and coronary grafting. Ventilation time, intensive care unit and hospital stay averaged 17 ± 12 hours, 2 ± 1, and 11 ± 9 days. Chest drainage was 470 ± 380 ml/24 hours. Permanent neurologic deficit did not occur. Wound dehiscence was observed in a single patient (2%). Thirty-day and hospital mortality were not observed.
Conclusions: Less invasive surgery on the aortic root, ascending aorta and aortic arch can be performed safely and reproducibly. Potential benefits include a minimized risk of wound dehiscence and reduced postoperative bleeding. The PUS does not compromise the quality of the operation.
Cytoprotective functions of amyloid precursor protein family members in stress signaling and aging
(2013)
Poster presentation: Molecular Neurodegeneration: Basic biology and disease pathways Cannes, France. 10-12 September 2013.
Background: The amyloid precursor protein (APP) is processed via two different metabolic pathways: the amyloidogenic and the non-amyloidogenic pathway, the latter of which leading to generation of the secreted N-terminal APP fragment sAPPα [1]. Previous studies from our group suggest that sAPPα exerts potent neuroprotective effects and inhibits stress-triggered cell death via modulation of gene expression, as well as by antagonizing different types of neurotoxic stress [2]. It was also observed that the biochemical processing of APP is downregulated during aging which in turn reduced the secretion of sAPPα [3]. Based on these observations, we have studied the potential physiological function of sAPPα/APP and APLPs (APP like proteins) on the regulation of age-associated, stress induced signaling pathways, apoptosis and senescence.
Materials and methods: SH-SY5Y, PC12, IMR90 cells were used as cellular models. Depletion of APP, APLP1 (APP like protein 1) and APLP2 (APP like protein 2) in SH-SY5Y cells was achieved by stable lentiviral knockdown. To analyze the protective function of sAPPα, we have used conditioned supernatants of wild type APP overexpressing HEK cells and recombinant His-tagged sAPPα purified from yeast. The cells were treated with sAPPα prior to the addition of different stress stimuli (MG132, epoxomicin, UV, H2O2) after which cell death, gene expression and senescence were analyzed by MTT assays, caspase activity assays, Western blots and X-Gal staining respectively.
Results: Our data show that sAPPα can antagonize premature senescence induced by repetitive short term induction of proteasomal stress in IMR-90 cells and apoptosis triggered by prolonged proteasomal stress and other death stimuli in PC12, SH-SY5Y and IMR90 cells which was accompanied by a sAPPα-dependent inhibition of the JNK stress signaling pathway. In contrast, no significant changes in cell viability and apoptosis were observed when APP knockdown cells were pretreated with sAPPα.
Conclusions: Our observations suggest that sAPPα can antagonize both apoptosis and cellular senescence and requires expression of holo-APP to mediate its cytoprotective effects. They also support the notion that the physiological function of APP is linked to modulation of neuronal and brain aging.
Network or graph theory has become a popular tool to represent and analyze large-scale interaction patterns in the brain. To derive a functional network representation from experimentally recorded neural time series one has to identify the structure of the interactions between these time series. In neuroscience, this is often done by pairwise bivariate analysis because a fully multivariate treatment is typically not possible due to limited data and excessive computational cost. Furthermore, a true multivariate analysis would consist of the analysis of the combined effects, including information theoretic synergies and redundancies, of all possible subsets of network components. Since the number of these subsets is the power set of the network components, this leads to a combinatorial explosion (i.e. a problem that is computationally intractable). In contrast, a pairwise bivariate analysis of interactions is typically feasible but introduces the possibility of false detection of spurious interactions between network components, especially due to cascade and common drive effects. These spurious connections in a network representation may introduce a bias to subsequently computed graph theoretical measures (e.g. clustering coefficient or centrality) as these measures depend on the reliability of the graph representation from which they are computed. Strictly speaking, graph theoretical measures are meaningful only if the underlying graph structure can be guaranteed to consist of one type of connections only, i.e. connections in the graph are guaranteed to be non-spurious. ...
When studying real world complex networks, one rarely has full access to all their components. As an example, the central nervous system of the human consists of 1011 neurons which are each connected to thousands of other neurons. Of these 100 billion neurons, at most a few hundred can be recorded in parallel. Thus observations are hampered by immense subsampling. While subsampling does not affect the observables of single neuron activity, it can heavily distort observables which characterize interactions between pairs or groups of neurons. Without a precise understanding how subsampling affects these observables, inference on neural network dynamics from subsampled neural data remains limited.
We systematically studied subsampling effects in three self-organized critical (SOC) models, since this class of models can reproduce the spatio-temporal activity of spontaneous activity observed in vivo. The models differed in their topology and in their precise interaction rules. The first model consisted of locally connected integrate- and fire units, thereby resembling cortical activity propagation mechanisms. The second model had the same interaction rules but random connectivity. The third model had local connectivity but different activity propagation rules. As a measure of network dynamics, we characterized the spatio-temporal waves of activity, called avalanches. Avalanches are characteristic for SOC models and neural tissue. Avalanche measures A (e.g. size, duration, shape) were calculated for the fully sampled and the subsampled models. To mimic subsampling in the models, we considered the activity of a subset of units only, discarding the activity of all the other units.
Under subsampling the avalanche measures A depended on three main factors: First, A depended on the interaction rules of the model and its topology, thus each model showed its own characteristic subsampling effects on A. Second, A depended on the number of sampled sites n. With small and intermediate n, the true A¬ could not be recovered in any of the models. Third, A depended on the distance d between sampled sites. With small d, A was overestimated, while with large d, A was underestimated.
Since under subsampling, the observables depended on the model's topology and interaction mechanisms, we propose that systematic subsampling can be exploited to compare models with neural data: When changing the number and the distance between electrodes in neural tissue and sampled units in a model analogously, the observables in a correct model should behave the same as in the neural tissue. Thereby, incorrect models can easily be discarded. Thus, systematic subsampling offers a promising and unique approach to model selection, even if brain activity was far from being fully sampled.
Two generic mechanisms for emergence of direction selectivity coexist in recurrent neural networks
(2013)
Poster presentation: Twenty Second Annual Computational Neuroscience Meeting: CNS*2013. Paris, France. 13-18 July 2013.
In the mammalian visual cortex, the time-averaged response of many neurons is maximal for stimuli moving in a particular direction. Such a direction selective response is not found in LGN, upstream of the visual processing pathway, suggesting that cortical networks play a strong role in the generation of direction selectivity. Here we investigate the mechanisms for the emergence of direction selectivity in the recurrent networks of nonlinear firing rate neurons in layer 4 of V1 receiving the input from LGN. In the model the LGN inputs are characterized by different receptive field positions, and their relative temporal phase shifts are reversed for the stimuli moving in the opposite direction. We propose that two distinct mechanisms result in the neuronal direction selective response in these recurrent networks. The first one is a result of nonlinear feed-forward summation of several time-shifted inputs. The second mechanism is based on the competition between neurons for firing in a winner-take-all regime. Both mechanisms rely on inhibitory interactions in the connectivity matrix of lateral connections, but the second one involves inhibitory loops. Typically, the first mechanism results in lower selectivity values than the second, but the time-course of acquiring direction selective response is faster for the first mechanism. Importantly, the two mechanisms have different input frequency tuning. The first mechanism, based on the nonlinear summation, result in a relatively narrow tuning curve around the preferred frequency of the stimulus in the case of the moving grating. In contrast, the direction selectivity arising from the second mechanism depends only weakly on the input frequency, i.e. has a broader tuning curve. These differences allow us to provide the recipe for identifying in experiment which of the two mechanisms is used by a given direction selective neuron. We then analyze how the statistics of the connections in the random recurrent networks affect the relative contributions from these two mechanisms and determine the distributions of the direction selectivity values. We identify the motifs in the connectivity matrix, which are required for each mechanism and show that the minimal conditions for both mechanisms are met in a very broad set of random recurrent networks with sufficiently strong inhibitory connections. Thus, we propose that these mechanisms coexist in generic recurrent networks with inhibition. Our results may account for the recent experimental observations that direction selectivity is present in dark-reared mice and ferrets [1,2]. It can also explain the emergence of direction selectivity in species lacking a spatially organized direction selectivity map.
Neuronal dynamics differs between wakefulness and sleep stages, so does the cognitive state. In contrast, a single attractor state, called self-organized critical (SOC), has been proposed to govern human brain dynamics for its optimal information coding and processing capabilities. Here we address two open questions: First, does the human brain always operate in this computationally optimal state, even during deep sleep? Second, previous evidence for SOC was based on activity within single brain areas, however, the interaction between brain areas may be organized differently. Here we asked whether the interaction between brain areas is SOC. ...
The 99th Annual Meeting of the Geologische Vereinigung (GV) and International Conference on Earth Control on Planetary Life and Environment, held in October 2009 at the Geosciences Centre of the Georg-August-Universität Göttingen, brings together researchers from all fields of Earth Sciences and beyond to shape an attractive interdisciplinary program on the geological history of Planet Earth and its control over and interaction with biological evolution, development of habitats, environmental and climate change as well as history and culture of Homo sapiens. This volume contains the abstracts of invited keynote lectures as well as all oral and poster presentations.
Meeting Abstract : Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie e.V. (GAA). 17. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie. Osnabrück, 25.-26.11.2010.
ntroduction: Several drugs require dose adjustment in patients with impaired renal function, which however, often goes undetected. Serum creatinine may be normal in patients while renal function is already reduced. The estimated GFR (eGFR) allows a more precise evaluation of the renal function. This study was carried out in a group practice for family medicine, in Frankfurt/ Main, Germany. The exploration aimed at investigating if patients with renal insufficiency were recognised and if their prescriptions were appropriate in terms of dose adjustment or contra-indications.
Methods: In patients (>65yrs) with renal insufficiency (creatinine clearance <60 ml/min), their prescribed medication was retrospectively explored (Observation period 1.1.2008 to 1.4.2009). The Cockroft-Gault formula was used as estimate for the eGFR, using a creatinine value from the patient’s charts. In 90 patients, a second eGFR could be estimated from a second creatinine value obtained within 3-6 months. The recommended dose of each prescription in the SmPC (Fachinformation“) was compared to the dose that had been actually prescribed.
Results: Out of 232 consecutively patients >65 yrs, 102 had an eGFR <60 ml/min, 16 of these had an eGFR <30 ml/min. The eGFR was closely correlated (r2=0.81) with an independent second eGFR. Out of these 102 patients, 48 had a serum creatinine level within the normal range. Renal adjustment was required in 263 of a total of 613 prescriptions. 72 prescriptions in a total of 45 patients were not appropriately adjusted (32) or prescribed despite a contraindication (40). For chronic prescriptions, metformin, ramipril, enalapril, HCTZ, and spironolactone accounted for 70% of inappropriate dosing; the magnitude of misdosing was 1.5 to 4 fold (median 2). 9 temporary prescriptions (of a total of 60 prescriptions) in 8 patients were not adjusted (cefuroxim, cefpodoxim, levofloxacin). We could not prove that patients with normal serum creatinine had a higher rate of inappropriate dosing than those with already elevated creatinine.
Discussion and conclusion: In this GP practice, we have demonstrated a considerable prevalence of inappropriate dosing in patients with impaired renal function. It remains to be elucidated whether surveillance of appropriate dosing in renal impairment can be optimized e.g. with CPOE.
Background: After induction of DNA double strand breaks (DSBs), the DNA damage response (DDR) is activated. One of the earliest events in DDR is the phosphorylation of serine 139 on the histone variant H2AX (gH2AX) catalyzed by phosphatidylinositol 3-kinases-related kinases. Despite being extensively studied, H2AX distribution[1] across the genome and gH2AX spreading around DSBs sites[2] in the context of different chromatin compaction states or transcription are yet to be fully elucidated.
Materials and methods: gH2AX was induced in human hepatocellular carcinoma cells (HepG2) by exposure to 10 Gy X-rays (250 kV, 16 mA). Samples were incubated 0.5, 3 or 24 hours post irradiation to investigate early, intermediate and late stages of DDR, respectively. Chromatin immunoprecipitation was performed to select H2AX, H3 and gH2AX-enriched chromatin fractions. Chromatin-associated DNA was then sequenced by Illumina ChIP-Seq platform. HepG2 gene expression and histone modification (H3K36me3, H3K9me3) ChIP-Seq profiles were retrieved from Gene Expression Omnibus (accession numbers GSE30240 and GSE26386, respectively).
Results: First, we combined G/C usage, gene content, gene expression or histone modification profiles (H3K36me3, H3K9me3) to define genomic compartments characterized by different chromatin compaction states or transcriptional activity. Next, we investigated H3, H2AX and gH2AX distributions in such defined compartments before and after exposure to ionizing radiation (IR) to study DNA repair kinetics during DDR. Our sequencing results indicate that H2AX distribution followed H3 occupancy and, thus, the nucleosome pattern. The highest H2AX and H3 enrichment was observed in transcriptionally active compartments (euchromatin) while the lowest was found in low G/C and gene-poor compartments (heterochromatin). Under physiological conditions, the body of highly and moderately transcribed genes was devoid of gH2AX, despite presenting high H2AX levels. gH2AX accumulation was observed in 5’ or 3’ flanking regions, instead. The same genes showed a prompt gH2AX accumulation during the early stage of DDR which then decreased over time as DDR proceeded.
Finally, during the late stage of DDR the residual gH2AX signal was entirely retained in heterochromatic compartments. At this stage, euchromatic compartments were completely devoid of gH2AX despite presenting high levels of non-phosphorylated H2AX.
Conclusions: We show that gH2AX distribution ultimately depends on H2AX occupancy, the latter following H3 occupancy and, thus, nucleosome pattern. Both H2AX and H3 levels were higher in actively transcribed compartments. However, gH2AX levels were remarkably low over the body of actively transcribed genes suggesting that transcription levels antagonize gH2AX spreading. Moreover, repair processes did not take place uniformly across the genome; rather, DNA repair was affected by genomic location and transcriptional activity. We propose that higher H2AX density in euchromaticcompartments results in high relative gH2AXconcentration soon after the activation of DDR, thus favoring the recruitment of the DNA repair machinery to those compartments. When the damage is repaired and gH2AX is removed, its residual fraction is retained in the heterochromatic compartments which are then targeted and repaired at later times.
The workshop “Transdisciplinary Research on Biodiversity, Steps towards Integrated Biodiversity Research” was organized on 14-15 November 2011 in Brussels by the German-based Institute for Social-Ecological Research (ISOE) in cooperation with the European Platform for Biodiversity Research Strategy (EPBRS) and the Belgian Biodiversity Platform.
The workshop was a follow up of the EPBRS summit “Positive Visions for Biodiversity” organized in November 2010, and its aim was to explore ways to further increase the capacities of transdisciplinary biodiversity research in Europe. It brought together researchers and experts, representatives and decision-makers from European institutions and research funding agencies, as well as members from civil society and the private sector.
Participants discussed and identified in working groups key research topics and the added value of transdisciplinary approaches for three main themes of the “Positive Visions for Biodiversity” summit:
1/ The integration of biodiversity into every part of life
2/ Values and behaviours to a more harmonious way of life
3/ Governance that is more transparent and effective and that balances global and local responsibilities.
During the final plenary panel discussion, participants highlighted recommendations for promoting transdisciplinary biodiversity research:
➢ Scientists have a role to play in raising awareness on the importance of biodiversity as a transdisciplinary issue.
➢ Environmental policy representatives at national and European level have to open up to and interact with other sectors to better advocate for global biodiversity agreements and mobilize more funding for transdisciplinary research on biodiversity.
➢ There is a need for scientists who are interested in comunicating and advocating. The biodiversity community needs people who are able to bridge between worlds, both science and advocacy, to get transdisciplinary biodiversity topics on European research agendas.
➢ Scientific academic training should provide means and opportunities to train these new professionals to become the “in-between” links. Current educational and insitutional frameworks need to be adapted to provide such training and career opportunities.
➢ Innovation should be understood in a broader sense than technology and products with market value. Research is needed on innovative ways to increase sustainable use, recycling of natural resources and learning from natural processes.
➢ The biodiversity community needs to reinforce its identity and build up larger influential groups to be able to advocate more efficiently at national and European levels.
Among the main barriers to developing and implementing an efficient transdisciplinary research on biodiversity issues, the current trends in European research agendas to focus on technological and product oriented research is particularly detrimental. Improving advocacy on biodiversity and the implementation of transdisciplinary biodiversity research will be critical for the next decade to ensure the necessary knowledge for informing political decisions.
The human immunodeficiency virus (HIV) is currently ranked sixth in the worldwide causes of death [1]. One treatment approach is to inhibit reverse transcriptase (RT), an enzyme essential for reverse transcription of viral RNA into DNA before integration into the host genome [2]. By using non-nucleoside RT inhibitors (NNRTIs) [3], which target an allosteric binding site, major side effects can be evaded. Unfortunately, high genetic variability of HIV in combination with selection pressure introduced by drug treatment enables the virus to develop resistance against this drug class by developing point mutations. This situation necessitates treatment with alternative NNRTIs that target the particular RT mutants encountered in a patient.
Previously, proteochemometric approaches have demonstrated some success in predicting binding of particular NNRTIs to individual mutants; however a structurebased approach may help to further improve the predictive success of such models. Hence, our aim is to rationalize the experimental activity of known NNRTIs against a variety of RT mutants by combining molecular modeling, long-timescale atomistic molecular dynamics (MD) simulation sampling and ensemble docking. Initial control experiments on known inhibitor-RT mutant complexes using this protocol were successful, and the predictivity for further complexes is currently being evaluated. In addition to predictive power, MD simulations of multiple RT mutants are providing fundamental insight into the dynamics of the allosteric NNRTI binding site which is useful for the design of future inhibitors. Overall, work of this type is hoped to contribute to the development of predictive efficacy models for individual patients, and hence towards personalized HIV treatment options.
Dual- or multi-target ligands have gained increased attention in the past years due to several advantages, including more simple pharmacokinetic and phamarcodynamic properties compared to a combined application of several drugs. Furthermore multi-target ligands often possess improved efficacy. We present a new approach for the discovery of dual-target ligands using aligned pharmacophore models combined with a shape-based scoring. Starting with two sets of known active compounds for each target, a number of different pharmacophore models is generated and subjected to pairwise graph-based alignment using the Kabsch-Algorithm. Since a compound may be able to bind to different targets in different conformations, the algorithm aligns pairs of pharmacophore models sharing the same features which are not necessarily at the exactly same spatial distance. Using the aligned models, a pharmacophore search on a multi-conformation-database is performed to find compounds matching both models. The potentially “dual” ligands are scored by a shape-based comparison with the known active molecules using ShaEP.
Using this approach, we performed a prospective fragment-based virtual screening for dual 5-LO/sEH inhibitors. Both enzymes play an important role in the arachidonic acid cascade and are involved in inflammatory processes, pain, cardiovascular diseases and allergic reactions. Beside several new selective inhibitors we were able to find a compound inhibiting both enzymes in low micromolar concentrations. The results indicate that the idea of aligned pharmacophore models can be successfully employed for the discovery of dual-target ligands.
Background: The rationale for gathering information from plants procuring nitrogen through symbiotic interactions controlled by a common genetic program for a sustainable biofuel production is the high energy demanding application of synthetic nitrogen fertilizers. We curated sequence information publicly available for the biofuel plant sugarcane, performed an analysis of the common SYM pathway known to control symbiosis in other plants, and provide results, sequences and literature links as an online database.
Methods: Sugarcane sequences and informations were downloaded from the nucEST database, cleaned and trimmed with seqclean, assembled with TGICL plus translating mapping method, and annotated. The annotation is based on BLAST searches against a local formatted plant Uniprot90 generated with CD-HIT for functional assignment, rpsBLAST to CDD database for conserved domain analysis, and BLAST search to sorghum's for Gene Ontology (GO) assignment. Gene expression was normalized according the Unigene standard, presented as ESTs/100 kb. Protein sequences known in the SYM pathway were used as queries to search the SymGRASS sequence database. Additionally, antimicrobial peptides described in the PhytAMP database served as queries to retrieve and generate expression profiles of these defense genes in the libraries compared to the libraries obtained under symbiotic interactions.
Results: We describe the SymGRASS, a database of sugarcane orthologous genes involved in arbuscular mycorrhiza (AM) and root nodule (RN) symbiosis. The database aggregates knowledge about sequences, tissues, organ, developmental stages and experimental conditions, and provides annotation and level of gene expression for sugarcane transcripts and SYM orthologous genes in sugarcane through a web interface. Several candidate genes were found for all nodes in the pathway, and interestingly a set of symbiosis specific genes was found.
Conclusions: The knowledge integrated in SymGRASS may guide studies on molecular, cellular and physiological mechanisms by which sugarcane controls the establishment and efficiency of endophytic associations. We believe that the candidate sequences for the SYM pathway together with the pool of exclusively expressed tentative consensus (TC) sequences are crucial for the design of molecular studies to unravel the mechanisms controlling the establishment of symbioses in sugarcane, ultimately serving as a basis for the improvement of grass crops.
In recent years, Hagedorn states have been used to explain the equilibrium and transport properties of a hadron gas close to the QCD critical temperature. These massive resonances are shown to lower h/s to near the AdS/CFT limit close to the phase transition. A comparison of the Hagedorn model to recent lattice results is made and it is found that the hadrons can reach chemical equilibrium almost immediately, well before the chemical freeze-out temperatures found in thermal fits for a hadron gas without Hagedorn states.
Direct photon emission in heavy-ion collisions is calculated within a relativistic micro+macro
hybrid model and compared to the microscopic transport model UrQMD. In the hybrid approach,
the high-density part of the collision is calculated by an ideal 3+1-dimensional hydrodynamic
calculation, while the early (pre-equilibrium-) and late (rescattering-) phase are calculated with
the transport model. Different scenarios of the transition from the macroscopic description to
the transport model description and their effects are studied. The calculations are compared to
measurements by the WA98-collaboration and predictions for the future CBM-experiment are
made.
We explore the shape and orientation of the freezeout region of non-central heavy ion collisions.
For this we fit the freezeout distribution with a tilted ellipsoid. The resulting tilt angle is compared
to the same tilt angle extracted via an azimuthally sensitive HBT analysis. This allows to access
the tilt angle experimentally, which is not possible directly from the freezeout distribution. We
also show a systematic study on the system decoupling time dependence on dNch/dh, using HBT
results from the UrQMD transport model. In this study we found that the decoupling time scales
with (dNch/dh)1/3 within each energy, but the scaling is broken across energies.
Euclidean strong coupling expansion of the partition function is applied to lattice Yang-Mills theory
at finite temperature, i.e. for lattices with a compactified temporal direction. The expansions
have a finite radius of convergence and thus are valid only for b <bc, where bc denotes the nearest
singularity of the free energy on the real axis. The accessible temperature range is thus the
confined regime up to the deconfinement transition. We have calculated the first few orders of
these expansions of the free energy density as well as the screening masses for the gauge groups
SU(2) and SU(3). The resulting free energy series can be summed up and corresponds to a glueball
gas of the lowest mass glueballs up to the calculated order. Our result can be used to fix
the lower integration constant for Monte Carlo calculations of the thermodynamic pressure via
the integral method, and shows from first principles that in the confined phase this constant is
indeed exponentially small. Similarly, our results also explain the weak temperature dependence
of glueball screening masses below Tc, as observed in Monte Carlo simulations. Possibilities and
difficulties in extracting bc from the series are discussed.
We report on the first steps of an ongoing project to add gauge observables and gauge corrections
to the well-studied strong coupling limit of staggered lattice QCD, which has been shown earlier
to be amenable to numerical simulations by the worm algorithm in the chiral limit and at finite
density. Here we show how to evaluate the expectation value of the Polyakov loop in the framework
of the strong coupling limit at finite temperature, allowing to study confinement properties
along with those of chiral symmetry breaking. We find the Polyakov loop to rise smoothly, thus
signalling deconfinement. The non-analytic nature of the chiral phase transition is reflected in the
derivative of the Polyakov loop. We also discuss how to construct an effective theory for non-zero
lattice coupling, which is valid to O(b).
Perturbation theory for non-abelian gauge theories at finite temperature is plagued by infrared
divergences which are caused by magnetic soft modes ~ g2T, corresponding to gluon fields of
a 3d Yang-Mills theory. While the divergences can be regulated by a dynamically generated
magnetic mass on that scale, the gauge coupling drops out of the effective expansion parameter
requiring summation of all loop orders for the calculation of observables. Some gauge invariant
possibilities to implement such infrared-safe resummations are reviewed. We use a scheme based
on the non-linear sigma model to estimate some of the contributions ~ g6 of the soft magnetic
modes to the QCD pressure through two loops. The NLO contribution amounts to ~ 10% of the
LO, suggestive of a reasonable convergence of the series.
The so-called sign problem of lattice QCD prohibits Monte Carlo simulations at finite baryon
density by means of importance sampling. Over the last few years, methods have been developed
which are able to circumvent this problem as long as the quark chemical potential is m=T <~1.
After a brief review of these methods, their application to a first principles determination of the
QCD phase diagram for small baryon densities is summarised. The location and curvature of the
pseudo-critical line of the quark hardon transition is under control and extrapolations to physical
quark masses and the continuum are feasible in the near future. No definite conclusions can as
yet be drawn regarding the existence of a critical end point, which turns out to be extremely quark
mass and cut-off sensitive. Investigations with different methods on coarse lattices show the lightmass
chiral phase transition to weaken when a chemical potential is switched on. If persisting on
finer lattices, this would imply that there is no chiral critical point or phase transition for physical
QCD. Any critical structure would then be related to physics other than chiral symmetry breaking.
The chiral critical surface is a surface of second order phase transitions bounding the region of
first order chiral phase transitions for small quark masses in the fmu;d;ms;mg parameter space.
The potential critical endpoint of the QCD (T;m)-phase diagram is widely expected to be part of
this surface. Since for m = 0 with physical quark masses QCD is known to exhibit an analytic
crossover, this expectation requires the region of chiral transitions to expand with m for a chiral
critical endpoint to exist. Instead, on coarse Nt = 4 lattices, we find the area of chiral transitions
to shrink with m, which excludes a chiral critical point for QCD at moderate chemical potentials
mB < 500 MeV. First results on finer Nt = 6 lattices indicate a curvature of the critical surface
consistent with zero and unchanged conclusions. We also comment on the interplay of phase
diagrams between the Nf = 2 and Nf = 2+1 theories and its consequences for physical QCD.
We report progress in our exploration of the finite-temperature phase structure of two-flavour lattice
QCD with twisted-mass Wilson fermions and a tree-level Symanzik-improved gauge action
for a temporal lattice size Nt = 8. Extending our investigations to a wider region of parameter
space we gain a global view of the rich phase structure. We identify the finite temperature transition/
crossover for a non-vanishing twisted-mass parameter in the neighbourhood of the zerotemperature
critical line at sufficiently high b . Our findings are consistent with Creutz’s conjecture
of a conical shape of the finite temperature transition surface. Comparing with NLO lattice
cPT we achieve an improved understanding of this shape.
Lattice simulations employing reweighting and Taylor expansion techniques have predicted a (m;T)-phase diagram according to general expectations, with an analytic quark-hadron crossover at m =0 turning into a first order transition at some critical chemical potential mE. By contrast, recent simulations using imgainary m followed by analytic continuation obtained a critical structure in the fmu;d;ms;T;mg parameter space favouring the absence of a critical point and first order line. I review the evidence for the latter scenario, arguing that the various raw data are not inconsistent with each other. Rather, the discrepancy appears when attempting to extract continuum results from the coarse (Nt =4) lattices simulated so far, and can be explained by cut-off effects. New (as yet unpublished) data are presented, which for Nf = 3 and on Nt = 4 confirm the scenario without a critical point. Moreover, simulations on finer Nt = 6 lattices show that even if there is a critical point, continuum extrapolation moves it to significantly larger values of mE than anticipated on coarse lattices.
We discuss the use of Wilson fermions with twisted mass for simulations of QCD thermodynamics.
As a prerequisite for a future analysis of the finite-temperature transition making use
of automatic O(a) improvement, we investigate the phase structure in the space spanned by the
hopping parameter k , the coupling b , and the twisted mass parameter m. We present results for
Nf = 2 degenerate quarks on a 163×8 lattice, for which we investigate the possibility of an Aoki
phase existing at strong coupling and vanishing m, as well as of a thermal phase transition at
moderate gauge couplings and non-vanishing m.
The QCD equation of state is not often discussed in cosmology. However, the relic density of
weakly interacting massive particles (WIMPs) depends on the entropy and the expansion rate of
the Universe when they freeze out, at a temperature in the range 400 MeV – 40GeV, where QCD
corrections are still important. We use recent analytic and lattice calculations of the QCD pressure
to produce a new equation of state suitable for use in relic density calculations. As an example,
we show that relic densities calculated by the dark matter package DarkSUSY receive corrections
of several per cent, within the observational accuracy of the Planck CMB mission, due for launch
in 2007.
I review recent developments in determining the QCD phase diagram by means of lattice simulations.
Since the invention of methods to side-step the sign problem a few years ago, a number
of additional variants have been proposed, and progress has been made towards understanding
some of the systematics involved. All available techniques agree on the transition temperature
as a function of density in the regime mq/T <~1. There are by now four calculations with signals
for a critical point, two of them at similar parameter values and with consistent results. However,
it also emerges that the location of the critical point is exceedingly quark mass sensitive. At the
same time sizeable finite volume, cut-off and step size effects have been uncovered, demanding
additional investigations with exact algorithms on larger and finer lattices before quantitative conclusions
can be drawn. Depending on the sign of these corrections, there is ample room for the
eventual phase diagram to look as expected or also quite different, with no critical point at all.
We review our knowledge of the phase diagram of QCD as a function of temperature, chemical potential and quark masses. The presence of tricritical lines at imaginary chemical potential m = i p 3 T, with known scaling behaviour in their vicinity, puts constraints on this phase diagram, especially in the case of two light flavors. We show first results in our project to determine the finite-temperature behaviour in the Nf = 2 chiral limit.
A lot of effort in lattice simulations over the last years has been devoted to studies of the QCD deconfinement transition. Most state-of-the-art simulations use rooted staggered fermions, while Wilson fermions are affected by large systematic uncertainties, such as coarse lattices or heavy sea quarks. Here we report on an ongoing study of the transition, using two degenerate flavours of nonperturbatively O(a) improved Wilson fermions. We start with Nt = 12 and 16 lattices and pion masses of 600 to 450 MeV, aiming at chiral and continuum limits with light quarks.
LatticeQCD using OpenCL
(2011)
We perform a detailed study of the adjoint static potential in the pseudoparticle approach, which is a model for SU(2) Yang-Mills theory. We find agreement with the Casimir scaling hypothesis and there is clear evidence for string breaking. At the same time the potential in the fundamental representation is linear for large separations. Our results are in qualitative agreement with results from lattice computations.
We present the status of runs performed in the twisted mass formalism with Nf =2+1+1 flavours of dynamical fermions: a degenerate light doublet and a mass split heavy doublet. The procedure for tuning to maximal twist will be described as well as the current status of the runs using both thin and stout links. Preliminary results for a few observables obtained on ensembles at maximal twist will be given. Finally, a reweighting procedure to tune to maximal twist will be described.
The pseudoparticle approach is a numericalmethod to compute path integrals without discretizing spacetime. The basic idea is to consider only those field configurations, which can be represented as a linear superposition of a small number of localized building blocks (pseudoparticles), and to replace the functional integration by an integration over the pseudoparticle degrees of freedom. In previous papers we have successfully applied the pseudoparticle approach to SU(2) Yang-Mills theory. In this work we discuss the inclusion of fermionic fields in the pseudoparticle approach. To test our method, we compute the phase diagram of the 1+1-dimensional Gross-Neveu model in the large-N limit as well as the chiral condensate in the crystal phase.
We present a numerical technique for calculating path integrals in non-compact U(1) and SU(2) gauge theories. The gauge fields are represented by a superposition of pseudoparticles of various types with their amplitudes and color orientations as degrees of freedom. Applied to Maxwell theory this technique results in a potential which is in excellent agreement with the Coulomb potential. For SU(2) Yang-Mills theory the same technique yields clear evidence of confinement. Varying the coupling constant exhibits the same scaling behavior for the string tension, the topological susceptibility and the critical temperature while their dimensionless ratios are similar to those obtained in lattice calculations.
We compute the static-light baryon spectrum with Nf = 2 flavors of sea quarks using Wilson twisted mass lattice QCD. As light valence quarks we consider quarks, which have the same mass as the sea quarks with corresponding pion masses in the range 340MeV<∼ mPS<∼ 525MeV, as well as partially quenched quarks, which have the mass of the physical s quark. We extract masses of states with isospin I = 0,1/2,1, with strangeness S = 0,−1,−2, with angular momentum of the light degrees of freedom j = 0,1 and with parity P = +,−. We present a preliminary extrapolation in the light u/d and an interpolation in the heavy b quark mass to the physical point and compare with available experimental results.
We present unambiguous evidence from lattice simulations of Nf = 3 QCD for two tricritical points in the (T;m) phase diagram at fixed imaginary m=T = ip=3 mod. 2p=3, one in the light and one in the heavy quark regime. Together with similar results in the literature for Nf = 2 this implies the existence of a chiral and of a deconfinement tricritical line at those values of imaginary chemical potentials. These tricritical lines represent the boundaries of the analytically continued chiral and deconfinement critical surfaces, respectively, which delimit the parameter space with first order phase transitions. It is demonstrated that the shape of the deconfinement critical surface is dictated by tricritical scaling and implies the weakening of the deconfinement transition with real chemical potential. A qualitatively similar effect holds for the chiral critical surface.
We perform a two-flavor dynamical lattice computation of the Isgur-Wise functions t1/2 and t3/2
at zero recoil in the static limit. We find t1/2(1) = 0.297(26) and t3/2(1) = 0.528(23) fulfilling
Uraltsev’s sum rule by around 80%. We also comment on a persistent conflict between theory and
experiment regarding semileptonic decays of B mesons into orbitally excited P wave D mesons,
the so-called “1/2 versus 3/2 puzzle”, and we discuss the relevance of lattice results in this
context.
We discuss the implementation and results of a recently developed microscopic method for calculating ion-ion interaction potentials and fusion cross-sections. The method uses the TDHF evolution to obtain the instantaneous many-body collective state using a density constraint. The ion-ion potential as well as the coordinate dependent mass are calculated from these states. The method fully accounts for the dynamical processes present in the TDHF time-evolution and provides a parameter-free way of calculating fusion cross-sections.
We study the implications on compact star properties of a soft nuclear equation of state determined from kaon production at subthreshold energies in heavy-ion collisions. On one hand, we apply these results to study radii and moments of inertia of light neutron stars. Heavy-ion data provides constraints on nuclear matter at densities relevant for those stars and, in particular, to the density dependence of the symmetry energy of nuclear matter. On the other hand, we derive a limit for the highest allowed neutron star mass of three solar masses. For that purpouse, we use the information on the nucleon potential obtained from the analysis of the heavy-ion data combined with causality on the nuclear equation of state.
We present and compare new types of algorithms for lattice QCD with staggered fermions in the limit of infinite gauge coupling. These algorithms are formulated on a discrete spatial lattice but with continuous Euclidean time. They make use of the exact Hamiltonian, with the inverse temperature beta as the only input parameter. This formulation turns out to be analogous to that of a quantum spin system. The sign problem is completely absent, at zero and non-zero baryon density. We compare the performance of a continuous-time worm algorithm and of a Stochastic Series Expansion algorithm (SSE), which operates on equivalence classes of time-ordered interactions. Finally, we apply the SSE algorithm to a first exploratory study of two-flavor strong coupling lattice QCD, which is manageable in the Hamiltonian formulation because the sign problem can be controlled.
It is widely believed that chiral symmetry is spontaneously broken at zero temperature in the strong coupling limit of staggered fermions, for any number of colors and flavors. Using Monte Carlo simulations, we show that this conventional wisdom, based on a mean-field analysis, is wrong. For sufficiently many fundamental flavors, chiral symmetry is restored via a bulk, first-order transition. This chirally symmetric phase appears to be analytically connected with the expected conformal window of manyflavor continuum QCD. We perform simulations in the chirally symmetric phase at zero quark mass for various system sizes L, and measure the torelon mass and the Dirac spectrum. We find that all observables scale with L, which is hence the only infrared length scale. Thus, the strong-coupling chirally restored phase appears as a convenient laboratory to study IR-conformality. Finally, we present a conjecture for the phase diagram of lattice QCD as a function of the bare coupling and the number of quark flavors.
We analyze the universal critical behavior at the chiral critical point in QCD with three degenerate quark masses. We confirm that this critical point lies in the universality class of the three dimensional Ising model. The symmetry of the Ising model, which is Z(2), is not directly realized in the QCD Hamiltonian. After making an ansatz for the magnetization- and energy-like operators as linear admixtures of the chiral condensate and the gluonic action, we determine several non-universal mixing and normalization constants. These parameters determine an unambiguous mapping of the critical behavior in QCD to that of the 3d-Ising model. We verify its validity by showing that the thus obtained orderparameter scales in accordance with the magnetic equation of state of the 3d-Ising model.
We explore the phase diagram of two flavour QCD at vanishing chemical potential using dynamical O(a)-improved Wilson quarks. In the approach to the chiral limit we use lattices with a temporal extent of Nt = 16 and spatial extent L = 32;48 and 64 to enable the extrapolation to the thermodynamic limit with small discretisation effects. In addition to an update on the scans at constant k, reported earlier, we present first results from scans along lines of constant physics at a pion mass of 290 MeV.We probe the transition using the Polyakov loop and the chiral condensate, as well as spectroscopic observables such as screening masses.
Pseudo-Critical Temperature and Thermal Equation of State from Nf = 2 Twisted Mass Lattice QCD
(2012)
We report about the current status of our ongoing study of the chiral limit of two-flavor QCD at finite temperature with twisted mass quarks. We estimate the pseudo-critical temperature Tc for three values of the pion mass in the range of mPS ~ 300 and 500 MeV and discuss different chiral scenarios. Furthermore, we present first preliminary results for the trace anomaly, pressure and energy density. We have studied several discretizations of Euclidean time up to Nt = 12 in order to assess the continuum limit of the trace anomaly. From its interpolation we evaluate the pressure and energy density employing the integral method. Here, we have focussed on two pion masses with mPS ~ 400 and 700 MeV.
We present a lattice QCD calculation of the heavy-light decay constants fB and fBs performed with Nf = 2 maximally twisted Wilson fermions, at four values of the lattice spacing. The decay constants have been also computed in the static limit and the results are used to interpolate the observables between the charmand the infinite-mass sectors, thus obtaining the value of the decay constants at the physical b quark mass. Our preliminary results are fB = 191(14)MeV, fBs = 243(14)MeV, fBs/ fB = 1.27(5). They are in good agreement with those obtained with a novel approach, recently proposed by our Collaboration (ETMC), based on the use of suitable ratios having an exactly known static limit.
We present first results from runs performed with Nf = 2+1+1 flavours of dynamical twisted mass fermions at maximal twist: a degenerate light doublet and a mass split heavy doublet. An overview of the input parameters and tuning status of our ensembles is given, together with a comparison with results obtained with Nf = 2 flavours. The problem of extracting the mass of the K- and D-mesons is discussed, and the tuning of the strange and charm quark masses examined. Finally we compare two methods of extracting the lattice spacings to check the consistency of our data and we present some first results of cPT fits in the light meson sector.
We analyze general convergence properties of the Taylor expansion of observables to finite chemical potential in the framework of an effective 2+1 flavor Polyakov-quark-meson model. To compute the required higher order coefficients a novel technique based on algorithmic differentiation has been developed. Results for thermodynamic observables as well as the phase structure obtained through the series expansion up to 24th order are compared to the full model solution at finite chemical potential. The available higher order coefficients also allow for resummations, e.g. Padé series, which improve the convergence behavior. In view of our results we discuss the prospects for locating the QCD phase boundary and a possible critical endpoint with the Taylor expansion method.
We present results of lattice QCD simulations with mass-degenerate up and down and mass-split strange and charm (Nf = 2+1+1) dynamical quarks using Wilson twisted mass fermions at maximal twist. The tuning of the strange and charm quark masses is performed at three values of the lattice spacing a ~ 0:06 fm, a ~ 0:08 fm and a ~ 0:09 fm with lattice sizes ranging from L ~ 1:9 fm to L ~ 3:9 fm. We perform a preliminary study of SU(2) chiral perturbation theory by combining our lattice data from these three values of the lattice spacing.
It is a long discussed issue whether light scalar mesons have sizeable four-quark components. We present an exploratory study of this question using Nf = 2+1+1 twisted mass lattice QCD. A mixed action approach ignoring disconnected contributions is used to calculate correlatormatrices consisting of mesonic molecule, diquark-antidiquark and two-meson interpolating operators with quantum numbers of the scalar mesons a0(980) (1(0++)) and k (1/2(0+)). The correlation matrices are analyzed by solving the generalized eigenvalue problem. The theoretically expected free two-particle scattering states are identified, while no additional low lying states are observed. We do not observe indications for bound four-quark states in the channels investigated.
The isospin, spin and parity dependent potential of a pair of static-light mesons is computed using Wilson twisted mass lattice QCD with two flavors of degenerate dynamical quarks. From the results a simple rule can be deduced stating, which isospin, spin and parity combinations correspond to attractive and which to repulsive forces.
A 5-gap timing RPC equipped with patterned electrodes coupled to both charge-sensitive and timing circuits yields a time accuracy of 77 ps along with a position accuracy of 38 μm. These results were obtained by calculating the straight-line fit residuals to the positions provided by a 3-layer telescope made out of identical detectors, detecting almost perpendicular cosmic-ray muons. The device may be useful for particle identification by time-of-flight, where simultaneous measurements of trajectory and time are necessary.
The QCD phase diagram as a function of temperature, T, and chemical potential for baryon
number, mB, is still unknown today, due to the sign problem, which prohibits direct Monte Carlo
simulations for non-vanishing baryon density. Investigations in models sharing chiral symmetry
with QCD predict a phase diagram, in which the transition corresponds to a smooth crossover at
zero density, but which is strengthened by chemical potential to turn into a first order transition
beyond some second order critical point. This contribution reviews the lattice evidence in favour
and against the existence of a critical point.
QCD at finite temperature and denisty remains intractable by Monte Carlo simulations for quark
chemical potentials m >∼T. It has been a long standing problem to derive effective theories from
QCD which describe the phase structure of the former with controlled errors. We propose a
solution to this problem by a combination of analytical and numerical methods. Starting from
lattice QCD with in Wilson’s formulation, we derive an effective action in terms of Polyakov
loops by means of combined strong coupling and hopping expansions. The theory correctly
reflects the centre-symmetry in the pure gauge limit and its breaking through quarks. It is valid
for heavy quarks and lattices up to Nt ∼ 6. Its sign problem can be solved and we are able to
calculate the deconfinement transition of QCD with heavy quarks for all chemical potentials.
We discuss recent applications of the partonic pQCD based cascade model BAMPS with focus on heavy-ion phenomeneology in hard and soft momentum range. The nuclear modification factor as well as elliptic flow are calculated in BAMPS for RHIC end LHC energies. These observables are also discussed within the same framework for charm and bottom quarks. Contributing to the recent jet-quenching investigations we present first preliminary results on application of jet reconstruction algorithms in BAMPS. Finally, collective effects induced by jets are investigated: we demonstrate the development of Mach cones in ideal matter as well in the highly viscous regime.
The modern phase diagram of strongly interacting matter reveals a rich structure at high-densities
due to phase transitions related to the chiral symmetry of quantum chromodynamics (QCD) and
the phenomenon of color superconductivity. These exotic phases have a significant impact on
high-density astrophysics, such as the properties of neutron stars, and the evolution of astrophysical systems as proto-neutron stars, core-collapse supernovae and neutron star mergers. Most recent pulsar mass measurements and constraints on neutron star radii are critically discussed.
Astrophysical signals for exotic matter and phase transitions in high-density matter proposed recently in the literature are outlined. A strong first order phase transition leads to the emergence of a third family of compact stars besides white dwarfs and neutron stars. The different microphysics of quark matter results in an enhanced r-mode stability window for rotating compact stars compared to normal neutron stars. Future telescope and satellite data will be used to extract signals from phase transitions in dense matter in the heavens and will reveal properties of the phases of dense QCD. Spectral line profiles out of x-ray bursts will determine the mass-radius ratio of compact stars. Gravitational wave patterns from collapsing neutron stars or neutron star mergers will even be able to constrain the stiffness of the quark matter equation of state. Future astrophysical data can therefore provide a crucial cross-check to the exploration of the QCD phase diagram with the heavy-ion program of the CBM detector at the FAIR facility.
The results of the microscopic transport calculations of -nucleus interactions within a GiBUU model are presented. The dominating mechanism of hyperon production is the strangeness exchange processes → γπ and → ΞK. The calculated rapidity spectra of Ξ hyperons are significantly shifted to forward rapidities with respect to the spectra of S = −1 hyperons. We argue that this shift should be a sensitive test for the possible exotic mechanisms of -nucleus annihilation. The production of the double Λ-hypernuclei by Ξ− interaction with a secondary target is calculated.
We study the light scalar mesons a_0(980) and kappa using N_f = 2+1+1 flavor lattice QCD. In order to probe the internal structure of these scalar mesons, and in particular to identify, whether a sizeable tetraquark component is present, we use a large set of operators, including diquark-antidiquark, mesonic molecule and two-meson operators. The inclusion of disconnected diagrams, which are technically rather challenging, but which would allow us to extend our work to e.g. the f_0(980) meson, is introduced and discussed.
Background: Undergoing systemic inflammation, the innate immune system releases excessive proinflammatory mediators, which finally can lead to organ failure. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), form the interface between bacterial and viral toxins and innate immunity. During sepsis, patients with diagnosed adrenal gland insufficiency are at high risk of developing a multiorgan dysfunction syndrome, which dramatically increases the risk of mortality. To date, little is known about the mechanisms leading to adrenal dysfunction under septic conditions. Here, we investigated the sepsis-related activation of the PRRs, cell inflammation, and apoptosis within adrenal glands.
Methods: Two sepsis models were performed: the polymicrobial sepsis model (caecal ligation and puncture (CLP)) and the LTA-induced intoxication model. All experiments received institutional approval by the Regierungspräsidium Darmstadt. CLP was performed as previously described [1], wherein one-third of the caecum was ligated and punctured with a 20-gauge needle. For LTA-induced systemic inflammation, TLR2 knockout (TLR2-/-) and WT mice were injected intraperitoneally with pure LTA (pLTA; 1 mg/kg) or PBS for 2 hours. To detect potential direct adrenal dysfunction, mice were additionally injected with adrenocorticotropic hormone (ACTH; 100 μg/kg) 1 hour after pLTA or PBS. Adrenals and plasma samples were taken. Gene expressions in the adrenals (rt-PCR), cytokine release (multiplex assay), and the apoptosis rate (TUNEL assay) within the adrenals were determined.
Results: In both models, adrenals showed increased mRNA expression of TLR2 and TLR4, various NLRs, cytokines as well as inflammasome components, NADPH oxidase subunits, and nitric oxide synthases (data not shown). In WT mice, ACTH alone had no effect on inflammation, while pLTA or pLTA/ACTH administration showed increased levels of the cytokines IL-1β, IL-6, and TNFα. TLR2-/- mice indicated no response as expected (Figure 1, left). Interestingly, surviving CLP mice showed no inflammatory adrenal response, whereas nonsurvivors had elevated cytokine levels (Figure 1, right). Additionally, we identified a marked increase in apoptosis of both chromaffin and steroid-producing cells in adrenal glands obtained from mice with sepsis as compared with their controls (Figure 2).
...
Conclusion: Taken together, sepsis-induced activation of the PRRs may contribute to adrenal impairment by enhancing tissue inflammation, oxidative stress and culminate in cellular apoptosis, while mortality seems to be associated with adrenal inflammation.
Background: Nerve injury induced protein 1 (Ninjurin 1 (Ninj1)) was first identified in Schwann cells and neurons contributing to cell adhesion and nerve regeneration. Recently, the role of Ninj1 has been linked to inflammatory processes in the central nervous system where functional repression reduced leukocyte infiltration and clinical disease activity during experimental autoimmune encephalomyelitis in mice [1]. But Ninj1 is also expressed outside the nervous system in various organs such as the liver and kidney as well as on leukocytes [2,3]. Therefore, we hypothesized that Ninj1 contributes to inflammation in general; that is, also outside the nervous system, with special interest in the pathogenesis of sepsis.
Methods: Ninj1 was repressed by transfecting HMEC-1 cells, a human dermal microvascular endothelial cell line with siRNA targeting Ninj1 (siNinj1) or a negative control (siC). Subsequently, cells were stimulated with 100 ng/ml LPS (TLR4 agonist), 3 μg/ml LTA (TLR2 agonist) or 100 n/ml poly(I:C) (TLR3 agonist) for 3 hours. The inflammatory response was analyzed by real-time PCR. In addition, transmigration of neutrophils across a HMEC-1 monolayer was measured using transwell plates (pore size 3 μm).
Results: Repression of Ninj1 by siRNA reduced Ninj1 mRNA expression in HMEC about 90% (Figure 1A). Reduced Ninj1 expression decreased neutrophil migration to 62.5% (Figure 1B) and TLR signaling. In detail, knockdown of Ninj1 significantly reduced TLR-2 and TLR-4 triggered expression of ICAM-1 and IL-6 (Figure 1C,D) while poly(I:C)-induced expression was only slightly reduced. To analyze a more specific TLR-3 target, we measured IP-10 mRNA expression, which was also significantly reduced in siNinj1-transfected cells (Figure 1E).
Conclusion: Our in vitro data strongly indicated that Ninj1 is involved in regulation of TLR signaling and therewith contributes to inflammation. In vivo experiments will clarify its impact on systemic inflammation.
8th International Conference on Nuclear Physics at Storage Rings Stori11, October 9-14, 2011 Laboratori Nazionale di Frascati, Italy.
Storage rings offer the possibility of measuring proton- and alpha-induced reactions in inverse kinematics. The combination of this approachwith a radioactive beamfacility allows, in principle, the determination of the respective cross sections for radioactive isotopes. Such data are highly desired for a better understanding of astrophysical nucleosynthesis processes like the p-process. A pioneering experiment has been performed at the Experimental Storage Ring (ESR) at GSI using a stable 96Ru beam at 9-11 AMeV and a hydrogen target. Monte-Carlo simulations of the experiment were made using the Geant4 code. In these simulations, the experimental setup is described in detail and all reaction channels can be investigated. Based on the Geant4 simulations, a prediction of the shape of different spectral components can be performed. A comparison of simulated predictions with the experimental results shows a good agreement and allows the extraction of the cross section.
Einleitung: Es wurden die Leistungen beim Verstehen im Störgeräusch von CI-Patienten mit unterschiedlichen Implantattypen verglichen. Der TEMPO+ Sprachprozessor (MED-EL, Implantat C40+) verwendet ein Mikrophon mit Kugelcharakteristik, während der ESPrit 3G Prozessor (COCHLEAR, Implantat CI24R(CA)) mit einem frontal ausgelegten Richtmikrophon ausgestattet ist.
Methode: Von den zwei untersuchten Patientengruppen (n=20) war eine mit einem C40+ Implantat (MED-EL, Innsbruck), die andere mit dem CI24RCA Implantat (Cochlear, Melbourne) versorgt. Es wurde die S0N180 Lautsprecheranordnung im Freifeld für den HSM-Test (Hochmair, Schulz und Moser, 1997) und die S0N0 Anordnung für den Oldenburger Satztest (Wagener, Kühnel und Kollmeier, 1999) verwendet. Der OLSA wurde mit festem Sprachpegel (65 dB SPL) und adaptivem Störgeräusch durchgeführt. Der HSM-Satztest wurde bei Signal-/ Rauschverhältnissen von 15 dB, 10 dB, 5 dB, 0dB sowie ohne Störgeräusch durchgeführt.
Ergebnisse: Im HSM-Satztest (S0N180) wurden signifikant bessere Leistungen beim Verstehen im Störgeräusch für die Gruppe mit dem Richtmikrophon nachgewiesen. Im Oldenburger Satztest zeigten sich keine signifikanten Unterschiede.
Schlussfolgerungen: Im Vergleich zu einem Mikrophon mit Kugelcharakteristik verbessert ein Richtmikrophon das Sprachverstehen in Situationen, in denen die Sprache frontal und der Störschall von hinten dargeboten werden.
This volume contains the proceedings of the 12th International Workshop on Termination (WST 2012), to be held February 19–23, 2012 in Obergurgl, Austria. The goal of the Workshop on Termination is to be a venue for presentation and discussion of all topics in and around termination. In this way, the workshop tries to bridge the gaps between different communities interested and active in research in and around termination. The 12th International Workshop on Termination in Obergurgl continues the successful workshops held in St. Andrews (1993), La Bresse (1995), Ede (1997), Dagstuhl (1999), Utrecht (2001), Valencia (2003), Aachen (2004), Seattle (2006), Paris (2007), Leipzig (2009), and Edinburgh (2010). The 12th International Workshop on Termination did welcome contributions on all aspects of termination and complexity analysis. Contributions from the imperative, constraint, functional, and logic programming communities, and papers investigating applications of complexity or termination (for example in program transformation or theorem proving) were particularly welcome. We did receive 18 submissions which all were accepted. Each paper was assigned two reviewers. In addition to these 18 contributed talks, WST 2012, hosts three invited talks by Alexander Krauss, Martin Hofmann, and Fausto Spoto.
The diagram-based method to prove correctness of program transformations consists of computing
complete set of (forking and commuting) diagrams, acting on sequences of standard reductions
and program transformations. In many cases, the only missing step for proving correctness of a
program transformation is to show the termination of the rearrangement of the sequences. Therefore
we encode complete sets of diagrams as term rewriting systems and use an automated tool
to show termination, which provides a further step in the automation of the inductive step in
correctness proofs.