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The asymmetric unit of the title compound, C28H42N2O5·H2O, consists of one half of the organic molecule and one half-molecule of water, both of which are located on a mirror plane which passes through the central C atoms and the hydroxyl group of the heterocyclic system. The hydroxyl group at the central ring is disordered over two equally occupied positions. The six-membered ring adopts a chair conformation, and the 2-hydroxybenzyl substituents occupy the sterically preferred equatorial positions. The aromatic rings make dihedral angles of 75.57 (9)° with the mean plane of the heterocyclic ring. The dihedral angle between the two aromatic rings is 19.18 (10)°. The molecular structure features two intramolecular phenolic O-H...N hydrogen bonds with graph-set motif S(6). In the crystal, molecules are connected via O-H...O hydrogen bonds into zigzag chains running along the a-axis direction.
Connecting narrative worlds
(2014)
The electric dipole strength distribution in 130Te has been investigated using the method of Nuclear Resonance Fluorescence. The experiments were performed at the Darmstadt High Intensity Photon Setup using bremsstrahlung as photon source and at the High Intensity -Ray Source, where quasi-monochromatic and polarized photon beams are provided. Average decay properties of 130Te below the neutron separation energy are determined. Comparing the experimental data to the predictions of the statistical model indicate, that nuclear structure effects play an important role even at sufficiently high excitation energies. Preliminary results will be presented.
Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis, and the values were consistent with those determined from the evaporation residue cross sections.
The Facility for Antiproton and Ion Research (FAIR), under construction at Darmstadt will provide intense relativistic beams of exotic nuclei at its Superconducting-FRagment Separator. High-resolution in-beam γ-ray spectroscopy will be performed in the HISPEC experiment, using the European Advanced GAmma-ray Tracking Array (AGATA). The PreSPEC-AGATA campaign is the predecessor of HISPEC and runs from 2012 to 2014 at GSI Helmholtzzentrum für Schwerionenforschung GmbH. Up to19 AGATA modules were used at GSI's F Ragment Separator in 2012. We report on the status of the experiment including preliminary results from performance commissioning.
The n_TOF facility operates at CERN with the aim of addressing the request of high accuracy nuclear data for advanced nuclear energy systems as well as for nuclear astrophysics. Thanks to the features of the neutron beam, important results have been obtained on neutron induced fission and capture cross sections of U, Pu and minor actinides. Recently the construction of another beam line has started; the new line will be complementary to the first one, allowing to further extend the experimental program foreseen for next measurement campaigns.
The production of charmonia in the antiproton-nucleus reactions at plab = 3 − 10 GeV/c is studied within the Glauber model and the generalized eikonal approximation. The main reaction channel is charmonium formation in an antiproton-proton collision. The target mass dependence of the charmonium transparency ratio allows to determine the charmonium-nucleon cross section. The polarization effects in the production of χc2 states are evaluated.
The simultaneous description of the hadronic yields, pion, kaon and proton spectra, elliptic flows and femtoscopy scales in hydrokinetic model of A+A collisions is presented at different centralities for the top RHIC and LHC energies. The hydrokinetic model is used in its hybrid version that allows one to switch correctly to the UrQMD cascade at the isochronic hypersurface which separates the cascade stage and decaying hydrodynamic one. The results are compared with pure hybrid model where hydrodynamics and hadronic cascade are matching just at the non-space-like hypersurface of chemical freeze-out. The initial conditions are based on both Glauber- and KLN- Monte-Carlo simulations and results are compared. It seems that the observables, especially femtoscopy data, prefer the Glauber initial conditions. The modification of the particle number ratios caused, in particular, by the particle annihilations at the afterburn stage is analyzed.
The HADES collaboration has searched for the anti-kaonic nuclear cluster “ppK−” in p+p collisions by its decay into pΛ. In the course of this analysis several cross checks had to be performed. This report discusses two examples thereof. In one test it was checked whether the presence of background events could introduce a bias on the applied partial wave analysis. The second item discussed here is the extraction of the total pK+Λ production cross section necessary to derive the absolute upper limit on the “ppK−” production cross section.
The study of neutron-induced reactions is of high relevance in a wide variety of fields, ranging from stellar nucleosynthesis and fundamental nuclear physics to applications of nuclear technology. In nuclear energy, high accuracy neutron data are needed for the development of Generation IV fast reactors and accelerator driven systems, these last aimed specifically at nuclear waste incineration, as well as for research on innovative fuel cycles. In this context, a high luminosity Neutron Time Of Flight facility, n_TOF, is operating at CERN since more than a decade, with the aim of providing new, high accuracy and high resolution neutron cross-sections. Thanks to the features of the neutron beam, a rich experimental program relevant to nuclear technology has been carried out so far. The program will be further expanded in the near future, thanks in particular to a new high-flux experimental area, now under construction.
We propose an effective theory of SU(3) gluonic matter where interactions between color-electric and color-magnetic gluons are constrained by the center and scale symmetries. Through matching to the dimensionally-reduced magnetic theories, the magnetic gluon condensate qualitatively changes its thermal behavior above the critical temperature. We argue its phenomenological consequences for the thermodynamics, in particular the dynamical breaking of scale invariance.
The so-called Pygmy Dipole Resonance, an additional structure of low-lying electric dipole strength, has attracted strong interest in the last years. Different experimental approaches have been used in the last decade in order to investigate this new interesting nuclear excitation mode. In this contribution an overview on the available experimental data is given.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
We review recent results on J/ψ production measured by the ALICE collaboration at the LHC. For pp collisions at √s = 7 TeV yields and spectra of inclusive and prompt J/ψ, as well as results on their polarization and the charged particle multiplicity dependence of yields are presented. Measurements of the nuclear modification factor RAA of inclusive J/ψ at mid-(|y| < 0.9) and forward-rapidities (2.5 < y < 4), covering the range to pt = 0, for centrality selected Pb-Pb collisions are discussed. Also, first results on the J/ψυ2 at forward-rapidities are shown.
During the 2011 Pb-Pb run, dedicated triggers were used by the ALICE Collaboration to enrich ultra-peripheral collisions (UPC) to measure the J/ψ production cross section and its rapidity dependence at a centre of mass energy of 2.76 TeV per nucleon pair. In this article, the ongoing studies on J/ψ photoproduction in UPC events are presented.
The neutron sensitivity of the C6D6 detector setup used at n_TOF facility for capture measurements has been studied by means of detailed GEANT4 simulations. A realistic software replica of the entire n_TOF experimental hall, including the neutron beam line, sample, detector supports and the walls of the experimental area has been implemented in the simulations. The simulations have been analyzed in the same manner as experimental data, in particular by applying the Pulse Height Weighting Technique. The simulations have been validated against a measurement of the neutron background performed with a natC sample, showing an excellent agreement above 1 keV. At lower energies, an additional component in the measured natC yield has been discovered, which prevents the use of natC data for neutron background estimates at neutron energies below a few hundred eV. The origin and time structure of the neutron background have been derived from the simulations. Examples of the neutron background for two different samples are demonstrating the important role of accurate simulations of the neutron background in capture cross-section measurements.
We report on the measurement of the inclusive Υ (1S) production in Pb–Pb collisions at √sNN = 2.76 TeV carried out at forward rapidity (2.5 < y < 4) and down to zero transverse momentum using its μ+μ−decay channel with the ALICE detector at the Large Hadron Collider. A strong suppression of the inclusive Υ (1S) yield is observed with respect to pp collisions scaled by the number of independent nucleon–nucleon collisions. The nuclear modification factor, for events in the 0–90% centrality range, amounts to 0.30 ± 0.05(stat) ± 0.04(syst). The observed Υ (1S) suppression tends to increase with the centrality of the collision and seems more pronounced than in corresponding mid-rapidity measurements. Our results are compared with model calculations, which are found to underestimate the measured suppression and fail to reproduce its rapidity dependence.
Transverse momentum spectra of π±, K± and p(p¯) up to pT = 20 GeV/c at mid-rapidity in pp, peripheral (60–80%) and central (0–5%) Pb–Pb collisions at √sNN = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pion ratios both show a distinct peak at pT ≈ 3 GeV/c in central Pb–Pb collisions. Below the peak, pT < 3 GeV/c, both ratios are in good agreement with hydrodynamical calculations, suggesting that the peak itself is dominantly the result of radial flow rather than anomalous hadronization processes. For pT > 10 GeV/c particle ratios in pp and Pb–Pb collisions are in agreement and the nuclear modification factors for π±, K± and p(p¯) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets.
Freeze-out radii extracted from three-pion cumulants in pp, p–Pb and Pb–Pb collisions at the LHC
(2014)
In high-energy collisions, the spatio-temporal size of the particle production region can be measured using the Bose–Einstein correlations of identical bosons at low relative momentum. The source radii are typically extracted using two-pion correlations, and characterize the system at the last stage of interaction, called kinetic freeze-out. In low-multiplicity collisions, unlike in high-multiplicity collisions, two-pion correlations are substantially altered by background correlations, e.g. mini-jets. Such correlations can be suppressed using three-pion cumulant correlations. We present the first measurements of the size of the system at freeze-out extracted from three-pion cumulant correlations in pp, p–Pb and Pb–Pb collisions at the LHC with ALICE. At similar multiplicity, the invariant radii extracted in p–Pb collisions are found to be 5–15% larger than those in pp, while those in Pb–Pb are 35–55% larger than those in p–Pb. Our measurements disfavor models which incorporate substantially stronger collective expansion in p–Pb as compared to pp collisions at similar multiplicity.
We report on a polarization measurement of inclusive J/ψ mesons in the di-electron decay channel at mid-rapidity at 2 < pT < 6 GeV/c in p + p collisions at √s = 200 GeV. Data were taken with the STAR detector at RHIC. The J/ψ polarization measurement should help to distinguish between different models of the J/ψ production mechanism since they predict different pT dependences of the J/ψ polarization. In this analysis, J/ψ polarization is studied in the helicity frame. The polarization parameter λθ measured at RHIC becomes smaller towards high pT , indicating more longitudinal J/ψ polarization as pT increases. The result is compared with predictions of presently available models.
The ALICE Collaboration at the LHC reports measurement of the inclusive production cross section of electrons from semi-leptonic decays of beauty hadrons with rapidity |y| < 0.8 and transverse momentum 1 < pT < 10 GeV/c, in pp collisions at √s = 2.76 TeV. Electrons not originating from semi-electronic decay of beauty hadrons are suppressed using the impact parameter of the corresponding tracks. The production cross section of beauty decay electrons is compared to the result obtained with an alternative method which uses the distribution of the azimuthal angle between heavy-flavour decay electrons and charged hadrons. Perturbative QCD predictions agree with the measured cross section within the experimental and theoretical uncertainties. The integrated visible cross section, σb→e = 3.47 ± 0.40(stat) +1.12 −1.33(sys) ± 0.07(norm) μb, was extrapolated to full phase space using Fixed Order plus Next-to-Leading Log (FONLL) calculations to obtain the total bb production ¯ cross section, σbb¯ = 130 ± 15.1(stat) +42.1 −49.8(sys) +3.4 −3.1(extr) ± 2.5(norm) ± 4.4(BR) μb.
The growing role of IT in real estate asset management – the appraisal process as a master sample
(2014)
FINANCIAL SERVICE PROVIDERS FACE SERIOUS PROBLEMS IF MANY OF THEIR CUSTOMERS LEAVE QUICKLY BECAUSE SUCH CUSTOMERS HAVE LITTLE LONG-TERM VALUE. STILL, CURRENT REPORTING PRIMARILY FOCUSES ON CURRENT PROFITABILITY THAT REPRESENTS THE SHORT-TERM VALUE OF THE CUSTOMERS. THE LONG-TERM VALUE TYPICALLY RECEIVES LITTLE ATTENTION. CUSTOMER EQUITY REPORTING PRESENTS A MEANS TO FOCUS ON THE LONG-TERM VALUE OF THE COMPANY'S CUSTOMERS. IT AVOIDS THE RISK THAT SHORT-TERM PROFITS ARE INCREASED AT THE EXPENSE OF LONG-TERM VALUE CREATION AND ITS CENTRAL METRIC, CUSTOMER EQUITY, SERVES AS AN EARLY WARNING INDICATOR FOR RISK MANAGEMENT SYSTEMS THAT FOCUS ON CUSTOMER LOSS.
Big data – more than a hype
(2014)
You reap what you sow! differences in knowledge exchange effectiveness between communication types
(2014)
FOR KNOWLEDGE-INTENSIVE ORGANIZATIONS IN THE FINANCE INDUSTRY, AN EFFECTIVE KNOWLEDGE EXCHANGE AMONG EMPLOYEES IS CRUCIAL FOR THE COMPETITIVE PERFORMANCE. THEREFORE, COMPANIES INCREASINGLY RELY ON SOCIAL MEDIA PLATFORMS TO FACILITATE COMMUNICATION AND COLLABORATION. TO ENHANCE OUR UNDERSTANDING OF SUCCESSFUL COMMUNICATION IN ENTERPRISE SOCIAL MEDIA, WE APPLY HUMAN CODING AND QUANTITATIVE ANALYSIS TO THE CONTENT AND TONE OF 15,505 ENTERPRISE MICROBLOGGING MESSAGES CREATED BY 1,166 EMPLOYEES OF AN INTERNATIONAL FINANCIAL SERVICE PROVIDER. OUR RESULTS SUGGEST THAT A MORE FACTUAL-ORIENTED COMMUNICATION TYPE BENEFITS FROM A HIGHER KNOWLEDGE EXCHANGE EFFECTIVENESS COMPARED TO A PRIMARILY SELF-DISCLOSING COMMUNICATION TYPE.
ALMOST 20% OF THE GERMAN POPULATION CURRENTLY HOLDS A CONSUMER LOAN. DESPITE ITS OBVIOUS IMPORTANCE FOR A PRIVATE HOUSEHOLD’S BALANCE SHEET, WE KNOW SURPRISINGLY LITTLE ABOUT IT. ONE PURPOSE OF THIS STUDY IS TO GIVE AN OVERVIEW OF THE GERMAN CONSUMER/INSTALLMENT LOAN MARKET. WE COMPARED FIVE WIDELY ACCEPTED DATA SOURCES AND FOUND DIFFERENCES IN THE LOAN PARTICIPATION RATE, EVEN ON AN AGGREGATED NATIONWIDE LEVEL. IN A SECOND STEP, WE TRY TO FIND REASONS FOR EXTRAORDINARY HIGH GROWTH RATES AMONG SENIORS’ DEBT PARTICIPATION RATES.
ORGANIZATIONAL MINDFULNESS (OM) SUPPORTS THE MANAGEMENT AND EMPLOYEES WORKING IN THE INCREASINGLY DYNAMIC WORK ENVIRONMENTS DRIVEN BY CLOUD COMPUTING OR MOBILE DEVICES. SPECIFICALLY, IN MINDFUL ORGANIZATIONS, SUCH AS FINANCIAL INSTITUTIONS, RELIABLE OUTCOMES ARISE FROM OM IN THE FACE OF COMPLEX INFORMATION SYSTEMS. HOWEVER, EXTANT IS RESEARCH HAS DISREGARDED THE MULTILEVEL STRUCTURE OF MINDFULNESS, ESPECIALLY THEIMPORTANCE OF MINDFUL ORGANIZING (MO) ON LOWER HIERARCHICAL LEVELS. BASED ON DATA FROM 256 USERS OF AN ORGANIZATION WIDE CLOUD-BASED DESKTOP-AS-A-SERVICE SYSTEM, WE FOUND A SIGNIFICANTLY POSITIVE INFLUENCE OF THE COMBINATION OF OM AND MO AS WELL AS DIFFERENTIAL EFFECTS FOR BOTH ON JOB PERFORMANCE.
THE WAY IN WHICH PEOPLE COMMUNICATE AFFECTS THEIR RELATIONSHIPS, SOCIAL NETWORK STRUCTURES AND ULTIMATELY THE SOCIAL CAPITAL ACQUIRED THROUGH THEIR CONNECTIONS. SOCIAL CAPITAL IS A KEY FACTOR FOR THE PERFORMANCE OF INDIVIDUALS AND ORGANIZATIONS. THEREFORE, COMPANIES IN THE FINANCIAL SERVICES INDUSTRY INCREASINGLY IMPLEMENT SOCIAL MEDIA PLATFORMS TO FACILITATE COMMUNICATION AMONG EMPLOYEES AND TO LEVERAGE THE SOCIAL CAPITAL BENEFITS. ANALYZING THE INDIVIDUAL NETWORK STRUCTURES OF DIFFERENT COMMUNICATION TYPES, WE FIND THAT A MORE SELF-DISCLOSING COMMUNICATION TYPE (“MEFORMER”) BENEFITS FROM A HIGHER EFFICACY IN BUILDING SOCIAL CAPITAL COMPARED TO A PRIMARILY FACTUAL-ORIENTED COMMUNICATION TYPE (“INFORMER”).
Customer equity reporting
(2014)
WHARTON SCHOOL OF BUSINESS AT UNIVERSITY OF PHILADELPHIA HAS JUSTLAUNCHED AN 8-WEEK ONLINE PROGRAM “STRATEGIC VALUE OF CUSTOMER RELATIONSHIPS – ONLINE” TAUGHT BY MARKETING PROFESSOR AND AUTHOR PETER FADER. HE INVITED PROFESSOR SKIERA, DIRECTOR OF THE E-FINANCE LAB, TO PHILADELPHIA TO LEARN ABOUT HIS THOUGHTS ON “CUSTOMER EQUITY REPORTING”. THIS ARTICLE SUMMARIZES SOME OF PROFESSOR FADER’S QUESTIONS AND PROFESSOR SKIERA’S REPLIES.
DIGITAL CURRENCIES ARE A GLOBALLY SPREADING PHENOMENON THAT IS FREQUENTLY AND PROMINENTLY ADDRESSED BY MEDIA, POLITICS AND ACADEMIA. WE AIM AT GIVING EMPIRICAL INSIGHTS ON WHETHER USERS’ INTEREST REGARDING DIGITAL CURRENCIES IS DRIVEN BY ITS APPEAL AS AN ASSET OR ITS UTILITY AS A CURRENCY. BASED ON OUR EVALUATION, WE FIND STRONG INDICATIONS THAT ESPECIALLY UNINFORMED USERS APPROACHING BITCOIN ARE NOT PRIMARILY INTERESTED IN AN ALTERNATIVE TRANSACTION SYSTEM, BUT SEEK TO PARTICIPATE IN AN ALTERNATIVE INVESTMENT VEHICLE.
Acute myeloid leukemia (AML) is characterized by an aberrant self-renewal of hematopoietic stem cells (HSC) and a block in differentiation. The major therapeutic challenge is the characterization of the leukemic stem cell as a target for the eradication of the disease. Until now the biology of AML-associated fusion proteins (AAFPs), such as the t(15;17)-PML/RARα, t(8;21)-RUNX1/RUNX1T1 and t(6;9)-DEK/NUP214, all able to induce AML in mice, was investigated in different models and genetic backgrounds, not directly comparable to each other. To avoid the bias of different techniques and models we expressed these three AML-inducing oncogenes in an identical genetic background and compared their influence on the HSC compartment in vitro and in vivo.
These AAFPs exerted differential effects on HSCs and PML/RARα, similar to DEK/NUP214, induced a leukemic phenotype from a small subpopulation of HSCs with a surface marker pattern of long-term HSC and characterized by activated STAT3 and 5. In contrast the established AML occurred from mature populations in the bone marrow. The activation of STAT5 by PML/RARα and DEK/NUP214 was confirmed in t(15;17)(PML/RARα) and t(6;9)(DEK/NUP214)-positive patients as compared to normal CD34+ cells. The activation of STAT5 was reduced upon the exposure to Arsenic which was accompanied by apoptosis in both PML/RARα- and DEK/NUP214-positive leukemic cells. These findings indicate that in AML the activation of STATs plays a decisive role in the biology of the leukemic stem cell. Furthermore we establish exposure to arsenic as a novel concept for the treatment of this high risk t(6;9)-positive AML.
Orientation: Publishing methodologically sound, empirically based studies in reputable accredited scientific journals are essential in order to advance knowledge and evidence-based practice in the field of industrial and organisational psychology.
Research purpose: The purpose of the research was to conduct a broad content analysis of the articles published in the South African Journal of Industrial Psychology (SAJIP) between 2004 and 2013. The study aimed to provide a descriptive overview of the most frequent content themes,published authors and institutions, research approaches, strategies, designs and analysis techniques, software packages and sample sizes in industrial and organisational (I-O) psychology utilised in the publications.
Motivation for study: The periodic analyses of published content in scholarly journals provide an index of the extent to which the publications reflect the scope of practice in a given discipline and broaden insight into the direction and relevance of research published in a journal.
Research design, approach and method: A broad systematic content analysis was conducted of 342 documented articles published in the SAJIP between 2004 and 2013. Descriptive data(frequencies and percentages) were used to report the findings.
Main findings: The publishing pattern of the SAJIP appeared to correspond with its focus and scope. Manuscripts utilising mostly cross-sectional quantitative correlational research designs with large samples (n > 201) were published in the SAJIP. The University of Johannesburg and Professor Sebastiaan (Ian) Rothmann were the largest contributors to publications between 2004 and 2013. Organisational psychology and psychometrics were the most prominent domains in I-O psychology research. Data were predominantly processed utilising SPSS.
Practical implications: The insights derived from the findings can be employed to plan future research initiatives in the field of I-O psychology.
Contribution/value-add: The findings provide valuable insight into the current status of the foci of I-O psychology research as published in the SAJIP between 2004 and 2013 and the contribution made by the SAJIP to advancing knowledge and evidence-based practice in I-O psychology.
This paper analyzes two contemporary, „third-generation“ perspectives within critical theory - Nancy Fraser’s and Axel Honneth’s - with the aim of examining the degree to which the two authors succeed in grounding the normative criteria of social critique in the perspectives of ’ordinary’ social actors, as opposed to speculative social theory. To that end, the author focuses on the influential debate between Fraser and Honneth Redistribution or Recognition? which concerns the appropriate normative foundations of a „post-metaphysical“ critical theory, and attempts to reconstruct the fundamental 29 disagreements between Fraser and Honneth over the meaning and tasks of critical theory. The author concludes that both critical theorists ultimately secure the normative foundations of critique through substantive theorizations of the social, which frame the two authors’ „reconstructions“ of the normativity of everyday social action, but argues that post-metaphysical critical theory does not have to abandon comprehensive social theory in order to be epistmologically „non-authoritarian“.
A potential clinical and etiological overlap between schizophrenia (SZ) and bipolar disorder (BD) has long been a subject of discussion. Imaging studies imply functional and structural alterations of the hippocampus in both diseases. Thus, imaging this core memory region could provide insight into the pathophysiology of these disorders and the associated cognitive deficits. To examine possible shared alterations in the hippocampus, we conducted a multi-modal assessment, including functional and structural imaging as well as neurobehavioral measures of memory performance in BD and SZ patients compared with healthy controls. We assessed episodic memory performance, using tests of verbal and visual learning (HVLT, BVMT) in three groups of participants: BD patients (n = 21), SZ patients (n = 21) and matched (age, gender, education) healthy control subjects (n = 21). In addition, we examined hippocampal resting state functional connectivity, hippocampal volume using voxel-based morphometry (VBM) and fibre integrity of hippocampal connections using diffusion tensor imaging (DTI). We found memory deficits, changes in functional connectivity within the hippocampal network as well as volumetric reductions and altered white matter fibre integrity across patient groups in comparison with controls. However, SZ patients when directly compared with BD patients were more severely affected in several of the assessed parameters (verbal learning, left hippocampal volumes, mean diffusivity of bilateral cingulum and right uncinated fasciculus). The results of our study suggest a graded expression of verbal learning deficits accompanied by structural alterations within the hippocampus in BD patients and SZ patients, with SZ patients being more strongly affected. Our findings imply that these two disorders may share some common pathophysiological mechanisms. The results could thus help to further advance and integrate current pathophysiological models of SZ and BD.
Highly promising preclinical data obtained in cultured cells and in nude mice bearing xenografts contrast with the rather modest clinical efficacy of Polo-like kinase 1 (Plk1) inhibitors. In the present study, we investigated if Plk1 might be a suitable target in hepatocellular carcinoma (HCC) and if a genetically engineered mouse tumor model that well reflects the tumor cell and micro-environmental features of naturally occurring cancers might be suitable to study anti-Plk1 therapy. Analysis of Plk1 expression in human HCC samples confirmed that HCC express much higher Plk1 levels than the adjacent normal liver tissue. Inhibition of Plk1 by an adenovirus encoding for a short hairpin RNA against Plk1 or by the small-molecule inhibitor BI 2536 reduced the viability of HCC cell lines and inhibited HCC xenograft progression in nude mice. Treatment of transforming growth factor (TGF) α/c-myc bitransgenic mice with BI 2536 during hepatocarcinogenesis reduced the number of dysplastic foci and of Ki-67-positive cells within the foci, indicating diminished tumorigenesis. In contrast, BI 2536 had no significant effect on HCC progression in the transgenic mouse HCC model as revealed by magnetic resonance imaging. Measurement of BI 2536 by mass spectrometry revealed considerably lower BI 2536 levels in HCC compared with the adjacent normal liver tissue. In conclusion, low intratumoral levels are a novel mechanism of resistance to the Plk1 inhibitor BI 2536. Plk1 inhibitors achieving sufficient intratumoral levels are highly promising in HCC treatment.
We report on posttransplant relapsed pediatric patients with B-precursor acute lymphoblastic leukemia with no further standard of care therapy who were treated with the T-cell engaging CD19/CD3-bispecific single-chain antibody construct blinatumomab on a compassionate use basis. Blast load was assessed prior to, during and after blinatumomab cycle using flow cytometry to detect minimal residual disease, quantitative polymerase chain reaction for rearrangements of the immunoglobulin or T-cell receptor genes, and bcr/abl mutation detection in one patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blinatumomab was administered as a 4-week continuous intravenous infusion at a dosage of 5 or 15 μg/m2/day. Nine patients received a total of 18 cycles. Four patients achieved complete remission after the first cycle of treatment; 2 patients showed a complete remission from the second cycle after previous reduction of blast load by chemotherapy. Three patients did not respond, of whom one patient proceeded to a second cycle without additional chemotherapy and again did not respond. Four patients were successfully retransplanted in molecular remission from haploidentical donors. After a median follow up of 398 days, the probability of hematologic event-free survival is 30%. Major toxicities were grade 3 seizures in one patient and grade 3 cytokine release syndrome in 2 patients. Blinatumomab can induce molecular remission in pediatric patients with posttransplant relapsed B-precursor acute lymphoblastic leukemia and facilitate subsequent allogeneic hematopoietic stem cell transplantation from haploidentical donor with subsequent long-term leukemia-free survival.
• Endomicroscopy is a new imaging tool for gastrointestinal endoscopy.
• Panchromoendoscopy with targeted biopsies has become the method of choice for surveillance of patients with inflammatory bowel disease.
• Endomicroscopy can be added after chromoendoscopy to clarify whether standard biopsies are still needed.
• This smart biopsy concept can increase the diagnostic yield of intraepithelial neoplasia and substantially reduce the need for biopsies.
• Endomicroscopy is still mainly used for research but clinical acceptance is increasing because of a multitude of positive studies about the diagnostic value of endomicroscopy.
The highly conserved eukaryotic process of macroautophagy (autophagy) is a non-specific bulk-degradation program critical for maintaining proper cellular homeostasis, and for clearing aged and damaged organelles. This decision is inextricably dependent upon prevailing metabolic demands and energy requirements of the cell. Soluble monomeric decorin functions as a natural tumor repressor that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered that decorin induces endothelial cell autophagy, downstream of VEGFR2. This process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted tumor suppressor gene. However, the signaling cascades responsible have remained elusive. In this report we discovered that Vps34, a class III phosphoinositide kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin triggered differential formation of Vps34/Beclin 1 complexes with concomitant dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the concurrent activation of pro-autophagic AMPK-mediated signaling cascades. Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling abrogated decorin-evoked autophagy. Collectively, these findings hint at the complexity of the underlying molecular relays necessary for decorin-evoked endothelial cell autophagy and reveal important therapeutic targets for augmenting autophagy and combatting tumor angiogenesis.
The highly conserved eukaryotic process of macroautophagy (autophagy) is a non-specific bulk-degradation program critical for maintaining proper cellular homeostasis, and for clearing aged and damaged organelles. This decision is inextricably dependent upon prevailing metabolic demands and energy requirements of the cell. Soluble monomeric decorin functions as a natural tumor repressor that antagonizes a variety of receptor tyrosine kinases. Recently, we discovered that decorin induces endothelial cell autophagy, downstream of VEGFR2. This process was wholly dependent upon Peg3, a decorin-inducible genomically imprinted tumor suppressor gene. However, the signaling cascades responsible have remained elusive. In this report we discovered that Vps34, a class III phosphoinositide kinase, is an upstream kinase required for Peg3 induction. Moreover, decorin triggered differential formation of Vps34/Beclin 1 complexes with concomitant dissolution of inhibitive Bcl-2/Beclin 1 complexes. Further, decorin inhibited anti-autophagic signaling via suppression of Akt/mTOR/p70S6K activity with the concurrent activation of pro-autophagic AMPK-mediated signaling cascades. Mechanistically, AMPK is downstream of VEGFR2 and inhibition of AMPK signaling abrogated decorin-evoked autophagy. Collectively, these findings hint at the complexity of the underlying molecular relays necessary for decorin-evoked endothelial cell autophagy and reveal important therapeutic targets for augmenting autophagy and combatting tumor angiogenesis.
The web and the social web play an increasingly important role as an information source for Members of Parliament and their assistants, journalists, political analysts and researchers. It provides important and crucial background information, like reactions to political events and comments made by the general public. The case study presented in this paper is driven by two European parliaments (the Greek and the Austrian parliament) and targets an effective exploration of political web archives. In this paper, we describe semantic technologies deployed to ease the exploration of the archived web and social web content and present evaluation results.
The World Wide Web is the largest information repository available today. However, this information is very volatile and Web archiving is essential to preserve it for the future. Existing approaches to Web archiving are based on simple definitions of the scope of Web pages to crawl and are limited to basic interactions with Web servers. The aim of the ARCOMEM project is to overcome these limitations and to provide flexible, adaptive and intelligent content acquisition, relying on social media to create topical Web archives. In this article, we focus on ARCOMEM’s crawling architecture. We introduce the overall architecture and we describe its modules, such as the online analysis module, which computes a priority for the Web pages to be crawled, and the Application-Aware Helper which takes into account the type of Web sites and applications to extract structure from crawled content. We also describe a large-scale distributed crawler that has been developed, as well as the modifications we have implemented to adapt Heritrix, an open source crawler, to the needs of the project. Our experimental results from real crawls show that ARCOMEM’s crawling architecture is effective in acquiring focused information about a topic and leveraging the information from social media.
The constantly growing amount of Web content and the success of the SocialWeb lead to increasing needs for Web archiving. These needs go beyond the pure preservationo of Web pages. Web archives are turning into “community memories” that aim at building a better understanding of the public view on, e.g., celebrities, court decisions and other events. Due to the size of the Web, the traditional “collect-all” strategy is in many cases not the best method to build Web archives. In this paper, we present the ARCOMEM (From Future Internet 2014, 6 689 Collect-All Archives to Community Memories) architecture and implementation that uses semantic information, such as entities, topics and events, complemented with information from the Social Web to guide a novel Web crawler. The resulting archives are automatically enriched with semantic meta-information to ease the access and allow retrieval based on conditions that involve high-level concepts.
Atrial fibrillation (AF) continues to be a leading cause of cerebrovascular morbidity and mortality resulting from cardioembolic stroke. Oral anticoagulation therapy has been shown to decrease the incidence of cardioembolic stroke in patients with AF by more than 50%. Appropriate use of anticoagulation with vitamin K antagonists requires precise adherence and monitoring. A number of factors that potentially induce patients' dissatisfaction reduce quality of patient life. New direct oral anticoagulants, such as the direct factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and the thrombin inhibitor dabigatran, were developed to overcome the limitations of the conventional anticoagulant drugs. However, models to optimize the benefit of therapy and to ensure that therapy can be safely continued are missing for the new oral anticoagulants. This review will briefly describe the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban with focus on their use for prevention of embolic events in AF. Moreover, it will discuss the safety, efficacy, cost data, and benefit for patients' quality of life and adherence.
The ( J, T ) = (1, 1) parity doublet in 20Ne at 11.26 MeV is a good candidate to study parity violation in nuclei. However, its energy splitting is known with insufficient accuracy for quantitative estimates of parity violating effects. To improve on this unsatisfactory situation, nuclear resonance fluorescence experiments using linearly and circularly polarized γ -ray beams were used to determine the energy difference of the parity doublet E = E(1−) − E(1+) = −3.2(±0.7)stat( +0.6 −1.2)sys keV and the ratio of their integrated cross sections I (+) s,0 /I (−) s,0 = 29(±3)stat( +14 −7 )sys. Shell-model calculations predict a parityviolating matrix element having a value in the range 0.46–0.83 eV for the parity doublet. The small energy difference of the parity doublet makes 20Ne an excellent candidate to study parity violation in nuclear excitations.
In this paper we discuss to what extent one can infer details of the interior structure of a black hole based on its horizon. Recalling that black hole thermal properties are connected to the non-classical nature of gravity, we circumvent the restrictions of the no-hair theorem by postulating that the black hole interior is singularity free due to violations of the usual energy conditions. Further these conditions allow one to establish a one-to-one, holographic projection between Planckian areal “bits” on the horizon and “voxels”, representing the gravitational degrees of freedom in the black hole interior. We illustrate the repercussions of this idea by discussing an example of the black hole interior consisting of a de Sitter core postulated to arise from the local graviton quantum vacuum energy. It is shown that the black hole entropy can emerge as the statistical entropy of a gas of voxels.
Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas with a very poor prognosis. Current therapies, based on historical regimens for aggressive B-cell lymphomas, have resulted in insufficient patient outcomes. The majority of patients relapse rapidly, and current 5-year overall survival rates are only 10–30%. It is evident that new approaches to treat patients with PTCL are required. In recent years, prospective studies in PTCL have been initiated, mainly in patients with relapsed/refractory disease. In some of these, selected histologic subtypes have been evaluated in detail. As a consequence, numerous new therapies have been developed and shown activity in PTCL, including: agents targeting the immune system (e.g. brentuximab vedotin, alemtuzumab, lenalidomide); histone deacetylase inhibitors (romidepsin, belinostat); antifolates (pralatrexate); fusion proteins (denileukin diftitox); nucleoside analogs (pentostatin, gemcitabine); and other agents (e.g. alisertib, plitidepsin, bendamustine, bortezomib). A variety of interesting novel combinations is also emerging. It is hoped that these innovative approaches, coupled with a greater understanding of the clinicopathologic features, pathogenesis, molecular biology, and natural history of PTCL will advance the field and improve outcomes in this challenging group of diseases. This review summarizes the currently available clinical evidence on the various approaches to treating relapsed/refractory PTCL, including the role of stem cell transplantation, with an emphasis on potential new drug therapies.
Based on a meta-analysis, Redick and Lindsey (2013) found that complex span and n-back tasks show an average correlation of r = 0.20, and concluded that "complex span and n-back tasks cannot be used interchangeably as working memory measures in research applications" (p. 1102). Here, we comment on this conclusion from a psychometric perspective. In addition to construct variance, performance on a test contains measurement error, task-specific variance, and paradigm-specific variance. Hence, low correlations among dissimilar indicators do not provide strong evidence for the existence, or absence, of a construct common to both indicators. One way to arrive at such evidence is to fit hierarchical latent factors that model task-specific, paradigm-specific, and construct variance. We report analyses for 101 younger and 103 older adults who worked on nine different working memory tasks. The data are consistent with a hierarchical model of working memory, according to which both complex span and n-back tasks are valid indicators of working memory. The working memory factor predicts 71% of the variance in a factor of reasoning among younger adults (83% for among older adults). When the working memory factor was restricted to any possible triplet of working memory tasks, the correlation between working memory and reasoning was inversely related to the average magnitude of the correlations among the indicators, indicating that more highly intercorrelated indicators may provide poorer coverage of the construct space. We stress the need to go beyond specific tasks and paradigms when studying higher-order cognitive constructs, such as working memory.
Smac (second mitochondria-derived activator of caspase) mimetics are considered as promising anticancer therapeutics and used to induce apoptosis by antagonizing inhibitor of apoptosis proteins, which are often abundantly expressed in cancer cells. Here, we identify interferon regulatory factor 1 (IRF1) as a novel critical regulator of Smac mimetic BV6-induced apoptosis and proinflammatory cytokine secretion with impact on the immune response. IRF1 knockdown rescues cells from BV6-induced apoptosis and attenuates BV6-stimulated upregulation of tumor necrosis factor-α (TNFα), indicating that IRF1 mediates BV6-triggered cell death, at least in part, by inducing TNFα. This notion is supported by data showing that exogenous supply of TNFα restores BV6-induced cell death in IRF-knockdown cells. Interestingly, IRF1 selectively controls the induction of nuclear factor-κB (NF-κB) target genes, as IRF1 depletion attenuates BV6-stimulated upregulation of TNFα and interleukin-8 (IL-8) but not p100 and RelB. Concomitant knockdown of IRF1 and p65 cooperate to inhibit BV6-induced cell death, implying a cooperative interaction of IRF1 and NF-κB. In addition, IRF1 silencing hampers TNFα induction by TNFα itself as an another prototypical NF-κB stimulus. Importantly, IRF1 depletion impedes BV6-stimulated secretion of additional proinflammatory cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IL-6 and monocyte chemoattractant protein-1, and migration of primary monocytes to BV6-treated tumor cells. In conclusion, this identification of IRF1 as a dual regulator of BV6-induced apoptosis and inflammatory cytokine secretion provides novel insights into determinants of sensitivity towards Smac mimetic and possible implications of Smac mimetic treatment on tumor microenvironment and immune response.
How to write (international) legal histories that would be true to their protagonists while simultaneously relevant to present audiences? Most of us would also want to write "critically" – that is to say, at least by aiming to avoid Eurocentrism, hagiography and commitment to an altogether old-fashioned view of international law as an instrument of progress. Hence we write today our histories "in context". But this cannot be all. Framing the relevant "context" is only possible by drawing upon more or less conscious jurisprudential and political preferences. Should attention be focused on academic debates, military power, class structures or assumptions about the longue durée? Such choices determine for us what we think of as relevant "contexts", and engage us as participants in large conversations about law and power that are not only about what once "was" but also what there will be in the future.
Political theology’s recent rise to academic prominence has, no doubt, been inspired by the sense of a certain staleness of standard (read: Anglo-American) analytical political and legal theory. Especially postcolonial and postmodern philosophy has resuscitated debates about the reality of secularization in Europe, pointing out that much of our shared political metaphysic is indeed that – a metaphysic – with close historical links to debates in theology. That should be no surprise. For almost half a millennium theology stood as the primus inter pares among the three "higher faculties" at European universities. The best minds at work in Europe explained the social and political changes to European audiences within a fully God-centric intellectual universe. Awareness of that fact, as Wim Decock points out in this massive and brilliant work, not only assists us in understanding the development of our political and legal vocabularies. It also enables us to grasp the contingency of our present debates, the way opposite standpoints on political and legal obligation refer back to assumptions about human nature, the roles of individual and society and the nature of "law" that are hard to detach from religious speculation. ...
The Rubin vase and duck-rabbit have two things in common: not only are they famous multistable figures, or 'Kippbilder', but before being discovered by scientists and philosophers, they both started their career as simple jokes. In contrast to usual understandings of 'Kippbilder', this paper will try to demonstrate that 'Kippbilder' can be a helpful model for understanding better dramatic, existential, and even religious events and their consequences. Multistable figures or 'Kippbilder' combine reversibility and irreversibility in an interesting way. While the so called first aspect change introduces an irreversible split, all subsequent aspect changes can be understood as an endless chain of reversible changes. After discussing the specificity of the Rubin vase and its aspect changes and focussing then on the distinction between first and further aspect changes, Di Blasi suggests the productive potential of the multistable figure as model for eventful events in discussing the conversion of Paul and his 'hōs mē' ('as if not').
Halobacillus halophilus, a moderately halophilic bacterium isolated from salt marshes, produces various compatible solutes to cope with osmotic stress. Glutamate and glutamine are dominant compatible solutes at mild salinities. Glutamine synthetase activity in cell suspensions of Halobacillus halophilus wild type was shown to be salt dependent and chloride modulated. A possible candidate to catalyze glutamine synthesis is glutamine synthetase A2, whose transcription is stimulated by chloride. To address the role of GlnA2 in the biosynthesis of the osmolytes glutamate and glutamine, a deletion mutant (ΔglnA2) was generated and characterized in detail. We compared the pool of compatible solutes and performed transcriptional analyses of the principal genes controlling the solute production in the wild type strain and the deletion mutant. These measurements did not confirm the hypothesized role of GlnA2 in the osmolyte production. Most likely the presence of another, yet to be identified enzyme has the main contribution in the measured activity in crude extracts and probably determines the total chloride-modulated profile. The role of GlnA2 remains to be elucidated.
The article aims to investigate, under the aspect of translation, the process of legal appropriation and reproduction of international law during the course of the 19th century. An occidental understanding of translation played an important role in the so-called process of universalization in the 19th century, as it made the complexity of global circulation of ideas invisible. Approaches proposed by scholars of Postcolonial, Cultural and Translation Studies are useful for re-reading histories of the circulation of European ideas, particularly the international law doctrines, from a different perspective. The great strides made in Translation and Cultural Studies in the last decades, as well as the discernment practiced in the scholarship of Postcolonial Studies, are important for a broader and more differentiated understanding of the processes of appropriation and reproduction of the doctrines of international law during the 19th century. The present article begins by tracing the connection between translation and universalization of concepts in 19th century international law; after a short excursus on the Western idea of translation, the attention is focused on the translation of international law textbooks. The conclusive section is dedicated to a comparison between Emer de Vattel’s Droit des gens and Andrés Bello’s Principios de Derecho de Jentes.
During embryonic development a large number of widely differing and specialized cell types with identical genomes are generated from a single totipotent zygote. Tissue specific transcription factors cooperate with epigenetic modifiers to establish cellular identity in differentiated cells and epigenetic regulatory mechanisms contribute to the maintenance of distinct chromatin states and cell-type specific gene expression patterns, a phenomenon referred to as epigenetic memory. This is accomplished via the stable maintenance of various epigenetic marks through successive rounds of cell division. Preservation of DNA methylation patterns is a well-established mechanism of epigenetic memory, but more recently it has become clear that many other epigenetic modifications can also be maintained following DNA replication and cell division. In this review, we present an overview of the current knowledge regarding the role of histone lysine methylation in the establishment and maintenance of stable epigenetic states.
The morphology of presynaptic specializations can vary greatly ranging from classical single-release-site boutons in the central nervous system to boutons of various sizes harboring multiple vesicle release sites. Multi-release-site boutons can be found in several neural contexts, for example at the neuromuscular junction (NMJ) of body wall muscles of Drosophila larvae. These NMJs are built by two motor neurons forming two types of glutamatergic multi-release-site boutons with two typical diameters. However, it is unknown why these distinct nerve terminal configurations are used on the same postsynaptic muscle fiber. To systematically dissect the biophysical properties of these boutons we developed a full three-dimensional model of such boutons, their release sites and transmitter-harboring vesicles and analyzed the local vesicle dynamics of various configurations during stimulation. Here we show that the rate of transmission of a bouton is primarily limited by diffusion-based vesicle movements and that the probability of vesicle release and the size of a bouton affect bouton-performance in distinct temporal domains allowing for an optimal transmission of the neural signals at different time scales. A comparison of our in silico simulations with in vivo recordings of the natural motor pattern of both neurons revealed that the bouton properties resemble a well-tuned cooperation of the parameters release probability and bouton size, enabling a reliable transmission of the prevailing firing-pattern at diffusion-limited boutons. Our findings indicate that the prevailing firing-pattern of a neuron may determine the physiological and morphological parameters required for its synaptic terminals.
Local active information storage as a tool to understand distributed neural information processing
(2014)
Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for today's digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and time in a distributed system, and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure the space-time dynamics of local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding.
Top-down influences on ambiguous perception: the role of stable and transient states of the observer
(2014)
The world as it appears to the viewer is the result of a complex process of inference performed by the brain. The validity of this apparently counter-intuitive assertion becomes evident whenever we face noisy, feeble or ambiguous visual stimulation: in these conditions, the state of the observer may play a decisive role in determining what is currently perceived. On this background, ambiguous perception and its amenability to top-down influences can be employed as an empirical paradigm to explore the principles of perception. Here we offer an overview of both classical and recent contributions on how stable and transient states of the observer can impact ambiguous perception. As to the influence of the stable states of the observer, we show that what is currently perceived can be influenced (1) by cognitive and affective aspects, such as meaning, prior knowledge, motivation, and emotional content and (2) by individual differences, such as gender, handedness, genetic inheritance, clinical conditions, and personality traits and by (3) learning and conditioning. As to the impact of transient states of the observer, we outline the effects of (4) attention and (5) voluntary control, which have attracted much empirical work along the history of ambiguous perception. In the huge literature on the topic we trace a difference between the observer's ability to control dominance (i.e., the maintenance of a specific percept in visual awareness) and reversal rate (i.e., the switching between two alternative percepts). Other transient states of the observer that have more recently drawn researchers' attention regard (6) the effects of imagery and visual working memory. (7) Furthermore, we describe the transient effects of prior history of perceptual dominance. (8) Finally, we address the currently available computational models of ambiguous perception and how they can take into account the crucial share played by the state of the observer in perceiving ambiguous displays.
Evaluating model fit in nonlinear multilevel structural equation models (MSEM) presents a challenge as no adequate test statistic is available. Nevertheless, using a product indicator approach a likelihood ratio test for linear models is provided which may also be useful for nonlinear MSEM. The main problem with nonlinear models is that product variables are non-normally distributed. Although robust test statistics have been developed for linear SEM to ensure valid results under the condition of non-normality, they have not yet been investigated for nonlinear MSEM. In a Monte Carlo study, the performance of the robust likelihood ratio test was investigated for models with single-level latent interaction effects using the unconstrained product indicator approach. As overall model fit evaluation has a potential limitation in detecting the lack of fit at a single level even for linear models, level-specific model fit evaluation was also investigated using partially saturated models. Four population models were considered: a model with interaction effects at both levels, an interaction effect at the within-group level, an interaction effect at the between-group level, and a model with no interaction effects at both levels. For these models the number of groups, predictor correlation, and model misspecification was varied. The results indicate that the robust test statistic performed sufficiently well. Advantages of level-specific model fit evaluation for the detection of model misfit are demonstrated.
Families are central to the social and emotional development of youth, and most families engage in musical activities together, such as listening to music or talking about their favorite songs. However, empirical evidence of the positive effects of musical family rituals on social cohesion and emotional well-being is scarce. Furthermore, the role of culture in the shaping of musical family rituals and their psychological benefits has been neglected entirely. This paper investigates musical rituals in families and in peer groups (as an important secondary socialization context) in two traditional/collectivistic and two secular/individualistic cultures, and across two developmental stages (adolescence vs. young adulthood). Based on cross-sectional data from 760 young people in Kenya, the Philippines, New Zealand, and Germany, our study revealed that across cultures music listening in families and in peer groups contributes to family and peer cohesion, respectively. Furthermore, the direct contribution of music in peer groups on well-being appears across cultural contexts, whereas musical family rituals affect emotional well-being in more traditional/collectivistic contexts. Developmental analyses show that musical family rituals are consistently and strongly related to family cohesion across developmental stages, whereas musical rituals in peer groups appear more dependent on the developmental stage (in interaction with culture). Contributing to developmental as well as cross-cultural psychology, this research elucidated musical rituals and their positive effects on the emotional and social development of young people across cultures. The implications for future research and family interventions are discussed.
In self-organized critical (SOC) systems avalanche size distributions follow power-laws. Power-laws have also been observed for neural activity, and so it has been proposed that SOC underlies brain organization as well. Surprisingly, for spiking activity in vivo, evidence for SOC is still lacking. Therefore, we analyzed highly parallel spike recordings from awake rats and monkeys, anesthetized cats, and also local field potentials from humans. We compared these to spiking activity from two established critical models: the Bak-Tang-Wiesenfeld model, and a stochastic branching model. We found fundamental differences between the neural and the model activity. These differences could be overcome for both models through a combination of three modifications: (1) subsampling, (2) increasing the input to the model (this way eliminating the separation of time scales, which is fundamental to SOC and its avalanche definition), and (3) making the model slightly sub-critical. The match between the neural activity and the modified models held not only for the classical avalanche size distributions and estimated branching parameters, but also for two novel measures (mean avalanche size, and frequency of single spikes), and for the dependence of all these measures on the temporal bin size. Our results suggest that neural activity in vivo shows a mélange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step. This implies that neural activity does not reflect a SOC state but a slightly sub-critical regime without a separation of time scales. Potential advantages of this regime may be faster information processing, and a safety margin from super-criticality, which has been linked to epilepsy.
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.
Symbiotic nitrogen fixation (SNF) in root nodules of grain legumes such as chickpea is a highly complex process that drastically affects the gene expression patterns of both the prokaryotic as well as eukaryotic interacting cells. A successfully established symbiotic relationship requires mutual signaling mechanisms and a continuous adaptation of the metabolism of the involved cells to varying environmental conditions. Although some of these processes are well understood today many of the molecular mechanisms underlying SNF, especially in chickpea, remain unclear. Here, we reannotated our previously published transcriptome data generated by deepSuperSAGE (Serial Analysis of Gene Expression) to the recently published draft genome of chickpea to assess the root- and nodule-specific transcriptomes of the eukaryotic host cells. The identified gene expression patterns comprise up to 71 significantly differentially expressed genes and the expression of twenty of these was validated by quantitative real-time PCR with the tissues from five independent biological replicates. Many of the differentially expressed transcripts were found to encode proteins implicated in sugar metabolism, antioxidant defense as well as biotic and abiotic stress responses of the host cells, and some of them were already known to contribute to SNF in other legumes. The differentially expressed genes identified in this study represent candidates that can be used for further characterization of the complex molecular mechanisms underlying SNF in chickpea.
Understanding the role of structure and social aspects regarding heat stress of people in urban areas requires an interdisciplinary scientific approach that connects methods from both natural sciences and social sciences. In this study, we combine three approaches to provide an interdisciplinary analysis of the structure and social components of heat stress in the city of Aachen, Germany. First, we assess the overall spatial structure of the urban heat island using spatially distributed measurements from mobile air temperature recordings on public transport units combined with spatially distributed geo-statistical data. The results indicate that the time of day matters: During the afternoon, areas with a relative low building density, like the industrial area northeast of the inner city, are the warmest, while surfaces in high-building-density areas like the inner city heat up faster during the evening. Second, we combine these measurements with place-based survey data collected in 2010 from residents aged 50 to 92 regarding their individual housing conditions, medical history and social integration to examine the match among heat-based stress of older residents, social conditions and elevated temperatures in their residential quarter. We identify disadvantaged areas for specific already-disadvantaged demographic groups in the city, pointing to a cumulation of inequalities, including heat stress among the most vulnerable. Third, we compare data of biometeorological measurements on urban public squares during the afternoon with results of the micrometeorological model ENVI-met to examine the spatial variability of the inner-city heat load. We complement the modelling results with on-site interviews to evaluate people’s heat perception at the same public places. A simulation shows that additional vegetation would increase thermal comfort at these public places, whereby the heat load assessed using the predicted mean vote (PMV) value would decrease by approximately 60 %. Furthermore, we demonstrate the strengths and weaknesses of heat stress simulation. ENVI-met allows for an overall reasonable representation of heat load during stable atmospheric conditions. However, due to the setup and structure of ENVI-met, large-scale atmospheric changes that occur during the day cannot readily be integrated into ENVI-met simulations.
Aim. To compare the efficacy, safety, and patient’s perception of two prostaglandin E2 application methods for induction of labour.
Method. Above 36th weeks of gestation, all women, who were admitted to hospital for induction of labour, were prospectively randomised to intravaginal 1 mg or intracervical 0.5 mg irrespective of cervical Bishop score. The main outcome variables were induction-to-delivery interval, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, rate of vaginal delivery, and patient’s perception using semantic differential questionnaire.
Results. Thirty-nine patients were enrolled in this study. There was no statistical significant difference between the two groups in regard to perceptions of induction. The median induction delivery time using intravaginal versus intracervical administration was 29.9 versus 12.8 hours, respectively (). No statistically difference between the groups was detected in regard to parity, gestation age, cervical Bishop score, number of foetal blood samples, PDA rate, rate of oxytocin augmentation, and mode of birth.
Summary. Irrespective of the cervical Bishop Score, intracervical gel had a shorter induction delivery time without impingement on the women’s perception of induction.
Altered microRNA (miRNA) expression is a hallmark of many cancer types. The combined analysis of miRNA and messenger RNA (mRNA) expression profiles is crucial to identifying links between deregulated miRNAs and oncogenic pathways. Therefore, we investigated the small non-coding (snc) transcriptomes of nine clear cell renal cell carcinomas (ccRCCs) and adjacent normal tissues for alterations in miRNA expression using a publicly available small RNA-Sequencing (sRNA-Seq) raw-dataset. We constructed a network of deregulated miRNAs and a set of differentially expressed genes publicly available from an independent study to in silico determine miRNAs that contribute to clear cell renal cell carcinogenesis. From a total of 1,672 sncRNAs, 61 were differentially expressed across all ccRCC tissue samples. Several with known implications in ccRCC development, like the upregulated miR-21-5p, miR-142-5p, as well as the downregulated miR-106a-5p, miR-135a-5p, or miR-206. Additionally, novel promising candidates like miR-3065, which i.a. targets NRP2 and FLT1, were detected in this study. Interaction network analysis revealed pivotal roles for miR-106a-5p, whose loss might contribute to the upregulation of 49 target mRNAs, miR-135a-5p (32 targets), miR-206 (28 targets), miR-363-3p (22 targets), and miR-216b (13 targets). Among these targets are the angiogenesis, metastasis, and motility promoting oncogenes c-MET, VEGFA, NRP2, and FLT1, the latter two coding for VEGFA receptors.
Physics at its core is an experimental pursuit. If one theory does not agree with experimental results, then the theory is wrong. However, it is becoming harder and harder to directly test some theories of fundamental physics at the high energy/small distance frontier exactly because this frontier is becoming technologically harder to reach. The Large Hadron Collider is getting near the limit of what we can do with present accelerator technology in terms of directly reaching the energy frontier. The motivation for this special issue was to try and collect together ideas and potential approaches to experimentally probe some of our ideas about physics at the high energy/small distance frontier. Some of the papers in this special issue directly deal with the issue of what happens to spacetime at small distance scales. In the paper by A. Aurilia and E. Spallucci a picture of quantum spacetime is given based on the effects of ultrahigh velocity length contractions on the structure of the spacetime. The work of P. Nicolini et al. further pursues the idea that spacetime has a minimal length. The consequences of this minimal length are investigated in terms of the effects it would have on the gravitational collapse of a star to form a black hole. In the article by G. Amelino-Camelia et al. the quantum structure of spacetime is studied through the Fermi LAT data on the Gamma Ray Burst GRB130427A. The article by S. Hossenfelder addressed the question of whether spacetime is fundamentally continuous or discrete and postulates that in the case when spacetime is discrete it might have defects which would have important observational consequences. ...
This paper studies the geometry and the thermodynamics of a holographic screen in the framework of the ultraviolet self-complete quantum gravity. To achieve this goal we construct a new static, neutral, nonrotating black hole metric, whose outer (event) horizon coincides with the surface of the screen. The spacetime admits an extremal configuration corresponding to the minimal holographic screen and having both mass and radius equalling the Planck units. We identify this object as the spacetime fundamental building block, whose interior is physically unaccessible and cannot be probed even during the Hawking evaporation terminal phase. In agreement with the holographic principle, relevant processes take place on the screen surface. The area quantization leads to a discrete mass spectrum. An analysis of the entropy shows that the minimal holographic screen can store only one byte of information, while in the thermodynamic limit the area law is corrected by a logarithmic term.
Background. Depression is the most common type of mental disorder in Germany. It is associated with a high level of suffering for individuals and imposes a significant burden on society. The aim of this study was to estimate the depression related costs in Germany taking a societal perspective.
Materials and Methods. Data were collected from the primary care monitoring for depressive patients trial (PRoMPT) of patients with major depressive disorder who were treated in a primary care setting. Resource utilisation and days of sick leave were observed and analysed over a 1-year period.
Results. Average depression related costs of €3813 were calculated. Significant differences in total costs due to sex were demonstrated. Male patients had considerable higher total costs than female patients, whereas single cost categories did not differ significantly. Further, differences in costs according to severity of disease and age were observed. The economic burden to society was estimated at €15.6 billion per year.
Conclusion. The study results show that depression poses a significant economic burden to society. There is a high potential for prevention, treatment, and patient management innovations to identify and treat patients at an early stage.
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.
In this article, I review select institutional and analytical traditions of Legal History in 20th century Germany, in order to put forth some recommendations for the future development of our discipline. A careful examination of the evolution of Legal History in Germany in the last twenty-five years, in particular, reveals radical transformations in the research framework: Within the study of law, there has been a shift in the internal reference points for Legal History. While the discipline is opening up to new understandings of law and to its neighboring disciplines, its institutional position at the law departments has become precarious. Research funding is being allocated in new ways and the German academic system is witnessing ever more internal differentiation. Internationally, German contributions and analytic traditions are receiving less attention and are being marginalized as new regions enter into a global dialogue on law and its history. The German tradition of research in Legal History had for long been setting benchmarks internationally; now it has to reflect upon and react to new global knowledge systems that have emerged in light of the digital revolution and the transnationalization of legal and academic systems. If legal historians in Germany accept the challenge these changing conditions pose, thrilling new intellectual and also institutional opportunities emerge. Especially the transnationalization of law and the need for a transnational legal scholarship offers fascinating perspectives for Legal History.
For centuries, it may have seemed as if standards of normative thinking now valid across the globe had first been instituted in Europe. These normative orders form the foundations of our verdicts that define and distinguish right and wrong, good and bad or even beautiful and ugly. But in order to better understand the global presence of such normative orders that evolved from within the European horizon, the history and implications of European expansion in the early modern era cannot be swept under the rug. ...
Complexin-1 and foxp1 expression changes are novel brain effects of
alpha-synuclein pathology
(2014)
As the second most frequent neurodegenerative disorder of the aging population, Parkinson’s disease (PD) is characterized by progressive deficits in spontaneous movement, atrophy of dopaminergic midbrain neurons and aggregation of the protein alpha-synuclein (SNCA). To elucidate molecular events before irreversible cell death, we studied synucleinopathy-induced expression changes in mouse brain and identified 49 midbrain/brainstem-specific transcriptional dysregulations. In particular complexin-1 (Cplx1), Rabl2a and 14-3-3epsilon (Ywhae) downregulation, as well as upregulation of the midbrain-specific factor forkhead box P1 (Foxp1) and of Rabgef1, were interesting as early mRNA level effects of alpha-synuclein triggered pathology. The protein levels of complexin-1 were elevated in midbrain/brainstem tissue of mice with A53T-SNCA overexpression and of mice with SNCA-knockout. The response of CPLX1 and Foxp1 levels to SNCA deficiency supports the notion that these factors are regulated by altered physiological function of alpha-synuclein. Thus, their analysis might be useful in PD stages before the advent of Lewy pathology. Because both alpha-synuclein and complexin-1 modulate vesicle release, our findings support presynaptic dysfunction as an early event in PD pathology.
Reciprocal exchanges can be understood as the updating of an initial belief about a partner. This initial level of trust is essential when it comes to establishing cooperation with an unknown partner, as cooperation cannot arise without a minimum of trust not justified by previous successful exchanges with this partner. Here we demonstrate the existence of a representation of the initial trust level before an exchange with a partner has occurred. Specifically, we can predict the Investor’s initial investment—i.e. his initial level of trust toward the unknown trustee in Round 1 of a standard 10-round Trust Game—from resting-state functional connectivity data acquired several minutes before the start of the Trust Game. Resting-state functional connectivity is, however, not significantly associated with the level of trust in later rounds, potentially mirroring the updating of the initial belief about the partner. Our results shed light on how the initial level of trust is represented. In particular, we show that a person’s initial level of trust is, at least in part, determined by brain electrical activity acquired well before the beginning of an exchange.
Talking about emotion and sharing emotional experiences is a key component of human interaction. Specifically, individuals often consider the reactions of other people when evaluating the meaning and impact of an emotional stimulus. It has not yet been investigated, however, how emotional arousal ratings and physiological responses elicited by affective stimuli are influenced by the rating of an interaction partner. In the present study, pairs of participants were asked to rate and communicate the degree of their emotional arousal while viewing affective pictures. Strikingly, participants adjusted their arousal ratings to match up with their interaction partner. In anticipation of the affective picture, the interaction partner’s arousal ratings correlated positively with activity in anterior insula and prefrontal cortex. During picture presentation, social influence was reflected in the ventral striatum, that is, activity in the ventral striatum correlated negatively with the interaction partner’s ratings. Results of the study show that emotional alignment through the influence of another person’s communicated experience has to be considered as a complex phenomenon integrating different components including emotion anticipation and conformity.
Nations are signified by their constructed or mythicized cultural memory, since "identity is part of memory discourse". There are shared historical legacies in Southeast European countries, among which the most significant are Byzantium and the Ottoman Empire: "It has been chiefly the Ottoman elements or the ones perceived as such which have mostly given rise to the current stereotype of the Balkans, so that it would not be an exaggeration to say that the Balkans are, in fact, the Ottoman legacy." Contrary to it, the Habsburg legacy and the belonging to the Habsburg Monarchy have mainly not been seen in the same, negative way. Consequently, there are two different understandings of national identity and different strategies in defining self-representation in the (previous) provinces of the two empires, which is also explicated in Southeast European operas. The construction of Croatian national identity is considered through the stage representations of the historical Siege of Szigetvár (1566).
The establishment of robust HCV cell culture systems and characterization of the viral life cycle provided the molecular basis for highly innovative, successful years in HCV drug development. With the identification of direct-acting antiviral agents (DAAs), such as NS3/4A protease inhibitors, NS5A replication complex inhibitors, nucleotide and non-nucleoside polymerase inhibitors, as well as host cell targeting agents, novel therapeutic strategies were established and competitively entered clinical testing. The first-in-class NS3/4A protease inhibitors telaprevir and boceprevir, approved in 2011, were recently outpaced by the pan-genotypic nucleotide polymerase inhibitor sofosbuvir that in combination with pegylated interferon and ribavirin, further shortens therapy durations and also offers the first interferon-free HCV treatment option. In the challenging race towards the goal of interferon-free HCV therapies, however, several oral DAA regimens without nucleotide polymerase inhibitors that combine a NS3/4A protease inhibitor, a NS5A inhibitor and/or a non-nucleoside polymerase inhibitor yielded competitive results. Second generation NS3/4A protease and NS5A inhibitors promise an improved genotypic coverage and a high resistance barrier. Results of novel DAA combination therapies without the backbone of a nucleotide polymerase inhibitor, as well as treatment strategies involving host targeting agents are reviewed herein.
Establishing coherent identity patterns for literary characters in novels is a difficult task. In this respect, we assume that readers rely on pre-stored cultural models in order to construct mental models of the text content, including character identity. By significantly extending the approach by Van Dijk and Kintsch and going beyond the related accounts of Schneider and of Culpeper, we aim to clarify the constitutive role of conceptual metaphor as proposed by Lakoff et al. in processes of literary identity construction. The analysis of a corpus of three contemporary novels supports our claim that conceptual metaphors and the mapping of domains involved interact with cultural models and connect text phenomena to such prior knowledge structures. On this basis, we provide an integrated model of literary identity construction which acknowledges the constitutive value of conceptual metaphors in literary identity construction.
Emotional competence has an important influence on development in school. We hypothesized that reading and discussing children’s books with emotional content increases children’s emotional competence. To examine this assumption, we developed a literature-based intervention, named READING and FEELING, and tested it on 104 second and third graders in their after-school care center. Children who attended the same care center but did not participate in the emotion-centered literary program formed the control group (n = 104). Our goal was to promote emotional competence and to evaluate the effectiveness of the READING and FEELING program. Emotional competence variables were measured prior to the intervention and 9 weeks later, at the end of the program. Results revealed significant improvements in the emotional vocabulary, explicit emotional knowledge, and recognition of masked feelings. Regarding the treatment effect for detecting masked feelings, we found that boys benefited significantly more than girls. These findings underscore the assumption that children’s literature is an appropriate vehicle to support the development of emotional competence in middle childhood.
This study explored the organization of the semantic field and the conceptual structure of moving experiences by investigating German-language expressions referring to the emotional state of being moved. We used present and past participles of eight psychological verbs as primes in a free word-association task, as these grammatical forms place their conceptual focus on the eliciting situation and on the felt emotional state, respectively. By applying a taxonomy of basic knowledge types and computing the Cognitive Salience Index, we identified joy and sadness as key emotional ingredients of being moved, and significant life events and art experiences as main elicitors of this emotional state. Metric multidimensional scaling analyses of the semantic field revealed that the core terms designate a cluster of emotional states characterized by low degrees of arousal and slightly positive valence, the latter due to a nearly balanced representation of positive and negative elements in the conceptual structure of being moved.
The radiative capture cross section of 238U is very important for the developing of new reactor technologies and the safety of existing ones. Here the preliminary results of the 238U(n,γ) cross section measurement performed at n_TOF with C6D6 scintillation detectors are presented, paying particular attention to data reduction and background subtraction.
Background: Recent studies have suggested substantial fluctuations of cognitive performance in adults both across and within days, but very little is known about such fluctuations in children. Children's sleep behavior might have an important influence on their daily cognitive resources, but so far this has not been investigated in terms of naturally occurring within-person variations in children's everyday lives.
Methods: In an ambulatory assessment study, 110 elementary school children (8–11 years old) completed sleep items and working memory tasks on smartphones several times per day in school and at home for 4 weeks. Parents provided general information about the children and their sleep habits.
Results: We identified substantial fluctuations in the children's daily cognitive performance, self-reported nightly sleep quality, time in bed, and daytime tiredness. All three facets were predictive of performance fluctuations in children's school and daily life. Sleep quality and time in bed were predictive of performance in the morning, and afternoon performance was related to current tiredness. The children with a lower average performance level showed a higher within-person coupling between morning performance and sleep quality.
Conclusions: Our findings contribute important insights regarding a potential source of performance fluctuations in children. The effect of varying cognitive resources should be investigated further because it might impact children's daily social, emotional, and learning-related functioning. Theories about children's cognitive and educational development should consider fluctuations on micro-longitudinal scales (e.g., day-to-day) to identify possible mechanisms behind long-term changes.
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.