Refine
Year of publication
- 2015 (2651) (remove)
Document Type
- Article (911)
- Part of Periodical (357)
- Book (333)
- Doctoral Thesis (188)
- Working Paper (180)
- Contribution to a Periodical (174)
- Report (161)
- Review (142)
- Part of a Book (100)
- Preprint (55)
Language
- German (1282)
- English (1262)
- Portuguese (26)
- French (18)
- Spanish (17)
- Croatian (14)
- Italian (12)
- Multiple languages (12)
- Turkish (5)
- Hebrew (1)
Is part of the Bibliography
- no (2651) (remove)
Keywords
- Literatur (44)
- Deutsch (37)
- Islamischer Staat (34)
- Rezension (30)
- taxonomy (29)
- IS (25)
- Rezeption (23)
- Terrorismus (23)
- new species (22)
- Deutschland (20)
Institute
- Präsidium (336)
- Medizin (253)
- Gesellschaftswissenschaften (239)
- Physik (185)
- Wirtschaftswissenschaften (149)
- Exzellenzcluster Die Herausbildung normativer Ordnungen (118)
- Center for Financial Studies (CFS) (115)
- Biowissenschaften (102)
- Frankfurt Institute for Advanced Studies (FIAS) (97)
- Informatik (96)
Die Arbeit mit Rechnungen bietet den Vorteil, dass es sich dabei fast immer um Originalquellen handelt. Rechnungen wurden üblicherweise nicht in Kompilationen aufgenommen oder nicht in Urkunden inseriert. Wenn sie abgeschrieben wurden, geschah das höchstens im Zuge des Abrechnungsprozesses und nicht, wie etwa bei Chroniken, um für ihre weitere Verbreitung zu sorgen. Unter den schriftlichen Quellen kommen die Rechnungen damit wohl der Definition eines Überrestes am nächsten: Sie wurden für die Mit-, nicht die Nachwelt erstellt. Das bringt allerdings den Nachteil mit sich, dass wir selten genau wissen, zu welchem Zweck eine Rechnung eigentlich verfertigt wurde. Keine Arenga klärt den Forscher über die Vorgeschichte und den Zusammenhang der Niederschrift auf. Erklärende Dokumente sind fast nie überliefert. Die Menschen, die Rechnungen erstellten und mit ihnen arbeiteten, lernten das durch und bei ihrer Arbeit, eventuell unter mündlicher Anleitung. ...
The present research investigates if and how a more digitally centered communication between supervisors and employees satisfies employees’ needs regarding the communication with their supervisors and influences employees’ attitudes toward the supervisor and the job. In a cross-sectional online study, 261 employees rated their supervisors’ actual and ideal use of different communication channels (i.e., telephone, face-to-face, email) regarding quality and quantity. Employees’ job satisfaction and their perceptions of their supervisors’ effectiveness and team identification were measured as dependent variables. Employees perceived face-to-face communication to be of higher quality than telephone and email communication, and they indicated a preference for more face-to-face communication with their supervisors than they actually had. Moreover, the perceived quality of communication, especially via face-to-face, was strongly and positively related to the dependent variables. These results provide insights into potential problems of increasing e-leadership in organizations. We conclude with recommendations to reduce these problems.
Die vorliegende Bachelorarbeit leistet einen Beitrag zur wissenschaftlichen Identifikation von intergenerationalen Unterschieden verschiedener Arbeitnehmergruppen. Insbesondere werden sowohl die Unterschiede zwischen den Generationen X und Y, in der Arbeitsbereitschaft, in unterschiedlichen Abschnitten des Berufslebens, als auch die Unterschiede zwischen der Wahrnehmung der Wichtigkeit von Arbeitgeberattraktivitätsattributen jener Generationen betrachtet. Ein besonderes Augenmerk liegt hierbei auf der Betrachtung von High-Potentials.
Since August 2009, German legislation allows for voluntary Say on Pay Votes (SoPV) during Annual General Meetings (AGMs). We examine 1,169 AGMs of all German listed firms with more than 10,000 agenda items over the period 2010-2013 to identify (1) determinants and approval rates of voluntary SoPVs, (2) the effect of voluntary SoPVs on AGM participation, and (3) the effect of SoP on executive compensation. Our data reveals that in the first four years of the voluntary say on pay regime every second firm in our sample has opted for having a SoPV. The propensity for a SoPV increases with firm size, abnormal executive compensation and free float of shares. Indeed, smaller firms with concentrated ownership do not only have a lower propensity for a SoPV, but also show a higher propensity to opt for only limited disclosure of executive compensation. Approval rates of SoPVs are lower than the approval rate for the average AGM agenda item and this effect is stronger in (i) widely held firms as well as in (ii) firms with abnormal executive compensation. Additionally, SoPVs actually can increase AGM participation; however, this result is particularly evident for widely held firms. Finally, we find stronger pay for performance elements within total executive compensation, particularly when the effect of executive compensation is lagged over the years following the vote. Overall, our results are consistent with the view that firms use voluntary SoPV to gain legitimation for executive remuneration policies in firms with low ownership concentration. This is enforced, where (small) shareholders consider executive compensation a part of the agency problem of listed firms, and where (small) shareholders consider SoPVs as a possibility to actively influence corporate decisions, with these decisions leading to a higher degree of alignment between executive management boards and shareholders.
TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment.
Background and aims: Individualization of treatment with peginterferon alfa and ribavirin in patients with chronic hepatitis C showed benefit in controlled trials and was implemented in treatment guidelines to increase response rates and to reduce side effects and costs. However, it is unknown whether individualization was adopted in routine daily practice and whether it translated into improved outcomes.
Methods: From a large noninterventional cohort study, clinical and virologic response data of 10,262 HCV patients who received peginterferon alfa-2a and ribavirin between 2003-2007 and 2008-2011 were analyzed. To account for treatment individualization, a matched-pair analysis (2,997 matched pairs) was performed. Variation in treatment duration and dosing of ribavirin were analyzed as indicators for individualization.
Results: Sustained virological response (SVR) rates were similar between 2003-2007 and 2008-2011 (62.0% vs. 63.7%). Patients with comorbidities were more abundant in the later period, (44.3% vs. 57.1%). The subsequent matched-pair analysis demonstrated higher SVR rates in the 2008-2011 period (64.3%) than in the 2003-2007 period (61.2%, p=0.008). More patients received abbreviated or extended treatment regimens in the later than the earlier period as an indicator of treatment individualization. To the same end, ribavirin doses were higher in the later period (12.6 versus 11.6 mg/kg/day). Factors independently associated with SVR included HCV genotype, low baseline viral load, younger age, route of infection, absence of concomitant diseases, lower APRI score, normal gamma-GT, higher ribavirin doses, no substitution for drug abuse, treatment duration, and treatment in the 2008-2011 period.
Conclusions: Treatment individualization with peginterferon alfa and ribavirin was implemented in daily routine between 2003-2007 and 2008-2011, SVR rates improved in the same period. These findings may be most relevant in resource-limited settings.
Background: Intestinal perforation or leakage increases morbidity and mortality of surgical and endoscopic interventions. We identified criteria for use of full-covered, extractable self-expanding metal stents (cSEMS) vs. "Over the scope"-clips (OTSC) for leak closure.
Methods: Patients who underwent endoscopic treatment for postoperative leakage, endoscopic perforation, or spontaneous rupture of the upper gastrointestinal tract between 2006 and 2013 were identified at four tertiary endoscopic centers. Technical success, outcome (e.g. duration of hospitalization, in-hospital mortality), and complications were assessed and analyzed with respect to etiology, size and location of leakage.
Results: Of 106 patients (male: 75 (71%), female: 31 (29%); age (mean ± SD): 62.5 ± 1.3 years, 72 (69%) were treated by cSEMS and 34 (31%) by OTSC. For cSEMS vs. OTSC, mean treatment duration was 41.1 vs. 25 days, p<0.001, leakage size 10 (1-50) vs. 5 (1-30) mm (median (range)), and complications were observed in 68% vs. 8.8%, p<0.001, respectively. Clinical success for primary interventional treatment was observed in 29/72 (40%) vs. 24/34 (70%, p = 0.006), and clinical success at the end of follow-up was 46/72 (64%) vs. 29/34 (85%) for patients treated by cSEMS vs. OTSC; p = 0.04.
Conclusion: OTSC is preferred in small-sized lesions and in perforation caused by endoscopic interventions, cSEMS in patients with concomitant local infection or abscess. cSEMS is associated with a higher frequency of complications. Therefore, OTSC might be preferred if technically feasible. Indication criteria for cSEMS vs. OTSC vary and might impede design of randomized studies.
Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
Study Design: Survey of 100 worldwide spine surgeons.
Objective: To develop a spine injury score for the AOSpine Thoracolumbar Spine Injury Classification System.
Methods: Each respondent was asked to numerically grade the severity of each variable of the AOSpine Thoracolumbar Spine Injury Classification System. Using the results, as well as limited input from the AOSpine Trauma Knowledge Forum, the Thoracolumbar AOSpine Injury Score was developed.
Results: Beginning with 1 point for A1, groups A, B, and C were consecutively awarded an additional point (A1, 1 point; A2, 2 points; A3, 3 points); however, because of a significant increase in the severity between A3 and A4 and because the severity of A4 and B1 was similar, both A4 and B1 were awarded 5 points. An uneven stepwise increase in severity moving from N0 to N4, with a substantial increase in severity between N2 (nerve root injury with radicular symptoms) and N3 (incomplete spinal cord injury) injuries, was identified. Hence, each grade of neurologic injury was progressively given an additional point starting with 0 points for N0, and the substantial difference in severity between N2 and N3 injuries was recognized by elevating N3 to 4 points. Finally, 1 point was awarded to the M1 modifier (indeterminate posterolateral ligamentous complex injury).
Conclusion: The Thoracolumbar AOSpine Injury Score is an easy-to-use, data-driven metric that will allow for the development of a surgical algorithm to accompany the AOSpine Thoracolumbar Spine Injury Classification System.
Effect of event selection on jetlike correlation measurement in d+Au collisions at √sNN = 200 GeV
(2015)
Dihadron correlations are analyzed in √sNN = 200 GeV d + Au collisions classified by forward charged particle multiplicity and zero-degree neutral energy in the Au-beam direction. It is found that the jetlike correlated yield increases with the event multiplicity. After taking into account this dependence, the non-jet contribution on the away side is minimal, leaving little room for a back-to-back ridge in these collisions.
Die Relevanz von MSC aus Fettgewebe (ASC) in der regenerativen Medizin überrascht in Anbetracht ihrer breit gefächerten Eigenschaften nicht. Neben antiinflammatorischen Eigenschaften und Hypoxieresistenz können sie in eine Vielzahl von Geweben differenzieren und in geschädigtes Gewebe migrieren, wo sie an Reperaturvorgängen beteiligt sind. Dabei stehen unterschiedliche Quellen zur Isolierung von MSC (und ASC) zur Verfügung. Um ASC therapeutisch einsetzen zu können, ist es essentiell ihre Quellen und ihr Potenzial zu erforschen. Es konnte gezeigt werden, dass perirenales Fettgewebe eine geeignete Quelle für ASC (prASC) darstellt. Der Nachweis der Oberflächenantigene CD73, CD90 und CD105 mittels Durchflusszytometrie sowie die Fähigkeit der prASC an Zellkulturplastik zu adhärieren, erlauben die Schlussfolgerung, dass es sich bei den nach einem bereits etablierten Verfahren isolierten Zellen um MSC handelt. Außerdem konnte durch eine zweiwöchige Kultivierung der prASC in supplementierten Medien die Differenzierung in Adipozyten, Chondrozyten sowie Osteozyten induziert werden. Der Nachweis erfolgte durch cytochemische Färbemethoden. In dieser Arbeit wurde die Differenzierung von prASC in Epithelzellen untersucht. Dafür wurden die Zellen in unterschiedlichen ATRA-haltigen Kulturmedien und konditioniertem Medium aus Tubulusepithelzellen kultiviert. Der Einfluss der Medien wurde mittels Western Blot, qPCR und Immunfluoreszenzfärbung nachgewiesen. Die Kultivierung mit ATRA führte zu einer signifikanten Erhöhung der Expression von CK18 und ZO-1. Dabei handelt es sich um Marker, die charakteristisch für Epithelzellen sind. Es konnte folglich gezeigt werden, dass humane prASC in vitro eindeutig in epithelialer Richtung differenzieren können. Unter dem Einfluss von ATRA-supplementierten Medien exprimierten die kultivierten Zellen Genprodukte, die Epithelzellen zuzuordnen sind.
Welche Bedeutung diese Erkenntnis hat ist noch unklar. Möglicherweise sind prASC, als Stammzellen aus Nischen mit anatomischer Nähe zu den Nieren, potente Kandidaten, um untergegangenes Nierengewebe, wie beispielsweise Tubulusepithelzellen, zu ersetzen.
Die vorliegende Arbeit wendet sich dem gegenwärtig aufgekommenen Phänomen der Ablösung vom Nazi-Klischee bei der Repräsentation von "Deutschen" zu und fokussiert in fünf zeitgenössischen Beispielen die visuelle Darstellung von Deutsch-sein in US-amerikanischen Fernsehserien.
Die nationale Identität des deutschen Volkes wird mittels verschiedener Bildmittel als zwiespältig, zwielichtig und damit widersprüchlich inszeniert. Dies lässt sich im Wesentlichen als Ergebnis der qualitativen Bildanalyse in den hier untersuchten Fernsehserien Malcolm Mittendrin (2002 - 2004), Scrubs (2005), Veronica Mars (2004 - 2006), How I Met Your Mother (2007 - 2012) und Breaking Bad (2012) zusammenfassen.
Ihre Widersprüchlichkeit wird schließlich als symbolische Konstruktion gedeutet, die der These des Lyrikers C. K. Williams folgt, "die Deutschen" seien zu einem Zeichen transzendiert. Damit bewegt sich die Darstellung von Deutsch-sein zwischen zwei Positionen, und zwar konkret zwischen dem, was es ist (bzw. was das Fernsehen den Zuschauer glauben lässt, was es ist), und dem, wofür es steht. Für die Ambivalenz der Darstellung von Deutsch-sein spielt die symbolische Bedeutung des deutschen Volkes, welche sich aus seiner Geschichte ergibt, eine wesentliche Rolle.
Die Gliederung der vorliegenden Arbeit orientiert sich an zwei Fragen: Auf welche besondere Weise wird Deutsch-sein visuell konstruiert (ästhetischer Mechanismus)? Welches Wissen über Deutsch-sein wird (re)produziert (sozialer Mechanismus via Zeichen)?
Objective: Cognitive models suggest that the self-concept of persons with psychosis can be fundamentally affected. Self-concepts were found to be related to different symptom domains when measured concurrently. Longitudinal investigations to disentangle the possible causal associations are rare.
Method: We examined a sample of 160 people with a diagnosis of schizophrenia who took part in a psychotherapy study. All participants had the DSM-IV diagnosis of a schizophrenia and pronounced negative symptoms. Neurocognition, symptoms, and self-concepts were assessed at two time points 12 months apart. Structural equation modeling was used to test whether symptoms influence self-concepts (scar-model) or self-concepts affect symptoms (vulnerability model).
Results: Negative symptoms correlated concurrently with self-concepts. Neurocognitive deficits are associated with more negative self-concepts 12 months later. Interpersonal self-concepts were found to be relevant for paranoia.
Conclusion: The findings implicate that if deficits in neurocognition are present, fostering a positive self-concept should be an issue in therapy. Negative interpersonal self-concept indicates an increased risk for paranoid delusions in the course of 1 year. New aspects for cognitive models in schizophrenia and clinical implications are discussed.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4-H2O) system, and the ternary system involving ammonia (H2SO4-H2O-NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a Chemical Ionization Mass Spectrometer (CIMS). From these measurements dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) mass spectrometry.
Sulfuric acid is an important gas influencing atmospheric new particle formation (NPF). Both the binary (H2SO4–H2O) system and the ternary system involving ammonia (H2SO4–H2O–NH3) may be important in the free troposphere. An essential step in the nucleation of aerosol particles from gas-phase precursors is the formation of a dimer, so an understanding of the thermodynamics of dimer formation over a wide range of atmospheric conditions is essential to describe NPF. We have used the CLOUD chamber to conduct nucleation experiments for these systems at temperatures from 208 to 248 K. Neutral monomer and dimer concentrations of sulfuric acid were measured using a chemical ionization mass spectrometer (CIMS). From these measurements, dimer evaporation rates in the binary system were derived for temperatures of 208 and 223 K. We compare these results to literature data from a previous study that was conducted at higher temperatures but is in good agreement with the present study. For the ternary system the formation of H2SO4·NH3 is very likely an essential step in the formation of sulfuric acid dimers, which were measured at 210, 223, and 248 K. We estimate the thermodynamic properties (dH and dS) of the H2SO4·NH3 cluster using a simple heuristic model and the measured data. Furthermore, we report the first measurements of large neutral sulfuric acid clusters containing as many as 10 sulfuric acid molecules for the binary system using chemical ionization–atmospheric pressure interface time-of-flight (CI-APi-TOF) mass spectrometry.
An individual's choices are shaped by its experience, a fundamental property of behavior important to understanding complex processes. Learning and memory are observed across many taxa and can drive behaviors, including foraging behavior. To explore the conditions under which memory provides an advantage, we present a continuous-space, continuous-time model of animal movement that incorporates learning and memory. Using simulation models, we evaluate the benefit memory provides across several types of landscapes with variable-quality resources and compare the memory model within a nested hierarchy of simpler models (behavioral switching and random walk). We find that memory almost always leads to improved foraging success, but that this effect is most marked in landscapes containing sparse, contiguous patches of high-value resources that regenerate relatively fast and are located in an otherwise devoid landscape. In these cases, there is a large payoff for finding a resource patch, due to size, value, or locational difficulty. While memory-informed search is difficult to differentiate from other factors using solely movement data, our results suggest that disproportionate spatial use of higher value areas, higher consumption rates, and consumption variability all point to memory influencing the movement direction of animals in certain ecosystems.
The implementation of pump-probe experiments with ultrashort laser pulses enables the study of dynamical processes in atoms or molecules, which may provide a deeper inside in their physical origin. The application of this method to systems as nitrous oxide, which is not only a simple example for polyatomic molecules but which also plays a crucial role in the greenhouse effect, promises interesting and beneficial findings. This thesis presents, on the one hand, the technical extension of an existing experimental setup for high-harmonic generation (HHG) and ultra-fast laser physics by an extreme ultraviolet (XUV) spectrometer for the in-situ observation of the harmonic spectrum during ongoing measurements. The present setup enables the production of short laser pulse trains in the XUV spectral range with durations of a few hundred attoseconds (1 as = 10^−18 s) via HHG and supports to perform XUV-IR pump-probe experiments using the infrared (IR) driving field with durations of a few femtoseconds. Moreover, a reaction microscope is implemented, which enables the coincident detection of several charged particles emerging from an ionization or dissociation process and to reconstruct their full 3-D-momentum vectors. With this technique it is possible to perform time-resolved momentum spectroscopy of few-particle quantum systems. Here, the design and the calibration of the XUV spectrometer is presented as well as a first application to the analysis of experimental data by providing information on the produced photon energies. On the other hand, the results of an XUV-pump IR-probe measurement on nitrous oxide (N2O) are discussed. With the broad harmonic spectrum (∼ 17 − 45 eV) it is possible to address several states of the singly and doubly ionized cation. One reaction channel is the single ionization into a stable state of N2O+. Here, the coincidently measured photoelectron energies allow the observation of sidebands, which served to estimate the pulse durations of the involved XUV pulse trains as well as of the fundamental IR pulses. Additionally, single ionization of nitrous oxide can lead to a dissociation into a charged and a neutral fragment. The four respective dissociation channels are compared by presenting their branching ratios, kinetic energy release (KER) distributions and their dependencies on the time delay between pump and probe pulse. In the production of the dication, there are two competitive processes: direct double ionization considering photon energies above the double-ionization threshold, and autoionization of singly ionized and excited molecules in the case of photon energies near the double-ionization threshold. In both cases, the ionization leads to a Coulomb explosion into two charged fragments, where the N − N bond or the N − O bond may dissociate. The influence of the IR-probe field on the ionization yield and the KER was investigated for both dissociation channels and compared. In addition, the corresponding photoelectron energy spectra are presented, which show indications for autoionizing states being involved, and their dependence on the delay and the KER of the respective ions is analyzed.
Wirtschafts- und Rechnungsbücher bieten mehrdimensionale Zugänge und erfordern multidisziplinäre Annäherungen. Dass sie weit mehr sind als Einnahmen- und Ausgabeverzeichnisse zeigen die hier vorliegenden 17 Beiträge mit Beispielen von Lübeck bis Lyon. Sie vereinen die Ergebnisse eines Workshops, der diese Gattung serieller Quellen von Seiten der Geschichtswissenschaft und der Historischen Sprachforschung, der Editions- und Medienwissenschaft sowie der historischen Wirtschafts- und Betriebswirtschaftswissenschaft in den Blick genommen hat.
There are strong indications that particles containing secondary organic aerosol (SOA) exhibit amorphous solid or semi-solid phase states in the atmosphere. This may facilitate deposition ice nucleation and thus influence cirrus cloud properties. However, experimental ice nucleation studies of biogenic SOA are scarce. Here, we investigated the ice nucleation ability of viscous SOA particles.
The SOA particles were produced from the ozone initiated oxidation of α-pinene in an aerosol chamber at temperatures in the range from −38 to −10 ◦C at 5–15 % relative humidity with respect to water to ensure their formation in a highly viscous phase state, i.e. semi-solid or glassy. The ice nucleation ability of SOA particles with different sizes was investigated with a new continuous flow diffusion chamber. For the first time, we observed heterogeneous ice nucleation of viscous α-pinene SOA in the deposition mode for ice saturation ratios between 1.3 and 1.4 significantly below the homogeneous freezing limit. The maximum frozen fractions found at temperatures between −36.5 and −38.3 °C ranged from 6 to 20 % and did not depend on the particle surface area. Global modelling of monoterpene SOA particles suggests that viscous biogenic SOA particles are indeed present in regions where cirrus cloud formation takes place. Hence, they could make up an important contribution to the global ice nuclei (IN) budget.
Under certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the CLOUD experiment at CERN, we deployed a new in-situ optical method to detect the viscosity of α-pinene SOA particles and measured their transition from the amorphous viscous to liquid state. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical liquid particles during deliquescence. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to spherical shape was observed as the RH was increased to between 35 % at −10 ◦C and 80 % at −38 ◦C, confirming previous calculations of the viscosity transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere.
Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
(2015)
Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study, we focus on a challenging size range, i.e. particles that have grown to diameters of 10 and 15nm following nucleation, and measure their water uptake. Water uptake constrains their chemical composition. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at subsaturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) experiments performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from α-pinene oxidation. The hygroscopicity parameter Κ decreased with increasing particle size indicating decreasing acidity of particles. No clear effect of the sulfuric acid monomer concentrations on the hygroscopicities of 10nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15nm particles sharply decreased with decreasing sulfuric acid monomer concentrations. In 20 particular, when the concentrations of sulfuric acid was 5.1 x 106 molecules cm exp -3 in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured Κ of 15nm particles was 0.3 ± 0.01 close to the value reported for dimethylamine sulfate (DMAS) (Κ DMAS ~ 0.28). Furthermore, the difference in Κ between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The Κ values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from α-pinene ozonolysis play a significant role in particle growth already at 10nm sizes.
In most habitats, vegetation provides the main structure of the environment. This complexity can facilitate biodiversity and ecosystem services. Therefore, measures of vegetation structure can serve as indicators in ecosystem management. However, many structural measures are laborious and require expert knowledge. Here, we used consistent and convenient measures to assess vegetation structure over an exceptionally broad elevation gradient of 866–4550m above sea level at Mount Kilimanjaro, Tanzania. Additionally, we compared (human)-modified habitats, including maize fields, traditionally managed home gardens, grasslands, commercial coffee farms and logged and burned forests with natural habitats along this elevation gradient. We distinguished vertical and horizontal vegetation structure to account for habitat complexity and heterogeneity. Vertical vegetation structure (assessed as number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) displayed a unimodal elevation pattern, peaking at intermediate elevations in montane forests, whereas horizontal structure (assessed as coefficient of variation of number, width and density of vegetation layers, maximum canopy height, leaf area index and vegetation cover) was lowest at intermediate altitudes. Overall, vertical structure was consistently lower in modified than in natural habitat types, whereas horizontal structure was inconsistently different in modified than in natural habitat types, depending on the specific structural measure and habitat type. Our study shows how vertical and horizontal vegetation structure can be assessed efficiently in various habitat types in tropical mountain regions, and we suggest to apply this as a tool for informing future biodiversity and ecosystem service studies.
Nein, in vorliegender Form hätte diese Doktorarbeit nie veröffentlicht werden dürfen, weist sie doch, hochgerechnet, eine sicherlich im vierstelligen Bereich liegende Zahl an Fehlern, Nachlässigkeiten, ja Schlampereien auf. Ein Leser, der sich bis zum bitteren Ende durchgekämpft hat, dürfte fassungslos auf einen Kampf zurückblicken, den der Autor seinerseits mit der, nein: gegen die deutsche Sprache führte, um dabei an elementaren Regeln der Grammatik, Zeichensetzung und bisweilen sogar an der Orthografie zu scheitern. A. Willershausen ist mithin nicht nur dem Genetiv und Dativ, sondern der deutschen Sprache überhaupt feind. Ähnlich sieht’s im Lateinischen und Französischen aus; oft sind nicht einmal gedruckte Texte korrekt wiedergegeben. Und ganz schlimm wird’s, wenn Deutsches und Französisches zusammenstoßen: "Vermittlung Gui de Boulognes […] Verhandlungen Talleyrands de Périgord auf der Poitier-Kampagnes" (S. 81, Anm. 349) ‒ "Sainte-Maria-Madelaine" (S. 196). Diese zwei Beispiele müssen hierfür aus Platzgründen genügen; generell gilt, dass mein Monita-Leporello sehr, sehr lang ist und bei Bedarf eingesehen werden kann. Doch jedem, der sich der Mühe der Lektüre nur eines einzigen Kapitels unterzieht, dürften die vielen Fehlleistungen ohnehin auffallen. Die Verantwortung für all das liegt natürlich beim Autor, aber sicher sind hier auch kritische Fragen an den Doktorvater und den Zweitgutachter sowie an einen Verlag zu stellen, der die Vorlage offensichtlich unbesehen, geschweige denn lektoriert zum Druck freigab. ...
1973 legte Thomas E. Morissey als Schüler von Brian Tierney seine – leider ungedruckt gebliebene – Dissertation »Franciscus de Zabarellis (1360–1417) and the Conciliarist Traditions« vor, um fortan bei diesem Thema zu bleiben, wie vorliegender Band belegt, der eine Auswahl von Aufsätzen aus den Jahren 1976 bis 2010 vereint, 15 davon als Nachdruck, zwei als Erstpublikation. Wer als Gelehrter Aufnahme in die »Variorum Reprints« bei Ashgate findet, gilt, zumindest in der angelsächsischen Welt, als Autorität auf seinem Gebiet, und in der Tat dürfte gegenwärtig allenfalls noch Dieter Girgensohn sich ähnlich gut wie Morissey im Leben und Werk des Paduaner Rechtsgelehrten auskennen, der als akademischer Lehrer und Autor ein großes, internationales Publikum fand und auch kirchenpolitisch von Einfluss war; selbst die nach seinem Tod in Padua Recht studierenden Nikolaus von Kues, Giuliano Cesarini oder Niccolò Tudeschi (Panormitanus) waren noch von seinem Geist geprägt. ...
Interleukin (IL)-22 is a STAT3-activating cytokine displaying characteristic AU-rich elements (ARE) in the 3'-untranslated region (3'-UTR) of its mRNA. This architecture suggests gene regulation by modulation of mRNA stability. Since related cytokines undergo post-transcriptional regulation by ARE-binding tristetraprolin (TTP), the role of this destabilizing protein in IL-22 production was investigated. Herein, we demonstrate that TTP-deficient mice display augmented serum IL-22. Likewise, IL-22 mRNA was enhanced in TTP-deficient splenocytes and isolated primary T cells. A pivotal role for TTP is underscored by an extended IL-22 mRNA half-life detectable in TTP-deficient T cells. Luciferase-reporter assays performed in human Jurkat T cells proved the destabilizing potential of the human IL-22-3'-UTR. Furthermore, overexpression of TTP in HEK293 cells substantially decreased luciferase activity directed by the IL-22-3'-UTR. Transcript destabilization by TTP was nullified upon cellular activation by TPA/A23187, an effect dependent on MEK1/2 activity. Accordingly, IL-22 mRNA half-life as determined in TPA/A23187-stimulated Jurkat T cells decreased under the influence of the MEK1/2 inhibitor U0126. Altogether, data indicate that TTP directly controls IL-22 production, a process counteracted by MEK1/2. The TTP-dependent regulatory pathway described herein likely contributes to the role of IL-22 in inflammation and cancer and may evolve as novel target for pharmacological IL-22 modulation.
Skizzenhaft soll im Folgenden die von Mauthner entwickelte, spezifische Form politischer Sprachkritik im Lichte von Reflexionen seiner jüdischen Zugehörigkeit betrachtet werden. Mauthners Sprachkritik erweist sich in dieser Perspektive als eine eigenständige Form von 'Sprachpolitik', die mit den zeitgleich von Ferdinand de Saussure entwickelten Anfängen einer linguistischen Sprachwissenschaft ebenso wenig gemein hat wie mit der vergleichenden Sprachforschung des 19. Jahrhunderts. Gegen einen 'Fetischismus mit Worten' in den Wissenschaften setzt der stupend belesene Sprachphilosoph einen aufgewerteten Dilettantismus, pointierte Bonmots und parodistische Verfahren.
Background: High reproducibility of LV mass and volume measurement from cine cardiovascular magnetic resonance (CMR) has been shown within single centers. However, the extent to which contours may vary from center to center, due to different training protocols, is unknown. We aimed to quantify sources of variation between many centers, and provide a multi-center consensus ground truth dataset for benchmarking automated processing tools and facilitating training for new readers in CMR analysis.
Methods: Seven independent expert readers, representing seven experienced CMR core laboratories, analyzed fifteen cine CMR data sets in accordance with their standard operating protocols and SCMR guidelines. Consensus contours were generated for each image according to a statistical optimization scheme that maximized contour placement agreement between readers.
Results: Reader-consensus agreement was better than inter-reader agreement (end-diastolic volume 14.7 ml vs 15.2–28.4 ml; end-systolic volume 13.2 ml vs 14.0–21.5 ml; LV mass 17.5 g vs 20.2–34.5 g; ejection fraction 4.2 % vs 4.6–7.5 %). Compared with consensus contours, readers were very consistent (small variability across cases within each reader), but bias varied between readers due to differences in contouring protocols at each center. Although larger contour differences were found at the apex and base, the main effect on volume was due to small but consistent differences in the position of the contours in all regions of the LV.
Conclusions: A multi-center consensus dataset was established for the purposes of benchmarking and training. Achieving consensus on contour drawing protocol between centers before analysis, or bias correction after analysis, is required when collating multi-center results.
Background: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.
Methods: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.
Results: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.
Conclusion: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.
Oxygen vacancies in strontium titanate surfaces (SrTiO3) have been linked to the presence of a two-dimensional electron gas with unique behavior. We perform a detailed density functional theory study of the lattice and electronic structure of SrTiO3 slabs with multiple oxygen vacancies, with a main focus on two vacancies near a titanium dioxide terminated SrTiO3 surface. We conclude based on total energies that the two vacancies preferably inhabit the first two layers, i.e. they cluster vertically, while in the direction parallel to the surface, the vacancies show a weak tendency towards equal spacing. Analysis of the nonmagnetic electronic structure indicates that oxygen defects in the surface TiO2 layer lead to population of Ti ${{t}_{2g}}$ states and thus itinerancy of the electrons donated by the oxygen vacancy. In contrast, electrons from subsurface oxygen vacancies populate Ti eg states and remain localized on the two Ti ions neighboring the vacancy. We find that both the formation of a bound oxygen-vacancy state composed of hybridized Ti 3eg and 4p states neighboring the oxygen vacancy as well as the elastic deformation after extracting oxygen contribute to the stabilization of the in-gap state.
Do economic fluctuations change the labour market attachment of mothers? How is the reentry process into the labour market after childbirth dependent on the country context women live in? Are these processes affected by occupational status? We address these questions using data from the National Longitudinal Study of Youth and the German Life History Study. Event history analyses demonstrate that in Germany and the United States, mothers who work in high occupational status jobs before birth return more quickly to their jobs and are less likely to interrupt their careers. During legally protected leave periods, mothers return at higher rates, exemplifying that family leaves strengthen mothers’ labour force attachment. Economic fluctuations mediate this latter finding, with different consequences in each country. In the United States, mothers tend to return to their jobs faster when unemployment is high. In Germany, mothers on family leave tend to return to their jobs later when unemployment is high. The cross-national comparison shows how similar market forces create distinct responses in balancing work and care.
The transition to a future electricity system based primarily on wind and solar PV is examined for all regions in the contiguous US. We present optimized pathways for the build-up of wind and solar power for least backup energy needs as well as for least cost obtained with a simplified, lightweight model based on long-term high resolution weather-determined generation data. In the absence of storage, the pathway which achieves the best match of generation and load, thus resulting in the least backup energy requirements, generally favors a combination of both technologies, with a wind/solar PV (photovoltaics) energy mix of about 80/20 in a fully renewable scenario. The least cost development is seen to start with 100% of the technology with the lowest average generation costs first, but with increasing renewable installations, economically unfavorable excess generation pushes it toward the minimal backup pathway. Surplus generation and the entailed costs can be reduced significantly by combining wind and solar power, and/or absorbing excess generation, for example with storage or transmission, or by coupling the electricity system to other energy sectors.
We set up and solve a rich life-cycle model of household decisions involving consumption of both perishable goods and housing services, stochastic and unspanned labor income, stochastic house prices, home renting and owning, stock investments, and portfolio constraints. The model features habit formation for housing consumption, which leads to optimal decisions closer in line with empirical observations. Our model can explain (i) that stock investments are low or zero for many young agents and then gradually increasing over life, (ii) that the housing expenditure share is age- and wealth-dependent, (iii) that perishable consumption is more sensitive to wealth and income shocks than housing consumption, and (iv) that non-housing consumption is hump-shaped over life.
Simple cells in primary visual cortex were famously found to respond to low-level image components such as edges. Sparse coding and independent component analysis (ICA) emerged as the standard computational models for simple cell coding because they linked their receptive fields to the statistics of visual stimuli. However, a salient feature of image statistics, occlusions of image components, is not considered by these models. Here we ask if occlusions have an effect on the predicted shapes of simple cell receptive fields. We use a comparative approach to answer this question and investigate two models for simple cells: a standard linear model and an occlusive model. For both models we simultaneously estimate optimal receptive fields, sparsity and stimulus noise. The two models are identical except for their component superposition assumption. We find the image encoding and receptive fields predicted by the models to differ significantly. While both models predict many Gabor-like fields, the occlusive model predicts a much sparser encoding and high percentages of ‘globular’ receptive fields. This relatively new center-surround type of simple cell response is observed since reverse correlation is used in experimental studies. While high percentages of ‘globular’ fields can be obtained using specific choices of sparsity and overcompleteness in linear sparse coding, no or only low proportions are reported in the vast majority of studies on linear models (including all ICA models). Likewise, for the here investigated linear model and optimal sparsity, only low proportions of ‘globular’ fields are observed. In comparison, the occlusive model robustly infers high proportions and can match the experimentally observed high proportions of ‘globular’ fields well. Our computational study, therefore, suggests that ‘globular’ fields may be evidence for an optimal encoding of visual occlusions in primary visual cortex.
Objectives: Previous studies investigating speech perception in noise have typically been conducted with static masker positions. The aim of this study was to investigate the effect of spatial separation of source and masker (spatial release from masking, SRM) in a moving masker setup and to evaluate the impact of adaptive beamforming in comparison with fixed directional microphones in cochlear implant (CI) users.
Design: Speech reception thresholds (SRT) were measured in S0N0 and in a moving masker setup (S0Nmove) in 12 normal hearing participants and 14 CI users (7 subjects bilateral, 7 bimodal with a hearing aid in the contralateral ear). Speech processor settings were a moderately directional microphone, a fixed beamformer, or an adaptive beamformer. The moving noise source was generated by means of wave field synthesis and was smoothly moved in a shape of a half-circle from one ear to the contralateral ear. Noise was presented in either of two conditions: continuous or modulated.
Results: SRTs in the S0Nmove setup were significantly improved compared to the S0N0 setup for both the normal hearing control group and the bilateral group in continuous noise, and for the control group in modulated noise. There was no effect of subject group. A significant effect of directional sensitivity was found in the S0Nmove setup. In the bilateral group, the adaptive beamformer achieved lower SRTs than the fixed beamformer setting. Adaptive beamforming improved SRT in both CI user groups substantially by about 3 dB (bimodal group) and 8 dB (bilateral group) depending on masker type.
Conclusions: CI users showed SRM that was comparable to normal hearing subjects. In listening situations of everyday life with spatial separation of source and masker, directional microphones significantly improved speech perception with individual improvements of up to 15 dB SNR. Users of bilateral speech processors with both directional microphones obtained the highest benefit.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Background: SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3.
Methods: We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631).
Results: Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%).
Conclusion: IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Twelve new country records are presented for Diplocladus compactus Gerstmeier and Weiss, 2009, D. louvelii (Spinola, 1844), D. oculicollis (Fairmaire, 1885), D. rufus (Pic, 1953) Strotocera brevefasciata Gerstmeier and Weiss, 2009, and S. emerita (Péringuey, 1899) and the distribution of S. chicoi Gerstmeier and Weiss, 2009, is corrected.
Vimentin is currently used to differentiate between malignant renal carcinomas and benign oncocytomas. Recent reports showing Vimentin positive oncocytomas seriously question the validity of this present diagnostic approach. Vimentin 3 is a spliced variant and ends with a unique C-terminal ending after exon 7 which differentiates it from the full length version that has 9 exons. Therefore, the protein size is different; the full length Vimentin version has a protein size of ~57 kDa and the truncated version of ~47 kDa. We designed an antibody, called Vim3, against the unique C-terminal ending of the Vimentin 3 variant. Using immune histology, immune fluorescence, Western blot, and qRT-PCR analysis, a Vim3 overexpression was detectable exclusively in oncocytoma, making the detection of Vim3 a potential specific marker for benign kidney tumors. This antibody is the first to clearly differentiate benign oncocytoma and the mimicking eosinophilic variants of the RCCs. This differentiation between malignant and benign RCCs is essential for operative planning, follow-up therapy, and patients' survival. In the future the usage of Vimentin antibodies in routine pathology has to be applied with care. Consideration must be given to Vimentin specific binding epitopes otherwise a misdiagnosis of the patients' tumor samples may result.
Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document.
This paper presents results from the "INUIT-JFJ/CLACE 2013" field campaign at the high alpine research station Jungfraujoch in January/February 2013. The chemical composition of ice particle residuals (IPR) in a size diameter range of 200–900 nm was measured in orographic, convective and non-convective clouds with a single particle mass spectrometer (ALABAMA) under ambient conditions characterized by temperatures between −28 and −4 °C and wind speed from 0.1 to 21 km h−1. Additionally, background aerosol particles in cloud free air were investigated. The IPR were sampled from mixed-phase clouds with two inlets which selectively extract small ice crystals in-cloud, namely the Counterflow Virtual Impactor (Ice-CVI) and the Ice Selective Inlet (ISI). The IPR as well as the aerosol particles were classified into seven different particle types: (1) black carbon, (2) organic carbon, (3) black carbon internally mixed with organic carbon, (4) minerals, (5) one particle group (termed "BioMinSal") that may contain biological particles, minerals, or salts, (6) industrial metals, and (7) lead containing particles. For any sampled particle population it was determined by means of single particle mass spectrometer how many of the analyzed particles belonged to each of these categories. Accordingly, between 20 and 30% of the IPR and roughly 42% of the background particles contained organic carbon. The measured fractions of minerals in the IPR composition varied from 6 to 33%, while the values for the "BioMinSal" group were between 15 and 29%. Four percent to 31% of the IPR contained organic carbon mixed with black carbon. Both inlets delivered similar results of the chemical composition and of the particle size distribution, although lead was found only in the IPR sampled by the Ice-CVI. The results show that the ice particle residual composition varies substantially between different cloud events, which indicates the influence of different meteorological conditions, such as origin of the air masses, temperature and wind speed.
During January/February 2013, at the High Alpine Research Station Jungfraujoch a measurement campaign was carried out, which was centered on atmospheric ice-nucleating particles (INP) and ice particle residuals (IPR). Three different techniques for separation of INP and IPR from the non-ice-active particles are compared. The Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI) sample ice particles from mixed phase clouds and allow for the analysis of the residuals. The combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Counterflow Virtual Impactor (IN-PCVI) provides ice-activating conditions to aerosol particles and extracts the activated INP for analysis.Collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine size, chemical composition and mixing state. All INP/IPR-separating techniques had considerable abundances (median 20 – 70 %) of instrumental contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH+IN-PCVI: steel particles). Also, potential sampling artifacts (e.g., pure soluble material) occurred with a median abundance of < 20 %. While these could be explained as IPR by ice break-up, for INP their IN-ability pathway is less clear. After removal of the contamination artifacts, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Soot was a minor contributor. Lead was detected in less than 10 % of the particles, of which the majority were internal mixtures with other particle types. Sea-salt and sulfates were identified by all three methods as INP/IPR. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also separated many submicron IPR. As strictly parallel sampling could not be performed, a part of the discrepancies between the different techniques may result from variations in meteorological conditions and subsequent INP/IPR composition. The observed differences in the particle group abundances as well as in the mixing state of INP/IPR express the need for further studies to better understand the influence of the separating techniques on the INP/IPR chemical
composition.
Der Beitrag ordnet die "Sagenbücher" von Alfred von Reumont (1808-1887) - Aachens Liederkranz und Sagenwelt (1829, Neubearbeitung 1873: Aachener Liederchronik) und Rheinlands Sagen, Geschichten und Legenden (1837) - in den Sagen-Diskurs ihrer Zeit ein, der im Rheinland vor allem durch die Rheinromantik geprägt wurde. Der Aufsatz schließt mit Bemerkungen zur Wahrnehmung des Verhältnisses von Sage und Geschichte im 19. Jahrhundert.
Partial wave analysis of the reaction p(3.5 GeV) + p → pK +Λ to search for the "ppK−" bound state
(2015)
Employing the Bonn–Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction p(3.5 GeV) + p → pK +Λ. This reaction might contain information about the kaonic cluster “ppK −” (with quantum numbers J P = 0− and total isospin I = 1/2) via its decay into pΛ. Due to interference effects in our coherent description of the data, a hypothetical KNN (or, specifically “ppK −”) cluster signal need not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectrum like pΛ. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a KNN cluster. At a confidence level of CLs = 95% such a cluster cannot contribute more than 2–12% to the total cross section with a pK +Λ final state, which translates into a production cross-section between 0.7 μb and 4.2 μb, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.
Ziel der Arbeit ist eine zusammenfassende floristisch-pflanzensoziologische Darstellung der Wälder des Saarlandes. Der Schwerpunkt liegt dabei auf den Verbänden Carpinion betuli, Tilio platyphylli-Acerion pseudoplatani, Fagion sylvaticae und dem Deschampsio flexuosae-Fagion. Das Quercion robori-petraeae sowie das Quercion pubescenti-petraeae werden ebenfalls beschrieben und interpre-tiert. Hier besteht allerdings weiterer Untersuchungsbedarf, um die standörtlichen wie floristisch-soziologischen Details noch besser heraus zu arbeiten.
Das Aufnahmematerial (539 Aufnahmen) stammt von Dr. Erhard Sauer (erhoben in den 1960er und 1970er Jahren im Rahmen der forstlichen Standortkartierung) und vom Autor selbst (erfasst zwischen 2003 und 2014). Alle Vegetationsaufnahmen wurden nach der Methode von Braun-Blanquet erfasst. Zur Beschreibung und Interpretation der Waldgesellschaften im Untersuchungsgebiet werden zudem die vorliegenden Arbeiten aus Teilgebieten des Saarlandes mit herangezogen. Synsystematisch folgt der Autor im Wesentlichen Oberdorfer und Härdtle et al., in dem die azidophilen Buchenwaldgesellschaf-ten der Ordnung Quercetalia robori-petraeae zugeordnet werden.
Das gesamte Gesellschaftsspektrum weist mit seinen diagnostischen Arten auf die ausgesprochen subatlantische Klimatönung des Untersuchungsgebietes hin. Die Luzulo-Fagenion- sowie die Quercion roboris-petraeae-Gesellschaften werden der westlichen Teucrium scorodonia-Vikariante zugerechnet. In den wärmeliebenden Carpinion-Gesellschaften des West-Saarlandes kommen bereits die mediterran-atlantisch verbreiteten Arten Dioscorea communis und Viola alba vor und in den Tilio-Acerion-Gesellschaften Polystichum setiferum, ebenfalls eine submediterran-subatlantische Art. Floristisch gut charakterisierte Kalk-Buchenwälder in submontan-montaner Höhenlage gibt es im Saarland nicht, weshalb Hordelymo-Fagetum und Carici-Fagetum nur fragmentarisch ausgebildet sind. Das schwer-punktmäßig subkontinental verbreitete Galio-Carpinetum beschränkt sich im subatlantisch getönten Untersuchungsgebiet auf extrazonale wärmeliebende Standorte.
We analyze the macroeconomic implications of increasing the top marginal income tax rate using a dynamic general equilibrium framework with heterogeneous agents and a fiscal structure resembling the actual U.S. tax system. The wealth and income distributions generated by our model replicate the empirical ones. In two policy experiments, we increase the statutory top marginal tax rate from 35 to 70 percent and redistribute the additional tax revenue among households, either by decreasing all other marginal tax rates or by paying out a lump-sum transfer to all households. We find that increasing the top marginal tax rate decreases inequality in both wealth and income but also leads to a contraction of the aggregate economy. This is primarily driven by the negative effects that the tax change has on top income earners. The aggregate gain in welfare is sizable in both experiments mainly due to a higher degree of distributional equality.
We analyze the macroeconomic implications of increasing the top marginal income tax rate using a dynamic general equilibrium framework with heterogeneous agents and a fiscal structure resembling the actual U.S. tax system. The wealth and income distributions generated by our model replicate the empirical ones. In two policy experiments, we increase the statutory top marginal tax rate from 35 to 70 percent and redistribute the additional tax revenue among households, either by decreasing all other marginal tax rates or by paying out a lump-sum transfer to all households. We find that increasing the top marginal tax rate decreases inequality in both wealth and income but also leads to a contraction of the aggregate economy. This is primarily driven by the negative effects that the tax change has on top income earners. The aggregate gain in welfare is sizable in both experiments mainly due to a higher degree of distributional equality.
BACKGROUND AND PURPOSE: We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease.
METHODS: Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD).
RESULTS: Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations.
CONCLUSIONS: We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS.
Emotional instability, difficulties in social adjustment, and disinhibited behavior are the most common symptoms of the psychiatric comorbidities in juvenile myoclonic epilepsy (JME). This psychopathology has been associated with dysfunctions of mesial-frontal brain circuits. The present work is a first direct test of this link and adapted a paradigm for probing frontal circuits during empathy for pain. Neural and psychophysiological parameters of pain empathy were assessed by combining functional magnetic resonance imaging (fMRI) with simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In JME patients, we observed reduced neural activation of the anterior cingulate cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy for pain in patients. At the same time, pupil dilation was positively related to neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally showed reduced functional connectivity with the primary and secondary somatosensory cortex, areas fundamentally implicated in processing the somatic cause of another's pain. Our results provide first evidence that alterations of mesial-frontal circuits directly affect psychosocial functioning in JME patients and draw a link of pupil dynamics with brain activity during emotional processing. The findings of reduced pain empathy related activation of the ACC and AI and aberrant functional integration of the ACC with somatosensory cortex areas provide further evidence for this network's role in social behavior and helps explaining the JME psychopathology and patients' difficulties in social adjustment.
Biodiversity is unevenly distributed on Earth. Highly diverse biotas are particularly expected in mountain systems, because altitudinal zonation provides a number of habitat alternatives, which could lead to lower extinction rates during climatic changes. Nevertheless, the impact of environmental changes on plant diversification (especially for sub-alpine taxa) in the course of mountain orogenesis remains poorly understood. This is also true for the highest and largest plateau on Earth, the Qinghai-Tibetan Plateau (QTP) and its surrounding areas.In this doctoral thesis, I investigated the impact of environmental changes on plant diversification and the floristic exchange between the QTP region and biodiversity hotspots of Southeast Asia as well as other parts of the world by using the sub-alpine genera Agapetes and Vaccinium (Vaccinieae, Ericaceae) as well as Tripterospermum (Gentianinae, Gentianaceae) as model systems. Furthermore, I examined the role of niche evolution and conservatism in a changing environment over time, and detected possible beneficial morphological traits of plants in the surroundings of the QTP by investigating subtropical Gentianinae (Crawfurdia, Kuepferia, Metagentiana, Sinogentiana, and Tripterospermum; Gentianaceae).
Das Enzym 5-Lipoxygenase (5-LO) spielt eine entscheidende Rolle in der Generierung von Leukotrienen. Diese fungieren als wichtige proinflammatorische Mediatoren. Darüber hinaus ist die 5-LO anhand ihrer N-terminalen Domäne in der Lage mit verschiedenen Proteinen zu interagieren. Unter den Interaktionspartnern befindet sich Dicer, ein Enzym welches für den finalen Schritt der microRNA (miRNA)-Biosynthese verantwortlich ist. MiRNA sind kurze, nicht kodierende RNA Stränge mit einer typischen Länge von etwa 23 Nukleotiden, die an der posttranskriptionalen Regulierung der Proteinbiosynthese beteiligt sind.
Ziel dieser Arbeit war es den Einfluss der 5-LO auf die miRNA-Prozessierung im zellulären Kontext zu untersuchen. Als Modellsystem wurde die MonoMac6 (MM6) Zelllinie ausgewählt. MM6-Zellen exprimieren im undifferenzierten Grundzustand nur geringe Mengen an 5-LO. Erst nach Differenzierung mittels transformierenden Wachstumsfaktors ß (TGFß) und Calcitriol kommt es zur Induktion der 5-LO Proteinbiosynthese. Darüber hinaus war es Basavarajappa et al. möglich die 5-LO-Expression in diesen Zellen mittels RNA-Interferenz stark herunter zu regulieren (Δ5-LO).
Um die Frage der Auswirkungen des 5-LO knockdowns auf die miRNA-Expression analysieren zu können, wurde ein Microarray in differenzierten Kontroll-und Δ5-LO-Zellen durchgeführt.Es wurden 37 miRNAs identifiziert deren Expression 5-LO abhängig ist. Dabei war das Niveau von 30 Vertretern in Abwesenheit der 5-LO erhöht, wohingegen die Expression von sieben miRNAs reduziert war. Unter diesen sieben herunter regulierten miRNAs befanden sich miR-99b-5p und miR-125a-5p, die einem gemeinsamen Cluster entstammen. Als Cluster wird eine Gruppe von miRNAs bezeichnet, die aus einem gemeinsamen primären Transkript (pri-miRNA) hervorgeht. Diese Eigenschaft führte zur Vermutung, dass bereits die Expression dieser pri-miRNA durch die 5-LO reguliert wird. Allerdings zeigte sichim Verlauf dieser Arbeit, dass die Expression der pri-miRNA 5-LO unabhängig verläuft. Im Gegensatz dazu wies die Zwischenstufe zwischen pri-miRNA und reifer miRNA eine reduzierte Expression in Δ5-LO Zellen auf. Für die Prozessierung dieser sogenannten precursor miRNAs (pre-miRNA) ist die Ribonuklease III Drosha verantwortlich, welche die pre-miRNA aus der jeweiligen pri-miRNAs chneidet. Das verringerte pre-miR-99b-und pre-miR-125a-Niveau ist daher ein Hinweis darauf, dass überDicerhinausmöglicherweise ebenfalls die Drosha Aktivität mittels 5-LO reguliert wird.
Des Weiteren wurde untersucht iniefern Leukotriene beziehungsweise 5-LO-Inhibitoren die Expression von miR-99b-5p und miR-125a-5p beeinflussen. Dabei stellte sich heraus, dass das miRNA-Niveau unabhängig von der vorhandenen Leukotrien-Menge ist. Das 5-LO aktivierende Protein (FLAP) besitzt dahingegen einen mit der 5-LO vergleichbaren Einfluss auf die reife miRNA. FLAP ist ein weiterer Interaktionspartner der 5-LO und essentiell für die Leukotrien-Biosynthese in vivo. Anhand von Protein-Lokalisationsstudien mittels Immunofluoreszenz konnte gezeigt werden, dass FLAP außerdem in der Lage zu sein scheint die Relokalisation der 5-LO aus dem Zytoplasma in den Nukleus einzuschränken. Im Zytoplasma ist die 5-LO in der Lage mit Dicer zu interagieren. Daten bezüglich einer Interaktion zwischen Drosha und 5-LO im Zellkern liegen bisher nicht vor. Eine etwaige Interaktion könnte allerdings helfen die reduzierten pre-miRNA Spiegel in Abwesenheit der 5-LO zu erklären.
Im Laufe dieser Arbeit wurden weiterhin die Auswirkungen von proinflammatorischen Lipopolysacchariden (LPS) auf die Prozessierung von miR-99b-5p und miR-125a-5p analysiert. Ausschließlich in Anwesenheit von 5-LO zeigte sich eine differenzierungsunabhängig gesteigerte Biosynthese der pri-und der reifen miRNA. Allerdings konnte kein Einfluss von LPS auf die 5-LO-Lokalisation beziehungsweise Expression festgestellt werden. Aufgrund dessen sind weiterführende Studien, die den Zusammenhang zwischen LPS induzierter miR-99b-5p- beziehungsweise miR-125a-5p-Biosynthese und 5-LO herstellen, nötig.
Abschließend hat sich diese Arbeit mit den Zielgenen der durch 5-LO regulierten miRNAs auseinandergesetzt. Es konnte gezeigt werden, dass in Abwesenheit von miR-99b-5p und miR-125a-5p die Freisetzung der beiden durch LPS stimulierten Zytokine Interleukin 6 (IL-6) und Tumornekrosefaktor α (TNFα) gesteigert ist. Interessanterweise besitzt TNFα einen stimulierenden Effekt auf die Leukotrien-Biosynthese. Allerdings konnte kein direkter Zusammenhang zwischen miR-99b-5p/miR-125a-5p Expression, TNFα und der 5-LO Aktivität hergestellt werden. Der Einsatz von miR-99b-5p-und miR-125a-5p-Inhibitoren zeigte keine Auswirkungen auf die Leukotrien-Biosynthese nach LPS Stimulation. Im Gegensatz dazu konnte in unstimulierten Zellen eine signifikante Aktivitätssteigerung in Abwesenheit von miR-125a-5p festgestellt werden. Diese Beobachtungen legen nahe, dass miR-125a-5p einen TNFα unabhängigen Einfluss auf die 5-LO Aktivität besitzt. In LPS stimulierten Zellen kommt es möglicherweise zu Überlagerungen dieses Effektes.
Zusammenfassend konnte in dieser Arbeit gezeigt werden, dass 5-LO eine regulierende Funktion auf die Reifung der beiden miRNAs miR-99b-5p und miR-125a-5p aufweist. Dieser Effekt könnte einer direkten Interaktion zwischen 5-LO und Dicer zuzuschreiben sein. Des Weiteren konnte gezeigt werden, dass die Regulierung der Expression bestimmter miRNAs mittels 5-LO nicht auf deren kanonischer enzymatischer Aktivität beruht. Diese Ergebnisse schlagen eine neue Richtung der 5-LO-Forschung ein und können in Zukunft dazu beitragen 5-LO vermittelte Effekte besser charakterisieren zu können.
Background: Hundreds of West African healthcare workers (HCW) have become ill with Ebola virus disease (EVD) and died during the recent outbreak. The occurrence of occupational infections in laboratories could be due to the lack of use of personal protective equipment, the failure to implement specific regulations about the use of equipment and how to work with hazardous materials. Our study attempted to assess the information as well as training level of HCW of a German high level isolation unit and their concern over an occupationally acquired EVD.
Methods: During the recent Ebola virus outbreak a survey was conducted among HCWs, using an anonymous questionnaire.
Results: Although 70% of our total study population stated that they have all the information needed to care for Ebola patients, only 18.2% of laboratory workers and 29.4% of the HCW of the virology department felt sufficiently trained. The HCW rated the Internet (64.3%) and the daily press (54.3%) as the most important sources of information. Medical literature (45.7%) and official institutions (40.4%) were rated less often.
Conclusions: Formulated pointedly, the HCW turned to popular science to get the information they need to feel safe. Further in house training regarding practical skills and reference to scientific literature would be a better solution to ensure workplace safety.
Direct photon production at mid-rapidity in Pb-Pb collisions at sNN−−−√=2.76 TeV was studied in the transverse momentum range 0.9<pT<14 GeV/c. Photons were detected with the highly segmented electromagnetic calorimeter PHOS and via conversions in the ALICE detector material with the e+e− pair reconstructed in the central tracking system. The results of the two methods were combined and direct photon spectra were measured for the 0-20%, 20-40%, and 40-80% centrality classes. For all three classes, agreement was found with perturbative QCD calculations for pT≳5 GeV/c. Direct photon spectra down to pT≈1 GeV/c could be extracted for the 20-40% and 0-20% centrality classes. The significance of the direct photon signal for 0.9<pT<2.1 GeV/c is 2.6σ for the 0-20% class. The spectrum in this pT range and centrality class can be described by an exponential with an inverse slope parameter of (297±12stat±41syst) MeV. State-of-the-art models for photon production in heavy-ion collisions agree with the data within uncertainties.
The centrality dependence of the charged-particle pseudorapidity density measured with ALICE in Pb-Pb collisions at sNN−−−√ over a broad pseudorapidity range is presented. This Letter extends the previous results reported by ALICE to more peripheral collisions. No strong change of the charged-particle pseudorapidity density distributions with centrality is observed, and when normalised to the number of participating nucleons in the collisions, the evolution over pseudorapidity with centrality is likewise small. The broad pseudorapidity range allows precise estimates of the total number of produced charged particles which we find to range from 162±22 (syst.) to 17170±770 (syst.) in 80-90% and 0-5 central collisions, respectively. The total charged-particle multiplicity is seen to approximately scale with the number of participating nucleons in the collision. This suggests that hard contributions to the charged-particle multiplicity are limited. The results are compared to models which describe dNch/dη at mid-rapidity in the most central Pb-Pb collisions and it is found that these models do not capture all features of the distributions.
We present measurements of the azimuthal dependence of charged jet production in central and semi-central sNN−−−√ = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as vch jet2. Jet finding is performed employing the anti-kT algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero vch jet2 is observed in semi-central collisions (30-50\% centrality) for 20 < pch jetT < 90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the v2 of single charged particles at high pT. Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions.
A detailed study of pseudorapidity densities and multiplicity distributions of primary charged particles produced in proton-proton collisions, at s√= 0.9, 2.36, 2.76, 7 and 8 TeV, in the pseudorapidity range |η|<2, was carried out using the ALICE detector. Measurements were obtained for three event classes: inelastic, non-single diffractive and events with at least one charged particle in the pseudorapidity interval |η|<1. The use of an improved track-counting algorithm combined with ALICE's measurements of diffractive processes allows a higher precision compared to our previous publications. A KNO scaling study was performed in the pseudorapidity intervals |η|< 0.5, 1.0 and 1.5. The data are compared to other experimental results and to models as implemented in Monte Carlo event generators PHOJET and recent tunes of PYTHIA6, PYTHIA8 and EPOS.
We report on results obtained with the Event Shape Engineering technique applied to Pb-Pb collisions at sNN−−−√=2.76 TeV. By selecting events in the same centrality interval, but with very different average flow, different initial state conditions can be studied. We find the effect of the event-shape selection on the elliptic flow coefficient v2 to be almost independent of transverse momentum pT, as expected if this effect is due to fluctuations in the initial geometry of the system. Charged hadron, pion, kaon, and proton transverse momentum distributions are found to be harder in events with higher-than-average elliptic flow, indicating an interplay between radial and elliptic flow.
The elliptic flow, v2, of muons from heavy-flavour hadron decays at forward rapidity (2.5<y<4) is measured in Pb--Pb collisions at sNN−−−√~=~2.76 TeV with the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v2 of muons from heavy-flavour hadron decays on the collision centrality, in the range 0--40\%, and on transverse momentum, pT, is studied in the interval 3<pT<10~GeV/c. A positive v2 is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10--20\% and 20--40\% centrality classes) for the pT interval from 3 to about 5 GeV/c. The v2 magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6<pT<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. The model calculations describe the measured v2 within uncertainties.
Measurement of electrons from heavy-flavour hadron decays in p–Pb collisions at √sNN = 5.02 TeV
(2015)
The production of electrons from heavy-flavour hadron decays was measured as a function of transverse momentum (pT) in minimum-bias p-Pb collisions at sNN−−−√=5.02 TeV with ALICE at the LHC. The measurement covers the pT interval 0.5<pT<12 GeV/c and the rapidity range −1.06<ycms<0.14 in the centre-of-mass reference frame. The contribution of electrons from background sources was subtracted using an invariant mass approach. The nuclear modification factor RpPb was calculated by comparing the pT-differential invariant cross section in p-Pb collisions to a pp reference at the same centre-of-mass energy, which was obtained by interpolating measurements at s√=2.76 TeV and s√=7 TeV. The RpPb is consistent with unity within uncertainties of about 25%, which become larger for pT below 1 GeV/c. The data are described by recent model calculations that include cold nuclear matter effects.
We report on two-particle charge-dependent correlations in pp, p-Pb, and Pb-Pb collisions as a function of the pseudorapidity and azimuthal angle difference, Δη and Δφ respectively. These correlations are studied using the balance function that probes the charge creation time and the development of collectivity in the produced system. The dependence of the balance function on the event multiplicity as well as on the trigger and associated particle transverse momentum (pT) in pp, p-Pb, and Pb-Pb collisions at sNN−−−√=7, 5.02, and 2.76 TeV, respectively, are presented. In the low transverse momentum region, for 0.2<pT<2.0 GeV/c, the balance function becomes narrower in both Δη and Δφ directions in all three systems for events with higher multiplicity. The experimental findings favor models that either incorporate some collective behavior (e.g. AMPT) or different mechanisms that lead to effects that resemble collective behavior (e.g. PYTHIA8 with color reconnection). For higher values of transverse momenta the balance function becomes even narrower but exhibits no multiplicity dependence, indicating that the observed narrowing with increasing multiplicity at low pT is a feature of bulk particle production.
We report on the inclusive production cross sections of J/ψ, ψ(2S), Υ(1S), Υ(2S) and Υ(3S), measured at forward rapidity with the ALICE detector in pp collisions at a center-of-mass energy s√=8 TeV. The analysis is based on data collected at the LHC and corresponds to an integrated luminosity of 1.28 pb−1. Quarkonia are reconstructed in the dimuon-decay channel. The differential production cross sections are measured as a function of the transverse momentum pT and rapidity y, over the pT ranges 0<pT<20 GeV/c for J/ψ, 0<pT<12 GeV/c for all other resonances, and for 2.5<y<4. The cross sections, integrated over pT and y, and assuming unpolarized quarkonia, are σJ/ψ=8.63±0.04±0.79 μb, σψ(2S)=1.18±0.08±0.21 μb, σΥ(1S)=68±6±7 nb, σΥ(2S)=25±5±4 nb and σΥ(3S)=9±4±1 nb, where the first uncertainty is statistical and the second one is systematic. These values agree, within at most 1.2σ, with measurements performed by the LHCb collaboration in the same rapidity range.
The first measurement of ϕ-meson production in p-Pb collisions at a nucleon-nucleon centre-of-mass energy sNN−−−√ = 5.02 TeV has been performed with the ALICE apparatus at the LHC. The ϕ-mesons have been identified in the dimuon decay channel in the transverse momentum (pT) range 1<pT<7 GeV/c, both in the p-going (2.03<y<3.53) and the Pb-going (−4.46<y<−2.96) directions, where y stands for the rapidity in the nucleon-nucleon centre-of-mass. Differential cross sections as a function of transverse momentum and rapidity are presented. The forward-backward asymmetry for ϕ-meson production is measured for 2.96<|y|<3.53, resulting in a factor ∼0.5 with no significant pT dependence within the uncertainties. The pT dependence of the ϕ nuclear modification factor RpPb exhibits an enhancement up to a factor 1.6 at pT = 3-4 GeV/c in the Pb-going direction. The pT dependence of the ϕ-meson cross section in pp collisions at s√ = 2.76 TeV, which is used to determine a reference for the p-Pb results, is also presented here for 1<pT<5 GeV/c and 2.5<y<4.
The production of prompt charmed mesons D0, D+ and D∗+, and their antiparticles, was measured with the ALICE detector in Pb-Pb collisions at the centre-of-mass energy per nucleon pair, sNN−−−√, of 2.76 TeV. The production yields for rapidity |y|<0.5 are presented as a function of transverse momentum, pT, in the interval 1-36 GeV/c for the centrality class 0-10% and in the interval 1-16 GeV/c for the centrality class 30-50%. The nuclear modification factor RAA was computed using a proton-proton reference at s√=2.76 TeV, based on measurements at s√=7 TeV and on theoretical calculations. A maximum suppression by a factor of 5-6 with respect to binary-scaled pp yields is observed for the most central collisions at pT of about 10 GeV/c. A suppression by a factor of about 2-3 persists at the highest pT covered by the measurements. At low pT (1-3 GeV/c), the RAA has large uncertainties that span the range 0.35 (factor of about 3 suppression) to 1 (no suppression). In all pT intervals, the RAA is larger in the 30-50% centrality class compared to central collisions. The D-meson RAA is also compared with that of charged pions and, at large pT, charged hadrons, and with model calculations.
Measurement of D+s production and nuclear modification factor in Pb-Pb collisions at √sNN = 2.76 TeV
(2015)
The production of prompt D+s mesons was measured for the first time in collisions of heavy nuclei with the ALICE detector at the LHC. The analysis was performed on a data sample of Pb-Pb collisions at a centre-of-mass energy per nucleon pair, sNN−−−√, of 2.76 TeV in two different centrality classes, namely 0-10% and 20-50%. D+s mesons and their antiparticles were reconstructed at mid-rapidity from their hadronic decay channel D+s→ϕπ+, with ϕ→K−K+, in the transverse momentum intervals 4<pT<12 GeV/c and 6<pT<12 GeV/c for the 0-10% and 20-50% centrality classes, respectively. The nuclear modification factor RAA was computed by comparing the pT-differential production yields in Pb-Pb collisions to those in proton-proton (pp) collisions at the same energy. This pp reference was obtained using the cross section measured at s√=7 TeV and scaled to s√=2.76 TeV. The RAA of D+s mesons was compared to that of non-strange D mesons in the 10% most central Pb-Pb collisions. At high pT (8<pT<12 GeV/c) a suppression of the D+s-meson yield by a factor of about three, compatible within uncertainties with that of non-strange D mesons, is observed. At lower pT (4<pT<8 GeV/c) the values of the D+s-meson RAA are larger than those of non-strange D mesons, although compatible within uncertainties. The production ratios D+s/D0 and D+s\D+ were also measured in Pb-Pb collisions and compared to their values in proton-proton collisions.
We present measurements of the azimuthal dependence of charged jet production in central and semi-central √sNN=2.76 TeV Pb–Pb collisions with respect to the second harmonic event plane, quantified as v2ch jet. Jet finding is performed employing the anti-kT algorithm with a resolution parameter R=0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero v2ch jet is observed in semi-central collisions (30–50% centrality) for 20<pTch jet<90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the v2 of single charged particles at high pT. Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions.
The production of electrons from heavy-flavour hadron decays was measured as a function of transverse momentum (pT) in minimum-bias p–Pb collisions at sNN=5.02 TeV using the ALICE detector at the LHC. The measurement covers the pT interval 0.5<pT<12 GeV/c and the rapidity range −1.065<ycms<0.135 in the centre-of-mass reference frame. The contribution of electrons from background sources was subtracted using an invariant mass approach. The nuclear modification factor RpPb was calculated by comparing the pT-differential invariant cross section in p–Pb collisions to a pp reference at the same centre-of-mass energy, which was obtained by interpolating measurements at s=2.76 TeV and s=7 TeV. The RpPb is consistent with unity within uncertainties of about 25%, which become larger for pT below 1 GeV/c. The measurement shows that heavy-flavour production is consistent with binary scaling, so that a suppression in the high-pT yield in Pb–Pb collisions has to be attributed to effects induced by the hot medium produced in the final state. The data in p–Pb collisions are described by recent model calculations that include cold nuclear matter effects.
We have performed the first measurement of the coherent ψ(2S) photo-production cross section in ultra-peripheral PbPb collisions at the LHC. This charmonium excited state is reconstructed via the ψ(2S)→l+l− and ψ(2S)→J/ψπ+π− decays, where the J/ψ decays into two leptons. The analysis is based on an event sample corresponding to an integrated luminosity of about 22 μb−1. The cross section for coherent ψ(2S) production in the rapidity interval −0.9<y<0.9 is dσψ(2S)coh/dy=0.83±0.19(stat+syst) mb. The ψ(2S) to J/ψ coherent cross section ratio is 0.34−0.07+0.08(stat+syst). The obtained results are compared to predictions from theoretical models.
Charged jet production cross sections in p–Pb collisions at √sNN=5.02 TeV measured with the ALICE detector at the LHC are presented. Using the anti-kT algorithm, jets have been reconstructed in the central rapidity region from charged particles with resolution parameters R=0.2 and R=0.4. The reconstructed jets have been corrected for detector effects and the underlying event background. To calculate the nuclear modification factor, RpPb, of charged jets in p–Pb collisions, a pp reference was constructed by scaling previously measured charged jet spectra at s=7 TeV. In the transverse momentum range 20≤pT,chjet≤120 GeV/c, RpPb is found to be consistent with unity, indicating the absence of strong nuclear matter effects on jet production. Major modifications to the radial jet structure are probed via the ratio of jet production cross sections reconstructed with the two different resolution parameters. This ratio is found to be similar to the measurement in pp collisions at √s=7 TeV and to the expectations from PYTHIA pp simulations and NLO pQCD calculations at √sNN=5.02 TeV.
The elliptic flow, v2, of muons from heavy-flavour hadron decays at forward rapidity (2.5<y<4) is measured in Pb–Pb collisions at √sNN=2.76 TeV with the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee–Yang zeros methods are used. The dependence of the v2 of muons from heavy-flavour hadron decays on the collision centrality, in the range 0–40%, and on transverse momentum, pT, is studied in the interval 3<pT<10 GeV/c. A positive v2 is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10–20% and 20–40% centrality classes) for the pT interval from 3 to about 5 GeV/c with a significance larger than 3σ, based on the combination of statistical and systematic uncertainties. The v2 magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6<pT<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions.
Measurement of an excess in the yield of J/ψ at very low pT in Pb–Pb collisions at √sNN = 2.76 TeV
(2015)
We report on the first measurement of an excess in the yield of J/ψ at very low transverse momentum (pT<0.3 GeV/c) in peripheral hadronic Pb-Pb collisions at sNN−−−√ = 2.76 TeV, performed by ALICE at the CERN LHC. Remarkably, the measured nuclear modification factor (RAA) of J/ψ in the rapidity range 2.5<y<4 reaches about 7 (2) in the pT range 0-0.3 GeV/c in the 70-90% (50-70%) centrality class. The J/ψ production cross section associated with the observed excess is obtained under the hypothesis that coherent photoproduction of J/ψ is the underlying physics mechanism. If confirmed, the observation of J/ψ coherent photoproduction in Pb-Pb collisions at impact parameters smaller than twice the nuclear radius opens new theoretical and experimental challenges and opportunities. In particular, coherent photoproduction accompanying hadronic collisions may provide insight into the dynamics of photoproduction and nuclear reactions, as well as become a novel probe of the Quark-Gluon Plasma.
The pseudorapidity (η) and transverse-momentum (pT) distributions of charged particles produced in proton-proton collisions are measured at the centre-of-mass energy s√ = 13 TeV. The pseudorapidity distribution in |η|< 1.8 is reported for inelastic events and for events with at least one charged particle in |η|< 1. The pseudorapidity density of charged particles produced in the pseudorapidity region |η|< 0.5 is 5.31 ± 0.18 and 6.46 ± 0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15 < pT < 20 GeV/c and |η|< 0.8 for events with at least one charged particle in |η|< 1. The correlation between transverse momentum and particle multiplicity is also investigated by studying the evolution of the spectra with event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators.
The pseudorapidity density of charged particles (dNch/dη) at mid-rapidity in Pb-Pb collisions has been measured at a center-of-mass energy per nucleon pair of sNN−−−√ = 5.02 TeV. It increases with centrality and reaches a value of 1943±54 in |η|<0.5 for the 5% most central collisions. A rise in dNch/dη as a function of sNN−−−√ for the most central collisions is observed, steeper than that observed in proton-proton collisions and following the trend established by measurements at lower energy. The centrality dependence of dNch/dη as a function of the average number of participant nucleons, ⟨Npart⟩, calculated in a Glauber model, is compared with the previous measurement at lower energy. A constant factor of about 1.2 describes the increase in 2⟨Npart⟩⟨dNch/dη⟩ from sNN−−−√ = 2.76 TeV to sNN−−−√ = 5.02 TeV for all centrality intervals, within the measured range of 0-80% centrality. The results are also compared to models based on different mechanisms for particle production in nuclear collisions.
We report on measurements of a charge-dependent flow using a novel three-particle correlator with ALICE in Pb-Pb collisions at the LHC, and discuss the implications for observation of local parity violation and the Chiral Magnetic Wave (CMW) in heavy-ion collisions. Charge-dependent flow is reported for different collision centralities as a function of the event charge asymmetry. While our results are in qualitative agreement with expectations based on the CMW, the nonzero signal observed in higher harmonics correlations indicates a possible significant background contribution. We also present results on a differential correlator, where the flow of positive and negative charges is reported as a function of the mean charge of the particles and their pseudorapidity separation. We argue that this differential correlator is better suited to distinguish the differences in positive and negative charges expected due to the CMW and the background effects, such as local charge conservation coupled with strong radial and anisotropic flow.
Transverse momentum (pT) spectra of pions, kaons, and protons up to pT=20 GeV/c have been measured in Pb-Pb collisions at sNN−−−√=2.76 TeV using the ALICE detector for six different centrality classes covering 0-80%. 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 that decreases towards more peripheral collisions. For pT>10 GeV/c, the nuclear modification factor is found to be the same for all three particle species in each centrality interval within systematic uncertainties of 10-20%. This suggests there is no direct interplay between the energy loss in the medium and the particle species composition in the hard core of the quenched jet. For pT<10 GeV/c, the data provide important constraints for models aimed at describing the transition from soft to hard physics.
The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors, the activity of Nrf2 is inhibited by its interaction with the Keap1 (kelch-like ECH-associated protein 1). Here, we describe (3S)-1-[4-[(2,3,5,6-tetramethylphenyl) sulfonylamino]-1-naphthyl]pyrrolidine-3-carboxylic acid (RA839), a small molecule that binds noncovalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of ∼6 μm, as demonstrated by x-ray co-crystallization and isothermal titration calorimetry. Whole genome DNA arrays showed that at 10 μm RA839 significantly regulated 105 probe sets in bone marrow-derived macrophages. Canonical pathway mapping of these probe sets revealed an activation of pathways linked with Nrf2 signaling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knock-out macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me), RA839 prevented the induction of both inducible nitric-oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice, RA839 acutely induced Nrf2 target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2.
Background. Bile leakage testing may help to detect and reduce the incidence of biliary leakage after hepatic resection. This review was performed to investigate the value of the White-test in identifying intraoperative biliary leakage and avoiding postoperative leakage.
Material and methods. A systematic review and meta-analysis was performed. Two researchers performed literature research. Primary outcome measure was the incidence of post-hepatectomy biliary leakage; secondary outcome measure was the ability of detecting intraoperative biliary leakage with the help of the White-test.
Results. A total of 4 publications (including original data from our center) were included in the analysis. Evidence levels of the included studies had medium quality of 2b (individual cohort studies including low quality randomized controlled trials). Use of the White-test led to a significant reduction of post-operative biliary leakage [OR: 0.3 (95% CI: 0.14, 0.63), p = 0.002] and led to a significant higher intraoperative detection of biliary leakages [OR: 0.03 (95%CI: 0.02, 0.07), p < 0.00001].
Conclusion. Existing evidence implicates the use of the White-test after hepatic resection to identify bile leaks intraoperatively and thus reduce incidence of post-operative biliary leakage. Nonetheless, there is a requirement for a high-quality randomized controlled trial with adequately powered sample-size to confirm findings from the above described studies and further increase evidence in this field.
Macrophages respond to the Th2 cytokine IL-4 with elevated expression of arachidonate 15-lipoxygenase (ALOX15). Although IL-4 signaling elicits anti-inflammatory responses, 15-lipoxygenase may either support or inhibit inflammatory processes in a context-dependent manner. AMP-activated protein kinase (AMPK) is a metabolic sensor/regulator that supports an anti-inflammatory macrophage phenotype. How AMPK activation is linked to IL-4-elicited gene signatures remains unexplored. Using primary human macrophages stimulated with IL-4, we observed elevated ALOX15 mRNA and protein expression, which was attenuated by AMPK activation. AMPK activators, e.g. phenformin and aminoimidazole-4-carboxamide 1-β-d-ribofuranoside inhibited IL-4-evoked activation of STAT3 while leaving activation of STAT6 and induction of typical IL-4-responsive genes intact. In addition, phenformin prevented IL-4-induced association of STAT6 and Lys-9 acetylation of histone H3 at the ALOX15 promoter. Activating AMPK abolished cellular production of 15-lipoxygenase arachidonic acid metabolites in IL-4-stimulated macrophages, which was mimicked by ALOX15 knockdown. Finally, pretreatment of macrophages with IL-4 for 48 h increased the mRNA expression of the proinflammatory cytokines IL-6, IL-12, CXCL9, and CXCL10 induced by subsequent stimulation with lipopolysaccharide. This response was attenuated by inhibition of ALOX15 or activation of AMPK during incubation with IL-4. In conclusion, limiting ALOX15 expression by AMPK may promote an anti-inflammatory phenotype of IL-4-stimulated human macrophages.
This paper investigates systemic risk in the insurance industry. We first analyze the systemic contribution of the insurance industry vis-à-vis other industries by applying 3 measures, namely the linear Granger causality test, conditional value at risk and marginal expected shortfall, on 3 groups, namely banks, insurers and non-financial companies listed in Europe over the last 14 years. We then analyze the determinants of the systemic risk contribution within the insurance industry by using balance sheet level data in a broader sample. Our evidence suggests that i) the insurance industry shows a persistent systemic relevance over time and plays a subordinate role in causing systemic risk compared to banks, and that ii) within the industry, those insurers which engage more in non-insurance-related activities tend to pose more systemic risk. In addition, we are among the first to provide empirical evidence on the role of diversification as potential determinant of systemic risk in the insurance industry. Finally, we confirm that size is also a significant driver of systemic risk, whereas price-to-book ratio and leverage display counterintuitive results.
Hypoxia potentiates palmitate-induced pro-inflammatory activation of primary human macrophages
(2015)
Pro-inflammatory cytokines secreted by adipose tissue macrophages (ATMs) contribute to chronic low-grade inflammation and obesity-induced insulin resistance. Recent studies have shown that adipose tissue hypoxia promotes an inflammatory phenotype in ATMs. However, our understanding of how hypoxia modulates the response of ATMs to free fatty acids within obese adipose tissue is limited. We examined the effects of hypoxia (1% O2) on the pro-inflammatory responses of human monocyte-derived macrophages to the saturated fatty acid palmitate. Compared with normoxia, hypoxia significantly increased palmitate-induced mRNA expression and protein secretion of IL-6 and IL-1β. Although palmitate-induced endoplasmic reticulum stress and nuclear factor κB pathway activation were not enhanced by hypoxia, hypoxia increased the activation of JNK and p38 mitogen-activated protein kinase signaling in palmitate-treated cells. Inhibition of JNK blocked the hypoxic induction of pro-inflammatory cytokine expression, whereas knockdown of hypoxia-induced transcription factors HIF-1α and HIF-2α alone or in combination failed to reduce IL-6 and only modestly reduced IL-1β gene expression in palmitate-treated hypoxic macrophages. Enhanced pro-inflammatory cytokine production and JNK activity under hypoxia were prevented by inhibiting reactive oxygen species generation. In addition, silencing of dual-specificity phosphatase 16 increased normoxic levels of IL-6 and IL-1β and reduced the hypoxic potentiation in palmitate-treated macrophages. The secretome of hypoxic palmitate-treated macrophages promoted IL-6 and macrophage chemoattractant protein 1 expression in primary human adipocytes, which was sensitive to macrophage JNK inhibition. Our results reveal that the coexistence of hypoxia along with free fatty acids exacerbates macrophage-mediated inflammation.
Siglec-1 (sialoadhesin, CD169) is a surface receptor on human cells that mediates trans-enhancement of HIV-1 infection through recognition of sialic acid moieties in virus membrane gangliosides. Here, we demonstrate that mouse Siglec-1, expressed on the surface of primary macrophages in an interferon-α-responsive manner, captures murine leukemia virus (MLV) particles and mediates their transfer to proliferating lymphocytes. The MLV infection of primary B-cells was markedly more efficient than that of primary T-cells. The major structural protein of MLV particles, Gag, frequently co-localized with Siglec-1, and trans-infection, primarily of surface-bound MLV particles, efficiently occurred. To explore the role of sialic acid for MLV trans-infection at a submolecular level, we analyzed the potential of six sialic acid precursor analogs to modulate the sialylated ganglioside-dependent interaction of MLV particles with Siglec-1. Biosynthetically engineered sialic acids were detected in both the glycolipid and glycoprotein fractions of MLV producer cells. MLV released from cells carrying N-acyl-modified sialic acids displayed strikingly different capacities for Siglec-1-mediated capture and trans-infection; N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl side chain modifications resulted in up to 92 and 80% reduction of virus particle capture and trans-infection, respectively, whereas N-propanoyl or N-cyclopropylcarbamyl side chains had no effect. In agreement with these functional analyses, molecular modeling indicated reduced binding affinities for non-functional N-acyl modifications. Thus, Siglec-1 is a key receptor for macrophage/lymphocyte trans-infection of surface-bound virions, and the N-acyl side chain of sialic acid is a critical determinant for the Siglec-1/MLV interaction.
Low interest rates are becoming a threat to the stability of the life insurance industry, especially in countries such as Germany, where products with relatively high guaranteed returns sold in the past still represent a prominent share of the total portfolio. This contribution aims to assess and quantify the effects of the current low interest rate phase on the balance sheet of a representative German life insurer, given the current asset allocation and the outstanding liabilities. To do so, we generate a stochastic term structure of interest rates as well as stock market returns to simulate investment returns of a stylized life insurance business portfolio in a multi-period setting. Based on empirically calibrated parameters, we can observe the evolution of the life insurers’ balance sheet over time with a special focus on their solvency situation. To account for different scenarios and in order to check the robustness of our findings, we calibrate different capital market settings and different initial situations of capital endowment. Our results suggest that a prolonged period of low interest rates would markedly affect the solvency situation of life insurers, leading to a relatively high cumulative probability of default, especially for less capitalized companies. In addition, the new reform of the German life insurance regulation has a beneficial effect on the cumulative probability of default, as a direct consequence of the reduction of the payouts to policyholders.
The hepatitis C virus (HCV) was discovered in the late 1980s. Interferon (IFN)-α was proposed as an antiviral treatment for chronic hepatitis C at about the same time. Successive improvements in IFN-α-based therapy (dose finding, pegylation, addition of ribavirin) increased the rates of sustained virologic response, i.e. the rates of curing HCV infection. These rates were further improved by adding the first available direct-acting antiviral (DAA) drugs to the combination of pegylated IFN-α and ribavirin. An IFN-free era finally started in 2014, yielding rates of sustained virologic response over 90% in patients treated for 8 to 24 weeks with all-oral regimens. Major challenges however remain in implementation of these new treatment strategies, not only in low- to middle-income countries, but also in high-income countries where the price of these therapies is still prohibitive. Elimination of HCV infection through treatment in certain areas is possible but raises major public health issues.
The solution structure of the lantibiotic immunity protein NisI and its interactions with nisin
(2015)
Many Gram-positive bacteria produce lantibiotics, genetically encoded and posttranslationally modified peptide antibiotics, which inhibit the growth of other Gram-positive bacteria. To protect themselves against their own lantibiotics these bacteria express a variety of immunity proteins including the LanI lipoproteins. The structural and mechanistic basis for LanI-mediated lantibiotic immunity is not yet understood. Lactococcus lactis produces the lantibiotic nisin, which is widely used as a food preservative. Its LanI protein NisI provides immunity against nisin but not against structurally very similar lantibiotics from other species such as subtilin from Bacillus subtilis. To understand the structural basis for LanI-mediated immunity and their specificity we investigated the structure of NisI. We found that NisI is a two-domain protein. Surprisingly, each of the two NisI domains has the same structure as the LanI protein from B. subtilis, SpaI, despite the lack of significant sequence homology. The two NisI domains and SpaI differ strongly in their surface properties and function. Additionally, SpaI-mediated lantibiotic immunity depends on the presence of a basic unstructured N-terminal region that tethers SpaI to the membrane. Such a region is absent from NisI. Instead, the N-terminal domain of NisI interacts with membranes but not with nisin. In contrast, the C-terminal domain specifically binds nisin and modulates the membrane affinity of the N-terminal domain. Thus, our results reveal an unexpected structural relationship between NisI and SpaI and shed light on the structural basis for LanI mediated lantibiotic immunity.
The pseudorapidity (η) and transverse-momentum (pT) distributions of charged particles produced in proton–proton collisions are measured at the centre-of-mass energy √s=13 TeV. The pseudorapidity distribution in |η|<1.8 is reported for inelastic events and for events with at least one charged particle in |η|<1. The pseudorapidity density of charged particles produced in the pseudorapidity region |η|<0.5 is 5.31±0.18 and 6.46±0.19 for the two event classes, respectively. The transverse-momentum distribution of charged particles is measured in the range 0.15<pT<20 GeV/c and |η|<0.8 for events with at least one charged particle in |η|<1. The evolution of the transverse momentum spectra of charged particles is also investigated as a function of event multiplicity. The results are compared with calculations from PYTHIA and EPOS Monte Carlo generators.
We present results of a search for two hypothetical strange dibaryon states, i.e. the H-dibaryon and the possible Λn‾ bound state. The search is performed with the ALICE detector in central (0–10%) Pb–Pb collisions at √sNN=2.76 TeV, by invariant mass analysis in the decay modes Λn‾→d‾π+ and H-dibaryon →Λpπ−. No evidence for these bound states is observed. Upper limits are determined at 99% confidence level for a wide range of lifetimes and for the full range of branching ratios. The results are compared to thermal, coalescence and hybrid UrQMD model expectations, which describe correctly the production of other loosely bound states, like the deuteron and the hypertriton.
Unraveling the activation mechanism of taspase1 which controls the oncogenic AF4–MLL fusion protein
(2015)
We have recently demonstrated that Taspase1-mediated cleavage of the AF4–MLL oncoprotein results in the formation of a stable multiprotein complex which forms the key event for the onset of acute proB leukemia in mice. Therefore, Taspase1 represents a conditional oncoprotein in the context of t(4;11) leukemia. In this report, we used site-directed mutagenesis to unravel the molecular events by which Taspase1 becomes sequentially activated. Monomeric pro-enzymes form dimers which are autocatalytically processed into the enzymatically active form of Taspase1 (αββα). The active enzyme cleaves only very few target proteins, e.g., MLL, MLL4 and TFIIA at their corresponding consensus cleavage sites (CSTasp1) as well as AF4–MLL in the case of leukemogenic translocation. This knowledge was translated into the design of a dominant-negative mutant of Taspase1 (dnTASP1). As expected, simultaneous expression of the leukemogenic AF4–MLL and dnTASP1 causes the disappearance of the leukemogenic oncoprotein, because the uncleaved AF4–MLL protein (328 kDa) is subject to proteasomal degradation, while the cleaved AF4–MLL forms a stable oncogenic multi-protein complex with a very long half-life. Moreover, coexpression of dnTASP1 with a BFP-CSTasp1-GFP FRET biosensor effectively inhibits cleavage. The impact of our findings on future drug development and potential treatment options for t(4;11) leukemia will be discussed.
Background: Tumor associated macrophages (TAMs) are known to support tumor progression and their accumulation is generally associated with poor prognosis. The shift from a tumor-attacking to a tumor-supportive macrophage phenotype is based on an educational program that, at least in part, is initiated by apoptotic tumor cells.
Aims: We explored the macrophage phenotype shift during tumor progression by analyzing the macrophage NO-output system and examining potential NO targets.
Methods: Biochemical and Molecular Biology-orientated cell culture experiments, in part using 3d-tumor spheroid models as well as animal experiments were used.
Results: Apoptotic cells polarize macrophages towards a healing, tumor-supportive phenotype. Soluble mediators released from apoptotic cells, among them the lipid sphingosine-1-phosphate (S1P), cause expression of arginase 2 in macrophages, thereby lowering citrulline/NO formation but enhancing ornithine production. Mechanistically, this is achieved via the S1P2 receptor and the CRE (cAMP-response element) binding site in the arginase 2 promoter. Reduced NO-formation is also seen in ex vivo macrophages from a xenograft model allowing restricted vs. unrestricted tumor growth based on tumor-associated S1P-formation. The theoretical ability of NO to target hypoxia-inducible factor-1 (HIF-1) and jumonji histone demethylases (JHDMs) in cells of the tumor microenvironment will be discussed in light of the iNOS/arginase balance. Moreover, data on the importance of HIF-1 in macrophages for their interaction with tumor cells, polarization, and angiogenic potential will be presented.
Conclusions: We hypothesize that apoptotic death of tumor cells and associated macrophage activation facilitates the progression of malignant disease. The macrophage polarization program affects the NO-output system and the capacity of macrophages to support or restrict tumor growth.
Thought structures of modelling task solutions and their connection to the level of difficulty
(2015)
Although efforts have been made to integrate the concept of mathematical modelling in school, among others PISA and TIMSS revealed weaknesses of not only German students in the field of mathematical modelling. There may be various reasons starting from educational policy via curricular issues to practical instructional concerns. Studies show that mathematical modelling has not been arrived yet in everyday school class (Blum &BorromeoFerri, 2009, p. 47). Thus, the proportion of mathematical modelling in everyday school classes is low (Jordan et al., 2006). When focusing on the teachers’ point of view there are difficulties which may contribute to avoid modelling tasks in class. The development of reasonable modelling tasks, estimating the task space, valuating the task difficulty and assessing the student solutions are difficulties which occur to an increasing degree compared to ordinary mathematics tasks.The project MokiMaS (transl.: modeling competency in math classes of secondary education) aims at providing inter-year modelling tasks, whose task space and level of difficulty is known, together with an evaluation scheme. In particular a theory based method has been developed to determine the level of difficulty of modelling tasks on the basis of thought structures, representing the cognitive load of solution approaches. The current question is whether this method leads to a realistic rating. To go further into that question an evaluation scheme has been developed which is guided by the daily assessment work of teachers, to investigate the relation of task difficulty and student performance.
Hepatology highlights
(2015)
We construct net baryon number and strangeness susceptibilities as well as correlations between electric charge, strangeness and baryon number from experimental data at midrapidity of the ALICE Collaboration at CERN. The data were taken in central Pb–Pb collisions at sNN=2.76 TeV and cover one unit of rapidity. The resulting fluctuations and correlations are consistent with Lattice QCD results at the chiral crossover pseudocritical temperature Tc≃155 MeV. This agreement lends strong support to the assumption that the fireball created in these collisions is of thermal origin and exhibits characteristic properties expected in QCD at the transition from the quark gluon plasma to the hadronic phase. The volume of the fireball for one unit of rapidity at Tc is found to exceed 3000 fm3. A detailed discussion on uncertainties in the temperature and volume of the fireball is presented. The results are linked to pion interferometry measurements and predictions from percolation theory.
Intrinsically disordered protein (IDP) duplexes composed of two IDP chains cross-linked by bivalent partner proteins form scaffolds for assembly of multiprotein complexes. The N-terminal domain of dynein intermediate chain (N-IC) is one such IDP that forms a bivalent scaffold with multiple dynein light chains including LC8, a hub protein that promotes duplex formation of diverse IDP partners. N-IC also binds a subunit of the dynein regulator, dynactin. Here we characterize interactions of a yeast ortholog of N-IC (N-Pac11) with yeast LC8 (Dyn2) or with the intermediate chain-binding subunit of yeast dynactin (Nip100). Residue level changes in Pac11 structure are monitored by NMR spectroscopy, and binding energetics are monitored by isothermal titration calorimetry (ITC). N-Pac11 is monomeric and primarily disordered except for a single α-helix (SAH) at the N terminus and a short nascent helix, LH, flanked by the two Dyn2 recognition motifs. Upon binding Dyn2, the only Pac11 residues making direct protein-protein interactions are in and immediately flanking the recognition motifs. Dyn2 binding also orders LH residues of Pac11. Upon binding Nip100, only Pac11 SAH residues make direct protein-protein interactions, but LH residues at a distant sequence position and L1 residues in an adjacent linker are also ordered. The long distance, ligand-dependent ordering of residues reveals new elements of dynamic structure within IDP linker regions.
Sleep has been shown to subtly disrupt the spatial organization of functional connectivity networks in the brain, but in a way that largely preserves the connectivity within sensory cortices. Here we evaluated the hypothesis that sleep does impact sensory cortices, but through alteration of activity dynamics. We therefore examined the impact of sleep on hemodynamics using a method for quantifying non-random, high frequency signatures of the blood-oxygen-level dependent (BOLD) signal (amplitude variance asymmetry; AVA). We found that sleep was associated with the elimination of these dynamics in a manner that is restricted to auditory, motor and visual cortices. This elimination was concurrent with increased variance of activity in these regions. Functional connectivity between regions showing AVA during wakefulness maintained a relatively consistent hierarchical structure during wakefulness and N1 and N2 sleep, despite a gradual reduction of connectivity strength as sleep progressed. Thus, sleep is related to elimination of high frequency non-random activity signatures in sensory cortices that are robust during wakefulness. The elimination of these AVA signatures conjointly with preservation of the structure of functional connectivity patterns may be linked to the need to suppress sensory inputs during sleep while still maintaining the capacity to react quickly to complex multimodal inputs.
In many neural systems anatomical motifs are present repeatedly, but despite their structural similarity they can serve very different tasks. A prime example for such a motif is the canonical microcircuit of six-layered neo-cortex, which is repeated across cortical areas, and is involved in a number of different tasks (e.g. sensory, cognitive, or motor tasks). This observation has spawned interest in finding a common underlying principle, a ‘goal function’, of information processing implemented in this structure. By definition such a goal function, if universal, cannot be cast in processing-domain specific language (e.g. ‘edge filtering’, ‘working memory’). Thus, to formulate such a principle, we have to use a domain-independent framework. Information theory offers such a framework. However, while the classical framework of information theory focuses on the relation between one input and one output (Shannon’s mutual information), we argue that neural information processing crucially depends on the combination of multiple inputs to create the output of a processor. To account for this, we use a very recent extension of Shannon Information theory, called partial information decomposition (PID). PID allows to quantify the information that several inputs provide individually (unique information), redundantly (shared information) or only jointly (synergistic information) about the output. First, we review the framework of PID. Then we apply it to reevaluate and analyze several earlier proposals of information theoretic neural goal functions (predictive coding, infomax and coherent infomax, efficient coding). We find that PID allows to compare these goal functions in a common framework, and also provides a versatile approach to design new goal functions from first principles. Building on this, we design and analyze a novel goal function, called ‘coding with synergy’, which builds on combining external input and prior knowledge in a synergistic manner. We suggest that this novel goal function may be highly useful in neural information processing.