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Study of flavor dependence of the baryon-to-meson ratio in proton–proton collisions at √s = 13 TeV
(2024)
The production cross sections of D0 and Λ+c hadrons originating from beauty-hadron decays (i.e. non-prompt) were measured for the first time at midrapidity (|y|<0.5) by the ALICE Collaboration in proton-proton collisions at a center-of-mass energy s√=13 TeV. They are described within uncertainties by perturbative QCD calculations employing the fragmentation fractions of beauty quarks to baryons measured at forward rapidity by the LHCb Collaboration. The bb¯¯¯ production cross section per unit of rapidity at midrapidity, estimated from these measurements, is dσbb¯¯¯/dy||y|<0.5=83.1±3.5(stat.)±5.4(syst.)+12.3−3.2(extrap.)μb. The baryon-to-meson ratios are computed to investigate the hadronization mechanism of beauty quarks. The non-prompt Λ+c/D0 production ratio has a similar trend to the one measured for the promptly produced charmed particles and to the p/π+ and Λ/K0S ratios, suggesting a similar baryon-formation mechanism among light, strange, charm, and beauty hadrons. The pT-integrated non-prompt Λc/D0 ratio is found to be significantly higher than the one measured in e+e− collisions.
Study of flavor dependence of the baryon-to-meson ratio in proton–proton collisions at √s = 13 TeV
(2023)
The production cross sections of D0 and Λ+c hadrons originating from beauty-hadron decays (i.e. non-prompt) were measured for the first time at midrapidity (|y|<0.5) by the ALICE Collaboration in proton-proton collisions at a center-of-mass energy s√=13 TeV. They are described within uncertainties by perturbative QCD calculations employing the fragmentation fractions of beauty quarks to baryons measured at forward rapidity by the LHCb Collaboration. The bb¯¯¯ production cross section per unit of rapidity at midrapidity, estimated from these measurements, is dσbb¯¯¯/dy||y|<0.5=83.1±3.5(stat.)±5.4(syst.)+12.3−3.2(extrap.)μb. The baryon-to-meson ratios are computed to investigate the hadronization mechanism of beauty quarks. The non-prompt Λ+c/D0 production ratio has a similar trend to the one measured for the promptly produced charmed particles and to the p/π+ and Λ/K0S ratios, suggesting a similar baryon-formation mechanism among light, strange, charm, and beauty hadrons. The pT-integrated non-prompt Λc/D0 ratio is found to be significantly higher than the one measured in e+e− collisions.
K+K− pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons, or directly as non-resonant K+K− pairs. Measurements of K+K− photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon−proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K+K− pairs on lead ions in ultra-peripheral collisions using the ALICE detector, including the first investigation of direct K+K− production. There is significant K+K− production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1<MKK<1.4 GeV/c2 above the ϕ(1020) resonance, for rapidity |yKK|<0.8 and pT,KK<0.1 GeV/c, the measured coherent photoproduction cross section is dσ/dy = 3.37 ± 0.61 (stat.) ± 0.15 (syst.) mb. The center-of-mass energy per nucleon of the photon-nucleus (Pb) system WγPb,n ranges from 33 to 188 GeV, far higher than previous measurements on heavy-nucleus targets. The cross section is larger than expected for ϕ(1020) photoproduction alone. The mass spectrum is fit to a cocktail consisting of ϕ(1020) decays, direct K+K− photoproduction, and interference between the two. The confidence regions for the amplitude and relative phase angle for direct K+K− photoproduction are presented.
The ALICE experiment was proposed in 1993, to study strongly interacting matter at extreme energy densities via a comprehensive investigation of nuclear collisions at the LHC. Its physics programme initially focused on the determination of the properties of the Quark-Gluon Plasma (QGP), a deconfined state of quarks and gluons and was extended along the years, covering a diverse ensemble of observables related to Quantum Chromodynamics (QCD), the theory of strong interactions. The experiment has studied Pb-Pb, Xe-Xe, p-Pb and pp collisions in the multi-TeV energy range, during the Run 1 and Run 2 data taking periods at the LHC (2009-2018). The aim of this review article is to gather and summarise a selection of ALICE physics results and to discuss their implications on the current understanding of the macroscopic and microscopic properties of strongly interacting matter at the highest temperature reached in the laboratory. It will be shown that it is possible to have a quantitative description of the properties of the QGP produced in Pb--Pb collisions. We also show that various features, commonly ascribed to QGP formation, are detected for a wide range of interacting system sizes. Precision measurements of QCD-related observables not directly connected to the study of the QGP will also be discussed. Prospects for future measurements with the ALICE detector and its foreseen upgrades will also be briefly described.
K+K− pairs may be produced in photonuclear collisions, either from the decays of photoproduced ϕ(1020) mesons, or directly as non-resonant K+K− pairs. Measurements of K+K− photoproduction probe the couplings between the ϕ(1020) and charged kaons with photons and nuclear targets. The kaon−proton scattering occurs at energies far above those available elsewhere. We present the first measurement of coherent photoproduction of K+K− pairs on lead ions in ultra-peripheral collisions using the ALICE detector, including the first investigation of direct K+K− production. There is significant K+K− production at low transverse momentum, consistent with coherent photoproduction on lead targets. In the mass range 1.1<MKK<1.4 GeV/c2 above the ϕ(1020) resonance, for rapidity |yKK|<0.8 and pT,KK<0.1 GeV/c, the measured coherent photoproduction cross section is dσ/dy = 3.37 ± 0.61 (stat.) ± 0.15 (syst.) mb. The center-of-mass energy per nucleon of the photon-nucleus (Pb) system WγPb,n ranges from 33 to 188 GeV, far higher than previous measurements on heavy-nucleus targets. The cross section is larger than expected for ϕ(1020) photoproduction alone. The mass spectrum is fit to a cocktail consisting of ϕ(1020) decays, direct K+K− photoproduction, and interference between the two. The confidence regions for the amplitude and relative phase angle for direct K+K− photoproduction are presented.
This Letter presents the measurement of near-side associated per-trigger yields, denoted ridge yields, from the analysis of angular correlations of charged hadrons in proton-proton collisions at s√ = 13 TeV. Long-range ridge yields are extracted for pairs of charged particles with a pseudorapidity difference of 1.4<|Δη|<1.8 and a transverse momentum of 1<pT<2 GeV/c, as a function of the charged-particle multiplicity measured at midrapidity. This study extends the measurements of the ridge yield to the low multiplicity region, where in hadronic collisions it is typically conjectured that a strongly-interacting medium is unlikely to be formed. The precision of the new low multiplicity results allows for the first direct quantitative comparison with the results obtained in e+e− collisions at s√ = 91 GeV and s√ = 183−209 GeV, where initial-state effects such as pre-equilibrium dynamics and collision geometry are not expected to play a role. In the multiplicity range 8≲⟨Nch⟩≲24 where the e+e− results have good precision, the measured ridge yields in pp collisions are substantially larger than the limits set in e+e− annihilations. Consequently, the findings presented in this Letter suggest that the processes involved in e+e− annihilations do not contribute significantly to the emergence of long-range correlations in pp collisions.
The measurements of the inclusive J/ψ yield at midrapidity (|y|<0.9) and forward rapidity (2.5 <y< 4) in Pb−Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC are reported. The inclusive J/ψ production yields and nuclear modification factors, RAA, are measured as a function of the collision centrality, J/ψ transverse momentum (pT), and rapidity. The J/ψ average transverse momentum and squared transverse momentum (⟨pT⟩ and ⟨p2T⟩) are evaluated as a function of the centrality at midrapidity. Compared to the previous ALICE publications, here the entire Pb−Pb collisions dataset collected during the LHC Run 2 is used, which improves the precision of the measurements and extends the pT coverage. The pT-integrated RAA shows a hint of an increasing trend towards unity from semicentral to central collisions at midrapidity, while it is flat at forward rapidity. The pT-differential RAA shows a strong suppression at high pT with less suppression at low pT where it reaches a larger value at midrapidity compared to forward rapidity. The ratio of the pT-integrated yields of J/ψ to those of D0 mesons is reported for the first time for the central and semicentral event classes at midrapidity. Model calculations implementing charmonium production via the coalescence of charm quarks and antiquarks during the fireball evolution (transport models) or in a statistical approach with thermal weights are in good agreement with the data at low pT. At higher pT, the data are well described by transport models and a model based on energy loss in the strongly-interacting medium produced in nuclear collisions at the LHC.
The measurements of the inclusive J/ψ yield at midrapidity (|y|<0.9) and forward rapidity (2.5 <y< 4) in Pb−Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the LHC are reported. The inclusive J/ψ production yields and nuclear modification factors, RAA, are measured as a function of the collision centrality, J/ψ transverse momentum (pT), and rapidity. The J/ψ average transverse momentum and squared transverse momentum (⟨pT⟩ and ⟨p2T⟩) are evaluated as a function of the centrality at midrapidity. Compared to the previous ALICE publications, here the entire Pb−Pb collisions dataset collected during the LHC Run 2 is used, which improves the precision of the measurements and extends the pT coverage. The pT-integrated RAA shows a hint of an increasing trend towards unity from semicentral to central collisions at midrapidity, while it is flat at forward rapidity. The pT-differential RAA shows a strong suppression at high pT with less suppression at low pT where it reaches a larger value at midrapidity compared to forward rapidity. The ratio of the pT-integrated yields of J/ψ to those of D0 mesons is reported for the first time for the central and semicentral event classes at midrapidity. Model calculations implementing charmonium production via the coalescence of charm quarks and antiquarks during the fireball evolution (transport models) or in a statistical approach with thermal weights are in good agreement with the data at low pT. At higher pT, the data are well described by transport models and a model based on energy loss in the strongly-interacting medium produced in nuclear collisions at the LHC.
Measurements of inclusive charged-particle jet production in pp and p-Pb collisions at center-of-mass energy per nucleon-nucleon collision sNN−−−√=5.02 TeV and the corresponding nuclear modification factor RchjetpPb are presented, using data collected with the ALICE detector at the LHC. Jets are reconstructed in the central rapidity region |ηjet|<0.5 from charged particles using the anti-kT algorithm with resolution parameters R=0.2, 0.3, and 0.4. The pT-differential inclusive production cross section of charged-particle jets, as well as the corresponding cross section ratios, are reported for pp and p-Pb collisions in the transverse momentum range 10<pchT,jet<140 GeV/c and 10<pchT,jet<160 GeV/c, respectively, together with the nuclear modification factor RchjetpPb in the range 10<pchT,jet<140 GeV/c. The analysis extends the pT range of the previously-reported charged-particle jet measurements by the ALICE Collaboration. The nuclear modification factor is found to be consistent with one and independent of the jet resolution parameter with the improved precision of this study, indicating that the possible influence of cold nuclear matter effects on the production cross section of charged-particle jets in p-Pb collisions at sNN−−−√=5.02 TeV is smaller than the current precision. The obtained results are in agreement with other minimum bias jet measurements available for RHIC and LHC energies, and are well reproduced by the NLO perturbative QCD POWHEG calculations with parton shower provided by PYTHIA8 as well as by JETSCAPE simulations.
Modification of charged-particle jets in event-shape engineered Pb–Pb collisions at √sNN = 5.02 TeV
(2024)
Charged-particle jet yields have been measured in semicentral Pb−Pb collisions at center-of-mass energy per nucleon-nucleon collision sNN−−−√=5.02 TeV with the ALICE detector at the LHC. These yields are reported as a function of the jet transverse momentum, and further classified by their angle with respect to the event plane and the event shape, characterized by ellipticity, in an effort to study the path-length dependence of jet quenching. Jets were reconstructed at midrapidity from charged-particle tracks using the anti-kT algorithm with resolution parameters R= 0.2 and 0.4, with event-plane angle and event-shape values determined using information from forward scintillating detectors. The results presented in this letter show that, in semicentral Pb−Pb collisions, there is no significant difference between jet yields in predominantly isotropic and elliptical events. However, out-of-plane jets are observed to be more suppressed than in-plane jets. Further, this relative suppression is greater for low transverse momentum (< 50 GeV/c) R= 0.2 jets produced in elliptical events, with out-of-plane to in-plane jet-yield ratios varying up to 5.2σ between different event-shape classes. These results agree with previous studies indicating that jets experience azimuthally anisotropic suppression when traversing the QGP medium, and can provide additional constraints on the path-length dependence of jet energy loss.
The pseudorapidity dependence of elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of charged particles measured in Pb-Pb collisions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV and in Xe-Xe collisions at sNN−−−√=5.44 TeV with ALICE at the LHC are presented. The measurements are performed in the pseudorapidity range −3.5<η<5 for various centrality intervals using two- and multi-particle cumulants with the subevent method. The flow probability density function (p.d.f.) is studied with the ratio of flow coefficient v2 calculated with four- and two-particle cumulant, and suggests that the variance of flow p.d.f. is independent of pseudorapidity. The decorrelation of the flow vector in the longitudinal direction is probed using two-particle correlations. The results measured with respect to different reference regions in pseudorapidity exhibit differences, argued to be a result of saturating decorrelation effect above a certain pseudorapidity separation, in contrast to previous publications which assign this observation to non-flow effects. The results are compared to 3+1 dimensional hydrodynamic and the AMPT transport model calculations. Neither of the models is able to simultaneously describe the pseudorapidity dependence of measurements of anisotropic flow and its fluctuations. The results presented in this work highlight shortcomings in our current understanding of initial conditions and subsequent system expansion in the longitudinal direction. Therefore, they provide input for its improvement.
The pseudorapidity dependence of elliptic (v2), triangular (v3), and quadrangular (v4) flow coefficients of charged particles measured in Pb-Pb collisions at a centre-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV and in Xe-Xe collisions at sNN−−−√=5.44 TeV with ALICE at the LHC are presented. The measurements are performed in the pseudorapidity range −3.5<η<5 for various centrality intervals using two- and multi-particle cumulants with the subevent method. The flow probability density function (p.d.f.) is studied with the ratio of flow coefficient v2 calculated with four- and two-particle cumulant, and suggests that the variance of flow p.d.f. is independent of pseudorapidity. The decorrelation of the flow vector in the longitudinal direction is probed using two-particle correlations. The results measured with respect to different reference regions in pseudorapidity exhibit differences, argued to be a result of saturating decorrelation effect above a certain pseudorapidity separation, in contrast to previous publications which assign this observation to non-flow effects. The results are compared to 3+1 dimensional hydrodynamic and the AMPT transport model calculations. Neither of the models is able to simultaneously describe the pseudorapidity dependence of measurements of anisotropic flow and its fluctuations. The results presented in this work highlight shortcomings in our current understanding of initial conditions and subsequent system expansion in the longitudinal direction. Therefore, they provide input for its improvement.
Measurements of inclusive charged-particle jet production in pp and p-Pb collisions at center-of-mass energy per nucleon-nucleon collision sNN−−−√=5.02 TeV and the corresponding nuclear modification factor RchjetpPb are presented, using data collected with the ALICE detector at the LHC. Jets are reconstructed in the central rapidity region |ηjet|<0.5 from charged particles using the anti-kT algorithm with resolution parameters R=0.2, 0.3, and 0.4. The pT-differential inclusive production cross section of charged-particle jets, as well as the corresponding cross section ratios, are reported for pp and p-Pb collisions in the transverse momentum range 10<pchT,jet<140 GeV/c and 10<pchT,jet<160 GeV/c, respectively, together with the nuclear modification factor RchjetpPb in the range 10<pchT,jet<140 GeV/c. The analysis extends the pT range of the previously-reported charged-particle jet measurements by the ALICE Collaboration. The nuclear modification factor is found to be consistent with one and independent of the jet resolution parameter with the improved precision of this study, indicating that the possible influence of cold nuclear matter effects on the production cross section of charged-particle jets in p-Pb collisions at sNN−−−√=5.02 TeV is smaller than the current precision. The obtained results are in agreement with other minimum bias jet measurements available for RHIC and LHC energies, and are well reproduced by the NLO perturbative QCD POWHEG calculations with parton shower provided by PYTHIA8 as well as by JETSCAPE simulations.
Understanding the role of parton mass and Casimir colour factors in the quantum chromodynamics parton shower represents an important step in characterising the emission properties of heavy quarks. Recent experimental advances in jet substructure techniques have provided the opportunity to isolate and characterise gluon emissions from heavy quarks. In this work, the first direct experimental constraint on the charm-quark splitting function is presented, obtained via the measurement of the groomed shared momentum fraction of the first splitting in charm jets, tagged by a reconstructed D0 meson. The measurement is made in proton-proton collisions at s√ = 13 TeV, in the low jet transverse-momentum interval of 15≤pjet chT<30 GeV/c where the emission properties are sensitive to parton mass effects. In addition, the opening angle of the first perturbative emission of the charm quark, as well as the number of perturbative emissions it undergoes, is reported. Comparisons to measurements of an inclusive-jet sample show a steeper splitting function for charm quarks compared with gluons and light quarks. Charm quarks also undergo fewer perturbative emissions in the parton shower, with a reduced probability of large-angle emissions.
Understanding the role of parton mass and Casimir colour factors in the quantum chromodynamics parton shower represents an important step in characterising the emission properties of heavy quarks. Recent experimental advances in jet substructure techniques have provided the opportunity to isolate and characterise gluon emissions from heavy quarks. In this work, the first direct experimental constraint on the charm-quark splitting function is presented, obtained via the measurement of the groomed shared momentum fraction of the first splitting in charm jets, tagged by a reconstructed D0 meson. The measurement is made in proton-proton collisions at s√ = 13 TeV, in the low jet transverse-momentum interval of 15≤pjet chT<30 GeV/c where the emission properties are sensitive to parton mass effects. In addition, the opening angle of the first perturbative emission of the charm quark, as well as the number of perturbative emissions it undergoes, is reported. Comparisons to measurements of an inclusive-jet sample show a steeper splitting function for charm quarks compared with gluons and light quarks. Charm quarks also undergo fewer perturbative emissions in the parton shower, with a reduced probability of large-angle emissions.
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
The design, construction, and commissioning of the ALICE Time-Projection Chamber (TPC) is described. It is the main device for pattern recognition, tracking, and identification of charged particles in the ALICE experiment at the CERN LHC. The TPC is cylindrical in shape with a volume close to 90 m3 and is operated in a 0.5 T solenoidal magnetic field parallel to its axis.
In this paper we describe in detail the design considerations for this detector for operation in the extreme multiplicity environment of central Pb–Pb collisions at LHC energy. The implementation of the resulting requirements into hardware (field cage, read-out chambers, electronics), infrastructure (gas and cooling system, laser-calibration system), and software led to many technical innovations which are described along with a presentation of all the major components of the detector, as currently realized. We also report on the performance achieved after completion of the first round of stand-alone calibration runs and demonstrate results close to those specified in the TPC Technical Design Report.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams.
The paper provides an overview and an economic analysis of the development of the corporate governance of German banks since the 1950s, highlighting peculiarities – as seen from the meanwhile prevailing standard model perspective – of the German case. These peculiarities refer to the specific German notion and legal-institutional regime of corporate governance in general as well as to the specific three-pillar structure of the German banking system.
The most striking changes in the corporate governance of German banks during the past 50 years occurred in the case of the large shareholder-owned banks. For them, capital markets have become an important element of corporate governance, and their former orientation towards the interests of a broadly defined set of stakeholders has largely been replaced by a one-sided concentration on shareholders’ interests. In contrast, the corporate governance regimes of the smaller local public savings banks and the local cooperative banks have remained virtually unchanged. They acknowledge a broader horizon of stakeholder interests and put an emphasis on monitoring.
The Great Financial Crisis, beginning in 2007, has led to a considerable reassessment in the academic and political debate on bank governance. On an international level, it has revived the older notion that, in view of their high leverage and their innate complexity, banks are “special” and bank corporate governance also – and needs to be seen in this light, not least because research indicates that banks with a strong and one-sided shareholder orientation – and thus with what appears to be the best corporate governance according to the standard model – have suffered most in the crisis. In the German case, the crisis has shown that the smaller local banks have survived the crisis much better than large private and public banks, whose funding strongly depends on wholesale markets. This may point to certain advantages of their governance and ownership regimes. But the differences in the performance during the crisis years may also, or even more so, be a consequence of the business models of large vs small banks than of their different governance regimes.
Hochwasserereignisse sind von besonderer Bedeutung, da sie die Auenlandschaft räumlich und zeitlich strukturieren und so eine große Vielfalt an Habitaten schaffen. Mollusken sind von großem Artenreichtum, der in den mitteleuropäischen Flussauen am höchsten ist. Sie sind relativ leicht zu determinieren und besitzen zudem eine geringe Mobilität und dementsprechend kleine Minimalareale. Darüber hinaus sind Ökologie und Habitatansprüche der meisten Arten gut bekannt. Dadurch eignen sich Mollusken sehr gut zur ökologischen Charakterisierung (Indikation) und zur naturschutzfachlichen Bewertung von Auenökosystemen. Obwohl in zahlreichen Studien bereits Molluskenzönosen in Auen beschrieben wurden, ist über die Reaktion von Mollusken auf Hochwasser, insbesondere Extremhochwasser, wenig bekannt, zumal kaum Daten vorliegen, die den Zustand vor und nach einem Extremereignis beschreiben. In diesem Beitrag werden die kurz- und mittelfristigen Auswirkungen des Sommerhochwassers 2002 auf Molluskengemeinschaften im Auengrünland der Mittleren Elbe beschrieben.
Mollusken eignen sich aufgrund ihrer spezifischen Eigenschaften sehr gut zur ökologischen Charakterisierung, naturschutzfachlichen Bewertung und Beweissicherung bei bevorstehenden Veränderungen innerhalb ihrer Lebensräume. Durch ihre geringe aktive Mobilität sind sie sehr stark an ihren Lebensraum gebunden. Ihre Biologie, Ökologie und Habitatansprüche sind gut bekannt. Gerade in Flussauen erreichen Mollusken sehr hohe Arten- und je nach standörtlichen Verhältnissen sehr hohe Individuenzahlen. Im Herbst 2006 sowie im Frühjahr und Herbst 2007 wurden Molluskenproben auf den Wiesen im Roßlauer Oberluch und auf zwei Referenzstandorten in der Kliekener Altaue entnommen mit dem Ziel, den Status Quo vor der Deichöffnung festzuhalten und die Entwicklung dieser Artengruppe nach der Deichrückverlegungsmaßnahme zu analysieren. Bislang liegen die Status-Quo-Ergebnisse der Herbst- und Frühjahrsaufsammlungen aus den Jahren 2006 und 2007 vor.
Der Botanische Arbeitskreis Nordharz e.V. 1) führte vom 10.-11.8.1996 eine Kartierungsexkursion in das Gebiet um Sangerhausen durch2). Zum Zeitpunkt der Exkursionsvorbereitung war kein Kartierer im Rahmen der laufenden Sachsen-Anhalt-Kartierung in diesem Meßtischblatt tätig. Ziel war daher die Erfassung des Grundbestandes in den vier Quadranten. Die erste Augusthälfte wurde gewählt, um mit den Sommer- und Spätsommeraspekten ein möglichst breites Artenspektrum erschließen zu können. Allein der Frühjahrsaspekt blieb damit unberücksichtigt. Im nachfolgenden wird über bemerkenswerte Pflanzenfunde berichtet, sowohl Neufunde gegenüber dem Kenntnisstand, der die Grundlage für den Florenatlas der neuen Bundesländer bildete3), als auch Bestätigungen seltener und überregional bedeutsamer Artenvorkommen. Alle Funde beziehen sich, wenn nicht anders angegeben, auf das Meßtischblatt 4533, so daß den Fundorten nur die Quadrantennummer vorangestellt wird.
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
Measurements of the π±, K±, and proton double differential yields emitted from the surface of the 90-cm-long carbon target (T2K replica) were performed for the incoming 31 GeV/c protons with the NA61/SHINE spectrometer at the CERN SPS using data collected during 2010 run. The double differential π± yields were measured with increased precision compared to the previously published NA61/SHINE results, while the K± and proton yields were obtained for the first time. A strategy for dealing with the dependence of the results on the incoming proton beam profile is proposed. The purpose of these measurements is to reduce significantly the (anti)neutrino flux uncertainty in the T2K long-baseline neutrino experiment by constraining the production of (anti)neutrino ancestors coming from the T2K target.
We present measurements of ρ0, ω and K∗0 spectra in π−+ C production interactions at 158 GeV / c and ρ0 spectra at 350 GeV / c using the NA61/SHINE spectrometer at the CERN SPS. Spectra are presented as a function of the Feynman’s variable xF in the range 0<xF<1 and 0<xF<0.5 for 158 and 350 GeV / c respectively. Furthermore, we show comparisons with previous measurements and predictions of several hadronic interaction models. These measurements are essential for a better understanding of hadronic shower development and for improving the modeling of cosmic ray air showers.
Alix/AIP1 is an adaptor protein involved in regulating the function of receptor and cytoskeleton-associated tyrosine kinases. Here, we investigated its interaction with and regulation by Src. Tyr319 of Alix bound the isolated Src homology-2 (SH2) domain and was necessary for interaction with intact Src. A proline-rich region in the C terminus of Alix bound the Src SH3 domain, but this interaction was dependent on the release of the Src SH2 domain from its Src internal ligand either by interaction with Alix Tyr319 or by mutation of Src Tyr527. Src phosphorylated Alix at a C-terminal region rich in tyrosines, an activity that was stimulated by the presence of the Alix binding partner SETA/CIN85. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2. As a consequence of this, Src antagonized the negative regulation of receptor tyrosine kinase internalization and cell adhesion by Alix. We propose a model whereby Src antagonizes the effects of Alix by phosphorylation of its C terminus, leading to the disruption of interactions with target proteins.
The ubiquitin (Ub) ligase Cbl plays a critical role in attenuation of receptor tyrosine kinase (RTK) signaling by inducing ubiquitination of RTKs and promoting their sorting for endosomal degradation. Herein, we describe the identification of two novel Cbl-interacting proteins, p70 and Clip4 (recently assigned the names Sts-1 and Sts-2, respectively), that inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. Sts-1 and Sts-2 contain SH3 domains that interacted with Cbl, Ub-associated domains, which bound directly to mono-Ub or to the EGFR/Ub chimera as well as phosphoglycerate mutase domains that mediated oligomerization of Sts-1/2. Ligand-induced recruitment of Sts-1/Sts-2 into activated EGFR complexes led to inhibition of receptor internalization, reduction in the number of EGFR-containing endocytic vesicles, and subsequent block of receptor degradation followed by prolonged activation of mitogenic signaling pathways. On the other hand, interference with Sts-1/Sts-2 functions diminished ligand-induced receptor degradation, cell proliferation, and oncogenic transformation in cultured fibroblasts. We suggest that Sts-1 and Sts-2 represent a novel class of Ub-binding proteins that regulate RTK endocytosis and control growth factor-induced cellular functions.
The association of Schlen k’s hydrocarbon was studied by means of osmometric and magnetic measurements. The mixed chain-ring-association can be explained satisfactorily assuming that two different dimers and four monomer species participate in the equilibria, including a monomeric diamagnetic ring. The equilibria existing between the different species are discussed. For the equilibria between the monomer and dimer species, which can be detected in solutions of normal viscosity by means of ESR-measurements, the unexpected values of ΔH=0 for the enthalpie of association and ΔS= +19.7 e. u. for the entropie of association were found.
The cis-trans-isomerism of the WITTIG hydrocarbon was investigated in solid state and solution by means of fluorescence spectroscopy. The fluorescence behavior of both isomers in 2-methyltetrahydrofurane was determined as a function of concentration, temperature, and wavelength of exciting radiation. Furthermore, irradiation experiments were undertaken with light of various wavelengths.
The results obtained are in agreement with the assumption that the WITTIG hydrocarbon behaves with regard to the cis-trans-isomerism like a 1,3-butadien derivative, i.e. a thermal but no photochemical cis-trans-isomerisation can be detected. The enthalpy difference between the two isomers was estimated to ΔΗ = 250 ± 50 cal/mole. It could be shown that the fluorescence of the cis-isomer is quenched by the trans-isomer. This quenching occurs probably according to the resonance energy transfer mechanism.
Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 3-year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. (trial registered at www.clinicaltrials.gov: NCT00355862) (EudraCT Number: 2005-005362-36)
On the observation of mesospheric air inside the arctic stratospheric polar vortex in early 2003
(2005)
During several balloon flights inside the Arctic polar vortex in early 2003, unusual trace gas distributions were observed, which indicate a strong influence of mesospheric air in the stratosphere. The tuneable diode laser (TDL) instrument SPIRALE (Spectroscopie InFrarouge par Absorption de Lasers Embarqués) measured unusually high CO values (up to 600 ppb) on 27 January at about 30 km altitude. The cryosampler BONBON sampled air masses with very high molecular Hydrogen, extremely low SF6 and enhanced CO values on 6 March at about 25 km altitude. Finally, the MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) Fourier Transform Infra-Red (FTIR) spectrometer showed NOy values which are significantly higher than NOy* (the NOy derived from a correlation between N2O and NOy under undisturbed conditions), on 21 and 22 March in a layer centred at 22 km altitude. Thus, the mesospheric air seems to have been present in a layer descending from about 30 km in late January to 25 km altitude in early March and about 22 km altitude on 20 March. We present corroborating evidence from a model study using the KASIMA (KArlsruhe Simulation model of the Middle Atmosphere) model that also shows a layer of mesospheric air, which descended into the stratosphere in November and early December 2002, before the minor warming which occurred in late December 2002 lead to a descent of upper stratospheric air, cutting of a layer in which mesospheric air is present. This layer then descended inside the vortex over the course of the winter. The same feature is found in trajectory calculations, based on a large number of trajectories started in the vicinity of the observations on 6 March. Based on the difference between the mean age derived from SF6 (which has an irreversible mesospheric loss) and from CO2 (whose mesospheric loss is much smaller and reversible) we estimate that the fraction of mesospheric air in the layer observed on 6 March, must have been somewhere between 35% and 100%.
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).
Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).
Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
Biophysical parameters can accelerate drug development; e.g., rigid ligands may reduce entropic penalty and improve binding affinity. We studied systematically the impact of ligand rigidification on thermodynamics using a series of fasudil derivatives inhibiting protein kinase A by crystallography, isothermal titration calorimetry, nuclear magnetic resonance, and molecular dynamics simulations. The ligands varied in their internal degrees of freedom but conserve the number of heteroatoms. Counterintuitively, the most flexible ligand displays the entropically most favored binding. As experiment shows, this cannot be explained by higher residual flexibility of ligand, protein, or formed complex nor by a deviating or increased release of water molecules upon complex formation. NMR and crystal structures show no differences in flexibility and water release, although strong ligand-induced adaptations are observed. Instead, the flexible ligand entraps more efficiently water molecules in solution prior to protein binding, and by release of these waters, the favored entropic binding is observed.
Sleep is regulated in a time-of-day dependent manner and profits working memory. However, the impact of the circadian timing system as well as contributions of specific sleep properties to this beneficial effect remains largely unexplored. Moreover, it is unclear to which extent inter-individual differences in sleep-wake regulation depend on circadian phase and modulate the association between sleep and working memory. Here, sleep electroencephalography (EEG) was recorded during a 40-h multiple nap protocol, and working memory performance was assessed by the n-back task 10 times before and after each scheduled nap sleep episode. Twenty-four participants were genotyped regarding a functional polymorphism in adenosine deaminase (rs73598374, 12 G/A-, 12 G/G-allele carriers), previously associated with differences in sleep-wake regulation. Our results indicate that genotype-driven differences in sleep depend on circadian phase: heterozygous participants were awake longer and slept less at the end of the biological day, while they exhibited longer non rapid eye movement (NREM) sleep and slow wave sleep concomitant with reduced power between 8–16 Hz at the end of the biological night. Slow wave sleep and NREM sleep delta EEG activity covaried positively with overall working memory performance, independent of circadian phase and genotype. Moreover, REM sleep duration benefitted working memory particularly when occurring in the early morning hours and specifically in heterozygous individuals. Even though based on a small sample size and thus requiring replication, our results suggest genotype-dependent differences in circadian sleep regulation. They further indicate that REM sleep, being under strong circadian control, boosts working memory performance according to genotype in a time-of-day dependent manner. Finally, our data provide first evidence that slow wave sleep and NREM sleep delta activity, majorly regulated by sleep homeostatic mechanisms, is linked to working memory independent of the timing of the sleep episode within the 24-h cycle.
Blood vessels form de novo through the tightly regulated programs of vasculogenesis and angiogenesis. Both processes are distinct but one of the steps they share is the formation of a central lumen, when groups of cells organized as vascular cords undergo complex changes to achieve a tube-like morphology. Recently, a protein termed epidermal growth factor-like domain 7 (EGFL7) was described as a novel endothelial cell-derived factor involved in the regulation of the spatial arrangement of cells during vascular tube assembly. With its impact on tubulogenesis and vessel shape EGFL7 joined the large family of molecules governing blood vessel formation. Only recently, the molecular mechanisms underlying EGFL7's effects have been started to be elucidated and shaping of the extracellular matrix (ECM) as well as Notch signaling might very well play a role in mediating its biological effects. Further, findings in knock-out animal models suggest miR-126, a miRNA located within the egfl7 gene, has a major role in vessel development by promoting VEGF signaling, angiogenesis and vascular integrity. This review summarizes our current knowledge on EGFL7 and miR-126 and we will discuss the implications of both bioactive molecules for the formation of blood vessels.
Two aircraft instruments for the measurement of total odd nitrogen (NOy) were compared side by side aboard a Learjet A35 in April 2003 during a campaign of the AFO2000 project SPURT (Spurengastransport in der Tropopausenregion). The instruments albeit employing the same measurement principle (gold converter and chemiluminescence) had different inlet configurations. The ECO-Physics instrument operated by ETH-Zürich in SPURT had the gold converter mounted outside the aircraft, whereas the instrument operated by FZ-Jülich in the European project MOZAIC III (Measurements of ozone, water vapour, carbon monoxide and nitrogen oxides aboard Airbus A340 in-service aircraft) employed a Rosemount probe with 80 cm of FEP-tubing connecting the inlet to the gold converter. The NOy concentrations during the flight ranged between 0.3 and 3 ppb. The two data sets were compared in a blind fashion and each team followed its normal operating procedures. On average, the measurements agreed within 7%, i.e. within the combined uncertainty of the two instruments. This puts an upper limit on potential losses of HNO3 in the Rosemount inlet of the MOZAIC instrument. Larger transient deviations were observed during periods after calibrations and when the aircraft entered the stratosphere. The time lag of the MOZAIC instrument observed in these instances is in accordance with the time constant of the MOZAIC inlet line determined in the laboratory for HNO3.
Two aircraft instruments for the measurement of total odd nitrogen (NOy) were compared side by side aboard a Learjet A35 in April 2003 during a campaign of the AFO2000 project SPURT (Spurengastransport in der Tropopausenregion). The instruments albeit employing the same measurement principle (gold converter and chemiluminescence) had different inlet configurations. The ECO-Physics instrument operated by ETH-Zürich in SPURT had the gold converter mounted outside the aircraft, whereas the instrument operated by FZ-Jülich in the European project MOZAIC III (Measurements of ozone, water vapour, carbon monoxide and nitrogen oxides aboard Airbus A340 in-service aircraft) employed a Rosemount probe with 80 cm of FEP-tubing connecting the inlet to the gold converter. The NOy concentrations during the flight ranged between 0.3 and 3 ppb. The two data sets were compared in a blind fashion and each team followed its normal operating procedures. On average, the measurements agreed within 6%, i.e. within the combined uncertainty of the two instruments. This puts an upper limit on potential losses of HNO3 in the Rosemount inlet of the MOZAIC instrument. Larger transient deviations were observed during periods after calibrations and when the aircraft entered the stratosphere. The time lag of the MOZAIC instrument observed in these instances is in accordance with the time constant of the MOZAIC inlet line determined in the laboratory for HNO3.
Background: Although childhood sexual and/or physical abuse (CSA/CPA) is known to have severe psychopathological consequences, there is little evidence on psychotherapeutic interventions for adolescents and young adults suffering from post-traumatic stress disorder (PTSD). Equally sparse are data on moderators of treatment response on PTSD-related epigenetic changes, health care costs and loss of productivity, alterations in cognitive processing, and on how successful interventions affect all of these factors. Early treatment may prevent later (co)morbidity. In this paper, we present a study protocol for the evaluation of a newly developed psychotherapeutic manual for PTSD after CSA/CPA in adolescents and young adults – the Developmentally Adapted Cognitive Processing Therapy (D-CPT).
Methods/design: In a multicenter randomized controlled trial (RCT) D-CPT is compared to treatment as usual (TAU). A sample of 90 adolescent outpatients aged 14 to 21 years will be randomized to one of these conditions. Four assessments will be carried out at baseline, at end of treatment, and 3 and 6 months after end of therapy. Each time, patients will be assessed via clinical interviews and a wide range of questionnaires. In addition to PTSD symptoms and comorbidities, we will evaluate moderators of treatment response, epigenetic profiles, direct and indirect costs of this disorder, and neurophysiological processing of threat cues in PTSD and their respective changes in the course of these two treatments (D-CPT and TAU).
Discussion: The study will provide new insights in the understudied field of PTSD in adolescents and young adults. A newly developed intervention will be evaluated in this therapeutically underserved population. Results will provide data on treatment efficacy, direct and indirect treatment costs, as well as on associations of treatment outcome and PTSD intensity both to epigenetic profiles and to the neurobiological processing of threat cues. Besides, they will help to learn more about the psychopathology and possible new objective correlates of PTSD.
Trial registration: Germanctr.de identifier: DRKS00004787.
EGFL7 enhances surface expression of integrin α5β1 to promote angiogenesis in malignant brain tumors
(2018)
Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti‐VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab. Although its application in human GBM only increased progression‐free periods but did not improve overall survival, physicians and researchers still utilize this treatment option due to the lack of adequate alternatives. In an attempt to improve the efficacy of anti‐VEGF treatment, we explored the role of the egfl7 gene in malignant glioma. We found that the encoded extracellular matrix protein epidermal growth factor‐like protein 7 (EGFL7) was secreted by glioma blood vessels but not glioma cells themselves, while no major role could be assigned to the parasitic miRNAs miR‐126/126*. EGFL7 expression promoted glioma growth in experimental glioma models in vivo and stimulated tumor vascularization. Mechanistically, this was mediated by an upregulation of integrin α5β1 on the cellular surface of endothelial cells, which enhanced fibronectin‐induced angiogenic sprouting. Glioma blood vessels that formed in vivo were more mature as determined by pericyte and smooth muscle cell coverage. Furthermore, these vessels were less leaky as measured by magnetic resonance imaging of extravasating contrast agent. EGFL7‐inhibition using a specific blocking antibody reduced the vascularization of experimental gliomas and increased the life span of treated animals, in particular in combination with anti‐VEGF and the chemotherapeutic agent temozolomide. Data allow for the conclusion that this combinatorial regimen may serve as a novel treatment option for GBM.
Recent studies suggest that synaptic lysophosphatidic acids (LPAs) augment glutamate-dependent cortical excitability and sensory information processing in mice and humans via presynaptic LPAR2 activation. Here, we studied the consequences of LPAR2 deletion or antagonism on various aspects of cognition using a set of behavioral and electrophysiological analyses. Hippocampal neuronal network activity was decreased in middle-aged LPAR2−/− mice, whereas hippocampal long-term potentiation (LTP) was increased suggesting cognitive advantages of LPAR2−/− mice. In line with the lower excitability, RNAseq studies revealed reduced transcription of neuronal activity markers in the dentate gyrus of the hippocampus in naïve LPAR2−/− mice, including ARC, FOS, FOSB, NR4A, NPAS4 and EGR2. LPAR2−/− mice behaved similarly to wild-type controls in maze tests of spatial or social learning and memory but showed faster and accurate responses in a 5-choice serial reaction touchscreen task requiring high attention and fast spatial discrimination. In IntelliCage learning experiments, LPAR2−/− were less active during daytime but normally active at night, and showed higher accuracy and attention to LED cues during active times. Overall, they maintained equal or superior licking success with fewer trials. Pharmacological block of the LPAR2 receptor recapitulated the LPAR2−/− phenotype, which was characterized by economic corner usage, stronger daytime resting behavior and higher proportions of correct trials. We conclude that LPAR2 stabilizes neuronal network excitability upon aging and allows for more efficient use of resting periods, better memory consolidation and better performance in tasks requiring high selective attention. Therapeutic LPAR2 antagonism may alleviate aging-associated cognitive dysfunctions.
We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(α,γ)16O fusion reaction and to reach lower center-ofmass energies than measured so far.
The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-to-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
During several balloon flights inside the Arctic polar vortex in early 2003, unusual trace gas distributions were observed, which indicate a strong influence of mesospheric air in the stratosphere. The tuneable diode laser (TDL) instrument SPIRALE (Spectroscopie InFrarouge par Absorption de Lasers Embarqués) measured unusually high CO values (up to 600 ppb) on 27 January at about 30 km altitude. The cryosampler BONBON sampled air masses with very high molecular Hydrogen, extremely low SF6 and enhanced CO values on 6 March at about 25 km altitude. Finally, the MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) Fourier Transform Infra-Red (FTIR) spectrometer showed NOy values which are significantly higher than NOy* (the NOy derived from a correlation between N2O and NOy under undisturbed conditions), on 21 and 22 March in a layer centred at 22 km altitude. Thus, the mesospheric air seems to have been present in a layer descending from about 30 km in late January to 25 km altitude in early March and about 22 km altitude on 20 March. We present corroborating evidence from a model study using the KASIMA (KArlsruhe Simulation model of the Middle Atmosphere) model that also shows a layer of mesospheric air, which descended into the stratosphere in November and early December 2002, before the minor warming which occurred in late December 2002 lead to a descent of upper stratospheric air, cutting of a layer in which mesospheric air is present. This layer then descended inside the vortex over the course of the winter. The same feature is found in trajectory calculations, based on a large number of trajectories started in the vicinity of the observations on 6 March. Based on the difference between the mean age derived from SF6 (which has an irreversible mesospheric loss) and from CO2 (whose mesospheric loss is much smaller and reversible) we estimate that the fraction of mesospheric air in the layer observed on 6 March, must have been somewhere between 35% and 100%.
The introduction of a common currency as well as the harmonization of rules and regulations in Europe has significantly reduced distance in all its guises. With reduced costs of overcoming space, this emphasizes centripetal forces and it should foster consolidation of financial activity. In a national context, as a rule, this led to the emergence of one financial center. Hence, Europeanization of financial and monetary affairs could foretell the relegation of some European financial hubs such as Frankfurt and Paris to third-rank status. Frankfurt’s financial history is interesting insofar as it has lost (in the 1870s) and regained (mainly in the 1980s) its preeminent place in the German context. Because Europe is still characterized by local pockets of information-sensitive assets as well as a demand for variety the national analogy probably does not hold. There is room in Europe for a number of financial hubs of an international dimension, including Frankfurt.
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.