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The components of the nuclear inertia tensor, functions of the separation distance R and of the radius of the light fragment R2, BRR(R,R2), BRR2(R,R2), and BR2R2(R,R2) are calculated within the Werner-Wheeler approximation, by using the parametrization of two intersected symmetric or asymmetric spheres. Analytical relationships are derived. When projected to a path R2=R2(R), the reduced mass is obtained at the touching point. The two one-dimensional parametrizations with R2=const, and the volume V2=const previously studied, are found to be particular cases of the present more general approach. Illustrations for the cold fission, cluster radioactivity, and α decay of 252Cf are given.
Objective: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.
Design: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.
Results: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.
Conclusion: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
A measurement of charged hadron pair correlations in two-dimensional ηφ space is presented. The analysis is based on total 30 million central Be + Be collisions observed in the NA61/SHINE detector at the CERN SPS for incident beam momenta of 19A, 30A, 40A, 75A, and 150A GeV/c. Measurements were carried out for unlike-sign and like-sign charge hadron pairs independently. The C(η, φ) correlation functions were compared with results from a similar analysis on p + p interactions at similar beam momenta per nucleon. General trends of the backto-back correlations are similar in central Be + Be collisions and p + p interactions, but are suppressed in magnitude due to the increased combinatorial background. Predictions from the Epos and UrQMD models are compared to the measurements. Evolution of an enhancement around (η, φ) = (0, 0) with incident energy is observed in central Be + Be collisions. It is not predicted by both models and almost non-existing in proton–proton collisions at the same momentum per nucleon.
Two-particle correlations on transverse rapidity in Au+Au collisions at √sNN = 200 GeV at STAR
(2022)
Two-particle correlation measurements projected onto two-dimensional, transverse rapidity coordinates (yT1,yT2), allow access to dynamical properties of the QCD medium produced in relativistic heavy-ion collisions that angular correlation measurements are not sensitive to. We report non-identified charged-particle correlations for Au + Au minimum-bias collisions at sNN−−−√ = 200 GeV taken by the STAR experiment at the Relativistic Heavy-Ion Collider (RHIC). Correlations are presented as 2D functions of transverse rapidity for like-sign, unlike-sign and all charged-particle pairs, as well as for particle pairs whose relative azimuthal angles lie on the near-side, the away-side, or at all relative azimuth. The correlations are constructed using charged particles with transverse momentum pT≥0.15 GeV/c, pseudorapidity from −1 to 1, and azimuthal angles from −π to π. The significant correlation structures that are observed evolve smoothly with collision centrality. The major correlation features include a saddle shape plus a broad peak with maximum near yT≈3, corresponding to pT≈ 1.5 GeV/c. The broad peak is observed in both like- and unlike-sign charge combinations and in near- and away-side relative azimuthal angles. The all-charge, all-azimuth correlation measurements are compared with the theoretical predictions of {\sc hijing} and {\sc epos}. The results indicate that the correlations for peripheral to mid-central collisions can be approximately described as a superposition of nucleon + nucleon collisions with minimal effects from the QCD medium. Strong medium effects are indicated in mid- to most-central collisions.
We present measurements of two-particle differential number correlation functions R2 and transverse momentum correlation functions P2, obtained from p-Pb collisions at 5.02 TeV and Pb-Pb collisions at 2.76 TeV. The results are obtained using charged particles in the pseudorapidity range |η|< 1.0, and transverse momentum range 0.2<pT<2.0 GeV/c as a function of pair separation in pseudorapidity, |Δη|, azimuthal angle, Δφ, and for several charged-particle multiplicity classes. Measurements are carried out for like-sign and unlike-sign charged-particle pairs separately and combined to obtain charge-independent and charge-dependent correlation functions. We study the evolution of the width of the near-side peak of these correlation functions with collision centrality. Additionally, we study Fourier decompositions of the correlators in Δφ as a function of the pair separation |Δη|. Significant differences in the dependence of their harmonic coefficients on multiplicity classes are found. These differences can be exploited, in theoretical models, to obtain further insight into charged-particle production and transport in heavy-ion collisions. Moreover, an upper limit of non-flow contributions to flow coefficients vn measured in Pb-Pb collisions based on the relative strength of Fourier coefficients measured in p-Pb interactions is estimated.
One of the most challenging problems in solid state systems is the microscopic analysis of electronic correlations. A paramount minimal model that encodes correlation effects is the Hubbard Hamiltonian, which—regardless of its simplicity—is exactly solvable only in a few limiting cases and approximate many-body methods are required for its solution. In this review, an overview on the non-perturbative two-particle self-consistent method (TPSC), which was originally introduced to describe the electronic properties of the single-band Hubbard model, is presented. A detailed derivation of the multi-orbital generalization of TPSC is introduced here and particular features of the method on exemplary interacting models in comparison to dynamical mean-field theory results are discussed.
Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at LHC energies, provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at s√=7 TeV and sNN−−−√=5.02 TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.
Two-particle transverse momentum differential correlators, recently measured in Pb--Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at s√=7 TeV and sNN−−−√=5.02 TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p--Pb to Pb--Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.
Two-particle transverse momentum differential correlators, recently measured in Pb--Pb collisions at energies available at the CERN Large Hadron Collider (LHC), provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at √s=7 TeV and sNN−−−√=5.02 TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p--Pb to Pb--Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed.
Late Paleozoic (Variscan) magmatism is widespread in Central Europe. The Lusatian Block is located in the NE Bohemian Massif and it is part of the Saxothuringian Zone of the Variscan orogen. It is bordered by two major NW-trending shear zones, the Intra-Sudetic Fault Zone towards NE and the Elbe Fault Zone towards SW. The scarce Variscan igneous rocks of the Lusatian Block are situated close to these faults. We investigated 19 samples from Variscan plutonic and volcanic rocks of the Lusatian Block, considering all petrological varieties (biotite-bearing granites from the Koenigshain and Stolpen plutons, amphibole-bearing granites from three boreholes, several volcanic dykes, and two volcanites from the intramontane Weissig basin). We applied whole-rock geochemistry (18 samples) and zircon evaporation dating (19 samples). From the evaporation data, we selected six representative samples for additional zircon SHRIMP and CA–ID–TIMS dating. For the Koenigshain pluton, possible protoliths were identified using whole-rock Nd-isotopes, and zircon Hf- and O-isotopes. The new age data allow a subdivision of Variscan igneous rocks in the Lusatian Block into two distinct magmatic episodes. The spatial relation of the two age groups to either the Elbe Fault Zone (298–299 Ma) or the Intra-Sudetic Fault Zone (312–313 Ma) together with reports on the fault-bound character of the dated intrusions suggests an interpretation as two major post-collisional faulting episodes. This assumption of two distinct magmatic periods is confirmed by a compilation of recently published zircon U–Pb CA–ID–TIMS data on further Variscan igneous rocks from the Saxothuringian Zone. New geochemical data allow us to exclude a dominant sedimentary protolith for the Koenigshain pluton as supposed by previous investigations. This conclusion is mainly based on new O- and Hf-isotope data on zircon and the scarcity of inherited zircons. Instead, acid or intermediate igneous rocks are supposed as the main source for these I-type granitoids from the Koenigshain pluton.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
We report the results of the femtoscopic analysis of pairs of identical pions measured in p-Pb collisions at sNN−−−√=5.02 TeV. Femtoscopic radii are determined as a function of event multiplicity and pair momentum in three spatial dimensions. As in the pp collision system, the analysis is complicated by the presence of sizable background correlation structures in addition to the femtoscopic signal. The radii increase with event multiplicity and decrease with pair transverse momentum. When taken at comparable multiplicity, the radii measured in p-Pb collisions, at high multiplicity and low pair transverse momentum, are 10-20% higher than those observed in pp collisions but below those observed in A-A collisions. The results are compared to hydrodynamic predictions at large event multiplicity as well as discussed in the context of calculations based on gluon saturation.
We report the results of the femtoscopic analysis of pairs of identical pions measured in p-Pb collisions at sNN−−−√=5.02 TeV. Femtoscopic radii are determined as a function of event multiplicity and pair momentum in three spatial dimensions. As in the pp collision system, the analysis is complicated by the presence of sizable background correlation structures in addition to the femtoscopic signal. The radii increase with event multiplicity and decrease with pair transverse momentum. When taken at comparable multiplicity, the radii measured in p-Pb collisions, at high multiplicity and low pair transverse momentum, are 10-20% higher than those observed in pp collisions but below those observed in A-A collisions. The results are compared to hydrodynamic predictions at large event multiplicity as well as discussed in the context of calculations based on gluon saturation.
We report the results of the femtoscopic analysis of pairs of identical pions measured in p-Pb collisions at sNN−−−√=5.02 TeV. Femtoscopic radii are determined as a function of event multiplicity and pair momentum in three spatial dimensions. As in the pp collision system, the analysis is complicated by the presence of sizable background correlation structures in addition to the femtoscopic signal. The radii increase with event multiplicity and decrease with pair transverse momentum. When taken at comparable multiplicity, the radii measured in p-Pb collisions, at high multiplicity and low pair transverse momentum, are 10-20% higher than those observed in pp collisions but below those observed in A-A collisions. The results are compared to hydrodynamic predictions at large event multiplicity as well as discussed in the context of calculations based on gluon saturation.
The two-proton correlation function at midrapidity from Pb+Pb central collisions at 158 AGeV has been measured by the NA49 experiment. The results are compared to model predictions from static thermal Gaussian proton source distributions and transport models RQMD and VENUS. An effective proton source size is determined by minimizing CHI-square/ndf between the correlation functions of the data and those calculated for the Gaussian sources, yielding 3.85 +-0.15(stat.) +0.60-0.25(syst.) fm. Both the RQMD and the VENUS model are consistent with the data within the error in the correlation peak region.
Background: The surgical treatment of giant olfactory groove meningiomas (OGMs) with marked perilesional brain oedema is still a surgical challenge. After tumour resection, increase of brain oedema may occur causing dramatic neurological deterioration and even death of the patient. The objective of this paper is to describe surgical features of a two-step staged resection of these tumours performed to counter increase of postoperative brain oedema.
Methods: This two-step staged resection procedure was carried out in a consecutive series of 19 patients harbouring giant OGMs. As first step, a bifrontal craniectomy was performed followed by a right-sided interhemispherical approach. About 80% of the tumour mass was resected leaving behind a shell-shaped tumour remnant. In the second step, carried out after the patients’ recovery from the first surgery and decline of oedema, the remaining part of the tumour was removed completely followed by duro- and cranioplasty.
Results: Ten patients recovered quickly from first surgery and the second operation was performed after a mean of 12.4 days. In eight patients, the second operation was carried out later between day 25 and 68 due to surgery-related complications, development of a trigeminal zoster, or to a persisting frontal brain oedema. Mean follow-up was 49.3 months and all but one patient had a good outcome regardless of surgery-related complications.
Conclusions: Our results suggest that a two-step staged resection of giant OGMs minimizes the increase of postoperative brain oedema as far as possible and translates into lower morbidity and mortality.
We present an effective model for timing-dependent synaptic plasticity (STDP) in terms of two interacting traces, corresponding to the fraction of activated NMDA receptors and the concentration in the dendritic spine of the postsynaptic neuron. This model intends to bridge the worlds of existing simplistic phenomenological rules and highly detailed models, thus constituting a practical tool for the study of the interplay of neural activity and synaptic plasticity in extended spiking neural networks. For isolated pairs of pre- and postsynaptic spikes, the standard pairwise STDP rule is reproduced, with appropriate parameters determining the respective weights and timescales for the causal and the anticausal contributions. The model contains otherwise only three free parameters, which can be adjusted to reproduce triplet nonlinearities in hippocampal culture and cortical slices. We also investigate the transition from time-dependent to rate-dependent plasticity occurring for both correlated and uncorrelated spike patterns.
Objectives: Immune checkpoint inhibitors have become the standard of care for metastatic non–small-cell lung cancer (NSCLC) progressing during or after platinum-based chemotherapy. Real-world clinical practice tends to represent more diverse patient characteristics than randomized clinical trials. We sought to evaluate overall survival (OS) outcomes in the total study population and in key subsets of patients who received nivolumab for previously treated advanced NSCLC in real-world settings in France, Germany, or Canada.
Materials and methods: Data were pooled from two prospective observational cohort studies, EVIDENS and ENLARGE, and a retrospective registry in Canada. Patients included in this analysis were aged ≥18 years, had stage IIIB/IV NSCLC, and received nivolumab after at least one prior line of systemic therapy. OS was estimated in the pooled population and in various subgroups using the Kaplan-Meier method. Timing of data collection varied across cohorts (2015–2019).
Results: Of the 2585 patients included in this analyses, 1235 (47.8 %) were treated in France, 881 (34.1 %) in Germany, and 469 (18.1 %) in Canada. Median OS for the total study population was 11.3 months (95 % CI: 10.5–12.2); this was similar across France, Germany, and Canada. The OS rate was 49 % at 1 year and 28 % at 2 years for the total study population. In univariable Cox analyses, the presence of epidermal growth factor receptor mutations in nonsquamous disease, liver, or bone metastases were associated with significantly shorter OS, whereas tumor programmed death ligand 1 expression and Eastern Cooperative Oncology Group performance status 0–1 were associated with significantly prolonged OS. Similar OS was noted across subgroups of age and prior lines of therapy.
Conclusion: OS rates in patients receiving nivolumab for previously treated advanced NSCLC in real-world clinical practice closely mirrored those in phase 3 studies, suggesting similar effectiveness of nivolumab in clinical trials and clinical practice.
A wall-sized canvas by Twombly hanging in a purpose-built pavilion by Renzo Piano, commissioned by the Menil Collection in Houston, bears the scrawled inscription »Anatomy of Melancholy.« Untitled (Say Goodbye Catullus, to the Shores of Asia Minor) is the culminating statement of the artist’s maturity: begun in 1972, it was first exhibited in 1994. In this monumental cenotaph, Twombly’s painting displays phrases from Archilochos, Catullus, Keats and Rilke, as well as the title of Burton’s famous tome, worked into the fabric of the composition, integral to the iconic content. It is the aching heart of the select permanent exhibition of his oeuvre at the pavilion, known as the Twombly Gallery (www.menil.org/twombly.html). The austerity of Piano’s architectural setting, as well as the cunningly filtered Texas sunlight, makes this a site of cult, like the chapel containing the dark, final canvases of Mark Rothko, situated around the corner in the same urban grove of old oak. The setting is a modern Dodona, remote seat of the oaken oracle of Zeus, and it makes an evocative home for Twombly’s enigmatic constructions. These disarm conventional vocabularies of aesthetic response, drawing attention to words and snatches of verse as points of association and recognition. Looking at them involves siting a phrase such as »Anatomy of Melancholy« in other dimensions – in lines, patches, figures, colors.
Informational economies of scope between lending and underwriting are a mixed blessing for universal banks. While they can reduce the cost of raising capital for a firm, they also reduce incentives in the underwriting business. We show that tying lending and underwriting helps to overcome this dilemma. First, risky debt in tied deals works as a bond to increase underwriting incentives. Second, with limitations on contracting, tying reduces the underwriting rents as the additional incentives from debt can substitute for monetary incentives. In addition, reducing the yield on the tied debt is a means to pay for the rent in the underwriting business and to transfer informational benefits to the client. Thus, tying is a double edged sword for universal banks. It helps to compete against specialized investment banks, but it can reduce the rent to be earned in investment banking when universal banks compete against each other. We derive several empirical predictions regarding the characteristics of tied deals. JEL Classification: G21, G24, D49
Tynommatidae, n. stat., elevated from Tynommatinae, is established as a schizopetalidean family encompassing the western North American callipodidans previously assigned to the Mediterranean Schizopetalidae. It is considered a valid taxon despite somewhat anatomically dissimilar subfamilies, and Colactidinae, Texophoninae, Diactidinae, and Aspidiophoninae constitute tribal elevations and additional new statuses. With a subbasal telopodal prefemoral process, Diactis hedini, n. sp., requires rediagnoses of all three diactidine genera, Diactis Loomis, 1937, and Florea and Caliactis, both by Shelley, 1996, and suggests that telopodal branches ‘B’ in congeners and Florea represent distal relocations of the process along the stem. Similarities in the sizes and shapes of the pleurotergal carinae suggest a sister-group relationship with the other, and partly sympatric, New World family, Abacionidae, which is supported by gonopodal similarities between Colactidinae and Abacion Rafi nesque, 1820. The Western Interior Seaway of the Cretaceous Period, Mesozoic Era, ~141–66 million years ago, appears to have fueled divergence by isolating “proto-abacionid stock” in “Appalachia,” the Eastern North American land mass, which has subsequently spread well into previously inundated areas. The allopatric position of Texophoninae, on the Gulf Coast of south Texas around 1,136 km (710 mi) east of the most proximate familial records, is attributed to this waterway, which eradicated faunal linkages with “proto-Tynommatidae” in “Laramidia,” the Western North American land mass. Texophoninae probably survived the Cretaceous on insular refugia; however, it is rarely encountered anymore and seems destined for imminent extinction. Representatives of the east-Asian families, Caspiopetalidae, Paracortinidae, and Sinocallipodidae, also possess demarcated pleurotergal crests and, implausible though it seems, may share ancestry with the North American taxa vis-à-vis the “Asiamerica” and or “Boreotropic” concepts.
This paper aims to provide type hierarchies for Korean passive constructions on the basis of their forms within the HPSG framework. The type hierarchies proposed in this paper are based on the classification of Korean passives; suffixal passives, auxiliary passives, inherent passives, and passive light verb constructions. Verbs are divided into five subtypes in accordance with the possibility of passivization. We also provide type hierarchies for verbal nouns and passive light verbs.
De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT) and the condensation (KS) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
De novo fatty acid biosynthesis in humans is accomplished by a multidomain protein, the Type I fatty acid synthase (FAS). Although ubiquitously expressed in all tissues, fatty acid synthesis is not essential in normal healthy cells due to sufficient supply with fatty acids by the diet. However, FAS is overexpressed in cancer cells and correlates with tumor malignancy, which makes FAS an attractive selective therapeutic target in tumorigenesis. Herein, we present a crystal structure of the condensing part of murine FAS, highly homologous to human FAS, with octanoyl moieties covalently bound to the transferase (MAT—malonyl‐/acetyltransferase) and the condensation (KS—β‐ketoacyl synthase) domain. The MAT domain binds the octanoyl moiety in a novel (unique) conformation, which reflects the pronounced conformational dynamics of the substrate‐binding site responsible for the MAT substrate promiscuity. In contrast, the KS binding pocket just subtly adapts to the octanoyl moiety upon substrate binding. Besides the rigid domain structure, we found a positive cooperative effect in the substrate binding of the KS domain by a comprehensive enzyme kinetic study. These structural and mechanistic findings contribute significantly to our understanding of the mode of action of FAS and may guide future rational inhibitor designs.
Cytokine regulation of high-output nitric oxide (NO) derived from inducible NO synthase (iNOS) is critically involved in inflammation biology and host defense. Herein, we set out to characterize the role of type I interferon (IFN) as potential regulator of hepatic iNOS in vitro and in vivo. In this regard, we identified in murine Hepa1-6 hepatoma cells a potent synergism between pro-inflammatory interleukin-β/tumor necrosis factor-α and immunoregulatory IFNβ as detected by analysis of iNOS expression and nitrite release. Upregulation of iNOS by IFNβ coincided with enhanced binding of signal transducer and activator of transcription-1 to a regulatory region at the murine iNOS promoter known to support target gene expression in response to this signaling pathway. Synergistic iNOS induction under the influence of IFNβ was confirmed in alternate murine Hepa56.1D hepatoma cells and primary hepatocytes. To assess iNOS regulation by type I IFN in vivo, murine acetaminophen (APAP)-induced sterile liver inflammation was investigated. In this model of acute liver injury, excessive necroinflammation drives iNOS expression in diverse liver cell types, among others hepatocytes. Herein, we demonstrate impaired iNOS expression in type I IFN receptor-deficient mice which associated with diminished APAP-induced liver damage. Data presented indicate a vital role of type I IFN within the inflamed liver for fine-tuning pathological processes such as overt iNOS expression.
Type species designations are reviewed and discussed far six New World Hispinae genera. Valid designations are: Oediopalpa cyanipennis (Fab.), Homalispa (Homalispa) batesii Baly, H. (Xanthispa) cimicoides (Guerin), Demotispa pallida Baly, Cephaloleia nigricornis (Fab.), and Coraliomela brunnea (Thunberg).
Purpose: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) replicates predominantly in the upper respiratory tract and is primarily transmitted by droplets and aerosols. Taking the medical history for typical COVID-19 symptoms and PCR-based SARS-CoV-2 testing have become established as screening procedures. The aim of this work was to describe the clinical appearance of SARS-CoV-2-PCR positive patients and to determine the SARS-CoV-2 contact risk for health care workers (HCW).
Methods: The retrospective study included n = 2283 SARS-CoV-2 PCR tests from n = 1725 patients with otorhinolaryngological (ORL) diseases performed from March to November 2020 prior to inpatient treatment. In addition, demographic data and medical history were assessed.
Results: n = 13 PCR tests (0.6%) were positive for SARS-CoV-2 RNA. The positive rate showed a significant increase during the observation period (p < 0.01). None of the patients had clinical symptoms that led to a suspected diagnosis of COVID-19 before PCR testing. The patients were either asymptomatic (n = 4) or had symptoms that were interpreted as symptoms typical of the ORL disease or secondary diagnoses (n = 9).
Conclusion: The identification of SARS-CoV-2-positive patients is a considerable challenge in clinical practice. Our findings illustrate that taking a medical history alone is of limited value and cannot replace molecular SARS-CoV-2 testing, especially for patients with ORL diseases. Our data also demonstrate that there is a high probability of contact with SARS-CoV-2-positive patients in everyday clinical practice, so that the use of personal protective equipment, even in apparently “routine cases”, is highly recommended.
This paper contributes to the clarification of the concept of “typicality” discussed in contemporary philosophy of physics by conceiving the nomological status of a typical behaviour such as that expressed in the Second Law of Thermodynamics as a “minutis rectis law”. A brief sketch of the discovery of “typicality” shows that there were ideas of typical behaviour not only in physics but also in sociology. On this basis and in analogy to the Second Law of Thermodynamics, it is shown that the nomological status of sociological laws such as Gresham’s Law can also be conceived as “minutis rectis laws”.
Different languages employ different morphosyntactic devices for expressing genericity. And, of course, they also make use of different morphosyntactic and semantic or pragmatic cues which may contribute to the interpretation of a sentence as generic rather than episodic. [...] We will advance the strong hypo thesis that it is a fundamental property of lexical elements in natural language that they are neutral with respect to different modes of reference or non-reference. That is, we reject the idea that a certain use of a lexical element, e.g. a use which allows reference to particular spatio-temporally bounded objects in the world, should be linguistically prior to all other possible uses, e.g. to generic and non-specific uses. From this it follows that we do not consider generic uses as derived from non-generic uses as it is occasionally assumed in the literature. Rather, we regard these two possibilities of use as equivalent alternative uses of lexical elements. The typological differences to be noted therefore concern the formal and semantic relationship of generic and non-generic uses to each other; they do not pertain to the question of whether lexical elements are predetermined for one of these two uses. Even supposing we found a language where generic uses are always zero-marked and identical to lexical sterns, we would still not assume that lexical elements in this language primarily have a generic use from which the non-generic uses are derived. (Incidentally, none of the languages examined, not even Vietnamese, meets this criterion.)
Typology and complexity
(2005)
For the Workshop I was asked to talk about complexity in language from a typological perspective. My way of approaching this topic was to ask myself some questions, and then see where the answers led. The first one was of course, "What sort of system are we looking at complexity in - what kind of system is language?"
The present study, based on a typological survey of ca. 70 languages, offers a systematization of consonantal insertions by classifying them into three main types: grammatical, phonetic, and prosodic insertions. The three epenthesis types essentially differ from each other in terms of preferred sounds, domains of application, the role of segmental context, their occurrence cross-linguistically, the extent of variation and phonetic explication.
The present investigation is significantly different from other analyses of consonantal epentheses in the sense that it neither invokes markedness nor diachronic state of the processes under discussion. Instead, it considers the different nature of the epenthetic segments by referring to the representational levels and/or domains which are relevant for their appearance.
Poster presentation: NO-sensitive guanylyl cyclases (GC) are the principal receptors for nitric oxide (NO) and convert GTP into the second messenger cGMP. We showed that GC is prone to tyrosine phosphorylation in COS1 cells overexpressing the human holoenzyme. Similar results were obtained in PC12 cells and in rat aortic tissue slices. The major phosphorylation site was mapped to position 192 in the regulatory domain of the beta1 subunit. Tyrosine phosphorylation of GC was reduced in the presence of the inhibitors PP1 and PP2 indicating that Src-like kinases are critically involved in phosphorylation. Moreover, co-immunoprecipitation experiments revealed an interaction between Src and GC. To further analyse the relevance of this posttranslational modification we generated a phospho-specific antibody raised against pTyr192. This antibody clearly distinguishes between phosphorylated and non-phosphorylated GC and may be a powerful tool to analyse the subcellular localisation of the phosphorylated enzyme.
Chunk parsing has focused on the recognition of partial constituent structures at the level of individual chunks. Little attention has been paid to the question of how such partial analyses can be combined into larger structures for complete utterances. The TüSBL parser extends current chunk parsing techniques by a tree-construction component that extends partial chunk parses to complete tree structures including recursive phrase structure as well as function-argument structure. TüSBLs tree construction algorithm relies on techniques from memory-based learning that allow similarity-based classification of a given input structure relative to a pre-stored set of tree instances from a fully annotated treebank. A quantitative evaluation of TüSBL has been conducted using a semi-automatically constructed treebank of German that consists of appr. 67,000 fully annotated sentences. The basic PARSEVAL measures were used although they were developed for parsers that have as their main goal a complete analysis that spans the entire input.This runs counter to the basic philosophy underlying TüSBL, which has as its main goal robustness of partially analyzed structures.
This memorandum describes the approach of the U.S. Securities and Exchange Commission (the "SEC") in monitoring and, where appropriate, regulating the use of research reports by investment banking firms in connection with securities transactions. The memorandum addresses the historical system of regulation, which continues in large measure to apply. It also examines the new initiatives taken, following a number of prominent corporate, accounting and banking scandals and a significant decline in U.S. and international capital markets, to supplement the current system in what some have dubbed the "post-Enron era".
NADH: ubiquinone oxidoreductase (complex I) is the first enzyme complex of the respiratory chain. Complex I is a redox-driven proton pump that contributes to the proton motive force that drives ATP synthase. The structure of complex I has been analyzed by x-ray crystallography and electron cryo-microscopy and is now well-described. The ubiquinone (Q) reduction site of complex I is buried in the peripheral arm and a tunnel-like structure is thought to provide access for the hydrophobic substrate from the membrane. Several intermediate binding positions for Q in the tunnel were identified in molecular simulations. Structural data showed the binding of native Q molecules and short chain analogs and inhibitors in the access pathway and in the Q reduction site, respectively. We here review the current knowledge on the interaction of complex I with Q and discuss recent hypothetical models for the coupling mechanism.
Legionella pneumophila, a Gram-negative intracellular bacterium, is one of the major causes of Legionnaires’ disease, a specific type of atypical pneumonia. Despite intensive research efforts that elucidated many relevant structural, molecular and medical insights into Legionella’s pathogenicity, Legionnaires’ disease continues to present an ongoing public health concern. Legionella’s virulence is based on its ability to simultaneously hijack multiple molecular pathways of the host cell to ensure its fast replication and dissemination. Legionella usurps the host ubiquitin system through multiple effector proteins, using the advantage of both conventional and unconventional (phosphoribosyl-linked) ubiquitination, thus providing optimal conditions for its replication. In this review, we summarize the current understanding of L. pneumophila from medical, biochemical and molecular perspectives. We describe the clinical disease presentation, its diagnostics and treatment, as well as host-pathogen interactions, with the emphasis on the ability of Legionella to target the host ubiquitin system upon infection. Furthermore, the interdisciplinary use of innovative technologies enables better insights into the pathogenesis of Legionnaires’ disease and provides new opportunities for its treatment and prevention.
Ubiquitylation is a three-step process, which results in the attachment of the small protein ubiquitin (Ub) to lysine residues on a substrate protein. SUMO proteins are ubiquitin (Ub)-related modifiers implicated in the regulation of gene transcription, cell cycle, DNA repair and protein localization. The molecular mechanisms by which the sumoylation of target proteins regulates diverse cellular functions remain poorly understood. During my PhD I isolated and characterized SUMO1 and SUMO2 binding motifs. Using Yeast Two Hybrid system, bioinformatics and NMR spectroscopy we defined a common SUMO-interacting motif (SIM) and map its binding surfaces on SUMO1 and SUMO2. This motif forms a β-strand that could bind in parallel or anti-parallel orientation to the β2-strand of SUMO due to the environment of the hydrophobic core. A negative charge imposed by a stretch of neighboring acidic amino acids and/or phosphorylated serine residues determines its specificity in binding to distinct SUMO paralogues and can modulate the spatial orientation of SUMO-SIM interactions. Mutation of the SUMO interacting motif of TTRAP (TRAFS and TNF receptor associated protein) influences both its localization and dynamic behaviour in living cells. Ubiquitin (Ub)-binding domains (UBDs) are key elements in conveying Ub-based cellular signals. UBD-containing proteins interact with ubiquitylated targets and control numerous biological processes including receptor trafficking, DNA repair, virus budding and gene transcription. They themselves undergo UBD-dependent monoubiquitylation, which promotes intramolecular binding of the UBD to the attached Ub and consequently leads to their functional inhibition. During the second part of my PhD I could show that, in contrast to the established ubiquitylation pathway, the presence of UBDs allows the monoubiquitylation of host protein independently of classical E3 ligases. UBDs of different types including UBA, UIM, UBM, NFZ and UBZ, can directly cooperate with E2 Ub-conjugating enzymes to promote monoubiquitylation of their host proteins. Using FRET technology I verified that the E2 enzyme and the substrate directly interact in cells. Moreover, UBD-containing proteins Stam2 and Sts2 promote self-ubiquitylation and not ubiquitylation of other targets or form polyUb chains from free Ub. Our study revealed a yet unappreciated role of E2 enzymes in ubiquitylation reactions of UBD containing proteins.
Ubiquitin ligases and beyond
(2012)
First paragraph (this article has no abstract): In a review published in 2004 [1] and that still repays reading today, Cecile Pickart traced the evolution of research on ubiquitination from its origins in the proteasomal degradation of proteins through the revelation that it has a central role in cell cycle regulation and the recognition of regulatory roles for ubiquitin in intracellular membrane transport, cell signalling, transcription, translation, and DNA repair.
By adopting a variety of shapes, proteins can perform a wide number of functions in the cell, from being structural elements or enabling communication with the environment to performing complex enzymatic reactions needed to sustain metabolism. The number of proteins in the cell is limited by the number of genes encoding them. However, several mechanisms exist to increase the overall number of protein functions. One of them are post-translational modifications, i.e. covalent attachment of various molecules onto proteins. Ubiquitin was the first protein to be found to modify other proteins, and, faithful to its evocative name, it is involved in nearly all the activities of a cell. Ubiquitylation of proteins was believed for a long time only to be responsible for proteasomal degradation of modified proteins. However, with the discovery of various types of ubiquitylation, such as mono-, multiple- or poly-ubiquitylation, new functions of this post-translational modification emerged. Mono-ubiquitylation has been implicated in endocytosis, chromatin remodelling and DNA repair, while poly-ubiquitylation influences the half-life of proteins or modulates signal transduction pathways. DNA damage repair and tolerance are example of pathways extensively regulated by ubiquitylation. PCNA, a protein involved in nearly all types of DNA transaction, can undergo both mono- and poly-ubiquitylation. These modifications are believed to change the spectrum of proteins that interact with PCNA. Monoubiquitylation of PCNA is induced by stalling of replication forks when replicative polymerases (pols) encounter an obstacle, such as DNA damage or tight DNA-protein complexes. It is believed that monoubiquitylation of PCNA stimulates the exchange between replicative pols to one of polymerases that can synthesize DNA across various lesions, a mechanism of damage tolerance known as translesion synthesis (TLS). Our work has helped to understand why monoubiqutylation of PCNA favours this polymerase switch. We have identified two novel domains with the ability to bind Ub non-covalently. These domains are present in all the members of Y polymerases performing TLS, and were named Ub-binding zinc finger (UBZ) (in polη and polκ) and Ub-binding motif (UBM) (in polι and Rev1). We have shown that these domains enable Y polymerases to preferentially gain access to PCNA upon stalling of replication, when the action of translesion polymerases is required. While the region of direct interaction between Y pols and PCNA had been known (BRCT domain in Rev1 and PIP box motif (PIP) in three others members), we propose that Ub-binding domains (UBDs) in translesion Y pols enhance the PIP- or BRCT-domain-mediated interaction between these polymerases and PCNA by binding to the Ub moiety attached onto PCNA. Following these initial studies, we have also discovered that Y polymerases themselves undergo monoubiquitylation and that their UBDs mediate this modification. This auto-ubiquitylation is believed to lead to an intramolecular interaction between UBD and Ub attached in cis onto the UBD-containing protein. We have mapped monoubiquitylation sites in polη in the C-terminal portion of the protein containing the nuclear localization signal (NLS) and the PIP box. Beside PIP, the NLS motif is also involved in direct interaction of polη with PCNA. Based on these findings, we propose that monoubiquitylation of either NLS or PIP masks them from potential interaction with PCNA. Lastly, using several functional assays, we have demonstrated the importance of all these three motifs in the C-terminus of polη (UBZ, NLS and PIP) for efficient TLS. We have also constructed a mimic of monoubiquitylated polη by genetically fusing polη with Ub. Interestingly, this chimera is deficient in TLS as compared to the wild-type protein. Altogether, these studies demonstrate that the C-terminus of polη constitutes a regulatory module involved in multiple-site interaction with monoubiquitylated PCNA, and that monoubiquitylation of this region inhibits the interaction between polη and PCNA. Our work has also revealed that the UBDs of Y pols as well as of other proteins implicated in DNA damage repair and tolerance, such as the Werner helicase-interacting protein 1 (Wrnip1), are required for their proper sub-nuclear localization. All these proteins localize to discrete focal structures inside the nucleus and mutation of their UBDs results in inability to accumulate in these foci. Interestingly, by exchanging UBDs between different proteins we have learned that each UBD seems to have a distinct functional role, surprisingly not limited to Ubbinding ability. In fact, swapping the UBZ of Wrnip1 with the UBM of polι abolished the localization of Wrnip1 to foci despite preserving the Ub-binding ability of the chimeric protein. In summary, this work provides an overview of how post-translation modification of proteins by Ub can regulate several DNA transactions. Firstly, key regulators (e.g. PCNA) can be differentially modified by Ub. Secondly, specialized UBDs (e.g. UBM, UBZ) embedded only in a subset of proteins act as modules able to recognize these modifications. Thirdly, by means of mediating auto-ubiquitylation, UBDs can modulate the behaviour of host proteins by allowing for either in cis or in trans Ub-UBD interactions.
Ubiquitination is a widespread post-translational modification that controls multiple steps in autophagy, a major lysosome-mediated intracellular degradation pathway. A variety of ubiquitin chains are attached as selective labels on protein aggregates and dysfunctional organelles, thus promoting their autophagy-dependent degradation. Moreover, ubiquitin modification of autophagy regulatory components is essential to positively or negatively regulate autophagy flux in both non-selective and selective pathways. We review the current findings that elucidate the components, timing, and kinetics of the multivalent role of ubiquitin signals in control of amplitude and selectivity of autophagy pathways as well as their impact on the development of human diseases.
Ubiquitination, and its control by deubiquitinating enzymes (DUBs), mediates protein stability, function, signaling and cell fate. The ovarian tumor (OTU) family DUB OTULIN (FAM105B) exclusively cleaves linear (Met1-linked) poly-ubiquitin chains and plays important roles in auto-immunity, inflammation and infection. OTULIN regulates Met1-linked ubiquitination downstream of tumor necrosis factor receptor 1 (TNFR1), toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) receptor activation and interacts with the Met1 ubiquitin-specific linear ubiquitin chain assembly complex (LUBAC) E3 ligase. However, despite extensive research efforts, the receptor and cytosolic roles of OTULIN and the distributions of multiple Met1 ubiquitin-associated E3-DUB complexes in the regulation of cell fate still remain controversial and unclear. Apart from that, novel ubiquitin-independent OTULIN functions have emerged highlighting an even more complex role of OTULIN in cellular homeostasis. For example, OTULIN interferes with endosome-to-plasma membrane trafficking and the OTULIN-related pseudo-DUB OTULINL (FAM105A) resides at the endoplasmic reticulum (ER). Here, we discuss how OTULIN contributes to cell fate control and highlight novel ubiquitin-dependent and -independent functions.
Rho GTPases control fundamental cellular processes and Cdc42 is a well-studied member of the family that controls filopodia formation and cell migration. Although the regulation of Cdc42 activity by nucleotide binding is well documented, the mechanisms driving its proteostasis are not clear. Here, we demonstrate that the highly conserved, RING domain containing E3 ubiquitin ligase XIAP controls the protein stability of Cdc42. XIAP binds to Cdc42 and directly conjugates poly ubiquitin chains to the Lysine 166 of Cdc42 targeting it for proteasomal degradation. Depletion of XIAP led to an increased protein stability and activity of Cdc42 in normal and tumor cells. Consistently, loss of XIAP enhances filopodia formation in a Cdc42-dependent manner and this phenomenon phenocopies EGF stimulation. Further, XIAP depletion promotes lung colonization of tumor cells in mice in a Cdc42-dependent manner. These observations shed molecular insights into ubiquitin-dependent regulation of Cdc42 and that of actin cytoskeleton.
Under basal conditions, the proapoptotic protein Bid is a long-lived protein. Pro-apoptotic stimuli such as tumor necrosis factor-alpha (TNFalpha) or Fas induce its caspase-8-mediated cleavage into two fragments. The COOH-terminal cleavage fragment of Bid (tBid) becomes localized to mitochondrial membranes and triggers the release of cytochrome c. Here we show that tBid is ubiquitinated and subsequently degraded by the 26 S proteasome. Degradation of tBid is significantly inhibited by the proteasome inhibitors MG-132 and lactacystin. In contrast, caspase-specific or lysosomal inhibitors do not affect tBid stability. Furthermore, mutation of the putative ubiquitin acceptor sites within tBid results in a stabilized protein as assessed by pulse-chase analysis. To address whether tBid degradation might be regulated by interaction with other Bcl-2-like proteins, cotransfection studies were performed. However, neither the presence of proapoptotic Bax nor antiapoptotic Bcl-2 or Bcl-XL affected tBid degradation. Finally, we determined the functional role of tBid degradation. Overexpression of stabilized tBid proteins significantly enhanced cytochrome c release and subsequent apoptosis induction approximately 2-fold compared with wild type tBid. Similarly, tBid-induced apoptosis was considerably amplified by inhibition of tBid degradation using the proteasome-specific inhibitor MG-132. Thus, proteasomal degradation of tBid limits the extent of apoptosis in living cells.
In this review, we focus on the ubiquitination process within the endoplasmic reticulum associated protein degradation (ERAD) pathway. Approximately one third of all synthesized proteins in a cell are channeled into the endoplasmic reticulum (ER) lumen or are incorporated into the ER membrane. Since all newly synthesized proteins enter the ER in an unfolded manner, folding must occur within the ER lumen or co-translationally, rendering misfolding events a serious threat. To prevent the accumulation of misfolded protein in the ER, proteins that fail the quality control undergo retrotranslocation into the cytosol where they proceed with ubiquitination and degradation. The wide variety of misfolded targets requires on the one hand a promiscuity of the ubiquitination process and on the other hand a fast and highly processive mechanism. We present the various ERAD components involved in the ubiquitination process including the different E2 conjugating enzymes, E3 ligases, and E4 factors. The resulting K48-linked and K11-linked ubiquitin chains do not only represent a signal for degradation by the proteasome but are also recognized by the AAA+ ATPase Cdc48 and get in the process of retrotranslocation modified by enzymes bound to Cdc48. Lastly we discuss the conformations adopted in particular by K48-linked ubiquitin chains and their importance for degradation.
The inhibitory glycine receptor (GlyR) in developing spinal neurones is internalized efficiently upon antagonist inhibition. Here we used surface labeling combined with affinity purification to show that homopentameric α1 GlyRs generated inXenopus oocytes are proteolytically nicked into fragments of 35 and 13 kDa upon prolonged incubation. Nicked GlyRs do not exist at the cell surface, indicating that proteolysis occurs exclusively in the endocytotic pathway. Consistent with this interpretation, elevation of the lysosomal pH, but not the proteasome inhibitor lactacystin, prevents GlyR cleavage. Prior to internalization, α1 GlyRs are conjugated extensively with ubiquitin in the plasma membrane. Our results are consistent with ubiquitination regulating the endocytosis and subsequent proteolysis of GlyRs residing in the plasma membrane. Ubiquitin-conjugating enzymes thus may have a crucial role in synaptic plasticity by determining postsynaptic receptor numbers.
Ubiquitylation in immune disorders and cancer: from molecular mechanisms to therapeutic implications
(2012)
Conjugation of ubiquitin to proteins (ubiquitylation) has emerged to be one of the most crucial post-translational modifications controlling virtually all cellular processes. What was once regarded as a mere signal for protein degradation has turned out to be a major regulator of molecular signalling networks. Deregulation of ubiquitin signalling is closely associated with various human pathologies. Here, we summarize the current knowledge of ubiquitin signalling in immune deficiencies and cancer as well as the available therapeutic strategies targeting the ubiquitin system in combating these pathogenic conditions.
This Paper will look at the changing nature of asset management, and will examine the nature of the European framework for collective investment undertakings, enshrined in the UCITS Directive2 in that light. This question whether the UCITS Directive in its current form remains an appropriate European response to the changing investment management landscape is an issue with which the European Commission is actively engaging through its Green Paper on the Enhancement of the EU Framework for Investment Funds, published in July 2005.3 But before considering these important questions, it is necessary to begin with an idea of what a collective investment, more specifically a UCITS actually is and how it fits conceptually in the broader world of pooled investments.....
Ufocandona hannaleeae gen. et sp. nov. (Crustacea, Ostracoda) from an artesian well in Texas, USA
(2017)
We describe a new genus, Ufocandona gen. nov. with its type species Ufocandona hannaleeae gen. et sp. nov., from an artesian well in San Marcos, Texas, USA. The new genus has diagnostic characteristics that distinguish it from other genera in Candonidae, including the asymmetric shape of the valves, the smooth central area on the external surface of the valves, the hexagonal ornamentations around the marginal ends of the carapace, the dense spines on the marginal edges of the right valve and the dorsal prolongation and tubercles seen from inside the ventral edges of the left valve. Additional differences in the soft body parts of the male and female (e.g., claw-like uropod, shape of hemipenis, long Y aesthetascs, two short or reduced exopods on antenna, reduced numbers of setae and segments on other extremities) distinguish the new genus from others in the family. The discovery of this species from a deep artesian well contributes important information to our understanding of groundwater species diversity in a biologically diverse aquifer where the ostracod fauna has been unstudied.
Seabirds in the UK were generally more productive in 2005 than in 2004, when productivity for many species reached an all-time low. A presumed scarcity of sandeels in 2004, especially in the North Sea, led to widespread starvation of chicks in the Northern Isles and in many places along the east coast of Britain (there is also recent evidence that prey fish were of unusually low energy content in 2004 around SE Scotland). The likely knock-on effect for 2005 was that there were few larger sandeels present (those that hatched in 2004) and it is thought that feeding on these fish allow adults to attain breeding condition in spring. This food scarcity and a cold spring led to what was among the latest breeding seasons on record. However, a late appearance of young sandeels allowed some chicks to fledge, and alternative prey species (such as sprat and small haddock) were taken also. However, it is thought that some chicks starved in this late season, as sandeels become unavailable in late summer, when they settle on the seabed. Unusually, 2005 was a very poor breeding season for many species in NW Scotland, which was spared the food shortages of 2004 and previous years; preferred prey during chick rearing were scarce in this region in 2005.
We demonstrate ultra-sharp (≲10 nm) lateral p-n junctions in graphene using electronic transport, scanning tunneling microscopy, and first principles calculations. The p-n junction lies at the boundary between differentially-doped regions of a graphene sheet, where one side is intrinsic and the other is charge-doped by proximity to a flake of α-RuCl3 across a thin insulating barrier. We extract the p-n junction contribution to the device resistance to place bounds on the junction width. We achieve an ultra-sharp junction when the boundary between the intrinsic and doped regions is defined by a cleaved crystalline edge of α-RuCl3 located 2 nm from the graphene. Scanning tunneling spectroscopy in heterostructures of graphene, hexagonal boron nitride, and α-RuCl3 shows potential variations on a sub-10 nm length scale. First principles calculations reveal the charge-doping of graphene decays sharply over just nanometers from the edge of the α-RuCl3 flake.
We demonstrate ultra-sharp (≲10 nm) lateral p-n junctions in graphene using electronic transport, scanning tunneling microscopy, and first principles calculations. The p-n junction lies at the boundary between differentially-doped regions of a graphene sheet, where one side is intrinsic and the other is charge-doped by proximity to a flake of α-RuCl3 across a thin insulating barrier. We extract the p-n junction contribution to the device resistance to place bounds on the junction width. We achieve an ultra-sharp junction when the boundary between the intrinsic and doped regions is defined by a cleaved crystalline edge of α-RuCl3 located 2 nm from the graphene. Scanning tunneling spectroscopy in heterostructures of graphene, hexagonal boron nitride, and α-RuCl3 shows potential variations on a sub-10 nm length scale. First principles calculations reveal the charge-doping of graphene decays sharply over just nanometers from the edge of the α-RuCl3 flake.
Oral e-Poster Presentations - Booth 2: Neuro-Oncology C (Imaging&Monitoring), September 27, 2023, 1:00 PM - 2:30 PM
Background: Repetitive TMS (rTMS) can be used to non-invasively map cortical language areas. Commonly, frequencies of 5-10 Hz are used to induce speech errors. We could recently show that frequencies of 30 and 50 Hz are advantageous to achieve higher reliability. However, high-frequent rTMS applied over perisylvian regions still suffer from limited tolerability. Using short-train or paired-pulse TMS (pp-TMS) might offer a good alternative to rTMS to interfere with speech production. In this study, we, therefore, compared 30 Hz rTMS to pp-TMS aiming at improved language mapping.
Methods: 13 healthy, right-handed subjects (f=6, 25-41 years) were investigated using two different rTMS protocols: (i) 30 Hz rTMS and (ii) pp-TMS. TMS protocols were applied in a pseudo-randomized order during a picture naming task (picture-to-trigger interval: 0 ms) over cortical language areas. In a subsequent study, we compared pp-TMS also to short trains of three TMS pulses and repetitive paired pulse TMS. Language errors were post-hoc analysed by two independent raters and were assigned to eight different error categories. The level of pain was assessed on a subjective 0-10 numeric rating scale (NRS). Moreover, language error distribution was analysed using a cortical parcellation system.
Results: 30 Hz rTMS evoked a significantly higher number of errors than the pp-protocol, i.e., 18 ± 12 % vs. 10 ± 7 % (p<0.05). However, pp-TMS was significantly better tolerated with a mean NRS of 2.3 ± 1.6 vs. 3.4 ± 1.5 (p<0.05, FDR-corrected). Of note, pp-TMS could induce a higher number of anomias (15 ± 15 %) than repetitive TMS protocols (4 ± 7 %; p<0.1, FDR-corrected), but less dysarthria. The cortical distribution of errors differed between the two protocols. The results of train-of-three TMS were similar to the pp-TMS protocol.
Conclusions: Due to its better tolerability, pp-TMS might offer the possibility to stimulate regions which are particularly prone to direct facial / trigeminal nerve stimulation, e.g., the inferior frontal gyrus. Moreover, pp-TMS seems advantageous for mapping patients who are comparatively susceptible to rTMS side effects and with regard to safety in general.
In three-dimensional light microscopy, the heterogeneity of the optical density in a specimen ultimately limits the achievable penetration depth and hence the three-dimensional resolution. The most direct approach to reduce aberrations, improve the contrast and achieve an optimal resolution is to minimise the impact of changes of the refractive index along an optical path. Many implementations of light sheet fluorescence microscopy operate with a large chamber filled with an aqueous immersion medium and a further inner container with the specimen embedded in a possibly entirely different non-aqueous medium. In order to minimise the impact of the latter on the optical quality of the images, we use multi-facetted cuvettes fabricated from vacuum-formed ultra-thin fluorocarbon (FEP) foils. The ultra-thin FEP-foil cuvettes have a wall thickness of about 10–12 µm. They are impermeable to liquids, but not to gases, inert, durable, mechanically stable and flexible. Importantly, the usually fragile specimen can remain in the same cuvette from seeding to fixation, clearing and observation, without the need to remove or remount it during any of these steps. We confirm the improved imaging performance of ultra-thin FEP-foil cuvettes with excellent quality images of whole organs such us mouse oocytes, of thick tissue sections from mouse brain and kidney as well as of dense pancreas and liver organoid clusters. Our ultra-thin FEP-foil cuvettes outperform many other sample-mounting techniques in terms of a full separation of the specimen from the immersion medium, compatibility with aqueous and organic clearing media, quick specimen mounting without hydrogel embedding and their applicability for multiple-view imaging and automated image segmentation. Additionally, we show that ultra-thin FEP foil cuvettes are suitable for seeding and growing organoids over a time period of at least ten days. The new cuvettes allow the fixation and staining of specimens inside the holder, preserving the delicate morphology of e.g. fragile, mono-layered three-dimensional organoids.
This study presents an ultra-wideband, elliptical slot, planar monopole antenna for early breast cancer microwave imaging. The on-body antenna's operation is optimised by direct contact with the patient's skin. With a compact size of 9 × 7 mm, the antenna covers a wide bandwidth from 16 to 24 GHz for reflection coefficients lower than –10 dB. Besides, it also features an electrode for electrical impedance tomography applications. Verification on a volunteer's breast gives an excellent agreement with the simulation for the defined bandwidth. Furthermore, as the first stage of the system's characterisation, pork fat is also used to demonstrate the possibility to enhance the transmission between the antennas within the high loss environment. Those results propose the feasibility of implementing a high-frequency radar system for breast cancer detection.
Light absorption of myoglobin triggers diatomic ligand photolysis and a spin crossover transition of iron(II) that initiate protein conformational change. The photolysis and spin crossover reactions happen concurrently on a femtosecond timescale. The microscopic origin of these reactions remains controversial. Here, we apply quantum wavepacket dynamics to elucidate the ultrafast photochemical mechanism for a heme–carbon monoxide (heme–CO) complex. We observe coherent oscillations of the Fe–CO bond distance with a period of 42 fs and an amplitude of ∼1 Å. These nuclear motions induce pronounced geometric reorganization, which makes the CO dissociation irreversible. The reaction is initially dominated by symmetry breaking vibrations inducing an electron transfer from porphyrin to iron. Subsequently, the wavepacket relaxes to the triplet manifold in ∼75 fs and to the quintet manifold in ∼430 fs. Our results highlight the central role of nuclear vibrations at the origin of the ultrafast photodynamics of organometallic complexes.
Objective: To evaluate two ultrafast cone-beam CT (UF-CBCT) imaging protocols with different acquisition and injection parameters regarding image quality and required contrast media during image-guided hepatic transarterial chemoembolization (TACE).
Methods: In 80 patients (male: 46, female: 34; mean age: 56.8 years; range: 33–83) UF-CBCT was performed during TACE for intraprocedural guidance. Imaging was performed using two ultrafast CBCT acquisition protocols with different acquisition and injection parameters (imaging protocol 1: acquisition time 2.54 s, and contrast 6 mL with 3 s delay; imaging protocol 2: acquisition time 2.72 s, and contrast 7 mL with 6 s delay). Image evaluation was performed with both qualitative and quantitative methods. Contrast injection volume and dose parameters were compared using values from the literature.
Results: Imaging protocol 2 provided significantly better (P < 0.05) image quality than protocol 1 at the cost of slightly higher contrast load and patient dose. Imaging protocol 1 provided good contrast perfusion but it mostly failed to delineate the tumors (P < 0.05). On the contrary, imaging protocol 2 showed excellent enhancement of hepatic parenchyma, tumor, and feeding vessels.
Conclusion: Tumor delineation, visualization of hepatic parenchyma, and feeding vessels are clearly possible using imaging protocol 2 with ultrafast CBCT imaging. A reduction of required contrast volume and patient dose were achieved due to the ultrafast CBCT imaging.
In the last twenty years, there has been splendid progress in energy conversion technologies to have sustainable energy sources. For example, solar cells contribute significantly to energy production as the sun is an enormous source for renewable energy. Currently, the most common commercialized photovoltaic devices are silicon-based. The scientists' main targets are high efficiency, low cost, environmentally friendly, and easy to synthesize new semiconductor materials to replace silicon. Furthermore, understanding the photophysical properties of these materials is very important for designing high efficient photoconversion systems.
This thesis investigates the photophysics of lead-based wide-bandgap perovskites with different dimensionality (2D, 3D) and how they can be optimized for optoelectronic applications. In chapter 1, we present the background and progress in perovskite research. The basic concepts of semiconductor and spectroscopic methods of the applied techniques in this work are discussed in chapter 2.
In the first project (chapter 3.1), we used our time-resolved techniques to study the ultrafast dynamics of energy transfer from the inorganic to the organic layer in a series of three lead-based mixed-halide 2D perovskites containing benzyl ammonium (BA), 1-naphthyl methyl ammonium (NMA), and 1-pyrene methyl ammonium (PMA) thin films.
In the second project (chapter 3.2), we used time-resolved spectroscopic techniques to study the effect of adding 5% of Cs on the dynamics of a mixed-cation wide bandgap bromide-based 3D perovskite.
In another side project (chapter 4), we present the photophysics properties of newly synthesized new Schiff bases containing indole moieties using piperidine as an organic base catalyst and Au@TiO2 as a heterogeneous catalyst. Finally, the results of this work are summarized in Chapter 5 with an outlook and a discussion of open questions for further research.
Photoinduzierte Energietransferprozesse und -reaktionen spielen in vielen Gebieten von Chemie, Physik und Biologie eine wichtige Rolle. Zu den prominentesten Beispielen zählen der Lichtsammelprozess in der Photosynthese und der Anregungsenergietransfer in funktionellen Materialien. Der Fokus dieser Arbeit liegt auf letzterem Bereich, genauer auf organischer Elektronik und flexiblen Donor-Akzeptor-Bausteinen und Schaltern. Im Besonderen werden hier zwei verschiedene Typen von funktionellen organischen Systemen betrachtet: zum einen oligomere Fragmente organischer halbleitender Polymere wie Oligo-p-Phenylen-Vinylen (OPV) und Oligo-Thiophen (OT), welche als Bausteine für neuartige organische Solarzellen dienen, und zum anderen kleine funktionelle Donor-Akzeptor-Einheiten wie Dithienylethen-Bordipyrromethen (DTE-BODIPY). Letzteres wurde in Kooperation mit den experimentellen Gruppen von K. Rück-Braun (TU Berlin) und J. Wachtveitl (Goethe Universität) untersucht. Um die relevanten Energietransfermechanismen genauer zu verstehen, wurden an diesen Systemen elektronische Strukturrechnungen und quantendynamische Untersuchungen durchgeführt. Hierzu wurden mittels ab initio-Methoden Modell-Hamiltonians parametrisiert und mit hochdimensionalen quantendynamischen oder semiklassischen Methoden kombiniert. Während die Parametrisierung für kleinere Fragmente durchgeführt wurde, lässt sich der so parametrisierte Hamiltonian ohne Weiteres auf größere Systeme erweitern. Die dynamischen Studien der betreffenden Systeme wurden mittels der Multikonfigurationellen Zeitabhängigen Hartree (MCTDH) Methode durchgeführt, welche eine vollständige quantendynamische Beschreibung des Systems zulässt. Für größere Systeme wurde die semiklassische Ehrenfest Methode in Verbindung mit dem Langevin-Ansatz zur Beschreibung von Umgebungseffekten genutzt. Hierzu wurde ein eigens für diese Methode und Systeme geschriebenes Programm eingesetzt. Im Falle der OT- und OPV-Oligomere wurde die Dynamik bei Vorliegen eines strukturellen Defekts untersucht. Ziel war es hierbei, die dynamischen Phänomene, welche durch die Photoanregung induziert werden, zu untersuchen. Des Weiteren wurde untersucht, ob das Konzept von „spektroskopischen Einheiten“, welche die Lokalisierung der Anregung durch strukturelle Defekte beschreibt, in diesen Systemen zutrifft. Hierzu wurden die Systeme in einer Frenkel-Basis definiert, welche ein auf einem Monomer lokalisiertes Elektron-Loch-Paar beschreibt. Delokalisierte elektronische Anregungen können somit als Superposition solcher Frenkel-Zustände beschrieben werden. Neben der Frenkel-Basis wurde aber auch eine verallgemeinerte Elektron-Loch-Basis verwendet, welche über zusätzliche Ladungstransferzustände eine räumliche Separation von Elektronen und Löchern erlaubt.Die Parametrisierung des OPV- und OT-Hamiltonians erfolgte mittels der Algebraischen Diagrammatischen Konstruktions (ADC(2))-Methode, welche in Kombination mit einer Übergangs-Dichte-Matrix-Analyse eine sehr akkurate Beschreibung der Frenkel- und Ladungstransferzustände basierend auf den supermolekularen Zuständen erlaubt. Um vibronische Effekte auf die Dynamik miteinzubeziehen,wurden nieder- und hochfrequente Torsions- und alternierende Bindungslängenmoden des Systems im Hamiltonian berücksichtigt. Hierzu wurden eindimensionale Schnitte der Potentialflächen entlang dieser Koordinaten berechnet und mittels einer Transformation in diabatische Potentialflächen überführt. Mit diesem Setup wurden die quantendynamischen und semiklassischen Simulationen für ein OPV/OT-Hexamer und ein 20-mer durchgeführt. Die Ergebnisse dieser Simulationen zeigen, dass der Energietransfer auf einer Subpikosekunden-Zeitskala stattfindet und eine starke Abhängigkeit vom Vorliegen eines strukturellen Defekts aufweist. Des Weiteren konnte auf einer Zeitskala von 100 Femtosekunden eine Lokalisierung des Exzitons beobachtet werden. Fluktuationseffekte werden zudem über Quantenfluktuationen im Falle von MCTDH bzw. über thermische Fluktuationen im Falle des Ehrenfest-/Langevin-Ansatzes berücksichtigt. Letzterer ist jedoch nicht in der Lage, die kohärente Charakteristik der mit den Schwingungsmoden gekoppelten Exziton- und Lokalisierungsdynamik wiederzugeben. Dagegen kann dieser Ansatz erfolgreich genutzt werden, um eine fluktuationsgetriebene „Hopping“-Dynamik des quasi- stationären Zustandes auf einer längeren Zeitskala in Abhängigkeit von der Temperatur zu beschreiben. Die Beschreibung der Photodynamik der DTE-BODIPY-Dyade zielt darauf ab, experimentell beobachtete vibrationelle Schwingungen des BODIPY-Fragments zu erklären, die ohne eine direkte Anregung dieses Fragments zustande kommen. Diese wurden nach einer selektiven Anregung des DTE-Fragments in zeitaufgelösten UV/Vis Anreg-Abtast-Experimenten beobachtet. Der Fokus der Untersuchung liegt daher auf der Beschreibung der photoinduzierten intramolekulare Energieumverteilung (IVR) auf einer Subpikosekunden-Zeitskala. Die DTE-BODIPY Dyade wurde mittels eines Hamiltonians, welcher durch TDDFT Rechnungen parametrisiert wurde, dargestellt. Basierend auf den Normalmoden des Systems, wurden lokale DTE- und BODIPY-Moden konstruiert, wobei einige dieser Moden miteinander gekoppelt sind und die Photoanregung des DTE auf das BODIPY-Fragment übertragen. Hierbei zeigte sich, dass die Zeitskala und die charakteristischen Frequenzen des Experiments mittels der hochdimensionalen MCTDH-Methode gut reproduziert wurden. Aus den Simulationen ergab sich zudem, dass der beobachtete Energietransfer stark von einem Reservoir von vibrationell angeregten lokalen DTE-Moden beeinflusst wird. Der untersuchte IVR- Prozess zeigt zudem eine ausgeprägte Abhängigkeit von lokalen Kopplungen und der Kopplung an eine Umgebung.
Dodecins, a group of flavin-binding proteins with a dodecameric quaternary structure, are able to incorporate two flavins within each of their six identical binding pockets building an aromatic tetrade with two tryptophan residues. Dodecin from the archaeal Halobacterium salinarum is a riboflavin storage device. We demonstrate that unwanted side reactions induced by reactive riboflavin species and degradation of riboflavin are avoided by ultrafast depopulation of the reactive excited state of riboflavin. Intriguingly, in this process, the staggered riboflavin dimers do not interact in ground and photoexcited states. Rather, within the tetrade assembly, each riboflavin is kept under the control of the respective adjacent tryptophan, which suggests that the stacked arrangement is a matter of optimizing the flavin load. We further identify an electron transfer in combination with a proton transfer as a central element of the effective excited state depopulation mechanism. Structural and functional comparisons of the archaeal dodecin with bacterial homologs reveal diverging evolution. Bacterial dodecins bind the flavin FMN instead of riboflavin and exhibit a clearly different binding pocket design with inverse incorporations of flavin dimers. The different adoption of flavin changes photochemical properties, making bacterial dodecin a comparably less efficient quencher of flavins. This supports a functional role different for bacterial and archaeal dodecins.
Polyacrylamide gel electrophoresis (PAGE) and immunoblotting (Western blotting) are the most common methods in life science. In conjunction with these methods, the polyhistidine-tag has proven to be a superb fusion tag for protein purification as well as specific protein detection by immunoblotting, which led to a vast amount of commercially available antibodies. Nevertheless, antibody batch-to-batch variations and nonspecific binding complicate the laborious procedure. The interaction principle applied for His-tagged protein purification by metal-affinity chromatography using N-nitrilotriacetic acid (NTA) was employed to develop small high-affinity lock-and-key molecules coupled to a fluorophore. These multivalent NTA probes allow specific detection of His-tagged proteins by fluorescence. Here, we report on HisQuick-PAGE as a fast and versatile immunoblot alternative, using such high-affinity fluorescent super-chelator probes. The procedure allows direct, fast, and ultra-sensitive in-gel detection and analysis of soluble proteins as well as intact membrane protein complexes and macromolecular ribonucleoprotein particles.
A new experimental setup, for pump-probe fs DFWM measurements, which is based on a femtosecond laser system, has been constructed. It allows for the investigation of molecular species in the gas phase at different temperatures, from ~30 K in a seeded supersonic jet up to ~500 K in a heat-pipe oven. In comparison to other RCS methods the employed fs DFWM technique is less complicated and gives much higher signal-to-noise ratio [BFZ86, FeZ95a, CKS89, CCH90, HCF91, WRM02, Rie02]. A general computer code for the simulation of fs DFWM spectra of nonrigid asymmetric top molecules has been developed. This new DFWM code in combination with a non-linear fitting routine allows one to determine rotational and centrifugal distortion constants and obtain information on the polarizability tensor components from the experimental spectra. Fs DFWM spectroscopy was successfully applied to the medium-sized molecules benzene and benzene-d6 in a gas cell and in a supersonic jet. The spectrum from a seeded expansion has been measured up to delay time of 3.9 ns (restricted by the length of the delay stage) with excellent signal-to-noise ratio (102-103). In that way 87 and 72 J-type transients have been recorded for benzene and benzene-d6, correspondingly. A relative accuracy on the order of 10-5 has been achieved for the rotational constant. From the room temperature experiments, precise values of centrifugal distortion constants DJ and DJK have been extracted. The literature data for cyclohexane have been revised and a new precise rotational constant B0 has been obtained, which is (+5.5 MHz) shifted from the one reported in the former Raman investigation by Peters et al. [PWW73]. Additionally, high-level ab initio calculations of cyclohexane have been carried out using a large number of basis sets at several levels of theory. In particular, the vibrational averaging effects have been examined in order to critically compare the experimentally determined and theoretically evaluated rotational constants. The contribution of highly symmetric vibrational modes to vibrational averaging effects was clarified. More structural information could be obtained from fs DFWM measurements of asymmetric top species, since different type of rotational recurrences can appear, and all three rotational constants (A, B, C) can be extracted. On the other hand the analysis of the asymmetric top spectra is no longer trivial. In fact the simple formula for rotational recurrence periods of symmetric top species (Tab. 2.1) can not be applied to asymmetric top molecules. Thus, in order to extract high-resolution data for asymmetric species, a complete fitting of the experimental spectra is necessary. The fs DFWM and (1+2') PPI method have been applied to the asymmetric top molecules pyridine in the ground (S0) and pDFB in the S0 and electronically excited (S1) states. By fitting the measured fs DFWM spectra the rotational and centrifugal distortion constants have been extracted with good precision and the value of the parametrized polarizability angle of pDFB was obtained. In this work, the first application of fs DFWM spectroscopy to a molecular cluster has been reported. Also, the chemical equilibrium between monomeric and dimeric species was studied. In particular formic and acetic acid have been investigated in a gas cell and in a supersonic expansion. Many spectral features have been observed and analized in the fs DFWM spectrum of formic acid vapor in a gas cell at room temperature. Most of them were attributed to rotational recurrences of the formic acid monomer, but also spectral feature originating from the formic acid dimer of O-H×××O/O×××H-O type have been detected and analyzed. From the fitted simulation, the rotational and centrifugal distortion constants, and parametrized polarizability angle were extracted for the dimeric structure of O-H×××O/O×××HO type. With the assumption of unperturbed monomers a center-of-mass distance of R = 2.990 ± 0.001 Å for the monomers within the dimer has been calculated from the spectroscopic results. This distance is 0.028 Å smaller than that reported from electron diffraction [ABM69]. Thus, the centers-of-mass distance was assigned as the main point of disagreement between results of fs DFWM and electron diffraction experiments. In contrast to formic acid, acetic acid shows strong recurrences from dimeric species even in the fs DFWM spectra at room temperature. This is explained in terms of different symmetry of the moments-of-inertia tensor, which modulates the intensity of RRs (the fs DFWM signal is in general stronger from symmetric species). Due to the symmetric nature of the acetic acid dimer, only the sum (B+C) of the rotational constants has been extracted. The changes of geometrical parameters upon dimer formation have been analyzed for, both, formic and acetic acid. A heat-pipe oven has been used in order to overcome the main drawback of fs DFWM spectroscopy – the square dependence of the signal intensity on the sample number density. Two-ring molecules (cyclohexylbenzene, para-cyclohexylaniline and nicotine) with low vapor pressure (<0.1 mbar) at room temperature have been investigated. From the analysis of the experimental and ab-initio results for CHB and pCHA a nearly perpendicular conformation of the aromatic vs. cyclohexane ring for both system is inferred. The enlargement of the benzene ring of CHB in the electronically excited state (S1) has been found to cause the smaller rotational constants in S1. This conclusion has been drawn from the comparison of the ground and electronically excited state experimental rotational constants in combination with ab-initio calculations. The extraction of precise structural information for nicotine was not possible due to it weak fs DFWM signal. However, the fact that fs DFWM technique can be applied to conformational analysis of molecular species in an equilibrium mixture opens other applications for this kind of spectroscopy. In general the results obtained in this work show that the fs DFWM technique, being an experimental implementation of RCS, provides one with an important tool for structural analysis of molecular species in the gas phase in particular for the species to which microwave spectroscopy can not be applied. It gives spectra with excellent signal-to-noise ratio even at low number density samples expanded in a seeded supersonic jet. It provides an alternative and innovative approach towards rotational Raman spectroscopy of large polyatomic molecules applicable under various experimental conditions (broad temperature and pressure range). With the introduction of femtosecond (10-15s) laser pulses (usually picosecond (10-12s) laser pulses were used in RCS) an improvement in time-resolution and therefore in precision for the rotational constants by more than one order of magnitude has been achieved. Molecular systems in the ground electronic state without permanent dipole moment and chromophore can be studied with high precision, providing thereby molecular benchmark systems for the electronic structure theory. As has been shown, the study of molecular clusters by fs DFWM spectroscopy is possible, but its potential are restricted by the square dependence of the fs DFWM signal from the sample number density, which is even more important for supersonic jet expansions. Here, the application of near-resonant and resonant FWM schemes should help in order to compensate for the low sample concentration. With the introduction of the heat pipe oven for fs DFWM experiments, the investigation of large nonvolatile molecules under equilibrium conditions is possible now. In our laboratory the first results on the structural analysis of different conformers of pyrrolidine in the gas phase have been obtained [MaR04]. This method can have even more prospects for the structural investigations of large molecular species in combination with new non-thermal gas phase sources for nonvolatile molecules, like laser desorption [CTL89], laser oblation [MHL83], electrospray [FMM90], laser induced liquid beam ion desorption [KAB96, Sob00] etc. A very recent application of the fs DFWM technique is the investigation of the influence of strong laser fields on molecular gas phase sample, which could range from active alignment [PPB03] over molecular deformation to field ionization [CSD03]. In regards to future development in fs DFWM spectroscopy for more complex molecules one has to take into account, how large amplitude motions such as the van der Waals vibrations or internal rotation (see section 6.4.2) affect the rotational coherences. In any case, femtosecond Degenerate Four-Wave Mixing as experimental implementation of Rotational Coherence Spectroscopy can be considered as an innovative, developing, and powerful method for the structural investigation of the molecular species, which are hard to study by classical frequency-resolved spectroscopy [FeZ95a, Dan01, Rie02].
The family of phytochrome photoreceptors contains proteins with different domain architectures and spectral properties. Knotless phytochromes are one of the three main subgroups classified by their distinct lack of the PAS domain in their photosensory core module, which is in contrast to the canonical PAS-GAF-PHY array. Despite intensive research on the ultrafast photodynamics of phytochromes, little is known about the primary kinetics in knotless phytochromes. Here, we present the ultrafast Pr ⇆ Pfr photodynamics of SynCph2, the best-known knotless phytochrome. Our results show that the excited state lifetime of Pr* (~200 ps) is similar to bacteriophytochromes, but much longer than in most canonical phytochromes. We assign the slow Pr* kinetics to relaxation processes of the chromophore-binding pocket that controls the bilin chromophore’s isomerization step. The Pfr photoconversion dynamics starts with a faster excited state relaxation than in canonical phytochromes, but, despite the differences in the respective domain architectures, proceeds via similar ground state intermediate steps up to Meta-F. Based on our observations, we propose that the kinetic features and overall dynamics of the ultrafast photoreaction are determined to a great extent by the geometrical context (i.e., available space and flexibility) within the binding pocket, while the general reaction steps following the photoexcitation are most likely conserved among the red/far-red phytochromes.
Photoinduced electron transfer from organic dye molecules to semiconductor nanoparticles is the first and most important reaction step for the mechanism in the so called “wet solar cells” [1]. The time scale between the photoexcitation of the dye and the electron injection into the conduction band of the
semiconductor colloid varies from a few tens of femtoseconds to nanoseconds, depending on the specific electron transfer parameters of the system, e.g., electronic coupling or free energy values of donor and acceptor molecules [2–10]. We show that visible pump/ white light probe is a very efficient tool to investigate the electron injection reaction allowing to observe simultaneously the relaxation of the excited dye, the injection process of the electron, the cooling of the injected electron and the charge recombination reaction.
Abstract
The mineralogy, chemical composition, and physical properties of cratonic mantle eclogites with oceanic crustal protoliths can be modified by secondary processes involving interaction with fluids and melts, generated in various slab lithologies upon subduction (auto‐metasomatism) or mantle metasomatism after emplacement into the cratonic lithosphere. Here we combine new and published data to isolate these signatures and evaluate their effects on the chemical and physical properties of eclogite. Mantle metasomatism involving kimberlite‐like, ultramafic carbonated melts (UM carbonated melts) is ubiquitous though not pervasive, and affected between ~20% and 40% of the eclogite population at the various localities investigated here, predominantly at ~60–150 km depth, overlapping cratonic midlithospheric seismic discontinuities. Its hallmarks include lower jadeite component in clinopyroxene and grossular component in garnet, an increase in bulk‐rock MgO ± SiO2, and decrease in FeO and Al2O3 contents, and LREE‐enrichment accompanied by higher Sr, Pb, Th, U, and in part Zr and Nb, as well as lower Li, Cu ± Zn. This is mediated by addition of a high‐temperature pyroxene from a UM carbonated melt, followed by redistribution of this component into garnet and clinopyroxene. As clinopyroxene‐garnet trace‐element distribution coefficients increase with decreasing garnet grossular component, clinopyroxene is the main carrier of the metasomatic signatures. UM carbonated melt‐metasomatism at >130–150 km has destroyed the diamond inventory at some localities. These mineralogical and chemical changes contribute to low densities, with implications for eclogite gravitational stability, but negligible changes in shear‐wave velocities, and, if accompanied by H2O‐enrichment, will enhance electrical conductivities compared to unenriched eclogites.
Plain Language Summary
Oceanic crust formed at spreading ridges is recycled in subduction zones and undergoes metamorphism to eclogite. Some of this material is captured in the overlying lithospheric mantle, where it is exhumed by passing magmas. Having formed in spreading ridges, these eclogites have proven invaluable archives for the onset of plate tectonics, for the construction of cratons during subduction/collision, as probes of the convecting mantle from which their precursors formed, and as generators of heterogeneity upon recycling into Earth's convecting mantle. During subduction and until exhumation, interaction with fluids and melts (called metasomatism) can change the mineralogy, chemical composition, and physical properties of mantle eclogites, complicating their interpretation, but a comprehensive study of these effects is lacking so far. We investigated mantle eclogites from ancient continents (cratons) around the globe in order to define hallmarks of metasomatism by subduction‐related fluids and small‐volume ultramafic carbonated mantle melts. We find that the latter is pervasive and occurs predominantly at midlithospheric depths where seismic discontinuities are detected, typically causing diamond destruction and a reduction in density. This has consequences for their gravitational stability and for the interpretation of shearwave velocities in cratons.
In der modernen Festkörperphysik spielen elektronisch stark korrelierte Systeme mit ihrem komplexen Vielteilchenverhalten eine zentrale Rolle. Insbesondere das Wechselspiel zwischen thermischen und Quantenfluktuationen in den Ladungs- und Spinfreiheitsgraden führt zur Entstehung verschiedenster neuartiger Grundzustände.
Die vorliegende Dissertation „Ultrasonic and Magnetic Investigations in frustrated Lowdimensional Spin Systems“ beschäftigt sich mit den besonderen physikalischen Eigenschaften niedrig dimensionaler Spinsysteme. Diese Materialklasse, die auch zu den stark korrelierten Systemen zählt, wird seit vielen Jahren intensiv sowohl experimentell als auch theoretisch untersucht. Auf theoretischer Seite sind die niedrigdimensionalen Spinsysteme besonders interessant, da sie als Modellsysteme die exakte Beschreibung des Grundzustandes und des Anregungsspektrums ermöglichen. Von experimenteller Seite ist es in den letzten Jahrzehnten gelungen, verschiedenste Materialklassen niedrigdimensionaler Spinsysteme zu synthetisieren.
In der vorliegenden Arbeit werden die grundlegenden Theorien und physikalischen Konzepte niedrigdimensionaler Spinsysteme diskutiert. Insbesondere auch die Spin-Phonon-Wechselwirkung dieser Materialien, die für die hier beobachteten elastischen Anomalien verantwortlich ist. Weiterhin wird auch das elastische Verhalten bei magnetischen Phasenübergängen beschrieben.
Da die Ultraschallexperimente einen Schwerpunkt dieser Arbeit bilden, wird der Versuchsaufbau zur phasenempfindlichen Detektion von Schallgeschwindigkeit und Ultraschalldämfung ausführlich beschrieben. Diese Messmethode ist ideal zur Untersuchung der Spin-Phonon Wechselwirkung geeignet.
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
Synechococcus (Anacystis nidulans, strain L 1402-1) were grown at + 37 °C in an atmosphere of 0.04 vol.% CO2 using different light conditions. Changing the culture conditions caused alterations in pigment ratios and ultrastructure of Synechococcus. In comparison to the low white and red light grown cells under strong white light the number of thylakoids decreased and an accumulation of storage carbohydrates could be observed. The number of the polyhedral bodies also varied with culture conditions. The results are discussed with reference to the pigment composition and the function of the polyhedral bodies.
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth´s atmosphere. Individual UTTCs may exist for many hours as an only 200--300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere.
Mechanisms by which subvisible cirrus clouds (SVCs) might contribute to dehydration close to the tropical tropopause are not well understood. Recently Ultrathin Tropical Tropopause Clouds (UTTCs) with optical depths around 10-4 have been detected in the western Indian ocean. These clouds cover thousands of square kilometers as 200-300 m thick distinct and homogeneous layer just below the tropical tropopause. In their condensed phase UTTCs contain only 1-5% of the total water, and essentially no nitric acid. A new cloud stabilization mechanism is required to explain this small fraction of the condensed water content in the clouds and their small vertical thickness. This work suggests a mechanism, which forces the particles into a thin layer, based on upwelling of the air of some mm/s to balance the ice particles, supersaturation with respect to ice above and subsaturation below the UTTC. In situ measurements suggest that these requirements are fulfilled. The basic physical properties of this mechanism are explored by means of a single particle model. Comprehensive 1-D cloud simulations demonstrate this stabilization mechanism to be robust against rapid temperature fluctuations of +/- 0.5 K. However, rapid warming (Delta T > 2 K) leads to evaporation of the UTTC, while rapid cooling (Delta T < -2 K) leads to destabilization of the particles with the potential for significant dehydration below the cloud
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth's atmosphere. Individual UTTCs may exist for many hours as an only 200–300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere.
Mechanisms by which subvisible cirrus clouds (SVCs) might contribute to dehydration close to the tropical tropopause are not well understood. Recently Ultrathin Tropical Tropopause Clouds (UTTCs) with optical depths around 10−4 have been detected in the western Indian ocean. These clouds cover thousands of square kilometers as 200–300 m thick distinct and homogeneous layer just below the tropical tropopause. In their condensed phase UTTCs contain only 1–5% of the total water, and essentially no nitric acid. A new cloud stabilization mechanism is required to explain this small fraction of the condensed water content in the clouds and their small vertical thickness. This work suggests a mechanism, which forces the particles into a thin layer, based on upwelling of the air of some mm/s to balance the ice particles, supersaturation with respect to ice above and subsaturation below the UTTC. In situ measurements suggest that these requirements are fulfilled. The basic physical properties of this mechanism are explored by means of a single particle model. Comprehensive 1-D cloud simulations demonstrate this stabilization mechanism to be robust against rapid temperature fluctuations of +/−0.5 K. However, rapid warming (ΔT>2 K) leads to evaporation of the UTTC, while rapid cooling (ΔT<−2 K) leads to destabilization of the particles with the potential for significant dehydration below the cloud.
In this thesis, Planck size black holes are discussed. Specifically, new families of black holes are presented. Such black holes exhibit an improved short scale behaviour and can be used to implement gravity self-complete paradigm. Such geometries are also studied within the ADD large extra dimensional scenario. This allows black hole remnant masses to reach the TeV scale. It is shown that the evaporation endpoint for this class of black holes is a cold stable remnant. One family of black holes considered in this thesis features a regular de Sitter core that counters gravitational collapse with a quantum outward pressure. The other family of black holes turns out to nicely fit into the holographic information bound on black holes, and lead to black hole area quantization and applications in the gravitational entropic force. As a result, gravity can be derived as emergent phenomenon from thermodynamics.
The thesis contains an overview about recent quantum gravity black hole approaches and concludes with the derivation of nonlocal operators that modify the Einstein equations to ultraviolet complete field equations.
"Ulysses, Dante, and Other Stories" presents a unique form of creative scholarship. It employs Dante's late medieval take on Ulysses and his tragic pursuit of 'virtue and knowledge' as a prism that refracts an ancient myth of journey and return into a modern story of discovery and nostalgia. Working notes, fragments from Ulysses' many stories, personal memories, illuminations, and rewritings combine to form a new chain of narratives about the desire to create, the art of travelling, and the will of self-reinvention.
Sea pens (Cnidaria: Anthozoa: Pennatulacea) constitute a distinctive group of colonial marine invertebrates. They inhabit the world`s oceans, from shallow to deep waters. Studies about this group in Argentina are scarce, and no species have been described in the area in over a decade. Based on samples collected in Mar del Plata Submarine Canyon at about 3000 m deep we describe a new species of sea pen, Umbellula pomona Risaro, Williams & Lauretta sp. nov. This is a spiculate Umbellula that differs from other species of Umbellula with sclerites, by the number, development and distribution of the autozooids in its terminal cluster, as well as the shape of its axis. Molecular data also distinguishes it from other known species. Of the forty-three described species approximately ten are considered valid for the genus Umbellula, four of them are registered for the South Atlantic Ocean and only three are described for the Antarctic region. Since sampling efforts in this area have been scarce, the number of species of sea pens from the region is likely to increase substantially in the coming years.
Umbyquyra gen. nov., a new Theraphosinae genus with stridulatory bristles on the palpal trocanther of pedipalp trochanter and first leg, is proposed. The genus differs from the other genera with stridulatory bristles on the same segments, Acanthoscurria Ausserer, 1871, Cyrtopholis Simon, 1892, Longilyra Gabriel, 2014 and Nesipelma Schmidt & Kovarik, 1996, by having a palpal bulb with a very short and acuminate embolus and four short keels; separated tibial apophysis; and female spermathecae resembling those of Cyrtopholis, with two seminal receptacles with elongated ducts emerging from a common area. Cyrtopholis palmarum Schiapelli & Gerschman, 1945 and C. schmidti Rudloff, 1996 from Brazil and Acanthoscurria acuminata Schmidt & Tesmoingt in Schmidt, 2005 from Bolivia are transferred to the new genus. The female of Umbyquyra palmarum (Schiapelli & Gerschman, 1945) gen. et comb. nov. and the male of U. schmidti (Rudloff, 1996) gen. et comb. nov. are described for the first time. Cyrtopholis zorodes Mello-Leitão, 1923 is considered a junior synonym of Acanthoscurria gomesiana Mello-Leitão, 1923 and Cyrtopholis meridionalis (Keyserling, 1891) is considered a nomen dubium. Eight new species from Brazil are described: Umbyquyra paranaiba gen. et sp. nov., U. cuiaba gen. et sp. nov., U. araguaia gen. et sp. nov., U. sapezal gen. et sp. nov., U. belterra gen. et sp. nov., U. caxiuana gen. et sp. nov., U. tucurui gen. et sp. nov. and U. tapajos gen. et sp. nov. Data and maps on the geographic distribution are provided.
In this Letter, we propose a new scenario emerging from the conjectured presence of a minimal length ℓ in the spacetime fabric, on the one side, and the existence of a new scale invariant, continuous mass spectrum, of un-particles on the other side. We introduce the concept of un-spectral dimension DU of a d-dimensional, euclidean (quantum) spacetime, as the spectral dimension measured by an “un-particle” probe. We find a general expression for the un-spectral dimension DU labelling different spacetime phases: a semi-classical phase, where ordinary spectral dimension gets contribution from the scaling dimension dU of the un-particle probe; a critical “Planckian phase”, where four-dimensional spacetime can be effectively considered two-dimensional when dU=1; a “Trans-Planckian phase”, which is accessible to un-particle probes only, where spacetime as we currently understand it looses its physical meaning.
A new species of Autostichidae, Eraina beechei nov. sp., is described from specimens collected in the Andean mountains of Ñuble, Biobío. Diagnostic characters for the species are presented; photographs of adults, illustrations of male and female genitalia, and a key for identifi cation of Eraina species are provided.
Many current approaches to the formal definition of vegetation units have the disadvantage of leaving a large amount of relevés unclassified. In this paper I propose a new method for the unambiguous assignment of relevés, which is based on the summarised cover value of diagnostic species. In the first step, a relevé is assigned to the class with the highest cover score. For this purpose, the character and differential species of the class as well as the character species of all subordinated syntaxa are considered diagnostic. Once the class has been determined, the assignment proceeds successively to the lower ranks. This method, which may be called “summarised percentage cover approach”, uses solely the diagnostic species of syntaxa for the assignment of relevés to vegetation units, making additional formal definitions unnecessary. As a test data set, I used 487 relevés of fringe vegetation and grasslands of nutrient-poor sites sampled in the Vienna Woods (Wienerwald), Austria. All relevés were provisorily classified at alliances level, mostly following the assignment of the original authors. TWINSPAN and DCA were applied to evaluate this preliminary classification. Diagnostic species for both the alliance and the class level were identified using the total cover value ratio as fidelity measure. The subjective classification was largely confirmed by the numerical methods. On basis of the summarised cover of Trifolio-Geranietea and Festuco-Brometea species, between 64% (Geranion sanguinei) and 99% (Seslerio-Festucion pallentis) of the relevés were reassigned to the same class as in the original classification. The fact that a considerable amount of relevés originally classified as Geranion sanguinei was reassigned to grasslands reflects the problems in delimiting fringe communities rather than a poor performance of the assignment method. The “summarised percentage cover approach” allows not only for the unequivocal assignment of relevés to an existing classification system, but may also help to improve classifications by clarifying the delimitation of higher syntaxa.
The mammalian target of rapamycin and the integrated stress response are central cellular hubs regulating translation upon stress. The precise proteins and pathway specificity of translation targets of these pathways remained largely unclear. We recently described a new method for quantitative translation proteomics and found that both pathways control translation of the same sets of proteins.
Uncaging approach, native membrane dynamics and lipidic cubic phases in biomolecular solid-state NMR
(2019)
It was previously shown for the Escherichia coli diacylglycerol kinase (DgkA) that enzyme-reactions at the membrane interface can be monitored by solid-state NMR. However, such studies can face problems due to limited accessibility of the active sites: Natural substrates for membrane enzymes, but also ligands for membrane proteins or lipid mediators, are either partitioning into the membrane and cannot be added easily, or if soluble exhibit accessibility restrictions, as they cannot freely pass through lipid bilayers. This situation complicates quantitative kinetic analysis of biochemical processes such as enzyme activity, ligand binding, but also oligomerization or folding reactions in the membrane or at its interface under MAS NMR conditions.
To overcome these limitations the feasibility and possible advantages of the uncaging approach as a new tool for biomolecular solid-state NMR to trigger reactions by light have been explored. DgkA’s enzymatic activity, exemplary of a biochemical process on the membrane interface, was thereby triggered in situ during MAS by light-induced release of its substrates that were rendered inactive with photolabile protecting groups. To be capable of uncaging sufficient amounts of substrate during MAS to follow the enzymatic reaction via 31P real-time NMR measurements, several illumination variants including an existing illumination setup to study retinal proteins under cryogenic conditions via DNP enhanced NMR were tested. As uncaging of micromole amounts of substrates requires a higher flux compared to initiation of a photocycle in retinal proteins, a new illumination setup was built with Bruker Biospin and Leoni Fibertech. It consists of a modified MAS probe and a suitable fiber bundle, allowing to efficiently couple light from high power LEDs into a sapphire rotor containing the sample, without disturbing the magnetic field homogeneity or sample rotation. By reducing the sample volume to the illuminated area up to 60 mM ATP were released by uncaging NPE ATP to initiate DgkA’s activity in several tested membrane mimetics. These mimetics included liposomes and bicelles, which are well established in the field of biomolecular solid state NMR as well as the optically transparent lipidic cubic phase of monoolein, widely used in membrane protein crystallography, but not yet well characterized as membrane mimetic under MAS conditions. A unique and powerful but compared to time and spatial resolution often underrepresented advantage of the uncaging approach for biophysical studies has been demonstrated by successful uncaging of a non-miscible lipid substrate to trigger DgkA’s kinase reaction: Initiation of processes that cannot easily be triggered by mixing. Examples of these are reactions involving highly hydrophobic, membrane partitioning compounds including lipid substrates, ligands or interaction partners, but also oligomerization or folding of biomacromolecules. The herein performed experiments therefore serve as a first demonstration of the uncaging approach’s feasibility and compatibility with a wide variety of membrane mimetics and give a first indication of its potential for a variety of biomolecular solid state NMR experiments.
As high accessibility for solutes has been a second focus for the choice of membrane mimetics, DgkA’s activity in the lipidic cubic phases of monoacylglycerols with its two continuous networks of water channels has been further characterized. Kinetic parameters obtained from 31P real time solid state NMR experiments revealed that DgkA’s activity is similar to activities obtained in swollen cubic phases in a bath solution with wider water channels. Diffusion of ATP in a non swollen cubic phase was however strongly reduced compared to ATP in solution as diffusion measurements showed. Therefore, saturation of the enzyme required distinctly higher ATP concentrations. These results thereby underline the advantage of a non invasive and label free method like NMR to directly gain information about enzymatic reactions of immobilized enzymes in porous materials. The obtained wealth of information from 31P real time NMR experiments and biochemical assays in different membrane mimetics in presence and absence of lipid substrates and activators also provided further insight into DgkA’s enzymatic activity. It confirms ATP binding and hydrolysis in the absence of a lipid substrate, in agreement with the proposed mode of substrate binding, and allowed to estimate the in vivo relevance of previously observed ATPase activity in liposomes.
Further exploration of the cubic phase as membrane mimetic for protein solid state NMR revealed its high stability under MAS at elevated temperatures and capacity to reconstitute sufficient amounts of DgkA. Unlike monoolein, DgkA was cross-polarizable in a cubic phase and exhibited similar dynamics compared to DgkA reconstituted into liposomes, allowing to acquire the herein shown dipolar coupling based 2D protein spectra. As lipidic cubic phases are not containing phospholipids, monoacylglycerols could be especially useful as membrane mimetics for 31P correlation spectra. Initial experiments under DNP conditions, where in liposomes line broadening causes severe overlap of phospholipid signals and unspecific cross polarization highlight this aspect.
In summary, herein reported results of the experiments performed with lipidic cubic phases demonstrate that they are robust and versatile membrane mimetics. They could be of advantage for a variety of solid-state NMR experiments where either optical transparency for efficient illumination is desired, accessibility for solutes and membrane components under MAS is required, or interference of phosphorous signals of other membrane mimetics must be avoided.
In the second chapter of this thesis 1H solid-state NMR as a label free method to probe membrane order and dynamics directly within a cellular and disease relevant context was used to observe the effects of soluble epoxide hydrolase (sEH) encoding gene knock-outs on membrane dynamics. Knock-out of the sEH encoding gene changed the overall membrane dynamics in the physiological temperature range of native membranes derived from mouse brains, making the bulk membrane more dynamic. To confirm that these effects are related to the enzymatic activity of sEH, substrates and products of sEH were added to evaluate their effects on membrane dynamics. 19,20 dihydroxydocosapentaenoic acid (DHDP), a product of sEH, partially reversed the knock out phenotype in a concentration dependent manner whereas the substrate 19,20 epoxydocosapentaenoic acid did not cause any effects. As both polyunsaturated fatty acids did not show differences in phase behavior in a simple phospholipid bilayer these results provide evidence that the previously observed concentration dependent DHDP induced relocation of cholesterol away from detergent resistant lipid raft fractions is associated with alteration of membrane dynamics. Therefore, also the effect of cholesterol removal via cyclodextrin on membrane dynamics was analyzed. Removal of cholesterol led to a similar temperature profile of wild type and knock out membranes thereby supporting the hypothesis that DHDP induced relocation of cholesterol is causing altered membrane dynamics. These alterations have been shown by the lead authors of the collaborative research project to induce relocation of various membrane proteins and are involved in the development of diabetic retinopathy. Furthermore, in this context inhibition of sEH has been shown to inhibit diabetic retinopathy and proposed as target for prevention of one of the leading causes of blindness in the developed world.
To gain a better understanding of complex mechanisms in biological systems, simultaneous control over multiple processes is key. To this purpose selective photouncaging has been developed. Photo-uncaging is an experimental scheme in which a molecule of interest has been inactivated synthetically and is activated by light. Usually a bond is cleaved and a leaving group is set free. The molecule which inactivates the molecule of interest and sets the leaving group free is called (photo-)cage. In a selective photo-uncaging scheme a number of leaving groups can be released independently, usually by irradiation with light of different wavelengths. This approach is, however, seriously limited in its applicability due to the properties of the involved cages and irradiation schemes. A major drawback is the usually quite broad UV-Vis absorption of the cages. This makes a selective activation by light difficult and limits the maximal number of independent cages severely.
Therefore, the aim of this thesis is to introduce the Vibrationally Promoted Electronic Resonance (VIPER) 2D-IR pulse sequence in a alternative selective uncaging scheme.
The VIPER 2D-IR pulse sequence is a spectroscopic tool which allows to generate 2D-IR signals whose lifetime are independent of the vibrational relaxation lifetime. It has been first used to monitor chemical exchange. It consists of a narrowband infared pump pulse, a subsequent UV-Vis pump pulse and a broadband infrared probe pulse. The UV-Vis pump pulse is off-resonant with regard to the UV-Vis absorption band. Electronic excitation becomes only possible, if the infrared pump pulse modulates the UV-Vis transition of the IR-excited molecule. This modulation brings the UV-Vis transition in resonance with the UV-Vis pump pulse. Thereby, only the molecules which were pre-excited with the infrared pulse can be excited into the electronically excited state. A computational prediction of the modulation was carried out by Jan von Cosel in the Burghardt group.
The narrowband infrared pump pulse can be used to selectively excite a subensemble of molecules in a mixture into an electronically excited state even if the UV-Vis spectra of all molecules are virtually identical. For this the sub-ensemble needs to exhibit an identifiable infrared spectrum. Combined with the introduction of isotope labels, which lead to changes in the infrared absorption spectra, the larger selectivity in the infrared region can be exploited for an alternative selective uncaging approach. In VIPER uncaging the infrared pump pulse selects the species and the subsequent UV-Vis pulse provides the energy needed for electronic excitation upon which the photo cleavage can occur.
After an introduction of the principle idea of uncaging and VIPER spectroscopy, the concept of VIPER uncaging is introduced and its limits and requirements are discussed. Some examples for possible VIPER cages are reviewed.
A coumarin molecule (7-diethylamino coumarin) which can release an azide group was chosen as a first test molecule for VIPER uncaging. Its isotopomers were characterized to determine suitable spectroscopic markers for successful uncaging and to find fitting experimental conditions. The chosen coumarin cage has an UV-Vis absorption band at approximately 380 nm and a steep flank on the high wavelength side of the band. The quantum yield for the azide compound is between 10-20 % depending on the solvent’s water content. The release was found to be on a picosecond timescale which is among the fastest known photo reactions, but the photo reaction mechanism has proven to be not straightforward. For the VIPER experiment on the mixture two isotopomers were chosen with a 13C atom at different positions. In one species a ring mode of the coumarin is changed by the 13C atom. In the other isotopomer the carbonyl stretching mode is influenced. The change in the ring mode region allows to select one species or the other with the infrared pre-excitation. Because of experimental difficulties only isotopomers with the same leaving group could be used. The successful selective electronic excitation of the individual isotopomers in a mixture was monitored by probing the carbonyl region.
As a second VIPER cage, para-hydroxyphenacyl (pHP) was chosen. A thiocyanate group was selected as leaving group. pHP cages have their electronic transition in the UV, with a maximum absorption at 290 nm. The shape of the spectrum is suitable and the quantum yield is very high, with values in the literature of up to 90 %. Also the photo reaction is well studied and the expected byproducts are well characterized. The chosen isotopologues were characterized spectroscopically. The resulting data on the photo reaction were in agreement with the mechanism proposed in the literature. The mixture for the VIPER experiment consisted of two isotopologues, where for one species all the C atoms in the ring were labelled and for the other the C-atom in the thiocyanate leaving group was labelled. Here the release of the different leaving groups, labelled and unlabelled thiocyanate, could be monitored selectively. This shows that it is possible to selectively release a molecule in a mixture of caged molecules by applying the VIPER pulse sequence.
The samples were synthesized by Matiss Reinfelds from the Heckel group and the VIPER experiments were done together with Carsten Neumann and with support
of the Bredenbeck group.
The leaving groups were chosen because of their infrared absorption which allowed to directly monitor the successful cleavage by spectroscopy. This was needed for the proof-of-concept experiment and to allow direct optimization of the experimental parameters but is not necessarily a requirement for VIPER uncaging.
Concerning the selectivity of the VIPER uncaging, the approach is at the moment mainly limited by the infrared pulse energy. The selective VIPER excitation is competing with unselective excitation directly by just the UV-Vis pulse. A more intense infrared pump pulse would increase only the selective VIPER excitation and thereby improve the contrast to the unspecific background.
To address this issue, the first steps towards an alternative infrared light generation are undertaken. In this alternative approach the infrared light for preexcitation is directly generated by difference frequency generation of the laser output, i.e. the high energy 800 nm fundamental, and the output of a non-collinear optical parametric amplifier (NOPA). To achieve a narrowband pump pulse the pulses are chirped before mixing. In the scope of this thesis a NOPA has been installed and the mixing has been tested with available test crystal medium. While infrared wavelength region and power were not in the aspired range with this alternative crystal the feasibility of mixing between a NOPA output and the fundamental could be shown.
Other possibilities to increase the contrast to the unspecific background excitation by the UV-Vis pump pulse are discussed. For most applications of selective VIPER uncaging the detection by fs-laser spectroscopy will not be needed and could be replaced by other methods e.g. chromatography. This will allow the experimental parameters of the VIPER pulse sequence to be changed in a way which reduces unspecific excitation i.e. reducing the UV-Vis-pump energy and result in much better contrast.
In conclusion, the experimental data in this thesis shows the VIPER pulse sequence to be applicable to selective uncaging schemes and indicates measures to arrive at the specificity necessary for uncaging applications. This thesis was focused on uncaging photo reactions with isotopomers and isotopologues, but other types of photo reactions could in principle be controlled in the same way. It should be possible to address different isomers in mixtures or different ground states of proteins selectively. The discussed experiments are a significant step towards control over photo reactions in mixtures.
We assemble a data set of more than eight million German Twitter posts related to the war in Ukraine. Based on state-of-the-art methods of text analysis, we construct a daily index of uncertainty about the war as perceived by German Twitter. The approach also allows us to separate this index into uncertainty about sanctions against Russia, energy policy and other dimensions. We then estimate a VAR model with daily financial and macroeconomic data and identify an exogenous uncertainty shock. The increase in uncertainty has strong effects on financial markets and causes a significant decline in economic activity as well as an increase in expected inflation. We find the effects of uncertainty to be particularly strong in the first months of the war.
Quantitative models have several advantages compared to qualitative methods for pest risk assessments (PRA). Quantitative models do not require the definition of categorical ratings and can be used to compute numerical probabilities of entry and establishment, and to quantify spread and impact. These models are powerful tools, but they include several sources of uncertainty that need to be taken into account by risk assessors and communicated to decision makers. Uncertainty analysis (UA) and sensitivity analysis (SA) are useful for analyzing uncertainty in models used in PRA, and are becoming more popular. However, these techniques should be applied with caution because several factors may influence their results. In this paper, a brief overview of methods of UA and SA are given. As well, a series of practical rules are defined that can be followed by risk assessors to improve the reliability of UA and SA results. These rules are illustrated in a case study based on the infection model of Magarey et al. (2005) where the results of UA and SA are shown to be highly dependent on the assumptions made on the probability distribution of the model inputs.
In cases in which there is the possibility of massive human losses, the threshold likelihood of their occurrence, and the non-excessive costs of their prevention, we ought to act now. This is all the more definitely the case because it may well be that this is the time-of-last-opportunity to head off one or more potential disasters, all of which may still be preventable by sufficiently rapid reductions in carbon emissions from the combustion of fossil fuel. It is unfair that the present generation should incur as heavy a burden as it does of seizing the last opportunity for prevention of disasters like large sea-level rises, but the unfairness is not sufficient to make the burden unreasonable to bear, especially since it is not in fact as heavy as often believed.
Good quality data on precipitation are a prerequisite for applications like short-term weather forecasts, medium-term humanitarian assistance, and long-term climate modelling. In Sub-Saharan Africa, however, the meteorological station networks are frequently insufficient, as in the Cuvelai-Basin in Namibia and Angola. This paper analyses six rainfall products (ARC2.0, CHIRPS2.0, CRU-TS3.23, GPCCv7, PERSIANN-CDR, and TAMSAT) with respect to their performance in a crop model (APSIM) to obtain nutritional scores of a household’s requirements for dietary energy and further macronutrients. All products were calibrated to an observed time series using Quantile Mapping. The crop model output was compared against official yield data. The results show that the products (i) reproduce well the Basin’s spatial patterns, and (ii) temporally agree to station records (r = 0.84). However, differences exist in absolute annual rainfall (range: 154 mm), rainfall intensities, dry spell duration, rainy day counts, and the rainy season onset. Though calibration aligns key characteristics, the remaining differences lead to varying crop model results. While the model well reproduces official yield data using the observed rainfall time series (r = 0.52), the products’ results are heterogeneous (e.g., CHIRPS: r = 0.18). Overall, 97% of a household’s dietary energy demand is met. The study emphasizes the importance of considering the differences among multiple rainfall products when ground measurements are scarce.
Volatility is a widely recognized measure of market risk. As volatility is not observed it has to be estimated from market prices, i.e., as the implied volatility from option prices. The volatility index VIX making volatility a tradeable asset in its own right is computed from near- and next-term put and call options on the S&P 500 with more than 23 days and less than 37 days to expiration and non-vanishing bid. In the present paper we quantify the information content of the constituents of the VIX about the volatility of the S&P 500 in terms of the Fisher information matrix. Assuming that observed option prices are centered on the theoretical price provided by Heston's model perturbed by additive Gaussian noise we relate their Fisher information matrix to the Greeks in the Heston model. We find that the prices of options contained in the VIX basket allow for reliable estimates of the volatility of the S&P 500 with negligible uncertainty as long as volatility is large enough. Interestingly, if volatility drops below a critical value of roughly 3%, inferences from option prices become imprecise because Vega, the derivative of a European option w.r.t. volatility, and thereby the Fisher information nearly vanishes.
We investigate the applicability of the well-known multilevel Monte Carlo (MLMC) method to the class of density-driven flow problems, in particular the problem of salinisation of coastal aquifers. As a test case, we solve the uncertain Henry saltwater intrusion problem. Unknown porosity, permeability and recharge parameters are modelled by using random fields. The classical deterministic Henry problem is non-linear and time-dependent, and can easily take several hours of computing time. Uncertain settings require the solution of multiple realisations of the deterministic problem, and the total computational cost increases drastically. Instead of computing of hundreds random realisations, typically the mean value and the variance are computed. The standard methods such as the Monte Carlo or surrogate-based methods are a good choice, but they compute all stochastic realisations on the same, often, very fine mesh. They also do not balance the stochastic and discretisation errors. These facts motivated us to apply the MLMC method. We demonstrate that by solving the Henry problem on multi-level spatial and temporal meshes, the MLMC method reduces the overall computational and storage costs. To reduce the computing cost further, parallelization is performed in both physical and stochastic spaces. To solve each deterministic scenario, we run the parallel multigrid solver ug4 in a black-box fashion.
We analyze the repercussions of different kinds of uncertainty on cash demand, including uncertainty of the digital infrastructures, confidence crises of the financial system, natural disasters, political uncertainties, and inflationary crises. Based on a comprehensive literature survey, theoretical considerations and complemented by case studies, we derive a classification scheme how cash holdings typically evolve in each of these types of uncertainty by separating between demand for domestic and international cash as well as between transaction and store of value balances. Hereby, we focus on the stabilizing macroeconomic properties of cash and recommend guidelines for cash supply by central banks and the banking system. Finally, we exemplify our analysis with five case studies from the developing world, namely Venezuela, Zimbabwe, Afghanistan, Iraq, and Libya.
We find that high macroeconomic uncertainty is associated with greater accumulation of physical capital, despite a reduction in investment and valuations. To reconcile this puzzling evidence, we show that uncertainty predicts lower depreciation and utilization of existing capital, which dominates the investment slowdown. Motivated by these dynamics, we develop a quantitative production-based model in which firms implement precautionary savings through reducing utilization rather than raising invest-ment. Through this novel intensive-margin mechanism, uncertainty shocks command a quarter of the equity premium in general equilibrium, while flexibility in utilization adjustments helps explain uncertainty risk exposures in the cross-section of industry returns.
A convex body is unconditional if it is symmetric with respect to reflections in all coordinate hyperplanes. We investigate unconditional lattice polytopes with respect to geometric, combinatorial, and algebraic properties. In particular, we characterize unconditional reflexive polytopes in terms of perfect graphs. As a prime example, we study the signed Birkhoff polytope. Moreover, we derive constructions for Gale-dual pairs of polytopes and we explicitly describe Gröbner bases for unconditional reflexive polytopes coming from partially ordered sets.
Unconventional green
(2023)
We analyze the effects of the PEPP (Pandemic Emergency Purchase Programme), the temporary quantitative easing implemented by the ECB immediately after the burst of the Covid-19 pandemic. We show that the differences in aim, size and flexibility with respect to the traditional Corporate Sector Purchase Programme (CSPP) were able to significantly involve, in addition to the directly targeted bonds, also the green bond segment. Via a standard difference- in-differences model we estimate that the yield on green bonds declined by more than 20 basis points after the PEPP. In order to take into account also the differences attributable to the eligibility to the programme, we employ a triple difference estimator. Bonds that at the same time were green and eligible benefitted of an additional premium of 39 basis points.
We assess the effect and the timing of the corporate arm of the ECB quantitative easing (CSPP) on corporate bond issuance. Because of several contemporaneous measures, to isolate the programme effects we rely on one key eligibility feature: the euro denomination of newly issued bonds. We find that the significant increase in bonds issuance by eligible firms is due to the CSPP and that this effect took at least six months to unfold. This result holds even when comparing firms with similar ratings, thus providing evidence that unconventional monetary policy can foster a financing diversification regardless of firms’ risk profile. We also highlight the impact of the programme on the real economic activity. The evidence suggests that while all firms increased investment in capital expenditures and intangible assets, the CSPP induced eligible firms to invest in marketable and equity securities, to repurchase their own stocks, to hold cash and to carry out short-term investment.