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We introduce Implied Volatility Duration (IVD) as a new measure for the timing of uncertainty resolution, with a high IVD corresponding to late resolution. Portfolio sorts on a large cross-section of stocks indicate that investors demand on average about seven percent return per year as a compensation for a late resolution of uncertainty. In a general equilibrium model, we show that `late' stocks can only have higher expected returns than `early' stocks if the investor exhibits a preference for early resolution of uncertainty. Our empirical analysis thus provides a purely market-based assessment of the timing preferences of the marginal investor.
We study the thermodynamic properties of infinite nuclear matter with the Ultrarelativistic Quantum Molecular Dynamics (URQMD), a semiclassical transport model, running in a box with periodic boundary conditions. It appears that the energy density rises faster than T4 at high temperatures of T approx. 200 - 300 MeV. This indicates an increase in the number of degrees of freedom. Moreover, We have calculated direct photon production in Pb+Pb collisions at 160 GeV/u within this model. The direct photon slope from the microscopic calculation equals that from a hydrodynamical calculation without a phase transition in the equation of state of the photon source.
Background: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC).
Methods: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization.
Results: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR).
Conclusion: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
Anticoagulation with warfarin and rivaroxaban ameliorates experimental autoimmune encephalomyelitis
(2017)
Background: In multiple sclerosis, coagulation factors have been shown to modulate inflammation. In this translational study, we investigated whether long-term anticoagulation with warfarin or rivaroxaban has beneficial effects on the course of autoimmune experimental encephalomyelitis (EAE).
Methods: Female SJL/J mice treated with anticoagulants namely warfarin or rivaroxaban were immunized with PLP139–151. Stable anticoagulation was maintained throughout the entire experiment. Mice without anticoagulation treated with the vehicle only were used as controls. The neurological deficit was recorded during the course of EAE, and histopathological analyses of inflammatory lesions were performed.
Results: In preventive settings, both treatment with warfarin and rivaroxaban reduced the maximum EAE score as compared to the control group and led to a reduction of inflammatory lesions in the spinal cord. In contrast, therapeutic treatment with warfarin had no beneficial effects on the clinical course of EAE. Signs of intraparenchymal hemorrhage at the site of the inflammatory lesions were not observed.
Conclusion: We developed long-term anticoagulation models that allowed exploring the course of EAE under warfarin and rivaroxaban treatment. We found a mild preventive effect of both warfarin and rivaroxaban on neurological deficits and local inflammation, indicating a modulation of the disease induction by anticoagulation.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
THIS PROJECT PROVIDES A PERFORMANCE MEASURE ON THE EFFECT OF LATENCY IN THE CONTEXT OF THE COMPETITIVE ADVANTAGE OF IT. BASED ON A DATASET OF DEUTSCHE BÖRSE’S ELECTRONIC TRADING SYSTEM XETRA, AN EMPIRICAL ANALYSIS IS APPLIED. THAT WAY, WE QUANTIFY THE IMPACT OF LATENCY FROM A CUSTOMER’S POINT OF VIEW.
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is predominantly present in the cytoplasm and the survival of the Jak2(V617F)+ HEL cells is impeded through the inhibition of the cytoplasmic functions of Stat5.
The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA) ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX) scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment.
Lower leg fractures in children and adolescents - comparison of conservative vs. ECMES treatment
(2021)
Background: Lower leg fractures are one of the most common fractures in pediatric age. In general, treatment of lower leg fractures is predominantly non-operative, requiring clinical and radiological controls. Nevertheless, it can be observed that in recent years tibial shaft fractures have increasingly been treated surgically. The aim of the present study is to investigate treatment strategies in the context of different fracture types of the lower leg Methods: In this retrospective chart review, we analyzed 168 children with a diaphyseal fracture of the lower leg admitted to a trauma center between 2005 and 2017. The fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (AO-PCCF). Results: The frequency of fractures based on the AO-PCCF classification was as follows: Simple oblique fracture of the tibia (43.5%, n = 73), hereof 32 toddler's fractures, multifragmentary oblique fracture of the tibia in 14.3% (n = 24) and simple oblique fracture of both, tibia and fibula in 18 patients (10.7%). Most pediatric fractures were treated conservatively by cast (n = 125). Thirty-seven patients received an ECMES, whereas 3 patients were treated with an external fixator and also 3 fractures were stabilized by plate osteosynthesis. Conservatively treated patients were significantly younger (mean age 6.0) compared to patients treated with ECMES (mean age 10.2) or plate osteosynthesis (PO)/external fixator (EF) (mean age 11.3), even if toddler's fractures (mean age 2.0) are excluded (mean age 7.4). There was no difference in time to full weight-bearing, hospitalization of patients treated with ECMES compared to conservative therapy although ECMES-treated fractures show more instability. The consolidation time was significantly higher in ECMES treated patients compared to conservative therapy. Conclusion: Pediatric patients (≤4 years) with lower leg fractures most often showed simple oblique fractures of the tibia, half of them toddler's fractures, which were treated predominantly by conservative therapy. All in all, the consolidation time was longer in intramedullary nailing (ECMES) than in conservative therapy. Nevertheless, time to full weight bearing and duration of cast was the same in both groups, even though ECMES treated fractures show more instability.
mRNA-Abbau ist ein essentieller Prozess der Genexpression, der den Zellen ermöglicht, die Qualität und die Quantität der mRNA zu kontrollieren. Besonders unter Stressbedingungen könnte der mRNA-Abbau eine bedeutende Rolle neben der Speicherung von mRNAs sowie der Regulation der Proteinhomöostase zum Schutz vor schädigenden Einflüssen spielen. Studien mit Hefen und Säugerzellen zeigten, dass dem 5'-3'mRNA-Abbau ein wichtige Rolle sowohl unter normalen Bedingungen als auch unter Stressbedingungen zukommt und dieser in zytoplasmatischen Processing bodies (P-bodies) stattfindet. Im Rahmen dieser Arbeit sollten Erkenntnisse über den 5'-3'mRNA-Abbau erhalten werden. Im Vordergrund stand die Frage nach der Existenz von P-bodies in Arabidopsis thaliana und die Identifikation und Charakterisierung deren Komponenten. Weiterhin sollten Erkenntnisse über die Rolle der P-bodies unter Stressbedingungen gewonnen werden. Dabei sollten besonders Informationen über die Beziehungen zwischen den P-bodies und RNA Stressgranula (mRNA Speicherkompartimente) und Hitzestressgranula (Regulation der Proteinhomöostase) erhalten werden. Das komplette sequenzierte Genom von Arabidopsis thaliana eignete sich zur Identifikation von mRNA-Abbauproteine kodierender Gene. Unter Verwendung von Aminosäuresequenzen bereits bekannter mRNA-Abbauproteine aus Hefe und Säugerzellen konnten Homologe für die Decappingproteine Dcp1 und Dcp2 sowie für die Proteine LSm1,2,5,8 als Untereinheiten des LSm1-7 Komplexes, welcher an der Regulation der Decappingreaktion beteiligt ist, identifiziert werden. Über Hefe-Zwei-Hybrid Analysen konnten anschließend Protein-Protein-Interaktionen zwischen den untersuchten Proteinen identifiziert werden. Weiterhin konnte unter Einsatz der BIFC-Analyse gezeigt werden, dass die Interaktionen zwischen den untersuchten Proteinen hauptsächlich in zytoplasmatischen Strukturen stattfanden. Aufbauend auf diesen Befunden wurde ein Antikörper gegen Dcp1 als Marker für die zytoplasmatischen Strukturen erstellt. Dieser ermöglichte erstmals die Detektion der endogenen Strukturen in Arabidopsis thaliana. Die weitere Charakterisierung über Immunofluoreszenzanalysen zeigten, dass diese P-bodies sind. Wie die P-bodies anderer Organismen sind sie hochdynamisch und benötigen untranslatierte mRNA für die Assemblierung. Die Größe und Anzahl der P-bodies hängt dabei vom Verhältniss des Zuflusses von mRNA und der mRNA-Abbaurate ab. Weiterhin konnte beobachtet werden, das die P-bodies besonders groß unter Stressbedingungen sind und deuten eine wichtige Funktion des mRNA-Abbaus unter Stress an. Dies führte zu der Frage nach der Beziehung der P-bodies zu RNA Stressgranula, die der Speicherung von mRNA unter Stressbedingungen dienen, sowie zu Hitzestressgranula, die an der Aufrechterhaltung der Proteinhomöostase beteiligt sind. Durch Kolokalisationsanalysen mit Markern der RNA Stressgranula, der Hitzestressgranula und der P-bodies konnte erstmals gezeigt werden, dass es sich um voneinander unabhängige Mikrokompartimente handelt, und dass unter Stressbedingungen die zellulären Prozesse mRNA-Abbau, mRNA-Speicherung und Aufrechterhaltung der Proteinhomöostase auf einzelne Mikrkompartimente beschränkt sind. Allerdings konnte zwischen P-bodies und RNA Stressgranula häufig eine räumliche Nähe beobachtet werden. Dies deutet auf einen Austausch von Komponenten zwischen diesen Strukturen hin. Zusammen zeigen die erhaltenen Ergebnisse, dass die identifizierten Proteine Komponenten des 5'-3'mRNA-Abbaus darstellen, und dass der 5'-3'mRNA-Abbau in Pflanzen auch in P-bodies stattfindet. Die Identifizierung und Charakterisierung der pflanzlichen P-bodies bildet eine Grundlage für zukünftige Untersuchungen. Vor allem die massive Bildung von P-bodies unter Stressbedingungen und die Interaktion der P-bodies mit RNA Stressgranula zeigen neue Aspekte der pflanzlichen Hitzestressantwort auf.
We estimate the energy density epsilon pile-up at mid-rapidity in central Pb+Pb collisions from 2 200 GeV/nucleon. epsilon is decomposed into hadronic and partonic contributions. A detailed analysis of the collision dynamics in the framework of a microscopic transport model shows the importance of partonic degrees of freedom and rescattering of leading (di)quarks in the early phase of the reaction for Elab 30 GeV/nucleon. In Pb+Pb collisions at 160 GeV/nucleon the energy density reaches up to 4 GeV/fm3, 95% of which are contained in partonic degrees of freedom.
Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.
Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.
Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Der eine gibt nur wenige Cents, der nächste lässt beim Trinkgeld etwas mehr springen. Am Extra-Obolus, der Rechnung plus X, scheiden sich die Geister. Ein Forschungsseminar an der Goethe-Universität hat zum Thema Trinkgeld ein Semester lang Gäste und Kellner/innen befragt – mit überraschenden Ergebnissen.
The behavior of hadronic matter at high baryon densities is studied within Ultrarelativistic Quantum Molecular Dynamics (URQMD). Baryonic stopping is observed for Au+Au collisions from SIS up to SPS energies. The excitation function of flow shows strong sensitivities to the underlying equation of state (EOS), allowing for systematic studies of the EOS. Effects of a density dependent pole of the rho-meson propagator on dilepton spectra are studied for different systems and centralities at CERN energies.
The behavior of hadronic matter at high baryon densities is studied within Ultrarelativistic Quantum Molecular Dynamics (URQMD). Baryonic stopping is observed for Au+Au collisions from SIS up to SPS energies. The excitation function of flow shows strong sensitivities to the underlying equation of state (EOS), allowing for systematic studies of the EOS. Dilepton spectra are calculated with and without shifting the rho pole. Except for S+Au collisions our calculations reproduce the CERES data.
Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.
Compelling evidence for the creation of a new form of matter has been claimed to be found in Pb+Pb collisions at SPS. We discuss the uniqueness of often proposed experimental signatures for quark matter formation in relativistic heavy ion collisions. It is demonstrated that so far none of the proposed signals like J/psi meson production/suppression, strangeness enhancement, dileptons, and directed flow unambigiously show that a phase of deconfined matter has been formed in SPS Pb+Pb collisions. We emphasize the need for systematic future measurements to search for simultaneous irregularities in the excitation functions of several observables in order to come close to pinning the properties of hot, dense QCD matter from data.
An experiment addressing electron capture (EC) decay of hydrogen-like 142Pm60+ions has been conducted at the experimental storage ring (ESR) at GSI. The decay appears to be purely exponential and no modulations were observed. Decay times for about 9000 individual EC decays have been measured by applying the single-ion decay spectroscopy method. Both visually and automatically analysed data can be described by a single exponential decay with decay constants of 0.0126(7)s−1 for automatic analysis and 0.0141(7)s−1 for manual analysis. If a modulation superimposed on the exponential decay curve is assumed, the best fit gives a modulation amplitude of merely 0.019(15), which is compatible with zero and by 4.9 standard deviations smaller than in the original observation which had an amplitude of 0.23(4).