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Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.
We examine the relationship between household wealth and self-control. Although self-control has been linked to consumption and financial behavior, its measurement remains an open issue. We employ a definition of self-control failure that follows literature in psychology, suggesting that three factors can render self-control defective: lack of planning, lack of monitoring, and lack of commitment to pre-set plans. Our measure combines those three ingredients and can be computed using a standard representative survey. We find that self-control failure is strongly associated with different household net wealth measures and with self-assessed financial distress.
Heterogenous subtypes of breast cancer need to be analyzed separately. Pooling of datasets can provide reasonable sample sizes but dataset bias is an important concern. We assembled a combined dataset of 579 Affymetrix microarrays from triple negative breast cancer (TNBC) in Gene Expression Omnibus (GEO) series GSE31519. We developed a method for selecting comparable datasets and to control for the amount of dataset bias of individual probesets.
Mechanics has an important role during morphogenesis, both in the generation of forces driving cell shape changes and in determining the effective material properties of cells and tissues. Drosophila dorsal closure has emerged as a reference model system for investigating the interplay between tissue mechanics and cellular activity. During dorsal closure, the amnioserosa generates one of the major forces that drive closure through the apical contraction of its constituent cells. We combined quantitation of live data, genetic and mechanical perturbation and cell biology, to investigate how mechanical properties and contraction rate emerge from cytoskeletal activity. We found that a decrease in Myosin phosphorylation induces a fluidization of amnioserosa cells which become more compliant. Conversely, an increase in Myosin phosphorylation and an increase in actin linear polymerization induce a solidification of cells. Contrary to expectation, these two perturbations have an opposite effect on the strain rate of cells during DC. While an increase in actin polymerization increases the contraction rate of amnioserosa cells, an increase in Myosin phosphorylation gives rise to cells that contract very slowly. The quantification of how the perturbation induced by laser ablation decays throughout the tissue revealed that the tissue in these two mutant backgrounds reacts very differently. We suggest that the differences in the strain rate of cells in situations where Myosin activity or actin polymerization is increased arise from changes in how the contractile forces are transmitted and coordinated across the tissue through ECadherin-mediated adhesion. Altogether, our results show that there is an optimal level of Myosin activity to generate efficient contraction and suggest that the architecture of the actin cytoskeleton and the dynamics of adhesion complexes are important parameters for the emergence of coordinated activity throughout the tissue.
9.01 This chapter outlines the development of Contingent Convertible Securities (CoCos) for financial institutions from their theoretical origins to their current form under the European Union’s Fourth Capital Requirements Directive framework and its Bank Recovery and Resolution Directive and examines the effect the framework and the directive have had on their design and ability to fulfill the ends for which they were initially conceived. It examines this from two viewpoints: the policy goals CoCos are meant to achieve and the corporate law issues raised by the requirements of CRD IV. On the policy side we conclude that CRD IV and the RRD have significantly limited the amount of CoCos a financial institution is likely to issue, but expanded their possible forms by including write-down as well as convertible structures and narrowed the differences between them and pure regulatory bail-in structures, thus calling into question whether they are truly ‘going concern’ rather than ‘gone concern’ capital. On the company law side we conclude that a number of issues, in particular the limits on an authorization of management to issue CoCos and shares, the scope of the shareholders’ right of pre-emption, the concept of dilution and the distinction between contributions in cash and in kind merit closer attention than they appear to have received in the current discussion on CoCos.
Der diesjährige 9. Trockenrasen-Sonderteil von Tuexenia beginnt mit einem Bericht über die aktuellen Aktivitäten der European Dry Grassland Group (EDGG). Zunächst geben wir einen Überblick über die Entwicklung der Mitgliederzahl. Dann berichten wir vom letzten European Dry Grassland Meeting in Zamość (Polen, 2013) und vom letzten European Dry Grassland Field Workshop in Chakassien (Russland, 2013) und informieren über künftige Veranstaltungen der EDGG. Anschließend erläutern wir die Publikationsaktivitäten der EDGG. Im zweiten Teil des Editorials geben wir eine Einführung zu den fünf Artikeln des diesjährigen Trockenrasen-Sonderteils: Zwei davon beschäftigen sich mit der Syntaxonomie von Trockenrasen in Osteuropa: Der eine Artikel präsentiert erstmalig eine nach internationalen Nomenklaturregeln gültige Liste der Trockenrasengesellschaften Serbiens während der andere die Ergebnisse des zweiten EDGG-Field Workshop 2010 nach Podolien (Ukraine) vorstellt. Im dritten Artikel werden kryophytische Steppen in Südsibirien (Russland) analysiert. Der vierte Artikel analysiert in Böhmen (Tschechien) die bestimmenden Kräfte für Artenreichtum und Artenzusammensetzung der Trockenrasen. Der fünfte Artikel befasst sich mit der Auswahl von Wiederansiedlungsarten am Beispiel der Steppenrasen in Thüringen (Deutschland).
The pi-calculus is a well-analyzed model for mobile processes and mobile computations.
While a lot of other process and lambda calculi that are core languages of higher-order concurrent and/or functional programming languages use a contextual semantics observing the termination behavior of programs in all program contexts, traditional program equivalences in the pi-calculus are bisimulations and barbed testing equivalences, which observe the communication capabilities of processes under reduction and in contexts.
There is a distance between these two approaches to program equivalence which makes it hard to compare the pi-calculus with other languages. In this paper we contribute to bridging this gap by investigating a contextual semantics of the synchronous pi-calculus with replication and without sums.
To transfer contextual equivalence to the pi-calculus we add a process Stop as constant which indicates success and is used as the base to define and analyze the contextual equivalence which observes may- and should-convergence of processes.
We show as a main result that contextual equivalence in the pi-calculus with Stop conservatively extends barbed testing equivalence in the (Stop-free) pi-calculus. This implies that results on contextual equivalence can be directly transferred to the (Stop-free) pi-calculus with barbed testing equivalence.
We analyze the contextual ordering, prove some nontrivial process equivalences, and provide proof tools for showing contextual equivalences. Among them are a context lemma, and new notions of sound applicative similarities for may- and should-convergence.
I numerically solve realistically calibrated life cycle consumption-investment problems in continuous time featuring stochastic mortality risk driven by jumps, unspanned labor income as well as short-sale and liquidity constraints and a simple insurance. I compare models with deterministic and stochastic hazard rate of death to a model without mortality risk. Mortality risk has only minor effects on the optimal controls early in the life cycle but it becomes crucial in later years. A diffusive component in the hazard rate of death has no significant impact, whereas a jump component is desired by the agent and influences optimal controls and wealth evolution. The insurance is used to ensure optimal bequest such that there is no accidental bequest. In the absence of the insurance, the biggest part of bequest is accidental.
Consumption-based asset pricing with rare disaster risk : a simulated method of moments approach
(2014)
The rare disaster hypothesis suggests that the extraordinarily high postwar U.S. equity premium resulted because investors ex ante demanded compensation for unlikely but calamitous risks that they happened not to incur. Although convincing in theory, empirical tests of the rare disaster explanation are scarce. We estimate a disaster-including consumption-based asset pricing model (CBM) using a combination of the simulated method of moments and bootstrapping. We consider several methodological alternatives that differ in the moment matches and the way to account for disasters in the simulated consumption growth and return series. Whichever specification is used, the estimated preference parameters are of an economically plausible size, and the estimation precision is much higher than in previous studies that use the canonical CBM. Our results thus provide empirical support for the rare disaster hypothesis, and help reconcile the nexus between real economy and financial markets implied by the consumption-based asset pricing paradigm.
he observed hump-shaped life-cycle pattern in individuals' consumption cannot be explained by the classical consumption-savings model. We explicitly solve a model with utility of both consumption and leisure and with educational decisions affecting future wages. We show optimal consumption is hump shaped and determine the peak age. The hump results from consumption and leisure being substitutes and from the implicit price of leisure being decreasing over time; more leisure means less education, which lowers future wages, and the present value of foregone wages decreases with age. Consumption is hump shaped whether the wage is hump shaped or increasing over life.
Construction and commissioning of a setup to study ageing phenomena in high rate gas detectors
(2014)
In high-rate heavy-ion experiments, gaseous detectors encounter big challenges in terms of degradation of their performance due to a phenomenon dubbed ageing. In this thesis, a setup for high precision ageing studies has been constructed and commissioned at the GSI detector laboratory. The main objective is the study of ageing phenomena evoked by materials used to build gaseous detectors for the Compressed Baryonic Matter (CBM) experiment at the future Facility for Antiproton and Ion Research (FAIR).
The precision of the measurement, e.g., of the gain of a gaseous detector, is a key element in ageing studies: it allows to perform the measurement at realistic rates in an acceptable time span. It is well known the accelerating ageing employing high intensity sources might produce misleading results. The primary objective is to build an apparatus which allows very accurate measurements and is thus sensitive to minute degradations in detector performance. The construction and commissioning of the
setup has been carried out in two steps. During the first step of this work, a simpler setup which already existed in the detector laboratory of GSI had been utilised to define all conditions related to ageing studies. The outcome of these studies defined the properties and characteristics that must be met to build and operate a new, sophisticated and precise setup. The already existing setup consisted of two identical Multi Wire Proportional Chambers (MWPCs), a gas mixing station, an 55Fe source, an x-ray generator, an outgassing box and stainless steel tubing. In a first step, the gain and electric field configuration of the MWPCs were simulated by a combination of a gas simulation (Magboltz) and electric field simulation program (Garfield). The performance and operating conditions of the chambers have been thoroughly characterised before utilising them in first preparatory ageing test. The main diagnostic parameter in ageing studies is the detector gain, thus it is mandatory for precise ageing studies to minimise the systematic and statistical variation of the pressure and temperature corrected gain. To achieve the required accuracy, several improvements of the chamber design and the gas system have been implemented. In addition, the temperature measurement has been optimised. During the preparatory tests, several ageing studies have been carried out. The ageing effect of seven materials and gases have been carried out during these tests: RTV-3145, Ar/CO2 gas, Durostone flushed with Ar/Isobutane gas, Vetronit G11, Vetronit G11 contaminated with Micro 3000 and Gerband 705. The results of these studies went into the design of the new sophisticated ageing setup. For example some tests revealed that there was, even after cleaning, a certain level of contamination with "ageing agents" in the existing setup, which made it imperative to ensure a very high level cleanness of all components during the construction of the setup. The curing period of some testing samples like glues or the gas flow rate were found to be very important factors that must be taken into account to obtain comparable results. Very important changes in the chamber design have been made, i.e., the aluminium-Kapton cathodes used in MWPCs have been replaced with multi-wire planes and the fibreglass housing of the chamber has been changed to metal. The second step started with building the new setup which was designed based on the findings from the first step. The new ageing setup consists of three MWPCs, two moving platforms, an 55Fe source, a copper-anode x-ray generator, two outgassing boxes, both flexible and rigid stainless steel tubes. Before fabrication of the chambers, simulations of their electric field and the gain have been done using Magboltz and Garfield programs. After that, the chambers were installed and tested. A 0.3% peak-to-peak residual variation of the corrected gain has been achieved. Finally, the complete setup has been operated with full functionality in no-ageing conditions during one week. This test revealed very stable gain in all three chambers. After that two materials (Gerban 705 and RTV-3145) have been inserted in the two outgassing boxes and tested. They revealed an ageing rate of about 0.3%/mC/cm and 3%/mC/cm respectively. The final test proves the stability and accuracy of the ageing measurements carried out with the ageing setup at the detector laboratory at GSI which is ready to conduct the envisaged systematic ageing studies.
We present a simultaneous calculation of heavy single-Λ hypernuclei and compact stars containing hypernuclear core within a relativistic density functional theory based on a Lagrangian which includes the hyperon octet and lightest isoscalar-isovector mesons which couple to baryons with density-dependent couplings. The corresponding density functional allows for SU(6) symmetry breaking and mixing in the isoscalar sector, whereby the departures in the σ–Λ and σ–Σ couplings away from their values implied by the SU(3) symmetric model are used to adjust the theory to the laboratory and astronomical data. We fix σ–Λ coupling using the data on the single-Λ hypernuclei and derive an upper bound on the σ–Σ from the requirement that the lower bound on the maximum mass of a compact star is 2M⊙.
In this work the baryon number and strange susceptibility of second and fourth order are presented. The results at zero baryon-chemical potential are obtained using a well tested chiral effective model including all known hadron degrees of freedom and additionally implementing quarks and gluons in a PNJL-like approach. Quark and baryon number susceptibilities are sensitive to the fundamental degrees of freedom in the model and signal the shift from massive hadrons to light quarks at the deconfinement transition by a sharp rise at the critical temperature. Furthermore, all susceptibilities are found to be largely suppressed by repulsive vector field interactions of the particles. In the hadronic sector vector repulsion of baryon resonances restrains fluctuations to a large amount and in the quark sector above Tc even small vector field interactions of quarks quench all fluctuations unreasonably strong. For this reason, vector field interactions for quarks have to vanish in the deconfinement limit.
Consequences of a human TRPA1 genetic variant on the perception of nociceptive and olfactory stimuli
(2014)
Background: TRPA1 ion channels are involved in nociception and are also excited by pungent odorous substances. Based on reported associations of TRPA1 genetics with increased sensitivity to thermal pain stimuli, we therefore hypothesized that this association also exists for increased olfactory sensitivity.
Methods: Olfactory function and nociception was compared between carriers (n = 38) and non-carriers (n = 43) of TRPA1 variant rs11988795 G.A, a variant known to enhance cold pain perception. Olfactory function was quantified by assessing the odor threshold, odor discrimination and odor identification, and by applying 200-ms pulses of H2S intranasal. Nociception was assessed by measuring pain thresholds to experimental nociceptive stimuli (blunt pressure, electrical stimuli, cold and heat stimuli, and 200-ms intranasal pulses of CO2).
Results: Among the 11 subjects with moderate hyposmia, carriers of the minor A allele (n = 2) were underrepresented (34 carriers among the 70 normosmic subjects; p = 0.049). Moreover, carriers of the A allele discriminated odors significantly better than non-carriers (13.161.5 versus 12.361.6 correct discriminations) and indicated a higher intensity of the H2S stimuli (29.2613.2 versus 21612.8 mm VAS, p = 0.006), which, however, could not be excluded to have involved a trigeminal component during stimulation. Finally, the increased sensitivity to thermal pain could be reproduced.
Conclusions: The findings are in line with a previous association of a human TRPA1 variant with nociceptive parameters and extend the association to the perception of odorants. However, this addresses mainly those stimulants that involve a trigeminal component whereas a pure olfactory effect may remain disputable. Nevertheless, findings suggest that future TRPA1 modulating drugs may modify the perception of odorants.
Aims: We have provided evidence in former studies that cytokines (IL-8, TNF alpha, LBP, TGFß) measured in blood correlate negatively with lung function in deltaF508 homozygous patients. GAP junction proteins might be of importance for the influx of blood cells into the lung. Our aim was to assess the relationship between connexin genotypes and cytokines (IL-8, TNF-alpha, LBP, TGFß) in induced sputum and serum, and lung disease.
Methods: 36 patients homozygous for deltaF508 (median age 18 y, m/f 16/20, FEV1(%) 77) were examined. Sequence analysis was performed for genes encoding GAP junction protein alpha 1 (GJA1/connexin 43) and gap junction protein alpha 4 (GJA4/connexin 37). Cytokines were assessed in serum and induced sputum (IS) by chemiluminescence (DPC Biermann, Bad Homburg, Germany) as well as leukocyte counts.
Results: DNA analysis was performed in 35 patients. Whereas GJA1 showed only one rare heterozygous synonymous SNP (rs138386744) in one patient, four common SNPs were detected in GJA4. Two were synonymous changes, but the third variant (rs41266431) predicts an amino acid substitution (GTA → valine, ATA → isoleucine) as well as the fourth SNP (rs1764391: CCC→proline, TCC→serine). For rs41266431 patients with homozygosity for the G variant had higher IL-8 levels (median: 13.3/8.0 pg/ml, p=0.07) in serum as well as leukocytes in sputum (median: 2050/421 /µl p=0.041) than those showing heterozygosity (G/A). In individuals > 30 years lung function (FEV1 41.3/84.83 % predicted, p=0.07) was worse.
Conclusion: SNP rs41266431 seems a promising candidate for further investigations, suggesting GJA4 a potential disease modifying gene.
Connecting narrative worlds
(2014)
In this paper we discuss to what extent one can infer details of the interior structure of a black hole based on its horizon. Recalling that black hole thermal properties are connected to the non-classical nature of gravity, we circumvent the restrictions of the no-hair theorem by postulating that the black hole interior is singularity free due to violations of the usual energy conditions. Further these conditions allow one to establish a one-to-one, holographic projection between Planckian areal “bits” on the horizon and “voxels”, representing the gravitational degrees of freedom in the black hole interior. We illustrate the repercussions of this idea by discussing an example of the black hole interior consisting of a de Sitter core postulated to arise from the local graviton quantum vacuum energy. It is shown that the black hole entropy can emerge as the statistical entropy of a gas of voxels.
The paper considers the interdependence between word order, congruence and formal cases – the means which, together with lexical meaning and formal class markers, explicate the concrete syntactic relations in a sentence. There are languages (including the Slavic ones) in whose structure congruence is very important. They may or may not possess formal cases. Even if they have no formal cases their word order is relatively free due to the compensatory role of congruence, which is often, but not always, able to eliminate potential ambiguity in the sentence, assisted to a certain extent by animacy, definiteness, pronoun duplicates of the objects and extra-linguistic knowledge (and Modern Bulgarian is good enough to illustrate this). At the same time, even in congruence languages with formal cases there are strict word order rules. In both kinds of congruence languages the violation of these rules can make a sentence utterly unintelligible (the last is exemplified by a couple of lines from Spanish and Ukrainian poetry).
Introduction: Currently there are several advanced guiding techniques for pathoanatomical diagnosis of incidental solitary pulmonary nodules (iSPN): Electromagnetic navigation (EMN) with or without endobronchial ultrasound (EBUS) with miniprobe, transthoracic ultrasound (TTUS) for needle approach to the pleural wall and adjacent lung and computed tomography (CT) -guidance for (seldom if ever used) endobronchial or (common) transthoracical approach. In several situations one technique is not enough for efficient diagnosis, therefore we investigated a new diagnostic technique of endobronchial guided biopsies by a Cone Beam Computertomography (CBCT) called DynaCT (SIEMENS AG Forchheim, Germany). Method and Material: In our study 33 incidental solitary pulmonary nodules (iSPNs) (28 malignant, 5 benign; mean diameter 25 +/-12mm, shortest distance to pleura 25+/-18mm) were eligible according to in- and exclusion criteria. Realtime and onsite navigation were performed according to our standard protocol.22 All iSPN were controlled with a second technique when necessary and clinical feasible in case of unspecific or unexpected histological result. In all cases common guidelines of treatment of different iSPNs were followed in a routine manner. Results: Overall navigational yield (ny) was 91% and diagnostic yield (dy) 70%, dy for all accomplished malignant cases (n=28) was 82%. In the subgroup analysis of the invisible iSPN (n=12, 11 malignant, 1 benign; mean diameter 15+/-3mm) we found an overall dy of 75%. For the first time we describe a significant difference in specifity of biopsy results in regards to the position of the forceps in the 3-dimensional volume (3DV) of the iSPN in the whole sample group. Comparing the specifity of biopsies of a 3D-uncentered but inside the outer one third of an iSPN-3DV with the specifity of biopsies of centered forceps position (meaning the inner two third of an iSPN-3DV) reveals a significant (p=0,0375 McNemar) difference for the size group (>1cm) of 0,9 for centered biopsies vs. 0,3 for uncentered biopsies. Therefore only 3D-centered biopsies should be relied on especially in case of a benign result. Conclusion:The diagnostic yield of DynaCT navigation guided transbronchial biopsies (TBB) only with forceps is at least up to twofold higher than conventional TBB for iSPNs <2cm. The diagnostic yield of DynaCT navigation guided forceps TBB in invisible SPNs is at least in the range of other navigation studies which were performed partly with multiple navigation tools and multiple instruments. For future diagnostic and therapeutic approaches it is so far the only onsite and realtime extrathoracic navigation approach (except for computed tomography (CT)-fluoroscopy) in the bronchoscopy suite which keeps the working channel open. The system purchase represents an important investment for hospitals but it is a multidisciplinary and multinavigational tool with possible access via bronchial airways, transthoracical or vascular approach at the same time and on the same table without the need for an expensive disposable instrument use.
A hybrid form of tilapia was introduced into Port Sulphur, Louisiana and was subsequently managed by treatment with rotenone and stocking of native predatory fishes. Measurements of tilapia from before this management event were compared to measurements of tilapia in the two years after the treatment. Post-management tilapia were consistently deeper in body and had greater weight per unit length (condition) when compared to pre-management fish. Procrustes generalized least squares data supported this by consistently finding post-management tilapia to be consistently deeper in body and head shape than pre-management fish. Although this could indicate the effectiveness of stocking native predators, several other factors, including two cold winters, seasonal effects, and less competition, may have contributed to this result.