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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.
The availability of organelle genome sequences of bryophytes provides opportunity to mine this data. Therefore in this study microsatellites in chloroplast genome sequence of Pellia endiviifolia (Accession number: NC_019628), downloaded from the National Center for Biotechnology Information (NCBI) in fasta format, were identified. The sequence was mined with the help of MISA, a Perl script, to detect microsatellites. In total, 16 perfect microsatellites were identified in 120.546 kb sequence mined. An average length of 14.94 bp was calculated for mined microsatellites with a density of 1 SSR/7.09 kb. Depending on the repeat units, the length of microsatellites ranged from 12 to 18 bp. Tetranucleotides (7, 43.75%) were the most frequent repeat type, followed by mononucleotide (3, 18.75%) repeats. Dinucleotide, trinucleotide and pentanucleotide repeats were found with equal frequency (2, 12.5%). Interestingly, hexanucleotide repeats were completely absent in chloroplast genome of Pellia endiviifolia.
Research in the field of Digital Humanities, also known as Humanities Computing, has seen a steady increase over the past years. Situated at the intersection of computing science and the humanities, present efforts focus on making resources such as texts, images, musical pieces and other semiotic artifacts digitally available, searchable and analysable. To this end, computational tools enabling textual search, visual analytics, data mining, statistics and natural language processing are harnessed to support the humanities researcher. The processing of large data sets with appropriate software opens up novel and fruitful approaches to questions in the traditional humanities. This report summarizes the Dagstuhl seminar 14301 on “Computational Humanities - bridging the gap between Computer Science and Digital Humanities”.
1998 ACM Subject Classification I.2.7 Natural Language Processing, J.5 Arts and Humanities
In reply to internal or external danger stimuli, the body orchestrates an inflammatory response. The endogenous triggers of this process are the damage-associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of molecules that draw their origin either from inside the various compartments of the cell or from the extracellular space. Following interaction with pattern recognition receptors in cross-talk with various non-immune receptors, DAMPs determine the downstream signaling outcome of septic and aseptic inflammatory responses. In this review, the diverse nature, structural characteristics, and signaling pathways elicited by DAMPs will be critically evaluated.
Complexin-1 and foxp1 expression changes are novel brain effects of
alpha-synuclein pathology
(2014)
As the second most frequent neurodegenerative disorder of the aging population, Parkinson’s disease (PD) is characterized by progressive deficits in spontaneous movement, atrophy of dopaminergic midbrain neurons and aggregation of the protein alpha-synuclein (SNCA). To elucidate molecular events before irreversible cell death, we studied synucleinopathy-induced expression changes in mouse brain and identified 49 midbrain/brainstem-specific transcriptional dysregulations. In particular complexin-1 (Cplx1), Rabl2a and 14-3-3epsilon (Ywhae) downregulation, as well as upregulation of the midbrain-specific factor forkhead box P1 (Foxp1) and of Rabgef1, were interesting as early mRNA level effects of alpha-synuclein triggered pathology. The protein levels of complexin-1 were elevated in midbrain/brainstem tissue of mice with A53T-SNCA overexpression and of mice with SNCA-knockout. The response of CPLX1 and Foxp1 levels to SNCA deficiency supports the notion that these factors are regulated by altered physiological function of alpha-synuclein. Thus, their analysis might be useful in PD stages before the advent of Lewy pathology. Because both alpha-synuclein and complexin-1 modulate vesicle release, our findings support presynaptic dysfunction as an early event in PD pathology.
We study the effects of the recent economic crisis on firms׳ bidding behavior and markups in sealed bid auctions. Using data from Austrian construction procurements, we estimate bidders׳ construction costs within a private value auction model. We find that markups of all bids submitted decrease by 1.5 percentage points in the recent economic crisis, markups of winning bids decrease by 3.3 percentage points. We also find that without the government stimulus package this decrease would have been larger. These two pieces of evidence point to pro-cyclical markups.
Objective: Videolaryngoscopy has mainly been developed to facilitate difficult airway intubation. However, there is a lack of studies demonstrating this method's efficacy in pediatric patients. The aim of the present study was to compare the TruView infant EVO2 and the C-MAC videolaryngoscope with conventional direct Macintosh laryngoscopy in children with a bodyweight ≤10 kg in terms of intubation conditions and the time to intubation.
Methods: In total, 65 children with a bodyweight ≤10 kg (0-22 months) who had undergone elective surgery requiring endotracheal intubation were retrospectively analyzed. Our database was screened for intubations with the TruView infant EVO2, the C-MAC videolaryngoscope, and conventional direct Macintosh laryngoscopy. The intubation conditions, the time to intubation, and the oxygen saturation before and after intubation were monitored, and demographic data were recorded. Only children with a bodyweight ≤10 kg were included in the analysis.
Results: A total of 23 children were intubated using the C-MAC videolaryngoscope, and 22 children were intubated using the TruView EVO2. Additionally, 20 children were intubated using a standard Macintosh blade. The time required for tracheal intubation was significantly longer using the TruView EVO2 (52 sec vs. 28 sec for C-MAC vs. 26 sec for direct LG). However, no significant difference in oxygen saturation was found after intubation.
Conclusion: All devices allowed excellent visualization of the vocal cords, but the time to intubation was prolonged when the TruView EVO2 was used. The absence of a decline in oxygen saturation may be due to apneic oxygenation via the TruView scope and may provide a margin of safety. In sum, the use of the TruView by a well-trained anesthetist may be an alternative for difficult airway management in pediatric patients.
Comparing two methods of determining infiltration rates of permeable interlocking concrete pavers
(2014)
Adequate infiltration through Permeable Interlocking Concrete Pavements (PICPs) is critical to their hydraulic performance. Detected by monitoring infiltration performance, reduced infiltration rates can indicate that maintenance is required. Measurement of infiltration rates has previously been problematic on PICPs because of a lack of accepted standard methodologies and the practical difficulties in modifying existing testing methodologies. On large sites, standard methodologies necessitate multiple measurements to achieve accuracy. Standard methods also contend with practical issues such as sealing the rings to the surface to prevent lateral water flow. This study examined the performance of two PICP surface infiltration rate measurement methods: a modified double-ring infiltrometer (DRIT), and a specially designed rainfall simulation infiltrometer (RSIT). A positive correlation (R2 = 0.85) of results was found between the two, demonstrating that the RSIT was comparable to the DRIT. The modified DRIT produced surface infiltration results approximately 60% higher than the RSIT results. The RSIT provided lower variation between tests, requiring fewer measurements in large sites whilst still maintaining accuracy, thereby improving testing efficiency. The new RSIT method also eliminates some of the practical difficulties with existing methodologies such as unrealistic pressure heads artificially increasing infiltration rates, and the use of sealant under test measurement infiltration rings.
The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS), intermittent theta burst stimulation (iTBS), and 1 mA transcranial random noise stimulation (tRNS) within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs) in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.
We compared Chatham Island endemic species Xanthocnemis tuanuii to its congenerics from the New Zealand South Island: X. zealandica (newly collected specimens)and X. sinclairi (type specimens plus newly collected material). Two independent tests were performed –geometric morphometrics and molecular. Both analyses were consistent in supporting the status of X. tuanuiias a good species. Species differed statistically in the following morphological traits: head (dorsal view), male appendages (dorsal, lateral, posterior and ventral views), thorax (dorsal view), and penis (dorsal and lateral view). In addition to the original diagnostic features (mainly shape of the male superior appendages), a new morphological character is suggested here which reliably distinguishes the species based on the shape of the inferior appendages. There was no statistical support for the species status of X. sinclairi. The only feature re-ported as diagnostic (lower lobe of male superior appendages) was found to be variable and insufficient to warrant the previously proposed taxonomic rank for X. sinclairi. Molecular analysis of specimens showing identical appendages to the X. sinclairi holotype grouped them with X. zealandica specimens. Therefore X. sinclairi is synonymised with X. zealandica.
The endophallic structure of the genus Laius is studied and discussed based on the examination of 19 species from Asia to the Indian Ocean. The structure contains two primary sclerites (named gonoporal piece and ligula), a secondary sclerite on the basal part of the gonoporal piece (named additional sclerite) in some species, and a membranous basal area closely covered with many spines (named spinous area). Five species groups are recognized based on the morphology of the endophallic sclerites. The sympatric species have different body sizes and quite distinguishable endophallic sclerites (= different species group), while the allopatric species have overlapping body sizes and similar endophallic sclerites (= same species group). Three new species are described and six previously known species are redescribed with endophallic sclerites, and the descriptions of endophallic sclerites of the remaining ten species are added. The larva of Laius rodriguesensis sp. nov. is also described. The genus
Nossibeus Evers, 1994 is synonymised with Laius Guérin-Méneville, 1830.
Ecocriticism started out in the early 1990s in the framework of American literary studies - in the Anglo sense that equates "America" with the "United States." In fact, the new field's first professional organization, the Association for the Study of Literature and the Environment, was founded as an offshoot of academic interest focused on a particular region of the United States, in the backroom of a casino in Reno, Nevada, during the 1992 annual convention of the Western Literature Association. During its first decade, the bulk of ecocritical attention focused on American literature as shaped by Thoreau and British literature as shaped by Wordsworth - a limited but powerful concentration on nature writing in the genres of poetry, nonfiction prose, and the noveI, with particular attention to Native American literature. By the turn of the millennium, in a story that has by now been told repeatedly, interest in the literature-environment nexus had grown and diversified enough that ecocriticism almost literally exploded into a much broader research area encompassing multiple historical periods (from the Middle Ages to postmodernism), genres (from poetry to the graphic novel and narrative film), and regions: the Caribbean, Latin America, East Asia, and Western Europe all emerged as new areas of ecocritical exploration. New encounters between postcolonial theory and ecocritical analysis proved particularly productive for both fields: linking historical exploration and political ecology with literary analysis, the emergent "poco-eco" matrix opened new perspectives on the connections and disjunctures between imperialism, ecological crisis, and conservation. Over the last few years, the concept of "Environmental Humanities" has increasingly co me to accompany and to superimpose itself as an umbrella term on ecocriticism and comparable research areas in neighboring disciplines: environmental history, environmental anthropology, environmental philosophy, cultural geography, and political ecology. Driven by the impulse to connect environmental research across the humanities, to justify humanistic research at institutions often prone to cut first in the humanities, and to bring the knowledge generated through humanistic research into the public sphere, environmentally oriented scholars have used the term "Environmental Humanities" as a shorthand for what they hope will be a new vision of their discipline. As of this writing, the concept remains somewhat more aspirational than real. While ecocritics and environmental philosophers have long collaborated in Australia, and environmental historians and ecocritics sometimes collaborate in the United States, the disciplines that make up the Environmental Humanities have to date largely pursued their own disciplinary trajectories. But there are signs that the tide may have begun to turn. Various universities and research organizations have started programs in the field. The Swedish environmental historian Sverker Sörlin published a brief outline of the new interdisciplinary matrix in the journal 'BioScience' in 2012, and a longer manifesto followed from the editorial collective of the newly established journal 'Environmental Humanities' at Macquarie University in Australia (Rose et al. 2012). Another journal focusing on the environmental humanities began publication in early 2014 from the University of Oregon under the title 'Resilience'.
Synaptic dysfunction and synapse loss are key features of Alzheimer's pathogenesis. Previously, we showed an essential function of APP and APLP2 for synaptic plasticity, learning and memory. Here, we used organotypic hippocampal cultures to investigate the specific role(s) of APP family members and their fragments for dendritic complexity and spine formation of principal neurons within the hippocampus. Whereas CA1 neurons from APLP1-KO or APLP2-KO mice showed normal neuronal morphology and spine density, APP-KO mice revealed a highly reduced dendritic complexity in mid-apical dendrites. Despite unaltered morphology of APLP2-KO neurons, combined APP/APLP2-DKO mutants showed an additional branching defect in proximal apical dendrites, indicating redundancy and a combined function of APP and APLP2 for dendritic architecture. Remarkably, APP-KO neurons showed a pronounced decrease in spine density and reductions in the number of mushroom spines. No further decrease in spine density, however, was detectable in APP/APLP2-DKO mice. Mechanistically, using APPsalpha-KI mice lacking transmembrane APP and expressing solely the secreted APPsalpha fragment we demonstrate that APPsalpha expression alone is sufficient to prevent the defects in spine density observed in APP-KO mice. Collectively, these studies reveal a combined role of APP and APLP2 for dendritic architecture and a unique function of secreted APPs for spine density.
OBJECTIVES: Outcome of aortic valve replacement may be influenced by the choice of bioprosthesis. Pericardial heart valves are described to have a favourable haemodynamic profile compared with porcine valves, although the clinical notability of this finding is still controversially debated. Herein, we compared the long-term results of two commonly implanted bioprosthesis at a single centre.
METHODS: All consecutive patients undergoing isolated aortic valve replacement with either a Carpentier-Edwards Magna pericardial prosthesis or a Medtronic Mosaic porcine prosthesis between 2002 and 2008 were analysed regarding preoperative characteristics, short- and long-term survival, valve-related complications and echocardiographic findings.
RESULTS: The Medtronic Mosaic was implanted in 163 patients and the Carpentier-Edwards Magna in 295 patients. The sizes of implanted valves were 22.4 ± 1.5 mm for the Mosaic and 21.8 ± 1.8 mm for the Magna (P = 0.001). The long-term survival rate was 76 and 56% after 5 and 10 years for the Medtronic Mosaic, which was comparable with the Carpentier-Edwards Magna (77 and 57%; P = 0.92). Overall long-term survival was comparable with an age- and sex-matched Austrian general population for both groups. Valve-related adverse events were similar between groups. The postoperative mean transvalvular gradient was significantly increased in the Mosaic group (24 ± 9 mmHg vs 17 ± 7 mmHg; P < 0.001).
CONCLUSIONS: Both types of aortic bioprostheses offer excellent results after isolated aortic valve replacement. Despite relevant differences in gradients, long-term survival was comparable with the expected normal survival for both bioprostheses. Patients with a porcine heart valve had a higher postoperative transvalvular gradient.
Background: In Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences.
Methods/Design: Data on tumour and migration status will be collected for 1,200 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants.
Discussion: An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants.
Trial registration: German Clinical Trials Register DRKS00005056.
The cattle egret (Bubulcus ibis) has recently colonized Brazil. This process offers an excellent opportunity for the study of colonization and dispersal patterns across extensive areas by non-native birds. The aims of the present investigation were a) to determine the genetic diversity of the cattle egret in Brazil and Africa, b) evaluate genetic differentiation between populations in different regions of Brazil and Africa, and c) detect genetic signs of demographic expansion in these two areas. Mitochondrial DNA (mtDNA) Control Region (CR) sequences were obtained from 112 cattle egrets in four Brazilian and four African (Kenya, Ghana and Nigeria) populations. Genetic diversity (H, h, θ) and population structure (AMOVA, Fst) were assessed and the populations were tested for signs of recent demographic expansion. A total of 35 haplotypes were found: 22 exclusive to Africa, 10 exclusive to Brazil and three shared by both samples. The degree of genetic diversity, determined by mtDNA analysis, was similar between Brazil and Africa, demonstrating that the successful colonization of the non-native area occurred with no significant loss of diversity. The pairwise Fst values among the Brazilian and African populations were all significantly different. The population in southern Brazilian exhibited the lowest degree of differentiation with respect to the African population, followed by the southeastern and northeastern populations of the country. The genetic differentiation data suggest that the colonization of Brazil by the cattle egret began in the southern region and expanded to the southeastern and northeastern regions of the country. This genetic differentiation pattern is in accordance with the higher number of cattle per grazing area in southern Brazil, which may have favored the onset of the successful establishment of the species. The findings indicate that mtDNA genetic diversity was retained during the colonization process and colonization began in the southern region of the country. Moreover, signs of demographic expansion were detected in the African sample.
The potential for using revenues from extractive resources for inclusive growth in Africa is tremendous. However, the realisation of the transformative role that extractive industries could play in sustainable development has been elusive in most African countries. Extractive industries in most of these countries are plagued with numerous conflicts, some with serious casualties over the control, distribution, management and utilisation of the resources and revenues from extractive operations. Collaborative Governance in Extractive Industries in Africa presents the critical challenges facing extractive industries from different contexts, countries, sectors and settings. It features chapters with diverse angle of interest and analytical tools applied in examining the critical issues related particularly to mining and petroleum development in Africa. The contributors to this book have extensive academic and professional experience in policy research in the mining, oil and gas sectors in Africa and other regions. The book addresses the current gap in knowledge about appropriate governance regimes that could create the forum where the divergent interests and positions of various stakeholders of extractive resources and revenues could be handled - without any of them resorting to deadly conflicts. It presents the functionality of collaborative governance in enhancing for example, transparency, accountability, and equitable distribution of extractive revenues. Governance practitioners, policy- and decision makers could use the structures, components and procedures discussed in this book to develop training manuals, governance criteria and indicators for measuring and managing collaborative governance regime at the national and local levels. They will also find useful information about some of the critical elements that should guide the strategic implementation of the collaborative process.
Pocket gopher burrows were sampled from 22 counties within Arkansas to determine the associated faunal composition of three major families of Coleoptera (Histeridae, Leiodidae and Scarabaeidae) commonly associated with pocket gopher burrows. We collected eight species of Histeridae, four species of Leiodidae and eight species of Scarabaeidae from the burrows of Geomys breviceps Baird. Three of the Histeridae were new state records, Geomysaprinus goffi Ross, G. rugosifrons (Fall) and Margarinotus felipae (Lewis). All of the Leiodidae were new state records and one Scarabaeidae was a new state record, Dellacasiellus concavus (Say). The most commonly collected scarab beetles were Cryptoscatomaseter haldemani (Horn) and Geomyphilus insolitus (Brown). The most commonly collected hister beetle was Onthophilus kirni Ross. The Leiodidae were infrequently captured.
Coherent photo-production of sons in ultra-peripheral Pb-Pb collisions at the LHC measured by ALICE
(2014)
We present the differential cross section for coherent ρ0 photo-production at mid-rapidity (−0.5 < y < 0.5) measured by the ALICE experiment in Pb-Pb collisions at √sNN = 2.76 TeV at the LHC, as well as the total ρ0 cross section obtained by modelbased extrapolation to all rapidities. These cross sections are compared to various model predictions, as well as to earlier measurements at RHIC. In addition, we present results on nuclear breakup in coincidence with coherent ρ0 photo-production.
Cognitive flexibility and cognitive stability : neural and behavioral correlates in men and mice
(2014)
The ability to flexibly adjust behavior according to a changing environment is crucial to ensure a species' survival. However, the successful pursuit of goals also requires the stable maintenance of behavior in the face of potential distractors. Thus, cognitive flexibility and cognitive stability are important processes for the cognitive control of behavior. There is a large body of behavioral and neuroimaging research concerning cognitive control in general, but also specifically on cognitive flexibility and cognitive stability, albeit most often assessed in separate task paradigms. Nevertheless, whether cognitive flexibility and cognitive stability depend upon separate or shared neuronal bases is still a matter of debate. Complementing empirical research, computational models have become an important strategy in neuroscientific research, as they have the potential of providing mechanistic explanations of empirical observations, for example by allowing for the direct manipulation of molecular parameters in simulated neural networks. The computational model underlying the so-called Dual-State Theory contains specific hypotheses with respect to cognitive flexibility and cognitive stability. The neural networks simulated by this model exhibit multiple stable firing states, i.e., the neural network can maintain a high firing state also without continuing external input due to a network architecture consisting of recurrently connected neurons. Transitions between such network states, also called attractor states, can be induced by external input, and represent working memory contents or active task rules. Simulations showed that the stability of these attractor states, and thus of task rule representations, depend on the dopamine state of the system and can consequently vary between persons. The Dual-State Theory predicts an antagonistic relationship between cognitive flexibility and cognitive stability, as robust attractor states would facilitate the inhibition of distractors, but impair efficient task switching, while rather unstable attractor states would promote efficient transitions between representations but would also come at the cost of increased distractibility.
Based on the Dual-State Theory, a task paradigm was designed allowing for the simultaneous assessment of cognitive flexibility, in the sense of rule-based task switching, and cognitive stability, in the sense of inhibiting irrelevant distractors. Furthermore, a behavioral measure was developed to assess the individual attractor state stability, named spontaneous switching rate (SSR). In the first study of this work, this paradigm was tested in a sample of healthy human subjects using functional magnetic resonance imaging (fMRI). An overlapping fronto-parietal network was activated for both cognitive flexibility and cognitive stability. Furthermore, behavioral as well as neuroimaging results are in favor of an antagonistic relationship between cognitive flexibility and cognitive stability. A specific prefrontal region, the inferior frontal junction (IFJ), was implied to potentially contain the relevant neural networks mediating the transitions between attractor states, i.e., task rule representations, as its activity was modulated by the SSR such that persons with rather unstable attractor states activated it less during task switching while showing better performance. Most importantly, functional connectivity of the IFJ was antagonistically modulated by the SSR: more flexible persons connected it less to another prefrontal area during task switching, while showing higher functional connectivity during distractor inhibition.
In a second study, a larger human sample was assessed and further hypotheses derived from the Dual-State Theory on variability of neural processing were tested: we hypothesized that persons with high brain signal variability should have less stable network states and thus benefit on tasks requiring cognitive flexibility but suffer from it when the task requires a higher degree of cognitive stability. Furthermore, recent fMRI-research on brain signal variability revealed beneficial effects of higher brain signal variability on cognitive performance in general. Using a novel customized analysis pipeline to measure trial-to-trial fMRI-signal variability, we indeed found differential effects of brain signal variability: higher levels of brain signal variability were found to be beneficial for effectiveness, i.e., performance in terms of error rates, for both cognitive flexibility and stability. However, brain signal variability impaired the efficiency in terms of response times of inhibiting distractors, i.e., cognitive stability.
Due to further predictions of the Dual-State Theory concerning schizophrenia and the dopaminergic system, it was considered valuable to pursue a translational approach and thus allowing for the employment of animal models of psychiatric diseases. Consequently, in a first step the human paradigm was translated for a murine population using an innovative touchscreen approach. Results showed analogous behavioral effects in wildtype mice as before in healthy humans: the antagonistic relation between cognitive flexibility and cognitive stability was replicated and also for mice, a behavioral measure for the individual attractor stability was established and validated, named the individual spontaneous switching score.
To conclude, we established a novel paradigm assessing both cognitive flexibility and stability simultaneously showing an antagonistic relationship between these two cognitive functions on the behavioral level in two different species, which supports predictions from the Dual-State Theory. This was further underlined by evidence on the activation, functional connectivity and signal variability level in the human brain.
Background: Recent studies have suggested substantial fluctuations of cognitive performance in adults both across and within days, but very little is known about such fluctuations in children. Children's sleep behavior might have an important influence on their daily cognitive resources, but so far this has not been investigated in terms of naturally occurring within-person variations in children's everyday lives.
Methods: In an ambulatory assessment study, 110 elementary school children (8–11 years old) completed sleep items and working memory tasks on smartphones several times per day in school and at home for 4 weeks. Parents provided general information about the children and their sleep habits.
Results: We identified substantial fluctuations in the children's daily cognitive performance, self-reported nightly sleep quality, time in bed, and daytime tiredness. All three facets were predictive of performance fluctuations in children's school and daily life. Sleep quality and time in bed were predictive of performance in the morning, and afternoon performance was related to current tiredness. The children with a lower average performance level showed a higher within-person coupling between morning performance and sleep quality.
Conclusions: Our findings contribute important insights regarding a potential source of performance fluctuations in children. The effect of varying cognitive resources should be investigated further because it might impact children's daily social, emotional, and learning-related functioning. Theories about children's cognitive and educational development should consider fluctuations on micro-longitudinal scales (e.g., day-to-day) to identify possible mechanisms behind long-term changes.
In his major theoretical work on experimentation, "Towards a History of Epistemic Things" (1997), Hans-Jörg Rheinberger writes: 'If experimental systems have a life of their own, precisely what kind of life they have remains to be determined.' Rheinberger is alluding to the slogan Ian Hacking gave to the post-Kuhnian 'practical turn' in the history and epistemology of science.
The work presented in this thesis is devoted to two classes of mathematical population genetics models, namely the Kingman-coalescent and the Beta-coalescents. Chapters 2, 3 and 4 of the thesis include results concerned with the first model, whereas Chapter 5 presents contributions to the second class of models.
During this study clumped isotope analysis of carbonates was established at the Goethe University of Frankfurt, Germany. Therefore, preparation protocols and analytical parameters were elaborated to obtain precise and accurate Δ47 data. Briefly, analyte CO2 was cleaned cryogenically using glass extraction lines to remove traces of water that enable re-equilibration of C–O bonds in the gases. Furthermore, analyte CO2 was passed through a gas chromatograph (GC) to clean it from contaminants that produce isobaric interferences with m/z 47. Initially, phosphoric acid digestions of carbonates was conducted at 25 °C in McCrea-type reaction vessels. Afterwards samples were reacted at 90 °C using a common acid bath. Mass spectrometric analyses were performed using a MAT 253 equipped with a dual inlet system. Δ47 values were directly projected to the absolute scale using CO2 gases equilibrated at distinct temperatures.
In cooperation with Stefano Bernasconi and his research group at ETH Zurich we studied the non-linearity that occurs for the measurement of m/z 47. This effect results from secondary electrons created by the m/z 44 beam. These electrons cause a negative background on the m/z 47 collector. A correction procedure was proposed that relies on the determination of the negative background on the m/z 47 Faraday cup. This approach might reduce time-consuming analyses of heated gases which were used so far to account for the observed non-linearity. However, the suggested correction of the negative background on the m/z 47 cup is only applicable if the slit width of the m/z 44 beam is significantly wider than that of the m/z 47 beam.
This thesis, furthermore, presents a comparison of the different phosphoric acid digestion techniques which are commonly used for carbonate clumped isotope analysis. For calcitic and aragonitic material digested at 25 °C in McCrea-type vessels we observed that the sample size has an effect on Δ47 data: higher mean Δ47 values and a larger scatter of data were received for samples <7 mg than for larger aliquots. For carbonate samples digested at 90 °C in a common acid bath no sample size effect was determined. We assume that secondary re-equilibration of CO2 with water preferentially occurs at 25 °C producing the observed differences. However, a sample size effect can be avoided if reaction temperature is increased to 90 °C.
In order to make carbonate Δ47 data obtained from acid digestions at 90 °C comparable to Δ47 data received from reactions at 25 °C the difference of the acid fractionation factores (Δ47*25-90) between both temperatures has to be known. For the determination of the Δ47*25-90 value we have considered Δ47 data made at 25 °C from samples >7 mg only. For calicte and aragonite we obtained differences in fractionation factores of 0.075‰ and 0.066‰, respectively. These Δ47*25-90 values are coincident with the theoretical prediction of 0.069‰ proposed for calcite (Guo et al., 2009).
Moreover, this dissertation comprises a calibration study of the clumped isotope thermometer based on various natural calcites that grew between 9 and 38 °C. The samples include a brachiopod shell, a bivalve shell, an eggshell of an ostrich and foraminifera tests which formed from distinct biomineralizing processes. Furthermore we included an authigenic carbonate crystallized from biological-induced precipitation. The following linear relationship between 1/T2 and Δ47 was determined (with Δ47 in ‰ and T in K):
Δ47 = 0.0327 (± 0.0026) x 106 / T2 + 0.3030 (± 0.0308) (R2 = 0.9915)
This equation differs from the pioneering Ghosh et al. (2006a) calibration. However, our regression line is statistically indistinguishable from that of Henkes et al. (2013) which is based on aragonitic mollusks and calcitic brachiopod shells. Both studies have in common that calibration data were, at first, directly referenced to the absolute scale. In addition, both datasets rely on similar digestion techniques. Furthermore, the two calibrations are conform with the theoretical prediction of Guo et al. (2009).
The calcite calibration of the clumped isotope paleothermometer received in this study was applied to Δ47 data measured for Silurian brachiopods shells from Gotland/Sweden. Prior to isotopic analysis the fossils were intensively investigated for their preservation state (CL, SEM, trace elements). The lowest T(Δ47) values of ca. 28 to 33 °C were estimated from ultrastructurally well-preserved regions of some shells. For these samples also the lowest δ18Ow values of Silurian seawater were determined. These estimates of ca. −1‰ confirm the assumption that the δ18O value of the Silurian ocean was buffered to (0 ± 1)‰.
Nevertheless, most studied shells were characterized by a patchwork of pristine and altered shell portions resulting in elevated T(Δ47) values which plot mostly between 40 and 60 °C. Our results indicate that the clumped isotopic composition of the shells were altered at low water-rock ratios, not affecting the δ18O values. Δ47 and δ18O data of associated diagenetic phases (sparitic and micritic phases of the inner fillings of the fossils) provide evidence that the sparitic cements grew during several diagenetic events which occurred at different temperatures in fluid-buffered systems. We, furthermore, conclude that the micritic phases lithified at a very early diagenetic stage with the δ18O values being most probably close to a Silurian seawater composition
Background: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).
Methods: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31).
Results: Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy).We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3- and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3- and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years.
Conclusion: Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.
We demonstrate high-density labelling of cellular DNA and RNA using click chemistry and perform confocal and super-resolution microscopy. We visualize the crescent and ring-like structure of densely packed RNA in nucleoli. We further demonstrate click chemistry with unnatural amino acids for super-resolution imaging of outer-membrane proteins of E. coli.
Chronic non-communicable diseases (NCDs) such as hypertension, stroke, diabetes and cancers, are major causes of disability and death in Ghana. NCDs are not only public health problems. They are also developmental problems, because the rising prevalence of long-term chronic conditions has major social and financial implications for affected individuals, families, healthcare providers and the government. This University of Ghana Readers volume from the Regional Institute for Population Studies presents social and medical science research on Ghana's NCD burden. The body of multidisciplinary research spans the last fifty years and offers important insights on NCD prevalence and experience as well as cultural, health systems and policy responses. This volume will be an essential resource for researchers and students in the health sciences, healthcare providers, health policymakers, and lay individuals with an interest in Ghana's contemporary public health challenges.
Chronic ethanol abuse is known to increase susceptibility to infections after injury, in part, by modification of macrophage function. Several intracellular signalling mechanisms are involved in the initiation of inflammatory responses, including the nuclear factor-κB (NF-κB) pathway. In this study, we investigated the systemic and hepatic effect of chronic ethanol feeding on in vivo activation of NF-κB in NF-κB(EGFP) reporter gene mice. Specifically, the study focused on Kupffer cell proinflammatory cytokines IL-6 and TNF-α and activation of NF-κB after chronic ethanol feeding followed by in vitro stimulation with lipopolysaccharide (LPS). We found that chronic ethanol upregulated NF-κB activation and increased hepatic and systemic proinflammatory cytokine levels. Similarly, LPS-stimulated IL-1 β release from whole blood was significantly enhanced in ethanol-fed mice. However, LPS significantly increased IL-6 and TNF-α levels. These results demonstrate that chronic ethanol feeding can improve the responsiveness of macrophage LPS-stimulated IL-6 and TNF-α production and indicate that this effect may result from ethanol-induced alterations in intracellular signalling through NF-κB. Furthermore, LPS and TNF-α stimulated the gene expression of different inflammatory mediators, in part, in a NF-κB-dependent manner.
With its broad spectrum of cults and coexisting religions Graeco-Roman antiquity seems, at first glance, to be the embodiment of religious freedom. Yet, a closer analysis shows that a concept of tolerance or the idea of religious freedom did not exist. Political institutions could easily suppress religious practices that were regarded as offensive. Fighting against the oppression of Christians appears to have increased under the influence of oecumenical paganism during the reign of the Severans. In this time, the Christian thinkerTertullian discovered and articulated the concept of religious freedom. However, he did not do so emphatically and the concept was not very successful in antiquity. With the Christianization of the Roman Empire it disappeared soon, although its rediscovery in later epochs contributed heavily to the formation of the European norm of religious freedom.
In this thesis, a novel 257 kHz chopper device was numerically developed, technically designed and experimentally commissioned; a 4-solenoid, low-energy ion beam transport line was numerically investigated, installed and experimentally commissioned; and a novel massless beam-separation system was numerically developed.
The chopper combines a pulsed electric field with a static magnetic field in an ExB or Wien-filter type field configuration. Chopped beam pulses with a 257 kHz repetition rate and rise times of 110 ns were experimentally achieved using a 14 keV helium beam.
Due to the achieved results, the complete LEBT line for the future Frankfurt Neutron Source FRANZ is ready to deliver a dc or a pulsed beam. At the same time, the LEBT section represents an attractive test stand for the study of low-energy ion beams. It combines magnetic lenses, which allow space-charge compensated beam transport, and a chopper system capable of producing short beam pulses in the hundred nanosecond range. Since these beam pulses are transported onwards, their longitudinal and transverse properties can be analyzed. The pulse duration and time of flight are well below the rise time for the space-charge compensation through residual gas ionization. This opens the possibility for dedicated investigations of the transport of short, low-energy beam pulses including longitudinal and transverse space-charge effects and of relevant issues like the dynamics of space-charge compensation and electron effects in short pulses.
Background: High-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) is a treatment option for pediatric patients with relapsed nephroblastoma. We present long term results of 9 patients treated between 1993 and 2013 at our center.
Procedure: Reinduction therapy was carried out according to GPOH and SIOP recommendations. The conditioning regimen consisted of carboplatin (1 200 mg/m²), etoposide (800 mg/m² or 40 mg/kg) and melphalan (180 mg/m²). Purging of the grafts with immunomagnetic CD34 positive selection was performed in 5 patients.
Results: 8 of 9 Patients (90%) are alive without evidence of disease after a median follow-up of 8.5 years. Leukocyte engraftment occurred after a median of 10 days (range 8-12). Median numbers of 667/µl CD3+, 329/µl CD4+, 369/µl CD8+T cells and 949/µl B cells were reached after 180 days. No negative impact of CD34 selection was observed. No transplantation-related death occurred. Acute toxicity comprised mucositis III°-IV° in all and veno-occlusive disease in one patient. Long term effects probably related to treatment occurred in 3/7 evaluable patients and comprised hearing impairment, reduced renal phosphate reabsorption, mild creatinine elevation and hypothyroidism (n=1, each).
Conclusion: Thus, in our experience HDC with ASCR is an effective treatment of recurrent or refractory nephroblastoma with acceptable side effects. However, a randomized trial proving its efficiency with a high level of evidence is needed.