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Ethyl acetate is an important organic solvent and currently produced from fossil carbon resources. Microbial synthesis of this ester from sugar-rich waste could be an interesting alternative. Therefore, synthesis of ethyl acetate by Kluyveromyces marxinanus DSM 5422 from delactosed whey permeate (DWP) was studied in an aerated stirred bioreactor at 40 °C. DWP is mainly composed of residual lactose and minerals. The minerals inhibited yeast growth, as witnessed by an increased lag period, a reduced growth rate, and an extended process duration. All experiments were therefore carried out with diluted DWP. In a series of batch experiments, the pH of iron-deficient DWP medium varied between 4.8 and 5.9. The pH of the cultivation medium significantly influenced cell growth and product syntheses, with the highest ethyl acetate yield of 0.347 g g–1 and lowest by-product formation achieved at pH 5.1. It is likely that this effect is due to pH-dependent iron chelation, which affects the iron bioavailability and the intracellular iron content, thus affecting growth and metabolite synthesis. The viability of yeast cells was always high despite the harsh conditions in DWP medium, which enabled extended usage of the biomass in repeated-batch and fed-batch cultivations. These two culture techniques increased the volume of DWP processed per time by 32 and 84% for the repeated-batch and the fed-batch cultivation, respectively, without a drop of the ester yield. Key points: • Delactosed whey permeate was converted to ethyl acetate with a high rate and yield. • The formation of ethyl acetate in DWP medium at iron limitation is pH-dependent. • Highly active yeasts from batch processes enabled extension as fed and repeated batch. [ABSTRACT FROM AUTHOR]

Carbon nanofiber nonwovens (CFN) are powerful electrode materials with exceptional performance in energy storage devices, such as batteries and supercapacitors. Small fiber‐diameters together with hierarchical porosity endow CFN‐electrode materials with large surface areas and high electrical capacitance. Porosity of the fiber surface is often realized by corrosive activation methods such as wet‐etching or using oxidative gases at elevated temperatures. In this study, we present a chemical‐free, environmental‐friendly, and easily controllable surface activation method using an atmospheric pressure plasma‐jet. We investigate the best instant for activation along the process chain and show that the surface area of nanofiber nonwovens can be tailored by adjusting the plasma exposure‐dose. Plasma‐activated CFNs show an almost 20‐fold increase in capacitance (CspPJ = 10.1 F/g) in an electrochemical supercapacitor setup compared to nonactivated CFN (CspnoPJ = 0.55 F/g). [ABSTRACT FROM AUTHOR]

This article takes up the sport policy and sports science debate on the recognition of competitive computer and video games—so-called eSport—as sport and pursues the goal of differentiating sport and eSport on the basis of systems theory considerations and reflecting on the functions and consequences of recognizing eSport as sport. It begins by addressing the questions of how sport can be observed at all with the help of theories and which epistemological position underlies the systems theory approach. This is followed by a consideration of sport in terms of systems theory as a social functional system and by reflection on forms of structural coupling between the sport system and other social functional systems. In light of these theoretical considerations, the connectivity of eSport to the sport system as well as the functions and consequences of such an integration for structural couplings between the sport system and the systems of health, education, the economy, mass media, and politics are analyzed. The article concludes with an outline of perspectives for future scientific observation of sport and eSport. [ABSTRACT FROM AUTHOR]

Stereolithography is a lithography‐based additive manufacturing technology, in which liquid photoreactive resins are solidified by ultraviolet or visible light in a layer‐wise approach. Additive manufacturing technologies are used in personalized medicine, for example, for the production of otoplastics, dentistry, prosthetics but also in tissue engineering. Here, biocompatibility of the produced parts is mandatory. In this work a chemistry is further investigated which is rarely used in stereolithography—thiol‐ene click chemistry. Polymers made by thiol‐ene chemistry have various promising optical, mechanical, biological, and chemical properties for medical applications. In this work new photo resins based on thiol‐ene click chemistry are developed and the resulting polymers are analyzed to determine the suitability of these materials as thiol‐ene photo resins. Furthermore, the influence of crosslinker functionality in systems with equal degree of crosslinking and the concept of prepolymerization of two bifunctional components for thiol‐ene photo resins will be presented in this study. [ABSTRACT FROM AUTHOR]

The carbonization of polyacrylonitrile (PAN) by direct laser writing to produce microsupercapacitors directly on‐chip is reported. The process is demonstrated by producing interdigitated carbon finger electrodes directly on a printed circuit board (PCB), which is then employed to characterize the supercapacitor electrodes. By varying the laser power, the process can be tuned from carbonization to material ablation. This allows to not only convert pristine PAN films into carbon electrodes, but also to pattern and cut away non‐carbonized material to produce completely freestanding carbon electrodes. While the carbon electrodes adhere well to the printed circuit board, non‐carbonized PAN is peeled off the substrate. Specific capacities as high as 260 µF cm⁻2 are achieved in a supercapacitor with 16 fingers. [ABSTRACT FROM AUTHOR]

Ethyl acetate is currently produced from fossil carbon resources. This ester could also be microbially synthesized from sugar‐rich wastes of the food industry. Wild‐type strains with GRAS status are preferred for such applications. Production of ethyl acetate by wild‐type yeasts has been repeatedly reported, but comparative studies with several strains at various induction modes are largely missing. Here, synthesis of ethyl acetate by three yeasts with GRAS status, Kluyveromyces marxianus DSM 5422, Cyberlindnera jadinii DSM 2361 and Wickerhamomyces anomalus DSM 6766, was studied under identical and well‐defined conditions in an aerated bioreactor, by inducing the ester synthesis via iron or oxygen limitation. Balancing the ester synthesis was based on measured concentrations of ethyl acetate in the exhaust gas, delivering masses of synthesized ester and synthesis rates in a high temporal resolution. All tested yeasts synthesized ethyl acetate under these conditions, but the intensity varied with the strain and induction mode. The highest yields were achieved under iron limitation with K. marxianus (0.182 g g–1) and under oxygen limitation with W. anomalus (0.053 g g–1). Iron limitation proved to be the better inducer for ester synthesis while oxygen limitation favored ethanol formation. K. marxianus DSM 5422 was the most potent producer of ethyl acetate exhibiting the highest biomass‐specific synthesis rate of 0.5 g g–1h–1 under moderate iron limitation. [ABSTRACT FROM AUTHOR]

Microbial consortia can be used to catalyze complex biotransformations. Tools to control the behavior of these consortia in a technical environment are currently lacking. In the present study, a synthetic biology approach was used to build a model consortium of two Saccharomyces cerevisiae strains where growth and expression of the fluorescent marker protein EGFP by the receiver strain is controlled by the concentration of α‐factor pheromone, which is produced by the emitter strain. We have developed a quantitative experimental and theoretical framework to describe population dynamics in the model consortium. We measured biomass growth and metabolite production in controlled bioreactor experiments, and used flow cytometry to monitor changes of the subpopulations and protein expression under different cultivation conditions. This dataset was used to parameterize a segregated mathematical model, which took into account fundamental growth processes, pheromone‐induced growth arrest and EGFP production, as well as pheromone desensitization after extended exposure. The model was able to predict the growth dynamics of single‐strain cultures and the consortium quantitatively and provides a basis for using this approach in actual biotransformations. [ABSTRACT FROM AUTHOR]

Abstract This paper describes a systematic analysis of liquid-phase infiltrated molybdenum (Mo) copper (Cu) composites, deformed by various levels, and elucidates the impact of (i) the copper content, and (ii) the rolling reduction on the evolution of the material properties. The rolling-induced change of the thermo-physical properties can be traced back to (ii-a) the evolution of the geometry (viz. the flattening of the molybdenum and the copper phase during rolling) and (ii-b) the evolution of the crystallographic texture. Four infiltrated ingots with a copper content of 23, 39, 48 and 54 vol % were produced. Each ingot was gradually rolled down to a final degree of deformation of 0.5, 1, 1.5, 2 and 2.38, which corresponds to a rolling reduction of 39%, 63%, 78%, 86% and 90%. In summary, four material compositions (23, 39, 48 and 54 vol % Cu) in six conditions (as-infiltrated and five as-rolled conditions) were examined. The evolution of the microstructure is correlated with the evolution of the mechanical and thermo-physical properties such as hardness (HV2), Young's modulus, E , electrical conductivity, σ , thermal conductivity, k , and the coefficient of thermal expansion, α (CTE, in the range of 350 °C (623 K) – 750 °C (1023 K)). It was found, that the same thermal conductivity can be gained by using either a low copper-content composite that features a low degree of deformation or by using a high copper-content composite that was rolled down to a high degree of deformation. Furthermore, we were able to demonstrate that peculiarities in the CTE-over-T curves can be traced back to the plastic deformation of the copper phase, which is affected by rolling-induced residual stresses and recrystallisation processes during the CTE measurement. Graphical abstract Image 1 Highlights • Four liquid-phase infiltrated MoCu ingots were produced (Cu: 23, 39, 48, 54 vol %). • The ingots were rolled down to five degrees of deformation (0.5, 1, 1.5, 2 and 2.38). • Evolution of the thermal conductivity and expansion behaviour were analysed. • Material properties = f (copper content, degree of deformation (geometry, texture)). • The peculiar expansion behaviour is caused by the plastic deformation of the Cu phase. [ABSTRACT FROM AUTHOR]

The accurate determination of protein concentration is an important though non-trivial task during the development of a biopharmaceutical. The fundamental prerequisite for this is the availability of an accurate extinction coefficient. Common approaches for the determination of an extinction coefficient for a given protein are either based on the theoretical prediction utilizing the amino acid sequence or the photometric determination combined with a measurement of absolute protein concentration. Here, we report on an improved SV-AUC based method utilizing an analytical ultracentrifuge equipped with absorbance and Rayleigh interference optics. Global fitting of datasets helped to overcome some of the obstacles encountered with the traditional method employing synthetic boundary cells. Careful calculation of dn/dc values taking glycosylation and solvent composition into account allowed the determination of the extinction coefficients of monoclonal antibodies and an Fc-fusion protein under native as well as under denaturing conditions. An intra-assay precision of 0.9% and an accuracy of 1.8% compared to the theoretical value was achieved for monoclonal antibodies. Due to the large number of data points of a single dataset, no meaningful difference between the ProteomeLab XL-I and the new Optima AUC platform could be observed. Thus, the AUC-based approach offers a precise, convenient and versatile alternative to conventional methods like total amino acid analysis (AAA). [ABSTRACT FROM AUTHOR]

Background Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types. Tumors inhibit antitumor response by modulating the immune checkpoint proteins programmed death ligand 1 (PD-L1) and its cognate receptor PD1. The expression of these genes has been implicated in evasion of immune response and resistance to targeted therapies. Methods Blood samples were collected from gastric (GC), colorectal (CRC), lung (NSCLC), breast (BC), prostate cancer (PC) patients, and a healthy control group. ctRNA was purified from fractionated plasma, and following reverse transcription, levels of PD-L1 expression were analyzed using qPCR. Results PD-L1 expression was detected in the plasma ctRNA of all cancer types at varying frequencies but no PD-L1 mRNA was detected in cancer-free individuals. The frequencies of PD-L1 expression were significantly different among the various cancer types but the median relative PD-L1 expression values were not significantly different. In 12 cases where plasma and tumor tissue were available from the same patients, there was a high degree of concordance between expression of PD-L1 protein in tumor tissues and PD-L1 gene expression in plasma, and both methods were equally predictive of response to nivolumab. Conclusions PD-L1 mRNA can be detected and quantitated in ctRNA of cancer patients. These results pave the way for further studies aimed at determining whether monitoring the levels of PD-L1 mRNA in blood can identify patients who are most likely to benefit from the conventional treatment. [ABSTRACT FROM AUTHOR]

Background Extensive clinical investigations are mandatory to evaluate the safety and reactogenicity of vaccines. The recording of common adverse events like injection site soreness or general discomfort derives from individual subjective perceptions. Thermal imaging at the injection site possibly provides a non-subjective and a non-invasive approach to supplement this evaluation. Results A protocol for quantified injection-site infrared imaging included 86 participants during a flu vaccine campaign, 40% of whom had a thermal reaction of 1 °C; 25–30% had no thermal response. There was little subjective pain reporting and no clinical correlations were observed except with post-vaccination erythema. Higher responses were linked with advanced age and multiple previous vaccinations. Conclusion Evan if influenza vaccine was only moderately reactogenic, a thermal response was detectable in about 70% of vaccinees, though no relationship to reactogenicity was seen. Infrared imaging might however be a prospective tool for individual studies of vaccine-induced vascular responses. [ABSTRACT FROM AUTHOR]

This paper attempts to elucidate fundamental mechanisms of the brittle-to-ductile transition (BDT) in textured, pre-deformed, polycrystalline body-centred cubic metals. For this purpose, five tungsten sheets have been rolled out from one and the same sintered ingot representing degrees of deformation of 1.8, 2.5, 3.0, 3.4, and 4.1 (logarithmic notation). Electron backscatter diffraction measurements display the evolution of the microstructure with increasing degree of deformation. The mean grain size of the five sheets in the normal direction is 1.1, 0.59, 0.48, 0.37, and 0.3 μm. Toughness tests based on the K-concept have been performed and the brittle-to-ductile transition temperature of the five sheets has been determined. The crack system used was the L-T crack system. The results have been benchmarked against the BDT temperature of a sintered ingot. The results show a decrease of the BDT temperature with increasing degree of deformation starting from 600 °C (873 K) for the sintered ingot via 115 °C (388 K), 85 °C (358 K), 75 °C (348 K), 60 °C (333K) down to − 65 °C (208 K) for the most heavily deformed tungsten plate. The results are discussed against the background of (i) rolling induced lattice defects such as (i-a) vacancies, (i-b) dislocations (i-c) grain boundaries, (ii) crystallographic texture, (iii) the state of stress, (iv) impurities, (v) sinter pores, and (vi) the geometrical arrangement of areas with low and high fracture toughness. The authors postulate that the BDT is still controlled by the kink-pair nucleation process of a screw dislocation and that the BDT temperature scales with the spacing of dislocation sources (e.g. grain boundary ledges, low angle boundaries, debris loops) along the crack front. [ABSTRACT FROM AUTHOR]

The article offers a lexical study of the lemma ›oraculum‹ based on selected examples in Latin Christian literature up to Augustine. It examines to what extent the pagan spectrum of meaning is taken up and how far the term is processed and transformed in a Christian context. A continuous line in Christian literature is the critical, apologeticprotreptic, confrontation with pagan oracles. Approaches to the concept of oracle can be found in the area of dreams (Tertullian) and in the attempt to take pagan oracle sayings as witnesses of Christian truths (eg. Lactantius). The decisive step towards Christian transformation is the application of the term to the biblical scriptures. This prevails shortly after Constantine (Firmicus Maternus) and reaches a climax (esp. in Ambrose) when Christianity was established as the state religion and pagan cults were pushed back and finally prohibited. Speaking of the oracula of Holy Scripture is based on the traditional meaning of oraculum as a ›divine saying‹ (in oral or written form). It is applied to the Old Testament, especially to the ›prophets‹ following the scheme of announcement and fulfilment, but is also seen in the New Testament. Further connections to the pagan tradition are the high authority of the divine word, its darkness and ambiguity, that compels interpretation of an expert, as well as the scheme of question and answer. As in pagan usage both divinely inspired individuals and the human spirit itself, can also be classified as ›oracles‹. In contrast to the pagan oracle, however, in Christian ›oracles‹ it is the one God, thus the infallible truth that speaks. While pagan oracles promise (deceptively) answers to everyday earthly worries, God's words have existential meaning. Observing these truths is decisive for the eschatological fate. [ABSTRACT FROM AUTHOR]

Zeolites are microporous materials driving industrial scale adsorption, ion exchange, and catalytic processes. Their water content dramatically impacts their properties, but its quantification with Karl Fisher titration or thermal gravimetric analysis is problematic. When standard addition of water is combined with 1H magic angle spinning (MAS) NMR detection, absolute quantification of water in microporous materials becomes possible. The method was demonstrated on five different, commercially available zeolites. [ABSTRACT FROM AUTHOR]

The quality of Web services is an important factor for businesses that advertise or sell their services in the Internet. Failures can directly lead to fewer costumers or security problems. However, the testing of complex Web services that are organized in service-oriented architectures is a difficult and complex problem. Model-based testing (MBT) is one solution to deal with the complexity of the testing. With MBT, testers do not define the tests directly, but rather specify the structure and behavior of the System Under Test using models. Then, a test strategy is used to derive test cases automatically from the models. However, MBT yields a large amount of tests for complex systems which require lots of resources for their execution, thereby limiting its potential. Within this article, we discuss how cloud computing can be used to provide the required resources for scaling up test campaigns with large amounts of test cases derived using MBT. [ABSTRACT FROM AUTHOR]

The Swiss Heart Foundation has launched a web-based platform with information on cardiovascular risk factors including a risk calculator. Absolute risk and he art age are calculated based on age, gender, preexisting illnesses, systolic blood pressure, smoking and cholesterol. In addition, the number of cigarettes smoked, energy expenditure with physical activity as well as nutritional habits and stress are assessed and a relative risk compared to a person with optimal life style habits is calculated according to large studies. Results are depicted in colored figures and a personal rep ort. Users can set goals, define changes in their life style, and improvements are graphically shown. Registered users can save their individual data in a secure form at, construct a longitudinal course and have reminders sent to them by e-mail. [ABSTRACT FROM AUTHOR]

Merging recent empirical findings into an overinvestment framework this paper describes a recursive process of monetary policy interactions between industrialised and emerging market economies that provides an explanation of what may have led to the current global low interest rate environment. Based on the overinvestment framework we show that in the prevailing asymmetric world monetary system, monetary policies of industrialised countries can fuel credit booms in emerging markets. We argue that the absorption of inflationary pressure by emerging markets during boom periods and the fear of feedback effects of crises in emerging markets encourage delayed monetary tightening in industrialised countries. [ABSTRACT FROM AUTHOR]

The goals of cardiac rehabilitation are (re-)conditioning and secondary prevention in patients with heart disease or an elevated cardiovascular risk profile. Rehabilitation is based on motivation through education, on adapted physical activity, instruction of relaxation techniques, psychological support and optimized medication. It is performed preferably in groups either in outpatient or inpatient settings. The Swiss working group on cardiac rehabilitation provides a network of institutions with regular quality auditing. Positive effects of rehabilitation programs on mortality and morbidity have been established by numerous studies. Although a majority of patients after cardiac surgery are being referred to rehabilitation, these services are notoriously underused after catheter procedures. [ABSTRACT FROM AUTHOR]

Polar lipid pattern determination is often used for the taxonomic classification of halophilic Archaea in addition to a genomic characterization. During the analysis of polar lipid extracts from the recently described haloarchaeon Natrononomonas moolapensis , an unknown glycolipid was detected. Fragmentation patterns observed from preliminary mass spectrometric analysis initially suggested the presence of a sulfo-hexosyl-phosphatidylglycerol. However, by NMR spectroscopy and enzymatic assays the existence of two isomeric molecules with different hexoses (1-(6-sulfo- d -glcp/galf-β1,2-glycero)-phospho-2,3-diphytanylglycerol) could be shown. The structural origin from phosphatidylglycerol distinguishes these glycolipids within Archaea , because all other characterized haloarchaeal glycolipids consist of diphytanylglycerol directly linked to an oligoglycosyl moiety. Now the door is open to investigate the physical and functional consequences of these architectural differences of the head groups. [ABSTRACT FROM AUTHOR]

A new method for determining the fluorophore distribution along the propagation axis of an ultrashort optical pulse is presented. The axial resolution is obtained by temporal gating of the backward emitted fluorescence via optical parametric amplification, and we demonstrated a resolution in the order of a few 100 μm. With this approach, sampling of the fluorophore concentration of thin layers without using optics with a large numerical aperture will be possible, such as investigating the human retina via time-resolved fluorescence measurements. Additionally, we verified the gain is orders of magnitude higher for coherent seeding, making optical parametric gating very interesting for discriminating between coherently and incoherently scattered light for other multimodal imaging applications. [ABSTRACT FROM AUTHOR]

B Inside Cover b : In article number 2100625 by Andreas Hoffmann and co-workers, a bi- and a trifunctional "ene"-monomer (blue) and a bifunctional thiolmonomer (green) react under UV-light in a thiol-ene click polymerization. Depicted is the influence of a prepolymerization step on the network homogeneity of the polymer network compared to a system synthesized in one step. Novel Thiol-Ene Photo Resins for Stereolithography with Enhanced Mechanical and Optical Properties. [Extracted from the article]

On-Chip Direct Laser Writing of PAN-Based Carbon Supercapacitor Electrodes B Back Cover b : Article number 2100731 describes the fabrication of a micro-supercapacitor on a printed circuit board. Volker Strauss, Alexander J. C. Kuehne, and co-workers develop a laser-carbonization process for polyacrylonitrile films, leading to patterned, interdigitated carbon electrodes. [Extracted from the article]

Background: Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients with resected CCC. Methods: 47 formalin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for FLT1, FLT4, HPSE, Hif1a, VEGFA/C, HB-EGF, PDGFA, PDGF-RA and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha). Results: EGFR, FLT1 and HPSE expression levels were significantly associated with overall survival (OS). FLT1 showed the strongest significant independent association with overall survival in a multivariate cox regression analysis when compared to the other genes and clinicopathological factors with a nearly 5 times higher relative risk (4.74) of dying earlier when expressed in low levels (p = 0.04). ROC Curve Analysis revealed that measuring EGFR potentially identifies patients at risk of a worsened outcome with a sensitivity of 80% and a specificity of 75% (p = 0.01). Conclusions: EGFR and FLT1 seem to be potential markers to identify those patients at high risk of dying from cholangiocarcinoma. Therefore these markers may help to identify patient subgroups in need for a more aggressive approach in a disease that is in desperate need for new approaches. [ABSTRACT FROM AUTHOR]

Abstract: This paper studies the monetary policy of the Federal Reserve (Fed) and the European Central Bank (ECB) with respect to stock or/and foreign exchange markets from 1979 to 2009. I find that during the Greenspan era stock markets played a role in US monetary policy. The Fed lowered interest rates when stock prices fell, but did not raise interest rates in response to rising stock prices. This asymmetry put a downward pressure on interest rates. For the ECB, the exchange rate to the dollar played a role in monetary policy decisions. While I do not find evidence of asymmetric monetary policy with respect to the stock market, the ECB may be argued to have indirectly followed the asymmetric US monetary policy via the exchange rate channel until 2006, the period until which the dollar depreciated heavily against the euro. With asset markets putting a downward pressure on interest rates, it is likely that the Fed and ECB contributed to recent boom-and-bust cycles by providing low-cost liquidity to flourishing markets. Relevance and implications of the findings are discussed. [Copyright &y& Elsevier]

It is one fundamental conviction of ancient philosophy that, in contrast to the vast majority, only few are able to gain knowledge of truth. This axiom, which also underlies Cicero's Hortensius, is adapted by the young Augustine. When looking for a concept of truth that combines the ideal of a philosophical existence with Christianity, he decides to join the Manichaeans. As opposed to the 'mainline church' of the catholica in which 'the many' are gathered, the Manichaeans appear to him as a small, elitist Christian community meeting higher intellectual as well as ethical demands. This claim seems to be particularly and impressively confirmed by the 'pauci electi'. Their approach has apparently strengthened Augustine's belief that true, higher Christianity is to be found amongst the Manichaeans. When he later devotes himself to the catholica and leads the fight against the Manichaeans, Augustine adheres to the conviction of the 'few wise'. Also within the catholica only few attain maximum insight and lead an appropriate life. At the same time, however, Augustine increasingly considers 'the many' as positive. These two aspects are combined in his epistemological concept of 'auctoritas': by means of their auctoritas, the few 'wise' within the Catholic Church are supposed to guide the many towards truth on their journey of faith and cause them to improve their moral conduct. Its big success is a major argument for the catholica, whilst the 'paucitas' of the Manichaeans (and all heretics) can be considered evidence of the groundlessness and absurdity of their doctrine. [ABSTRACT FROM AUTHOR]

A variety of approaches have been employed to generate binding proteins from non-antibody scaffolds. Utilizing a betasheet of the human ubiquitin for paratope creation we obtained binding proteins against tumor necrosis factor (TNF)-alpha. The bioactive form of this validated pharmacological target protein is a non-covalently linked homo-trimer. This structural feature leads to the observation of a certain heterogeneity concerning the binding mode of TNF-alpha binding molecules, for instance in terms of monomer/trimer specificity. We analyzed a ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular focus on its mode of interaction. Using enzyme-linked immunosorbent assays, specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal titration calorimetry we obtained comparable results regarding the affinity and detected an exothermic reaction with one ubiquitin-derived binding molecule binding one TNFalpha trimer. Using NMR spectroscopy and other analytical methods the 1:3 stoichiometry could be confirmed. Detailed binding analysis showed that the interaction is affected by the detergent Tween-20. Previously, this phenomenon was reported only for one other type of alternative scaffold-derived binding proteins - designed ankyrin repeat proteins - without further investigation. As demonstrated by size exclusion chromatography and NMR spectroscopy, the presence of the detergent increases the association rate significantly. Since the special architecture of TNF-alpha is known to be modulated by detergents, the access to the recognized epitope is indicated to be restricted by conformational transitions within the target protein. Our results suggest that the ubiquitin-derived binding protein targets a new epitope on TNFalpha, which differs from the epitopes recognized by TNF-alpha neutralizing antibodies. [ABSTRACT FROM AUTHOR]

Abstract: Global and localized granular surface flow is analyzed in a model that takes into account the basic forces between a flowing granular layer and an underlying granular bed. Starting from a quantitatively correct description of global stick–slip avalanches on the surfaces of heaps we are able to describe localized flows of various types as seen in experiments of Daerr and Douady [A. Daerr, S. Douady, Two types of avalanche behavior in granular media, Nature (London) 399 (1999) 241]. The descriptive level takes into account the free surface and the velocity of the flow solely. We limit our model to cases where this surface is effectively one-dimensional so that our model equations are consequently one-dimensional in space. With this kind of description we are able to account for the tight coupling between local grain velocity and local height of the so-called lonely waves. Our model shows the nature of a wave of mobilization and deposition. Granular material is set into motion in a domino-like manner. In addition destabilization of material behind an avalanche is taken into account. The front velocities are found to be constant and in general head and rear front travel with the same velocity in our model. The front velocities depend on the tilt angle of the heap that those localized structures run down on. A critical angle is observed above which the rear front velocity abruptly switches sign from positive (downslope) to negative (upslope) values. Furthermore, we find global influences of the surface shape of a flowing granular layer on Bagnold friction. This characteristic collisional friction between flowing layers and beds is shown to cause S-shaping of the free surface for rapid flow velocities. Finally, our model also explains the power spectrum of avalanches as experimentally detected by Jaeger et al. [H. Jaeger, C. Liu, S. Nagel, Relaxation at the angle of repose, Phys. Rev. Lett. 62 (1989) 40]. [ABSTRACT FROM AUTHOR]

Abstract: Tumor necrosis factor (TNF-α) inhibitors, used for the treatment of common inflammatory diseases, currently belong among the most important biotechnologically produced pharmaceuticals. So far four TNF-α antagonists have been approved by regulatory authorities for defined subsets of applications. Furthermore, numerous approaches are being taken to develop new protein-based pharmaceuticals and to broaden their application areas in the treatment of TNF-α -related diseases. Both the fundamental understanding of disease-related TNF-α activity and the subsequent development of corresponding drug candidates demand the availability of large amounts of TNF-α as a bioactive protein. We have therefore established a protocol for the rapid high-level synthesis of recombinant human TNF-α in Escherichia coli shake-flask cultures and the subsequent purification of the mature protein. Using the advantages of SUMO-fusion technology we were able to produce protein with an authentic N-terminus in high yield. Two immobilized metal ion-affinity chromatography steps with a protease cleavage step in between and subsequent size-exclusion chromatography were utilized to purify the protein. The protein was obtained from the last chromatography step as a trimer, while purity was at least 96% as estimated by SDS–PAGE. The identity of the protein was confirmed by MALDI-TOF mass spectrometry. Recombinant mature TNF-α was correctly folded as assessed by CD spectroscopy and its biological activity was confirmed by an L929 cell assay. [Copyright &y& Elsevier]

PURPOSE: The role of adjuvant chemotherapy in patients with locally advanced bladder cancer still remains to be defined. We hypothesized that assessing the gene expression of the chemotherapy response modifiers multidrug resistance gene 1 (MDR1) and excision repair cross-complementing 1 (ERCC1) may help identify the group of patients benefiting from cisplatin-based adjuvant chemotherapy. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 108 patients with locally advanced bladder cancer, who had been enrolled in AUO-AB 05/95, a phase 3 trial randomizing a maximum of three courses of adjuvant cisplatin and methotrexate (CM) versus methotrexate, vinblastine, epirubicin, and cisplatin (M-VEC), were included in the study. Tumor cells were retrieved by laser-captured microdissection and analyzed for MDR1 and ERCC1 expression using a quantitative real-time reverse transcription-polymerase chain reaction assay. Gene expression levels were correlated with clinical outcomes by multivariate Cox proportional hazards regression analysis. RESULTS: Expressions of MDR1 and ERCC1 were independently associated with overall progression-free survival (P = .001, relative risk = 2.9 and P = .01, relative risk = 2.24, respectively). The correlation of high MDR1 expression with inferior outcome was stronger in patients receiving M-VEC, whereas ERCC1 analysis performed equally in the CM and M-VEC groups. CONCLUSIONS: High MDR1 and ERCC1 gene expressions are associated with inferior outcome after cisplatin-based adjuvant chemotherapy for locally advanced bladder cancer. Prospective studies are warranted to define a role for MDR1 and ERCC1 analysis in individualizing multimodality treatment in locally advanced bladder cancer. [ABSTRACT FROM AUTHOR]

Death-associated protein kinase (DAPK) and adenomatous polyposis coli gene (APC) have been recently shown to be associated with outcome in patients with esophageal carcinoma, especially adenocarcinoma. We wanted to validate the correlation of these two markers with outcome by detecting methylated DNA sequences in peripheral blood. Circulating cell-free DNA extracted from blood plasma of 59 patients with esophageal cancer was analyzed before and after surgical resection by quantitative real-time methylation-specific RT-PCR (TaqMan™) assays. Thirty-six of 59 patients (61.0%) with esophageal cancer had detectable levels of methylated DAPK or APC promoter DNA and preoperative detection was significantly associated with an unfavorable prognosis as revealed by multivariate Cox proportional hazards regression analysis [Exp(b) = 4.578; P = 0.01]. The combination of both markers significantly increased sensitivity and specificity for discriminating between short (<2.5 years) and long survivors ( P = 0.04, ROC curve analysis). Postoperative APC detection was significantly different if residual tumor was apparent ( P = 0.03). Preoperative measurement of methylated DAPK and APC promoter DNA in peripheral blood may contribute to better estimate postoperative survival chances of patients with esophageal carcinoma, especially adenocarcinoma. The postoperative detection of methylated APC in peripheral blood might provide crucial information on apparent residual tumor and might be used as a “molecular” R0-Marker in addition to the pathologic examination. [ABSTRACT FROM AUTHOR]

1. Little is known about the predators of insect eggs in fresh waters. This study describes aspects of the life history of a scathophagid fly ( Acanthocnema sp.), whose larvae are predators of aquatic insect eggs. 2. Because the Acanthocnema predator oviposits its eggs on the surface of aquatic insect egg masses, all insect egg masses were collected regularly within a 200-m reach of Redwood Creek (California, U.S.A.) between September 2003 and June 2007. Acanthocnema predators were found predominantly within egg masses of the caddifly Neophylax rickeri (Trichoptera: Uenoidae). 3. There was a mean of 0.25 Acanthocnema individuals per N. rickeri egg mass ( n = 2367 egg masses). In general, N. rickeri egg masses were more commonly found clustered in aggregations (93.7%) than singly (6.3%), and Acanthonema were found more often within the aggregations of N. rickeri (98.7%) compared to singly laid egg masses (1.3%). 4. The duration of the Acanthocnema predator life stages was: egg 2.9 ± 0.8 (mean ± SD) days, larva 15.6 ± 10.2 days, pupa 80.3 ± 24.9 days and adult 7.2 ± 4.8 days. The short duration of the Acanthocnema egg stage (1–7 days) compared to that of its prey N. rickeri (2–4 weeks) raises the probability that the undeveloped eggs of N. rickeri would be available to the young predators upon hatching. Egg consumption of N. rickeri eggs by Acanthocnema averaged 262.6 eggs per larval period. 5. Acanthocnema had a bivoltine life cycle in which the first generation fed exclusively on N. rickeri egg masses in the winter and the second generation fed on the egg masses of several species, including other Trichoptera (Brachycentridae) and Diptera (Ceratopogonidae, Chironomidae) in the spring. These findings suggest differing feeding strategies by the first and second generations of Acanthocnema in response to the seasonal availability of prey species. This type of autecological information is important for understanding mechanisms of community interactions. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer still has one of the worst prognoses of all cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. Especially heparanase (HPSE) has recently been discussed as a key factor in pancreatic cancer.Materials and Methods: Paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma who were scheduled for primary surgical resection. Direct quantitative real-time reverse transcriptase polymerase chain reaction (TaqMan) assays were performed in triplicates to determine HPSE, hypoxia inducible factor-1 alpha (HIF1a), platelet-derived growth factor alpha (PDGFA), heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) gene expression levels.Results: HPSE was significantly correlated to PDGFA (p = 0.04) and HIF1a (p = 0.04). The correlation of HIF1a to bFGF and HB-EGF was significant (p = 0.04, p = 0.02). Stepwise multiple linear regression models showed a significant independent association of HPSE with lymph node metastasis (p = 0.025) and with dedifferentiation (p = 0.042).Conclusions: Heparanase seems to be significantly associated with lymph node metastasis (p = 0.025) as well as dedifferentiation (p = 0.042). We assume that HPSE plays a crucial role for the aggressiveness of pancreatic cancer. Larger studies including more patients seem to be warranted. [ABSTRACT FROM AUTHOR]

PURPOSE: Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma (age, 65; range, 34-85 years). After laser capture microdissection, direct quantitative real-time reverse transcription-polymerase chain reaction assays were performed in triplicates to determine HIF1a, PDGFA, VEGF, and bFGF gene expression levels. Multivariate Cox proportional hazards regression analysis was used to assess the impact of HIF1a gene expression on prognosis. RESULTS: HIF1a was significantly correlated to every gene we tested: bFGF (P = .04), VEGF (P = .02), and PDGFA (P = .03). Tumor size, P = .04, and high HIF1a mRNA expression (cutoff, 75th percentile) had a significant impact on survival, P = .009 (overall model fit, P = .02). High HIF1a expression had a sensitivity of 87.1% and a specificity of 55.6% for the diagnosis short (<6 months) versus long (6-60 months) survival. CONCLUSIONS: Measuring PDGFA, bFGF, and HIF1a expression may contribute to a better understanding of the prognosis of patients with pancreatic cancer and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Larger studies including patients treated with actual chemotherapeutics seem to be warranted. [ABSTRACT FROM AUTHOR]

Abstract: This article is a contribution towards the innovative development and practical application of structures reinforced by means of textile fabrics. Textile reinforcement embedded in fine-grained concrete not only finds application in new structures but may also be used for the additional strengthening of existing steel-reinforced concrete (RC) structures. The article focuses on a FE-model suitable for folded-plate structures. This so-called multi-reference-plane model (MRM) is capable of describing the structural behavior of RC structures strengthened by textile-reinforced concrete (TRC) layers, because those are characterized by a multi-Kirchhoff kinematics. New TRC structures may also be analyzed with the aid of the MRM as structures with one reference plane only. Experimental and numerical investigations demonstrate that structural responses of TRC structures are highly dependent on the spatial and temporal variation of the uncertain material and geometric data. For this reason the present paper concentrates on the generalized uncertainty modeling of material and geometric parameters with the aid of fuzzy and fuzzy random functions. The uncertainty models and the MRM are combined in the framework of the fuzzy stochastic finite element method (FSFEM). The introduced models are applied to three examples. [Copyright &y& Elsevier]

Aim. This paper reports a study to describe meanings that couples mutually assign to, and practices they develop, after the onset of cardiac disease and to understand the impact of the illness on the couples’ relationships in everyday life. Background. Patients as well as partners are affected by the onset of cardiovascular disease. Social support within intimate relationships has been shown to be important for patient survival and well-being, and couples’ coping strategies are pivotal for well-being and adjustment to the chronic condition in both patients with cardiovascular disease and their partners. Method. Twenty-four couples participated in this phenomenological study. Data were collected during 2003. Participants were interviewed after having been hospitalized due to an acute event and having participated in a rehabilitation programme. Three in-depth interviews were obtained for each dyad: one couple interview and two individual interviews with each partner of the dyad. Paradigm cases were sought and thematic analyses conducted. Findings. All couples experienced a ‘brush with death’ at the onset of heart disease, which called for changes in lifestyle. Three distinct patterns of dealing with the illness emerged. The first revealed that some couples assess the illness as a positive, transformative experience in their lives, bringing them closer together. The second showed that a proportion of couples experience the illness as a threat which imposes fear on both partners. The challenges are faced as mutual tasks and new routines are developed. The third pattern revealed couples who experience a missed opportunity to change. These couples are disenchanted about each other but return to life as usual. Conclusions. Nurses can use the information gained from this study to support couples in their attempts to come to terms with the illness, and can enhance their supportive role in rehabilitation efforts. [ABSTRACT FROM AUTHOR]

Abstract: In order to design packed columns for multiphase operation it is necessary to include reliable data on the flow behavior in the model. Since experiments inside packings are very difficult to perform, computational fluid dynamics (CFD) simulations are considered to be a sensible approach as numerical experiments. To obtain reliable results validation is inevitable. We present the validation of two- and three-phase film flow under transient conditions. This application is not abundant in literature. Numerical results are compared with data from own experiments. The usability of a VOF-like code for such applications is shown. [Copyright &y& Elsevier]

The technique of stir bar sorptive extraction is used for the determination of polycyclic aromatic hydrocarbons (PAH) in aqueous samples. The PAHs are extracted with 10-mm stir bars (Gerstel Twister) coated with 0.5 mm polydimethylsiloxane and analyzed with a gas chromatography–mass spectrometry system. The influence of methanol and hyamine addition to the samples for preventing wall effects is investigated at 100 ng/l. The results indicate improved sensitivity using hyamine addition to the samples. The optimal extraction time was found to be between 3 and 4 h. The reproducibility of the method, as determined by nine replicate measurements, is between 5 and 15% at 10 ng/l and between 3 and 9% at 50 ng/l. Carry-over, which was evaluated at 500 ng/l by desorbing the same Twister three times, seems to be negligible for most of the compounds. In worst cases, carry-over of up to 7% was found for indeno[1,2,3]pyrene, dibenz[a,h]anthracene, and benzo[g,h,i]perylene. The technique shows excellent linearities for 5 point calibrations. Detection limits are between 0.1 and 2 ng/l. [Copyright &y& Elsevier]

Carbon nanofiber nonwovens are promising materials for electrode or filtration applications; however, their utilization is obviated by a lack of high throughput production methods. In this study, we utilize a highly effective high-throughput method for the fabrication of polyacrylonitrile (PAN) nanofibers as a nonwoven on a dedicated substrate. The method employs rotational-, air pressure- and electrostatic forces to produce fibers from the inner edge of a rotating bell towards a flat collector. We investigate the impact of all above-mentioned forces on the fiber diameter, morphology, and bundling of the carbon-precursor PAN fibers. The interplay of radial forces with collector-facing forces has an influence on the uniformity of fiber deposition. Finally, the obtained PAN nanofibers are converted to carbon nonwovens by thermal treatment. [ABSTRACT FROM AUTHOR]

The synthesis of transition metal oxynitrides is complicated by extreme reaction conditions such as high temperatures and/or high pressures. Here, we show an unprecedented solution-based synthesis of narrowly dispersed titanium oxynitride nanoparticles of cubic shape and average size of 65 nm. Their synthesis is performed by using titanium tetrafluoride and lithium nitride as precursors alongside trioctylphosphine oxide (TOPO) and cetrimonium bromide (CTAB) as stabilizers at temperatures as low as 250 °C. The obtained nanoparticles are characterized in terms of their shape and optical properties, as well as their crystalline rock-salt structure, as confirmed by XRD and HRTEM analysis. We also determine the composition and nitrogen content of the synthesized particles using XPS and EELS. Finally, we investigate the applicability of our titanium oxynitride nanoparticles by compounding them into carbon fiber electrodes to showcase their applicability in energy storage devices. Electrodes with titanium oxynitride nanoparticles exhibit increased capacity compared to the pure carbon material. [ABSTRACT FROM AUTHOR]

Abstract: Jost [Jost, L., 2006. Entropy and diversity. Oikos, 113: 363–374.] recently discussed Hill''s [Hill, M., 1973. Diversity and evenness: a unifying notation and its consequences. Ecology, 54: 427–431.] effective number of species and concluded by naming it the “true” diversity. In this note we comment on parts of Jost''s work and argue that the true diversity is not what the name suggests. [Copyright &y& Elsevier]

Abstract: Background: Adult patients with congenital heart disease under follow-up often need to undergo diagnostic procedures which expose them to radiation. Aim: To evaluate radiation doses in adult patients with congenital heart disease during follow-up. Methods: Data on diagnostic procedures were used from the European Heart Survey on adult congenital heart disease, a multicenter retrospective cohort study. Lesions included in the survey were Atrial Septal Defect, Ventricular Septal Defect, Fallot, Fontan, Coarctation, Transposition of the Great Arteries, Marfan, and Cyanotic lesions. A total of 4110 patients (52% female) with a mean age of 32 years (range 17–85) were included. The follow-up time ranged from 0 to 72 months, with a median of 61 months. There were a total of 18,403 patient-years of follow-up. During this time, a mean of 4.5 visits per patient took place. Radiation doses were calculated using the number of examinations in each patient''s data file. Effective radiation doses are given in millisievert (mSv). Results: The average cumulative annual effective dose per patient was 0.46 mSv. The relative contributions to these doses were 3% by chest X-rays, 39% by computed tomography scans, 42% by angiography, and 16% by nuclear scans. Effective doses were higher in patients with Fontan, Coarctation, Marfan and Cyanotic lesions, as well as in patients with Atrial Septal Defects. Conclusions: Exposure to radiation during follow-up of patients with adult congenital heart disease mainly stems from computed tomography scans and angiography. Patients with Fontan, Coarctation, Marfan and Cyanotic lesions are more likely to get high doses from computed tomography. In these lesions, therefore, particular care should be taken to use non-ionizing imaging procedures whenever possible. [Copyright &y& Elsevier]

Stereolithography is one of the most promising technologies for the production of tailored implants. Within this study, we show the results of a new resin formulation for three-dimensional printing which is also useful for subsequent surface functionalization. The class of materials is based on monomers containing either thiol or alkene groups. By irradiation of the monomers at a wavelength of 266 nm, we demonstrated an initiator-free stereolithographic process based on thiol-ene click chemistry. Specimens made from this material have successfully been tested for biocompatibility. Using Fourier-transform infrared spectrometry and fluorescent staining, we are able to show that off-stoichiometric amounts of functional groups in the monomers allow us to produce scaffolds with functional surfaces. We established a new protocol to demonstrate the opportunity to functionalize the surface by copper-catalyzed azide-alkyne cycloaddition chemistry. Finally, we demonstrate a three-dimensional bioprinting concept for the production of potentially biocompatible polymers with thiol-functionalized surfaces usable for subsequent functionalization. [ABSTRACT FROM AUTHOR]

• 83 zeolites with 25 different frameworks have been tested as NH 3 -SCR catalyst. • Critical parameters that affect catalytic performance were identified. • Si/Al ratio, d6r content, framework density and pore dimensionality are important. • MOZ, SZR and GME zeolites were predicted to have good NH 3 -SCR performance. • Predictions towards new zeolites' NH 3 -SCR performance can be made. Low temperature performance is key for catalysts used in selective catalytic reduction of NO x with ammonia (NH 3 -SCR). The best performing NH 3 -SCR catalysts are based on small pore copper loaded zeolites. A key question remains which structural and compositional parameters make a copper zeolite catalytically active in this application. In this work a collection of 83 different zeolite samples having 25 different frameworks and compositional variations was evaluated to uncover the critical structural and compositional parameters governing catalytic activity at 150 °C. The Si/Al ratio, the content of double six-ring building units, the framework density and pore dimensionality were identified as having a strong impact on the catalytic activity of zeolites. A critical value for each of these parameters was determined. This knowledge was used to predict MOZ, SZR and GME as active NH 3 -SCR catalysts. They were synthesized respecting the compositional prerequisites and their catalytic evaluation confirmed the predicted high catalytic activity. [ABSTRACT FROM AUTHOR]

Use of computed tomography (CT) scans raises safety concern as lifetime cumulative ionising radiation exposure is associated with risk of developing malignancies. This study aimed to investigate use of abdominal CT scans in the Danish health care sector. Data on abdominal CT scans performed annually in the North Denmark Region between 2005 and 2018 were extracted from the regional registry with emphasis on patients with a medical history of a repeated abdominal CT scan within 28 days. An audit of the medical files was subsequently conducted in 100 randomly selected patient cases to evaluate clinical information being provided, in addition to justification for a repeated abdominal CT scan, and finally if other radiology modalities could have been applied. Number of annually performed abdominal CT scans in this demographically stable regional population increased by a factor 4.3 from 15 in 2005 to 65 in 2018 per 1,000 inhabitants. The audit revealed that 31% of the second abdominal CT scans within a 28 days period were categorized as either doubtful whether justified or not justified. Moreover, 20% of the CT scans were considered replaceable by ultrasonography. Annual performance of abdominal CT scans increased fourfold during the 14 years period. This tendency is probably attributable to changes in the Danish health care sector by which CT scan examination are used more frequently aiming at more accelerated patient investigation flow in conjunction with shorter length of hospitalization stay. Alertness is strongly warranted towards the associated risk of cancer due to life-time cumulative ionising radiation exposure by this strategy. [ABSTRACT FROM AUTHOR]

Effect of geometrical and hydraulic parameters on the behaviour of migrating fish at hydropower facilities To protect migrating fish from harmful turbine passages, bar racks and bypasses can be effective mitigation measures. The number of fish that are protected by facilities like these can be increased if the behaviour of fish is considered during its design process. The effect of hydraulic and geometrical aspects of bar racks was tested by means of ecohydraulic studies with eels, graylings, perches, salmons and roaches. The combination of behavioural studies and flow examination offers the possibility to gain insight into parameter‐behaviour interactions. These studies proved that apart from the approach velocity the bar rack spacing is the most influential parameter with regard to the screening effect of the bar rack as well as the searching behaviour of fish. [ABSTRACT FROM AUTHOR]