Did quantitative easing affect interest rates outside the US? New evidence based on interest rate differentials. CEPS Working Document No. 416/January 2016

This paper explores the effects of non-standard monetary policies on international yield relationships. Based on a descriptive analysis of international long-term yields, we find evidence that long-term rates followed a global downward trend prior to as well as during the financial crisis. Comparing interest rate developments in the US and the eurozone, it is difficult to detect a distinct impact of the first round of the Fed’s quantitative easing programme (QE1) on US interest rates for which the global environment – the global downward trend in interest rates – does not account. Motivated by these findings, we analyse the impact of the Fed’s QE1 programme on the stability of the US-euro long-term interest rate relationship by using a CVAR (cointegrated vector autoregressive) model and, in particular, recursive estimation methods. Using data gathered between 2002 and 2014, we find limited evidence that QE1 caused the break-up or destabilised the transatlantic interest rate relationship. Taking global interest rate developments into account, we thus find no significant evidence that QE had any independent, distinct impact on US interest rates.

Getting the most from public R&D spending in times of budgetary austerity. Bruegel Working Paper 2016/01, February 2016

This working paper reviews the evidence on the impact of public R&D spending. The authors first look at the evidence from micro-analysis of the impact of public intervention on private R&D and innovation, with a focus on the latest results from crosscountry micro-research performed within SIMPATIC. To analyse the impact of public R&D on growth, the micro-results on private R&D investment effects are complemented with a macro-perspective. To this end, the authors look at how public R&D performs in affecting GDP growth and jobs in applied macro-models most commonly used in EU policy analysis. They focus particularly on the NEMESIS model in development within the SIMPATIC project. The authors conclude with some policy recommendations from the reviewed micro and macro SIMPATIC evidence for designing public R&D projects and programmes.

How to get out of the crisis without reforms? The Belarusian authorities confront growing economic problems. OSW Commentary NUMBER 202/21.03.2016

2015 saw a drop in Belarus’s GDP for the first time in almost 20 years, which is primarily the result of a significant reduction in levels of production and export. As a consequence, there was also a serious depletion of the country’s foreign exchange reserves, as well as a progressive weakening of the Belarusian rouble. The macroeconomic figures from January and February 2016 show that these trends are not only continuing, but they are also becoming even more severe, which confirms that Belarus now finds itself in a prolonged economic crisis. On one hand, the reason for this state of affairs is the protracted economic recession in Russia, which is Belarus’s main economic partner, together with the drastic global decline in prices for fuel, which is a key Belarusian export. On the other hand, meanwhile, an equally important reason for the current crisis is the failure of the Belarusian economic model. President Aleksandr Lukashenko, out of fear that his authoritarian system of government will be dismantled and that public discontent will rise, has categorically rejected the proposals for even partial reforms put forward by some of his entourage, who are aware of the need for the immediate transformation of the country’s anachronistic and very costly economic model, based as it still is on quasi-Soviet management policies.

Business under supervision – pathologies serving the system of power in Russia. OSW COMMENTARY NUMBER 212 | 31.05.2016

The relations between Russia’s authorities and business circles are subordinated not so much to rational economic calculations as to the interests of political elites. The key interest in this case is maintaining the current model of government. The formal and informal supervision of business by law enforcement agencies is an important element of Russia’s economic reality. Despite the rhetoric of high-ranking officials, intended to suggest that the state is taking care of businesspeople’s interests, it is evident that there is no will to devise a systemic solution to the most urgent problems, including the state institutions’ disrespect for the rights of ownership.

Murine Model for Preclinical Studies of Var2CSA-Mediated Pathology Associated with Malaria in Pregnancy

Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenic P. berghei parasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) fused to a P. berghei exported protein (EMAP1) and characterize a var2CSA-based mouse model of PM. BALB/c mice were infected at midgestation with different doses of P. berghei-var2CSA (P. berghei-VAR) or P. berghei wild-type IEs. Infection with 10(4) P. berghei-VAR IEs induced a higher incidence of stillbirth and lower fetal weight than P. berghei At doses of 10(5) and 10(6) IEs, P. berghei-VAR-infected mice showed increased maternal mortality during pregnancy and fetal loss, respectively. Parasite loads in infected placentas were similar between parasite lines despite differences in maternal outcomes. Fetal weight loss normalized for parasitemia was higher in P. berghei-VAR-infected mice than in P. berghei-infected mice. In vitro assays showed that higher numbers of P. berghei-VAR IEs than P. berghei IEs adhered to placental tissue. Immunization of mice with P. berghei-VAR elicited IgG antibodies reactive to DBL1-6 recombinant protein, indicating that the topology of immunogenic epitopes is maintained between DBL1-6-EMAP1 on P. berghei-VAR and recombinant DBL1-6 (recDBL1-6). Our data suggested that impairments in pregnancy caused by P. berghei-VAR infection were attributable to var2CSA expression. This model provides a tool for preclinical evaluation of protection against PM induced by approaches that target var2CSA.

Drosophila melanogaster as a model for basal body research

The fruit fly, Drosophila melanogaster, is one of the most extensively studied organisms in biological research and has centrioles/basal bodies and cilia that can be modelled to investigate their functions in animals generally. Centrioles are nine-fold symmetrical microtubule-based cylindrical structures required to form centrosomes and also to nucleate the formation of cilia and flagella. When they function to template cilia, centrioles transition into basal bodies. The fruit fly has various types of basal bodies and cilia, which are needed for sensory neuron and sperm function. Genetics, cell biology and behaviour studies in the fruit fly have unveiled new basal body components and revealed different modes of assembly and functions of basal bodies that are conserved in many other organisms, including human, green algae and plasmodium. Here we describe the various basal bodies of Drosophila, what is known about their composition, structure and function.

Routine histological technique applied to a biological model for environmental studies

Introduction and aim Earthworms are an important test organisms used in several standard ecotoxicological tests (e.g. ISO, 2008, 2012; OECD, 2004, 1094) and they are also model organisms to test soil structure and permeability, as well as for important soil services as the degradation organic matter. Although histopathological changes have been demonstrated to be good biomarkers to assess the exposure of these animals to different physical and chemical stress agents, studies with clear and high quality images describing normal tissue conditions are scarce in the literature, so the aim of this work was to better characterize this biological model. Material and Methods Eight adult earthworms exposed to an artificial standard soil (OECD, 2004) for 28 days, were extracted and placed in a plastic box to depurate their gut content, fixed in 10% neutral-buffered formalin and processed for routine histopathological diagnosis. Results and discussion Satisfactory histological sections were obtained. Some difficulties were faced related with microtome sectioning, resulting in artefacts, namely lines across sections produced by a nick in the cutting edge of the microtome knife cutting tear, motivated by the presence of sand and other solid particles that persisted in the gut of earthworms. Nevertheless, it was possible to obtain representative figures from different earthworm sections. Conclusion Routine histological technique was effective for obtaining satisfactory histological sections and the knowledge of the histology of earthworms could be very useful for future application in environmental studies, using this biological model.

Characterization of histopathological lesions in a biological model for environmental studies: Eisenia andrei Bouché. Preliminar results

Introduction The strong expansion of the world production of plastics caused a severe accumulation of plastic debris in the environment, which makes them one of the most important contaminants, growing as a global environmental problem. Although the production in Europe has been relatively constant in the last 10 years, world plastic production continues to increase, affecting soil biota and their functions. Objectives Thus, in order to evaluate the effects of MP in soil-dwelling organisms, earthworms (Eisenia andrei Bouché), were exposed to standard artificial soil mixed with MPs and the authors documented, using microscopic figures, the pathological lesions found in this biological model. Material and Methods Eight adult earthworms extracted from soils contaminated with different concentrations of MP (mg/kgdw) with sizes ranging between 250-1000 m, were fixed in 10% neutral-buffered formalin and processed for routine histopathological diagnosis. Results and discussion Contrary to what would be expected, MP were not found throughout the GI tube of earthworms but several lesions were found in the individuals extracted from the soils with high MP concentrations, when compared with control group, namely epithelial intestinal atrophy and evidences of inflammatory responses to this stress agent. Conclusion Earthworms have probably avoided the consumption of the biggest MPs. However, evidences point for lesions that were likely caused by the smallest MPs that were likely egested during the depuration phase.

A contribuição dos Modelos de Avaliação para a previsão do retorno dos títulos finançeiros de empresa do PSI20 - Análise Comparativa entre Capital Asset Pricing Model e Arbitrage Pricing Theory

O crescimento económico de um país depende dos fundos disponíveis, quer para o financiamento da formação de capital quer para a sua reposição. Fundos obtidos pelas empresas e organismos públicos através de diversas formas, entre as quais, se destaca a emissão de valores mobiliários. Os aforradores, detentores de recursos, ao comprarem valores mobiliários, aliam uma alta rentabilidade a uma elevada liquidez na remuneração dos seus investimentos. As bolsas de valores são o meio onde as empresas, os organismos públicos e os aforradores, têm a possibilidade de verem esses interesses conciliados de uma maneira eficiente, eficaz e transparente, garantindo assim, uma maior liquidez aos títulos financeiros transaccionados em bolsa de valores. As empresas possuem várias alternativas de financiamento, o mercado de capitais é considerado pelos gestores, a fonte onde o rendimento ou o retorno obtido pode ser maior, perante a contrapartida de se incorrer um maior risco. Este mercado surge como alternativa aos empréstimos bancários, as empresas podem, dessa forma, adquirir financiamento de terceiros, os quais se tornarão accionistas dessa empresa. Podem emitir novas acções no mercado accionista de forma a atrair investidores externos que garantam a sustentabilidade do negócio. As acções possuem diversas caracteristicas e modalidades e fazem com que o capital da empresa seja partilhado por todos os seus accionistas, tendo em conta a proporção por eles adquirida individualmente. Esta dissertação investiga a dinâmica de compra e de venda das acções no mercado bolsista, os factores que determinam o seu preço, assim como os modelos que permitem a avaliação das mesmas e a inferência da taxa de retorno esperada por um investidor. A avaliação das acções é o tema de maior importância para esta análise, mais concretamente, a determinação e previsão do preço, e não apenas o preço propriamente dito, pois este é facultado diáriamente por vários jornais e também na internet. Perante o estudo da determinação de preços de uma acção num horizonte temporal, um investidor pode inferir se as suas acções estão a ser avaliadas sob um preço justo, e mais importante, pode apurar a sua previsão consoante dados e análises de factores. Outro ponto importante abordado nesta investigação tem que ver com a possibilidade das empresas em conhecer o modo como o mercado faz a sua avaliação a fim de tomar decisões certas acerca do orçamento de capital. Apenas se deve julgar a atractividade de um negócio se se souber como são avaliadas as acções. Nos mercados financeiros existe a tendência, por parte dos agentes económicos, de relacionarem o preço com o valor dos títulos financeiros. As decisões para a transacção de títulos financeiros são tomadas segundo a sua comparação. O preço ou cotação de mercado é formado em mercados organizados, pelo que depende das regras de funcionamento do mercado, tais como, os mínimos para transacção ou a variação máxima e mínima permitida. Estão associados a uma transação dependendo assim da procura e oferta dos títulos e incorporam ainda os custos de transacção. A ideia subjacente ao modelo Capital Asset Pricing Model é a de que, os investidores esperam uma recompensa pela preocupação dos investimentos realizados com risco ou com um retorno incerto. Quando se investe em títulos com risco, espera-se um retorno extra (comparando com os Bilhetes do Tesouro sem risco, recebe-se apenas os juros) ou um prémio de risco pela preocupação. A incerteza no retorno dos títulos provem de duas fontes, nomeadamente os factores macroeconómicos, pode-se chamar também, um factor comum, e os factores específicos inerentes à actividade da empresa. O facto comum é assumido como tendo um valor esperado zero pois é medido por nova informação respeitante à macroeconomia. O modelo assume duas ideias fundamentais: em primeiro lugar, existe consenso em relação ao facto dos investidores exigirem um retorno adicional por correrem riscos, e em segundo lugar, os investidores preocupam-se geralmente com o risco de mercado geral que não pode ser eliminado através de diversificação da carteira de investimentos. Este modelo pode ser bastante eficaz pois apenas considera um único factor para o cálculo da rendibilidade esperada de um título financeiro, que é a volatilidade do mercado no geral, a qual pode ser estudada. Ao contrário dos modelos multifactoriais, que incluem vários factores macroeconómicos tornando o objectivo da análise pouco intuitivo e complexo. Existem vários modelos para avaliação dos títulos de uma empresa cotada em bolsa de valores, geralmente estes modelos utilizam taxas de juro sem risco para equilibrar carteiras diversificadas, embora seja necessário analisar o retorno de um título ou carteira sob a influência de diversas variáveis macroeconómicas. Por exemplo outro modelo aplicado neste dissertação é o modelo Arbitrage Pricing Theory que perante o seu resultado comparado com o primeiro modelo, se pode definir qual dos modelos tem uma aplicação mais conclusiva para o mercado accionista português. Este modelo de avaliação por arbitragem estabelece uma relação linear entre o excedente do retorno esperado dos activos face à taxa de juro certa (sem risco) e um conjunto de variáveis. Pressupõe que a taxa de rentabilidade de um activo com risco é uma função linear de um conjunto de factores comuns a todos os activos financeiros. Tem como ideia subjacente, a constituição de uma carteira de não arbitragem, ou seja, uma carteira que não envolve qualquer risco (sistemático ou específico) e não requer investimento inicial pois a venda de certos activos gera fundos para adquirir novos. A metodologia implementada abrange o mercado financeiro e modelos possíveis para esta questão. Para responder às hipóteses de investigação efectuou-se a aplicação efectiva do modelo CAPM e do modelo APT, com a captação de dados oficiais em instituições financeiras e na Bolsa de Valores NYSE Euronext Lisbon. Considerou-se um período temporal num passado próximo de forma a poder obter-se conclusões concretas e indicadores precisos para a sua implementação e desenvolvimento no futuro. A principal conclusão desta dissertação relaciona-se com o facto de não se verificar a total validação da aplicação dos modelos, contudo o modelo CAPM é mais conclusivo do que o modelo APT, pois pode-se afirmar que tem aplicação prática em empresas que se conheça à priori a sua capitalização bolsista e beta anual. Por exemplo, aos títulos financeiros de empresas com capitalizações bolsistas inferiores a cinco mil milhões de euros e com um beta anual inferior a 1 poderá aplicar-se o modelo, assim como a títulos de empresas com capitalizações bolsistas superiores a dez mil milhões de euros e beta anual superior 1,5. Os sectores da Banca e do Papel também poderão ter potencial de aplicação do modelo.

Analysis of Lead-Acid batteries with a third-order dynamical model

Electrical energy storage is a really important issue nowadays. As electricity is not easy to be directly stored, it can be stored in other forms and converted back to electricity when needed. As a consequence, storage technologies for electricity can be classified by the form of storage, and in particular we focus on electrochemical energy storage systems, better known as electrochemical batteries. Largely the more widespread batteries are the Lead-Acid ones, in the two main types known as flooded and valve-regulated. Batteries need to be present in many important applications such as in renewable energy systems and in motor vehicles. Consequently, in order to simulate these complex electrical systems, reliable battery models are needed. Although there exist some models developed by experts of chemistry, they are too complex and not expressed in terms of electrical networks. Thus, they are not convenient for a practical use by electrical engineers, who need to interface these models with other electrical systems models, usually described by means of electrical circuits. There are many techniques available in literature by which a battery can be modeled. Starting from the Thevenin based electrical model, it can be adapted to be more reliable for Lead-Acid battery type, with the addition of a parasitic reaction branch and a parallel network. The third-order formulation of this model can be chosen, being a trustworthy general-purpose model, characterized by a good ratio between accuracy and complexity. Considering the equivalent circuit network, all the useful equations describing the battery model are discussed, and then implemented one by one in Matlab/Simulink. The model has been finally validated, and then used to simulate the battery behaviour in different typical conditions.

Type A aortic dissection model to improve endovascular research and technologies.

OBJECTIVE Type A aortic dissection is a life-threatening disease requiring immediate surgical treatment. With emerging catheter-based technologies, endovascular stent-graft implantation to treat aneurysms and dissections has become a standardized procedure. However, endovascular treatment of the ascending aorta remains challenging. Thus we designed an ascending aortic dissection model to allow simulation of endovascular treatment. METHODS Five formalin-fixed human aortas were prepared. The ascending aorta was opened semicircularly in the middle portion and the medial layer was separated from the intima. The intimal tube was readapted using running monofilament sutures. The preparations were assessed by 128-slice computed tomography. A bare-metal stent was implanted for thoracic endovascular aortic repair in 4 of the aortic dissection models. RESULTS Separation of the intimal and medial layer of the aorta was considered to be sufficient because computed tomography showed a clear image of the dissection membrane in each aorta. The dissection was located 3.9 ± 1.4 cm proximally from the aortic annulus, with a length of 4.6 ± 0.9 cm. Before stent implantation, the mean distance from the intimal flap to the aortic wall was measured as 0.63 ± 0.163 cm in the ascending aorta. After stent implantation, this distance decreased to 0.26 ± 0.12 cm. CONCLUSION This model of aortic dissection of the ascending human aorta was reproducible with a comparable pathological and morphological appearance. The technique and model can be used to evaluate new stent-graft technologies to treat type A dissection and facilitate training for surgeons.

Repurposing of antiparasitic drugs: the hydroxy-naphthoquinone buparvaquone inhibits vertical transmission in the pregnant neosporosis mouse model.

The three anti-malarial drugs artemiside, artemisone, and mefloquine, and the naphthoquinone buparvaquone known to be active against theileriosis in cattle and Leishmania infections in rodents, were assessed for activity against Neospora caninum infection. All four compounds inhibited the proliferation of N. caninum tachyzoites in vitro with IC50 in the sub-micromolar range, but artemisone and buparvaquone were most effective (IC50 = 3 and 4.9 nM, respectively). However, in a neosporosis mouse model for cerebral infection comprising Balb/c mice experimentally infected with the virulent isolate Nc-Spain7, the three anti-malarial compounds failed to exhibit any activity, since treatment did not reduce the parasite burden in brains and lungs compared to untreated controls. Thus, these compounds were not further evaluated in pregnant mice. On the other hand, buparvaquone, shown earlier to be effective in reducing the parasite load in the lungs in an acute neosporosis disease model, was further assessed in the pregnant mouse model. Buparvaquone efficiently inhibited vertical transmission in Balb/c mice experimentally infected at day 7 of pregnancy, reduced clinical signs in the pups, but had no effect on cerebral infection in the dams. This demonstrates proof-of-concept that drug repurposing may lead to the discovery of an effective compound against neosporosis that can protect offspring from vertical transmission and disease.

The strengh model of self-control in sport and exercise psychology

The strength model of self-control assumes that all acts of self-control (e.g., emotion regulation, persistence) are empowered by a single global metaphorical strength that has limited capacity. This strength can become temporarily depleted after a primary self-control act, which, in turn, can impair performance in subsequent acts of self-control. Recently, the assumptions of the strength model of self-control also have been adopted and tested in the field of sport and exercise psychology. The present review paper aims to give an overview of recent developments in self-control research based on the strength model of self-control. Furthermore, recent research on interventions on how to improve and revitalize self-control strength will be presented. Finally, the strength model of self-control has been criticized lately, as well as expanded in scope, so the present paper will also discuss alternative explanations of why previous acts of self-control can lead to impaired performance in sport and exercise.

Properties of granular analogue model materials: A community wide survey

We report the material properties of 26 granular analogue materials used in 14 analogue modelling laboratories. We determined physical characteristics such as bulk density, grain size distribution, and grain shape, and performed ring shear tests to determine friction angles and cohesion, and uniaxial compression tests to evaluate the compaction behaviour. Mean grain size of the materials varied between c. 100 and 400 μm. Analysis of grain shape factors shows that the four different classes of granular materials (14 quartz sands, 5 dyed quartz sands, 4 heavy mineral sands and 3 size fractions of glass beads) can be broadly divided into two groups consisting of 12 angular and 14 rounded materials. Grain shape has an influence on friction angles, with most angular materials having higher internal friction angles (between c. 35° and 40°) than rounded materials, whereas well-rounded glass beads have the lowest internal friction angles (between c. 25° and 30°). We interpret this as an effect of intergranular sliding versus rolling. Most angular materials have also higher basal friction angles (tested for a specific foil) than more rounded materials, suggesting that angular grains scratch and wear the foil. Most materials have an internal cohesion in the order of 20–100 Pa except for well-rounded glass beads, which show a trend towards a quasi-cohesionless (C < 20 Pa) Coulomb-type material. The uniaxial confined compression tests reveal that rounded grains generally show less compaction than angular grains. We interpret this to be related to the initial packing density after sifting, which is higher for rounded grains than for angular grains. Ring-shear test data show that angular grains undergo a longer strain-hardening phase than more rounded materials. This might explain why analogue models consisting of angular grains accommodate deformation in a more distributed manner prior to strain localisation than models consisting of rounded grains.

Establishment of a confluent monolayer model with human primary trophoblast cells: novel insights into placental glucose transport

STUDY HYPOTHESIS Using optimized conditions, primary trophoblast cells isolated from human term placenta can develop a confluent monolayer in vitro, which morphologically and functionally resembles the microvilli structure found in vivo. STUDY FINDING We report the successful establishment of a confluent human primary trophoblast monolayer using pre-coated polycarbonate inserts, where the integrity and functionality was validated by cell morphology, biophysical features, cellular marker expression and secretion, and asymmetric glucose transport. WHAT IS KNOWN ALREADY Human trophoblast cells form the initial barrier between maternal and fetal blood to regulate materno-fetal exchange processes. Although the method for isolating pure human cytotrophoblast cells was developed almost 30 years ago, a functional in vitro model with primary trophoblasts forming a confluent monolayer is still lacking. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Human term cytotrophoblasts were isolated by enzymatic digestion and density gradient separation. The purity of the primary cells was evaluated by flow cytometry using the trophoblast-specific marker cytokeratin 7, and vimentin as an indicator for potentially contaminating cells. We screened different coating matrices for high cell viability to optimize the growth conditions for primary trophoblasts on polycarbonate inserts. During culture, cell confluency and polarity were monitored daily by determining transepithelial electrical resistance (TEER) and permeability properties of florescent dyes. The time course of syncytia-related gene expression and hCG secretion during syncytialization were assessed by quantitative RT-PCR and enzyme-linked immunosorbent assay, respectively. The morphology of cultured trophoblasts after 5 days was determined by light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Membrane makers were visualized using confocal microscopy. Additionally, glucose transport studies were performed on the polarized trophoblasts in the same system. MAIN RESULTS AND THE ROLE OF CHANCE During 5-day culture, the highly pure trophoblasts were cultured on inserts coated with reconstituted basement membrane matrix . They exhibited a confluent polarized monolayer, with a modest TEER and a size-dependent apparent permeability coefficient (Papp) to fluorescently labeled compounds (MW ∼400-70 000 Da). The syncytialization progress was characterized by gradually increasing mRNA levels of fusogen genes and elevating hCG secretion. SEM analyses confirmed a confluent trophoblast layer with numerous microvilli, and TEM revealed a monolayer with tight junctions. Immunocytochemistry on the confluent trophoblasts showed positivity for the cell-cell adhesion molecule E-cadherin, the tight junction protein 1 (ZO-1) and the membrane proteins ATP-binding cassette transporter A1 (ABCA1) and glucose transporter 1 (GLUT1). Applying this model to study the bidirectional transport of a non-metabolizable glucose derivative indicated a carrier-mediated placental glucose transport mechanism with asymmetric kinetics. LIMITATIONS, REASONS FOR CAUTION The current study is only focused on primary trophoblast cells isolated from healthy placentas delivered at term. It remains to be evaluated whether this system can be extended to pathological trophoblasts isolated from diverse gestational diseases. WIDER IMPLICATIONS OF THE FINDINGS These findings confirmed the physiological properties of the newly developed human trophoblast barrier, which can be applied to study the exchange of endobiotics and xenobiotics between the maternal and fetal compartment, as well as intracellular metabolism, paracellular contributions and regulatory mechanisms influencing the vectorial transport of molecules. LARGE-SCALE DATA Not applicable. STUDY FUNDING AND COMPETING INTERESTS This study was supported by the Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland, and the Swiss National Science Foundation (grant no. 310030_149958, C.A.). All authors declare that their participation in the study did not involve factual or potential conflicts of interests.