Rationality and irrationality in the history of continental drift: Was the hypothesis of continental drift worthy of pursuit?

The revolution in geology, initiated with Alfred Wegener’s theory of continental drift, has been the subject of many philosophical discussions aiming at resolving the problem of rationality underlying this historical episode. Even though the debate included analyses in terms of scientific methodology, applications of concrete accounts of epistemic justification to this case study have been rare. In particular, the question as to whether Wegener’s theory was epistemically worthy of pursuit in the first half of the twentieth century, that is, in its early development, remained open or inadequately addressed. The aim of this paper is to offer an answer to this question. The evaluation of Drift will be done by means of an account of theory evaluation suitable for the context of pursuit, developed in ?e?elja and Straßer (accepted for publication). We will argue that pursuing the theory of continental drift was rational, i.e., that it was irrational to reject its pursuit as unworthy.     

Enhancing Validity and Reliability Through Feedback-Driven Exploration: A Study in the Context of Conjoint Analysis

This study proposes a research design for the enhancement of validity and reliability in conjoint analysis research. For this purpose, we are applying the concept of feedback-driven exploration to conjoint analysis and assess the proposed research design concerning its benefits and limitations in respect of validity and reliability of results. The article is of interest for the field of preference elicitation through stated preference methods, and for model validation in transdisciplinary research. By applying the principle of feedback-driven exploration, we allow for feedback loops between researchers, industry experts and survey participants in order to strengthen both validity and reliability. A multi-case study of the agricultural markets in Switzerland illustrates the functioning of the proposed research design. We find that feedback-driven exploration significantly increases validity and reliability by enhancing methodological rigor and implementing an error-correcting mechanism. Additionally, a better understanding of the underlying decision processes is supported by the design due to increased interaction between researchers, industry experts and market participants.     

Action Research in Inter-Organisational Networks: Impartial Studies or the Trojan Horse?

This article addresses the distinct ethical challenges of action research in inter-organisational projects. Traditionally, the literature on action research has distinguished between two researcher roles: The problem-solver and the observer. Based on an action research project in a Danish inter-organisational network, a third role as legitimiser is identified as an ethical challenge. Potentially, the legitimacy that the researchers carry as academic knowledge-generating actors may be used by a particular company to involve other companies in the network. Thus, the researchers may be perceived as bringing into the other organisations a Trojan Horse containing the interests of this particular company. Lack of clarity in defining the role of the action researcher may thus jeopardise the trustworthiness of the researchers and the action research project. On the basis of the case study analysis, the article develops a number of preliminary points of ethical consideration for future research analysis.     

The limits of the nuclear landscape

In 2011, 100 new nuclides were discovered. They joined the approximately 3,000 stable and radioactive nuclides that either occur naturally on Earth or are synthesized in the laboratory. Every atomic nucleus, characterized by a specific number of protons and neutrons, occupies a spot on the chart of nuclides, which is bounded by 'drip lines' indicating the values of neutron and proton number at which nuclear binding ends. The placement of the neutron drip line for the heavier elements is based on theoretical predictions using extreme extrapolations, and so is uncertain. However, it is not known how uncertain it is or how many protons and neutrons can be bound in a nucleus. Here we estimate these limits of the nuclear 'landscape' and provide statistical and systematic uncertainties for our predictions. We use nuclear density functional theory, several Skyrme interactions and high-performance computing, and find that the number of bound nuclides with between 2 and 120 protons is around 7,000. We find that extrapolations for drip-line positions and selected nuclear properties, including neutron separation energies relevant to astrophysical processes, are very consistent between the models used.     

Dissecting the genomic complexity underlying medulloblastoma

Medulloblastoma is an aggressively growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and shows tremendous biological and clinical heterogeneity. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently identified. WNT tumours, showing activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis. Group 3 and 4 tumours are molecularly less well characterized, and also present the greatest clinical challenges. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of what are, to our knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 and 4 patients.     

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.     

An abundance of small exoplanets around stars with a wide range of metallicities

The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets, supporting the model that planets form by accumulation of dust and ice particles. Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets. However, how the relationship between size and metallicity extends into the regime of terrestrial-sized exoplanets is unknown. Here we report spectroscopic metallicities of the host stars of 226 small exoplanet candidates discovered by NASA's Kepler mission, including objects that are comparable in size to the terrestrial planets in the Solar System. We find that planets with radii less than four Earth radii form around host stars with a wide range of metallicities (but on average a metallicity close to that of the Sun), whereas large planets preferentially form around stars with higher metallicities. This observation suggests that terrestrial planets may be widespread in the disk of the Galaxy, with no special requirement of enhanced metallicity for their formation.     

Large-scale prediction and testing of drug activity on side-effect targets

Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 μM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.     

Hit-and-run planetary collisions

Terrestrial planet formation is believed to have concluded in our Solar System with about 10 million to 100 million years of giant impacts, where hundreds of Moon- to Mars-sized planetary embryos acquired random velocities through gravitational encounters and resonances with one another and with Jupiter. This led to planet-crossing orbits and collisions that produced the four terrestrial planets, the Moon and asteroids. But here we show that colliding planets do not simply merge, as is commonly assumed. In many cases, the smaller planet escapes from the collision highly deformed, spun up, depressurized from equilibrium, stripped of its outer layers, and sometimes pulled apart into a chain of diverse objects. Remnants of these 'hit-and-run' collisions are predicted to be common among remnant planet-forming populations, and thus to be relevant to asteroid formation and meteorite petrogenesis.     

RNA biosynthesis in isolated prothoracic glands ofTenebrio molitor in vitro

Summary The prothoracic Glands ofTenebrio molitor synthesize in vitro mainly rRNA. The rate of RNA synthesis reaches a maximum at day 10 of the last larval instar, which coincides with the event of apolysis.The work was supported by the Deutsche Forschungsgemeinschaft. We thank Dr.H. Winter, Heidelberg, for helpful suggestions for the RNA separations.