Content & Watkins's account of natural axiomatizations

This paper briefly recounts the importance of the notion of natural axiomatizations for explicating hypothetico-deductivism, empirical significance, theoretical reduction, and organic fertility. Problems for the account of natural axiomatizations developed by John Watkins in Science and Scepticism and the revised account developed by Elie Zahar are demonstrated. It is then shown that Watkins's account can be salvaged from various counter-examples in a principled way by adding the demand that every axiom of a natural axiomatization should be part of the content of the theory being axiomatized. The crucial point here is that content cannot simply be identified with the set of logical consequences of a theory, but must be restricted to a proper subset of the consequence set. It is concluded that the revised Watkins account has certain advantages over the account of natural axiomatizations offered in Gemes (1993)

Ad Hoc Hypotheses and the Monsters within

Science is increasingly becoming automated. Tasks yet to be fully automated include the conjecturing, modifying, extending and testing of hypotheses. At present scientists have an array of methods to help them carry out those tasks. These range from the well-articulated, formal and unexceptional rules to the semi-articulated and variously understood rules-of-thumb and intuitive hunches. If we are to hand over at least some of the aforementioned tasks to machines, we need to clarify, refine and make formal, not to mention computable, even the more obscure of the methods scientists successfully employ in their inquiries. The focus of this essay is one such less-than-transparent methodological rule. I am here referring to the rule that ad hoc hypotheses ought to be spurned. This essay begins with a brief examination of some notable conceptions of ad hoc-ness in the philosophical literature. It is pointed out that there is a general problem afflicting most such conceptions, namely the intuitive judgments that are supposed to motivate them are not universally shared. Instead of getting bogged down in what ad hoc-ness exactly means, I shift the focus of the analysis to one undesirable feature often present in alleged cases of ad hoc-ness. I call this feature the ‘monstrousness’ of a hypothesis. A fully articulated formal account of this feature is presented by specifying what it is about the internal constitution of a hypothesis that makes it monstrous. Using this account, a monstrousness measure is then proposed and somewhat sketchily compared with the minimum description length approach

STIM2 regulates PKA-dependent phosphorylation and trafficking of AMPARs

STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside in the endoplasmic reticulum (ER) and regulate store-operated Ca2+ entry (SOCE). The function of STIMs in the brain is only beginning to be explored, and the relevance of SOCE in nerve cells is being debated. Here we identify STIM2 as a central organizer of excitatory synapses. STIM2, but not its paralogue STIM1, influences the formation of dendritic spines and shapes basal synaptic transmission in excitatory neurons. We further demonstrate that STIM2 is essential for cAMP/PKA-dependent phosphorylation of the AMPA receptor (AMPAR) subunit GluA1. cAMP triggers rapid migration of STIM2 to ER–plasma membrane (PM) contact sites, enhances recruitment of GluA1 to these ER-PM junctions, and promotes localization of STIM2 in dendritic spines. Both biochemical and imaging data suggest that STIM2 regulates GluA1 phosphorylation by coupling PKA to the AMPAR in a SOCE-independent manner. Consistent with a central role of STIM2 in regulating AMPAR phosphorylation, STIM2 promotes cAMP-dependent surface delivery of GluA1 through combined effects on exocytosis and endocytosis. Collectively our results point to a unique mechanism of synaptic plasticity driven by dynamic assembly of a STIM2 signaling complex at ER-PM contact sites

Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

The Rotterdam Study: 2010 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in close to a 1,000 research articles and reports (see www.epib.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods