Vrije wil en verantwoordelijkheid in evolutionair perspectief

In toenemende mate dragen evolutiebiologen en neurowetenschappers het idee uit dat onze praktijk van verantwoordelijkheid in het licht van de evolutietheorie niet te handhaven is. Hun argumentatie berust op de veronderstelling dat die praktijk alleen gerechtvaardigd is als mensen het vermogen hebben om zich aan de natuurwetten te onttrekken. In dit hoofdstuk betoog ik dat onze praktijk van verantwoordelijkheid slechts het vermogen om op basis van redenen te handelen veronderstelt en dat dit vermogen zich in de biologische strijd om het bestaan ontwikkeld kan hebben

A balancing act : analyzing a distributed lift system

The process-algebraic language µcrl is used to analyze an existing distributed system for lifting trucks. Four errors were found in the original design. We propose solutions for these problems and show by means of model-checking that the modified system meets the requirements

Three-Fluid Description of the Sympathetic Cooling of a Boson-Fermion Mixture

We present a model for sympathetic cooling of a mixture of fermionic and bosonic atomic gases in harmonic traps, based on a three-fluid description. The model confirms the experimentally observed cooling limit of about 0.2 T_F when only bosons are pumped. We propose sequential cooling -- first pumping of bosons and afterwards fermions -- as a way to obtain lower temperatures. For this scheme, our model predicts that temperatures less than 0.1 T_F can be reached.Comment: 9 pages, 6 figure

Lagekostenbedrijf in 2001

Kostprijsbeheersing is een belangrijk thema voor melkveebedrijven. Dit rapport bevatde resultaten van het onderzoek dat in 2001 op en voor het Lagekostenbedrijf is uitgevoerd

Levels of explanation in biological psychology

Until recently, the notions of function and multiple realization were supposed to save the autonomy of psychological explanations. Furthermore, the concept of supervenience presumably allows both dependence of mind on brain and non-reducibility of mind to brain, reconciling materialism with an independent explanatory role for mental and functional concepts and explanations. Eliminativism is often seen as the main or only alternative to such autonomy. It gladly accepts abandoning or thoroughly reconstructing the psychological level, and considers reduction if successful as equivalent with elimination. In comparison with the philosophy of mind, the philosophy of biology has developed more subtle and complex ideas about functions, laws, and reductive explanation than the stark dichotomy of autonomy or elimination. It has been argued that biology is a patchwork of local laws, each with different explanatory interests and more or less limited scope. This points to a pluralistic, domain-specific and multi-level view of explanations in biology. Explanatory pluralism has been proposed as an alternative to eliminativism on the one hand and methodological dualism on the other hand. It holds that theories at different levels of description, like psychology and neuroscience, can co-evolve, and mutually influence each other, without the higher-level theory being replaced by, or reduced to, the lower-level one. Such ideas seem to tally with the pluralistic character of biological explanation. In biological psychology, explanatory pluralism would lead us to expect many local and non-reductive interactions between biological, neurophysiological, psychological and evolutionary explanations of mind and behavior. This idea is illustrated by an example from behavioral genetics, where genetics, physiology and psychology constitute distinct but interrelated levels of explanation. Accounting for such a complex patchwork of related explanations seems to require a more sophisticated and precise way of looking at levels than the existing ideas on (reductive and non-reductive) explanation in the philosophy of mind

Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination

Constraints on axionlike particles with H.E.S.S. from the irregularity of the PKS 2155-304 energy spectrum

Axionlike particles (ALPs) are hypothetical light (sub-eV) bosons predicted in some extensions of the Standard Model of particle physics. In astrophysical environments comprising high-energy gamma rays and turbulent magnetic fields, the existence of ALPs can modify the energy spectrum of the gamma rays for a sufficiently large coupling between ALPs and photons. This modification would take the form of an irregular behavior of the energy spectrum in a limited energy range. Data from the H.E.S.S. observations of the distant BL Lac object PKS 2155-304 (z=0.116) are used to derive upper limits at the 95% C.L. on the strength of the ALP coupling to photons, ggammaa<2.1×10-11GeV-1 for an ALP mass between 15 and 60 neV. The results depend on assumptions on the magnetic field around the source, which are chosen conservatively. The derived constraints apply to both light pseudoscalar and scalar bosons that couple to the electromagnetic fieldFil: Medina, Maria Clementina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto Argentino de Radioastronomia (i); ArgentinaFil: H.E.S. S. collaboration

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals