Magic,semantics, and Putnam’s vat brains

In this paper we offer an exegesis of Hilary Putnam’s classic argument against the brain-in-a-vat hypothesis offered in his Reason, truth and history (1981). In it, Putnam argues that we cannot be brains in a vat because the semantics of the situation make it incoherent for anyone to wonder whether they are a brain in a vat. Putnam’s argument is that in order for ‘I am a brain in a vat’ to be true, the person uttering it would have to be able to refer successfully to those things: the vat, and the envatted brain. Putnam thinks that reference can’t be secured without relevant kinds of causal relations, which, if envatted, the brain would lack, and so, it fails to be able to meaningfully utter ‘I am a brain in a vat’. We consider the implications of Putnam’s arguments for Cartesian scepticism and suggest that there may yet be some ways out of Putnam’s arguments for the traditional sceptic. In conclusion, we discuss the role of Putnam’s arguments against the brain in a vat hypothesis in his larger defense of his own internal realism against metaphysical realism.     

Paying People to Participate in Research: Why not?

This paper argues against paying people to participate in research. Volunteering to participate as a subject in a research program is not like taking a job. The main difference is to do with the risks inherent in research. Experimentation on human beings is, by definition, trying out something with an unknown consequence and exposes people to risks of harm which cannot be known in advance. This is the main reason for independent review by committee of research programs. It is based on a recognition that researchers are not always capable of putting the interests of their subjects ahead of their research objectives. It is not simply a matter of individual autonomy. Society has an obligation, prior to the protection of individual freedom and autonomy, to establish basic safeguards that are equitable in their operation.
Any inducement for participating in research would add to the difficulty subjects have in adequately assessing the risks of participating in research. An acceptance of inducement to participate in research would further increase the inequity of research conducted on the impecunious for the benefit of the well-off.     

Currently available molluscicides

Views about the importance of the role of molluscicides in the integrated control of human schistosomiasis have passed through cyclical changes over the past 15 years. For a time, it was hoped that chemotherapy alone would achieve significant morbidity control; it has since become clear that molluscicides cannot be easily excluded from the anti-schistosome armoury. In this review, Sheena Perrett and Phil Whitfield summarize the evidence for this conclusion and provide an overview of currently available synthetic molluscicides and those natural product molluscicides currently under active investigation.     

A reappraisal of the proposed metabolic and antioxidant actions of butylated hydroxytoluene (BHT) in the liver

Butylated hydroxytoluene (BHT) was investigated for its metabolic actions in the perfused rat liver. Contrary to what is expected from an uncoupler, BHT up to 500 μM did not stimulate oxygen uptake nor did it inhibit gluconeogenesis from lactate. Transformation of fructose into glucose was also not affected by BHT; only lactate production was slightly increased at the concentration of 100 μM. The uncoupling effect of BHT in isolated mitochondria was confirmed, but only at concentrations above 10 μM; uncoupling at lower concentrations, 10^?9 to 10^?6 M, could not be confirmed. BHT, however, increased reactive oxygen species (ROS) production in isolated mitochondria, starting at the concentration of 10^?8 M. This is the opposite of what can be expected from a compound with proven ex vivo antioxidant action. One cannot exclude the possibility that, in mitochondria, stimulation of ROS production rather than uncoupling could be the most significant effect of BHT.     

Differential polarized phase fluorometric studies of the perturbation of phospholipid packing by BHT

Butylated hydroxytoluene (BHT) partitions effectively into lipids and modifies cellular function and behavior in numerous ways, particularly at low temperatures. In this study, the modification by BHT of the lifetime and dynamic rotational characteristics of diphenylhexatriene (DPH) in dipalmitoylphosphatidylcholine (DPPC) liposomes was investigated by phase fluorometry. BHT broadens the gel to liquid crystalline transition of DPPC by decreasing the lower end of the transition (T1), leaving the upper end (Th) unaffected. The lifetime of DPH in DPPC does not vary linearly with temperature but declines sharply above the main transition. The average lifetime of DPH is decreased to a greater extent below, compared to above, Th by BHT. This may be due to increased water penetration into the bilayer interior. Non-monoexponential decay also occurs below Th, probably due to a heterogeneous distribution of BHT, which would result in highly perturbed regions of greater than average BHT content. The motional parameter of DPH most affected by BHT is the order parameter (S) which decreased to a considerable extent below Th but is not affected above Th. In contrast, the rotational diffusion coefficient (R) of DPH is increased slightly above Th by BHT.     

Determination of stoichiometry of radioiodination of proteins

A sensitive method for the detection of small quantities of hydrophobic antioxidant free radical scavengers such as butylatedhydroxytoluene (BHT) and butylatedhydroxyanisole (BHA) in aqueous samples is described. The procedure involves extraction of the hydrophobic free radical scavenger into an organic solvent phase, followed by the subsequent reaction of an aliquot of this extract with the stable cation radical tris(p-bromophenyl)amminium hexachloroantimonate (TBACA). In experiments with BHT and BHA, the loss of TBACA absorbance at 730 nm was found to be linearly proportional to the amount of antioxidant added, with quantities of BHT as small as 200 pmol being easily detectable. In aqueous suspensions of dimyristoylphosphatidylcholine vesicles, assays of the aqueous BHT concentration showed that BHT partitioned strongly into the membrane phase, achieving very high BHT/phospholipid ratios. For a given concentration of BHT, partitioning into the membrane phase was greater in large, multilamellar liposomes than in either small, single-walled vesicles or in purified rat brain synaptic vesicle membranes. Direct assay of BHT and BHA in phospholipid membranes, however, was complicated by a nonspecific interaction between TBACA and the phospholipid.     

Defence against reactive oxygen species

As part of the European Commission Concerted Action on Functional Food which was managed by the International Life Sciences Institute (Europe) a series of Theme Papers was produced which examined the ‘state of the art’ with respect to the subject matter and made recommendations for research. This paper is a summary of the paper concerned with Defence Against Reactive Oxygen species. Having reviewed the scientific literature the authors concluded that certain stringent criteria, which they identified, would need to be satisfied in order to be able to conclude that free radical events are involved in certain human diseases, and that antioxidants are capable of modulating these events and thus reducing the risk of disease. Although there is some evidence that would lead to this conclusion the authors demonstrated that there is at present insufficient evidence available on which to base a firm conclusion that antioxidants are capable of reducing risk of disease, and very little evidence that addresses the important question as to how much of the nutrients concerned are required in the diet to achieve the objective of reducing risk. Research priorities address the need in particular for the development and validation of cellular markers of oxidative damage which are required before there can be new human studies that address the question. There is also a need for more information as to the pharmacokinetics of uptake from diet, distribution and cellular concentration of the antioxidants.     

Defense against reactive oxygen species

As part of the European Commission Concerted Action on Functional Food which was managed by the International Life Sciences Institute (Europe) a series of Theme Papers was produced which examined the 'state of the art' with respect to the subject matter and made recommendations for research. This paper is a summary of the paper concerned with Defence Against Reactive Oxygen species. Having reviewed the scientific literature the authors concluded that certain stringent criteria, which they identified, would need to be satisfied in order to be able to conclude that free radical events are involved in certain human diseases, and that antioxidants are capable of modulating these events and thus reducing the risk of disease. Although there is some evidence that would lead to this conclusion the authors demonstrated that there is at present insufficient evidence available on which to base a firm conclusion that antioxidants are capable of reducing risk of disease, and very little evidence that addresses the important question as to how much of the nutrients concerned are required in the diet to achieve the objective of reducing risk. Research priorities address the need in particular for the development and validation of cellular markers of oxidative damage which are required before there can be new human studies that address the question. There is also a need for more information as to the pharmacokinetics of uptake from diet, distribution and cellular concentration of the antioxidants.     

On the anti-atherogenic effect of the antioxidant BHT in cholesterol-fed rabbits: inverse relation between serum triglycerides and atheromatous lesions.

We have shown that inclusion of the antioxidant butylated hydroxytoluene (BHT) in the diet protects against development of atherosclerotic lesions in cholesterol-fed rabbits. In parallel, BHT treatment results in increased plasma triglyceride levels. The present study explores the relationship between the triglyceride-inducing and protective effects of BHT in two different studies. The combined material contains 22 rabbits fed cholesterol and 18 rabbits fed cholesterol in combination with 1% BHT. In the BHT group there was an inverse relationship between triglyceride exposure/cholesterol exposure and extent of lesions with r=0.74 (P=0.0005). Our results show that increased triglyceride exposure parallels the anti-atherogenic effect of BHT. There was no significant correlation between atheromatosis and serum BHT levels. beta-very low density lipoprotein (beta-VLDL) from cholesterol and BHT animals was triglyceride-enriched and smaller compared to beta-VLDL from cholesterol-fed animals, but there was no significant association between the anti-atherogenic effect of BHT and particle size or apolipoprotein pattern of LDL or beta-VLDL. LDL isolated from rabbits treated with cholesterol and BHT was less sensitive to oxidative modification than LDL isolated from rabbits treated with cholesterol only. In conclusion, our results demonstrate that the degree of triglyceride exposure may be an important modulator of the anti-atherogenic effect of an antioxidant.     

Modified low density lipoproteins activate human macrophages to secrete immunoreactive endothelin

This study attempted to determine if low density lipoproteins (LDL) induce the production of endothelins (ET) by human macrophages. Non-protected LDL from macrophage induced oxidation (n-LDL), copper-oxidized LDL (Ox-LDL), acetylated-LDL (Ac-LDL), butylated hydroxytoluene-LDL (BHT-LDL), BHT-Ac-LDL, polyinosinic acid (PiA, 1.5 micrograms/ml), phorbol myristate acetate (PMA; 0.5 microM) and BHT alone (20 microM) were studied. The different compounds had the following potency to stimulate the ET secretion: PMA greater than Ox-LDL greater than Ac-LDL greater than n-LDL greater than BHT-LDL greater than PiA greater than PiA + Ac-LDL greater than BHT. In conclusion, modified LDL stimulated ET secretion by human macrophages.     

Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity

Vaccination of mice with a peptide corresponding to the extracellular part of M2 protein coupled to the immunodominant domain of hepatitis B core can protect mice from a lethal challenge with influenza A virus. As the extracellular part of M2 protein is highly conserved in all known human influenza A strains, such a vaccine may protect against all human influenza A strains, which would represent a major advantage over current vaccine strategies. The present study demonstrates that protection is mediated exclusively by Abs, a very important feature of a successful preventive vaccine. However, these Abs neither bind efficiently to the free virus nor neutralize virus infection, but bind to M2 protein expressed on the surface of virus-infected cells. The presence of NK cells is important for protection, whereas complement is not, supposing that protection is mediated via Ab-dependent, cell-mediated cytotoxicity. The absence of neutralizing Abs results in much weaker protection than that achieved by vaccination with UV-inactivated influenza virus. Specifically, whereas neutralizing Abs completely eliminate signs of disease even at high viral challenge doses, M2-specific Abs cannot prevent infection, but merely reduce disease at low challenge doses. M2-specific Abs fail to protect from high challenge doses, as vaccinated mice undergo lethal infection under these conditions. In conclusion, protection mediated by M2-hepatitis B core vaccine would be insufficient during the yearly epidemics, for which full protection is desirable, and overall is clearly inferior to protection achieved by immunization with classical inactivated viral preparations.     

Genetic research and consent: On the crossroads of human and data research

This paper explores the legal and ethical concept of human subject research in order to determine whether genetic research with already available biosamples and data falls within this concept. Although the ethical concept seems to have evolved to recognize research based on data as human research, from a supranational legal perspective this form of research is not considered human subject research. Thus human subject research regulations do not apply and therefore do not invoke the requirement of obtaining consent prior to using an individual’s biosample or genetic data in research. Furthermore, it remains ambiguous in both the legal and ethical realm whether the use of biosamples or genetic data without additional links to the individual would invoke the same safeguards as research involving additional or specific identifiers. Seeing that research based on already available biosamples and genetic data is not governed by rules concerning human subject research, the second part of the paper analyses whether any consent requirements apply for the further use of already available bio‐samples or genetic data in research. Whereas further use of biosamples is subject to considerably lax consent requirements under Article 22 of the Oviedo Convention, under the General Data Protection Regulation further use of genetic data might not be subject to a prior consent requirement at all, unless it is stipulated in national laws. When it comes to clinical trials, however, sponsors will have the possibility under Article 28(2) of Regulation 536/2014 to obtain open consent for further use of data in any kind of future research.     

From ethnic minorities to ethnic majority policy: Multiculturalism and the shift to assimilationism in the Netherlands

Abstract

Recently in numerous European countries of immigration, there has been a widespread ‘moral panic’ about immigrants and ethnic diversity. In The Netherlands, a backlash has occurred in policy and in public discourse, with migrants being blamed for not meeting their responsibility to integrate and for practising ‘backward religions’. Why is it that a self-defined ‘liberal’ and ‘tolerant’ society demands conformity, compulsion and introduces seemingly undemocratic sanctions towards immigrants in a move towards assimilationism? These issues are analysed by providing an overview of modes of incorporation of immigrants in the Netherlands and it presents evidence on the socio-economic situation of immigrants. The article argues that patterns of disadvantage cannot be explained solely by the low human capital attributes of the original immigrants. In spite of multiculturalism, the causes have to be sought in pervasive institutional discrimination and the persistence of a culture of racism. The study argues that a shift to assimilation is more likely to create further societal divisions.     

Demonstration of shared antigenic determinants between Streptococcus mutans BHT cell membrane, human heart tissue and myosin using monoclonal antibodies to S. mutans

Monoclonal antibodies (MAb) raised to intact Streptococcus mutans P-4 cells (serotype e) were used to demonstrate the presence of shared antigenic determinant(s) between S. mutans BHT (serotype b) cell membranes and human heart tissue. MAb binding to both BHT membrane and human heart tissue was demonstrated by ELISA. Common antigens were identified by immunoblot analysis following separation of BHT membrane components and human heart antigens by SDS-PAGE. MAb 22C4 recognized three polypeptides from the BHT membrane preparation, having molecular masses of 42, 56 and 85 kDa. MAb 22C4 also recognized an 85 kDa component and a 200 kDa component from human heart tissue. MAb D159 was specific for a single 82 kDa polypeptide in BHT membrane, and also bound to two high molecular mass components in human heart (165 and 200 kDa). When both MAb D159 and 22C4 were first absorbed with S. mutans P-4 cells, subsequent reactivity to the aforementioned BHT membrane components was inhibited, indicating that these cross-reactive components are found in S. mutans P-4 as well as in S. mutans BHT micro-organisms. Competitive binding analysis showed that both MAb D159 and MAb 22C4 bound to myosin, indicating that S. mutans BHT membrane, human heart tissue and myosin share at least one immunodeterminant. This indicates that myosin could be the cross-reactive tissue component in human heart.     

Reply to ‘Measurement of nitrogenase activity in legume root nodules: In defense of the acetylene reduction assay’ by J.K. Vessey

This article is in response to that of Vessey (1994) who argues that the traditional, closed acetylene reduction assay can still be a valuable tool for measuring relative differences in nitrogenase activity of legumes. To counter this assertion we consider the practical uses of the traditional assay procedure in relation to real research situations. This requires the use of the assay to be considered separately in the different circumstances of pot-grown and field-grown plants. We conclude that for pot-grown legumes there are a few practical applications where the use of the traditional, closed assay procedure is valid and we accept that these can be extended by the careful use of calibrations against open, flow-through systems. However, we doubt that there are many situations where such a calibration approach would have practical advantages over using the flow-through system to obtain the actual measurements. We cannot recommend any form of the uncalibrated acetylene reduction assay for field-based studies and suggest that researchers consider the merits of simple, alternative measurements such as dry weight, yield and total nitrogen.     

Effect of butylated hydroxytoluene on bilineage differentiation of the human HL-60 myeloblastic leukemia cell

Butylated hydroxytoluene (BHT), which has both antioxidant and membrane active properties, has been reported to affect cellular differentiation. We studied its effect on the bipotent lineage differentiation of the important HL-60 human myeloblastic leukemia cell line using reduction of nitroblue tetrazolium, cell cycle analysis, population growth rate, monoclonal antibodies, and morphology. BHT markedly accelerated retinoic acid-induced myelocytic differentiation and dihydroxyvitamin D3-induced monocytic differentiation in a concentration and time-dependent manner. Butylated hydroxyanisole (BHA) had a comparable effect. Preincubation with the compounds was not necessary to evoke the acceleration Other antioxidants and inhibitors of eicosanoid synthesis were inactive. We conclude that the important food preservatives BHT and BHA accelerate the kinetics of terminal differentiation of human leukemia and that this effect is likely due at least in part to their membrane active properties.     

Reinvestigation of the role of the optic vesicle in embryonic lens induction

The induction of the lens by the optic vesicle in amphibians is often cited as support for the view that a single inductive event can lead to determination in a multipotent tissue. This conclusion is based on transplantation experiments whose results indicate that many regions of embryonic ectoderm which would normally form epidermis can form a lens if brought into contact with the optic vesicle. Although additional evidence argues that during normal development other tissues, acting before the optic vesicle, also contribute to lens induction, it is still widely held, on the basis of these transplantation experiments, that the optic vesicle alone can elicit lens formation in ectoderm. While testing this conclusion by transplanting optic vesicles beneath ventral ectoderm in Xenopus laevis embryos, it became apparent that contamination of optic vesicles by presumptive lens ectoderm cells can generate lenses in these experiments, illustrating the need for adequate host and donor marking procedures. Since previous studies rarely used host and donor marking, it was not clear whether they actually demonstrated that the optic vesicle can induce lenses. Using careful host and donor marking procedures with horseradish peroxidase as a lineage tracer, we show that the optic vesicle cannot stimulate lens formation in neurula- or gastrula-stage ectoderm of Xenopus laevis. Since the general conclusion that the optic vesicle is sufficient for lens induction rests on studies in many organisms, we felt it was important to begin to test this conclusion in other amphibians as well. Similar experiments were therefore performed with Rana Palustris embryos, since it was in this organism that optic vesicle transplant studies had originally argued that this tissue alone can cause lens induction. Under conditions similar to those used in the original report, but with careful controls to assess the origin of lenses in transplants, we found that the optic vesicle alone cannot elicit lens formation. Our data lead us to propose that the optic vesicle in amphibians is not generally sufficient for lens induction. Instead, we argue that lens induction occurs by a multistep process in which an essential phase in lens determination occurs as a result of inductive interactions preceding contact of ectoderm with the optic vesicle.     

Value, obligation and the asymmetry question

Is there a prima facie obligation to produce additional individuals whose lives would be worth living? In his paper ‘Is it Good to Make Happy People?’, Stuart Rachels argues not only that there is, but, also, that precisely as much weight should be assigned to the quality of life that would be enjoyed by such potential persons, if they were to be actualized, as to the quality of life enjoyed by actually existing persons. In response, I shall argue, first, that Rachels’ view is exposed to very serious objections, and secondly, that his arguments in support of his position involve a crucial assumption, which cannot be sustained, concerning the relation between, on the one hand, propositions about good-making and bad-making properties, and, on the other, propositions about right-making and wrong-making ones. I shall then argue that there is a very plausible position concerning the conditions under which an action can be morally wrong which entails the following asymmetry: there is a prima facie obligation not to bring into existence individuals whose lives are not worth living, but there is no corresponding obligation to create additional individuals whose lives would be worth living.