The dental amalgam issue. A review

Summary Using an interdisciplinary approach, the current position in the dental amalgam controversy and the potential impact of amalgam mercury on human health are reviewed. Aspects of materials science, corrosion, mercury exposure, toxicology, neurology and immunology are included.New data on mercury exposure from corroded amalgam fillings in vivo are presented. The exposure can reach levels considerably over known threshold limit values. Also, measurements of mercury absorption from intraoral air are presented. The vital importance of avoiding a galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled patient, who recovered after amalgam removal, has been included.It is concluded that discussion of the dental amalgam issue has suffered from the lack of an interdisciplinary approach. It would be wise to learn from the lesson of acrodynia, and consider amalgam mercury among other possible factors in neurological and immunological diseases of unclear etiology.     

The dental amalgam issue. A review

Using an interdisciplinary approach, the current position in the dental amalgam controversy and the potential impact of amalgam mercury on human health are reviewed. Aspects of materials science, corrosion, mercury exposure, toxicology, neurology and immunology are included. New data on mercury exposure from corroded amalgam fillings in vivo are presented. The exposure can reach levels considerably over known threshold limit values. Also, measurements of mercury absorption from intraoral air are presented. The vital importance of avoiding a galvanic amalgam-gold coupling is emphasized. The symptomatology of a disabled patient, who recovered after amalgam removal, has been included. It is concluded that discussion of the dental amalgam issue has suffered from the lack of an interdisciplinary approach. It would be wise to learn from the lesson of acrodynia, and consider amalgam mercury among other possible factors in neurological and immunological diseases of unclear etiology.     

Representing with imaginary models: Formats matter

Models such as the simple pendulum, isolated populations, and perfectly rational agents, play a central role in theorising. It is now widely acknowledged that a study of scientific representation should focus on the role of such imaginary entities in scientists’ reasoning. However, the question is most of the time cast as follows: How can fictional or abstract entities represent the phenomena? In this paper, I show that this question is not well posed. First, I clarify the notion of representation, and I emphasise the importance of what I call the “format” of a representation for the inferences agents can draw from it. Then, I show that the very same model can be presented under different formats, which do not enable scientists to perform the same inferences. Assuming that the main function of a representation is to allow one to draw predictions and explanations of the phenomena by reasoning with it, I conclude that imaginary models in abstracto are not used as representations: scientists always reason with formatted representations. Therefore, the problem of scientific representation does not lie in the relationship of imaginary entities with real systems. One should rather focus on the variety of the formats that are used in scientific practice.     

Successful visual epistemic representation

In this paper, I characterize visual epistemic representations as concrete two- or three-dimensional tools for conveying information about aspects of their target systems or phenomena of interest. I outline two features of successful visual epistemic representation: that the vehicle of representation contain sufficiently accurate information about the phenomenon of interest for the user's purpose, and that it convey this information to the user in a manner that makes it readily available to her. I argue that actual epistemic representation may involve tradeoffs between these features and is successful to the extent that they are present.     

Mathematical formalisms in scientific practice: From denotation to model-based representation

The present paper argues that ‘mature mathematical formalisms’ play a central role in achieving representation via scientific models. A close discussion of two contemporary accounts of how mathematical models apply—the DDI account (according to which representation depends on the successful interplay of denotation, demonstration and interpretation) and the ‘matching model’ account—reveals shortcomings of each, which, it is argued, suggests that scientific representation may be ineliminably heterogeneous in character. In order to achieve a degree of unification that is compatible with successful representation, scientists often rely on the existence of a ‘mature mathematical formalism’, where the latter refers to a—mathematically formulated and physically interpreted—notational system of locally applicable rules that derive from (but need not be reducible to) fundamental theory. As mathematical formalisms undergo a process of elaboration, enrichment, and entrenchment, they come to embody theoretical, ontological, and methodological commitments and assumptions. Since these are enshrined in the formalism itself, they are no longer readily obvious to either the novice or the proficient user. At the same time as formalisms constrain what may be represented, they also function as inferential and interpretative resources.     

Odor maps in the brain: Spatial aspects of odor representation in sensory surface and olfactory bulb

The olfactory sense detects and distinguishes a multitude of different odors. Recent progress in molecular as well as physiological approaches has elucidated basic principles of neuronal encoding of odorants, common to insects and vertebrates. The construction of neuronal representations for odors begins with the task of mapping the multidimensional odor space onto the two-dimensional sensory surface, and subsequently onto the olfactory bulb or antennal lobe. A distributed expression of odorant receptors, albeit restricted to subregions of the sensory surface (large, intermediate or small for zebrafish, mouse or drosophila, respectively), ensures a robust representation, insensitive to mechanical insult. Olfactory receptor neurons expressing the same odorant receptors converge to form a receptotopic map in the olfactory bulb or antennal lobe. The emerging coding principle is a chemotopic representation of odorants at the first brain level, realized either as combinatorial or as monospecific representation, depending on the odorant.     

Dose relationships of morning bright white light in seasonal affective disorders (SAD)

Bright white full spectrum light (greater than 2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.     

Measurement,coordination, and the relativized a priori

The problem of measurement is a central issue in the epistemology and methodology of the physical sciences. In recent literature on scientific representation, large emphasis has been put on the “constitutive role” played by measurement procedures as forms of representation. Despite its importance, this issue hardly finds any mention in writings on constitutive principles, viz. in Michael Friedman׳s account of relativized a priori principles. This issue, instead, was at the heart of Reichenbach׳s analysis of coordinating principles that has inspired Friedman׳s interpretation. This paper suggests that these procedures should have a part in an account of constitutive principles of science, and that they could be interpreted following the intuition originally present (but ultimately not fully developed) in Reichenbach׳s early work.     

Dose relationships of morning bright white light in seasonal affective disorders (SAD)

Summary Bright white full spectrum light (>2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.     

Forecasting business failure in China using case‐based reasoning with hybrid case respresentation

Case‐based reasoning (CBR) is a very effective and easily understandable method for solving real‐world problems. Business failure prediction (BFP) is a forecasting tool that helps people make more precise decisions. CBR‐based BFP is a hot topic in today's global financial crisis. Case representation is critical when forecasting business failure with CBR. This research describes a pioneer investigation on hybrid case representation by employing principal component analysis (PCA), a feature extraction method, along with stepwise multivariate discriminant analysis (MDA), a feature selection approach. In this process, sample cases are represented with all available financial ratios, i.e., features. Next, the stepwise MDA is used to select optimal features to produce a reduced‐case representation. Finally, PCA is employed to extract the final information representing the sample cases. All data signified by hybrid case representation are recorded in a case library, and the k‐nearest‐neighbor algorithm is used to make the forecasting. Thus we constructed a hybrid CBR (HCBR) by integrating hybrid case representation into the forecasting tool. We empirically tested the performance of HCBR with data collected for short‐term BFP of Chinese listed companies. Empirical results indicated that HCBR can produce more promising prediction performance than MDA, logistic regression, classical CBR, and support vector machine. Copyright © 2009 John Wiley & Sons, Ltd.     

美国公共卫生应急系统及其对中国的启示

SARS在中国的流行暴露出我国防治突发性传染病的公共卫生应急系统的弊端：疫情信息发布不公开、不透明，缺乏应对突发性传染病的必要准备，在公共卫生方面投入不足。相比之下，建立了公共卫生应急系统的国家，例如美国，损失则要小得多。我们要借鉴美国公共卫生应急系统的经验，完善我国的公共卫生应急系统。这就要求我们必须建立快捷、畅通、准确、及时的信息传递网络，成立常设的公共卫生应急系统，加大在公共卫生方面的投入。     

Reflections on Kant’s concept (and intuition) of space

In this paper, I investigate an important aspect of Kant’s theory of pure sensible intuition. I argue that, according to Kant, a pure concept of space warrants and constrains intuitions of finite regions of space. That is, an a priori conceptual representation of space provides a governing principle for all spatial construction, which is necessary for mathematical demonstration as Kant understood it.     

Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer’s disease: looking in the correct place at the right time?

Even though the etiology of Alzheimer’s disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies.     

The intriguing prion disorders

Prion diseases are among the most intriguing illnesses. Despite their rare incidence, they have captured enormous attention from the scientific community and general public. One of the most hotly debated issues in these diseases is the nature of the infectious material. In recent years increasing evidence has emerged supporting the protein-only hypothesis of prion transmission. In this model PrPSc (the pathological isoform of the prion protein, PrPC) represents the sole component of the infectious particle. However, uncertainties about possible additional factors involved in the conversion of PrPC into PrPSc remain despite extensive attempts to isolate and characterize these elusive components. In this article, we review recent developments concerning the protein-only hypothesis as well as the possible involvement of cellular factors in PrPC to PrPSc conformational change and their influence on the pathogenesis of prion diseases.     

Periostin in vitreoretinal diseases

Proliferative vitreoretinal diseases such as diabetic retinopathy, proliferative vitreoretinopathy (PVR), and age-related macular degeneration are a leading cause of decreased vision and blindness in developed countries. In these diseases, retinal fibro(vascular) membrane (FVM) formation above and beneath the retina plays an important role. Gene expression profiling of human FVMs revealed significant upregulation of periostin. Subsequent analyses demonstrated increased periostin expression in the vitreous of patients with both proliferative diabetic retinopathy and PVR. Immunohistochemical analysis showed co-localization of periostin with α-SMA and M2 macrophage markers in FVMs. In vitro, periostin blockade inhibited migration and adhesion induced by PVR vitreous and transforming growth factor-β2 (TGF-β2). In vivo, a novel single-stranded RNAi agent targeting periostin showed the inhibitory effect on experimental retinal and choroidal FVM formation without affecting the viability of retinal cells. These results indicated that periostin is a pivotal molecule for FVM formation and a promising therapeutic target for these proliferative vitreoretinal diseases.     

Functions and pathologies of BiP and its interaction partners

The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70) family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners, such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological characteristics of BiP and its interaction partners. Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008     

Defending eliminative structuralism and a whole lot more (or less)

Ontic structural realism argues that structure is all there is. In (French, 2014) I argued for an ‘eliminativist’ version of this view, according to which the world should be conceived, metaphysically, as structure, and objects, at both the fundamental and ‘everyday’ levels, should be eliminated. This paper is a response to a number of profound concerns that have been raised, such as how we might distinguish between the kind of structure invoked by this view and mathematical structure in general, how we should choose between eliminativist ontic structural realism and alternative metaphysical accounts such as dispositionalism, and how we should capture, in metaphysical terms, the relationship between structures and particles. In developing my response I shall touch on a number of broad issues, including the applicability of mathematics, the nature of representation and the relationship between metaphysics and science in general.     

Modelling and representing: An artefactual approach to model-based representation

The recent discussion on scientific representation has focused on models and their relationship to the real world. It has been assumed that models give us knowledge because they represent their supposed real target systems. However, here agreement among philosophers of science has tended to end as they have presented widely different views on how representation should be understood. I will argue that the traditional representational approach is too limiting as regards the epistemic value of modelling given the focus on the relationship between a single model and its supposed target system, and the neglect of the actual representational means with which scientists construct models. I therefore suggest an alternative account of models as epistemic tools. This amounts to regarding them as concrete artefacts that are built by specific representational means and are constrained by their design in such a way that they facilitate the study of certain scientific questions, and learning from them by means of construction and manipulation.     

Inhibition of protein misfolding and aggregation by natural phenolic compounds

Protein misfolding and aggregation into fibrillar deposits is a common feature of a large group of degenerative diseases affecting the central nervous system or peripheral organs, termed protein misfolding disorders (PMDs). Despite their established toxic nature, clinical trials aiming to reduce misfolded aggregates have been unsuccessful in treating or curing PMDs. An interesting possibility for disease intervention is the regular intake of natural food or herbal extracts, which contain active molecules that inhibit aggregation or induce the disassembly of misfolded aggregates. Among natural compounds, phenolic molecules are of particular interest, since most have dual activity as amyloid aggregation inhibitors and antioxidants. In this article, we review many phenolic natural compounds which have been reported in diverse model systems to have the potential to delay or prevent the development of various PMDs, including Alzheimer’s and Parkinson’s diseases, prion diseases, amyotrophic lateral sclerosis, systemic amyloidosis, and type 2 diabetes. The lower toxicity of natural compounds compared to synthetic chemical molecules suggest that they could serve as a good starting point to discover protein misfolding inhibitors that might be useful for the treatment of various incurable diseases.