Forty Years Later: Naming Without Necessity, Necessity Without Naming

The essay examines the proper treament of (i) naming (ii) necessity. (A) It argues their mutual independence (B) provides a treatment of naming separately from any idea of "designation" (C) gives treatment of de re modality without any use of possible worlds, essences, concepts, rigid designators (D) it argues an ultimate asymmetry-naming/referring is a key real notion of semantics; necessity should not be the central idea in the metaphysics of nature

The Calbindin-D28k binding site on inositol monophosphatase may allow inhibition independent of the lithium site of action

Among numerous reported biochemical effects the lithium-inhibitable enzyme inositol-monophosphatase (IMPase) remains a viable target for lithium's therapeutic mechanism of action. Calbindin-D28k (calbindin) interacts with IMPase enhancing its activity. In the present study in silico modeling of IMPase-calbindin binding using the program MolFit indicated that the 55-66 amino acid segment of IMPase anchors calbindin via Lys59 and Lys61 with a glutamate in between (Lys-Glu-Lys motif). The model further suggested that the Lys-Glu-Lys motif interacts with residues Asp24 and Asp26 of calbindin. Indeed, we found that differently from wildtype calbindin, IMPase was not activated by mutated calbindin in which Asp24 and Asp26 were replaced by alanine. Calbindin's effect was significantly reduced by a peptide with the sequence of amino acids 58-63 of IMPase (peptide 1) and by six amino-acid peptides including at least part of the Lys-Glu-Lys motif. The three amino-acid peptide Lys-Glu-Lys or five amino-acid peptides containing this motif were ineffective. Intracerebroventricular administration of peptide 1 resulted in a significant antidepressant-like reduced immobility in the Porsolt forced swim test (FST) compared with mice treated with a scrambled peptide or artificial cerebrospinal fluid. Based on the sequence of peptide 1, and to potentially increase the peptide's stability, cyclic and linear pre-cyclic analog peptides were synthesized. One cyclic and one linear pre-cyclic analog peptides exhibited an inhibitory effect on calbindin-activated brain IMPase activity in vitro. These findings may lead to the development of molecules capable of inhibiting IMPase activity at an alternative site than that of lithium

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41394/1/10350_2005_Article_167.pd

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Proactive forensic science in biometrics: Novel materials for fingerprint spoofing

Motivated by the need to prepare for the next generation of fingerprint spoofing, we applied the “proactive forensic science” strategy to the biometric field. The working concept, already successful in a few fields, aimed at adopting the sophisticated criminals' way of thinking, predicting their next move so that the crime‐fighting authorities can be one step ahead of them and take preventive measures, against biometric spoofing in this instance. This strategy involved the design, production, and characterization of innovative polymeric materials that could possibly serve in advanced fingerprint spoofs. Special attention was given to materials capable of fooling fingerprint readers equipped with spoof‐detecting abilities, known as “Presentation Attack Detection” (PAD) systems and often referred to as liveness detection. A series of direct cast fake fingerprints was produced from known commercially available spoofing materials, and was functionally tested to compare their performance with that of spoofs produced from the new polymers. The novel materials thus prepared were hydrogels based on polyethylene glycols (PEGs) that were chain‐extended. They showed good performance in deceiving security systems, considerably better than that of spoofs produced from commercial materials, and are, therefore, good spoofing candidates that law‐enforcement authorities should be aware of

The semantics of common nouns and the nature of semantics

In “Is semantics possible?” Putnam connected two themes: the very possibility of semantics (as opposed to formal model theory) for natural languages and the proper semantic treatment of common nouns. Putnam observed that abstract semantic accounts are modeled on formal languages model theory: the substantial contribution is rules for logical connectives (given outside the models), whereas the lexicon (individual constants and predicates) is treated merely schematically by the models. This schematic treatment may be all that is needed for an account of validity in a formal setting, but it does not help to understand how proper and common nouns function in reality (not in models). Putnam then initiated the empirical study of such nouns to indicate, (i), that the popular Frege-Carnap account of them as (“disguised” compound) predicates is empirically incorrect, and, (ii), that they offer a new paradigm for a naturalistic semantics of natural languages. We take Putnam’s program a couple of steps further. First, we investigate the semantics of common nouns and argue that they refer (to kinds), rather than apply by satisfaction/truth to a designation/denotation. Second, we point to general results about semantics as a theory whose fulcrum is the reference relation rather than satisfaction in models and validity across them

Having in Mind

The book presents a series of papers on the philosophy of Keith Donnellan. The papers are by J.Perry, A. Capuano, E. Eaker, A. Bianchi, H. Wettstein, T. Burge, D. Kaplan, J. Almog

Reference, inference and the semantics of pejoratives

The full-text of this book chapter is not available in ORA. Citation: Williamson, T. (2009). Reference, inference and the semantics of pejoratives. In: Almog, J. & Leonardi, P. (eds.) The Philosophy of David Kaplan. Oxford: Oxford University Press, pp. 137-158

Essays on Reference, Language, and Mind

The book republishes seven papers by Keith Donnellan, with a new introduction by the same Donnellan. There is a very short presentation of Donnellan by J. Almog