Achieving completeness: from constructive set theory to large cardinals

This thesis is an exploration of several completeness phenomena, both in the constructive and the classical settings. After some introductory chapters in the first part of the thesis where we outline the background used later on, the constructive part contains a categorical formulation of several constructive completeness theorems available in the literature, but presented here in an unified framework. We develop them within a constructive reverse mathematical viewpoint, highlighting the metatheory used in each case and the strength of the corresponding completeness theorems. The classical part of the thesis focuses on infinitary intuitionistic propositional and predicate logic. We consider a propositional axiomatic system with a special distributivity rule that is enough to prove a completeness theorem, and we introduce weakly compact cardinals as the adequate metatheoretical assumption for this development. Finally, we return to the categorical formulation focusing this time on infinitary first-order intuitionistic logic. We propose a first-order system with a special rule, transfinite transitivity, that embodies both distributivity as well as a form of dependent choice, and study the extent to which completeness theorems can be established. We prove completeness using a weakly compact cardinal, and, like in the constructive part, we study disjunction-free fragments as well. The assumption of weak compactness is shown to be essential for the completeness theorems to hold.

Language against the odds, or rather not:the weak central coherence hypothesis and language

EV is a child with a talent for learning language combined with Asperger syndrome. EV’s talent is evident in the unusual circumstances of her acquisition of both her first (Bulgarian) and second (German) languages and the unique patterns of both receptive and expressive language (in both the L1 and L2), in which she shows subtle dissociations in competence and performance consistent with an uneven cognitive profile of skills and abilities. We argue that this case provides support for theories of language learning and usage that require more general underlying cognitive mechanisms and skills. One such account, the Weak Central Coherence (WCC) hypothesis of autism, provides a plausible framework for the interpretation of the simultaneous co-occurrence of EV’s particular pattern of cognitive strengths and weaknesses. Furthermore, we show that specific features of the uneven cognitive profile of Asperger syndrome can help explain the observed language talent displayed by EV. Thus, rather than demonstrating a case where language learning takes place despite the presence of deficits, EV’s case illustrates how a pattern of strengths within this profile can specifically promote language learning.

Simultaneous temperature and strain measurement with enhanced resolution up to 20 times by using a compact hybrid optical waveguide Bragg grating

A hybrid waveguide Bragg grating in optical fiber was fabricated and characterized, showing thermal responsivity of 211pm/°C. Proposed being used in fiber sensor, it demonstrates enhanced resolution by 20x and 2x for temperature and strain.

Simultaneous temperature and strain measurement with enhanced resolution up to 20 times by using a compact hybrid optical waveguide Bragg grating

A hybrid waveguide Bragg grating in optical fiber was fabricated and characterized, showing thermal responsivity of 211pm/°C. Proposed being used in fiber sensor, it demonstrates enhanced resolution by 20x and 2x for temperature and strain.

The metabolism of n-methyl compounds

The metabolism of compounds containing the N-methyl group is discussed with particular consideration being made to the possible role of the product of oxidative metabolism, the N-hydroxymethyl moiety, in the generation of potentially toxic, reactive electrophiles. Particular pathways which are considered are: (i), the production of formaldehyde; (ii), the generation of iminium ions or imines; and (iii), the formation of N-formyl compounds which might act as formylating agents. 4-Chloro-N-(hydroxymethyl)benzamide and 3-(4-chlorophenyl)-1-hydroxy-methyl-1-methylurea (the product of oxidative metabolism of 3-(4-chlorophenyl)-1,1-dimethylurea) are model carbinolamides which do not readily release formaldehyde. The electrophilic properties of these model carbinolamides were investigated: neither reacted with nucleophiles such as cyanide or glutathione under physiological conditions. In contrast, N-(acetoxymethyl)-4-chlorobenzamide yielded the cyanomethylamide with potassium cyanide and S-(4-chlorobenzamidomethyl)glutathione with glutathione. 4-Chloro-N-(hydroxymethyl)benzamide and 3-(4-chlorophenyl)-1,1-dimethylurea were not biotransformed to electrophilic moieties when incubated with mouse hepatic 9000 x g supernatant and Acetyl-CoA or PAPS-generating system. N-(Acetoxymethyl)-4-chlorobenzamide was non-mutagenic to Salmonella typhimurium in the short term bacterial assay; but toxicity to the bacteria was observed. 4-Chloro-N-(hydroxymethyl)benzamide and 3-(4-chlorophenyl)-1,1-dimethylurea showed no mutagenicity or toxicity in the mutagenicity assay including an Aroclor-induced rat hepatic 9000 x g supernatant. Addition of Acetyl-CoA or a PAPS-generating system did not produce a mutagenic response. 4-Chloro-N-formlbenzamide did not act as a formylating agent towards the weak nucleophile aniline. However, 4-chloro-N-formylbenzamide, N-formylbenzamide, 3-(4-chlorophenyl)-1-formyl-1-methylurea and 3-(4-chlorophenyl)-1-formylurea are all metabolised by mouse hepatic mirosomes and post-microsomal supernatant. The results demonstrate the potential for N-hydroxymethyl compounds to generate highly reactive species if these are substrates for conjugation with sulphate (or acetate). The model compounds employed here, apparently do not show any ability to be conjugated themselves, however, other N-hydroxymethyl compounds might be readily conjugated. The formation of N-formyl compounds does not appear to be toxicologically significant, as adjudged on limited experiments performed, but rather represent a detoxification pathway.

Creep crack growth in cast steam turbine casing steels

The creep rupture properties of cast ½Cr½Mo¼V and 1Cr1Mo¼V alloy steel used in the manufacture of power station steam generating plant. have been investigated. The effects of constraint and geometry on the creep rupture properties are also considered. The validity of various criteria controlling macroscopic creep crack growth in cast CrMoV alloys has been examined. It is found that neither the stress intensity factor nor reference stress correlate satisfactorily the creep crack growth rates at the test temperature of 550°C. Certain minimum displacements must be achieved for crack initiation and propagation. It is found that this displacement as measured by crack opening displacement or crack aspect ratio, is the same in both compact tension and centre-cracked panel geometries, is invariant with crack length and decreases with increasing constraint. The effect of constraint on creep crack growth rate in the two geometries is less conclusive. A new model describing creep crack growth in cast CrMoV alloy steels has been developed. The model is based on the results from a numerical finite element creep analysis of the relaxation and redistribution of stress ahead of an incubating creep crack . It is found that macroscopic creep crack growth in a material undergoing either plane stress or plane strain deformation can be described by a fracture stress which is based on the Von Mises equivalent stress. It has been shown that this model is capable of rationalising all of the experimental crack velocity data from the cast CrMoV alloys. The resultant degree of data correlation is far superior to that obtained when using the stress intensity factor or reference stress. A cumulative damage creep fracture model based upon the results from the numerical analysis has been developed. It is found that the model is capable of predicting the behaviour of propagating creep cracks in cast CrMoV alloys from smooth bar creep rupture data.

Sparse signal representation by adaptive non-uniform B-spline dictionaries on a compact interval

Non-uniform B-spline dictionaries on a compact interval are discussed in the context of sparse signal representation. For each given partition, dictionaries of B-spline functions for the corresponding spline space are built up by dividing the partition into subpartitions and joining together the bases for the concomitant subspaces. The resulting slightly redundant dictionaries are composed of B-spline functions of broader support than those corresponding to the B-spline basis for the identical space. Such dictionaries are meant to assist in the construction of adaptive sparse signal representation through a combination of stepwise optimal greedy techniques.

Novel peptide antagonists of adrenomedullin and calcitonin gene-related peptide receptors:identification, pharmacological characterization, and interactions with position 74 in receptor activity-modifying protein 1/3

Human adrenomedullin (AM) is a 52-amino acid peptide belonging to the calcitonin peptide family, which also includes calcitonin gene-related peptide (CGRP) and AM2. The two AM receptors, AM(1) and AM(2), are calcitonin receptor-like receptor (CL)/receptor activity-modifying protein (RAMP) (RAMP2 and RAMP3, respectively) heterodimers. CGRP receptors comprise CL/RAMP1. The only human AM receptor antagonist (AM(22-52)) is a truncated form of AM; it has low affinity and is only weakly selective for AM(1) over AM(2) receptors. To develop novel AM receptor antagonists, we explored the importance of different regions of AM in interactions with AM(1), AM(2), and CGRP receptors. AM(22-52) was the framework for generating further AM fragments (AM(26-52) and AM(30-52)), novel AM/alphaCGRP chimeras (C1-C5 and C9), and AM/AM(2) chimeras (C6-C8). cAMP assays were used to screen the antagonists at all receptors to determine their affinity and selectivity. Circular dichroism spectroscopy was used to investigate the secondary structures of AM and its related peptides. The data indicate that the structures of AM, AM2, and alphaCGRP differ from one another. Our chimeric approach enabled the identification of two nonselective high-affinity antagonists of AM(1), AM(2), and CGRP receptors (C2 and C6), one high-affinity antagonist of AM(2) receptors (C7), and a weak antagonist selective for the CGRP receptor (C5). By use of receptor mutagenesis, we also determined that the C-terminal nine amino acids of AM seem to be responsible for its interaction with Glu74 of RAMP3. We provide new information on the structure-activity relationship of AM, alphaCGRP, and AM2 and how AM interacts with CGRP and AM(2) receptors.

What makes a good article? Generating an insightful manuscript

Purpose – The purpose of this editorial is to provide guidance to EJM authors about the structure and presentation of manuscripts that are likely to be insightful and that will probably provide contributions to knowledge. Design/methodology/approach – The approach is editorial advice based on the Editors' experience of receiving circa 500 manuscripts during their first year as Joint Editors of EJM, but which is also consistent with guidance in other leading journals. Findings – Guidance is provided for authors when preparing and revising their manuscripts, which is also a basis for further discussion and exchange concerning the effectiveness of communicating research outcomes. Research limitations/implications – The guidance is based on the views of the EJM Joint Editors, although it is consistent with other leading journals. Practical implications – Hopefully, authors will find the guidance helpful, although the editors emphasise that it is guidance and not a strict prescription that must be obeyed. Originality/value – Hopefully, the editorial provides more “food for thought” for authors.