Synapses, quantum theory and panpsychism

The introduction situates the ‘hard problem’ in its historical context and argues that the problem has two sides: the output side (the Kant-Eccles problem of the freedom of the Will) and the input side (the problem of qualia). The output side ultimately reduces to whether quantum mechanics can affect the operation of synapses. A discussion of the detailed molecular biology of synaptic transmission as presently understood suggests that such affects are unlikely. Instead an evolutionary argument is presented which suggests that our conviction of free agency is an evolutionarily induced illusion and hence that the Kant-Eccles problem is itself illusory. This conclusion is supported by well-known neurophysiology. The input side, the problem of qualia, of subjectivity, is not so easily outflanked. After a brief review of the neurophysiological correlates of consciousness (NCC) and of the Penrose-Hameroff microtubular neuroquantology it is again concluded that the molecular neurobiology makes quantum wave-mechanics an unlikely explanation. Instead recourse is made to an evolutionarily- and neurobiologically-informed panpsychism. The notion of an ‘emergent’ property is carefully distinguished from that of the more usual ‘system’ property used by most dual-aspect theorists (and the majority of neuroscientists) and used to support Llinas’ concept of an ‘oneiric’ consciousness continuously modified by sensory input. I conclude that a panpsychist theory, such as this, coupled with the non-classical understanding of matter flowing from quantum physics (both epistemological and scientific) may be the default and only solution to the problem posed by the presence of mind in a world of things.

Structural studies on antifolate drugs

Single crystal X-ray structure determinations are reported for eleven compounds all of which are either biologically active or potentially biologically important. The compounds fall into two distinct classes:- 1. Substituted diaminopyrimidines 2. Substituted aminopyrimidinones The first class of compounds were all selected on the basis of their common diaminopyrimidine nucleus which has been demonstrated to be a vital requirement for antifolate activity. They may all be described as non-classical or small molecule lipophilic dihydrofolate reductase (DHFR) inhibitors, as opposed to the classical folate analogues, having the ability to cross the blood-brain barrier, enter cells via a rapid passive diffusion process, and achieve high intracellular concentrations. Thus they are an excellent choice in the search for crystallography in the solid state, providing geometrical and distance data not available from any other analytical techniques to date; supporting and enhancing data obtained in the lower resolution studies of protein crystallography. The biological importance of these compounds is discussed and an attempt is made to relate/predict their pharmacological activity to observed structural features in the crystalline environment. Special attention is focussed on hydrogen bonding, confirmational flexibility and hydrophobicity of substituents; each of which appear to make contributions to tight binding in the enzyme active site. Chapter 9 describes the use of data from the literature and the solid state modelling of an observed enzyme-substrate interaction in an attempt to define it more accurately in terms of its geometric flexibility. Of the second class, one compound (ABPP) is reported; studies in two different crystal forms. In demonstrating both antiviral and high interferon inducing activity it is possible that this compound could be useful against cancer and also viral infections.

Studies on the chromosomal bets-lactamase of pseudomonas aeruginosa

The chromosomal ß-lactamase of Pseudomonas aeruginosa SAlconst (a derepressed laboratory strain) was isolated and purified. Two peaks of activity were observed on gel permeation chromatography (one major peak mol. wt. 45 kD and one minor peak of 54 kD). Preparations from 12 clinical derepressed strains showed identical results. Chromosomal ß-lactamase production in both normal and derepressed P. aeruginosa strains was induced both by iron restricted growth conditions and by penicillin G. The majority of the enzyme (80-90%) was found in the periplasm and cytoplasm but a significant amount (2-20%) was associated with the outer membrane (OM). The growth conditions did not affect the distribution of the enzyme between subcellular fractions although higher activity was found in the cells grown under iron limitation and/ or in the presence of ß-lactams. The penicillanate sulphone inhibitor, tazobactam, displayed irreversible kinetics whilst cloxacillin, cefotaxime, ampicillin and penicillin G were all competitive inhibitors of the enzyme. Similar results were obtained for the Enterobacter cloacae P99 [ß-lactamase, but tazobactam displayed a non-classical kinetic pattern for the Staphylococcus aureus PC1 ß-lactamase. The residues involved in ß-lactam hydrolysis by the P aeruginosa SAlconst enzyme were detennined by affinity labelling with tazobactam. A tryptic digestion fragment of the inhibited enzyme contained the amino acids D, T, S, E, P, G, A, C, V, M, I, Y, F, H, K, R. This suggests the involvement of the conserved SVSK, DAE and KTG motifs found in all penicillin sensitive proteins. A model of the 3-D structure of the active site of the P aeruginosa SAlconst chromosomal ß-!actamase was constructed from the published amino acid sequence of P aeruginosa chromosomal ß-lactamase and the a-carbon coordinates of the S. aureus PCI ß-lactamase by homology modelling and energy minimisation. The crystal structure of tazobactam was determined and energy minimised. Computer graphics docking identified Ser 72 as a possible residue involved in a secondary attack on the C5 position of tazobactam after initial ß-lactam hydrolysis by serine 70. The enhanced activity of tazobactam over sulbactam might be explained by the triazole substituent which might participate in favourable hydrogen bonding between N3 and active site residues.

Explicit Solutions of Nonlocal Boundary Value Problems, Containing Bitsadze-Samarskii Constraints

MSC 2010: 44A35, 35L20, 35J05, 35J25

Explicit Solution of Bitsadze-Samarskii Problem

Иван Димовски, Юлиан Цанков - В статията е намерено точно решение на задачата на Бицадзе-Самрски (1) за уравнението на Лаплас, като е използвано операционно смятане основано на некласическа двумернa конволюция. На това точно решение може да се гледа като начин за сумиране на нехармоничния ред по синуси на решението, получен по метода на Фурие.

Three-Dimensional Operational Calculi for Nonlocal Evolution Boundary Value Problems

Иван Христов Димовски, Юлиан Цанков Цанков - Построени са директни операционни смятания за функции u(x, y, t), непрекъснати в област от вида D = [0, a] × [0, b] × [0, ∞). Наред с класическата дюамелова конволюция, построението използва и две некласически конволюции за операторите ∂2x и ∂2y. Тези три едномерни конволюции се комбинират в една тримерна конволюция u ∗ v в C(D). Вместо подхода на Я. Микусински, основаващ се на конволюционни частни, се развива алтернативен подход с използване на мултипликаторните частни на конволюционната алгебра (C(D), ∗).

Exact Solutions of Nonlocal Boundary Value Problems for One- and Two-Dimensional Heat Equation

Иван Хр. Димовски, Юлиан Ц. Цанков - Предложен е метод за намиране на явни решения на клас двумерни уравнения на топлопроводността с нелокални условия по пространствените променливи. Методът е основан на директно тримерно операционно смятане. Класическата дюамелова конволюция е комбинирана с две некласически конволюции за операторите ∂xx и ∂yy в една тримерна конволюция. Съответното операционно смятане използва мултипликаторни частни. Мултипликаторните частни позволяват да се продължи принципът на Дюамел за пространствените променливи и да се намерят явни решения на разглежданите гранични задачи. Общите разглеждания са приложени в случая на гранични условия от типа на Йонкин. Намерени са експлицитни решения в затворен вид.

Exact Solutions of Nonlocal BVPs for the Multidimensional Heat Equations

MSC 2010: 44A35, 44A45, 44A40, 35K20, 35K05

Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.

On the microstructure, growth pattern and original porosity of belemnite rostra: insights from calcitic Jurassic belemnites

Calcitic belemnite rostra are usually employed to perform paleoenvironmental studies based on geochemical data. However, several questions, such as their original porosity and microstructure, remain open, despite they are essential to make accurate interpretations based on geochemical analyses.This paper revisits and enlightens some of these questions. Petrographic data demonstrate that calcite crystals of the rostrum solidum of belemnites grow from spherulites that successively develop along the apical line, resulting in a “regular spherulithic prismatic” microstructure. Radially arranged calcite crystals emerge and diverge from the spherulites: towards the apex, crystals grow until a new spherulite is formed; towards the external walls of the rostrum, the crystals become progressively bigger and prismatic. Adjacent crystals slightly vary in their c-axis orientation, resulting in undulose extinction. Concentric growth layering develops at different scales and is superimposed and traversed by a radial pattern, which results in the micro-fibrous texture that is observed in the calcite crystals in the rostra.Petrographic data demonstrate that single calcite crystals in the rostra have a composite nature, which strongly suggests that the belemnite rostra were originally porous. Single crystals consistently comprise two distinct zones or sectors in optical continuity: 1) the inner zone is fluorescent, has relatively low optical relief under transmitted light (TL) microscopy, a dark-grey color under backscatter electron microscopy (BSEM), a commonly triangular shape, a “patchy” appearance and relatively high Mg and Na contents; 2) the outer sector is non-fluorescent, has relatively high optical relief under TL, a light-grey color under BSEM and low Mg and Na contents. The inner and fluorescent sectors are interpreted to have formed first as a product of biologically controlled mineralization during belemnite skeletal growth and the non-fluorescent outer sectors as overgrowths of the former, filling the intra- and inter-crystalline porosity. This question has important implications for making paleoenvironmental and/or paleoclimatic interpretations based on geochemical analyses of belemnite rostra.Finally, the petrographic features of composite calcite crystals in the rostra also suggest the non-classical crystallization of belemnite rostra, as previously suggested by other authors.

Una planta sin clásicos. La berenjena en la farmacología medieval y renacentista

La berenjena (Solanum melongena L.) es una planta solanácea de múltiples variedades, cuyos ancestros salvajes se sitúan en Indochina y el este de África. Su cultivo fue muy temprano en zonas de China e India. Aun así, no se extendió al Occidente antiguo ni apenas se conoció, de ahí su ausencia en los textos clásicos de botánica y farmacología. Fueron los árabes quienes llevaron el cultivo de la planta por el Norte de África y Al-Andalus, de donde pasó ya a Europa. Los primeros testimonios occidentales de la berenjena aparecen en traducciones latinas de textos árabes, para incorporarse luego a la literatura farmacológica medieval y, más tarde ya, a la del Renacimiento, que empezó a tratar de ella por su posible parecido con una especie de mandrágora. Pese a que se le reconocían algunas virtudes medicinales, siempre se la tuvo bajo sospecha por ser de sabor poco agradable, indigesta y causante de algunas afecciones. Solo los botánicos de finales del Renacimiento describirían la planta y sus variedades con criterios más «científicos» y botánicos, ya sin apenas intereses farmacológicos.

Modal Control of Vibration in Rotating Machines and Other Generally Damped Systems

Second order matrix equations arise in the description of real dynamical systems. Traditional modal control approaches utilise the eigenvectors of the undamped system to diagonalise the system matrices. A regrettable consequence of this approach is the discarding of residual off-diagonal terms in the modal damping matrix. This has particular importance for systems containing skew-symmetry in the damping matrix which is entirely discarded in the modal damping matrix. In this paper a method to utilise modal control using the decoupled second order matrix equations involving non-classical damping is proposed. An example of modal control successfully applied to a rotating system is presented in which the system damping matrix contains skew-symmetric components.

Non-normal modal logics, quantification, and deontic dilemmas. A study in multi-relational semantics

This dissertation is devoted to the study of non-normal (modal) systems for deontic logics, both on the propositional level, and on the first order one. In particular we developed our study the Multi-relational setting that generalises standard Kripke Semantics. We present new completeness results concerning the semantic setting of several systems which are able to handle normative dilemmas and conflicts. Although primarily driven by issues related to the legal and moral field, these results are also relevant for the more theoretical field of Modal Logic itself, as we propose a syntactical, and semantic study of intermediate systems between the classical propositional calculus CPC and the minimal normal modal logic K.

Labelled tableaux for non-normal modal logics

In this paper we show how to extend KEM, a tableau-like proof system for normal modal logic, in order to deal with classes of non-normal modal logics, such as monotonic and regular, in a uniform and modular way.

C(alpha)-HOLDER CLASSICAL SOLUTIONS FOR NON-AUTONOMOUS NEUTRAL DIFFERENTIAL EQUATIONS

In this paper we discuss the existence of alpha-Holder classical solutions for non-autonomous abstract partial neutral functional differential equations. An application is considered.