Distinct contrast response functions in striate and extra-striate regions of visual cortex revealed with magnetoencephalography (MEG)

Objective: To spatially and temporally characterise the cortical contrast response function to pattern onset stimuli in humans. Methods: Magnetoencephalography (MEG) was used to investigate the human cortical contrast response function to pattern onset stimuli with high temporal and spatial resolution. A beamformer source reconstruction approach was used to spatially localise and identify the time courses of activity at various visual cortical loci. Results: Consistent with the findings of previous studies, MEG beamformer analysis revealed two simultaneous generators of the pattern onset evoked response. These generators arose from anatomically discrete locations in striate and extra-striate visual cortex. Furthermore, these loci demonstrated notably distinct contrast response functions, with striate cortex increasing approximately linearly with contrast, whilst extra-striate visual cortex followed a saturating function. Conclusions: The generators that underlie the pattern onset visual evoked response arise from two distinct regions in striate and extra-striate visual cortex. Significance: The spatially, temporally and functionally distinct mechanisms of contrast processing within the visual cortex may account for the disparate results observed across earlier studies and assist in elucidating causal mechanisms of aberrant contrast processing in neurological disorders. © 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A methodology for analysis and control of discrete event dynamic systems

The rapid developments in computer technology have resulted in a widespread use of discrete event dynamic systems (DEDSs). This type of system is complex because it exhibits properties such as concurrency, conflict and non-determinism. It is therefore important to model and analyse such systems before implementation to ensure safe, deadlock free and optimal operation. This thesis investigates current modelling techniques and describes Petri net theory in more detail. It reviews top down, bottom up and hybrid Petri net synthesis techniques that are used to model large systems and introduces on object oriented methodology to enable modelling of larger and more complex systems. Designs obtained by this methodology are modular, easy to understand and allow re-use of designs. Control is the next logical step in the design process. This thesis reviews recent developments in control DEDSs and investigates the use of Petri nets in the design of supervisory controllers. The scheduling of exclusive use of resources is investigated and an efficient Petri net based scheduling algorithm is designed and a re-configurable controller is proposed. To enable the analysis and control of large and complex DEDSs, an object oriented C++ software tool kit was developed and used to implement a Petri net analysis tool, Petri net scheduling and control algorithms. Finally, the methodology was applied to two industrial DEDSs: a prototype can sorting machine developed by Eurotherm Controls Ltd., and a semiconductor testing plant belonging to SGS Thomson Microelectronics Ltd.

Computer control of machines utilising independent drive mechanisms

The thesis describes an investigation into methods for the specification, design and implementation of computer control systems for flexible manufacturing machines comprising multiple, independent, electromechanically-driven mechanisms. An analysis is made of the elements of conventional mechanically-coupled machines in order that the operational functions of these elements may be identified. This analysis is used to define the scope of requirements necessary to specify the format, function and operation of a flexible, independently driven mechanism machine. A discussion of how this type of machine can accommodate modern manufacturing needs of high-speed and flexibility is presented. A sequential method of capturing requirements for such machines is detailed based on a hierarchical partitioning of machine requirements from product to independent drive mechanism. A classification of mechanisms using notations, including Data flow diagrams and Petri-nets, is described which supports capture and allows validation of requirements. A generic design for a modular, IDM machine controller is derived based upon hierarchy of control identified in these machines. A two mechanism experimental machine is detailed which is used to demonstrate the application of the specification, design and implementation techniques. A computer controller prototype and a fully flexible implementation for the IDM machine, based on Petri-net models described using the concurrent programming language Occam, is detailed. The ability of this modular computer controller to support flexible, safe and fault-tolerant operation of the two intermittent motion, discrete-synchronisation independent drive mechanisms is presented. The application of the machine development methodology to industrial projects is established.

The spatial arrangement patterns of senile plaques in senile dementia of the Alzheimer type (SDAT)

The spatial arrangement patterns of senile plaques have been studied in 10 micron cresyl violet stained sections cut from embedded portions of 20 brain regions from SDAT brains. Two studies are reported: an initial study using the Poisson distribution and a subsequent study using pattern analysis. The initial study indicated that plaques are arranged in discrete clumps in all brain regions when examined at x100 and x400 – suggesting that both small and larger scale clumping may be present. The pattern analysis study was applied to 8 cortical regions. This technique allows a more detailed study of pattern to be made. In all regions the technique revealed that the basic pattern of plaque arrangement is the regularly spaced discrete clump – which may be present on both large and small scales.

Mechanical vibration characteristics of bell-type pump maintings

This thesis describes an analytical and experimental study to determine the mechanical characteristics of the pump mounting, bell housing type. For numerical purposes, the mount was modelled as a thin circular cylindrical shell with cutouts, stiffened with rings and stringers; the boundary conditions were considered to be either clamped-free or clamped-supporting rigid heavy mass. The theoretical study was concerned with both the static response and the free vibration characteristics of the mount. The approach was based on the Rayleigh-Ritz approximation technique using beam characteristic (axial) and trigonometric (Circumferential) functions in the displacement series, in association with the Love - Timoshenko thin shell theory. Studies were carried out to determine the effect of the supported heavy mass on the static response, frequencies and mode shapes; in addition, the effects of stringers, rings and cutouts on vibration characteristics were investigated. The static and dynamic formulations were both implemented on the Hewlett Packard 9845 computer. The experimental study was conducted to evaluate the results of the natural frequencies and mode shapes, predicted numerically. In the experimental part, a digital computer was used as an experiment controller, which allowed accurate and quick results. The following observations were made: 1. Good agreements were obtained with the results of other investigators. 2. Satisfactory agreement was achieved between the theoretical and experimental results. 3. Rings coupled the axial modal functions of the plain cylinder and tended to increase frequencies, except for the torsion modes where frequencies were reduced. Stringers coupled the circumferential modal functions and tended to decrease frequencies. The effect of rings was stronger than that of stringers. 4. Cutouts tended to reduce frequencies; in general, but this depends on the location of the cutouts; if they are near the free edge then an increase in frequencies is obtained. Cutouts coupled both axial and circumferential modal functions. 5. The supported heavy mass had similar effects to those of the rings, but in an exaggerated manner, particularly in the reduction of torsion frequencies. 6. The method of analysis was found to be a convenient analytical tool for estimating the overall behaviour of the shell with cutouts.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation

Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuroprotective factor through the PACAP type 1 receptor, PAC1. In a previous work, we demonstrated that nerve growth factor augmented PAC1 gene expression through the activation of Sp1 via the Ras/MAPK pathway. We also observed that PAC1 expression in Neuro2a cells was transiently suppressed during in vitro ischemic conditions, oxygen-glucose deprivation (OGD). Because endoplasmic reticulum (ER) stress is induced by ischemia, we attempted to clarify how ER stress affects the expression of PAC1. Tunicamycin, which induces ER stress, significantly suppressed PAC1 gene expression, and salubrinal, a selective inhibitor of the protein kinase RNA-like endoplasmic reticulum kinase signaling pathway of ER stress, blocked the suppression. In luciferase reporter assay, we found that two Sp1 sites were involved in suppression of PAC1 gene expression due to tunicamycin or OGD. Immunocytochemical staining demonstrated that OGD-induced transglutaminase 2 (TG2) expression was suppressed by salubrinal or cystamine, a TG activity inhibitor. Further, the OGD-induced accumulation of cross-linked Sp1 in nuclei was suppressed by cystamine or salubrinal. Together with cystamine, R283, TG2-specific inhibitor, and siRNA specific for TG2 also ameliorated OGD-induced attenuation of PAC1 gene expression. These results suggest that Sp1 cross-linking might be crucial in negative regulation of PAC1 gene expression due to TG2 in OGD-induced ER stress. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling

Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Recent evidence indicates that maternal endothelial dysfunction in preeclampsia results from increased soluble Fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein. Factors responsible for excessive production of sFlt-1 in preeclampsia have not been identified. We tested the hypothesis that angiotensin II type 1 (AT1) receptor activating autoantibodies, which occur in women with preeclampsia, contribute to increased production of sFlt-1. IgG from women with preeclampsia stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in pregnant mice, human placental villous explants, and human trophoblast cells. Using FK506 or short-interfering RNA targeted to the calcineurin catalytic subunit mRNA, we determined that calcineurin/nuclear factor of activated T-cells signaling functions downstream of the AT1 receptor to induce sFlt-1 synthesis and secretion by AT1-receptor activating autoantibodies. AT1-receptor activating autoantibody–induced sFlt-1 secretion resulted in inhibition of endothelial cell migration and capillary tube formation in vitro. Overall, our studies demonstrate that an autoantibody from women with preeclampsia induces sFlt-1 production via angiotensin receptor activation and downstream calcineurin/nuclear factor of activated T-cells signaling. These autoantibodies represent potentially important targets for diagnosis and therapeutic intervention.

Vector Combinatorial Problems in a Space of Combinations with Linear Fractional Functions of Criteria

The paper considers vector discrete optimization problem with linear fractional functions of criteria on a feasible set that has combinatorial properties of combinations. Structural properties of a feasible solution domain and of Pareto–optimal (efficient), weakly efficient, strictly efficient solution sets are examined. A relation between vector optimization problems on a combinatorial set of combinations and on a continuous feasible set is determined. One possible approach is proposed in order to solve a multicriteria combinatorial problem with linear- fractional functions of criteria on a set of combinations.

Visualisation of bioinformatics datasets

Analysing the molecular polymorphism and interactions of DNA, RNA and proteins is of fundamental importance in biology. Predicting functions of polymorphic molecules is important in order to design more effective medicines. Analysing major histocompatibility complex (MHC) polymorphism is important for mate choice, epitope-based vaccine design and transplantation rejection etc. Most of the existing exploratory approaches cannot analyse these datasets because of the large number of molecules with a high number of descriptors per molecule. This thesis develops novel methods for data projection in order to explore high dimensional biological dataset by visualising them in a low-dimensional space. With increasing dimensionality, some existing data visualisation methods such as generative topographic mapping (GTM) become computationally intractable. We propose variants of these methods, where we use log-transformations at certain steps of expectation maximisation (EM) based parameter learning process, to make them tractable for high-dimensional datasets. We demonstrate these proposed variants both for synthetic and electrostatic potential dataset of MHC class-I. We also propose to extend a latent trait model (LTM), suitable for visualising high dimensional discrete data, to simultaneously estimate feature saliency as an integrated part of the parameter learning process of a visualisation model. This LTM variant not only gives better visualisation by modifying the project map based on feature relevance, but also helps users to assess the significance of each feature. Another problem which is not addressed much in the literature is the visualisation of mixed-type data. We propose to combine GTM and LTM in a principled way where appropriate noise models are used for each type of data in order to visualise mixed-type data in a single plot. We call this model a generalised GTM (GGTM). We also propose to extend GGTM model to estimate feature saliencies while training a visualisation model and this is called GGTM with feature saliency (GGTM-FS). We demonstrate effectiveness of these proposed models both for synthetic and real datasets. We evaluate visualisation quality using quality metrics such as distance distortion measure and rank based measures: trustworthiness, continuity, mean relative rank errors with respect to data space and latent space. In cases where the labels are known we also use quality metrics of KL divergence and nearest neighbour classifications error in order to determine the separation between classes. We demonstrate the efficacy of these proposed models both for synthetic and real biological datasets with a main focus on the MHC class-I dataset.

The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ:evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.

On a Class of Generalized Elliptic-type Integrals

The aim of this paper is to study a generalized form of elliptic-type integrals which unify and extend various families of elliptic-type integrals studied recently by several authors. In a recent communication [1] we have obtained recurrence relations and asymptotic formula for this generalized elliptic-type integral. Here we shall obtain some more results which are single and multiple integral formulae, differentiation formula, fractional integral and approximations for this class of generalized elliptic-type integrals.

Generalized Problem of Sratlikeness for Products of P-Valent Starlike Functions

∗ Partially supported by grant No. 433/94 NSF of the Ministry of Education and Science of the Republic of Bulgaria 1991 Mathematics Subject Classification:30C45

A Note on Coercivity of Lower Semicontinuous Functions and Nonsmooth Critical Point Theory

The first motivation for this note is to obtain a general version of the following result: let E be a Banach space and f : E → R be a differentiable function, bounded below and satisfying the Palais-Smale condition; then, f is coercive, i.e., f(x) goes to infinity as ||x|| goes to infinity. In recent years, many variants and extensions of this result appeared, see [3], [5], [6], [9], [14], [18], [19] and the references therein. A general result of this type was given in [3, Theorem 5.1] for a lower semicontinuous function defined on a Banach space, through an approach based on an abstract notion of subdifferential operator, and taking into account the “smoothness” of the Banach space. Here, we give (Theorem 1) an extension in a metric setting, based on the notion of slope from [11] and coercivity is considered in a generalized sense, inspired by [9]; our result allows to recover, for example, the coercivity result of [19], where a weakened version of the Palais-Smale condition is used. Our main tool (Proposition 1) is a consequence of Ekeland’s variational principle extending [12, Corollary 3.4], and deals with a function f which is, in some sense, the “uniform” Γ-limit of a sequence of functions.

Generalizing of Neural Nets: Functional Nets of Special Type

Special generalizing for the artificial neural nets: so called RFT – FN – is under discussion in the report. Such refinement touch upon the constituent elements for the conception of artificial neural network, namely, the choice of main primary functional elements in the net, the way to connect them(topology) and the structure of the net as a whole. As to the last, the structure of the functional net proposed is determined dynamically just in the constructing the net by itself by the special recurrent procedure. The number of newly joining primary functional elements, the topology of its connecting and tuning of the primary elements is the content of the each recurrent step. The procedure is terminated under fulfilling “natural” criteria relating residuals for example. The functional proposed can be used in solving the approximation problem for the functions, represented by its observations, for classifying and clustering, pattern recognition, etc. Recurrent procedure provide for the versatile optimizing possibilities: as on the each step of the procedure and wholly: by the choice of the newly joining elements, topology, by the affine transformations if input and intermediate coordinate as well as by its nonlinear coordinate wise transformations. All considerations are essentially based, constructively and evidently represented by the means of the Generalized Inverse.

Discrete solitons in coupled active lasing cavities

We examine the existence and stability of discrete spatial solitons in coupled nonlinear lasing cavities (waveguide resonators), addressing the case of active defocusing media, where the gain exceeds damping in the low-amplitude limit. A new family of stable localized structures is found: these are bright and gray cavity solitons representing the connections between homogeneous and inhomogeneous states. Solitons of this type can be controlled by discrete diffraction and are stable when the bistability of homogenous states is absent. © 2012 Optical Society of America.