Regulation of bone biology by prostaglandin endoperoxide H synthases (PGHS): A rose by any other name...

It is well established that prostaglandins are essential mediators of bone resorption and formation. In the early 1990s, it was discovered that enzymatic reactions producing prostaglandins were regulated by two cyclooxygenase enzymes, one producing prostaglandins constitutively in tissues like the stomach, prostaglandin endoperoxide H synthase-1 (PGHS-1 or COX-1), and another induced by mitogens or inflammatory mediators (PGHS-2 or COX-2). This neat distinction has not been maintained because both enzymes act in different cell systems to provide physiological signaling, constitutively or by induction under certain conditions. For example, the regulation patterns of PGHS-1 and PGHS-2 are distinct, but the evidence shows that PGHS-2 functions constitutively in the skeleton. PGHS-2 hits quickly been established, therefore, as a key regulator of bone biology, capable of rapid and transient expression in bone cells, and mediating osteoclastogenesis, mechanotransduction, bone formation and fracture repair. The goal of this review is to Summarize the current state of our knowledge of PGHS regulation of bone metabolism and to identify some of the key unresolved challenges and questions that require further study. (c) 2006 Elsevier Ltd. All rights reserved.

Clay mineralogical and isotopic (K-Ar, delta O-18, delta D) constraints on the evolution of the North Anatolian Fault Zone, Turkey

This study presents the first attempt to constrain the evolution of the North Anatolian Fault Zone (NAFZ) by age dating and isotope tracing of clay minerals formed during near-surface faulting. Extensive illitic clay mineralisation occurred along the NAFZ related to hydrothermal alteration of the fault gouges and pseudotachylytes. Samples representing the pre-fault protoliths outside the fault zone do not contain authigenic illitic clay minerals indicating that hydrothermal processes were confined to the areas within the fault zone. K-Ar age data indicate that the hydrothermal system and the associated illite authigenesis initiated at similar to 57 Ma. This process is interpreted to reflect the onset of significant strike-slip or transtensional faulting immediately after the continental collision related to the closure of the Neotethys Ocean. Following the initiation of the fault movements in the latest Paleocene-Early Eocene, displacements along the NAFZ have continued, with probably intensified fault activities at similar to 26 Ma and later than similar to 8 Ma. Oxygen isotope compositions of the illitic clays from different locations along the NAFZ are similar, with narrow ranges in delta O-18 values indicating clay precipitation from fluids with similar oxygen isotope compositions and crystallisation temperatures. The delta O-18 and delta D values of the calculated fluid isotopic composition (delta O-18=5.9 parts per thousand to 11.2 parts per thousand, delta D=-59 parts per thousand to -73 parts per thousand) are consistent with metamorphic and magmatic origin of fluids mobilised during active tectonism. The interpretation of the fluid flow history of the NAFZ is in agreement with that reported previously for some well-known large-scale high-angle fault zones, which similarly developed along collisional-type orogenic belts and are commonly associated with significant mesothermal ore mineralisation. (c) 2005 Elsevier B.V. All rights reserved.

Intelligent execution monitoring and error analysis in planning involving processes

An intelligent agent, operating in an external world which cannot be fully described in its internal world model, must be able to monitor the success of a previously generated plan and to respond to any errors which may have occurred. The process of error analysis requires the ability to reason in an expert fashion about time and about processes occurring in the world. Reasoning about time is needed to deal with causality. Reasoning about processes is needed since the direct effects of a plan action can be completely specified when the plan is generated, but the indirect effects cannot. For example, the action `open tap' leads with certainty to `tap open', whereas whether there will be a fluid flow and how long it might last is more difficult to predict. The majority of existing planning systems cannot handle these kinds of reasoning, thus limiting their usefulness. This thesis argues that both kinds of reasoning require a complex internal representation of the world. The use of Qualitative Process Theory and an interval-based representation of time are proposed as a representation scheme for such a world model. The planning system which was constructed has been tested on a set of realistic planning scenarios. It is shown that even simple planning problems, such as making a cup of coffee, require extensive reasoning if they are to be carried out successfully. The final Chapter concludes that the planning system described does allow the correct solution of planning problems involving complex side effects, which planners up to now have been unable to solve.

Ionic and molecular diffusion in cementitious materials

The work described in this thesis is an attempt to provide improved understanding of the effects of several factors affecting diffusion in hydrated cement pastes and to aid the prediction of ionic diffusion processes in cement-based materials. Effect of pore structure on diffusion was examined by means of comparative diffusion studies of quaternary ammonium ions with different ionic radii. Diffusivities of these ions in hydrated pastes of ordinary portland cement with or without addition of fly ash were determined by a quasi-steady state technique. The restriction of the pore geometry on diffusion was evaluated from the change of diffusivity in response to the change of ionic radius. The pastes were prepared at three water-cement ratios, 0.35, 0.50 and 0.65. Attempts were made to study the effect of surface charge or the electrochemical double layer at the pore/solution interface on ionic diffusion. An approach was to evaluate the zeta potentials of hydrated cement pastes through streaming potential measurements. Another approach was the comparative studies of the diffusion kinetics of chloride and dissolved oxygen in hydrated pastes of ordinary portland cement with addition of 0 and 20% fly ash. An electrochemical technique for the determination of oxygen diffusivity was also developed. Non-steady state diffusion of sodium potassium, chloride and hydroxyl ions in hydrated ordinary portland cement paste of water-cement ratio 0.5 was studied with the aid of computer-modelling. The kinetics of both diffusion and ionic binding were considered for the characterization of the concentration profiles by Fick's first and second laws. The effect of the electrostatic interactions between ions on the overall diffusion rates was also considered. A general model concerning the prediction of ionic diffusion processes in cement-based materials has been proposed.

Parametric study of the behaviour of reinforced concrete columns in fire

The research is concerned with the application of the computer simulation technique to study the performance of reinforced concrete columns in a fire environment. The effect of three different concrete constitutive models incorporated in the computer simulation on the structural response of reinforced concrete columns exposed to fire is investigated. The material models differed mainly in respect to the formulation of the mechanical properties of concrete. The results from the simulation have clearly illustrated that a more realistic response of a reinforced concrete column exposed to fire is given by a constitutive model with transient creep or appropriate strain effect The assessment of the relative effect of the three concrete material models is considered from the analysis by adopting the approach of a parametric study, carried out using the results from a series of analyses on columns heated on three sides which produce substantial thermal gradients. Three different loading conditions were used on the column; axial loading and eccentric loading both to induce moments in the same sense and opposite sense to those induced by the thermal gradient. An axially loaded column heated on four sides was also considered. The computer modelling technique adopted separated the thermal and structural responses into two distinct computer programs. A finite element heat transfer analysis was used to determine the thermal response of the reinforced concrete columns when exposed to the ISO 834 furnace environment. The temperature distribution histories obtained were then used in conjunction with a structural response program. The effect of the occurrence of spalling on the structural behaviour of reinforced concrete column is also investigated. There is general recognition of the potential problems of spalling but no real investigation into what effect spalling has on the fire resistance of reinforced concrete members. In an attempt to address the situation, a method has been developed to model concrete columns exposed to fire which incorporates the effect of spalling. A total of 224 computer simulations were undertaken by varying the amounts of concrete lost during a specified period of exposure to fire. An array of six percentages of spalling were chosen for one range of simulation while a two stage progressive spalling regime was used for a second range. The quantification of the reduction in fire resistance of the columns against the amount of spalling, heating and loading patterns, and the time at which the concrete spalls appears to indicate that it is the amount of spalling which is the most significant variable in the reduction of fire resistance.

Entrapment of plasmid DNA vaccines into liposomes by dehydration/rehydration

Intramuscular injection of naked plasmid DNA is known (1-3) to elicit humoral and cell-mediated immune responses against the encoded antigen. It is thought (2,3) that immunity follows DNA uptake by muscle cells, leading to the expression and extracellular release of the antigen which is then taken up by antigen presenting cells (APC). In addition, it is feasible that some of the injected DNA is taken up directly by APC. Disadvantages (1-3) of naked DNA vaccination include: uptake of DNA by only a minor fraction of muscle cells, exposure of DNA to deoxyribonuclease in the interstitial fluid thus necessitating the use of relatively large quantities of DNA, and, in some cases, injection into regenerating muscle in order to enhance immunity. We have recently proposed (1,4) that DNA immunization via liposomes (phospholipid vesicles) could circumvent the need of muscle involvement and instead facilitate (5) uptake of DNA by APC infiltrating the site of injection or in the lymphatics, at the same time protecting DNA from nuclease attack (6). Moreover, transfection of APC with liposomal DNA could be promoted by the judicial choice of vesicle surface charge, size and lipid composition, or by the co-entrapment, together with DNA, of plasmids expressing appropriate cytokines (e.g., interleukin 2), or immunostimulatory sequences.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.

Analyze impact of context information on rate adaptation algorithm in vehicular communication

Nowadays, road safety and traffic congestion are major concerns worldwide. This is why research on vehicular communication is very vital. In static scenarios vehicles behave typically like in an office network where nodes transmit without moving and with no defined position. This paper analyses the impact of context information on existing popular rate adaptation algorithms. Our simulation was done in MATLAB by observing the impact of context information on these algorithms. Simulation was performed for both static and mobile cases.Our simulations are based on IEEE 802.11p wireless standard. For static scenarios vehicles do not move and without defined positions, while for the mobile case, vehicles are mobile with uniformly selected speed and randomized positions. Network performance are analysed using context information. Our results show that in mobility when context information is used, the system performance can be improved for all three rate adaptation algorithms. That can be explained by that with range checking, when many vehicles are out of communication range, less vehicles contend for network resources, thereby increasing the network performances. © 2013 IEEE.

A comparative study on applying the method of fundamental solutions to the backward heat conduction problem

We investigate an application of the method of fundamental solutions (MFS) to the backward heat conduction problem (BHCP). We extend the MFS in Johansson and Lesnic (2008) [5] and Johansson et al. (in press) [6] proposed for one and two-dimensional direct heat conduction problems, respectively, with the sources placed outside the space domain of interest. Theoretical properties of the method, as well as numerical investigations, are included, showing that accurate and stable results can be obtained efficiently with small computational cost.

An overall profit Malmquist productivity index with fuzzy and interval data

Although crisp data are fundamentally indispensable for determining the profit Malmquist productivity index (MPI), the observed values in real-world problems are often imprecise or vague. These imprecise or vague data can be suitably characterized with fuzzy and interval methods. In this paper, we reformulate the conventional profit MPI problem as an imprecise data envelopment analysis (DEA) problem, and propose two novel methods for measuring the overall profit MPI when the inputs, outputs, and price vectors are fuzzy or vary in intervals. We develop a fuzzy version of the conventional MPI model by using a ranking method, and solve the model with a commercial off-the-shelf DEA software package. In addition, we define an interval for the overall profit MPI of each decision-making unit (DMU) and divide the DMUs into six groups according to the intervals obtained for their overall profit efficiency and MPIs. We also present two numerical examples to demonstrate the applicability of the two proposed models and exhibit the efficacy of the procedures and algorithms. © 2011 Elsevier Ltd.

Development of a physiologically-based pharmacokinetic model of the rat central nervous system

Central nervous system (CNS) drug disposition is dictated by a drug’s physicochemical properties and its ability to permeate physiological barriers. The blood–brain barrier (BBB), blood-cerebrospinal fluid barrier and centrally located drug transporter proteins influence drug disposition within the central nervous system. Attainment of adequate brain-to-plasma and cerebrospinal fluid-to-plasma partitioning is important in determining the efficacy of centrally acting therapeutics. We have developed a physiologically-based pharmacokinetic model of the rat CNS which incorporates brain interstitial fluid (ISF), choroidal epithelial and total cerebrospinal fluid (CSF) compartments and accurately predicts CNS pharmacokinetics. The model yielded reasonable predictions of unbound brain-to-plasma partition ratio (Kpuu,brain) and CSF:plasma ratio (CSF:Plasmau) using a series of in vitro permeability and unbound fraction parameters. When using in vitro permeability data obtained from L-mdr1a cells to estimate rat in vivo permeability, the model successfully predicted, to within 4-fold, Kpuu,brain and CSF:Plasmau for 81.5% of compounds simulated. The model presented allows for simultaneous simulation and analysis of both brain biophase and CSF to accurately predict CNS pharmacokinetics from preclinical drug parameters routinely available during discovery and development pathways.

Institute for Bulgarian Language, BAS

The paper presents the history, structure and ongoing activities of the Institute for Bulgarian Language of Bulgarian Academy of Sciences.

Thermal counterflow in a periodic channel with solid boundaries

We perform numerical simulations of finite temperature quantum turbulence produced through thermal counterflow in superfluid 4He, using the vortex filament model. We investigate the effects of solid boundaries along one of the Cartesian directions, assuming a laminar normal fluid with a Poiseuille velocity profile, whilst varying the temperature and the normal fluid velocity. We analyze the distribution of the quantized vortices, reconnection rates, and quantized vorticity production as a function of the wall-normal direction. We find that the quantized vortex lines tend to concentrate close to the solid boundaries with their position depending only on temperature and not on the counterflow velocity. We offer an explanation of this phenomenon by considering the balance of two competing effects, namely the rate of turbulent diffusion of an isotropic tangle near the boundaries and the rate of quantized vorticity production at the center. Moreover, this yields the observed scaling of the position of the peak vortex line density with the mutual friction parameter. Finally, we provide evidence that upon the transition from laminar to turbulent normal fluid flow, there is a dramatic increase in the homogeneity of the tangle, which could be used as an indirect measure of the transition to turbulence in the normal fluid component for experiments.