Uncertainty Analysis in New Seismic Hazard Study of Spain Aimed at the Revision of the Spanish Building Code.

In this paper we present a global overview of the recent study carried out in Spain for the new hazard map, which final goal is the revision of the Building Code in our country (NCSE-02). The study was carried our for a working group joining experts from The Instituto Geografico Nacional (IGN) and the Technical University of Madrid (UPM) , being the different phases of the work supervised by an expert Committee integrated by national experts from public institutions involved in subject of seismic hazard. The PSHA method (Probabilistic Seismic Hazard Assessment) has been followed, quantifying the epistemic uncertainties through a logic tree and the aleatory ones linked to variability of parameters by means of probability density functions and Monte Carlo simulations. In a first phase, the inputs have been prepared, which essentially are: 1) a project catalogue update and homogenization at Mw 2) proposal of zoning models and source characterization 3) calibration of Ground Motion Prediction Equations (GMPE’s) with actual data and development of a local model with data collected in Spain for Mw < 5.5. In a second phase, a sensitivity analysis of the different input options on hazard results has been carried out in order to have criteria for defining the branches of the logic tree and their weights. Finally, the hazard estimation was done with the logic tree shown in figure 1, including nodes for quantifying uncertainties corresponding to: 1) method for estimation of hazard (zoning and zoneless); 2) zoning models, 3) GMPE combinations used and 4) regression method for estimation of source parameters. In addition, the aleatory uncertainties corresponding to the magnitude of the events, recurrence parameters and maximum magnitude for each zone have been also considered including probability density functions and Monte Carlo simulations The main conclusions of the study are presented here, together with the obtained results in terms of PGA and other spectral accelerations SA (T) for return periods of 475, 975 and 2475 years. The map of the coefficient of variation (COV) are also represented to give an idea of the zones where the dispersion among results are the highest and the zones where the results are robust.

Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures

Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-d-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy.

Effects of nitric oxide-releasing aspirin versus aspirin on restenosis in hypercholesterolemic mice

Restenosis is due to neointimal hyperplasia, which occurs in the coronary artery after percutaneous transluminal coronary angioplasty (PTCA). During restenosis, an impairment of nitric oxide (NO)-dependent pathways may occur. Concomitant hypercholesterolemia may exacerbate restenosis in patients undergoing PTCA. Here, we show that a NO-releasing aspirin derivative (NCX-4016) reduces the degree of restenosis after balloon angioplasty in low-density lipoprotein receptor-deficient mice and this effect is associated with reduced vascular smooth muscle cell (VSMC) proliferation and macrophage deposition at the site of injury. Drugs were administered following both therapeutic or preventive protocols. We demonstrate that NCX-4016 is effective both in prevention and treatment of restenosis in the presence of hypercholesterolemia. These data indicate that impairment of NO-dependent mechanisms may be involved in the development of restenosis in hypercholesterolemic mice. Although experimental models of restenosis may not reflect restenosis in humans in all details, we suggest that a NO-releasing aspirin derivative could be an effective drug in reducing restenosis following PTCA, especially in the presence of hypercholesterolemia and/or gastrointestinal damage.

Sodium channels and pain

Although it is well established that hyperexcitability and/or increased baseline sensitivity of primary sensory neurons can lead to abnormal burst activity associated with pain, the underlying molecular mechanisms are not fully understood. Early studies demonstrated that, after injury to their axons, neurons can display changes in excitability, suggesting increased sodium channel expression, and, in fact, abnormal sodium channel accumulation has been observed at the tips of injured axons. We have used an ensemble of molecular, electrophysiological, and pharmacological techniques to ask: what types of sodium channels underlie hyperexcitability of primary sensory neurons after injury? Our studies demonstrate that multiple sodium channels, with distinct electrophysiological properties, are encoded by distinct mRNAs within small dorsal root ganglion (DRG) neurons, which include nociceptive cells. Moreover, several DRG neuron-specific sodium channels now have been cloned and sequenced. After injury to the axons of DRG neurons, there is a dramatic change in sodium channel expression in these cells, with down-regulation of some sodium channel genes and up-regulation of another, previously silent sodium channel gene. This plasticity in sodium channel gene expression is accompanied by electrophysiological changes that poise these cells to fire spontaneously or at inappropriate high frequencies. Changes in sodium channel gene expression also are observed in experimental models of inflammatory pain. Thus, sodium channel expression in DRG neurons is dynamic, changing significantly after injury. Sodium channels within primary sensory neurons may play an important role in the pathophysiology of pain.

The evolution of RNA viruses: A population genetics view

RNA viruses are excellent experimental models for studying evolution under the theoretical framework of population genetics. For a proper justification of this thesis we have introduced some properties of RNA viruses that are relevant for studying evolution. On the other hand, population genetics is a reductionistic theory of evolution. It does not consider or make simplistic assumptions on the transformation laws within and between genotypic and phenotypic spaces. However, such laws are minimized in the case of RNA viruses because the phenotypic space maps onto the genotypic space in a much more linear way than on higher DNA-based organisms. Under experimental conditions, we have tested the role of deleterious and beneficial mutations in the degree of adaptation of vesicular stomatitis virus (VSV), a nonsegmented virus of negative strand. We also have studied how effective population size, initial genetic variability in populations, and environmental heterogeneity shapes the impact of mutations in the evolution of vesicular stomatitis virus. Finally, in an integrative attempt, we discuss pros and cons of the quasispecies theory compared with classic population genetics models for haploid organisms to explain the evolution of RNA viruses.

Macro- and microglial responses in the fellow eyes contralateral to glaucomatous eyes

Most studies employing experimental models of unilateral glaucoma have used the normotensive contralateral eye as the normal control. However, some studies have recently reported the activation of the retinal macroglia and microglia in the uninjured eye, suggesting that the eye contralateral to experimental glaucoma should not be used as a control. This review analyzes the studies describing the contralateral findings and discusses some of the routes through which the signals can reach the contralateral eye to initiate the glial reactivation.

Fire behaviour of tabique walls

This paper present a study on the behaviour of tabique walls, concerning its fire resistance. This work is based on the experimental analysis of real scale tabique panels. Such walls were made in pine wood with an earth-based mortar finishing. In order to assess the earth-based mortar thickness effect on the fire resistance of the wall, three specimens were tested with three different mortar thicknesses of 15 mm, 10 mm and 5 mm. The earth-based mortar was previously analysed in the laboratory. The wooden structures were constructed based on traditional tabique technique. The experimental models were tested in a fire-resistance furnace, according to the ISO 834 standard fire. Temperatures were recorded using two data acquisition systems (spot measuring and field measuring). Fire resistance of test elements is expressed as the time during which the appropriate criteria have been satisfied so that one can predict the time before collapse, increasing both people and property safety. The obtained results are of great importance as they allow to improve the knowledge on tabique walls behaviour subjected to fire conditions. Two performance criteria were verified: the integrity criteria and the insulation criteria.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects.

The vaporization and physical properties of certain refractories.

pt. 1. Techniques and preliminary studies, by A. A. Hasapis, M. B. Panish and C. Rosen.--pt. 2. Experimental studies, by A. A. Hasapis and others.

Police handgun ammunition : incapacitation effects /

At head of title: Technology assessment program.

Complement factor 5a as a therapeutic target

The complement system is an innate immune defense mechanism that protects the host from infection and injury. Complement activation results in the formation of anaphylatoxins, including the biologically active protein C5a. This anaphylatoxin is a potent chemotactic agent for immune and inflammatory cells and induces cell activation. In situations of excessive or uncontrolled complement activation, the overproduction of C5a can cause deleterious effects to the host, and this process is implicated in the pathogenesis of numerous immunoinflammatory disease states, including rheumatoid arthritis, psoriasis, inflammatory bowel disease, ischemia-reperfusion injuries and others. The presence of C5a in a wide variety of condition's has prompted many groups to examine the potential of inhibiting this complement activation product, with the aim of controlling these diseases and reducing the pathologic process. However, to date there is no clinically available specific C5a inhibitor and development of this new drug class is still in a relatively early stage, although limited phase I and phase II human clinical trials have been undertaken in the last few years with selected agents. In this review, examination of the current evidence supporting a specific role of C5a in selected disease states and an overview of potential therapeutic C5a inhibitors will enable the critical evaluation of the potential for C5a as a therapeutic target.

Efffluent flux prediction in variably saturated soil zones within a septic tank-soil absorption trench

The treatment and hydraulic mechanisms in a septic tank-soil absorption system ( SAS) are highly influenced by the clogging layer or biomat zone which develops on bottom and lower sidewall surfaces within the trench. Flow rates through the biomat and sub-biomat zones are governed largely by the biomat hydraulic properties (resistance and hydraulic conductivity) and the unsaturated hydraulic conductivity of the underlying soil. One- and 2-dimensional models were used to investigate the relative importance of sidewall and vertical flow rates and pathways in SAS. Results of 1-dimensional modelling show that several orders of magnitude variation in saturated hydraulic conductivity (Ks) reduce to a 1 order of magnitude variation in long-term flow rates. To increase the reliability of prediction of septic trench hydrology, HYDRUS-2D was used to model 2-dimensional flow. In the permeable soils, under high trench loading, effluent preferentially flowed in the upper region of the trench where no resistant biomat was present (the exfiltration zone). By comparison, flow was more evenly partitioned between the biomat zones and the exfiltration zones of the low permeability soil. An increase in effluent infiltration corresponded with a greater availability of exfiltration zone, rather than a lower resistance of biomat. Results of modelling simulations demonstrated the important role that a permeable A horizon may play in limiting surface surcharge of effluent under high trench hydraulic loading.

Parallel 3D Simulation of a Fault Gouge using the Lattice Solid Model

Despite the insight gained from 2-D particle models, and given that the dynamics of crustal faults occur in 3-D space, the question remains, how do the 3-D fault gouge dynamics differ from those in 2-D? Traditionally, 2-D modeling has been preferred over 3-D simulations because of the computational cost of solving 3-D problems. However, modern high performance computing architectures, combined with a parallel implementation of the Lattice Solid Model (LSM), provide the opportunity to explore 3-D fault micro-mechanics and to advance understanding of effective constitutive relations of fault gouge layers. In this paper, macroscopic friction values from 2-D and 3-D LSM simulations, performed on an SGI Altix 3700 super-cluster, are compared. Two rectangular elastic blocks of bonded particles, with a rough fault plane and separated by a region of randomly sized non-bonded gouge particles, are sheared in opposite directions by normally-loaded driving plates. The results demonstrate that the gouge particles in the 3-D models undergo significant out-of-plane motion during shear. The 3-D models also exhibit a higher mean macroscopic friction than the 2-D models for varying values of interparticle friction. 2-D LSM gouge models have previously been shown to exhibit accelerating energy release in simulated earthquake cycles, supporting the Critical Point hypothesis. The 3-D models are shown to also display accelerating energy release, and good fits of power law time-to-failure functions to the cumulative energy release are obtained.

Adenocarcinoma of colon differentiating as dome epithelium of gut-associated lymphoid tissue

Aims: An early adenocarcinoma of the ascending colon was confined to a mass of gut-associated lymphoid tissue (GALT). The first description of an adenocarcinoma of colon differentiating as dome epithelium is presented. Methods and results: A plaque-like carcinoma was identified opposite the ileocaecal valve in an asymptomatic 56-year-old man with a family history of colorectal cancer. Malignant epithelium was confined to a mass of GALT filling but limited to the submucosa, Characterization of the neoplasm was undertaken by means of mucin histochemistry, immunohistochemistry, electron microscopy and assessment of DNA microsatellite instability status. The malignant epithelium comprised well differentiated columnar cells with a microvillous brush border and expressing MUC1, but no goblet cells or expression of MUC2. The demonstration of focal clusters of intraepithelial B-lymphocytes supported the presence of functioning M-cells within the malignant neoplasm. The cancer was DNA microsatellite stable despite the finding of tumour infiltrating lymphocytes. Conclusions: There is evidence for the origin of colorectal neoplasia from dome epithelium in both experimental models and microreconstruction studies of early adenomas in nonpolypotic human colorectal mucose, It is suggested that the lymphocyte-rich subset of colorectal cancer that expresses MUC1 but not MUC2 may be differentiating as dome epithelium of gut-associated lymphoid tissue.

Heterogeneity of MUC1 expression by human breast carcinoma cell lines in vivo and in vitro

Increased expression of the epithelial mucin MUC1 has been linked to tumor aggressiveness in human breast carcinoma. Recent studies have demonstrated that overexpression of MUC1 interferes with cell-substrate and cell-cell adhesion by masking cell surface integrins and E-cadherin. Additionally, the cytoplasmic tail of MUC1 is involved in signal transduction and interactions with catenins. In the present study, we have examined the in vitro expression of MUC1 mRNA and protein in a panel of 14 human breast cancer cell lines using northern blotting, western blotting, immunocytochemistry, and flow cytometry. Considerable variability of expression was noted not only between cell lines but also within several individual lines. Many cell lines such as BT 20, KPL-1, and T47D expressed abundant MUC1 whilst others such as MDA-MB-231 and MCF-7 showed intermediate expression, and MDA-MB-435 and MDA-MB-453 expressed very low levels. Low levels of MUC1 expression were associated with decreased expression of cytokeratin and increased expression of vimentin. Additionally, 12 of the cell lines were established as xenografts in immunocompromised (SCID) mice, and MUC1 expression in both the primary tumors as well as metastases was assessed immunohistochemically. In general, in vivo expression mirrored in vitro expression, although there was reduced in vivo expression in T47D and ZR-75-1 xenografts. Although we showed no correlation between tumorigenicity or metastasis and MUC1 expression, this study will assist development of experimental models to assess the influence of MUC1 of on breast cancer progression.