The Exodus evacuation model applied to building evacuation scenarios

The purpose of this paper is to demonstrate the potential of the EXODUS evacuation model in building environments. The latest PC/workstation version of EXODUS is described and is also applied to a large hypothetical supermarket/restaurant complex measuring 50 m x 40 m. A range of scenarios is presented where population characteristics (such as size, individual travel speeds, and individual response times), and enclosure configuration characteristics (such as number of exits, size of exits, and opening times of exits) are varied. The results demonstrate a wide range of occupant behavior including overtaking, queuing, redirection, and conflict avoidance. Evacuation performance is measured by a number of model predicted parameters including individual exit flow rates, overall evacuation flow rates, total evacuation time, average evacuation time per occupant, average travel distance, and average wait time. The simulations highlight the profound impact that variations in individual travel speeds and occupant response times have in determining the overall evacuation performance. 1. Jin, T., and Yamada T., "Experimental Study of Human Behavior in Smoke Filled Corridors," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 511-519. 2. Galea, E.R., and Galparsoro, J.M.P., "EXODUS: An Evacuation Model for Mass Transport Vehicles," UK CAA Paper 93006 ISBN 086039 543X, CAA London, 1993. 3. Galea, E.R., and Galparsoro, J.M.P., "A Computer Based Simulation Model for the Prediction of Evacuation from Mass Transport Vehicles," Fire Safety Journal, Vol. 22, 1994, pp. 341-366. 4. Galea, E.R., Owen, M., and Lawrence, P., "Computer Modeling of Human Be havior in Aircraft Fire Accidents," to appear in the Proceedings of Combus tion Toxicology Symposium, CAMI, Oklahoma City, OK, 1995. 5. Kisko, T.M. and Francis, R.L., "EVACNET+: A Computer Program to Determine Optimal Building Evacuation Plans," Fire Safety Journal, Vol. 9, 1985, pp. 211-220. 6. Levin, B., "EXITT, A Simulation Model of Occupant Decisions and Actions in Residential Fires," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 561-570. 7. Fahy, R.F., "EXIT89: An Evacuation Model for High-Rise Buildings," Pro ceedings of The Third International Sym posium on Fire Safety Science, 1991, pp. 815-823. 8. Thompson, P.A., and Marchant, E.W., "A Computer Model for the Evacuation of Large Building Populations," Fire Safety Journal, Vol. 24, 1995, pp. 131-148. 9. Still, K., "New Computer System Can Predict Human Behavior Response to Building Fires," FIRE 84, 1993, pp. 40-41. 10. Ketchell, N., Cole, S.S., Webber, D.M., et.al., "The Egress Code for Human Move ment and Behavior in Emergency Evacu ations," Engineering for Crowd Safety (Smith, R.A., and Dickie, J.F., Eds.), Elsevier, 1993, pp. 361-370. 11. Takahashi, K., Tanaka, T. and Kose, S., "An Evacuation Model for Use in Fire Safety Design of Buildings," Proceedings of The Second International Symposium on Fire Safety Science, 1988, pp. 551- 560. 12. G2 Reference Manual, Version 3.0, Gensym Corporation, Cambridge, MA. 13. XVT Reference Manual, Version 3.0 XVT Software Inc., Boulder, CO. 14. Galea, E.R., "On the Field Modeling Approach to the Simulation of Enclosure Fires, Journal of Fire Protection Engineering, Vol. 1, No. 1, 1989, pp. 11-22. 15. Purser, D.A., "Toxicity Assessment of Combustion Products," SFPE Handbook of Fire Protection Engineering, National Fire Protection Association, Quincy, MA, pp. 1-200 - 1-245, 1988. 16. Hankin, B.D., and Wright, R.A., "Pas senger Flows in Subways," Operational Research Quarterly, Vol. 9, 1958, pp. 81-88. 17. HMSO, The Building Regulations 1991 - Approved Document B, section B 1 (1992 edition), HMSO publications, London, pp. 9-40. 18. Polus A., Schofer, J.L., and Ushpiz, A., "Pedestrian Flow and Level of Service," Journal of Transportation Engineering, Vol. 109, 1983, pp. 46-47. 19. Muir, H., Marrison, C., and Evans, A., "Aircraft Evacuations: the Effect of Passenger Motivation and Cabin Con figuration Adjacent to the Exit," CAA Paper 89019, ISBN 0 86039 406 9, 1989. 20. Muir, H., Private communication to appear as a CAA report, 1996.

Polycyclic aromatic hydrocarbons (PAHS) (I): Measures of prevention and control

Measures of prevention and control against polycyclic aromatic hydrocarbons (PAHs) focus on an official food control, a code of best practice to reduce PAHs levels by controlling industry and in the development of a chemopreventive strategy. Regulation (EU) 835/2011 establishes maximum levels of PAHs for each food group. In addition, Regulations (EU) 333/2007 and 836/2011 set up the methods of sampling and analysis for its official control. Scientific studies prove that the chemopreventive strategy is effective against these genotoxic compounds effects. Most chemopreventive compounds studied with proven protective effects against PAHs are found in fruit and vegetables.

Two-hybrid analysis of the interaction between the fission yeast proteins Sal3 and Cdc25

Cdc25 is a mitosis triggering phosphatase in Schizosaccharomyces pombe, and is transported in to the nucleus during G2 phase by the importin-β protein Sal3. Cdc25 triggers mitosis and cell division by dephosphorylating tyrosine 15 of Cdc2. In sal3 mutants, Cdc25 is not transported into the nucleus and the cells halt in G2. The purpose of this study is to use a two-hybrid system to determine the nature of the relationship between Sal3 and Cdc25. Previous research has failed to detect any interaction between the two proteins, but specific modifications were made to the two-hybrid system in this study including the separation of Sal3 into its two binding domains, the addition of fluorescent tags to the fusion protein, and the reversal of plasmids in the fusion proteins. Unique PCR primers were successfully designed, based on a multiple alignment of Sal3 and its homologues, to separate Sal3 into its two domains.

BRCA1 Functions as a Differential Modulator of Chemotherapy-induced Apoptosis

We have evaluated the role played by BRCA1 in mediating the phenotypic response to a range of chemotherapeutic agents commonly used in cancer treatment. Here we provide evidence that BRCA1 functions as a differential mediator of chemotherapy-induced apoptosis. Specifically, we demonstrate that BRCA1 mediates sensitivity to apoptosis induced by antimicrotubule agents but conversely induces resistance to DNA-damaging agents. These data are supported by a variety of experimental models including cells with inducible expression of BRCA1, siRNA-mediated inactivation of endogenous BRCA1, and reconstitution of BRCA1-deficient cells with wild-type BRCA1. Most notably we demonstrate that BRCA1 induces a 10–1000-fold increase in resistance to a range of DNA-damaging agents, in particular those that give rise to double-strand breaks such as etoposide or bleomycin. In contrast, BRCA1 induces a >1000-fold increase in sensitivity to the spindle poisons, paclitaxel and vinorelbine. Fluorescence-activated cell sorter analysis demonstrated that BRCA1 mediates G2/M arrest in response to both antimicrotubule and DNA-damaging agents. However, poly(ADP-ribose) polymerase and caspase-3 cleavage assays indicate that the differential effect mediated by BRCA1 in response to these agents occurs through the inhibition or induction of apoptosis. Therefore, our data suggest that BRCA1 acts as a differential modulator of apoptosis depending on the nature of the cellular insult.

Properties of SEPT9 Isoforms and the requirement for GTP binding

Members of the evolutionarily conserved septin family of genes are emerging as key components of several cellular processes including membrane trafficking, cytokinesis, and cell-cycle control events. SEPT9 has been shown to have a complex genomic architecture, such that up to 15 different isoforms are possible by the shuffling of five alternate amino termini and three alternate carboxy termini. Genomic and transcriptional alterations of SEPT9 have been associated with neoplasia. The present study has used a Sept9-specific antibody to determine the pattern of isoform expression in a range of tumour cell lines. Western blot analysis indicated considerable variation in the relative amounts and isoform content of Sept9. Immunofluorescence studies showed a range of patterns of cytoplasmic localization ranging from mainly particulate to mainly filamentous. Expression constructs were also generated for each amino terminal isoform to investigate the patterns of localization of individual isoforms and the effects on cells of ectopic expression. The present study shows that the epsilon isoform appears filamentous in this overexpression system while the remaining isoforms are particulate and cytoplasmic. Transient transfection of individual constructs into tumour cell lines results in cell-cycle perturbation with a G2/M arrest and dramatic growth suppression, which was greatest in cell lines with the lowest amounts of endogenous Sept9. Similar phenotypic observations were made with GTP-binding mutants of all five N-terminal variants of Sept9. However, dramatic differences were observed in the kinetics of accumulation of wild-type versus mutant septin protein in transfected cells. In conclusion, the present study shows that the expression patterns of Sept9 protein are very varied in a panel of tumour cell lines and the functional studies are consistent with a model of septin function as a component of a molecular scaffold that contributes to diverse cellular functions. Alterations in the levels of Sept9 protein by overexpression of individual isoforms can clearly perturb cellular behaviour and may thus provide a mechanistic explanation for observations of deranged septin expression in neoplasia. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

CDK11(p58) protein kinase activity is associated with Bcl-2 down-regulation in pro-apoptosis pathway.

CDK11(p58), a G2/M-specific protein kinase, has been shown to be associated with apoptosis in many cell lines, with largely unknown mechanisms. Our previous study proved that CDK11(p58)-enhanced cycloheximide (CHX)-induced apoptosis in SMMC-7721 hepatocarcinoma cells. Here we report for the first time that ectopic expression of CDK11(p58) down-regulates Bcl-2 expression and its Ser70, Ser87 phosphorylation in CHX-induced apoptosis in SMMC-7721 cells. Overexpression of Bcl-2 counteracts the pro-apoptotic activity of CDK11(p58). Furthermore, we confirm that the kinase activity of CDK11(p58) is essential to the down-regulation of Bcl-2 as well as apoptosis. Taken together, these results demonstrate that CDK11(p58) down-regulates Bcl-2 in pro-apoptosis pathway depending on its kinase activity, which elicits survival signal in hepatocarcinoma cells.

Suppressing mitotic catastrophe: identifying mcs3 in Schizosaccharomyces pombe

In Schizosaccharomyces pombe (fission yeast), the transition from G2 phase of the cell cycle to mitosis is under strict regulation. The activation of Cdc2, a cyclin dependent serine/threonine protein kinase, is the critical control step in this process. The Cdc2/Cyclin-B (Cdc13) complex is regulated by Wee1 tyrosine kinase and Cdc25 tyrosine phosphatase, which work antagonistically to control progression into mitosis. Hyperactivation of the Cdc2/Cdc13 complex by phosphorylation results in premature mitosis, and as a consequence leads to genome instability. This is referred to as mitotic catastrophe, a lethal phenotype associated with chromosomal segregation abnormalities including chromosome breakage. Six mitotic catastrophe loci were found, five of which have been characterized and identified as various activators and repressors of the core mitotic control. The locus for mcs3 remains unknown. I used tetrad analysis in this study to determine the linkage distance between three genes suspected of flanking the region in which mcs3 is located. Linkage distances obtained in this study confirm that the SPBC428.10 and met17, as well as SPBC428.10 and wpl1 are tightly linked, suggesting this is an area of low recombination. Further linkage analysis should be conducted to determine the precise location of mcs3-12.

Characterisation of antibodies to chloramphenicol, produced in different species by enzyme-linked immunosorbent assay and biosensor technologies

Six polyclonal antisera to chloramphenicol (CAP) were successfully raised in camels, donkeys and goats. As a comparison of sensitivity, IC50 values ranged from 0.3 ng mL(-1) to 5.5 ng mL(-1) by enzyme-linked immunosorbent assay (ELISA) and from 0.7 ng mL(-1) to 1.7 ng mL(-1) by biosensor assay. The introduction of bovine milk extract improved the sensitivity of four of the antisera by ELISA and two by biosensor assay; a reduction in sensitivity of the remaining antisera ranged by a factor of 1.1-2.6. Porcine kidney extract reduced the sensitivity of all the antisera by a factor ranging from 1.1 to 7 by ELISA and a factor of 1.5 to 4 by biosensor. A low cross-reactivity with thiamphenicol (TAP) and florfenicol (FF) was displayed by antiserurn G2 (1.2% and 18%, respectively) when a homologous ELISA assay format was employed. No cross-reactivity was displayed by any of the antisera when a homologous biosensor assay format was employed. Switching to a heterologous ELISA format prompted three of the antisera to display more significant cross-reactivity with TAP and FF (53% and 82%, respectively, using Dl). The heterologous biosensor assay also increased the cross-reactivity of D1 for TAP and FF (56% and 129%, respectively) and of one other antiserum (Gl) to a lesser degree. However, unlike the ELISA, the heterologous biosensor assay produced a substantial reduction in sensitivity (by a factor of 6 for D1). (C) 2007 Elsevier B.V. All rights reserved.

Comet sensitivity in assessing DNA damage and repair in different cell cycle stages

The comet assay is a sensitive tool for estimation of DNA damage and repair at the cellular level, requiring only a very small number of cells. In comparing the levels of damage or repair in different cell samples, it is possible that small experimental effects could be confounded by different cell cycle states in the samples examined, if sensitivity to DNA damage, and repair capacity, varies with the cell cycle. We assessed this by arresting HeLa cells in various cell cycle stages and then exposing them to ionizing radiation. Unirradiated cells demonstrated significant differences in strand break levels measured by the comet assay (predominantly single-strand breaks) at different cell cycle stages, increasing from G1 into S and falling again in G2. Over and above this variation in endogenous strand break levels, a significant difference in susceptibility to breaks induced by 3.5 Gy ionizing radiation was also evident in different cell cycle phases. Levels of induced DNA damage fluctuate throughout the cycle, with cells in G1 showing slightly lower levels of damage than an asynchronous population. Damage increases as cells progress through S phase before falling again towards the end of S phase and reaching lowest levels in M phase. The results from repair experiments (where cells were allowed to repair for 10 min after exposure to ionizing radiation) also showed differences throughout the cell cycle with G1-phase cells apparently being the most efficient at repair and M-phase cells the least efficient. We suggest, therefore, that in experiments where small differences in DNA damage and repair are to be investigated with the comet assay, it may be desirable to arrest cells in a specific stage of the cell cycle or to allow for differential cycle distribution.

Hyperacetylation in prostate cancer induces cell cycle aberrations, chromatin reorganization and altered gene expression profiles.

Histone acetylation is a fundamental mechanism in the regulation of local chromatin conformation and gene expression. Research has focused on the impact of altered epigenetic environments on the expression of specific genes and their pathways. However, changes in histone acetylation also have a global impact on the cell. In this study we used digital texture analysis to assess global chromatin patterns following treatment with trichostatin A (TSA) and have observed significant alterations in the condensation and distribution of higher-order chromatin, which were associated with altered gene expression profiles in both immortalised normal PNT1A prostate cell line and androgen-dependent prostate cancer cell line LNCaP. Furthermore, the extent of TSA-induced disruption was both cell cycle and cell line dependent. This was illustrated by the identification of sub-populations of prostate cancer cells expressing high levels of H3K9 acetylation in the G2/M phase of the cell cycle that were absent in normal cell populations. In addition, the analysis of enriched populations of G1 cells showed a global decondensation of chromatin exclusively in normal cells.

WASP-37b: A 1.8 M J Exoplanet Transiting a Metal-poor Star

We report on the discovery of WASP-37b, a transiting hot Jupiter orbiting an m v = 12.7 G2-type dwarf, with a period of 3.577469 ± 0.000011 d, transit epoch T 0 = 2455338.6188 ± 0.0006 (HJD; dates throughout the paper are given in Coordinated Universal Time (UTC)), and a transit duration 0.1304+0.0018 –0.0017 d. The planetary companion has a mass M p = 1.80 ± 0.17 M J and radius R p = 1.16+0.07 –0.06 R J, yielding a mean density of 1.15+0.12 –0.15 ?J. From a spectral analysis, we find that the host star has M sstarf = 0.925 ± 0.120 M sun, R sstarf = 1.003 ± 0.053 R sun, T eff = 5800 ± 150 K, and [Fe/H] = –0.40 ± 0.12. WASP-37 is therefore one of the lowest metallicity stars to host a transiting planet.

Cdk1 participates in BRCA1-dependent S phase checkpoint control in response to DNA damage.

Cdk2 and cdk1 are individually dispensable for cell-cycle progression in cancer cell lines because they are able to compensate for one another. However, shRNA-mediated depletion of cdk1 alone or small molecule cdk1 inhibition abrogated S phase cell-cycle arrest and the phosphorylation of a subset of ATR/ATM targets after DNA damage. Loss of DNA damage-induced checkpoint control was caused by a reduction in formation of BRCA1-containing foci. Mutation of BRCA1 at S1497 and S1189/S1191 resulted in loss of cdk1-mediated phosphorylation and also compromised formation of BRCA1-containing foci. Abrogation of checkpoint control after cdk1 depletion or inhibition in non-small-cell lung cancer cells sensitized them to DNA-damaging agents. Conversely, reduced cdk1 activity caused more potent G2/M arrest in nontransformed cells and antagonized the response to subsequent DNA damage. Cdk1 inhibition may therefore selectively sensitize BRCA1-proficient cancer cells to DNA-damaging treatments by disrupting BRCA1 function.

The binary progenitor of Tycho Brahe's 1572 supernova

The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion(1-3). Unless the companion star is another white dwarf ( in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova(4,5) is one of only two type Ia supernovae observed in our Galaxy, and so provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0 - G2 star, similar to our Sun in surface temperature and luminosity ( but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer.

Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.

Methods: Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.

Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%).

Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.

Cyanoacrylate glue versus suture in peripheral nerve reanastomosis

OBJECTIVE: To assess the effectiveness of n-butyl-2-cyanoacrylate glue compared with microsuturing technique in peripheral nerve reanastomosis in rats.

STUDY DESIGN: Fourteen young adult white rats were used. Bilateral sciatic neurotomies were performed in 12 of them and then reanastomosed with 3 epineural microsutures in the right side (study group G1) and with n-butyl-2-cyanoacrylate glue in the left side (study group G2). On the remaining 2 rats (control group G3), sham surgery was done on both sides. Biopsies were harvested 12 weeks after surgery and examined under light microscope using Osmic acid stains. The number of nerve fibers was counted in the distal and proximal nerve segments, and the results were analyzed and compared in all groups.

RESULTS: Adequate regeneration with no anastomotic ruptures was seen 12 weeks after surgery in G1 and G2. The histomorphometric assessment showed no statistically significant difference (P = .960) in the neurotization index of G1 (89.01%) compared with G2 (88.97%). There was a significant (P = .001) reduction in the mean number of axon counts distal to the repair in G1 (271.3) and G2 (272.8) compared with that of the proximal segments of each study group (304.6 and 303, respectively, as well as to that of G3 (348.5).

CONCLUSION: Both n-butyl-2-cyanoacrylate adhesive and 3-microsuture techniques showed comparable neurotization indices and were equally adequate to stabilize the nerve during regeneration period.