Local anaesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro

Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3β, pGSK-3β(tyr216) and pGSK-3β(ser9) expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3β siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK-3β(Tyr216) in SKOV-3 but without measurable effect in PC3. GSK-3β inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct ‘anti-cancer’ properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer

Central equatorial Pacific zonal currents. I: The Sverdrup balance, nonlinearity and tropical instability waves. Annual mean dynamics

Several recent observational studies of central Pacific equatorial current dynamics have suggested that, in the vertical integral between the surface and the thermocline, the linear equatorial Sverdrup balance holds. However, in a high vertical resolution ocean general circulation model, we find that nonlinearity is an order (1) element of the local and the vertically integrated balances on and near the equator at 140W. Although this OGCM has been used in many studies of the tropical Pacific, its equatorial zonal momentum equation balances have never been described in detail and compared with observations. We describe the annual mean balances here, identify the similarities and differences between the model balances and observational estimates of the balances, and discuss various reasons why the model and the observations may disagree in the respects that they are found to do so. The term balances vary strongly with latitude and depth; the system is nonlinear and three dimensional. There is little tendency for pairs of terms (e.g., the meridional and vertical advection terms) to balance locally or in the vertical integral. Every term in the zonal momentum equation plays a role somewhere in the analysis region discussed here. Thus the generality of point estimates of these balances is small. The Tropical Instability Wave zonal momentum flux divergence, although not an O (1) term in the balance, acts like a \u27negative viscosity\u27 over the upper 40 m on the equator; its tendency is to drive westward flow. If the ocean balances resemble those of the model dynamics, gaining detailed perspective on the zonal balances will require a major observational effort. Because there is strong subseasonal and interannual variability of the flows in the central equatorial Pacific, time-mean balances are not simple to estimate. Further, special attention will have to be given to resolving the shears in the upper 50 m, because it is over these depths that the model and observational results differ most strongly. We suggest that the widely used technique of extrapolating the near-surface currents based on their shears in the uppermost bins of the ADCP profiles deserves careful scrutiny; subsampling the model flow profiles in this fashion leads to important errors. Until the strong vertically sheared very near-surface current field is observed accurately it will not be possible to determine if the model results are correct, but we suggest that the existing observational results should not be regarded as definitive

Casimir micro-sphere diclusters and three-body effects in fluids

Our previous article [Phys. Rev. Lett. 104, 060401 (2010)] predicted that Casimir forces induced by the material-dispersion properties of certain dielectrics can give rise to stable configurations of objects. This phenomenon was illustrated via a dicluster configuration of non-touching objects consisting of two spheres immersed in a fluid and suspended against gravity above a plate. Here, we examine these predictions from the perspective of a practical experiment and consider the influence of non-additive, three-body, and nonzero-temperature effects on the stability of the two spheres. We conclude that the presence of Brownian motion reduces the set of experimentally realizable silicon/teflon spherical diclusters to those consisting of layered micro-spheres, such as the hollow- core (spherical shells) considered here.Comment: 11 pages, 9 figure

Long-lived photoexcited states in polydiacetylenes with different molecular and supramolecular organization

With the aim of determining the importance of the molecular and supramolecular organization on the excited states of polydiacetylenes, we have studied the photoinduced absorption spectra of the red form of poly[1,6-bis(3,6-didodecyl-N-carbazolyl)-2,4-hexadiyne] (polyDCHD-S) and the results compared with those of the blue form of the same polymer. An interpretation of the data is given in terms of both the conjugation length and the interbackbone separation also in relation to the photoinduced absorption spectra of both blue and red forms of poly[1,6-bis(N-carbazolyl)-2,4-hexadiyne] (polyDCHD), which does not carry the alkyl substituents on the carbazolyl side groups. Information on the above properties is derived from the analysis of the absorption and Raman spectra of this class of polydiacetylenes

The Fundamental Diagram of Pedestrian Movement Revisited

The empirical relation between density and velocity of pedestrian movement is not completely analyzed, particularly with regard to the `microscopic' causes which determine the relation at medium and high densities. The simplest system for the investigation of this dependency is the normal movement of pedestrians along a line (single-file movement). This article presents experimental results for this system under laboratory conditions and discusses the following observations: The data show a linear relation between the velocity and the inverse of the density, which can be regarded as the required length of one pedestrian to move. Furthermore we compare the results for the single-file movement with literature data for the movement in a plane. This comparison shows an unexpected conformance between the fundamental diagrams, indicating that lateral interference has negligible influence on the velocity-density relation at the density domain $1 m^{-2}<\rho<5 m^{-2}$. In addition we test a procedure for automatic recording of pedestrian flow characteristics. We present preliminary results on measurement range and accuracy of this method.Comment: 13 pages, 9 figure

Temporally varying natural mortality: Sensitivity of a virtual population analysis and an exploration of alternatives

Cohort reconstructions (CR) currently applied in Pacific salmon management estimate temporally variant exploitation, maturation, and juvenile natural mortality rates but require an assumed (typically invariant) adult natural mortality rate (dA), resulting in unknown biases in the remaining vital rates. We explored the sensitivity of CR results to misspecification of the mean and/or variability of dA, as well as the potential to estimate dA directly using models that assumed separable year and age/cohort effects on vital rates (separable cohort reconstruction, SCR). For CR, given the commonly assumed dA = 0.2, the error (RMSE) in estimated vital rates is generally small (? 0.05) when annual values of dA are low to moderate (? 0.4). The greatest absolute errors are in maturation rates, with large relative error in the juvenile survival rate. The ability of CR estimates to track temporal trends in the juvenile natural mortality rate is adequate (Pearson's correlation coefficient > 0.75) except for high dA (? 0.6) and high variability (CV > 0.35). The alternative SCR models allowing estimation of time-varying dA by assuming additive effects in natural mortality, fishing mortality, and/or maturation rates did not outperform CR across all simulated scenarios, and are less accurate when additivity assumptions are violated. Nevertheless an SCR model assuming additive effects on fishing and natural (juvenile and adult) mortality rates led to nearly unbiased estimates of all quantities estimated using CR, along with borderline acceptable estimates of the mean dA under multiple sets of conditions conducive to CR. Adding an assumption of additive effects on the maturation rates allowed nearly unbiased estimates of the mean dA as well. The SCR models performed slightly better than CR when the vital rates covaried as assumed. These separable models could serve as a partial check on the validity of CR assumptions about the adult natural mortality rate, or even a preferred alternative if there is strong reason to believe the vital rates, including juvenile and adult natural mortality rates, covary strongly across years or age classes as assumed

Enhanced empirical data for the fundamental diagram and the flow through bottlenecks

In recent years, several approaches for modelling pedestrian dynamics have been proposed and applied e.g. for design of egress routes. However, so far not much attention has been paid to their 'quantitative' validation. This unsatisfactory situation belongs amongst others on the uncertain and contradictory experimental data base. The fundamental diagram, i.e. the density-dependence of the flow or velocity, is probably the most important relation as it connects the basic parameter to describe the dynamic of crowds. But specifications in different handbooks as well as experimental measurements differ considerably. The same is true for the bottleneck flow. After a comprehensive review of the experimental data base we give an survey of a research project, including experiments with up to 250 persons performed under well controlled laboratory conditions. The trajectories of each person are measured in high precision to analyze the fundamental diagram and the flow through bottlenecks. The trajectories allow to study how the way of measurement influences the resulting relations. Surprisingly we found large deviation amongst the methods. These may be responsible for the deviation in the literature mentioned above. The results are of particular importance for the comparison of experimental data gained in different contexts and for the validation of models.Comment: A contribution to: Pedestrian and Evacuation Dynamics 2008 (Springer) 12 pages, 7 figure

Association between labour market trends and trends in young people's mental health in ten European countries 1983-2005

<p>Abstract</p> <p>Background</p> <p>Mental health problems have become more common among young people over the last twenty years, especially in certain countries. The reasons for this have remained unclear. The hypothesis tested in this study is that national trends in young people's mental health are associated with national trends in young people's labour market.</p> <p>Methods</p> <p>National secular changes in the proportion of young people with mental health problems and national secular labour market changes were studied from 1983 to 2005 in Austria, Belgium, Denmark, Finland, Hungary, Norway, Spain, Sweden, Switzerland and the United Kingdom.</p> <p>Results</p> <p>The correlation between the national secular changes in the proportion of young people not in the labour force and the national secular changes in proportion of young people with mental health symptoms was 0.77 for boys and 0.92 for girls.</p> <p>Conclusion</p> <p>Labour market trends may have contributed to the deteriorating trend in mental health among young people. A true relationship, should other studies confirm it, would be an important aspect to take into account when forming labour market policies or policies concerning the delivery of higher education.</p