Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line

Local growth of osteosarcoma involves destruction of host bone by proteolytic mechanisms and/or host osteoclast activation. Osteoclast formation and activity are regulated by osteoblast-derived factors such as the osteoclast differentiating factor, receptor activator of NF-κB ligand (RANKL) and the inhibitor osteoprotegerin (OPG). We have investigated the in vitro effects of bisphosphonates on a clonal rat osteosarcoma cell line. The aminobisphosphonate pamidronate was added to UMR 106-01 cell cultures (10−8M to 10−4M up to 5 days). The non-aminobisphosphonate clodronate was administered for the same time periods (10−6M to 10−2M). Cell proliferation, apoptosis and mRNA expression was assessed. Both agents inhibited cell proliferation in a time- and dose-dependent manner. ELISA analysis demonstrated an increase in DNA fragmentation although there was no significant dose-related difference between the doses studied. Bisphosphonate-treated cultures had a greater subpopulation of cells exhibiting morphological changes of apoptosis. Expression of mRNA for osteopontin and RANKL was down-regulated by both agents, while the expression of mRNA for alkaline phosphatase, pro-α1(I) collagen and OPG was not altered. Out in vitro work suggests the bisphosphonates not only have direct effects on osteosarcoma cell growth and apoptosis, but also, by altering the relative expression of osteoclast-regulating factors, they may inhibit the activity of osteoclasts and their recruitment. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Dissipative Particle Dynamics with Energy Conservation

The stochastic differential equations for a model of dissipative particle dynamics with both total energy and total momentum conservation in the particle-particle interactions are presented. The corresponding Fokker-Planck equation for the evolution of the probability distribution for the system is deduced together with the corresponding fluctuation-dissipation theorems ensuring that the ab initio chosen equilibrium probability distribution for the relevant variables is a stationary solution. When energy conservation is included, the system can sustain temperature gradients and heat flow can be modeled.Comment: 7 pages, submitted to Europhys. Let

Factors Associated with the Diversification of the Gut Microbial Communities within Chimpanzees from Gombe National Park.

The gastrointestinal tract harbors large and diverse populations of bacteria that vary among individuals and within individuals over time. Numerous internal and external factors can influence the contents of these microbial communities, including diet, geography, physiology, and the extent of contact among hosts. To investigate the contributions of such factors to the variation and changes in gut microbial communities, we analyzed the distal gut microbiota of individual chimpanzees from two communities in Gombe National Park, Tanzania. These samples, which were derived from 35 chimpanzees, many of whom have been monitored for multiple years, provide an unusually comprehensive longitudinal depth for individuals of known genetic relationships. Although the composition of the great-ape microbiota has been shown to codiversify with host species, indicating that host genetics and phylogeny have played a major role in its differentiation over evolutionary timescales, the geneaological relationships of individual chimpanzees did not coincide with the similarity in their gut microbial communities. However, the inhabitants from adjacent chimpanzee communities could be distinguished based on the contents of their gut microbiota. Despite the broad similarity of community members, as would be expected from shared diet or interactions, long-term immigrants to a community often harbored the most distinctive gut microbiota, suggesting that individuals retain hallmarks of their previous gut microbial communities for extended periods. This pattern was reinforced in several chimpanzees sampled over long temporal scales, in which the major constituents of the gut microbiota were maintained for nearly a decade

Manipulating the critical temperature for the superfluid phase transition in trapped atomic Fermi gases

We examine the effect of the trapping potential on the critical temperature, $T_C$, for the BCS transition to a superfluid state in trapped atomic gases of fermions. $T_C$ for an arbitrary power law trap is calculated in the Thomas-Fermi approximation. For anharmonic traps, $T_C$ can be increased by several orders of magnitude in comparison to a harmonic trap. Our theoretical results indicate that, in practice, one could manipulate the critical temperature for the BCS phase transition by shaping the traps confining the atomic Fermi gases.Comment: 4 page

Characterizing energy budget variability at a Sahelian site:A test of NWP model behaviour

We use observations of surface and top-of-the-atmosphere (TOA) broadband radiation fluxes determined from the Atmospheric Radiation Measurement programme mobile facility, the Geostationary Earth Radiation Budget (GERB) and Spinning Enhanced Visible and Infrared Imager (SEVIRI) instruments and a range of meteorological variables at a site in the Sahel to test the ability of the ECMWF Integrated Forecasting System cycle 43r1 to describe energy budget variability. The model has daily average biases of −12 and 18 W m⁻² for outgoing longwave and reflected shortwave TOA radiation fluxes, respectively. At the surface, the daily average bias is 12(13) W m⁻² for the longwave downwelling (upwelling) radiation flux and −21(−13) W m⁻² for the shortwave downwelling (upwelling) radiation flux. Using multivariate linear models of observation–model differences, we attribute radiation flux discrepancies to physical processes, and link surface and TOA fluxes. We find that model biases in surface radiation fluxes are mainly due to a low bias in ice water path (IWP), poor description of surface albedo and model–observation differences in surface temperature. We also attribute observed discrepancies in the radiation fluxes, particularly during the dry season, to the misrepresentation of aerosol fields in the model from use of a climatology instead of a dynamic approach. At the TOA, the low IWP impacts the amount of reflected shortwave radiation while biases in outgoing longwave radiation are additionally coupled to discrepancies in the surface upwelling longwave flux and atmospheric humidity

Mediation in the Law Curriculum

Cited by Lord Neuberger in ‘Educating Future Mediators’ at the 4th Civil Mediation Council National Conference, May 201

Diffraction of a superfluid Fermi gas by an atomic grating

An atomic grating generated by a pulsed standing wave laser field is proposed to manipulate the superfluid state in a quantum degenerate gas of fermionic atoms. We show that in the presence of atomic Cooper pairs, the density oscillations of the gas caused by the atomic grating exhibit a much longer coherence time than that in the normal Fermi gas. Our result indicates that the technique of a pulsed atomic grating can be a potential candidate to detect the atomic superfluid state in a quantum degenerate Fermi gas.Comment: 4 pages, 2 figure

Lipase-catalyzed Reactions at Interfaces of Two-phase Systems and Microemulsions

This work describes the influence of two polar lipids, Sn-1/3 and Sn-2 monopalmitin, on the activity of lipase in biphasic systems and in microemulsions. In previous communications, we have shown that Sn-2 monoglycerides can replace Sn-1,3 regiospecific lipases at the oil–water interface, causing a drastically reduced rate of lipolysis. We here demonstrate that even if the lipase is expelled from the interface, it can catalyze esterification of the Sn-2 monoglyceride with fatty acids in both macroscopic oil–water systems and in microemulsions, leading to formation of di- and triglycerides

Introducing willingness-to-pay for noise changes into transport appraisal: an application of benefit transfer.

Numerous research studies have elicited willingness-to-pay values for transport-related noise, however, in many industrialised countries including the UK, noise costs and benefits are still not incorporated into appraisals for most transport projects and policy changes (Odgaard et al, 2005; Grant-Muller et al, 2001). This paper describes the actions recently taken in the UK to address this issue, comprising: primary research based on the city of Birmingham; an international review of willingness-to-pay evidence; development of values using benefit transfers over time and locations; and integration with appraisal methods. Amongst the main findings are: that the willingness-to-pay estimates derived for the UK are broadly comparable with those used in appraisal elsewhere in Europe; that there is a case for a lower threshold at 1 45dB(A)Leq,18hr1 rather than the more conventional 55dB(A); and that values per dB(A) increase with the noise level above this threshold. There are significant issues over the valuation of rail versus road noise, the neglect of non-residential noise and the valuation of high noise levels in different countries. Conclusions are drawn regarding the feasibility of noise valuation based on benefit transfers in the UK and elsewhere, and future research needs in this field are discussed