Increased gastrin-releasing peptide (GRP) receptor expression in tumour cells confers sensitivity to [Arg6,D-Trp7,9,NmePhe8]-substance P (6-11)-induced growth inhibition.

[Arg(6),D-Trp(7,9),N(me)Phe(8)]-substance P (6-11) (SP-G) is a novel anticancer agent that has recently completed phase I clinical trials. SP-G inhibits mitogenic neuropeptide signal transduction and small cell lung cancer (SCLC) cell growth in vitro and in vivo. Using the SCLC cell line series GLC14, 16 and 19, derived from a single patient during the clinical course of their disease and the development of chemoresistance, it is shown that there was an increase in responsiveness to neuropeptides. This was paralleled by an increased sensitivity to SP-G. In a selected panel of tumour cell lines (SCLC, non-SCLC, ovarian, colorectal and pancreatic), the expression of the mitogenic neuropeptide receptors for vasopressin, gastrin-releasing peptide (GRP), bradykinin and gastrin was examined, and their sensitivity to SP-G tested in vitro and in vivo. The tumour cell lines displayed a range of sensitivity to SP-G (IC(50) values from 10.5 to 119 microM). The expression of the GRP receptor measured by reverse transcriptase-polymerase chain reaction, correlated significantly with growth inhibition by SP-G. Moreover, introduction of the GRP receptor into rat-1A fibroblasts markedly increased their sensitivity to SP-G. The measurement of receptor expression from biopsy samples by polymerase chain reaction could provide a suitable diagnostic test to predict efficacy to SP-G clinically. This strategy would be of potential benefit in neuropeptide receptor-expressing tumours in addition to SCLC, and in tumours that are relatively resistant to conventional chemotherapy

Search for Doubly-Charged Higgs Bosons Decaying to Dileptons in proton anti-proton Collisions at s**(1/2) = 1.96 TeV

We present the results of a search for doubly charged Higgs bosons (H±±) decaying to dileptons (ll′) using ≈240  pb-1 of pp̅ collision data collected by the CDF II experiment at the Fermilab Tevatron. In our search region, given by same-sign ll′ mass mll′>80  GeV/c2 (100  GeV/c2 for ee channel), we observe no evidence for H±± production. We set limits on σ(pp̅ →H++H--→l+l′+l-l′-) as a function of the mass of the H±± and the chirality of its couplings. Assuming exclusive same-sign dilepton decays, we derive lower mass limits on HL±± of 133, 136, and 115  GeV/c2 in the ee, μμ, and eμ channels, respectively, and a lower mass limit of 113  GeV/c2 on HR±± in the μμ channel, all at the 95% confidence level

Search for quark-lepton compositeness and a heavy W boson using the ev channel in pp(overbar) collisions at (square root)s = 1.8 TeV

We present searches for quark-lepton compositeness and a heavy W′ boson at high electron-neutrino transverse mass. We use ∼110pb-1 of data collected in pp̅ collisions at √s = 1.8TeV by the CDF Collaboration during 1992–1995. The data are consistent with standard model expectations. Limits are set on the quark-lepton compositeness scale Λ, the ratio of partial cross sections σ(W′→eν)/σ(W→eν), and the mass of a W′ boson with standard model couplings. We exclude Λ<2.81TeV and a W′ boson with mass below 754GeV/c2 at the 95% confidence level. Combining with our previously published limit obtained using the muon channel, we exclude a W′ boson with mass below 786GeV/c2 at the 95% confidence level

Search for neutral supersymmetric Higgs bosons in pp(overbar) collisions at (square root)s = 1.8 TeV

We present the results of a search for neutral Higgs bosons produced in association with b quarks in pp̅ →bb̅ ϕ→bb̅ bb̅ final states with 91±7pb-1 of pp̅ collisions at √s = 1.8TeV recorded by the Collider Detector at Fermilab. We find no evidence of such a signal and the data are interpreted in the context of the neutral Higgs sector of the minimal supersymmetric extension of the standard model. With basic parameter choices for the supersymmetric scale and the stop-quark mixing, we derive 95% C.L. lower mass limits for neutral Higgs bosons for tanβ values in excess of 35

Production of Xc1 and Xc2 in pp(overbar) collisions at (square root)s = 1.8 TeV

We have measured the ratio of prompt production rates of the charmonium states χc1 and χc2 in 110pb-1 of pp̅ collisions at √s = 1.8TeV. The photon from their decay into J/ψγ is reconstructed through conversion into e+e- pairs. The energy resolution this technique provides makes the resolution of the two states possible. We find the ratio of production cross sections σχc2/σχc1 = 0.96±0.27(stat)±0.11(syst) for events with pT(J/ψ)>4.0GeV/c, |η(J/ψ)|1.0GeV/c

Mathematical modelling of cell layer growth in a hollow fibre bioreactor.

Generating autologous tissue grafts of a clinically useful volume requires efficient and controlled expansion of cell populations harvested from patients. Hollow fibre bioreactors show promise as cell expansion devices, owing to their potential for scale-up. However, further research is required to establish how to specify appropriate hollow fibre bioreactor operating conditions for expanding different cell types. In this study we develop a simple model for the growth of a cell layer seeded on the outer surface of a single fibre in a perfused hollow fibre bioreactor. Nutrient-rich culture medium is pumped through the fibre lumen and leaves the bioreactor via the lumen outlet or passes through the porous fibre walls and cell layer, and out via ports on the outer wall of the extra-capillary space. Stokes and Darcy equations for fluid flow in the fibre lumen, fibre wall, cell layer and extra-capillary space are coupled to reaction-advection-diffusion equations for oxygen and lactate transport through the bioreactor, and to a simple growth law for the evolution of the free boundary of the cell layer. Cells at the free boundary are assumed to proliferate at a rate that increases with the local oxygen concentration, and to die and detach from the layer if the local fluid shear stress or lactate concentration exceed critical thresholds. We use the model to predict operating conditions that maximise the cell layer growth for different cell types. In particular, we predict the optimal flow rate of culture medium into the fibre lumen and fluid pressure imposed at the lumen outlet for cell types with different oxygen demands and fluid shear stress tolerances, and compare the growth of the cell layer when the exit ports on the outside of the bioreactor are open with that when they are closed. Model simulations reveal that increasing the inlet flow rate and outlet fluid pressure increases oxygen delivery to the cell layer and, therefore, the growth rate of cells that are tolerant to high shear stresses, but may be detrimental for shear-sensitive cells. The cell layer growth rate is predicted to increase, and be less sensitive to the lactate tolerance of the cells, when the exit ports are opened, as the radial flow through the bioreactor is enhanced and the lactate produced by the cells cleared more rapidly from the cell layer

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS