1,104 research outputs found
Finite to infinite steady state solutions, bifurcations of an integro-differential equation
We consider a bistable integral equation which governs the stationary
solutions of a convolution model of solid--solid phase transitions on a circle.
We study the bifurcations of the set of the stationary solutions as the
diffusion coefficient is varied to examine the transition from an infinite
number of steady states to three for the continuum limit of the
semi--discretised system. We show how the symmetry of the problem is
responsible for the generation and stabilisation of equilibria and comment on
the puzzling connection between continuity and stability that exists in this
problem
Quantum Phase and Quantum Phase Operators: Some Physics and Some History
After reviewing the role of phase in quantum mechanics, I discuss, with the
aid of a number of unpublished documents, the development of quantum phase
operators in the 1960's. Interwoven in the discussion are the critical physics
questions of the field: Are there (unique) quantum phase operators and are
there quantum systems which can determine their nature? I conclude with a
critique of recent proposals which have shed new light on the problem.Comment: 19 pages, 2 Figs. taken from published articles, LaTeX, to be
published in Physica Scripta, Los Alamos preprint LA-UR-92-352
Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats
Abstract Rationale Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1). Objectives The aim of the study was to determine whether tiagabine acted as a discriminative stimulus and, if so, whether other GABAergic compounds would generalise to it. Materials and methods Rats were trained to discriminate tiagabine (30 mg/kg p.o.) from vehicle, and generalisation to drugs that modulate GABA was assessed. Results Gaboxadol (5-20 mg/kg p.o.), a selective extrasynaptic GABA A agonist, generalised to tiagabine, although the extent of the generalisation was inconclusive. Indiplon (1 mg/kg p.o.), a benzodiazepine-like hypnotic, also partially generalised to tiagabine, although zolpidem and S-zopiclone did not. Baclofen, a GABA B receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABA A receptor antagonist, blocked the tiagabine cue, but the less brainpenetrant salt form, bicuculline methochloride, had no effect. Conclusions These data suggest that tiagabine generates a discriminative stimulus in rats, and provides a central GABA-mediated cue, but is distinct from the other GABAergic compounds tested
Probing embryonic tissue mechanics with laser hole-drilling
We use laser hole-drilling to assess the mechanics of an embryonic epithelium
during development - in vivo and with subcellular resolution. We ablate a
subcellular cylindrical hole clean through the epithelium, and track the
subsequent recoil of adjacent cells (on ms time scales). We investigate dorsal
closure in the fruit fly with emphasis on apical constriction of amnioserosa
cells. The mechanical behavior of this epithelium falls between that of a
continuous sheet and a 2D cellular foam (a network of tensile interfaces).
Tensile stress is carried both by cell-cell interfaces and by the cells' apical
actin networks. Our results show that stress is slightly concentrated along
interfaces (1.6-fold), but only in early closure. Furthermore, closure is
marked by a decrease in the recoil power-law exponent - implying a transition
to a more solid-like tissue. We use the site- and stage-dependence of the
recoil kinetics to constrain how the cellular mechanics change during closure.
We apply these results to test extant computational models.Comment: 23 pages with 9 figures (require color
Bessel Process and Conformal Quantum Mechanics
Different aspects of the connection between the Bessel process and the
conformal quantum mechanics (CQM) are discussed. The meaning of the possible
generalizations of both models is investigated with respect to the other model,
including self adjoint extension of the CQM. Some other generalizations such as
the Bessel process in the wide sense and radial Ornstein- Uhlenbeck process are
discussed with respect to the underlying conformal group structure.Comment: 28 Page
Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)
Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ā„1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2ā12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authorsā knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months
Cold and Ultracold Molecules: Science, Technology, and Applications
This article presents a review of the current state of the art in the
research field of cold and ultracold molecules. It serves as an introduction to
the Special Issue of the New Journal of Physics on Cold and Ultracold Molecules
and describes new prospects for fundamental research and technological
development. Cold and ultracold molecules may revolutionize physical chemistry
and few body physics, provide techniques for probing new states of quantum
matter, allow for precision measurements of both fundamental and applied
interest, and enable quantum simulations of condensed-matter phenomena.
Ultracold molecules offer promising applications such as new platforms for
quantum computing, precise control of molecular dynamics, nanolithography, and
Bose-enhanced chemistry. The discussion is based on recent experimental and
theoretical work and concludes with a summary of anticipated future directions
and open questions in this rapidly expanding research field.Comment: 82 pages, 9 figures, review article to appear in New Journal of
Physics Special Issue on Cold and Ultracold Molecule
Interleukin-6 trans signalling enhances photodynamic therapy by modulating cell cycling
Photodynamic therapy (PDT) of solid tumours causes tissue damage that elicits local and systemic inflammation with major involvement of interleukin-6 (IL-6). We have previously reported that PDT-treated cells lose responsiveness to IL-6 cytokines. Therefore, it is unclear whether PDT surviving tumour cells are subject to regulation by IL-6 and whether this regulation could contribute to tumour control by PDT. We demonstrate in epithelial tumour cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans-signalling is established. Soluble interleukin-6 receptor-Ī± (IL-6RĪ±) (sIL-6RĪ±) and IL-6 were released by leucocytes in the presence of conditioned medium from PDT-treated tumour cells. Cells that had lost their membrane receptor IL-6RĪ± due to PDT responded to treatment with the IL-6RāIL-6 complex (Hyper-IL-6) with activation of signal transducers and activator of transcription (STAT3) and ERK. Photodynamic therapy-treated cells, which were maintained during post-PDT recovery in presence of IL-6 or Hyper-IL-6, showed an enhanced suppression of proliferation. Cytokine-dependent inhibition of proliferation correlated with a decrease in cyclin E, CDK2 and Cdc25A, and enhancement of p27kip1 and hypophosphorylated Rb. The IL-6 trans-signalling-mediated attenuation of cell proliferation was also effective in vivo detectable by an improved Colon26 tumour cure by PDT combined with Hyper-IL-6 treatment. Prevention of IL-6 trans-signalling using soluble gp130 reduced curability. The data suggest that the post-PDT tumour milieu contains the necessary components to establish effective IL-6 trans-signalling, thus providing a means for more effective tumour control
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