382 research outputs found
Quantum Superposition of Massive Objects and Collapse Models
We analyze the requirements to test some of the most paradigmatic collapse
models with a protocol that prepares quantum superpositions of massive objects.
This consists of coherently expanding the wave function of a
ground-state-cooled mechanical resonator, performing a squared position
measurement that acts as a double slit, and observing interference after
further evolution. The analysis is performed in a general framework and takes
into account only unavoidable sources of decoherence: blackbody radiation and
scattering of environmental particles. We also discuss the limitations imposed
by the experimental implementation of this protocol using cavity quantum
optomechanics with levitating dielectric nanospheres.Comment: 19 pages, 17 figure
Theory of decoherence in a matter wave Talbot-Lau interferometer
We present a theoretical framework to describe the effects of decoherence on
matter waves in Talbot-Lau interferometry. Using a Wigner description of the
stationary beam the loss of interference contrast can be calculated in closed
form. The formulation includes both the decohering coupling to the environment
and the coherent interaction with the grating walls. It facilitates the
quantitative distinction of genuine quantum interference from the expectations
of classical mechanics. We provide realistic microscopic descriptions of the
experimentally relevant interactions in terms of the bulk properties of the
particles and show that the treatment is equivalent to solving the
corresponding master equation in paraxial approximation.Comment: 20 pages, 4 figures (minor corrections; now in two-column format
Ectopic expression of the beta-cell specific transcription factor Pdx1 inhibits glucagon gene transcription
Aims/hypothesis: The transcription factor Pdx1 is required for the development and differentiation of all pancreatic cells. Beta-cell specific inactivation of Pdx1 in developing or adult mice leads to an increase in glucagon-expressing cells, suggesting that absence of Pdx1could favour glucagon gene expression by a default mechanism. Method: We investigated the inhibitory role of Pdx1 on glucagon gene expression in vitro. The glucagonoma cell line InR1G9 was transduced with a Pdx1-encoding lentiviral vector and insulin and glucagon mRNA levels were analysed by northern blot and real-time PCR. To understand the mechanism by which Pdx1 inhibits glucagon gene expression, we studied its effect on glucagon promoter activity in non-islet cells using transient transfections and gel-shift analysis. Results: In glucagonoma cells transduced with a Pdx1-encoding lentiviral vector, insulin gene expression was induced while glucagon mRNA levels were reduced by 50 to 60%. In the heterologous cell line BHK-21, Pdx1 inhibited by 60 to 80% the activation of the α-cell specific element G1 conferred by Pax-6 and/or Cdx-2/3. Although Pdx1 could bind three AT-rich motifs within G1, two of which are binding sites for Pax-6 and Cdx-2/3, the affinity of Pdx1 for G1 was much lower as compared to Pax-6. In addition, Pdx1 inhibited Pax-6 mediated activation through G3, to which Pdx1 was unable to bind. Moreover, a mutation impairing DNA binding of Pdx1 had no effect on its inhibition on Cdx-2/3. Since Pdx1 interacts directly with Pax-6 and Cdx-2/3 forming heterodimers, we suggest that Pdx1 inhibits glucagon gene transcription through protein to protein interactions with Pax-6 and Cdx-2/3. Conclusion/interpretation: Cell-specific expression of the glucagon gene can only occur when Pdx1 expression extinguishes from the early α cell precurso
Proliferation of sorted human and rat beta cells
Aims/hypothesis: The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors. Methods: Human beta cells were purified by FACS by virtue of their high zinc content using Newport Green, and excluding ductal and dead cells. Rat beta cells were sorted by autofluorescence or using the same method developed for human cells. Cells were plated on poly-l-lysine or ECMs from rat or human bladder carcinoma cells or bovine corneal ECM and incubated in the presence of BrdU with or without growth factors. Results: The newly developed method for sorting human beta cells yields a population containing 91.4 ± 2.8% insulin-positive cells with a low level of spontaneous apoptosis and a robust secretory response to glucose. Beta cells from 8-week-old rats proliferated in culture and this was increased by ECM. Among growth factors, only human growth hormone (hGH) and the glucagon-like peptide-1 analogue liraglutide enhanced proliferation of rat beta cells, with a significant increase on both poly-l-lysine and ECM. By contrast, sorted adult human beta cells from 16 donors aged 48.9 ± 14.3years (range 16-64years) failed to replicate demonstrably in vitro regardless of the substratum or growth factors used. Conclusions/interpretation: These findings indicate that, in our conditions, the fully differentiated human adult insulin-producing beta cell was unable to proliferate in vitro. This has important implications for any attempt to expand cells from pancreases of donors of this age group. By contrast, the rat beta cells used here were able to divide in vitro, and this was enhanced by ECM, hGH and liraglutid
Autonomous and self-sustained circadian oscillators displayed in human islet cells
Aims/hypothesis: Following on from the emerging importance of the pancreas circadian clock on islet function and the development of type 2 diabetes in rodent models, we aimed to examine circadian gene expression in human islets. The oscillator properties were assessed in intact islets as well as in beta cells. Methods: We established a system for long-term bioluminescence recording in cultured human islets, employing lentivector gene delivery of the core clock gene Bmal1 (also known as Arntl)-luciferase reporter. Beta cells were stably labelled using a rat insulin2 promoter fluorescent construct. Single-islet/cell oscillation profiles were measured by combined bioluminescence-fluorescence time-lapse microscopy. Results: Human islets synchronised in vitro exhibited self-sustained circadian oscillations of Bmal1-luciferase expression at both the population and single-islet levels, with period lengths of 23.6 and 23.9h, respectively. Endogenous BMAL1 and CRY1 transcript expression was circadian in synchronised islets over 48h, and antiphasic to REV-ERBα (also known as NR1D1), PER1, PER2, PER3 and DBP transcript circadian profiles. HNF1A and PDX1 exhibited weak circadian oscillations, in phase with the REV-ERBα transcript. Dispersed islet cells were strongly oscillating as well, at population and single-cell levels. Importantly, beta and non-beta cells revealed oscillatory profiles that were well synchronised with each other. Conclusions/interpretation: We provide for the first time compelling evidence for high-amplitude cell-autonomous circadian oscillators displayed in human pancreatic islets and in dispersed human islet cells. Moreover, these clocks are synchronised between beta and non-beta cells in primary human islet cell culture
Internally Electrodynamic Particle Model: Its Experimental Basis and Its Predictions
The internally electrodynamic (IED) particle model was derived based on
overall experimental observations, with the IED process itself being built
directly on three experimental facts, a) electric charges present with all
material particles, b) an accelerated charge generates electromagnetic waves
according to Maxwell's equations and Planck energy equation and c) source
motion produces Doppler effect. A set of well-known basic particle equations
and properties become predictable based on first principles solutions for the
IED process; several key solutions achieved are outlined, including the de
Broglie phase wave, de Broglie relations, Schr\"odinger equation, mass,
Einstein mass-energy relation, Newton's law of gravity, single particle self
interference, and electromagnetic radiation and absorption; these equations and
properties have long been broadly experimentally validated or demonstrated. A
specific solution also predicts the Doebner-Goldin equation which emerges to
represent a form of long-sought quantum wave equation including gravity. A
critical review of the key experiments is given which suggests that the IED
process underlies the basic particle equations and properties not just
sufficiently but also necessarily.Comment: Presentation at the 27th Int Colloq on Group Theo Meth in Phys, 200
Autonomous and self-sustained circadian oscillators displayed in human islet cells
Aims/hypothesis: Following on from the emerging importance of the pancreas circadian clock on islet function and the development of type 2 diabetes in rodent models, we aimed to examine circadian gene expression in human islets. The oscillator properties were assessed in intact islets as well as in beta cells. Methods: We established a system for long-term bioluminescence recording in cultured human islets, employing lentivector gene delivery of the core clock gene Bmal1 (also known as Arntl)-luciferase reporter. Beta cells were stably labelled using a rat insulin2 promoter fluorescent construct. Single-islet/cell oscillation profiles were measured by combined bioluminescence-fluorescence time-lapse microscopy. Results: Human islets synchronised in vitro exhibited self-sustained circadian oscillations of Bmal1-luciferase expression at both the population and single-islet levels, with period lengths of 23.6 and 23.9h, respectively. Endogenous BMAL1 and CRY1 transcript expression was circadian in synchronised islets over 48h, and antiphasic to REV-ERBα (also known as NR1D1), PER1, PER2, PER3 and DBP transcript circadian profiles. HNF1A and PDX1 exhibited weak circadian oscillations, in phase with the REV-ERBα transcript. Dispersed islet cells were strongly oscillating as well, at population and single-cell levels. Importantly, beta and non-beta cells revealed oscillatory profiles that were well synchronised with each other. Conclusions/interpretation: We provide for the first time compelling evidence for high-amplitude cell-autonomous circadian oscillators displayed in human pancreatic islets and in dispersed human islet cells. Moreover, these clocks are synchronised between beta and non-beta cells in primary human islet cell culture
Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function
OBJECTIVE— Somatostatin (SST) is secreted by islet δ-cells and by extraislet neuroendocrine cells. SST receptors have been identified on α- and β-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating α- and β-cell function. However, the specific intraislet function of δ-cell SST remains uncertain. We have used Sst−/− mice to investigate the role of δ-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo
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