Altered intra-nuclear organisation of heterochromatin and genes in ICF syndrome.

The ICF syndrome is a rare autosomal recessive disorder, the most common symptoms of which are immunodeficiency, facial anomalies and cytogenetic defects involving decondensation and instability of chromosome 1, 9 and 16 centromeric regions. ICF is also characterised by significant hypomethylation of the classical satellite DNA, the major constituent of the juxtacentromeric heterochromatin. Here we report the first attempt at analysing some of the defining genetic and epigenetic changes of this syndrome from a nuclear architecture perspective. In particular, we have compared in ICF (Type 1 and Type 2) and controls the large-scale organisation of chromosome 1 and 16 juxtacentromeric heterochromatic regions, their intra-nuclear positioning, and co-localisation with five specific genes (BTG2, CNN3, ID3, RGS1, F13A1), on which we have concurrently conducted expression and methylation analysis. Our investigations, carried out by a combination of molecular and cytological techniques, demonstrate the existence of specific and quantifiable differences in the genomic and nuclear organisation of the juxtacentromeric heterochromatin in ICF. DNA hypomethylation, previously reported to correlate with the decondensation of centromeric regions in metaphase described in these patients, appears also to correlate with the heterochromatin spatial configuration in interphase. Finally, our findings on the relative positioning of hypomethylated satellite sequences and abnormally expressed genes suggest a connection between disruption of long-range gene-heterochromatin associations and some of the changes in gene expression in ICF. Beyond its relevance to the ICF syndrome, by addressing fundamental principles of chromosome functional organisation within the cell nucleus, this work aims to contribute to the current debate on the epigenetic impact of nuclear architecture in development and disease

Some Remarks on the Neutrino Oscillation Phase in a Gravitational Field

The weak gravitational field expansion method to account for the gravitationally induced neutrino oscillation effect is critically examined. It is shown that the splitting of the neutrino phase into a ``kinematic'' and a ``gravitational'' phase is not always possible because the relativistic factor modifies the particle interference phase splitting condition in a gravitational field.Comment: 4 pages, no figure

The general treatment of high/low energy particle interference phase in a gravitational field

The interference phase of the high energy mass neutrinos and the low energy thermal neutrons in a gravitational field are studied. For the mass neutrinos, we obtain that the phase calculated along the null is equivalent to the half phase along the geodesic in the high energy limit, which means that the correct relative phase of the mass neutrinos is either the null phase or the half geodesic phase. Further we point out the importance of the energy condition in calculating the mass neutrino interference phase. Moreover, we apply the covariant phase to the calculation of the thermal neutron interference phase, and obtain the consistent result with that exploited in COW experiment.Comment: 14 pages, 1 figur

Quantum theory's last challenge

Quantum mechanics is now 100 years old and still going strong. Combining general relativity with quantum mechanics is the last hurdle to be overcome in the "quantum revolution".Comment: (9 pages, LaTex) This is the preprint version of an article that appeared in the issue 6813 (volume 408) of Nature, as part of a 3-article celebration of the 100th anniversary of Planck's solution of the black-body-radiation proble

Real time Faraday spectrometer

This invention is comprised of a charged particle spectrometer that contains a detection system which embodies the benefits of both foil-light emissions and faraday cups, yet it does not interfere with the particle beam. 5 Figs. (GHH

Gravitational Waves from the Dynamical Bar Instability in a Rapidly Rotating Star

A rapidly rotating, axisymmetric star can be dynamically unstable to an m=2 "bar" mode that transforms the star from a disk shape to an elongated bar. The fate of such a bar-shaped star is uncertain. Some previous numerical studies indicate that the bar is short lived, lasting for only a few bar-rotation periods, while other studies suggest that the bar is relatively long lived. This paper contains the results of a numerical simulation of a rapidly rotating gamma=5/3 fluid star. The simulation shows that the bar shape is long lived: once the bar is established, the star retains this shape for more than 10 bar-rotation periods, through the end of the simulation. The results are consistent with the conjecture that a star will retain its bar shape indefinitely on a dynamical time scale, as long as its rotation rate exceeds the threshold for secular bar instability. The results are described in terms of a low density neutron star, but can be scaled to represent, for example, a burned-out stellar core that is prevented from complete collapse by centrifugal forces. Estimates for the gravitational-wave signal indicate that a dynamically unstable neutron star in our galaxy can be detected easily by the first generation of ground based gravitational-wave detectors. The signal for an unstable neutron star in the Virgo cluster might be seen by the planned advanced detectors. The Newtonian/quadrupole approximation is used throughout this work.Comment: Expanded version to be published in Phys. Rev. D: 13 pages, REVTeX, 13 figures, 9 TeX input file

Spin, gravity, and inertia

The gravitational effects in the relativistic quantum mechanics are investigated. The exact Foldy-Wouthuysen transformation is constructed for the Dirac particle coupled to the static spacetime metric. As a direct application, we analyze the non-relativistic limit of the theory. The new term describing the specific spin (gravitational moment) interaction effect is recovered in the Hamiltonian. The comparison of the true gravitational coupling with the purely inertial case demonstrates that the spin relativistic effects do not violate the equivalence principle for the Dirac fermions.Comment: Revtex, 12 pages, no figures, accepted in Phys. Rev. Let

A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors

Gravitation: Global Formulation and Quantum Effects

A nonintegrable phase-factor global approach to gravitation is developed by using the similarity of teleparallel gravity with electromagnetism. The phase shifts of both the COW and the gravitational Aharonov-Bohm effects are obtained. It is then shown, by considering a simple slit experiment, that in the classical limit the global approach yields the same result as the gravitational Lorentz force equation of teleparallel gravity. It represents, therefore, the quantum mechanical version of the classical description provided by the gravitational Lorentz force equation. As teleparallel gravity can be formulated independently of the equivalence principle, it will consequently require no generalization of this principle at the quantum level.Comment: Latex (IOP style), 14 pages, 3 figures. To appear in Classical and Quantum Gravit

An interferometric gravitational wave detector as a quantum-gravity apparatus

As a consequence of the extreme precision of the measurements it performs, an interferometric gravitational wave detector is a macroscopic apparatus for which quantum effects are not negligible. I observe that this property can be exploited to probe some aspects of the interplay between Quantum Mechanics and Gravity.Comment: LaTex, 7 pages. Version accepted for publication in Nature. Under press embargo until publicatio