Bose-Einstein condensation of photons in an optical microcavity

Bose-Einstein condensation, the macroscopic ground state accumulation of particles with integer spin (bosons) at low temperature and high density, has been observed in several physical systems, including cold atomic gases and solid state physics quasiparticles. However, the most omnipresent Bose gas, blackbody radiation (radiation in thermal equilibrium with the cavity walls) does not show this phase transition, because the chemical potential of photons vanishes and, when the temperature is reduced, photons disappear in the cavity walls. Theoretical works have considered photon number conserving thermalization processes, a prerequisite for Bose-Einstein condensation, using Compton scattering with a gas of thermal electrons, or using photon-photon scattering in a nonlinear resonator configuration. In a recent experiment, we have observed number conserving thermalization of a two-dimensional photon gas in a dye-filled optical microcavity, acting as a 'white-wall' box for photons. Here we report on the observation of a Bose-Einstein condensation of photons in a dye-filled optical microcavity. The cavity mirrors provide both a confining potential and a non-vanishing effective photon mass, making the system formally equivalent to a two-dimensional gas of trapped, massive bosons. By multiple scattering off the dye molecules, the photons thermalize to the temperature of the dye solution (room temperature). Upon increasing the photon density we observe the following signatures for a BEC of photons: Bose-Einstein distributed photon energies with a massively populated ground state mode on top of a broad thermal wing, the phase transition occurring both at the expected value and exhibiting the predicted cavity geometry dependence, and the ground state mode emerging even for a spatially displaced pump spot

Melody, an ENU mutation in Caspase 3, alters the catalytic cysteine residue and causes sensorineural hearing loss in mice

Progeny from the Harwell N-ethyl-N-nitrosourea (ENU) recessive mutagenesis screen were assessed for auditory defects. A pedigree was identified with multiple progeny lacking response to a clickbox test. Auditory brainstem response (ABR) analysis showed that homozygous mutant mice were profoundly deaf and the line was named melody. We subsequently mapped this mutation to a 6-Mb region on chromosome 8 and identified a point mutation in melody that results in a C163S substitution in the catalytic site of Caspase 3, a cysteine protease involved in apoptosis. Melody fails to complement a null Caspase-3 mutant. Scanning electron microscopy (SEM) has revealed disorganised sensory hair cells and hair cell loss. Histological analysis of melody has shown degeneration of spiral ganglion cells in homozygote mice, with a gradient of severity from apical to basal turns. Melody heterozygotes also show evidence of loss of spiral ganglion neurons, suggesting that the C163S mutation may show dominant negative effects by binding and sequestering proteins at the active site. The melody line provides a new model for studying the role of Caspase 3 in deafness and a number of other pathways and systems

An ENU-Induced Mutation of Nrg1 Causes Dilated Pupils and a Reduction in Muscarinic Receptors in the Sphincter Pupillae

BACKGROUND: N-ethyl-N-nitrosourea (ENU)-induced mutagenesis is a powerful tool for the study of gene function and the generation of human disease models. A large number of mouse mutants obtained by ENU-induced mutagenesis with a variety of phenotypes have been recovered. However, after genetic confirmation testing, only approximately 50% of the abnormal phenotypes were found to be heritable. METHODOLOGY/PRINCIPAL FINDINGS: A mouse mutant, Dp1, with a dilated pupil phenotype was induced with an N-ethyl-N-nitrosourea (ENU) mutagenesis strategy. Sequence analysis for Nrg1 reveals a G>A base substitution that flanks exon E59, encoding for an EGFβ domain, in the 5' splice donor site. The mutation affects but does not abolish the splicing of EGFβ-type Nrg1 mRNA in Dp1 mice and produces several different transcripts by activating other, cryptic splice sites. These types of protein isoforms are expected, and the result shows that, in the mutant, the effect is a decrease in but not an elimination of the high affinity EGFβ-type Nrg1 isoforms. This is partially compensated for by an increase in expression of the low affinity alpha forms or inactive proteins, suggesting that the mutation results in a hypomorphic allele. Interestingly, genetic model testing shows that Dp1 is a mutation that results in a dilated pupil phenotype that is inherited with very low penetrance when heterozygous and with complete penetrance when homozygous. Pharmacological and immunohistochemical tests show a reduction of muscarinic (M) receptors in the sphincter pupillae of Dp1 mice, which is a major cause of dilated pupils. CONCLUSIONS/SIGNIFICANCE: This study is the first report of an Nrg1 mutation being associated with a dilated pupil phenotype and the reduction of M receptors. This report may help in establishing more mutant mouse lines and models of human genetic disease and can be applied to other organisms. Dp1 mice are a valuable resource for the further clarification of Nrg1 biological function

Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope

We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently-known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi-LAT energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cut-off at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch D., Rea N., Burnett

Fermi Large Area Telescope observations of PSR J1836+5925

The discovery of the gamma-ray pulsar PSR J1836+5925, powering the formerly unidentified EGRET source 3EG J1835+5918, was one of the early accomplishments of the Fermi Large Area Telescope (LAT). Sitting 25 degrees off the Galactic plane, PSR J1836+5925 is a 173 ms pulsar with a characteristic age of 1.8 million years, a spindown luminosity of 1.1$\times10^{34}$ erg s$^{-1}$, and a large off-peak emission component, making it quite unusual among the known gamma-ray pulsar population. We present an analysis of one year of LAT data, including an updated timing solution, detailed spectral results and a long-term light curve showing no indication of variability. No evidence for a surrounding pulsar wind nebula is seen and the spectral characteristics of the off-peak emission indicate it is likely magnetospheric. Analysis of recent XMM observations of the X-ray counterpart yields a detailed characterization of its spectrum, which, like Geminga, is consistent with that of a neutron star showing evidence for both magnetospheric and thermal emission.Comment: Accepted to Astrophysical Journa

The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone

A Myo6 Mutation Destroys Coordination between the Myosin Heads, Revealing New Functions of Myosin VI in the Stereocilia of Mammalian Inner Ear Hair Cells

Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential for auditory and vestibular function in mammals, since genetic mutations lead to hearing impairment and vestibular dysfunction in both humans and mice. Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function. Structural changes in the Tailchaser hair bundles include mislocalization of the kinocilia and branching of stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and delivery of endocytic vesicles to the early endosome revealed that the mutant phenotype displays disrupted motor function. The actin-activated ATPase rates measured for the D179Y mutation are decreased, and indicate loss of coordination of the myosin VI heads or ‘gating’ in the dimer form. Proper coordination is required for walking processively along, or anchoring to, actin filaments, and is apparently destroyed by the proximity of the mutation to the nucleotide-binding pocket. This loss of myosin VI function may not allow myosin VI to transport its cargoes appropriately at the base and within the stereocilia, or to anchor the membrane of stereocilia to actin filaments via its cargos, both of which lead to structural changes in the stereocilia of myosin VI–impaired hair cells, and ultimately leading to deafness

NMR studies of p7 protein from hepatitis C virus

The p7 protein of hepatitis C virus (HCV) plays an important role in the viral lifecycle. Like other members of the viroporin family of small membrane proteins, the amino acid sequence of p7 is largely conserved over the entire range of genotypes, and it forms ion channels that can be blocked by a number of established channel-blocking compounds. Its characteristics as a membrane protein make it difficult to study by most structural techniques, since it requires the presence of lipids to fold and function properly. Purified p7 can be incorporated into phospholipid bilayers and micelles. Initial solid-state nuclear magnetic resonance (NMR) studies of p7 in 14-O-PC/6-O-PC bicelles indicate that the protein contains helical segments that are tilted approximately 10° and 25° relative to the bilayer normal. A truncated construct corresponding to the second transmembrane domain of p7 is shown to have properties similar to those of the full-length protein, and was used to determine that the helix segment tilted at 10° is in the C-terminal portion of the protein. The addition of the channel blocker amantadine to the full-length protein resulted in selective chemical shift changes, demonstrating that NMR has a potential role in the development of drugs targeted to p7

Estimating the number of colorectal cancer patients treated with anti-tumour therapy in 2015: the analysis of the Czech National Cancer Registry

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) represents a serious health care problem in the Czech Republic, introducing a need for a prospective modelling of the incidence and prevalence rates. The prevalence of patients requiring anti-tumour therapy is also of great importance, as it is directly associated with planning of health care resources.</p> <p>Methods</p> <p>This work proposes a population-based model for the estimation of stage-specific prevalence of CRC patients who will require active anti-tumour therapy in a given year. Its applicability is documented on records of the Czech National Cancer Registry (CNCR), which is used to estimate the number of patients potentially treated with anti-tumour therapy in the Czech Republic in 2015.</p> <p>Results</p> <p>Several scenarios are adopted to cover the plausible development of the incidence and survival rates, and the probability of an anti-tumour therapy initiation. Based on the scenarios, the model predicts an increase in CRC prevalence from 13% to 30% in comparison with the situation in 2008. Moreover, the model predicts that 10,074 to 11,440 CRC patients will be indicated for anti-tumour therapy in the Czech Republic in 2015. Considering all patients with terminal cancer recurrence and all patients primarily diagnosed in stage IV, it is predicted that 3,485 to 4,469 CRC patients will be treated for the metastatic disease in 2015, which accounts for more than one third (34-40%) of all CRC patients treated this year.</p> <p>Conclusions</p> <p>A new model for the estimation of the number of CRC patients requiring active anti-tumour therapy is proposed in this paper. The model respects the clinical stage as the primary stratification factor and utilizes solely the population-based cancer registry data. Thus, no specific hospital data records are needed in the proposed approach. Regarding the short-term prediction of the CRC burden in the Czech Republic, the model confirms a continuous increase in the burden that must be accounted for in the future planning of health care in the Czech Republic.</p

Investigation of the Acetylation Mechanism by GCN5 Histone Acetyltransferase

The histone acetylation of post-translational modification can be highly dynamic and play a crucial role in regulating cellular proliferation, survival, differentiation and motility. Of the enzymes that mediate post-translation modifications, the GCN5 of the histone acetyltransferase (HAT) proteins family that add acetyl groups to target lysine residues within histones, has been most extensively studied. According to the mechanism studies of GCN5 related proteins, two key processes, deprotonation and acetylation, must be involved. However, as a fundamental issue, the structure of hGCN5/AcCoA/pH3 remains elusive. Although biological experiments have proved that GCN5 mediates the acetylation process through the sequential mechanism pathway, a dynamic view of the catalytic process and the molecular basis for hGCN5/AcCoA/pH3 are still not available and none of theoretical studies has been reported to other related enzymes in HAT family. To explore the molecular basis for the catalytic mechanism, computational approaches including molecular modeling, molecular dynamic (MD) simulation and quantum mechanics/molecular mechanics (QM/MM) simulation were carried out. The initial hGCN5/AcCoA/pH3 complex structure was modeled and a reasonable snapshot was extracted from the trajectory of a 20 ns MD simulation, with considering post-MD analysis and reported experimental results. Those residues playing crucial roles in binding affinity and acetylation reaction were comprehensively investigated. It demonstrated Glu80 acted as the general base for deprotonation of Lys171 from H3. Furthermore, the two-dimensional QM/MM potential energy surface was employed to study the sequential pathway acetylation mechanism. Energy barriers of addition-elimination reaction in acetylation obtained from QM/MM calculation indicated the point of the intermediate ternary complex. Our study may provide insights into the detailed mechanism for acetylation reaction of GCN5, and has important implications for the discovery of regulators against GCN5 enzymes and related HAT family enzymes