Dynamics of a bubble formed in double stranded DNA

We study the fluctuational dynamics of a tagged base-pair in double stranded DNA. We calculate the drift force which acts on the tagged base-pair using a potential model that describes interactions at base pairs level and use it to construct a Fokker-Planck equation.The calculated displacement autocorrelation function is found to be in very good agreement with the experimental result of Altan-Bonnet {\it et. al.} Phys. Rev. Lett. {\bf 90}, 138101 (2003) over the entire time range of measurement. We calculate the most probable displacements which predominately contribute to the autocorrelation function and the half-time history of these displacements.Comment: 11 pages, 4 figures. submitted to Phys. Rev. Let

Bubble coalescence in breathing DNA: Two vicious walkers in opposite potentials

We investigate the coalescence of two DNA-bubbles initially located at weak segments and separated by a more stable barrier region in a designed construct of double-stranded DNA. The characteristic time for bubble coalescence and the corresponding distribution are derived, as well as the distribution of coalescence positions along the barrier. Below the melting temperature, we find a Kramers-type barrier crossing behaviour, while at high temperatures, the bubble corners perform drift-diffusion towards coalescence. The results are obtained by mapping the bubble dynamics on the problem of two vicious walkers in opposite potentials.Comment: 7 pages, 4 figure

Quantitative test of the barrier nucleosome model for statistical positioning of nucleosomes up- and downstream of transcription start sites

The positions of nucleosomes in eukaryotic genomes determine which parts of the DNA sequence are readily accessible for regulatory proteins and which are not. Genome-wide maps of nucleosome positions have revealed a salient pattern around transcription start sites, involving a nucleosome-free region (NFR) flanked by a pronounced periodic pattern in the average nucleosome density. While the periodic pattern clearly reflects well-positioned nucleosomes, the positioning mechanism is less clear. A recent experimental study by Mavrich et al. argued that the pattern observed in S. cerevisiae is qualitatively consistent with a `barrier nucleosome model', in which the oscillatory pattern is created by the statistical positioning mechanism of Kornberg and Stryer. On the other hand, there is clear evidence for intrinsic sequence preferences of nucleosomes, and it is unclear to what extent these sequence preferences affect the observed pattern. To test the barrier nucleosome model, we quantitatively analyze yeast nucleosome positioning data both up- and downstream from NFRs. Our analysis is based on the Tonks model of statistical physics which quantifies the interplay between the excluded-volume interaction of nucleosomes and their positional entropy. We find that although the typical patterns on the two sides of the NFR are different, they are both quantitatively described by the same physical model, with the same parameters, but different boundary conditions. The inferred boundary conditions suggest that the first nucleosome downstream from the NFR (the +1 nucleosome) is typically directly positioned while the first nucleosome upstream is statistically positioned via a nucleosome-repelling DNA region. These boundary conditions, which can be locally encoded into the genome sequence, significantly shape the statistical distribution of nucleosomes over a range of up to ~1000 bp to each side.Comment: includes supporting materia

Professionalism and the Millbank Tendency: The Political Sociology of New Labour's employees

This article analyses party employees, one of the most under-researched subjects in the study of British political parties. We draw on a blend of quantitative and qualitative data in order to shed light on the social and political profiles of Labour Party staff, and on the question of their professionalisation. The latter theme is developed through a model derived from the sociology of professions. While a relatively limited proportion of party employees conform to the pure ideal-type of professionalism, a considerably greater number manifest enough of the core characteristics of specialisation, commitment, mobility, autonomy and self-regulation to be reasonably described as 'professionals in pursuit of political outcomes'

Back-to-back emission of the electrons in double photoionization of helium

We calculate the double differential distributions and distributions in recoil momenta for the high energy non-relativistic double photoionization of helium. We show that the results of recent experiments is the pioneering experimental manifestation of the quasifree mechanism for the double photoionization, predicted long ago in our papers. This mechanism provides a surplus in distribution over the recoil momenta at small values of the latter, corresponding to nearly "back-to-back" emission of the electrons. Also in agreement with previous analysis the surplus is due to the quadrupole terms of the photon-electron interaction. We present the characteristic angular distribution for the "back-to-back" electron emission. The confirmation of the quasifree mechanism opens a new area of exiting experiments, which are expected to increase our understanding of the electron dynamics and of the bound states structure. The results of this Letter along with the recent experiments open a new field for studies of two-electron ionization not only by photons but by other projectiles, e.g. by fast electrons or heavy ions.Comment: 10 pages, 2 figure

Long-term event-free survival with an embolised prosthetic valve leaflet in the thoracic aorta

We report the case of a patient who underwent a redo surgery for a leaflet escape from a Bjork-Shiley tilting disc mitral prosthesis inserted 18 years previously. The escaped disc remained lodged in the thoracic aorta without any complication. She ultimately died of terminal heart failure 13 years after the second operation. We believe this to be the longest survival with a dislodged leaflet from a mechanical valve. Removal of dislodged disc is recommended in literature but there may be a place for watchful observation in exceptional cases with no haemodynamic compromise

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Polyhedral vesicles

Polyhedral vesicles with a large bending modulus of the membrane such as the gel phase lipid membrane were studied using a Brownian dynamics simulation. The vesicles exhibit various polyhedral morphologies such as tetrahedron and cube shapes. We clarified two types of line defects on the edges of the polyhedrons: cracks of both monolayers at the spontaneous curvature of monolayer $C_{\text {0}}<0$, and a crack of the inner monolayer at $C_{\text {0}}\ge0$. Around the latter defect, the inner monolayer curves positively. Our results suggested that the polyhedral morphology is controlled by $C_{\text {0}}$.Comment: 4 pages, 5 figure

High expression of focal adhesion kinase (p125(FAK)) in node-negative breast cancer is related to overexpression of HER-2/neu and activated Akt kinase but does not predict outcome

INTRODUCTION: Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility and apoptosis. In breast carcinoma, FAK overexpression has been linked to cancer progression but the prognostic relevance remains unknown. In particular, with regard to lymph node-negative breast cancer it is important to identify high-risk patients who would benefit from further adjuvant therapy. METHODS: We analyzed 162 node-negative breast cancer cases to determine the prognostic relevance of FAK expression, and we investigated the relationship of FAK with major associated signaling pathways (HER2, Src, Akt and extracellular regulated kinases) by immunohistochemistry and western blot analysis. RESULTS: Elevated FAK expression did not predict patient outcome, in contrast to tumor grading (P = 0.005), Akt activation (P = 0.0383) and estrogen receptor status (P = 0.0033). Significant positive correlations were observed between elevated FAK expression and HER2 overexpression (P = 0.001), as well as phospho-Src Tyr-215 (P = 0.021) and phospho-Akt (P < 0.001), but not with phospho-ERK1/2 (P = 0.108). Western blot analysis showed a significant correlation of FAK Tyr-861 activation and HER2 overexpression (P = 0.01). CONCLUSIONS: Immunohistochemical detection of FAK expression is of no prognostic significance in node-negative breast cancer but provides evidence that HER2 is involved in tumor malignancy and metastatic ability of breast cancer through a novel signaling pathway participating FAK and Src