Genomic biomarkers in prostate cancer.

Prostate cancer is the most common non-cutaneous cancer among men in the United States. In the last decade there has been a rapid expansion in the field of biomarker assays for diagnosis, prognosis, and treatment prediction in prostate cancer. The evidence base for these assays is rapidly evolving. With several commercial assays available at each stage of the disease, deciding which genomic assays are appropriate for which patients can be nuanced for physicians. In an effort to help guide these decisions in clinical practice, we aim to give an update on the current status of the biomarker field of prostate cancer

An Experiment in Visual Ethnography

This paper is an output from my attendance at an ESRC-funded ‘Live Sociology’ course at Goldsmiths College, London in 2006. The material here is based on a photography exercise and on discussions that took place during the workshop sessions.This paper discusses a one-day exercise in visual ethnography using a digital camera to take photographs of Deptford in South East London. For me, this represented an experiment in using photography in social research.ESR

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

The democratic engagement of Britain's ethnic minorities

Democratic engagement is a multi-faceted phenomenon that embraces citizens' involvement with electoral politics, their participation in ‘conventional’ extra-parliamentary political activity, their satisfaction with democracy and trust in state institutions, and their rejection of the use of violence for political ends. Evidence from the 2010 BES and EMBES shows that there are important variations in patterns of democratic engagement across Britain's different ethnic-minority groups and across generations. Overall, ethnic-minority engagement is at a similar level to and moved by the same general factors that influence the political dispositions of whites. However, minority democratic engagement is also strongly affected by a set of distinctive ethnic-minority perceptions and experiences, associated particularly with discrimination and patterns of minority and majority cultural engagement. Second-generation minorities who grew up in Britain are less, rather than more, likely to be engaged

Diverse phenotypes resulting from polyphosphate kinase gene (ppk1) inactivation in different strains of Helicobacter pylori

Connections among biochemical pathways should help buffer organisms against environmental stress and affect the pace and trajectory of genome evolution. To explore these ideas, we studied consequences of inactivating the gene for polyphosphate kinase 1 (ppk1) in strains of Helicobacter pylori, a genetically diverse gastric pathogen. The PPK1 enzyme catalyzes synthesis of inorganic polyphosphate (poly P), a reservoir of high-energy phosphate bonds with multiple roles. Prior analyses in less-fastidious microbes had implicated poly P in stress resistance, motility, and virulence. In our studies, ppk1 inactivation caused the expected near-complete absence of poly P (>250-fold decrease) but had phenotypic effects that differed markedly among unrelated strains: (i) poor initial growth on standard brain heart infusion agar (five of six strains tested); (ii) weakened colonization of mice (4 of 5 strains); (iii) reduced growth on Ham's F-12 agar, a nutritionally limiting medium (8 of 11 strains); (iv) heightened susceptibility to metronidazole (6 of 17 strains); and (v) decreased motility in soft agar (1 of 13 strains). Complementation tests confirmed that the lack of growth of one Δppk1 strain on F-12 agar and the inability to colonize mice of another were each due to ppk1 inactivation. Thus, the importance of ppk1 to H. pylori differed among strains and the phenotypes monitored. We suggest that quantitative interactions, as seen here, are common among genes that affect metabolic pathways and that H. pylori's high genetic diversity makes it well suited for studies of such interactions, their underlying mechanisms, and their evolutionary consequences

Increased Expression of Tissue Factor and Receptor for Advanced Glycation End Products in Peripheral Blood Mononuclear Cells of Patients With Type 2 Diabetes Mellitus with Vascular Complications

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase–polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin–stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 ± 0.06 in patients with complications and 0.05 ± 0.06 patients without complications (P = .004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 ± 0.29 in patients with complications and 0.21 ± 0.18 in patients without complications (P = .003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/106 PBMCs) was 18.4 ± 13.2 in patients with complications and 6.96 ± 5.2 in patients without complications (P = .003). It increased 3-fold in both groups after stimulation (P = .001). TF antigen (pg/106 PBMCs) was 33.7 ± 28.6 in patients with complications, 10.4 ± 7.8 in patients without complications (P = .02). Stimulation tripled TF antigen in both groups of patients (P = .001). The RAGE/TF axis is up-regulated inT2Dpatients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D

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

Dynamical scaling of the DNA unzipping transition

We report studies of the equilibrium and the dynamics of a general set of lattice models which capture the essence of the force-induced or mechanical DNA unzipping transition. Besides yielding the whole equilibrium phase diagram in the force vs temperature plane, which reveals the presence of an interesting re-entrant unzipping transition for low T, these models enable us to characterize the dynamics of the process starting from a non-equilibrium initial condition. The thermal melting of the DNA strands displays a model dependent time evolution. On the contrary, our results suggest that the dynamical mechanism for the unzipping by force is very robust and the scaling behaviour does not depend on the details of the description we adopt.Comment: 6 pages, 4 figures, A shorter version of this paper appeared in Phys. Rev. Lett. 88, 028102 (2002

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'