Self-organization of intrinsically disordered proteins with folded N-termini

Thousands of human proteins lack recognizable tertiary structure in most of their chains. Here we hypothesize that some use their structured N-terminal domains (SNTDs) to organise the remaining protein chain via intramolecular interactions, generating partially structured proteins. This model has several attractive features: as protein chains emerge, SNTDs form spontaneously and serve as nucleation points, creating more compact shapes. This reduces the risk of protein degradation or aggregation. Moreover, an interspersed pattern of SNTD-docked regions and free loops can coordinate assembly of sub-complexes in defined loop-sections and enables novel regulatory mechanisms, for example through posttranslational modifications of docked regions

Barrier potential for laser written graphitic wires in diamond

Diamond substrates supporting an internal array of conductive graphitic wires inscribed by a femtosecond pulse laser, are useful for the detection of ionising radiation in a range of applications. Various parameters involved in the laser fabrication process were investigated in this paper to understand their impact on the electrical properties of the wires. The study revealed an effect, whereby the wires exhibit insulating behaviour until a barrier potential is overcome. When high enough voltages are applied, the wires display ohmic behaviour. The magnitude of the barrier potential, which in some cases exceeds 300 V, is shown to be strongly dependent on the laser fabrication parameters. Through process optimisation, the potential barrier may be minimised and effectively removed, coinciding with reduced values of the wire resistance

Detection statistics in the micromaser

We present a general method for the derivation of various statistical quantities describing the detection of a beam of atoms emerging from a micromaser. The user of non-normalized conditioned density operators and a linear master equation for the dynamics between detection events is discussed as are the counting statistics, sequence statistics, and waiting time statistics. In particular, we derive expressions for the mean number of successive detections of atoms in one of any two orthogonal states of the two-level atom. We also derive expressions for the mean waiting times between detections. We show that the mean waiting times between de- tections of atoms in like states are equivalent to the mean waiting times calculated from the uncorrelated steady state detection rates, though like atoms are indeed correlated. The mean waiting times between detections of atoms in unlike states exhibit correlations. We evaluate the expressions for various detector efficiencies using numerical integration, reporting re- sults for the standard micromaser arrangement in which the cavity is pumped by excited atoms and the excitation levels of the emerging atoms are measured. In addition, the atomic inversion and the Fano-Mandel function for the detection of de-excited atoms is calculated for compari- son to the recent experimental results of Weidinger et al. [1], which reports the first observation of trapping states.Comment: 26 pages, 11 figure

Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival ofdiagnosis

Prompt optical observations of GRB050319 with the Swift UVOT

The UVOT telescope on the Swift observatory has detected optical afterglow emission from GRB 050319. The flux declines with a power law slope of alpha = -0.57 between the start of observations some 230 seconds after the burst onset (90s after the burst trigger) until it faded below the sensitivity threshold of the instrument after ~5 x 10^4s. There is no evidence for the rapidly declining component in the early light curve that is seen at the same time in the X-ray band. The afterglow is not detected in UVOT shortward of the B-band, suggesting a redshift of about 3.5. The optical V-band emission lies on the extension of the X-ray spectrum, with an optical to X-ray slope of beta = -0.8. The relatively flat decay rate of the burst suggests that the central engine continues to inject energy into the fireball for as long as a few x 10^4s after the burst.Comment: 16 pages, 4 figures, accepted by Ap

The Two-Component Afterglow of Swift GRB 050802

This paper investigates GRB 050802, one of the best examples of a it Swift gamma-ray burst afterglow that shows a break in the X-ray lightcurve, while the optical counterpart decays as a single power-law. This burst has an optically bright afterglow of 16.5 magnitude, detected throughout the 170-650nm spectral range of the UVOT on-board Swift. Observations began with the XRT and UVOT telescopes 286s after the initial trigger and continued for 1.2 x 10^6s. The X-ray lightcurve consists of three power-law segments: a rise until 420s, followed by a slow decay with alpha_2 = 0.63 +/- 0.03 until 5000s, after which, the lightcurve decays faster with a slope of alpha_3 = 1.59 +/- 0.03. The optical lightcurve decays as a single power-law with alpha_O = 0.82 +/- 0.03 throughout the observation. The X-ray data on their own are consistent with the break at 5000s being due to the end of energy injection. Modelling the optical to X-ray spectral energy distribution, we find that the optical afterglow can not be produced by the same component as the X-ray emission at late times, ruling out a single component afterglow. We therefore considered two-component jet models and find that the X-ray and optical emission is best reproduced by a model in which both components are energy injected for the duration of the observed afterglow and the X-ray break at 5000s is due to a jet break in the narrow component. This bright, well-observed burst is likely a guide for interpreting the surprising finding of Swift that bursts seldom display achromatic jet breaks.Comment: 13 pages, 5 figures, accepted MNRA

Swift-UVOT detection of GRB 050318

We present observations of GRB 050318 by the Ultra-Violet and Optical Telescope (UVOT) on-board the Swift observatory. The data are the first detections of a Gamma Ray Burst (GRB) afterglow decay by the UVOT instrument, launched specifically to open a new window on these transient sources. We showcase UVOTs ability to provide multi-color photometry and the advantages of combining UVOT data with simultaneous and contemporaneous observations from the high-energy detectors on the Swift spacecraft. Multiple filters covering 1,800-6,000 Angstroms reveal a red source with spectral slope steeper than the simultaneous X-ray continuum. Spectral fits indicate that the UVOT colors are consistent with dust extinction by systems at z = 1.2037 and z = 1.4436, redshifts where absorption systems have been pre-identified. However, the data can be most-easily reproduced with models containing a foreground system of neutral gas redshifted by z = 2.8 +/- 0.3. For both of the above scenarios, spectral and decay slopes are, for the most part, consistent with fireball expansion into a uniform medium, provided a cooling break occurs between the energy ranges of the UVOT and Swifts X-ray instrumentation.Comment: 15 pages, 4 figures, ApJ Letters, in pres

Swift-UVOT Observations of the X-Ray Flash 050406

We present Swift-UVOT data on the optical afterglow of the X-ray flash of 2005 April 6 (XRF 050406) from 88s to \sim 10^5s after the initial prompt gamma-ray emission. Our observations in the V, B and U bands are the earliest that have been taken of an XRF optical counterpart. Combining the early -time optical temporal and spectral properties with \gamma- and simultaneous X-ray data taken with the BAT and XRT telescopes on-board Swift, we are able to constrain possible origins of the XRF. The prompt emission had a FRED profile (fast-rise, exponential decay) with a duration of T_90 = 5.7\pm 0.2s, putting it at the short end of the long-burst duration distribution. The absence of photoelectric absorption red-ward of 4000 \AA in the UV/optical spectrum provides a firm upper limit of z\leq 3.1 on the redshift, thus excluding a high redshift as the sole reason for the soft spectrum. The optical light curve is consistent with a power-law decay with slope alpha = -0.75\pm 0.26 (F_{\nu}\propto t^{\alpha}), and a maximum occurring in the first 200s after the initial gamma-ray emission. The softness of the prompt emission is well described by an off-axis structured jet model, which is able to account for the early peak flux and shallow decay observed in the optical and X-ray bands.Comment: 14 pages, 4 figures, accepted for publication in ApJ; typos corrected and upper limits in table 1 changed from background subtracted count rate in extraction region to the error associated with thi

Ultraviolet, Optical, and X-Ray Observations of the Type Ia Supernova 2005am with Swift

We present ultraviolet and optical light curves in six broadband filters and grism spectra obtained by Swift's Ultraviolet/Optical Telescope for the Type Ia supernova SN2005am. The data were collected beginning about four days before the B-band maximum, with excellent coverage of the rapid decline phase and later observations extending out to 69 days after the peak. The optical and near UV light curve match well those of SN1992A. The other UV observations constitute the first set of light curves shorter than 2500 Angstroms and allow us to compare the light curve evolution in three UV bands. The UV behavior of this and other low redshift supernovae can be used to constrain theories of progenitor evolution or to interpret optical light curves of high redshift supernovae. Using Swift's X-Ray Telescope, we also report the upper limit to SN2005am's X-ray luminosity to be 1.77 x 10^40 erg s^-1 in the 0.3--10 keV range from 58,117 s of exposure time.Comment: 15 pages, including 3 figures and 2 tables, submitted to Astrophysical Journa

Interventions for behaviour change and self-management in stroke secondary prevention: protocol for an overview of reviews

Abstract Background Stroke secondary prevention guidelines recommend medication prescription and adherence, active education and behavioural counselling regarding lifestyle risk factors. To impact on recurrent vascular events, positive behaviour/s must be adopted and sustained as a lifestyle choice, requiring theoretically informed behaviour change and self-management interventions. A growing number of systematic reviews have addressed complex interventions in stroke secondary prevention. Differing terminology, inclusion criteria and overlap of studies between reviews makes the mechanism/s that affect positive change difficult to identify or replicate clinically. Adopting a two-phase approach, this overview will firstly comprehensively summarise systematic reviews in this area and secondly identify and synthesise primary studies in these reviews which provide person-centred, theoretically informed interventions for stroke secondary prevention. Methods An overview of reviews will be conducted using a systematic search strategy across the Cochrane Database of Systematic Reviews, PubMed and Epistomonikas. Inclusion criteria: systematic reviews where the population comprises individuals post-stroke or TIA and where data relating to person-centred risk reduction are synthesised for evidence of efficacy when compared to standard care or no intervention. Primary outcomes of interest include mortality, recurrent stroke and other cardiovascular events. In phase 1, two reviewers will independently (1) assess the eligibility of identified reviews for inclusion; (2) rate the quality of included reviews using the ROBIS tool; (3) identify unique primary studies and overlap between reviews; (4) summarise the published evidence supporting person-centred behavioural change and self-management interventions in stroke secondary prevention and (5) identify evidence gaps in this field. In phase 2, two independent reviewers will (1) examine person-centred, primary studies in each review using the Template for Intervention Description and Replication (TIDieR checklist), itemising, where present, theoretical frameworks underpinning interventions; (2) group studies employing theoretically informed interventions by the intervention delivered and by the outcomes reported (3) apply GRADE quality of evidence for each intervention by outcome/s identified from theoretically informed primary studies. Disagreement between reviewers at each process stage will be discussed and a third reviewer consulted. Discussion This overview will comprehensively bring together the best available evidence supporting person-centred, stroke secondary prevention strategies in an accessible format, identifying current knowledge gaps