On the nature of pulse profile variations and timing noise in accreting millisecond pulsars

Timing noise in the data on accretion-powered millisecond pulsars (AMP) appears as irregular pulse phase jumps on timescales from hours to weeks. A large systematic phase drift is also observed in the first discovered AMP SAX J1808.4 - 3658. To study the origin of these timing features, we use here the data of the well studied 2002 outburst of SAX J1808.4 - 3658. We develop first a model for pulse profile formation accounting for the screening of the antipodal emitting spot by the accretion disk. We demonstrate that the variations of the visibility of the antipodal spot associated with the receding accretion disk cause a systematic shift in Fourier phases, observed together with the changes in the pulse form. We show that a strong secondary maximum can be observed only in narrow intervals of inner disk radii, which explains the very short appearance of the double-peaked profiles in SAX J1808.4 - 3658. By directly fitting the pulse profile shapes with our model, we find that the main parameters of the emitting spot, such as its mean latitude and longitude as well as the emissivity pattern, change irregularly causing small shifts in pulse phase, and the strong profile variations are caused by the increasing inner disk radius. We finally notice that significant variations in the pulse profiles in the 2002 and 2008 outbursts of SAX J1808.4 - 3658 happen at fluxes differing by a factor of 2, which can be explained if the inner disk radius is not a simple function of the accretion rate, but depends on the previous history. © 2009. The American Astronomical Society

Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion, and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial

Abstract Background In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post-treatment reaction), and cosmetic outcome of MAL, BF-200 ALA, and low-concentration HAL in the PDT of non-aggressive BCCs. Methods Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9?98.3) for MAL, 90.9% (95% CI = 76.4?96.9) for BF-200 ALA, and 87.9% (95% CI = 72.7?95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post-treatment reactions, or cosmetic outcome. Conclusions PDT with low-concentration HAL and BF-200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.Peer reviewe

Microseminoprotein-Beta Expression in Different Stages of Prostate Cancer

Microseminoprotein-beta (MSMB, MSMB) is an abundant secretory protein contributed by the prostate, and is implicated as a prostate cancer (PC) biomarker based on observations of its lower expression in cancerous cells compared with benign prostate epithelium. However, as the current literature on MSMB is inconsistent, we assessed the expression of MSMB at the protein and mRNA levels in a comprehensive set of different clinical stages of PC. Immunohistochemistry using monoclonal and polyclonal antibodies against MSMB was used to study protein expression in tissue specimens representing prostatectomies (n = 261) and in diagnostic needle biopsies from patients treated with androgen deprivation therapy (ADT) (n = 100), and in locally recurrent castration-resistant PC (CRPC) (n = 105) and CRPC metastases (n = 113). The transcript levels of MSMB, nuclear receptor co-activator 4 (NCOA4) and MSMB-NCOA4 fusion were examined by qRT-PCR in prostatectomy samples and by RNA-sequencing in benign prostatic hyperplasia, PC, and CRPC samples. We also measured serum MSMB levels and genotyped the single nucleotide polymorphism rs10993994 using DNA from the blood of 369 PC patients and 903 controls. MSMB expression in PC (29% of prostatectomies and 21% of needle biopsies) was more frequent than in CRPC (9% of locally recurrent CRPCs and 9% of CRPC metastases) (p<0.0001). Detection of MSMB protein was inversely correlated with the Gleason score in prostatectomy specimens (p = 0.024). The read-through MSMB-NCOA4 transcript was detected at very low levels in PC. MSMB levels in serum were similar in cases of PC and controls but were significantly associated with PC risk when adjusted for age at diagnosis and levels of free or total PSA (p<0.001). Serum levels of MSMB in both PC patients and controls were significantly associated with the rs10993994 genotype (p<0.0001). In conclusion, decreased expression of MSMB parallels the clinical progression of PC and adjusted serum MSMB levels are associated with PC risk

Simulation of Beam-Beam Effects and Tevatron Experience

Effects of electromagnetic interactions of colliding bunches in the Tevatron had a variety of manifestations in beam dynamics presenting vast opportunities for development of simulation models and tools. In this paper the computer code for simulation of weak-strong beam-beam effects in hadron colliders is described. We report the collider operational experience relevant to beam-beam interactions, explain major effects limiting the collider performance and compare results of observations and measurements with simulations.Comment: 23 pages, 17 figure

Can processes make relationships work? The Triple Helix between structure and action

This contribution seeks to explore how complex adaptive theory can be applied at the conceptual level to unpack Triple Helix models. We use two cases to examine this issue – the Finnish Strategic Centres for Science, Technology & Innovation (SHOKs) and the Canadian Business-led Networks of Centres of Excellence (BL-NCE). Both types of centres are organisational structures that aspire to be business-led, with a considerable portion of their activities driven by (industrial) users’ interests and requirements. Reflecting on the centres’ activities along three dimensions – knowledge generation, consensus building and innovation – we contend that conceptualising the Triple Helix from a process perspective will improve the dialogue between stakeholders and shareholders

Tevatron Beam Halo Collimation System: Design, Operational Experience and New Methods

Collimation of proton and antiproton beams in the Tevatron collider is required to protect CDF and D0 detectors and minimize their background rates, to keep irradiation of superconducting magnets under control, to maintain long-term operational reliability, and to reduce the impact of beam-induced radiation on the environment. In this article we briefly describe the design, practical implementation and performance of the collider collimation system, methods to control transverse and longitudinal beam halo and two novel collimation techniques tested in the Tevatron.Comment: 25 p

Heterozygous junctophilin-2 (JPH2) p. (Thr161Lys) is a monogenic cause for HCM with heart failure

During the last two decades, mutations in sarcomere genes have found to comprise the most common cause for hypertrophic cardiomyopathy (HCM), but still significant number of patients with dominant HCM in the family are left without molecular genetic diagnosis. Next generation sequencing (NGS) does not only enable evaluation of established HCM genes but also candidate genes for cardiomyopathy are frequently tested which may lead to a situation where conclusive interpretation of the variant requires extensive family studies. We aimed to characterize the phenotype related to a variant in the junctophilin-2 (JPH2) gene, which is less known non-sarcomeric candidate gene. In addition, we did extensive review of the literature and databases about JPH2 variation in association with cardiac disease. We characterize nine Finnish index patients with HCM and heterozygous for JPH2 c.482C>A, p. (Thr161Lys) variant were included and segregation studies were performed. We identified 20 individuals affected with HCM with or without systolic heart failure and conduction abnormalities in the nine Finnish families with JPH2 p.(Thr161Lys) variant. We found 26 heterozygotes with the variant and penetrance was 71% by age 60 and 100% by age 80. Cosegregation of the variant with HCM phenotype was observed in six families. Main clinical features were left ventricular hypertrophy, arrhythmia vulnerability and conduction abnormalities including third degree AV-block. In some patients end-stage severe left ventricular heart failure with normal or mildly enlarged diastolic dimensions was detected. In conclusion, we propose that the heterozygous JPH2 p.(Thr161Lys) variant is a new Finnish mutation causing atypical HCM.Peer reviewe