Random telegraph signals in charge coupled devices

An investigation of fluctuating pixels resulting from proton irradiation of an E2V Technologies CCD47-20 device is presented. The device structure,experimental set up and irradiation methodology are described, followed by a detailed analysis of radiation induced random telegraph signals,RTS. The characteristics of the observed flickering pixels are discussed in detail and the proposed models explaining the mechanism behind the phenomena are viewed in light of the collected data

Proton induced leakage current in CCDs

The effect of different proton fluences on the performance of two E2V Technologies CCD47-20 devices was investigated with particular emphasis given to the analysis of 'random telegraph signal' (RTS) generation, bright pixel generation and induced changes in base dark current level. The results show that bright pixel frequency increases as the mean energy of the proton beam is increased, and that the base dark current level after irradiation scales with the level of ionization damage. For the RTS study, 500 pixels on one device were monitored over a twelve hour period. This data set revealed a number of distinct types of pixel change level fluctuation and a system of classification has been devised. Previously published RTS data is discussed and reviewed in light of the new data

Low noise charge injection in the CCD22

The inclusion of a charge injection structure on a charge coupled device (CCD) allows for the mitigation of charge transfer loss which can be caused by radiation induced charge trapping defects. Any traps present in the pixels of the CCD are filled by the injected charge as it is swept through the device and consequently, the charge transfer efficiency is improved in subsequently acquired images. To date, a number of different types of CCD have been manufactured featuring a variety of charge injection techniques. The e2v Technologies CCD22, used in the EPIC MOS focal plane instruments of XMM-Newton, is one such device and is the subject of this paper. A detailed understanding of charge injection operation and the use of charge injection to mitigate charge transfer losses resulting from radiation damage to CCDs will benefit a number of space projects planned for the future, including the ESA GAIA and X-ray Evolving Universe Spectrometry (XEUS) missions.The charge injection structure and mode of operation of the CCD22 are presented, followed by a detailed analysis of the uniformity and repeatability of the charge injection amplitude across the columns of the device. The effects of proton irradiation on the charge injection characteristics are also presented, in particular the effect of radiation induced bright pixels on the injected charge level

The impact of low energy proton damage on the operational characteristics of EPIC-MOS CCDs

The University of Tübingen 3.5 MeV Van de Graaf accelerator facility was used to investigate the effect of low energy protons on the performance of the European Photon Imaging Camera (EPIC), metal–oxide semiconductor (MOS), charge coupled devices (CCDs). Two CCDs were irradiated in different parts of their detecting areas using different proton spectra and dose rates. Iron-55 was the calibration source in all cases and was used to measure any increases in charge transfer inefficiency (CTI) and spectral resolution of the CCDs. Additional changes in the CCD bright pixel table and changes in the low X-ray energy response of the device were examined. The Monte Carlo code Stopping Range of Ions in Matter (SRIM) was used to model the effect of a 10 MeV equivalent fluence of protons interacting with the CCD. Since the non-ionising energy loss (NIEL) function could not be applied effectively at such low proton energies. From the 10 MeV values, the expected CTI degradation could be calculated and then compared to the measured CTI changes

Hydrothermal liquefaction of organic waste streams on a continuous pilot scale reactor

Hydrothermal liquefaction (HTL) is a promising technology for biofuel production and treatment of organic wastes and biomass. Due to the wet nature of the process where biomass is heated in an aqueous slurry at 350°C and 200 bar, wet biomass and wet wastes are particularly suited for the process. The current study investigates the utilization of wastewater treatment sludges and other organic wastes for the production of sustainable petroleum replacement products. The work has been carried out on a pilot scale continuous hydrothermal liquefaction reactor with a novel oscillating flow system and heat exchanger. The influence of these are discussed in terms of heat recovery and operability of the plant. The reactor was run at 50 L/h with maximum solids loadings of ~25% and short residence times of80% was accomplished, leading to an energy efficient process. During operation of the HTL system, approximately 5 units of energy are created in the form of bio-crude for every unit of energy invested for heating and pumping the slurry (EROI\u3e5). We present and discuss the results of processing diverse samples ranging from high ash (sewage sludge), lignocellulosics (miscanthus) and manure to microalgae. The potential of mixing different waste biomasses such as sludge and lignocellulosics, plastics and lignocellulosics is explored during this research and synergistic effects on bio-crude yields and fuel quality are observed, leading to higher carbon and energy recoveries. Water phase recycling of the HTL process water was employed during the liquefaction of pine where a significant increase in bio-crude yields, energy recovery and energy return on investment could be achieved. Initial results on bio-crude upgrading via catalytic hydrotreatment are also presented, demonstrating the feasibility of the HTL process as a viable pathway towards drop in replacement fuels. The current presentation gives a realistic insight into the processing of diverse biomass feedstocks at pilot scale, showing the potential of the technology while areas for future development and bottlenecks are highlighted

An explorative analysis of ERCC1-19q13 copy number aberrations in a chemonaive stage III colorectal cancer cohort

BACKGROUND: Platinum-based chemotherapy has long been used in the treatment of a variety of cancers and functions by inducing DNA damage. ERCC1 and ERCC4 are involved in the removal of this damage and have previously been implicated in resistance to platinum compounds. The aim of the current investigation is to determine the presence, frequency and prognostic impact of ERCC1 or ERCC4 gene copy number alterations in colorectal cancer (CRC). METHODS: Fluorescent in situ hybridization probes directed at ERCC1 and ERCC4 with relevant reference probes were constructed. Probes were tested in a CRC cell line panel and in tumor sections from 152 stage III CRC chemonaive patients. Relationships between biomarker status and clinical endpoints (overall survival, time to recurrence, and local recurrence in rectal cancer) were analyzed by survival statistics. RESULTS: ERCC1-19q13 copy number alterations were observed in a single cell line metaphase (HT29). In patient material, ERCC1-19q13 copy number gains (ERCC1-19q13/CEN-2 ≥ 1.5) were detected in 27.0% of specimens, whereas ERCC1-19q13 deletions (ERCC1-19q13/CEN-2 < 0.8) were only detected in 1.3%. ERCC1-19q13 gain was significantly associated with longer survival (multivariate analysis, HR: 0.45, 95% CI: 0.20-1.00, p = 0.049) in patients with colon tumors, but not rectal tumors. No ERCC4 aberrations were detected and scoring was discontinued after 50 patients. CONCLUSIONS: ERCC1-19q13 copy number gains occur frequently in stage III CRC and influences survival in patients with colon tumors. Future studies will investigate the effect of ERCC1-19q13 aberrations in a platinum-treated patient population with the aim of developing a predictive biomarker profile for oxaliplatin sensitivity in CRC

Methodological challenges in collecting social and behavioural data regarding the HIV epidemic among gay and other men who have sex with men in Australia

©2014 Zablotska et al. Background: Behavioural surveillance and research among gay and other men who have sex with men (GMSM) commonly relies on non-random recruitment approaches. Methodological challenges limit their ability to accurately represent the population of adult GMSM. We compared the social and behavioural profiles of GMSM recruited via venue-based, online, and respondent-driven sampling (RDS) and discussed their utility for behavioural surveillance. Methods: Data from four studies were selected to reflect each recruitment method. We compared demographic characteristics and the prevalence of key indicators including sexual and HIV testing practices obtained from samples recruited through different methods, and population estimates from respondent-driven sampling partition analysis. Results: Overall, the socio-demographic profile of GMSM was similar across samples, with some differences observed in age and sexual identification. Men recruited through time-location sampling appeared more connected to the gay community, reported a greater number of sexual partners, but engaged in less unprotected anal intercourse with regular (UAIR) or casual partners (UAIC). The RDS sample overestimated the proportion of HIV-positive men and appeared to recruit men with an overall higher number of sexual partners. A single-website survey recruited a sample with characteristics which differed considerably from the population estimates with regards to age, ethnically diversity and behaviour. Data acquired through time-location sampling underestimated the rates of UAIR and UAIC, while RDS and online sampling both generated samples that underestimated UAIR. Simulated composite samples combining recruits from time-location and multi-website online sampling may produce characteristics more consistent with the population estimates, particularly with regards to sexual practices. Conclusion: Respondent-driven sampling produced the sample that was most consistent to population estimates, but this methodology is complex and logistically demanding. Time-location and online recruitment are more cost-effective and easier to implement; using these approaches in combination may offer the potential to recruit a more representative sample of GMSM

A Novel, Orally Delivered Antibody Therapy and Its Potential to Prevent Clostridioides difficile Infection in Pre-clinical Models

Clostridioides difficile infection (CDI) is a toxin-mediated infection in the gut and a major burden on healthcare facilities worldwide. We rationalized that it would be beneficial to design an antibody therapy that is delivered to, and is active at the site of toxin production, rather than neutralizing the circulating and luminal toxins after significant damage of the layers of the intestines has occurred. Here we describe a highly potent therapeutic, OraCAb, with high antibody titers and a formulation that protects the antibodies from digestion/inactivation in the gastrointestinal tract. The potential of OraCAb to prevent CDI in an in vivo hamster model and an in vitro human colon model was assessed. In the hamster model we optimized the ratio of the antibodies against each of the toxins produced by C. difficile (Toxins A and B). The concentration of immunoglobulins that is effective in a hamster model of CDI was determined. A highly significant difference in animal survival for those given an optimized OraCAb formulation versus an untreated control group was observed. This is the first study testing the effect of oral antibodies for treatment of CDI in an in vitro gut model seeded with a human fecal inoculum. Treatment with OraCAb successfully neutralized toxin production and did not interfere with the colonic microbiota in this model. Also, treatment with a combination of vancomycin and OraCAb prevented simulated CDI recurrence, unlike vancomycin therapy alone. These data demonstrate the efficacy of OraCAb formulation for the treatment of CDI in pre-clinical models

Mechanisms of topoisomerase I (<em>TOP1</em>) gene copy number increase in a stage III colorectal cancer patient cohort

BACKGROUND: Topoisomerase I (Top1) is the target of Top1 inhibitor chemotherapy. The TOP1 gene, located at 20q12-q13.1, is frequently detected at elevated copy numbers in colorectal cancer (CRC). The present study explores the mechanism, frequency and prognostic impact of TOP1 gene aberrations in stage III CRC and how these can be detected by fluorescent in situ hybridization (FISH). METHODS: Nine CRC cell line metaphase spreads were analyzed by FISH with a TOP1 probe in combination with a reference probe covering either the centromeric region of chromosome 20 (CEN-20) or chromosome 2 (CEN-2). Tissue sections from 154 chemonaive stage III CRC patients, previously studied with TOP1/CEN-20, were analyzed with TOP1/CEN-2. Relationships between biomarker status and overall survival (OS), time to recurrence (TTR) in CRC and time to local recurrence (LR; rectal cancer only) were determined. RESULTS: TOP1 aberrations were observed in four cell line metaphases. In all cell lines CEN-2 was found to reflect chromosomal ploidy levels and therefore the TOP1/CEN-2 probe combination was selected to identify TOP1 gene gains (TOP1/CEN-2≥1.5). One hundred and three patients (68.2%) had TOP1 gain, of which 15 patients (14.6%) harbored an amplification (TOP1/CEN-20≥2.0). TOP1 gene gain did not have any association with clinical endpoints, whereas TOP1 amplification showed a non-significant trend towards longer TTR (multivariate HR: 0.50, p = 0.08). Once amplified cases were segregated from other cases of gene gain, non-amplified gene increases (TOP1/CEN-2≥1.5 and TOP1/CEN-20<2.0) showed a trend towards shorter TTR (univariate HR: 1.57, p = 0.07). CONCLUSIONS: TOP1 gene copy number increase occurs frequently in stage III CRC in a mechanism that often includes CEN-20. Using CEN-2 as a measurement for tumor ploidy levels, we were able to discriminate between different mechanisms of gene gain, which appeared to differ in prognostic impact. TOP1 FISH guidelines have been updated

Frontal lobe changes occur early in the course of affective disorders in young people

<p>Abstract</p> <p>Background</p> <p>More severe and persistent forms of affective disorders are accompanied by grey matter loss in key frontal and temporal structures. It is unclear whether such changes precede the onset of illness, occur early in the course or develop gradually with persistence or recurrence of illness. A total of 47 young people presenting with admixtures of depressive and psychotic symptoms were recruited from specialist early intervention services along with 33 age matched healthy control subjects. All participants underwent magnetic resonance imaging and patients were rated clinically as to current stage of illness. Twenty-three patients were identified as being at an early 'attenuated syndrome' stage, while the remaining were rated as having already reached the 'discrete disorder' or 'persistent or recurrent illness' stage. Contrasts were carried out between controls subjects and patients cohorts with attenuated syndromes and discrete disorders, separately.</p> <p>Results</p> <p>The patients that were identified as having a discrete or persisting disorder demonstrated decreased grey matter volumes within distributed frontal brain regions when contrasted to both the control subjects as well as those patients in the attenuated syndrome stage. Overall, patients who were diagnosed as more advanced in terms of the clinical stage of their illness, exhibited the greatest grey matter volume loss of all groups.</p> <p>Conclusions</p> <p>This study suggests that, in terms of frontal grey matter changes, a major transition point may occur in the course of affective illness between early attenuated syndromes and later discrete illness stages.</p