Slope Stability Evaluation for an Existing Steep Cut in Weathered Volcanics, Hong Kong

This case study concerns an investigation of a major existing soil slope. It is a 60m (197 ft) high cutting slope, at 40 degrees to 60 degrees to the horizontal, exhibiting a considerably greater degree of stability than was obtained by a series of geotechnical investigations and analyses. The common practice of correlation between widely spaced borings is shown to be inappropriate at this site because of the highly variable ground conditions. Rather, the comprehensive geological comprehensive engineering investigation carried out has enabled a detailed appreciation of the distribution and nature of weathered materials at the site. Transitional materials with soil-like appearance and weak rock properties have been identified. Based on this information, slope stability evaluation was carried out with more realistic results and with greater confidence

Assessment of proton radiation-induced charge transfer inefficiency in the CCD273 detector for the Euclid Dark Energy Mission

Euclid is a medium class mission selected for launch in 2019, with a primary goal to study the dark universe using the weak lensing and baryonic acoustic oscillations techniques. Weak lensing depends on accurate shape measurements, therefore it is beneficial that the effects of radiation-induced charge transfer inefficiency (CTI) in the Euclid CCD over the six year mission are understood and minimised. This paper describes the initial evaluation of the tolerance to radiation induced charge transfer inefficiency (CTI) of the CCD273 produced by e2v technologies plc, making comparisons with the previous CCD selected for Euclid the CCD203. The CCD273 benefits from the inclusion of a charge injection structure for trap suppression and a reduction in the register channel width. The improvement in tolerance to radiation induced serial CTI achieved by reducing the channel width from 50 um to 20 um was measured experimentally to be a factor of 1.7, which compares well to a factor of 1.9 found using a charge volume model

VIS: the visible imager for Euclid

Euclid-VIS is a large format visible imager for the ESA Euclid space mission in their Cosmic Vision program, scheduled for launch in 2019. Together with the near infrared imaging within the NISP instrument it forms the basis of the weak lensing measurements of Euclid. VIS will image in a single r+i+z band from 550-900 nm over a field of view of ~0.5 deg2. By combining 4 exposures with a total of 2240 sec, VIS will reach to V=24.5 (10{\sigma}) for sources with extent ~0.3 arcsec. The image sampling is 0.1 arcsec. VIS will provide deep imaging with a tightly controlled and stable point spread function (PSF) over a wide survey area of 15000 deg2 to measure the cosmic shear from nearly 1.5 billion galaxies to high levels of accuracy, from which the cosmological parameters will be measured. In addition, VIS will also provide a legacy imaging dataset with an unprecedented combination of spatial resolution, depth and area covering most of the extra-Galactic sky. Here we will present the results of the study carried out by the Euclid Consortium during the Euclid Definition phase.Comment: 10 pages, 6 figure

Mitigating radiation-induced charge transfer inefficiency in full-frame CCD applications by ‘pumping’ traps

The charge transfer efficiency of a CCD is based on the average level of signal lost per pixel over a number of transfers. This value can be used to directly compare the relative performances of different structures, increases in radiation damage or to quantify improvements in operating parameters. This number does not however give sufficient detail to mitigate for the actual signal loss/deference in either of the transfer directions that may be critical to measuring shapes to high accuracy, such as those required in astronomy applications (e.g. for Gaia’s astrometry or the galaxy distortion measurements for Euclid) based in the radiation environment of space. Pocket-pumping is an established technique for finding the location and activation levels of traps; however, a number of parameters in the process can also be explored to identify the trap species and location to sub-pixel accuracy. This information can be used in two ways to increase the sensitivity of a camera. Firstly, the clocking process can be optimised for the time constant of the majority of traps in each of the transfer directions, reducing deferred charge during read out. Secondly, a correction algorithm can be developed and employed during the post-processing of individual frames to move most of any deferred signal back into the charge packet it originated from. Here we present the trap-pumping techniques used to optimise the charge transfer efficiency of p- and n-channel e2v CCD204s and describe the use of trap-pumped images for on-orbit calibration and ground based image correction algorithms

Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia.

High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment-related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4). Receptor tyrosine kinase (RTK)/Ras/MAPK signaling pathway mutations were found in two-thirds of patients, including novel mutations in ROS1, which mediates phosphorylation of the PTPN11-encoded protein SHP2. Mutations in FLT3 significantly co-occurred with DOT1L (p=0.04), suggesting functional cooperation in leukemogenesis. We detected an extraordinary level of tumor heterogeneity, with microclonal (mutant allele fraction <0.10) KRAS, NRAS, FLT3, and/or PTPN11 hotspot mutations evident in 31/57 (54.4%) patients. Multiple KRAS and NRAS codon 12 and 13 microclonal mutations significantly co-occurred within tumor samples (p=4.8x10-4), suggesting ongoing formation of and selection for Ras-activating mutations. Future work is required to investigate whether tumor microheterogeneity impacts clinical outcome and to elucidate the functional consequences of epigenetic dysregulation in HD-ALL, potentially leading to novel therapeutic approaches

Functional improvement and correlations with symptomatic improvement in adults with attention deficit hyperactivity disorder receiving long-acting methylphenidate

Item does not contain fulltextBACKGROUND: Data on the relationship between core symptoms and daily functioning in adults with attention deficit hyperactivity disorder (ADHD) are limited. Daily functioning was assessed as part of an open-label extension, and associations with symptom scores were evaluated. METHOD: After a 5-week double-blind study with adults with ADHD receiving osmotic-controlled release oral delivery system (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo, participants were eligible for a 7-week open-label extension in which all patients received OROS MPH. Data for the Conners' Adult ADHD Rating Scale - Observer: Screening Version (CAARS-O:SV) (primary endpoint) have been presented previously. Secondary endpoints included the observer self-reported short version of the CAARS (CAARS-S:S) and the Clinical Global Impressions - Severity Scale (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) respectively. In post-hoc analyses, changes in CAARS-O:SV were evaluated in subgroups. Relationships between symptom and functional outcomes were evaluated in a multivariate regression analysis. RESULTS: A total of 370 patients entered the open-label extension. Significant improvements from baseline in CAARS-O:SV were similar regardless of sex, ADHD subtype, prior treatment or psychiatric co-morbidity. Significant improvements from double-blind baseline were also seen for the CAARS-S:S, CGI-S, SDS and Q-LES-Q. Improvements in the CAARS-O:SV Hyperactivity/Impulsivity subscale were associated with improvements in SDS total and subscale scores, and in the Q-LES-Q score at open-label endpoint. Improvements in CAARS-O:SV Inattention subscale and CGI-S scores were not significantly associated with functional changes. CONCLUSIONS: Improvements in ADHD symptoms relating to hyperactivity and impulsivity in adults receiving OROS MPH are associated with improvements in daily functioning and quality of life.1 januari 201

Identification and characterization of an irreversible inhibitor of CDK2

Irreversible inhibitors that modify cysteine or lysine residues within a protein kinase ATP binding site offer, through their distinctive mode of action, an alternative to ATP-competitive agents. 4-((6-(Cyclohexylmethoxy)- 9H-purin-2-yl)amino)benzenesulfonamide (NU6102) is a potent and selective ATP-competitive inhibitor of CDK2 in which the sulfonamide moiety is positioned close to a pair of lysine residues. Guided by the CDK2/NU6102 structure, we designed 6-(cyclohexylmethoxy)-N-(4-(vinylsulfonyl)phenyl)-9H-purin-2-amine (NU6300), which binds covalently to CDK2 as shown by a co-complex crystal structure. Acute incubation with NU6300 produced a durable inhibition of Rb phosphorylation in SKUT-1B cells, consistent with it acting as an irreversible CDK2 inhibitor. NU6300 is the first covalent CDK2 inhibitor to be described, and illustrates the potential of vinyl sulfones for the design of more potent and selective compounds

Client and therapist views of contextual factors related to termination from psychotherapy: A comparison between unilateral and mutual terminators

Contextual variables potentially influencing premature termination were examined. Clients (n = 83) and therapists (n = 35) provided parallel data on early working alliance, psychotherapy termination decision (unilateral vs. mutual), clients’ reasons for termination, and barriers to treatment participation. When clients unilaterally ended therapy, therapists were only partially aware of either the extent of clients’ perceived improvements or their dissatisfaction. When termination was mutually determined, there were no differences between client and therapist ratings of termination reasons. Although working alliance and barriers to treatment participation were rated as lower in the context of unilateral termination by clients and therapists, all clients rated the early alliance and barriers to treatment more highly than did therapists. Results have implications for understanding premature termination and suggest future research examining the utility of therapist feedback regarding contextual variables in terms of retaining clients in therapy