Systematic evaluation of design choices for software development tools

[Abstract]: Most design and evaluation of software tools is based on the intuition and experience of the designers. Software tool designers consider themselves typical users of the tools that they build and tend to subjectively evaluate their products rather than objectively evaluate them using established usability methods. This subjective approach is inadequate if the quality of software tools is to improve and the use of more systematic methods is advocated. This paper summarises a sequence of studies that show how user interface design choices for software development tools can be evaluated using established usability engineering techniques. The techniques used included guideline review, predictive modelling and experimental studies with users

Incremental Semantic Evaluation for Interactive Systems: Inertia, Pre-emption, and Relations

Although schemes for incremental semantic evaluation have been explored and refined for more than two decades, the demands of user interaction continue to outstrip the capabilities of these schemes. The feedback produced by a semantic evaluator must support the user's programming activities: it must be structured in a way that provides the user with meaningful insight into the program (directly, or via other tools in the environment) and it must be timely. In this paper we extend an incremental attribute evaluation scheme with three techniques to better meet these demands within the context of a modeless editing system with a flexible tool integration paradigm. Efficient evaluation in the presence of syntax errors (which arise often under modeless editing) is supported by giving semantic attributes inertia: a tendency to not change unless necessary. Pre-emptive evaluation helps to reduce the delays associated with a sequence of edits, allowing an evaluator to "keep pace" with the user. Relations provide a general means to capture semantic structure (for the user, other tools, and as attributes within an evaluation) and are treated efficiently using a form of differential propagation. The combination of these three techniques meets the demands of user interaction; leaving out any one does not

Databases for Software Engineering Environments - The Goal has not yet been attained

We argue that, despite a substantial number of proposed and existing new database systems, a suitable database system for software development environments and especially process-centred environments does not yet exist. We do so by first reviewing and refining the requirements for such systems. We then review a number of available and archetypical database systems and show that they do not meet these requirements

Associations of statin adherence and lipid targets with adverse outcomes in myocardial infarction survivors:a retrospective cohort study

Objectives: To examine associations between statin adherence and lipid target achievement in myocardial infarction (MI) survivors, and their associations with mortality and recurrent MIs. Design: Retrospective cohort study using linked clinical records within the National Health Service Greater Glasgow and Clyde (NHS GGC) Data Safe Haven. Setting: Routine clinical practice in the NHS GGC area between January 2009 and July 2017. Participants: Patients ≥18 years who experienced a non-fatal MI hospital admission (ICD10: I21, I22) between January 2009 and July 2014 (n=11 031), followed up from the date of MI admission until July 2017 or death, whichever occurred first. Primary and secondary outcome measures: Statin adherence was estimated using encashed prescriptions and lipid results from routine biochemistry data. Primary lipid and statin adherence targets were LDL ≤1.8 mmol/L and adherence ≥50%, and were related to all-cause death, deaths due to cardiovascular disease (CVD) (ICD10: I00–I99 as the underlying cause), and recurrent MI in unadjusted models and models adjusting for age, sex, socioeconomic deprivation and year of MI. Results: Over 4.5 years follow-up, 76% achieved LDL ≤1.8 mmol/L, and 84.5% had average adherence ≥50%. Patients with adherence <50% had an increased risk of not meeting LDL ≤1.8 mmol/L, in adjusted models (OR 2.03, 95% CI 1.78 to 2.31, p<0.0001). In univariable models, not meeting LDL ≤1.8 mmol/L was associated with increased risks of all-cause mortality (HR 1.27, 95% CI 1.16 to 1.39, p<0.0001) and CVD mortality (HR 1.29, 95% CI 1.11 to 1.51, p=0.0013). Adherence <50% was associated with increased risks of all-cause mortality (HR 1.58, 95% CI 1.44 to 1.74, p<0.0001) and CVD mortality (HR 1.60, 95% CI 1.36 to 1.88, p<0.0001). Adjustment for confounders did not abrogate these associations. Neither exposure was associated with recurrent MIs. Conclusions: Non-achievement of lipid and adherence targets are associated with increased risks of all-cause and CVD mortality. Further work is required to optimise their use to improve outcomes in clinical practice

Incremental Context-Sensitive Evaluation in Context

Although techniques for implementing or generating incremental semantic evaluators have been explored and refined for more than two decades, several pragmatic concerns still impede the use of such techniques in practical development environments. This report not only addresses some of these concerns, but furthermore demonstrates the need to consider the problem of incremental semantic evaluation in context. The practical concerns addressed here stem from both user interaction and architectural requirements. In particular an innovative preemptive evaluation scheme is presented which helps to reduce delays associated with semantic evaluation over a sequence of edits. Furthermore, a technique for assigning attributes to syntactically erroneous material (the introduction of which is inevitable in a syntax recognition editor) is described, as well as a novel approach to handling "long-distance" semantic effects using fine-grained incremental evaluation of relations

Dynamical Tides in Eccentric Binaries and Tidally-Excited Stellar Pulsations in KEPLER KOI-54

Recent observation of the tidally-excited stellar oscillations in the main-sequence binary KOI-54 by the KEPLER satellite provides a unique opportunity for studying dynamical tides in eccentric binary systems. We develop a general theory of tidal excitation of oscillation modes of rotating binary stars, and apply our theory to tidally excited gravity modes (g-modes) in KOI-54. The strongest observed oscillations, which occur at 90 and 91 times the orbital frequency, are likely due to prograde m=2 modes (relative to the stellar spin axis) locked in resonance with the orbit. The remaining flux oscillations with frequencies that are integer multiples of the orbital frequency are likely due to nearly resonant m=0 g-modes; such axisymmetric modes generate larger flux variations compared to the m=2 modes, assuming that the spin inclination angle of the star is comparable to the orbital inclination angle. We examine the process of resonance mode locking under the combined effects of dynamical tides on the stellar spin and orbit and the intrinsic stellar spindown. We show that KOI-54 can naturally evolve into a state in which at least one m=2 mode is locked in resonance with the orbital frequency. Our analysis provides an explanation for the fact that only oscillations with frequencies less than 90-100 times the orbital frequency are observed. We have also found evidence from the published KEPLER result that three-mode nonlinear coupling occurs in the KOI-54 system. We suggest that such nonlinear mode coupling may explain the observed oscillations that are not harmonics of the orbital frequency.Comment: 15 pages, 5 figures, accepted by MNRA

Voxel-based supervised machine learning of peripheral zone prostate cancer using noncontrast multiparametric MRI

Purpose: The aim of this study was to develop and assess the performance of supervised machine learning technique to classify magnetic resonance imaging (MRI) voxels as cancerous or noncancerous using noncontrast multiparametric MRI (mp-MRI), comprised of T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and advanced diffusion tensor imaging (DTI) parameters. Materials and methods: In this work, 191 radiomic features were extracted from mp-MRI from prostate cancer patients. A comprehensive set of support vector machine (SVM) models for T2WI and mp-MRI (T2WI + DWI, T2WI + DTI, and T2WI + DWI + DTI) were developed based on novel Bayesian parameters optimization method and validated using leave-one-patient-out approach to eliminate any possible overfitting. The diagnostic performance of each model was evaluated using the area under the receiver operating characteristic curve (AUROC). The average sensitivity, specificity, and accuracy of the models were evaluated using the test data set and the corresponding binary maps generated. Finally, the SVM plus sigmoid function of the models with the highest performance were used to produce cancer probability maps. Results: The T2WI + DWI + DTI models using the optimal feature subset achieved the best performance in prostate cancer detection, with the average AUROC, sensitivity, specificity, and accuracy of 0.93 ± 0.03, 0.85 ± 0.05, 0.82 ± 0.07, and 0.83 ± 0.04, respectively. The average diagnostic performance of T2WI + DTI models was slightly higher than T2WI + DWI models (+3.52%) using the optimal radiomic features. Conclusions: Combination of noncontrast mp-MRI (T2WI, DWI, and DTI) features with the framework of a supervised classification technique and Bayesian optimization method are able to differentiate cancer from noncancer voxels with high accuracy and without administration of contrast agent. The addition of cancer probability maps provides additional functionality for image interpretation, lesion heterogeneity evaluation, and treatment management.</p

Kinesin-like protein CENP-E is upregulated in rheumatoid synovial fibroblasts

INTRODUCTION: Articular destruction by invading synovial fibroblasts is a typical feature in rheumatoid arthritis (RA). Recent data support the hypothesis that key players in this scenario are transformed-appearing synovial fibroblasts at the site of invasion into articular cartilage and bone. They maintain their aggressive phenotype toward cartilage, even when first cultured and thereafter coimplanted together with normal human cartilage into severe combined immunodeficient mice for an extended period of time. However, little is known about the upregulation of genes that leads to this aggressive fibroblast phenotype. To inhibit this progressive growth without interfering with pathways of physiological matrix remodelling, identification of pathways that operate specifically in RA synovial fibroblasts is required. In order to achieve this goal, identification of genes showing upregulation restricted to RA synovial fibroblasts is essential. AIMS: To identify specifically expressed genes using RNA arbitrarily primed (RAP)-polymerase chain reaction (PCR) for differential display in patients with RA. METHODS: RNA was extracted from cultured synovial fibroblasts from 10 patients with RA, four patients with osteoarthritis (OA), and one patient with psoriatic arthritis. RAP-PCR was performed using different arbitrary primers for first-strand and second-strand synthesis. First-strand and second-strand synthesis were performed using arbitrary primers: US6 (5' -GTGGTGACAG-3') for first strand, and Nuclear 1+ (5' -ACGAAGAAGAG-3'), OPN28 (5' -GCACCAGGGG-3'), Kinase A2+ (5' -GGTGCCTTTGG-3')and OPN24 (5' -AGGGGCACCA-3') for second-strand synthesis. PCR reactions were loaded onto 8 mol/l urea/6% polyacrylamide-sequencing gels and electrophoresed.Gel slices carrying the target fragment were then excised with a razor blade, eluated and reamplified. After verifying their correct size and purity on 4% agarose gels, the reamplified products derived from the single-strand confirmation polymorphism gel were cloned, and five clones per transcript were sequenced. Thereafter, a GenBank(®) analysis was performed. Quantitative reverse transcription PCR of the segments was performed using the PCR MIMIC(®) technique.In-situ expression of centromere kinesin-like protein-E (CENP-E) messenger (m)RNA in RA synovium was assessed using digoxigenin-labelled riboprobes, and CENP-E protein expression in fibroblasts and synovium was performed by immunogold-silver immunohistochemistry and cytochemistry. Functional analysis of CENP-E was done using different approaches (eg glucocorticoid stimulation, serum starvation and growth rate analysis of synovial fibroblasts that expressed CENP-E). RESULTS: In RA, amplification of a distinct PCR product suitable for sequencing could be observed. The indicated complementary DNA fragment of 434 base pairs from RA mRNA corresponded to nucleotides 6615-7048 in the human centromere kinesin-like protein CENP-E mRNA (GenBank(®) accession No. emb/Z15005).The isolated sequence shared greater than 99% nucleic acid (P = 2.9e(-169)) identity with the human centromere kinesin-like protein CENP-E. Two base changes at positions 6624 (A to C) and 6739 (A to G) did not result in alteration in the amino acid sequence, and therefore 100% amino acid identity could be confirmed. The amplification of 10 clones of the cloned RAP product revealed the presence of CENP-E mRNA in every fibroblast culture examined, showing from 50% (271.000 ± 54.000 phosphor imager arbitrary units) up to fivefold (961.000 ± 145.000 phosphor imager arbitrary units) upregulation when compared with OA fibroblasts. Neither therapy with disease-modifying antirheumatic drugs such as methotrexate, gold, resochine or cyclosporine A, nor therapy with oral steroids influenced CENP-E expression in the RA fibroblasts. Of the eight RA fibroblast populations from RA patients who were receiving disease-modifying antirheumatic drugs, five showed CENP-E upregulation; and of the eight fibroblast populations from RA patients receiving steroids, four showed CENP-E upregulation. Numerous synovial cells of the patients with RA showed a positive in situ signal for the isolated CENP-E gene segment, confirming CENP-E mRNA production in rheumatoid synovium, whereas in OA synovial tissue CENP-E mRNA could not be detected. In addition, CENP-E expression was independent from medication. This was further confirmed by analysis of the effect of prednisolone on CENP-E expression, which revealed no alteration in CENP-E mRNA after exposure to different (physiological) concentrations of prednisolone. Serum starvation also could not suppress CENP-E mRNA completely. DISCUSSION: Since its introduction in 1992, numerous variants of the differential display method and continuous improvements including RAP-PCR have proved to have both efficiency and reliability in examination of differentially regulated genes. The results of the present study reveal that RAP-PCR is a suitable method to identify differentially expressed genes in rheumatoid synovial fibroblasts. The mRNA, which has been found to be upregulated in rheumatoid synovial fibroblasts, codes for a kinesin-like motor protein named CENP-E, which was first characterized in 1991. It is a member of a family of centromere-associated proteins, of which six (CENP-A to CENP-F) are currently known. CENP-E itself is a kinetochore motor, which accumulates transiently at kinetochores in the G(2) phase of the cell cycle before mitosis takes place, appears to modulate chromosome movement and spindle elongation,and is degraded at the end of mitosis. The presence or upregulation of CENP-E has never been associated with RA. The three-dimensional structure of CENP-E includes a coiled-coil domain. This has important functions and shows links to known pathways in RA pathophysiology. Coiled-coil domains can also be found in jun and fos oncogene products, which are frequently upregulated in RA synovial fibroblasts. They are also involved in DNA binding and transactivation processes resembling the situation in AP-1 (Jun/Fos)-dependent DNA-binding in rheumatoid synovium. Most interestingly, these coiled-coil motifs are crucial for the assembly of viral proteins, and the upregulation of CENP-E might reflect the influence of infectious agents in RA synovium. We also performed experiments showing that serum starvation decreased, but did not completely inhibit CENP-E mRNA expression. This shows that CENP-E is related to, but does not completely depend on proliferation of these cells. In addition, we determined the growth rate of CENP-E high and low expressors, showing that it was independent from the amount of CENP-E expression. supporting the statement that upregulation of CENP-E reflects an activated RA fibroblast phenotype. In summary, the results of the present study support the hypothesis that CENP-E, presumably independently from medication, may not only be upregulated, but may also be involved in RA pathophysiology

The Grizzly, September 21, 1993

Israel and PLO Reach Peace Agreement • The Quilt: To Remember, To Educate, To Celebrate • Russian TV Crew Filming at Ursinus • New Reimert Policies for \u2793-\u2794 • Jurassic Park: It\u27s Only a Movie • Bernie Bernie Headflap Wins the Battle Again! • The Newly Roomie Game • A Unique Affair Awaits Us: Javapalooza \u2793 to Entertain Ursinus • Ursinus Needs AIDS Policy • More Than a Number • The New Wismer? Or a Police State? • Field Hockey Struggles Early • Men\u27s X-Country Starts off 2-0 • Lady Bears Search for Consistencyhttps://digitalcommons.ursinus.edu/grizzlynews/1318/thumbnail.jp