Open source software for workflow management : the case of YAWL

"This column is distinguished from previous Impact columns in that it concerns the development tightrope between research and commercial take-up and the role of the LGPL in an open source workflow toolkit produced in a University environment. Many ubiquitous systems have followed this route, (Apache, BSD Unix, ...), and the lessons this Service Oriented Architecture produces cast yet more light on how software diffuses out to impact us all." Michiel van Genuchten and Les Hatton Workflow management systems support the design, execution and analysis of business processes. A workflow management system needs to guarantee that work is conducted at the right time, by the right person or software application, through the execution of a workflow process model. Traditionally, there has been a lack of broad support for a workflow modeling standard. Standardization efforts proposed by the Workflow Management Coalition in the late nineties suffered from limited support for routing constructs. In fact, as later demonstrated by the Workflow Patterns Initiative (www.workflowpatterns.com), a much wider range of constructs is required when modeling realistic workflows in practice. YAWL (Yet Another Workflow Language) is a workflow language that was developed to show that comprehensive support for the workflow patterns is achievable. Soon after its inception in 2002, a prototype system was built to demonstrate that it was possible to have a system support such a complex language. From that initial prototype, YAWL has grown into a fully-fledged, open source workflow management system and support environment

An intelligent building model of sustainable architecture in a mechanism of open systems evolution

This paper argues a model of open systems evolution based on evolutionary thermodynamics and complex system science, as a design paradigm for sustainable architecture. The mechanism of open system evolution is specified in mathematical simulations and theoretical discourses. According to the mechanism, the authors propose an intelligent building model of sustainable design by a holistic information system of the end-users, the building and nature. This information system is used to control the consumption of energy and material resources in building system at microscopic scale, to adapt the environmental performance of the building system to the natural environment at macroscopic scale, for an evolutionary emergence of sustainable performance of buildings.

PLGA-based microparticles for the sustained release of BMP-2

The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture), as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

Content and functionality of alcohol and other drug websites : results of an online survey

Background: There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood. ----- ----- Objective: To investigate content and functionality preferences for AOD and other health websites. Methods: An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences. ----- ----- Results: Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents. ----- ----- Conclusions: Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.

Online alcohol interventions : a systematic review

Background: There has been a significant increase in the availability of online programs for alcohol problems. A systematic review of the research evidence underpinning these programs is timely. Objectives: Our objective was to review the efficacy of online interventions for alcohol misuse. Systematic searches of Medline, PsycINFO, Web of Science, and Scopus were conducted for English abstracts (excluding dissertations) published from 1998 onward. Search terms were: (1) Internet, Web*; (2) online, computer*; (3) alcohol*; and (4) E\effect*, trial*, random* (where * denotes a wildcard). Forward and backward searches from identified papers were also conducted. Articles were included if (1) the primary intervention was delivered and accessed via the Internet, (2) the intervention focused on moderating or stopping alcohol consumption, and (3) the study was a randomized controlled trial of an alcohol-related screen, assessment, or intervention. Results: The literature search initially yielded 31 randomized controlled trials (RCTs), 17 of which met inclusion criteria. Of these 17 studies, 12 (70.6%) were conducted with university students, and 11 (64.7%) specifically focused on at-risk, heavy, or binge drinkers. Sample sizes ranged from 40 to 3216 (median 261), with 12 (70.6%) studies predominantly involving brief personalized feedback interventions. Using published data, effect sizes could be extracted from 8 of the 17 studies. In relation to alcohol units per week or month and based on 5 RCTs where a measure of alcohol units per week or month could be extracted, differential effect sizes to post treatment ranged from 0.02 to 0.81 (mean 0.42, median 0.54). Pre-post effect sizes for brief personalized feedback interventions ranged from 0.02 to 0.81, and in 2 multi-session modularized interventions, a pre-post effect size of 0.56 was obtained in both. Pre-post differential effect sizes for peak blood alcohol concentrations (BAC) ranged from 0.22 to 0.88, with a mean effect size of 0.66. Conclusions: The available evidence suggests that users can benefit from online alcohol interventions and that this approach could be particularly useful for groups less likely to access traditional alcohol-related services, such as women, young people, and at-risk users. However, caution should be exercised given the limited number of studies allowing extraction of effect sizes, the heterogeneity of outcome measures and follow-up periods, and the large proportion of student-based studies. More extensive RCTs in community samples are required to better understand the efficacy of specific online alcohol approaches, program dosage, the additive effect of telephone or face-to-face interventions, and effective strategies for their dissemination and marketing.

Reconnecting the interrupted landscape : a cultural landscape approach to Australian open-cut coal mining landscapes

In the late 20th century, a value-shift began to influence political thinking, recognising the need for environmentally, socially and culturally sustainable resource development. This shift entailed moves away from thinking of nature and culture as separate entities - The former existing merely to serve the latter. Cultural landscape theory recognises 'nature' as at once both 'natural', and as a 'cultural' construct. As such it may offer a framework through which to progress in the quest for 'sustainable development'. This 2005 Masters thesis makes a contribution to that quest by asking whether contemporary developments in cultural landscape theory can contribute to rehabilitation strategies for Australian open-cut coal mining landscapes, an examplar resource development landscape. A thematic historial overview of landscape values and resource development in Australis post-1788, and a review of cultural landscape theory literature contribute to the formation of the theoretical framework: "reconnecting the interrupted landscape". The author then explores a possible application of this framework within the Australian open-cut coal mining landscape.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).

Involvement of Exo1b in DNA damage-induced apoptosis

Apoptosis is essential for the maintenance of inherited genomic integrity. During DNA damage-induced apoptosis, mechanisms of cell survival, such as DNA repair are inactivated to allow cell death to proceed. Here, we describe a role for the mammalian DNA repair enzyme Exonuclease 1 (Exo1) in DNA damage-induced apoptosis. Depletion of Exo1 in human fibroblasts, or mouse embryonic fibroblasts led to a delay in DNA damage-induced apoptosis. Furthermore, we show that Exo1 acts upstream of caspase-3, DNA fragmentation and cytochrome c release. In addition, induction of apoptosis with DNA-damaging agents led to cleavage of both isoforms of Exo1. The cleavage of Exo1 was mapped to Asp514, and shown to be mediated by caspase-3. Expression of a caspase-3 cleavage site mutant form of Exo1, Asp514Ala, prevented formation of the previously observed fragment without any affect on the onset of apoptosis. We conclude that Exo1 has a role in the timely induction of apoptosis and that it is subsequently cleaved and degraded during apoptosis, potentially inhibiting DNA damage repair.

Phosphorylation of Exo1 modulates homologous recombination repair of DNA double-strand breaks

DNA double-strand break (DSB) repair via the homologous recombination pathway is a multi-stage process, which results in repair of the DSB without loss of genetic information or fidelity. One essential step in this process is the generation of extended single-stranded DNA (ssDNA) regions at the break site. This ssDNA serves to induce cell cycle checkpoints and is required for Rad51 mediated strand invasion of the sister chromatid. Here, we show that human Exonuclease 1 (Exo1) is required for the normal repair of DSBs by HR. Cells depleted of Exo1 show chromosomal instability and hypersensitivity to ionising radiation (IR) exposure. We find that Exo1 accumulates rapidly at DSBs and is required for the recruitment of RPA and Rad51 to sites of DSBs, suggesting a role for Exo1 in ssDNA generation. Interestingly, the phosphorylation of Exo1 by ATM appears to regulate the activity of Exo1 following resection, allowing optimal Rad51 loading and the completion of HR repair. These data establish a role for Exo1 in resection of DSBs in human cells, highlighting the critical requirement of Exo1 for DSB repair via HR and thus the maintenance of genomic stability.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Sharing with Creative Commons : a business model for content creators

Creative Commons (CC) is often seen as a social movement, dismissed by critics as a tool for hobbyists or academics who do not sell their creations to make a living. However, this paper argues that the licensing of creative copyright works under a CC licence does not preclude commercial gain. If used wisely, CC licences can be a useful tool for creators in their quest for commercial success. In particular, this paper argues that the sharing of creative works online under a CC licence allows creators to circumvent traditional distribution channels dominated by content intermediaries, whilst maintaining a level of control over their copyright works (i.e. explicitly reserving some rights but not all rights). This will be illustrated by case studies on how CC is being used by content creators and intermediaries respectively, and how successful their respective methods are in harnessing this tool.

Electrospraying a reproducible method for production of polymeric microspheres for biomedical applications

The ability to reproducibly load bioactive molecules into polymeric microspheres is a challenge. Traditional microsphere fabrication methods typically provide inhomogeneous release profiles and suffer from lack of batch to batch reproducibility, hindering their potential to up-scale and their translation to the clinic. This deficit in homogeneity is in part attributed to broad size distributions and variability in the morphology of particles. It is thus desirable to control morphology and size of non-loaded particles in the first instance, in preparation for obtaining desired release profiles of loaded particles in the later stage. This is achieved by identifying the key parameters involved in particle production and understanding how adapting these parameters affects the final characteristics of particles. In this study, electrospraying was presented as a promising technique for generating reproducible particles made of polycaprolactone, a biodegradable, FDA-approved polymer. Narrow size distributions were obtained by the control of electrospraying flow rate and polymer concentration, with average particle sizes ranging from 10 to 20 um. Particles were shown to be spherical with a homogenous embossed texture, determined by the polymer entanglement regime taking place during electrospraying. No toxic residue was detected by this process based on preliminary cell work using DNA quantification assays, validating this method as suitable for further loading of bioactive components.

Effects of different practice task constraints on fluctuations of player heart rate in small-sided football games

This paper analyzes effects of different practice task constraints on heart rate (HR) variability during 4v4 smallsided football games. Participants were sixteen football players divided into two age groups (U13, Mean age: 12.4±0.5 yrs; U15: 14.6±0.5). The task consisted of a 4v4 sub-phase without goalkeepers, on a 25x15 m field, of 15 minutes duration with an active recovery period of 6 minutes between each condition. We recorded players’ heart rates using heart rate monitors (Polar Team System, Polar Electro, Kempele, Finland) as scoring mode was manipulated (line goal: scoring by dribbling past an extended line; double goal: scoring in either of two lateral goals; and central goal: scoring only in one goal). Subsequently, %HR reserve was calculated with the Karvonen formula. We performed a time-series analysis of HR for each individual in each condition. Mean data for intra-participant variability showed that autocorrelation function was associated with more short-range dependence processes in the “line goal” condition, compared to other conditions, demonstrating that the “line goal” constraint induced more randomness in HR response. Relative to inter-individual variability, line goal constraints demonstrated lower %CV and %RMSD (U13: 9% and 19%; U15: 10% and 19%) compared with double goal (U13: 12% and 21%; U15: 12% and 21%) and central goal (U13: 14% and 24%; U15: 13% and 24%) task constraints, respectively. Results suggested that line goal constraints imposed more randomness on cardiovascular stimulation of each individual and lower inter-individual variability than double goal and central goal constraints.