Specification and validation of process constraints for flexible workflows

Workflow systems have traditionally focused on the so-called production processes which are characterized by pre-definition, high volume, and repetitiveness. Recently, the deployment of workflow systems in non-traditional domains such as collaborative applications, e-learning and cross-organizational process integration, have put forth new requirements for flexible and dynamic specification. However, this flexibility cannot be offered at the expense of control, a critical requirement of business processes. In this paper, we will present a foundation set of constraints for flexible workflow specification. These constraints are intended to provide an appropriate balance between flexibility and control. The constraint specification framework is based on the concept of pockets of flexibility which allows ad hoc changes and/or building of workflows for highly flexible processes. Basically, our approach is to provide the ability to execute on the basis of a partially specified model, where the full specification of the model is made at runtime, and may be unique to each instance. The verification of dynamically built models is essential. Where as ensuring that the model conforms to specified constraints does not pose great difficulty, ensuring that the constraint set itself does not carry conflicts and redundancy is an interesting and challenging problem. In this paper, we will provide a discussion on both the static and dynamic verification aspects. We will also briefly present Chameleon, a prototype workflow engine that implements these concepts. (c) 2004 Elsevier Ltd. All rights reserved.

Development of the Minimum Information Specification for in situ Hybridization and Immunohistochemistry Experiments (MISFISHIE)

We describe the creation process of the Minimum Information Specification for In Situ Hybridization and Immunohistochemistry Experiments (MISFISHIE). Modeled after the existing minimum information specification for microarray data, we created a new specification for gene expression localization experiments, initially to facilitate data sharing within a consortium. After successful use within the consortium, the specification was circulated to members of the wider biomedical research community for comment and refinement. After a period of acquiring many new suggested requirements, it was necessary to enter a final phase of excluding those requirements that were deemed inappropriate as a minimum requirement for all experiments. The full specification will soon be published as a version 1.0 proposal to the community, upon which a more full discussion must take place so that the final specification may be achieved with the involvement of the whole community. This paper is part of the special issue of OMICS on data standards.

A model of specification-based testing of interactive systems

In this paper we present a model of specification-based testing of interactive systems. This model provides the basis for a framework to guide such testing. Interactive systems are traditionally decomposed into a functionality component and a user interface component; this distinction is termed dialogue separation and is the underlying basis for conceptual and architectural models of such systems. Correctness involves both proper behaviour of the user interface and proper computation by the underlying functionality. Specification-based testing is one method used to increase confidence in correctness, but it has had limited application to interactive system development to date.

Central projections of Drosophila sensory neurons in the transition from embryo to larva

Sensory axons of different sensory modalities project into typical domains within insect ganglia. Tactile and gustatory axons project into a ventral layer of neuropil and proprioceptive afferents, including chordotonal axone, into an intermediate or dorsal layer. Here, we describe the central projections of sensory neurons in the first instar Drosophila larva, relating them to the projection of the same sensory afferents in the embryo and to sensory afferents of similar type in other insects. Several neurons show marked morphologic changes in their axon terminals in the transition between the embryo and larva. During a short morphogenetic period late in embryogenesis, the axon terminals of the dorsal bipolar dendrite stretch receptor change their shape and their distribution within the neuromere. In the larva, external sense organ neurons (es) project their axons into a ventral layer of neuropil. Chordotonal sensory neurons (ch) project into a slightly more dorsal region that is comparable to their projection in adults. The multiple dendrite (md) neurons show two distinctive classes of projection. One group of md neurons projects into the ventral-most neuropil region, the same region into which es neurons project. Members of this group are related by lineage to es neurons or share a requirement for expression of the same proneural gene during development. Other md neurons project into a more dorsal region. Sensory receptors projecting into dorsal neuropil possibly provide proprioceptive feedback from the periphery to central motorneurons and are candidates for future genetic and cellular analysis of simple neural circuitry. J. Comp. Neurol. 425:34-44, 2000. (C) 2000 Wiley-Liss, Inc.

A framework for specification-based testing

Test templates and a test template framework are introduced as useful concepts in specification-based testing. The framework can be defined using any model-based specification notation and used to derive tests from model-based specifications-in this paper, it is demonstrated using the Z notation. The framework formally defines test data sets and their relation to the operations in a specification and to other test data sets, providing structure to the testing process. Flexibility is preserved, so that many testing strategies can be used. Important application areas of the framework are discussed, including refinement of test data, regression testing, and test oracles.

Specification and Evaluation of Safety Properties in a Component-Based Software Engineering Process

Over the past years, component-based software engineering has become an established paradigm in the area of complex software intensive systems. However, many techniques for analyzing these systems for critical properties currently do not make use of the component orientation. In particular, safety analysis of component-based systems is an open field of research. In this chapter we investigate the problems arising and define a set of requirements that apply when adapting the analysis of safety properties to a component-based software engineering process. Based on these requirements some important component-oriented safety evaluation approaches are examined and compared.

Specification, refinement and verification of concurrent systems - An integration of Object-Z and CSP

This paper presents a method of formally specifying, refining and verifying concurrent systems which uses the object-oriented state-based specification language Object-Z together with the process algebra CSP. Object-Z provides a convenient way of modelling complex data structures needed to define the component processes of such systems, and CSP enables the concise specification of process interactions. The basis of the integration is a semantics of Object-Z classes identical to that of CSP processes. This allows classes specified in Object-Z to he used directly within the CSP part of the specification. In addition to specification, we also discuss refinement and verification in this model. The common semantic basis enables a unified method of refinement to be used, based upon CSP refinement. To enable state-based techniques to be used fur the Object-Z components of a specification we develop state-based refinement relations which are sound and complete with respect to CSP refinement. In addition, a verification method for static and dynamic properties is presented. The method allows us to verify properties of the CSP system specification in terms of its component Object-Z classes by using the laws of the the CSP operators together with the logic for Object-Z.

Interferon-gamma enhances cytotoxic T lymphocyte recognition of endogenous peptide in keratinocytes without lowering the requirement for surface peptide

Keratinocytes expressing the human papillomavirus (HPV) type 16 E7 protein, as a transgene driven by the K14 promoter, form a murine model of HPV-mediated epithelial cancers in humans. Our previous studies have shown that K14E7 transgenic skin grafts onto syngeneic mice are not susceptible to immune destruction despite the demonstrated presence of a strong, systemic CTL response directed against the E7 protein. Consistent with this finding, we now show that cultured, E7 transgenic keratinocytes (KC) express comparable endogenous levels of E7 protein to a range of CTL-sensitive E7-expressing cell lines but are not susceptible to CTL-mediated lysis in vitro . E7 transgenic and non-transgenic KC are susceptible to conventional mechanisms of CTL-mediated lysis, including perforin and Fas/FasL interaction when an excess of exogenous peptide is provided. The concentration of exogenous peptide required to render a cell susceptible to lysis was similar between KC and other conventional CTL targets (e.g. EL-4), despite large differences in H-2D(b) expression at the cell surface. Furthermore, exposure of KC to IFN-gamma increased H-2D(b) expression, but did not substantially alter the exogenous peptide concentration required to sensitize cells for half maximal lysis. In contrast, the lytic sensitivity of transgenic KC expressing endogenous E7 is modestly improved by exposure to IFN-gamma. Thus, failure of CTL to eliminate KC expressing endogenous E7, and by inference squamous tumours expressing E7, may reflect the need for a sustained, local inflammatory environment during the immune effector phase.

Complementation analysis of the flavivirus Kunjin NS3 and NS5 proteins defines the minimal regions essential for formation of a replication complex and shows a requirement of NS3 in cis for virus assembly

We have previously reported successful trans-complementation of defective Kunjin virus genomic RNAs with a range of large lethal deletions in the nonstructural genes NSI, NS3, and NS5 (A. A. Khromykh et al., J. Virol. 74:3253-3263, 2000). In this study we have mapped further the minimal region in the NS5 gene essential for efficient trans-complementation of genome-length RNAs in repBHK cells to the first 316 of the 905 codons. To allow amplification and easy detection of complemented defective RNAs with deletions apparently affecting virus assembly, we have developed a dual replicon complementation system. In this system defective replicon RNAs with a deletion(s) in the nonstructural genes also encoded the puromycin resistance gene (PAC gene) and the reporter gene for beta-galactosidase (beta-Gal). Complementation of these defective replicon RNAs in repBHK cells resulted in expression of PAC and beta-Gal which allowed establishment of cell lines stably producing replicating defective RNAs by selection with puromycin and comparison of replication efficiencies of complemented defective RNAs by beta-Gal assay. Using this system we demonstrated that deletions in the C-terminal 434 codons of NS3 (codons 178 to 611) were complemented for RNA replication, while any deletions in the first 178 codons were not. None of the genome-length RNAs containing deletions in NS3 shown to be complementable for RNA replication produced secreted defective viruses during complementation in repBHK cells. In contrast, structural proteins produced from these complemented defective RNAs were able to package helper replicon RNA. The results define minimal regions in the NS3 and NS5 genes essential for the formation of complementable replication complex and show a requirement of NS3 in cis for virus assembly.

Model specification tests in nonparametric stochastic regression models

In this paper, we consider testing for additivity in a class of nonparametric stochastic regression models. Two test statistics are constructed and their asymptotic distributions are established. We also conduct a small sample study for one of the test statistics through a simulated example. (C) 2002 Elsevier Science (USA).

Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes

Although it is the best characterized in vitro model of GH action, the mechanisms used by GH to induce differentiation of murine 3T3-F442A preadipocytes remain unclear. Here we have examined the role of three transcriptional regulators in adipogenesis. These regulators are either rapidly induced in response to GH [Stra13, signal transducer and activator of transcription (Stat) 3] or of central importance to GH signaling (Stat5). Retroviral transfection of 3T3-F442A preadipocytes was used to increase expression of Stra13, Stat3, and Stat5a. Only Stat5a transfection increased the expression of adipogenic markers peroxisome proliferator-activated receptor gamma, CCAAT enhancer binding protein (C/EBP)alpha, and adipose protein 2/fatty acid-binding protein in response to GH, as determined by quantitative RT-PCR. Transfection with constitutively active Stat3 and Stat5a revealed that constitutively active Stat5a but not Stat3 was able to replace the GH requirement for adipogenesis. Constitutively active Stat5a but not Stat3 was able to increase the formation of lipid droplets and expression of alpha-glycerol phosphate dehydrogenase toward levels seen in mature adipocytes. Constitutively active Stat5a was also able to increase the expression of transcripts for C/EBPalpha to similar levels as GH, and of C/EBPbeta, peroxisome proliferator-activated receptor gamma, and adipose protein 2/fatty acid-binding protein transcripts to a lesser extent. An in vivo role for GH in murine adipogenesis is supported by significantly decreased epididymal fat depot size in young GH receptor-deleted mice, before manifestation of the lipolytic actions of GH. We conclude that Stat5 is a critical factor in GH-induced, and potentially prolactin-induced, murine adipogenesis.