Context of processes : achieving thorough documentation in provenance systems through context awareness

To fully understand real world processes, having evidence which is as comprehensive as possible is essential. Comprehensive evidence enables the reviewer to have some confidence that they are aware of the nuances of a past scenario and can act appropriately upon them in the future. There are examples of this throughout everyday life the outcome of a court case could be affected by available evidence or an antique could be considered more valuable if certain facts about its history are known. Similarly, in computer systems, evidence of processes allow users to make more informed decisions than if it were not captured. Where computer based experimentation has enabled scientists to perform complicated experiments quickly with ease, understanding the precise circumstances of the process which created a particular set of results is important. Significant recent research has sought to address the problem of understanding the provenance of an data item—the process which led to that data item. Increasingly, these experiments are being performed using systems which are distributed, large scale and open. Comprehensive evidence in these environments is achieved when both documentation of the actions per formed and the circumstances in which they occur are captured. Therefore, in order for a user to achieve confidence in results, we argue the importance of documenting the context of a process. This thesis addresses the problem of how context may be suitably modeled, captured and queried to later answer questions concerning data origin. We begin by defining context as any information describing a scenario which has some bearing on a process's outcome. Based on a number of use cases from a Functional Magnetic Resonance Imaging (fMRI) workflow, we present a model for representation of context. Our model treats each actor in a process as capable of progressing over a number of finite states as they perform actions. We show that each state can be encoded by using a set of monitored variables from an actor's host. Each transition between states therefore is a series of variable changes and this model is shown to be capable of measuring similarity of context when comparing multiple executions of the same process. It also allows us to consider future state changes for actors based on their past execution. We evaluate through the use of our own context capture system which allows common monitoring tools to be used as an indication of state change and recording of context transparently from stake holders. Our experimental findings suggest our approach to both be acceptable in terms of performance (with an overhead of 4–8% against a non context capturing approach) and use case satisfaction.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Context of processes : achieving thorough documentation in provenance systems through context awareness

To fully understand real world processes, having evidence which is as comprehensive as possible is essential. Comprehensive evidence enables the reviewer to have some confidence that they are aware of the nuances of a past scenario and can act appropriately upon them in the future. There are examples of this throughout everyday life the outcome of a court case could be affected by available evidence or an antique could be considered more valuable if certain facts about its history are known. Similarly, in computer systems, evidence of processes allow users to make more informed decisions than if it were not captured. Where computer based experimentation has enabled scientists to perform complicated experiments quickly with ease, understanding the precise circumstances of the process which created a particular set of results is important. Significant recent research has sought to address the problem of understanding the provenance of an data item—the process which led to that data item. Increasingly, these experiments are being performed using systems which are distributed, large scale and open. Comprehensive evidence in these environments is achieved when both documentation of the actions per formed and the circumstances in which they occur are captured. Therefore, in order for a user to achieve confidence in results, we argue the importance of documenting the context of a process. This thesis addresses the problem of how context may be suitably modeled, captured and queried to later answer questions concerning data origin. We begin by defining context as any information describing a scenario which has some bearing on a process's outcome. Based on a number of use cases from a Functional Magnetic Resonance Imaging (fMRI) workflow, we present a model for representation of context. Our model treats each actor in a process as capable of progressing over a number of finite states as they perform actions. We show that each state can be encoded by using a set of monitored variables from an actor's host. Each transition between states therefore is a series of variable changes and this model is shown to be capable of measuring similarity of context when comparing multiple executions of the same process. It also allows us to consider future state changes for actors based on their past execution. We evaluate through the use of our own context capture system which allows common monitoring tools to be used as an indication of state change and recording of context transparently from stake holders. Our experimental findings suggest our approach to both be acceptable in terms of performance (with an overhead of 4–8% against a non context capturing approach) and use case satisfaction.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The context of processes: achieving thorough documentation in provenance systems through context awareness

To fully understand real world processes, having evidence which is as comprehensive as possible is essential. Comprehensive evidence enables the reviewer to have some confidence that they are aware of the nuances of a past scenario and can act appropriately upon them in the future. There are examples of this throughout everyday life the outcome of a court case could be affected by available evidence or an antique could be considered more valuable if certain facts about its history are known. Similarly, in computer systems, evidence of processes allow users to make more informed decisions than if it were not captured. Where computer based experimentation has enabled scientists to perform complicated experiments quickly with ease, understanding the precise circumstances of the process which created a particular set of results is important. Significant recent research has sought to address the problem of understanding the provenance of an data item—the process which led to that data item. Increasingly, these experiments are being performed using systems which are distributed, large scale and open. Comprehensive evidence in these environments is achieved when both documentation of the actions per formed and the circumstances in which they occur are captured. Therefore, in order for a user to achieve confidence in results, we argue the importance of documenting the context of a process. This thesis addresses the problem of how context may be suitably modeled, captured and queried to later answer questions concerning data origin. We begin by defining context as any information describing a scenario which has some bearing on a process's outcome. Based on a number of use cases from a Functional Magnetic Resonance Imaging (fMRI) workflow, we present a model for representation of context. Our model treats each actor in a process as capable of progressing over a number of finite states as they perform actions. We show that each state can be encoded by using a set of monitored variables from an actor's host. Each transition between states therefore is a series of variable changes and this model is shown to be capable of measuring similarity of context when comparing multiple executions of the same process. It also allows us to consider future state changes for actors based on their past execution. We evaluate through the use of our own context capture system which allows common monitoring tools to be used as an indication of state change and recording of context transparently from stake holders. Our experimental findings suggest our approach to both be acceptable in terms of performance (with an overhead of 4–8% against a non context capturing approach) and use case satisfaction

High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility

Transcriptional regulators lacking enzymatic activity or binding pockets with targetable molecular features have typically been considered “undruggable,” and a reductionist approach based on identification of their molecular targets has largely failed. We have demonstrated that the Ewing sarcoma chimeric transcription factor, EWSR1-FLI1, maintains accessible chromatin at disease-specific regions. We adapted formaldehyde-assisted isolation of regulatory elements (FAIRE), an assay for accessible chromatin, to screen an epigenetically targeted small molecule library for compounds that reverse the disease-associated signature. This approach can be applied broadly for discovery of chromatin-based developmental therapeutics and offers significant advantages because it does not require the selection of a single molecular target. Using this approach, we identified a specific class of compounds with therapeutic potential

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Structures of three members of Pfam PF02663 (FmdE) implicated in microbial methanogenesis reveal a conserved α+β core domain and an auxiliary C-terminal treble-clef zinc finger

The first structures from the FmdE Pfam family (PF02663) reveal that some members of this family form tightly intertwined dimers consisting of two domains (N-terminal α+β core and C-terminal zinc-finger domains), whereas others contain only the core domain. The presence of the zinc-finger domain suggests that some members of this family may perform functions associated with transcriptional regulation, protein–protein interaction, RNA binding or metal-ion sensing

Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron

The crystal structure of a novel MACPF protein, which may play a role in the adaptation of commensal bacteria to host environments in the human gut, was determined and analyzed