Refactoring Process Models in Large Process Repositories.

With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are introduced and complexity is increased. If no continuous investment is made in keeping models simple, changes are becoming increasingly costly and error-prone. Though refactoring techniques are widely used in software engineering to address related problems, this does not yet constitute state-of-the art in business process management. Process designers either have to refactor process models by hand or cannot apply respective techniques at all. This paper proposes a set of behaviour-preserving techniques for refactoring large process repositories. This enables process designers to eectively deal with model complexity by making process models better understandable and easier to maintain

The Depsipeptide Romidepsin Reverses HIV-1 Latency In Vivo.

UNLABELLED: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7-7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4-5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46-103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1-2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. TRIAL REGISTRATION: clinicaltrials.gov NTC02092116

New approaches using mass spectrometry to investigate changes to cytokinin and abscisic acid (ABA) concentrations in soil

Phytohormones such as cytokinins, abscisic acid (ABA) and auxins play a vital role in plant development and regulatory processes. Their role within the plant is a focus for much research, with studies using recent advances in mass spectrometry performance allowing the quantification of low levels of phytohormones extracted from plant tissues. Despite these advances, external factors influencing the production of phytohormones are less well studied. Here, a new approach is presented for the extraction of a range of phytohormones from plant growth media (soil and hydroponic solution), their identification using high mass accuracy mass spectrometry and subsequent quantification using multiple reaction monitoring (MRM). The ability to detect phytohormones in matrices other than plant tissue presents the opportunity to study further the influence of factors such as below ground organisms and soil bacteria on phytohormone production. This novel approach was therefore applied to the plant growth media from a series of experiments comparing plant growth in the presence and absence of earthworms. A small but significant increase in ABA concentration was observed in the presence of earthworms, increasing even further when plants were also present. This finding suggests that earthworms could stimulate plant ABA production. This experiment and its outcomes demonstrate the value of studying phytohormones outside plant tissue, and the potential value of further research in this area

Increased risk of high-grade dysplasia and colorectal cancer in inflammatory bowel disease patients with recurrent low-grade dysniasia

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