Enhancing workflow-nets with data for trace completion

The growing adoption of IT-systems for modeling and executing (business) processes or services has thrust the scientific investigation towards techniques and tools which support more complex forms of process analysis. Many of them, such as conformance checking, process alignment, mining and enhancement, rely on complete observation of past (tracked and logged) executions. In many real cases, however, the lack of human or IT-support on all the steps of process execution, as well as information hiding and abstraction of model and data, result in incomplete log information of both data and activities. This paper tackles the issue of automatically repairing traces with missing information by notably considering not only activities but also data manipulated by them. Our technique recasts such a problem in a reachability problem and provides an encoding in an action language which allows to virtually use any state-of-the-art planning to return solutions

Predictive Monitoring of Business Processes

Modern information systems that support complex business processes generally maintain significant amounts of process execution data, particularly records of events corresponding to the execution of activities (event logs). In this paper, we present an approach to analyze such event logs in order to predictively monitor business goals during business process execution. At any point during an execution of a process, the user can define business goals in the form of linear temporal logic rules. When an activity is being executed, the framework identifies input data values that are more (or less) likely to lead to the achievement of each business goal. Unlike reactive compliance monitoring approaches that detect violations only after they have occurred, our predictive monitoring approach provides early advice so that users can steer ongoing process executions towards the achievement of business goals. In other words, violations are predicted (and potentially prevented) rather than merely detected. The approach has been implemented in the ProM process mining toolset and validated on a real-life log pertaining to the treatment of cancer patients in a large hospital

Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice

Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin — 1 surgical and the other genetic — to quantitatively track RCT following injection of [3H]-cholesterol–loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti–VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis

The structural basis of small molecule targetability of monomeric Tau protein

The therapeutic targeting of intrinsically disordered proteins (IDPs) by small molecules has been a challenge due to their heterogeneous conformational ensembles. A potential therapeutic strategy to alleviate the aggregation of IDPs is to maintain them in their native monomeric state by small molecule binding. This study investigates the structural basis of small molecule druggability of native monomeric Tau whose aggregation is linked to the onset of Tauopathies such as Alzheimer’s disease. Initially, two available monomeric conformational ensembles of a shorter Tau construct K18 (also termed Tau4RD) were analyzed which revealed striking structural differences between the two ensembles, while similar number of hot spots and small molecule binding sites were identified on monomeric Tau ensembles as on tertiary folded proteins of similar size. Remarkably, some critical fibril forming sequence regions of Tau (V306-K311, V275-K280) participated in hot spot formation with higher frequency compared to other regions. As an example of small molecule binding to monomeric Tau, it was shown that methylene blue (MB) bound to monomeric K18 and full-length Tau selectively with high affinity (Kd = 125.8 nM and 86.6 nM, respectively) with binding modes involving Cys291 and Cys322, previously reported to be oxidized in the presence of MB. Overall, our results provide structure-based evidence that Tau can be a viable drug target for small molecules and indicate that specific small molecules may be able to bind to monomeric Tau and influence the way in which the protein interacts among itself and with other proteins

Predictive Process Monitoring Methods: Which One Suits Me Best?

Predictive process monitoring has recently gained traction in academia and is maturing also in companies. However, with the growing body of research, it might be daunting for companies to navigate in this domain in order to find, provided certain data, what can be predicted and what methods to use. The main objective of this paper is developing a value-driven framework for classifying existing work on predictive process monitoring. This objective is achieved by systematically identifying, categorizing, and analyzing existing approaches for predictive process monitoring. The review is then used to develop a value-driven framework that can support organizations to navigate in the predictive process monitoring field and help them to find value and exploit the opportunities enabled by these analysis techniques

Preparing veterinary students for extramural clinical placement training: issues identified and a possible solution

Catriona Bell – ORCID: 0000-0001-8501-1697 https://orcid.org/0000-0001-8501-1697Item not available in this repository.Item previously deposited in the University of Edinburgh repository at: https://www.research.ed.ac.uk/en/publications/fa503683-7a33-4bb5-bcd9-8850b1949d9dExtramural clinical placement training is an important part of many veterinary degree programs and provides students with valuable learning experiences in private practice, often focusing on the management of typical first-opinion cases. In the United Kingdom, the Royal College of Veterinary Surgeons (RCVS) has a mandatory requirement that students take 26 weeks of clinical placement or extramural studies (EMS) before graduation. However, if students are to maximize their learning opportunities during these placements, it is important that they be adequately prepared. In response to recent topical issues surrounding EMS in the United Kingdom, the current project undertook an iterative consultation process with key stakeholders, including students and placement providers, to identify key issues associated with students attending placements. These findings then informed the development and content of a computer-aided learning (CAL) package titled “The EMS Driving Licence” that aimed to improve the preparation of students for placements. The CAL package included sections covering the main identified areas of concern: Preparation (including what to take), Working With People (staff and clients), Professionalism (including confidentiality), Frequently Asked Questions (from students), and Top Tips (from practitioners). The CAL package was evaluated by students, and feedback was gathered by means of a questionnaire. Students recognized that the content addressed many of their concerns, and all reported that they would recommend the package to others. The CAL package has been made available to all UK veterinary schools and has received backing from the RCVS as part of their current recommendations on EMS to the UK veterinary profession.The development of the EMS Driving Licence was supported by a mini-project grant from the Higher Education Academy Subject Centre for Medicine, Dentistry and Veterinary Medicine, Newcastle Upon Tyne, UK. The evaluation was supported by an Innovation Fund award from the Centre for Excellence in Professional Placement Learning, University of Plymouth, Plymouth, UK.https://doi.org/10.3138/jvme.37.2.19037pubpub

New semisynthetic vinca alkaloids: chemical, biochemical and cellular studies

A new semisynthetic anti-tumour bis-indol compound, KAR-2 [3′-(β-chloroethyl)-2′,4′-dioxo-3,5′-spiro-oxazolidino-4-deacetoxy-vinblastine] with lower toxicity than vinca alkaloids used in chemotherapy binds to calmodulin but, in contrast to vinblastine, does not exhibit anti-calmodulin activity. To investigate whether the modest chemical modification of bis-indol structure is responsible for the lack of anti-calmodulin potency and for the different pharmacological effects, new derivatives have been synthesized for comparative studies. The synthesis of the KAR derivatives are presented. The comparative studies showed that the spiro-oxazolidino ring and the substitution of a formyl group to a methyl one were responsible for the lack of anti-calmodulin activities. The new derivatives, similar to the mother compounds, inhibited the tubulin assembly in polymerization tests in vitro, however their inhibitory effect was highly dependent on the organization state of microtubules; bundled microtubules appeared to be resistant against the drugs. The maximal cytotoxic activities of KAR derivatives in in vivo mice hosting leukaemia P388 or Ehrlich ascites tumour cells appeared similar to that of vinblastine or vincristine, however significant prolongation of life span could be reached with KAR derivatives only after the administration of a single dose. These studies plus data obtained using a cultured human neuroblastoma cell line showed that KAR compounds displayed their cytotoxic activities at significantly higher concentrations than the mother compounds, although their antimicrotubular activities were similar in vitro. These data suggest that vinblastine/vincristine damage additional crucial cell functions, one of which could be related to calmodulin-mediated processes. © 1999 Cancer Research Campaig

The Long Term Response of Birds to Climate Change: New Results from a Cold Stage Avifauna in Northern England

The early MIS 3 (55–40 Kyr BP associated with Middle Palaeolithic archaeology) bird remains from Pin Hole, Creswell Crags, Derbyshire, England are analysed in the context of the new dating of the site’s stratigraphy. The analysis is restricted to the material from the early MIS 3 level of the cave because the upper fauna is now known to include Holocene material as well as that from the Late Glacial. The results of the analysis confirm the presence of the taxa, possibly unexpected for a Late Pleistocene glacial deposit including records such as Alpine swift, demoiselle crane and long-legged buzzard with southern and/or eastern distributions today. These taxa are accompanied by more expected ones such as willow ptarmigan /red grouse and rock ptarmigan living today in northern and montane areas. Finally, there are temperate taxa normally requiring trees for nesting such as wood pigeon and grey heron. Therefore, the result of the analysis is that the avifauna of early MIS 3 in England included taxa whose ranges today do not overlap making it a non-analogue community similar to the many steppe-tundra mammalian faunas of the time. The inclusion of more temperate and woodland taxa is discussed in the light that parts of northern Europe may have acted as cryptic northern refugia for some such taxa during the last glacial. These records showing former ranges of taxa are considered in the light of modern phylogeographic studies as these often assume former ranges without considering the fossil record of those taxa. In addition to the anomalous combination of taxa during MIS 3 living in Derbyshire, the individuals of a number of the taxa are different in size and shape to members of the species today probably due to the high carrying capacity of the steppe-tundra

Carotid Baroreflex Activation: Past, Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension