Dynamic process fragment injection in a service orchestration engine

The EU Project Allow Ensembles aims to develop a new design principle for large-scale collective systems (CAS) based on the concepts of cells and ensembles, where cells represent a concrete functionality in a system, and the ensembles are collections of cells which collaborate in order to fulfill a certain goal in a given context. Adaptive Pervasive Flows (APF) are based on workflow technology and utilized in pervasive environments to model the cell's behavior. During runtime, APF instances must be able to adapt their behavior, e.g. due to failures or changes in their environment, in order to be able to fulfill a certain goal. For this purpose, APFs may contain a particular type of activities, known as abstract activities. Abstract activities partially specify the flow behavior, which must then be resolved during runtime into one or multiple concrete activities, which in turn must be injected into the running flow. In the scope of this thesis, APFs are specified using an extension of the WS-BPEL language. The WS-BPEL language, provide the necessary mechanisms for extending the language for modeling custom process activities and specifying their behavior. In this thesis we focus on the WS-BPEL language and on an extended version of the Apache ODE orchestration engine, for business process modeling and execution respectively. With respect to the injection of pervasive process fragments, which contain one or multiple activities and properties, the language and execution engine requirements and constraints are investigated. For this purpose, a State-of-the-Art analysis on generic process fragment injection approaches is first driven. Once the constraints are detected, we present the formalization of the required language extension based on WS-BPEL language, and conduct a specification of requirements and architectural design of the final prototype based on the Apache Orchestration Director Engine (Apache ODE). For integration purposes in the overall required execution environment, the Enterprise Service Bus Apache ServiceMix 4.3 is used

Semispecific TPPII inhibitor Ala-Ala-Phe-chloromethylketone (AAF-cmk) displays cytotoxic activity by induction of apoptosis, autophagy and protein aggregation in U937 cells

Introduction. The main component of extralysosomal proteolysis is the ubiquitin-proteasome system (UPS), which is supplemented by tripeptidyl peptidase II (TPPII). That system is a target for anticancer strategies by using proteasome inhibitors. Data from several studies on leukemic cells share evidence for the beneficial and potential role of TPPII in cell survivability. Therefore, the aim of this work was to analyze the effect of AAF-cmk, a membrane permeable semi-specific TPPII inhibitor, on human monocytic leukemic cells U937 for translational research. Material and methods. We studied the viability of U937 cells incubated with AAF-cmk using tetrazolium salt reduction assay (MTT) and apoptosis induction by assessing caspase activation by Western blotting and Annexin V binding assays. Transmission electron microscopy (TEM), a gold standard for apoptosis and autophagy detection, was used to assess the ultrastructure of U937 cells. Results. Incubation of cells with AAF-cmk reduced their viability and induced apoptosis by intrinsic pathway. In groups treated with AAF-cmk, activation of caspases 9 and 3 was observed and caspase inhibition by zVDA restored cell viability. TEM revealed the presence of ultrastructural features of apoptosis and authophagy. Moreover, we identified two types of protein aggregates. The first one was found in close proximity to the endoplasmic reticulum (ER) and corresponds to Aggresome-Like Structure (ALIS); however, the second novel type of aggregate was not related to ER elements, but rather to free cytosolic ribosomes. This type did not correspond to the aggresome neither in localization nor the structure, thus we referred these aggregates as ALiSNER (Aggresome-Like Structure Not Associated With the ER). Conclusions. Our results provide novel and important findings about the role of TPPII in protein homeostasis and cell survival. Since semispecific TPPII inhibitor AAF-cmk displays cytotoxic activity against leukemic U937 cells in vitro it can be considered as a potential anticancer agent

Comparison of composition engines and identification of shortcomings with respect to cloud computing

Most workflow engines are currently not Cloud-aware. This is due to multiple reasons like no support for transparent scalability, no multi-tenancy support, no ability to store process related data in a Cloud storage, or no support for quality of service enforcements. Recently Cloud based workflow services appeared in the workflow landscape and promise to run workflows in the Cloud. This student reports evaluates current state of the art BPEL and BPMN workflow engines and Cloud based workflow services according to their Cloud- awareness and general workflow functionalities. Identified shortcomings are described and prioritized. As a result of this evaluation the workflow engine WSO2 Stratos is best suited for running workflows in the Cloud, but it lacks native clustering support and quality of service enforcement

Elective lung resection increases spatial QRS-T angle and QTc interval

Background: Lung resection changes intra-thoracic anatomy, which may affect electrocardiographic results. While postoperative cardiac arrhythmias have been recognized after lung resection, no study has documented changes in vectorcardiographic variables in patients undergoing this surgery. The purpose of this study was to analyse changes in spatial QRS-T angle (spQRS-T) and corrected QT interval (QTc) after lung resection.Methods: Adult patients undergoing elective lung resection under general anaesthesia were studied. The patients were allocated into four groups: those undergoing (1) left lobectomy (LL); (2) left pneumonectomy (LP); (3) right lobectomy (RL); and (4) right pneumonectomy (RP). The spQRS-T angle and QTc interval were measured one day before surgery (baseline) and 24, 48 and 72 h after surgery.Results: Seventy-one adult patients (47 men and 24 women) aged 47–80 (65 ± 7) years were studied. In the study group as a whole, lung resection was associated with significant increases in spQRS-T (p < 0.001) and QTc (p < 0.05 at 24 and 48 h and p < 0.01 at 72 h). The greatest changes were noted in patients undergoing LP. Postoperative atrial fibrillation (AF) was noted in 6.4% of patients studied, in whom the widest spQRS-T angle and the most prolonged QTc intervals were also noted.Conclusions: Lung resection widens the spQRS-T angle and prolongs the QTc interval, especially in patients undergoing LP. While postoperative AF was a relatively rare complication after lung resection in this study, it was associated with the widest spQRS-T angles and most prolonged QTc intervals

Synthesis of novel, peptidic kinase inhibitors with cytostatic/cytotoxic activity

The utility of a novel, chemoenzymatic procedure for the stereocontrolled synthesis of small peptides is presented in the preparation and structure optimisation of dipeptides with cytostatic/cytotoxic activity. The method uses Passerini multicomponent reaction for the preparation of racemic scaffold which is then enantioselectively hydrolysed by hydrolytic enzymes. Products of these transformations are further functionalised towards title compounds. Both activity and selectivity towards tumor cells is optimised. Final compound is shown to be an inhibitor of the protein kinase signaling pathway. (C) 2014 Elsevier Ltd. All rights reserved

Classification of Cell-in-Cell Structures: Different Phenomena with Similar Appearance

A phenomenon known for over 100 years named “cell-in-cell” (CIC) is now undergoing its renaissance, mostly due to modern cell visualization techniques. It is no longer an esoteric process studied by a few cell biologists, as there is increasing evidence that CICs may have prognostic and diagnostic value for cancer patients. There are many unresolved questions stemming from the difficulties in studying CICs and the limitations of current molecular techniques. CIC formation involves a dynamic interaction between an outer or engulfing cell and an inner or engulfed cell, which can be of the same (homotypic) or different kind (heterotypic). Either one of those cells appears to be able to initiate this process, which involves signaling through cell–cell adhesion, followed by cytoskeleton activation, leading to the deformation of the cellular membrane and movements of both cells that subsequently result in CICs. This review focuses on the distinction of five known forms of CIC (cell cannibalism, phagoptosis, enclysis, entosis, and emperipolesis), their unique features, characteristics, and underlying molecular mechanisms

Homotypic Entosis as a Potential Novel Diagnostic Marker in Breast Cancer

Homotypic entotic figures, which are a form of “cell-in-cell” structures, are considered a potential novel independent prognostic marker in various cancers. Nevertheless, the knowledge concerning the biological role of this phenomenon is still unclear. Since breast cancer cells are remarkably entosis-competent, we aimed to investigate and compare the frequency of entoses in a primary breast tumor and in its lymph node metastasis. Moreover, as there are limited data on defined molecular markers of entosis, we investigated entosis in correlation with classical breast cancer biomarkers used in routine pathomorphological diagnostics (HER2, ER, PR, and Ki67). In the study, a cohort of entosis-positive breast cancer samples paired into primary lesions and lymph node metastases was used. The inclusion criteria were a diagnosis of NOS cancer, lymph node metastases, the presence of entotic figures in the primary lesion, and/or lymph node metastases. In a selected, double-negative, HER2-positive NOS breast cancer case, entoses were characterized by a correlation between an epithelial–mesenchymal transition and proliferation markers. We observed that in the investigated cohort entotic figures were positively correlated with Ki67 and HER2, but not with ER or PR markers. Moreover, for the first time, we identified Ki67-positive mitotic inner entotic cells in clinical carcinoma samples. Our study performed on primary and secondary breast cancer specimens indicated that entotic figures, when examined by routine HE histological staining, present potential diagnostic value, since they correlate with two classical prognostic factors of breast cancer