Multigrid-reduction-in-time for Eddy Current problems

Parallel-in-time methods have shown success for reducing the simulation time of many time-dependent problems. Here, we consider applying the multigrid-reduction-in-time (MGRIT) algorithm to a voltage-driven eddy current model problem.Comment: Contribution from GAMM 2019 conferenc

Применение генетических алгоритмов в задачах проектирования бизнес-процессов на моделях Узел-Функция-Объект

В статті розглядаються питання проектування бізнес-процесів на моделях Вузол-Функція-Об’єкт. Пропонується використати імітаційне моделювання та методи випадкового пошуку, а саме, генетичні алгоритми для пошуку раціонального рішення в задачах моделювання бізнес-процесів. Виконана адаптація генетичних алгоритмів до розв’язання даних задач на моделях Вузол-Функція-Об’єкт. Розроблений опис початкових варіантів ВФО діаграм моделюємого бізнес-процесу; опис цільової функції моделі бізнес-процесу; опис операторів генетичного алгоритму для ВФО моделей

Parallel-in-Time Simulation of an Electrical Machine using MGRIT

We apply the multigrid-reduction-in-time (MGRIT) algorithm to an eddy current simulation of a two-dimensional induction machine supplied by a pulse-width-modulation signal. To resolve the fast-switching excitations, small time steps are needed, such that parallelization in time becomes highly relevant for reducing the simulation time. The MGRIT algorithm is well suited for introducing time parallelism in the simulation of electrical machines using existing application codes, as MGRIT is a non-intrusive approach that essentially uses the same time integrator as a traditional time-stepping algorithm. We investigate effects of spatial coarsening on MGRIT convergence when applied to two numerical models of an induction machine, one with linear material laws and a full nonlinear model. Parallel results demonstrate significant speedup in the simulation time compared to sequential time stepping, even for moderate numbers of processors.Comment: 14 page

Evaluation of effects caused by differentially spliced Ets-1 transcripts in fibroblasts

The transcription factor Ets-1 is known to be involved in a broad variety of cellular functions such as cell proliferation, migration, invasion, apoptosis and angiogenesis. In nearly all these reports, the full-length Ets-1 (p51) is commonly considered to be the active form and the role of the Ets-1?VII splice variant (p42) has not been addressed. Therefore, we studied the functional effects of p42 Ets-1 in comparison to p51 Ets-1 expression in a well-characterized mouse fibroblast cell line. Furthermore, the specific role of Ets-1 was evaluated using mouse fibroblasts with a reduced Ets-1 expression caused by RNAi and compared to fibroblasts with a binding inhibition of the whole ETS transcription factor family by stably overexpressing the ETS DNA binding domain as transdominant-negative mutant. Our results demonstrate that p42 Ets-1 has quite different functions and target genes compared to p51 Ets-1 (e.g. TIMP-4, MMP-3, MMP-9, MMP-13). In some cases (e.g. in cytokine expression) p42 Ets-1 is a functional transcription factor which acts in the same manner as a transdominant-negative approach

Analysing Molecular Mechanism Related to Therapy- Resistance in In-vitro Models of Ovarian Cancer

Ovarian cancer is among the most common cause of cancer death and ranks first in the number of deaths each year in the field of gynaecological malignancies. This is due to its late diagnosis and the development of chemoresistance. Platinum derivates, including cisplatinum and carboplatin in combination with paclitaxel, are the first-line chemotherapeutic agents. Platinum derivates irreversibly intercalates into the DNA and creates inter- and intra-strand DNA cross-links. During cell division, platinum-DNA-adducts block the replication machinery, inducing DNA damage and apoptosis. Nearly all patients respond to first-line chemotherapy before it comes later to recurrence of the disease. At time of recurrence, tumours are usually more aggressive, form metastasis in secondary tissues and acquire resistance to conventional chemotherapeutics. Drug resistance is a common problem in tumour therapy not only restricted to ovarian cancer. It is characterized by gene mutations, increased DNA repair, reduced drug efficacy and enhanced drug clearance and detoxification. Up to now the complex molecular mechanism of chemoresistance is not well understood. Increasing evidence points towards AKT over-expression and alteration of the PI3K/AKT/mTOR cascade as a central mechanistic reason for this resistance

Non-Coding RNAs and Resistance to Anticancer Drugs in Gastrointestinal Tumors

Non-coding RNAs are important regulators of gene expression and transcription. It is well established that impaired non-coding RNA expression especially the one of long non-coding RNAs and microRNAs is involved in a number of pathological conditions including cancer. Non-coding RNAs are responsible for the development of resistance to anticancer treatments as they regulate drug resistance-related genes, affect intracellular drug concentrations, induce alternative signaling pathways, alter drug efficiency via blocking cell cycle regulation, and DNA damage response. Furthermore, they can prevent therapeutic-induced cell death and promote epithelial–mesenchymal transition (EMT) and elicit non-cell autonomous mechanisms of resistance. In this review, we summarize the role of non-coding RNAs for different mechanisms resulting in drug resistance (e.g., drug transport, drug metabolism, cell cycle regulation, regulation of apoptotic pathways, cancer stem cells, and EMT) in the context of gastrointestinal cancers

Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay

Anti-angiogenic strategies are emerging as an important tool for the treatment of cancer and inflammatory diseases. In the present investigation we isolated several isoflavones from a tempeh (fermented soyabean) extract. The isolated isoflavones were identified as 5,7,4′-trihydroxyisoflavone (genistein), 7,4′-dihydroxyisoflavone (daidzein), 6,7,4′-trihydroxyisoflavone (factor 2), 7,8,4′-trihydroxyisoflavone (7,8,4′-TriOH) and 5,7,3′,4′-tetrahydroxyisoflavone (orobol). The effects on angiogenesis of these isoflavones were evaluated in the chicken chorioallantoic membrane assay; their capacity to inhibit vascular endothelial growth factor-induced endothelial cell proliferation and expression of the Ets 1 transcription factor, known to be implicated in the regulation of new blood vessel formation, were also investigated. We found that all isoflavones inhibited angiogenesis, albeit with different potencies. Compared with negative controls, which slightly inhibited in vivo angiogenesis by 6·30 %, genistein reduced angiogensis by 75·09 %, followed by orobol (67·96 %), factor 2 (56·77 %), daidzein (48·98 %) and 7,8,4′-TriOH (24·42 %). These compounds also inhibited endothelial cell proliferation, with orobol causing the greatest inhibition at lower concentrations. The isoflavones also inhibited Ets 1 expression, providing some insight into the molecular mechanisms of their action. Furthermore, the chemical structure of the different isoflavones suggests a structure-activity relationship. Our present findings suggest that the new isoflavones might be added to the list of low molecular mass therapeutic agents for the inhibition of angiogenesi

Characterisation of the immune-related transcriptome in resected biliary tract cancers

Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906