17 research outputs found
Έλεγχος μίας μονάδας κατεργασίας με κυκλικά περιστρεφόμενη τράπεζα
Στην παρούσα διπλωματική εργασία θα παρουσιαστεί μία βιομηχανική κυκλικά περιστρεφόμενη τράπεζα της βιβλιογραφίας παρουσία σφαλμάτων. Θα παρουσιαστεί μία δομοστοιχειωτή μοντελοποίηση των υποσυστημάτων με χρήση πεπερασμένων ντετερμινιστικών αυτόματων και πιο συγκεκριμένα χρησιμοποιώντας τη μεθοδολογία Ramadge Wonham. Αρχικά θα παρουσιαστούν οι επιθυμητές προδιαγραφές λειτουργείας και ασφάλειας σε μορφή απλών κανόνων. Στη συνέχεια, οι επιθυμητές προδιαγραφές θα παρουσιαστούν στη μορφή κανονικών γλωσσών. Θα υλοποιηθούν οι επιθυμητές γλώσσες ως πεπερασμένα ντετερμινιστικά αυτόματα, επόπτες, και θα σχεδιαστή με δομοστοιχειωτή αρχιτεκτονική ελέγχου.In this diploma thesis, an industrial circular table of the literature will be presented in the presence of fault. A modular modeling of subsystems using finite deterministic automata and more specifically using the Ramadge Wonham framework will be presented. Initially, the desired operation and safety specifications will be presented in the form of simple rules. Next, the desired specifications will be presented in the form of regular languages. The desired languages will be implemented as finite deterministic automata, supervisors, and will be designed with a modular control architecture
Modular Supervisory Control for the Coordination of a Manufacturing Cell with Observable Faults
In the present paper, a manufacturing cell in the presence of faults, coming from the devices of the process, is considered. The modular modeling of the subsystems of the cell is accomplished using of appropriate finite deterministic automata. The desired functionality of the cell as well as appropriate safety specifications are formulated as eleven desired languages. The desired languages are expressed as regular expressions in analytic forms. The languages are realized in the form of appropriate general type supervisor forms. Using these forms, a modular supervisory design scheme is accomplished providing satisfactory performance in the presence of faults as well guaranteeing the safety requirements. The aim of the present supervisor control scheme is to achieve tolerance of basic characteristics of the process coordination to upper-level faults, despite the presence of low-level faults in the devices of the process. The complexity of the supervisor scheme is computed
DNA Damage Repair: Predictor of Platinum Efficacy in Ovarian Cancer?
Ovarian cancer (OC) is the seventh most common type of cancer in women worldwide. Treatment for OC usually involves a combination of surgery and chemotherapy with carboplatin and paclitaxel. Platinum-based agents exert their cytotoxic action through development of DNA damage, including the formation of intra- and inter-strand cross-links, as well as single-nucleotide damage of guanine. Although these agents are highly efficient, intrinsic and acquired resistance during treatment are relatively common and remain a major challenge for platinum-based therapy. There is strong evidence to show that the functionality of various DNA repair pathways significantly impacts tumor response to treatment. Various DNA repair molecular components were found deregulated in ovarian cancer, including molecules involved in homologous recombination repair (HRR), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end-joining (NHEJ), and base excision repair (BER), which can be possibly exploited as novel therapeutic targets and sensitive/effective biomarkers. This review attempts to summarize published data on this subject and thus help in the design of new mechanistic studies to better understand the involvement of the DNA repair in the platinum drugs resistance, as well as to suggest new therapeutic perspectives and potential targets
DNA Damage Repair: Predictor of Platinum Efficacy in Ovarian Cancer?
Ovarian cancer (OC) is the seventh most common type of cancer in women
worldwide. Treatment for OC usually involves a combination of surgery
and chemotherapy with carboplatin and paclitaxel. Platinum-based agents
exert their cytotoxic action through development of DNA damage,
including the formation of intra- and inter-strand cross-links, as well
as single-nucleotide damage of guanine. Although these agents are highly
efficient, intrinsic and acquired resistance during treatment are
relatively common and remain a major challenge for platinum-based
therapy. There is strong evidence to show that the functionality of
various DNA repair pathways significantly impacts tumor response to
treatment. Various DNA repair molecular components were found
deregulated in ovarian cancer, including molecules involved in
homologous recombination repair (HRR), nucleotide excision repair (NER),
mismatch repair (MMR), non-homologous end-joining (NHEJ), and base
excision repair (BER), which can be possibly exploited as novel
therapeutic targets and sensitive/effective biomarkers. This review
attempts to summarize published data on this subject and thus help in
the design of new mechanistic studies to better understand the
involvement of the DNA repair in the platinum drugs resistance, as well
as to suggest new therapeutic perspectives and potential targets
Inflammation and Immunity Gene Expression Patterns and Machine Learning Approaches in Association with Response to Immune-Checkpoint Inhibitors-Based Treatments in Clear-Cell Renal Carcinoma
Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Despite the rapid evolution of targeted therapies, immunotherapy with checkpoint inhibition (ICI) as well as combination therapies, the cure of metastatic ccRCC (mccRCC) is infrequent, while the optimal use of the various novel agents has not been fully clarified. With the different treatment options, there is an essential need to identify biomarkers to predict therapeutic efficacy and thus optimize therapeutic approaches. This study seeks to explore the diversity in mRNA expression profiles of inflammation and immunity-related circulating genes for the development of biomarkers that could predict the effectiveness of immunotherapy-based treatments using ICIs for individuals with mccRCC. Gene mRNA expression was tested by the RT2 profiler PCR Array on a human cancer inflammation and immunity crosstalk kit and analyzed for differential gene expression along with a machine learning approach for sample classification. A number of mRNAs were found to be differentially expressed in mccRCC with a clinical benefit from treatment compared to those who progressed. Our results indicate that gene expression can classify these samples with high accuracy and specificity
A Polymerase Chain Reaction-Based Method to Detect Gene-Specific Adducts Induced by Anticancer Drugs. Clinical Application in Multiple Myeloma.
Development and validation of a PCR-based assay for the selection of patients more likely to benefit from therapeutic treatment with alkylating drugs.
Previous studies have indicated that the levels of DNA damage induced in peripheral blood mononuclear cells by the alkylating drugs melphalan, cisplatin and carboplatin can serve as useful biomarkers predictive of the therapeutic response of cancer patients to these drugs
Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.
Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR) pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780) and one resistant (A2780/C30) to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs) from OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05). Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03). Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05). We conclude that perturbations of DNA repair pathways as measured in PBMCs from OC patients correlate with the drug sensitivity of these cells and reflect the individualized response to platinum-based chemotherapy
A Polymerase Chain Reaction-Based Method to Detect Gene-Specific Adducts Induced by Anticancer Drugs. Clinical Application in Multiple Myeloma.
Aberrant DNA Damage Response Pathways May Predict the Outcome of Platinum Chemotherapy in Ovarian Cancer
Ovarian carcinoma (OC) is the most lethal gynecological malignancy.
Despite the advances in the treatment of OC with combinatorial regimens,
including surgery and platinum-based chemotherapy, patients generally
exhibit poor prognosis due to high chemotherapy resistance. Herein, we
tested the hypothesis that DNA damage response (DDR) pathways are
involved in resistance of OC patients to platinum chemotherapy. Selected
DDR signals were evaluated in two human ovarian carcinoma cell lines,
one sensitive (A2780) and one resistant (A2780/C30) to platinum
treatment as well as in peripheral blood mononuclear cells (PBMCs) from
OC patients, sensitive (n = 7) or resistant (n = 4) to subsequent
chemotherapy. PBMCs from healthy volunteers (n = 9) were studied in
parallel. DNA damage was evaluated by immunofluorescence gamma H2AX
staining and comet assay. Higher levels of intrinsic DNA damage were
found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA
damage levels were significantly higher in OC patients relative to
healthy volunteers, as well as in platinum-sensitive patients relative
to platinum-resistant ones (all P < 0.05). Following carboplatin
treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30
cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA
repair efficiency was significantly higher in healthy volunteers than in
platinum-resistant patients and lowest in platinum-sensitive ones
(t(1/2) for loss of gamma H2AX foci: 2.7 +/- 0.5h, 8.8 +/- 1.9h and 15.4
+/- 3.2h, respectively; using comet assay, t(1/2) of platinum-induced
damage repair: 4.8 +/- 1.4h, 12.9 +/- 1.9h and 21.4 +/- 2.6h,
respectively; all P < 0.03). Additionally, the carboplatin-induced
apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs,
apoptosis rates were inversely correlated with DNA repair efficiencies
of these cells, being significantly higher in platinum-sensitive than in
platinum-resistant patients and lowest in healthy volunteers (all P <
0.05). We conclude that perturbations of DNA repair pathways as measured
in PBMCs from OC patients correlate with the drug sensitivity of these
cells and reflect the individualized response to platinum-based
chemotherapy