Cancer is in general not a result of an abnormality of a single gene but a consequence of changes in many genes, it is therefore of great importance to understand the roles of different oncogenic and tumor suppressor pathways in tumorigenesis. In recent years, there have been many computational models developed to study the genetic alterations of different pathways in the evolutionary process of cancer. However, most of the methods are knowledge-based enrichment analyses and inflexible to analyze user-defined pathways or gene sets. In this paper, we develop a nonparametric and data-driven approach to testing for the dynamic changes of pathways over the cancer progression. Our method is based on an expansion and refinement of the pathway being studied, followed by a graph-based multivariate test, which is very easy to implement in practice. The new test is applied to the rich Cancer Genome Atlas data to study the (epi)genetic alterations of 186 KEGG pathways in the development of serous ovarian cancer. To make use of the comprehensive data, we incorporate three data types in the analysis representing gene expression level, copy number and DNA methylation level. Our analysis suggests a list of nine pathways that are closely associated with serous ovarian cancer progression, including cell cycle, ERBB, JAK-STAT signaling and p53 signaling pathways. By pairwise tests, we found that most of the identified pathways contribute only to a particular transition step. For instance, the cell cycle and ERBB pathways play key roles in the early-stage transition, while the ECM receptor and apoptosis pathways contribute to the progression from stage III to stage IV. The proposed computational pipeline is powerful in detecting important pathways and gene sets that drive cancers at certain stage(s). It offers new insights into the understanding of molecular mechanism of cancer initiation and progression. © 2020 Elsevier Ltd
5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent, but its hepatotoxic potential poses clinical challenges, as it induces oxidative stress, inflammation, and apoptosis in liver tissue. Butein, a natural chalcone flavonoid that possesses varied biological activity, such as anticancer, anti-inflammatory, and antiplatelet effects. This study aimed to evaluate the possible protective effects of Butein against 5-FU-induced hepatotoxicity in rats. Male albino rats were divided into 4 Groups (of 7 animals each): control, 5-FU, and two Butein-pretreated Groups (50 and 100 mg/kg/day, orally for 14 days) each before a single intraperitoneal dose of 150 mg/kg 5-FU, which was injected on day 14. Serum liver enzymes (ALT and AST), cytokines
... Show MoreA three-stage learning algorithm for deep multilayer perceptron (DMLP) with effective weight initialisation based on sparse auto-encoder is proposed in this paper, which aims to overcome difficulties in training deep neural networks with limited training data in high-dimensional feature space. At the first stage, unsupervised learning is adopted using sparse auto-encoder to obtain the initial weights of the feature extraction layers of the DMLP. At the second stage, error back-propagation is used to train the DMLP by fixing the weights obtained at the first stage for its feature extraction layers. At the third stage, all the weights of the DMLP obtained at the second stage are refined by error back-propagation. Network structures an
... Show MoreThe activation and reaction energies of the C-C and C-H bonds cleavage in pyrene molecule are calculated applying the Density Functional Theory and 6-311G Gaussian basis. Different values for the energies result for the different bonds, depending on the location of the bond and the structure of the corresponding transition states. The C-C bond cleavage reactions include H atom migration, in many cases, leading to the formation of CH2 groups and H-C≡C- acetylenic fragments. The activation energy values of the C-C reactions are greater than 190.00 kcal/mol for all bonds, those for the C-H bonds are greater than 160.00 kcal/mol. The reaction energy values for the C-C bonds range between 56.497 to 191.503 kcal/mol. As for the C-H cleavage rea
... Show MoreBreast cancer (BC) is the most commonly diagnosed cancer in women. The metabolism of iron is closely regulated by hepcidin which exerts its action by interacting with a ferroportin.
The aim of the present study was to assess the alterations in the levels of some serum biomarkers that have a role in iron homeostasis (hepcidin and ferroportin) in addition to hematological parameters (hemoglobin, leukocyte and platelets count) in different stages of BC.
This study included 66 women with BC. The patients were categorized as follows : group 1 includes :22 patients with stage I disease ,group 2 includes: 22 patients with stage II disease ,and group 3 include: 22 patients with stage III disease .Group 4 includes :22 appare
... Show MoreAccelerates operating managements in the facilities contemporary business environment toward redefining processes and strategies that you need to perform tasks of guaranteeing them continue in an environment performance dominated by economic globalization and the circumstances of uncertainty attempt the creation of a new structure through multiple pages seek to improve profitability and sustainable growth in performance in a climatefocuses on the development of institutional processes, reduce costs and achieve customer satisfaction to meet their demands and expectations are constantly changing. The research was presented structural matrix performance combines methodology Alsigma in order to improve customer satisfaction significantly bet
... Show MoreTo ensure that a software/hardware product is of sufficient quality and functionality, it is essential to conduct thorough testing and evaluations of the numerous individual software components that make up the application. Many different approaches exist for testing software, including combinatorial testing and covering arrays. Because of the difficulty of dealing with difficulties like a two-way combinatorial explosion, this brings up yet another problem: time. Using client-server architectures, this research introduces a parallel implementation of the TWGH algorithm. Many studies have been conducted to demonstrate the efficiency of this technique. The findings of this experiment were used to determine the increase in speed and co
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