Epigenetic Regulation of Cancer-Associated Genes in Ovarian Cancer

The involvement of epigenetic aberrations in the development and progression of tumors is now well established. However, most studies have focused on the epigenetic inactivation of tumor suppressor genes during tumorigenesis and little is known about the epigenetic activation of cancer-associated genes, except for the DNA hypomethylation of some genes. Recently, we reported that the overexpression of cancer-promoting genes in ovarian cancer is associated with the loss of repressive histone modifications. This discovery suggested that epigenetic derepression may contribute to ovarian tumorigenesis by constituting a possible mechanism for the overexpression of oncogenes or cancer-promoting genes in tumors. The emerging importance of epigenetic aberrations in tumor initiation and in the regulation of cancer-initiating cells, suggests that epigenetically regulated genes may be promising therapeutic targets and biomarkers. Given that the current challenges in ovarian cancer include the identification of biomarkers for early cancer detection and the discovery of novel therapeutic targets for patients with recurrent malignancies undergoing chemotherapy, understanding the epigenetic changes that occur in ovarian cancer is crucial. This review looks at epigenetic mechanisms involved in the regulation of cancer-associated genes, including the contribution of epigenetic derepression to the activation of cancer-associated genes in ovarian cancer. In addition, possible epigenetic therapies targeting epigenetically dysregulated genes are discussed. A better understanding of the epigenetic changes in ovarian cancer will contribute to the improvement of patient outcomes

Development of Double-Sided Interior Permanent Magnet Flat Linear Brushless Motor and Its Control Using Linear Optical Potentiometer

A new 6/4 double-sided interior permanent-magnet (IPM) flat linear brushless motor (IPM-FLBM) and novel optical potentiometer mechanism for a linear motion-control system are presented in this dissertation. For this purpose, new detent-force-minimization methodologies for the IPMFLBM are studied on the basis of the superposition principle. The end-effect force is reduced by a new two-dimensional optimization using the step-shaped end frames. The cogging force is minimized through a destructive interference using the slot-phase shift between the upper and lower stators. A base model prototype with the detent force of only 1.5% of the maximum thrust force is developed using the electrical solid steel. Analytic modeling techniques of the base model prototype with slot-phase shift and alternate teeth windings are investigated. A variable winding function is newly developed to evaluate the inductances of the salient motor with the alternate teeth windings. The steady-state thrust force is modeled for this linear brushless AC (BLAC) motor. Their validities are demonstrated experimentally. The electromagnetic and steady-state performance analyses of a new prototype using a soft magnetic composite (SMC) material are also studied using a simplified nonlinear magnetic equivalent circuit (MEC) analysis. Its iron and copper losses are investigated in terms of the thermal limitation. The feasibility of the IPM-FLBM using the SMC material is demonstrated through the comparisons of the average steady-state thrust and ripple forces for these two prototype linear motors. A novel low-cost high-precision absolute displacement-sensing mechanism using optoelectronic components is developed. The working principle that is based on the change of the optical power that is reflected off the monotone-colored pattern track from a light emitting diode (LED) to a red-green-blue (RGB) photo diode (PD) is presented. The performance of the proposed optical potentiometer (OP) mechanism is verified by the bandwidth (BW) of 4.42 kHz and nonlinearity of 2.8% are achieved. A novel low-ripple 12-step current control scheme using a single current sensing resistor is developed using the six Hall-effect sensors for the force control of the IPMFLBM. Its performances are experimentally verified and compared with a conventional field-oriented control (FOC) scheme. In the end, the position-control loop, which includes the 12-step current control loop, double-sided IPM-FLBM, and linear optical potentiometer (LOP), is designed using a proportional controller with a lead compensator. The performances of the linear motion-control system are demonstrated through the various experiments in the time and frequency domains

Response of dual-layered structures subjected to shock pressure wave

The response of coated, metallic structures subjected to shock pressure waves is studied. The coating is either an elastic material or nearly incompressible rubber of variable stiffness separating the structure from an air or water medium. The stress, nodal velocity, and internal energy of the coated structure are compared to a system without a coating (homogeneous system) to examine the effect of various coating types and configurations on the response of the structure to shock conditions. The results show that a mismatch of impedance, pc0, between the coating and structure governs the degree of energy exchange between the coating and structure at the interface. The impedance mismatch between the structure and a rubber coating at the threshold value is termed the critical difference. If the impedance mismatch exceeds the critical difference, the dynamic response will be more adverse. A softer coating generally has a smaller impedance and tends to concentrate stress wave energy in the underlying structureDefense Nuclear Agency, Alexandria, VAhttp://archive.org/details/responseofdualla00brasMIPR No. 94-573N

Overexpression of Cancer-Associated Genes via Epigenetic Derepression Mechanisms in Gynecologic Cancer

Like other cancers, most gynecologic cancers are caused by aberrant expression of cancer-related genes. Epigenetics is one of the most important gene expression mechanisms, which contribute to cancer development and progression by regulating cancer-related genes. Since the discovery of differential gene expression patterns in cancer cells when compared with normal cells, extensive efforts have been made to explore the origins of abnormal gene expression in cancer. Epigenetics, the study of inheritable changes in gene expression that do not alter DNA sequence is a key area of this research. DNA methylation and histone modification are well-known epigenetic mechanisms, while microRNAs and alternative splicing have recently been identified as important regulators of epigenetic mechanisms. These mechanisms not only affect specific target gene expression but also regulate the functioning of other epigenetic mechanisms. Moreover, these diverse epigenetic regulations occur simultaneously. Epigenetic regulation of gene expression is extraordinarily complicated and all epigenetic mechanisms to be studied at once to determine the exact gene regulation mechanisms. Traditionally, the contribution of epigenetics to cancer is thought to be mediated through the inactivation of tumor suppressor genes expression. But recently, it is arising that some oncogenes or cancer-promoting genes (CPGs) are overexpressed in diverse type of cancers through epigenetic derepression mechanism, such as DNA and histone demethylation. Epigenetic derepression arises from diverse epigenetic changes, and all of these mechanisms actively interact with each other to increase oncogenes or CPGs expression in cancer cell. Oncogenes or CPGs overexpressed through epigenetic derepression can initiate cancer development, and accumulation of these abnormal epigenetic changes makes cancer more aggressive and treatment resistance. This review discusses epigenetic mechanisms involved in the overexpression of oncogenes or CPGs via epigenetic derepression in gynecologic cancers. Therefore, improved understanding of these epigenetic mechanisms will provide new targets for gynecologic cancer treatment

Semi-automatic Filtering of Translation Errors in Triangle Corpus

The meaning that Justice has after a conflict in a society might vary regarding the political development and cultural and shared values of a certain society. Rawls, in his Theory of Justice gives his idea of what justice is and presents two principles of justice that he argues are required to live in a good society: a first principle that secures equal rights and liberties for all individuals and a second egalitarian principle that restrains the consequences of economic inequalities within societies. He also introduces the concept of “overlapping consensus” which I will use regarding the idea of Reconciliation, at the end of this paper. In the cases presented in this paper (i.e. Argentina and South Africa), essential human rights were violated, therefore wrongdoers made the society unjust. The aim of this thesis is to elucidate the conditions that are necessary to re-establish justice when a society goes through a conflict. I will introduce some ideas concerning that issue: ideas of retribution, reparation and reconciliation. These are seen as different paths for several countries when trying to tackle to the matter of achieving justice. In my view, this question can be answered appealing first to an intuitive conception of moral justice that may exist at an individual and collective level, as well. The ethical dilemmas both levels have are in relation to the harm done, punishments and how to balance them, limiting, for instance, the punishment in order to accomplish a just and a better society. I will also present how shared values can result from a process of reconciliation, which is considered as the ideal alternative to achieve justice. However, when the equilibrium between members of a community is broken, some people claim that punishment can restore that lost equilibrium that existed before in the community. Nevertheless, peace, reconciliation and justice cannot be constructed under the basis of silence. One way to keep memory alive is to let survivors, for instance, narrate what they have lived through; telling stories also creates a new space to share with others their experiences, revealing their fears and emotions. Regarding this theme, I will present the NUNCA MAS (Never Again) report, which is fundamental as it gives some testimonies, facts and proposals that will help to reach a consensus and therefore, future reconciliations. Why is important to achieve justice? Because then members of a certain community will be able to interact in the present with common shared values and thus, deal with the past. Not to consider reconciliation as one important step to achieve justice, and only think in terms of punishment, instead of giving way to peace and justice, could perhaps promote the possibility of further conflicts. To consider both punishment and reconciliation might just be one possible blueprint in the long and difficult way of searching for a just society