A Mechanistic Investigation of Insulin Receptor Substrate 2 Function in Breast Cancer Progression

The advancement of cancer treatment depends on understanding the biological processes that contribute to disease progression. The spread of tumor cells from the primary site to distant organs is the biggest obstacle to efficacious treatment. The insulin receptor substrate (IRS) proteins IRS1 and IRS2 are cytoplasmic adaptor proteins that organize signaling events downstream of the Insulin receptor (IR) and the Insulin-like growth factor receptor 1 (IGF1R). Both of these receptors have been implicated in cancer progression. The IRS proteins share a significant level of homology and are both capable of recruiting and activating phosphatidylinositol-3 kinase (PI3K). Despite these similarities, signaling through IRS1 and IRS2 leads to distinct tumor cell outcomes in vitro and in vivo. In vitro, IRS1 regulates cell proliferation and growth and IRS2 regulates metabolism, survival and invasion. In vivo, Irs2 is a positive regulator of tumor metastasis, whereas Irs1 does not promote metastasis. The major objective of this thesis work was to further the understanding of the mechanism by which IRS2 signaling regulates tumor progression. To investigate how IRS-1 and IRS-2 regulate distinct tumor cell outcomes, I examined the involvement of the microtubule cytoskeleton in IRS-dependent signaling. I determined that IRS2-mediated AKT activation is dependent upon an intact microtubule cytoskeleton, whereas IRS1-mediated AKT signaling occurs independently of microtubules. As a result, drugs that disrupt microtubules promote apoptosis in cells that signal through IRS2, but cells that signal through IRS1 are resistant to the effects of microtubule disruption. However, AKT inhibition sensitizes IRS1-dependent cells to apoptotic cell death upon microtubule disruption. From a clinical perspective, my studies identify IRS2 as a potential biomarker for the response of breast cancer patients to anti-microtubule drug therapy. To investigate further the mechanism of IRS2 contributions to tumor progression, I employed a mutagenesis approach to identify structural requirements of IRS2 for its function. I established that the ability of IRS2 to activate PI3K is necessary for its regulation of both invasion and tumor initiating cell (TIC) self-renewal. I also identified two independent regions within the IRS2 C-terminus that are required for invasion and self-renewal, respectively. Characterization of the invasion-promoting region identified BMP2-induced protein kinase (BMP2K) as an interacting protein. Suppression of BMP2K expression in mammary tumor cells disrupts IRS2-mediated tumor cell invasion. Taken together, my work advances the understanding of how IRS2 contributes to breast cancer progression and provides a molecular understanding for the development of novel approaches for the treatment of breast cancer and other malignancies that rely upon IRS2

The conformal transformation's controversy: what are we missing?

An alternative interpretation of the conformal transformations of the metric is discussed according to which the latter can be viewed as a mapping among Riemannian and Weyl-integrable spaces. A novel aspect of the conformal transformation's issue is then revealed: these transformations relate complementary geometrical pictures of a same physical reality, so that, the question about which is the physical conformal frame, does not arise. In addition, arguments are given which point out that, unless a clear statement of what is understood by "equivalence of frames" is made, the issue is a semantic one. For definiteness, an intuitively "natural" statement of conformal equivalence is given, which is associated with conformal invariance of the field equations. Under this particular reading, equivalence can take place only if the metric is defined up to a conformal equivalence class. A concrete example of a conformal-invariant theory of gravity is then explored. Since Brans-Dicke theory is not conformally invariant, then the Jordan's and Einstein's frames of the theory are not equivalent. Otherwise, in view of the alternative approach proposed here, these frames represent complementary geometrical descriptions of a same phenomenon. The different points of view existing in the literature are critically scrutinized on the light of the new arguments.Comment: 17 pages, no figures. version accepted by General Relativity and Gravitation journa

The role of social and emotional competence on risk behaviors in adolescence

The purpose of this study was to investigate the relation between social and emotional competence and substance use in adolescence, including tobacco, alcohol and illicit drugs. The sample included 3,494 students, mean age 15 years old, in the 8th and 10th grades of the public school system from Portugal. Data were collected using the Health Behavior in School-aged Children (HBSC) survey. For the purpose of this study, the questionnaire included questions about social and emotional competence and risk behavior, specifically past 30-day tobacco use, drunkenness, and illicit drugs use. Results showed that adolescent social and emotional competence was negatively related to substance use. All social-emotional competence subscales were significantly associated with illicit drug use. In addition empathy, cooperation and communication, and goals and aspirations subscales, were significantly associated with tobacco use. Results demonstrate the potential importance of social and emotional competence in levels of substance use among Portuguese adolescents, and may be used to inform the development of Portuguese substance use prevention programspeer-reviewe

Embedded system for individual recognition based on ECG biometrics

Biometric recognition is emerging has an alternative solution for applications where the privacy of the information is crucial. This paper presents an embedded biometric recognition system based on the Electrocardiographic signals (ECG) for individual identification and authentication. The proposed system implements a real-time state-of-the-art recognition algorithm, which extracts information from the frequency domain. The system is based on a ARM Cortex 4. Preliminary results show that embedded platforms are a promising path for the implementation of ECG-based applications in real-world scenario

Embedded System for ECG Biometrics

Comunication in Internationa Conference with Peer Review First International Congress on Cardiovasular Technologies - CARDIOTECHNIX, Vilamoura, Portugal, 2013Biometric recognition has recently emerged as part of applications where the privacy of the information is crucial, as in the health care field. This paper presents an embedded system for individual recognition based on Electrocardiographic (ECG) biometrics. The proposed system implements a real-time state-of-the-art recognition algorithm, which extracts information from the frequency domain, on an architecture based ARM Cortex 4. The system is designed to be free-standing, non-intrusive and easy to use on different environments. Preliminary results show the successful on-the-fly implementation in a embedded platform, enabling its usage on a myriad of operations

Early cost accounting practices and private ownership: The Silk Factory Company of Portugal, 1745-1747

This paper contributes to an understanding of the historical development of management accounting by presenting an example of cost accounting practice in Portugal in the first half of the 18th century. It explores the integration of cost and financial accounting systems within a double- entry accounting framework by the Silk Factory Company (SFC) between 1745 and 1747. The SFC\u27s methods of product costing, pricing, inventory accounting, expense recognition, and production control are reviewed within the political, economic, and social context of Portugal at the time. The SFC is revealed to have used job-order product costing, with allocations of overhead costs, allowances for wastage and shrinkage, and elements of rudimentary standard costing. Our findings provide evidence of the existence of cost accounting and management control techniques at a private rather than a state-owned enterprise prior to the industrial revolution

Development of a Body for a Pneumatic Crawler for Radioactive Waste Pipelines

The goal of this thesis was to develop a body for a crawler robot to navigate DOE Hanford Site transfer pipelines in a timely fashion. Previous work in pipe crawlers was analyzed and different configurations were studied by this author in order to design a suitable device. Tests were done in CAD to verify the device would fit and be able to travel within the confines of the pipelines’3” inner diameter and 90° elbows with 4.25”radii. Pipelines in Hanford can transition into 2” pipe and this was also taken into consideration when selecting the dimensions for the device. Manufacturing methods and materials were selected in order to ensure minimal cost and time for manufacture. The manufactured device was tested for speed in straight sections and elbows, pulling force, and adaptability to changes in pipe dimension from 3” to 2”. Modifications were made based on test results

Caustics, catastrophes, and symmetries in curved beams

In this paper, a meaningful classification of optical caustic beams in two dimensions is presented. It is demonstrated that the phase symmetry of the beam's angular spectrum governs the optical catastrophe, which describes the wave properties of ray singularities, for cusp (symmetric phase) and fold (antisymmetric phase) caustics. In contrast to the established idea, the caustic classification arises from the phase symmetry rather than from the phase power, thus breaking the commonly accepted concept that fold and cusp caustics are related to the Airy and Pearcey functions, respectively. Nevertheless, the role played by the spectral phase power is to control the degree of caustic curvature. These findings provide straightforward engineering of caustic beams by addressing the spectral phase into a spatial light modulator or glass plate.Fil: Vaveliuk, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Opticas. Provincia de Buenos Aires. Gobernación. Comision de Invest.científicas. Centro de Investigaciones Opticas. Universidad Nacional de la Plata. Centro de Investigaciones Opticas; ArgentinaFil: Lencina, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Opticas. Provincia de Buenos Aires. Gobernación. Comision de Invest.científicas. Centro de Investigaciones Opticas. Universidad Nacional de la Plata. Centro de Investigaciones Opticas; ArgentinaFil: Rodrigo, Jose A.. Universidad Complutense de Madrid; EspañaFil: Martinez Matos, Oscar. Universidad Complutense de Madrid; Españ

RUNX1 and breast cancer

News on: Runx1 stabilizes the mammary epithelial cell phenotype and prevents epithelial to mesenchymal transition, by Hong et al. Oncotarget. 2017; 8:17610-27. doi: 10.18632/oncotarget.15381