Determining Mechanisms of Response to Polo-like Kinase 1 Inhibition in Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The discovery of genetic alterations in some patients (~15%) has made it possible to use targeted therapies without the use of chemotherapy. To identify potential therapeutic targets in NSCLC, we systematically evaluated two cancer cell line databases with sensitivity data for a broad range of drugs. We identified polo-like kinase 1 (Plk1) as the most promising target for further investigation based on a subset of sensitive cell lines and inhibitors that were in advanced clinical development. To identify potential biomarkers of response and mechanisms of Plk1 inhibitor-induced apoptosis, we performed an integrated analysis of gene and protein expression, gene mutation, and drug sensitivity using three Plk1 inhibitors (volasertib, BI2536, GSK461364) in a large panel of NSCLC cell lines. We observed that the NSCLC cell lines have varying sensitivities to Plk1 inhibition, with a smaller subset demonstrating sensitivity to all three inhibitors. Plk1 inhibition led to increase of cells with 4N DNA content, but only sensitive cell lines underwent substantial apoptosis following Plk1 inhibition. NSCLC lines with a high epithelial-mesenchymal transition gene signature score (i.e., mesenchymal lines) were more sensitive to Plk1 inhibitors than epithelial lines (

Early Intervention in College Mathematics Courses: A Component of the STEM RRG Program Funded by the US Department of Education

Student preparedness in entry level college mathematics courses has decreased in the past. In order for students to be successful in these courses, early intervention is required. Texas A&M International University (TAMIU) has implemented an early intervention program, the Mathematics Enrichment Program (MEP), which will target freshman students entering College Algebra courses in Spring 2009. This project is part of the STEM Recruitment, Retention, and Graduation program, recently funded by the US Department of Education. This paper will highlight the components of the project, most importantly the extent of the intervention, how the project is planned, and preliminary results

The Impact of Some Mahayana Concepts on Sinhalese Buddhism.

This study attempts to examine the influence of some specific Mahayana concepts on Sinhalese Buddhism. The first chapter serves as a historical backdrop to the inflow of various non-orthodox movements into Ceylon and records the continuous impact of the Mahayana on the Theravada from the earliest times. The second chapter deals with the development of the concept of the threefold bodhi and examines in some detail the way in which the goal of Ceylon Buddhism shifted from, the Theravada arahantship to the Mahayana ideal of Buddhahood. Furthermore it suggests that this new ideal was virtually absorbed into Ceylon Buddhism, The next chapter discusses the Mahayana doctrines of trikaya, vajrakaya , sunyata, karuna and prajna as adopted by Sinhalese writers without much concern for the philosophical import which these par excellence Mahayana concepts had for Mahayanists themselves. The fourth chapter is devoted to a discussion of particular emphasis given to the cult of Maitreya which was stimulated by the Mahayana. The growth of the concept of the ten Bodhisattvas and of innumerable Buddhas is also examined. The fifth chapter treats at length the worship of Mahayana Bodhisattvas. It tends to show how certain deities underwent various metamorphoses; local gods began in time to be worshipped as Mahayana gods, and Mahayana gods had lost their identity and merged with local gods. The last chapter deals with the development of the Bodhisattva ideal of kingship in Ceylon and countries in South East Asia, It also compares the nature of this cult in these countries with that which prevailed in Ceylon. It contends that the cult first developed in Ceylon and was used as an instrument for the legitimization of the king's authority. Thus it rejects the conventional view that the fall of the Khmer empire was the result of the introduction of Sinhalese Buddhism there

Probabilistic Models for Anomaly Detection Based on Usage of Network Traffic

Recent advances in intrusions and attacks reflect vulnerabilities in computer networks. Innovative methods and tools can help attack defenses, prevent attack propagations, detect and respond to such attacks in a timely manner. Intrusion detection and prevention systems search for unauthorized use, recognize anomalous behavior, and prevent attempts to deny services.  These systems gather and analyze information from the network, identify possible breaches of the security profile, as well as misuses. We have been experimenting with methods for introducing important concepts related to intrusion detection and improving undergraduate research experiences and education. To achieve this goal, probabilistic models are introduced to students in computer, information system and network security courses. This article presents a set of probabilistic methods and statistical models for network traffic anomaly detection. It also describes some prospects and how models have ripened from theories to big data analysis applications. Keywords: Intrusion, conditional probability, network system, regression, data analysi

Sinhalese Derived Buddhism in Southwest China

Sinhalese Theravada culture is strong in Southeast Asia – Myanmar, Thailand,Laos, Cambodia and southern Vietnam. Sinhalese Theravada culture is little known inthe Mahayana dominated China. The paper examines the strong presence of Theravadain Southwest China among non-Han nationalities such as Dai, Blang, De'ang and WaAchang.The illustrated paper which traces the growth and present state of Sinhaladerived culture, is based on participant observation, texts and a case study of theXishuangbanna region.Theravada culture pervades many aspects of daily life in Southwest China,especially the Xishuangbanna region. Theravada developed in Yunnan during 7th -12thcentury, initially from Myanmar where Sinhalese Buddhism spread widely from the 11thcentury. The second wave came from Chiangmai, Thailand where again the Sinhalainfluence began in 13th century. Although the Cultural Revolution of the 1960‟sdestroyed this tradition, the local population could rapidly revive it as TheravadaBuddhism had infiltrated many aspects of their daily life. The final phase came directfrom Sri Lanka in the 1960‟s when Dai monks came to Sri Lanka to study. Many of theold temples with their Tipitaka libraries still remain, and some of the palm leafmanuscripts have been translated by the Chinese government. Enthusiasm has furtherincreased after the recently opened large Buddhist Centre in Jinghong, the capital ofXishuangbanna with a Kelaniya University trained Dai monk in charge.There is a strong imprint of Sinhalese derived Theravada culture in SouthwestChina. It is suggested that Sri Lanka could tap her potential as a dominant player in theuse of Buddhism as soft power to foster close relations for the benefit of both SouthwestChina and Sri Lanka.Key words: Southwest china, Sinhalese derived Theravada, Buddhism as soft powe

Exploring Buddhist Ethics for New Technologies

Ongoing developments in information, bio- and nano-technology are reorderingevolution, and transforming our very physical and mental bases. An examination of theliterature indicates that the dominant, Eurocentric ethical systems for these newtechnologies are derived from Christianity, Judaism or Islam (“Abrahamaic” religions)or from presumably "secular" roots. The ethical system in the Abrahamaic religions is“revealed” by “God”, but the new developments challenge some of the coreAbrahamaic ethical assumptions. Western "secular ethics" are ultimately derived fromthe idea of "humanity”, a Eurocentric concept of humans as “sacred” which probablyderives from the ideas of the Renaissance Humanists. But, in an increasingly nonhumanand “post-human” world, humanity has to be transcended in search of ethics. Asthe production, consumption and creative bases of the world increasingly shift to Asia,Asian thought could provide answers to these culture impregnated issues. A majortrans-Asian approach, Buddhism, is not revealed, and has a strong core of observationsand philosophy. Buddhist approaches with change and process as its core have directrelevance to a future where both the human and his environment are constructed andreconstructed.The paper explores the literature of the core Buddhist position on the humanbody and mind, as well as the environment he operates in, as not given or sacred butconstructed and changing.The paper concludes that an orientation from this core Buddhist perspective ofcontinuous change, no permanent self and both human and nature as constructed wouldfit better as a cultural orientation to examine and live in a future where humans andnature are continuously reinvented and reconstructed. Buddhist ethics from such aperspective may better fit the emerging world.Key words: New technologies, Ethics, Eurocentrism, Buddhism

Development, Evaluation and Analysis of a 20-Year Deferred Annuity Product

This project analyzes an annuity product that suits the needs of today's American family under moderate assumptions. It helps in the study of the pricing accuracy in a mutual life insurance company and to better understand the extent of the analysis and computations involved in developing a 20-year deferred annuity product designed for a group of 1000 people; ages ranging from 30 - 40 years and having a 5 year old child.pricing accuracy, mutual life insurance company, 20-year deferred annuity product