Sphingosine Kinase 1 Promotes Malignant Progression in Colon Cancer and Independently Predicts Survival of Patients With Colon Cancer by Competing Risk Approach in South Asian Population

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.

METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.

RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.

CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.

A practical taxonomy of methods and literature for managing uncertain spatial data in geographic information systems

Perfect information is seldom available to man or machines due to uncertainties inherent in real world problems. Uncertainties in geographic information systems (GIS) stem from either vague/ambiguous or imprecise/inaccurate/incomplete information and it is necessary for GIS to develop tools and techniques to manage these uncertainties. There is a widespread agreement in the GIS community that although GIS has the potential to support a wide range of spatial data analysis problems, this potential is often hindered by the lack of consistency and uniformity. Uncertainties come in many shapes and forms, and processing uncertain spatial data requires a practical taxonomy to aid decision makers in choosing the most suitable data modeling and analysis method. In this paper, we: (1) review important developments in handling uncertainties when working with spatial data and GIS applications; (2) propose a taxonomy of models for dealing with uncertainties in GIS; and (3) identify current challenges and future research directions in spatial data analysis and GIS for managing uncertainties.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Memory mixed with desire : a preliminary study of philosophy and literature in the works of Friedrich Nietzsche and Milan Kundera

Memory Mixed with Desire: A preliminary study of Philosophy and Literature in the works of Friedrich Nietzsche and Milan Kundera Robert Spinelli Brock University, Department of Philosophy This thesis studies intertextuality in the works of Friedrich Nietzsche and Milan Kundera through the primary themes of memory and forgetting. The thesis starts with two introductory chapters that delineate memory according to Nietzsche and Kundera respectively. From here, I move into a discussion of Nietzsche's Ubermensch as an example of the type of forgetting that Nietzsche sees as a cure for the overabundance of memory that has led to Christian morality. Next, I explore the Kunderan concept of kitsch as the polar opposite of what Nietzsche has sought in his philosophy, finishing the chapter by tying the two thinkers together in a Kunderan critique of Nietzsche. The thesis ends with a chapter devoted to the Eternal Return beginning with an exegesis of Nietzsche's idea and ending with a similar exegesis of Kundera's treatment of this thought. What I suggest in this chapter is that the Eternal Return might itself be a form of kitsch even in its attempt to revalue existence.

American Desi : representation and reproduction in diaspora /

This study explores ~ow South Asian diasporic film represents and reproduces South Asian identity in the diaspora. It commences with a review of the literature in cultural studies and post-colonial theory on identity in the diaspora. A textual analysis of three films: American Desi, Bollywood/Hollywood, and East Is East, helps frame the characteristics of South Asian diasporic film. Theoretical concepts of diaspora and identity are extended to this reading of the films. In-depth, open-ended, semi structured interviews were conducted with eight participants to test the validity of theoretical concepts through participants' own reading of American Desi. Findings indicate that while theoretical concepts of identity can be usefully applied at the level of the text, these perspectives do not always easily explain participants' interpretation of the film in relation to their everyday experiences.

South Asian Women's Identities: A Media and Personal Narrative Analysis

This study examines issues of racism and sexism through the lens of Critical Race Theory and the interaction of personal and composite narratives. Specifically, the study explores how mainstream media’s hegemonic portrayal of South Asian culture and the 2007 socalled honour killing of Aqsa Parvez contribute to post-9/11 Islamophobia. The researcher presents a personal narrative that draws upon her experiences growing up in Dubai, U.A.E., and in Ontario, Canada and critically analyzes majoritarian stories related to Parvez as well as “counter-perspectives” that challenge such views. Study findings highlight the impact of 9/11 and Parvez’s murder on the researcher’s identity formation, and how media portray Muslim women as oppressed beings who live under the yoke of patriarchy. Results also indicate that although certain articles offer a counter-perspective that challenge dominant narratives, most recent media representations of the Parvez story equate Islam with honour killings and thus foster continued Islamophobia.

Face to face with the mexicans : the domestic life, educational, social, and bussines ways statesmanship and literature, legendary and general history of the mexicana people.

UANL

LMS software study and a practical application in language and literature didactics. 'Aplicación práctica en Didáctica de la lengua y la literatura del software LMS'.

Resumen en español

Towards an interface of language and literature. 'Hacia una interfaz de la Lengua y la Literatura'.

Se analiza la conveniencia de usar textos simplificados o en su formato original para propositos pedagógicos dentro de la enseñanza de la segunda lengua. El autor considera que ambas clases de textos (simplificados u originales) pueden formar el nivel intermedio de aprendizaje de lenguas extranjeras.

AQA GCSE English language and literature. Foundation.

Recurso aprobado por AQA, ha sido escrito para apoyar a los estudiantes en la preparación del General Certificate of Secondary Education (GCSE) inglés lengua y literatura inglesas. Todas las unidades son totalmente compatibles con recursos digitales. Estructurado en diecisiete unidades: las siete primeras ayudarán con los exámenes, las unidades restantes con evaluaciones controladas. Incluye secciones de gramática, ortografía y puntuación.