Increased geranylgeranylated K-Ras contributes to antineoplastic effects of farnesyltransferase inhibitors.

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are preferentially farnesylated. Small molecule inhibitors of farnesyltransferase (FTIs) have been developed as a means to alter Ras signaling. Our initial studies with FTIs in malignant and non-malignant cells revealed FTI-induced cell cycle arrest, reduced proliferation, and increased Ras signaling. These findings led us to the hypothesis that FTI induced increased GG’d Ras. We further hypothesized that the specific effects of FTI on cell cycle and growth result from increased signal strength of GG’d Ras. Our results did show that increase in GG’d K-Ras in particular results in reduced cell viability and cell cycle arrest. Genetically engineered constructs capable of only one type of prenylation confirmed that GG’d K-Ras recapitulated the effect of FTI in 293T cells. In tumor cell lines ERK and p38 MAPK pathways were both strongly activated in response to FTI, indicating the increased activity of GG’d K-Ras results in antiproliferative signals specifically through these pathways. These results collectively indicate FTI increases active GG’d K-Ras which activates ERK and p38 MAPKs to reduced cell viability and induce cell cycle arrest in malignant cells. This is the first report that identifies increased activity of GG’d K-Ras contributes to antineoplastic effects from FTI by increasing the activity of downstream MAPKs. Our observations suggest increased GG’d K-Ras activity, rather than inhibition of farnesylated Ras, is a major source of the cytostatic and cytotoxic effects of FTI. Our data may allow for determination of which patients would benefit from FTI by excluding tumors or diseases which have strong K-Ras signaling.

Vestimentas compartidas y otros cuidados : Las formas de la generosidad en el Ms. K-III-4 (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient)

El artículo lleva a cabo una revisión de las formas de la generosidad presentes en los tres poemas que componen el Ms. K-III-4 de la Biblioteca de San Lorenzo de El Escorial (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient), para dar cuenta -a través de las referencias compartidas, los motivos comunes y las configuraciones similares- de la organización unitaria del códice y de su singularidad

Vestimentas compartidas y otros cuidados : Las formas de la generosidad en el Ms. K-III-4 (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient)

El artículo lleva a cabo una revisión de las formas de la generosidad presentes en los tres poemas que componen el Ms. K-III-4 de la Biblioteca de San Lorenzo de El Escorial (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient), para dar cuenta -a través de las referencias compartidas, los motivos comunes y las configuraciones similares- de la organización unitaria del códice y de su singularidad

Vestimentas compartidas y otros cuidados : Las formas de la generosidad en el Ms. K-III-4 (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient)

El artículo lleva a cabo una revisión de las formas de la generosidad presentes en los tres poemas que componen el Ms. K-III-4 de la Biblioteca de San Lorenzo de El Escorial (Libro de Apolonio, Vida de Santa María Egipciaca, Libre dels tres reys d'Orient), para dar cuenta -a través de las referencias compartidas, los motivos comunes y las configuraciones similares- de la organización unitaria del códice y de su singularidad

Table 1. Mean geochemical values for Baseline (pre-injection) and Monitor-1 (post-injection) samples, and the percent change between the two weighted means

The Weyburn Oil Field, Saskatchewan is the site of a large (5000 tonnes/day of CO2) CO2-EOR injection project By EnCana Corporation. Pre- and post-injection samples (Baseline and Monitor-1, respectively) of produced fluids from approximately 45 vertical wells were taken and chemically analyzed to determine changes in the fluid chemistry and isotope composition between August 2000 and March 2001. After 6 months of CO2 injection, geochemical parameters including pH, [HCO3], [Ca], [Mg], and ?13CO2(g) point to areas in which injected CO2 dissolution and reservoir carbonate mineral dissolution have occurred. Pre-injection fluid compositions suggest that the reservoir brine in the injection area may be capable of storing as much as 100 million tonnes of dissolved CO2. Modeling of water-rock reactions show that clay minerals and feldspar, although volumetrically insignificant, may be capable of acting as pH buffers, allowing injected CO2 to be stored as bicarbonate in the formation water or as newly precipitated carbonate minerals, given favorable reaction kinetics.

MRI texture analysis as means for addressing rehydration and milk diffusion of cereals

Cereals microstructure is one of the primary quality attributes of cereals. Cereals rehydration and milk diffusion depends on such microstructure and thus, the crispiness and the texture, which will make it more palatable for the final consumer. Magnetic Resonance Imaging (MRI) is a very powerful topographic tool since acquisition parameter leads to a wide possibility for identifying textures, structures and liquids mobility. It is suited for non-invasive imaging of water and fats. Rehydration and diffusion cereals processes were measured by MRI at different times and using two different kinds of milk, varying their fat level. Several images were obtained. A combination of textural analysis (based on the analysis of histograms) and segmentation methods (in order to understand the rehydration level of each variety of cereals) were performed. According to the rehydration level, no advisable clustering behavior was found. Nevertheless, some differences were noticeable between the coating, the type of milk and the variety of cereals

Improvement for detection of microcalcifications through clustering algorithms and artificial neural networks

A new method for detecting microcalcifications in regions of interest (ROIs) extracted from digitized mammograms is proposed. The top-hat transform is a technique based on mathematical morphology operations and, in this paper, is used to perform contrast enhancement of the mi-crocalcifications. To improve microcalcification detection, a novel image sub-segmentation approach based on the possibilistic fuzzy c-means algorithm is used. From the original ROIs, window-based features, such as the mean and standard deviation, were extracted; these features were used as an input vector in a classifier. The classifier is based on an artificial neural network to identify patterns belonging to microcalcifications and healthy tissue. Our results show that the proposed method is a good alternative for automatically detecting microcalcifications, because this stage is an important part of early breast cancer detection

Stress Detection by means of Stress Physiological Template

This paper describes a stress detection system based on fuzzy logic and two physiological signals: Galvanic Skin Response and Heart Rate. Instead of providing a global stress classification, this approach creates an individual stress templates, gathering the behaviour of individuals under situations with different degrees of stress. The proposed method is able to detect stress properly with a rate of 99.5%, being evaluated with a database of 80 individuals. This result improves former approaches in the literature and well-known machine learning techniques like SVM, k-NN, GMM and Linear Discriminant Analysis. Finally, the proposed method is highly suitable for real-time applications

Secure access control by means of human stress detection

This paper proposes a stress detection system based on fuzzy logic and the physiological signals heart rate and galvanic skin response. The main contribution of this method relies on the creation of a stress template, collecting the behaviour of previous signals under situations with a different level of stress in each individual. The creation of this template provides an accuracy of 99.5% in stress detection, improving the results obtained by current pattern recognition techniques like GMM, k-NN, SVM or Fisher Linear Discriminant. In addition, this system can be embedded in security systems to detect critical situations in accesses as cross-border control. Furthermore, its applications can be extended to other fields as vehicle driver state-of-mind management, medicine or sport training.