Development of a multi-gene PCR assay for the prediction of the response to hormone therapy in breast cancer

Deux tiers des cancers du sein expriment des récepteurs hormonaux ostrogéniques (tumeur ER-positive) et la croissance de ces tumeurs est stimulée par l’estrogène. Des traitements adjuvant avec des anti-estrogènes, tel que le Tamoxifen et les Inhibiteurs de l’Aromatase peuvent améliorer la survie des patientes atteinte de cancer du sein. Toutefois la thérapie hormonale n’est pas efficace dans toutes les tumeurs mammaires ER-positives. Les tumeurs peuvent présenter avec une résistance intrinsèque ou acquise au Tamoxifen. Présentement, c’est impossible de prédire quelle patiente va bénéficier ou non du Tamoxifen. Des études préliminaires du laboratoire de Dr. Mader, ont identifié le niveau d’expression de 20 gènes, qui peuvent prédire la réponse thérapeutique au Tamoxifen (survie sans récidive). Ces marqueurs, identifié en utilisant une analyse bioinformatique de bases de données publiques de profils d’expression des gènes, sont capables de discriminer quelles patientes vont mieux répondre au Tamoxifen. Le but principal de cette étude est de développer un outil de PCR qui peut évaluer le niveau d’expression de ces 20 gènes prédictif et de tester cette signature de 20 gènes dans une étude rétrospective, en utilisant des tumeurs de cancer du sein en bloc de paraffine, de patients avec une histoire médicale connue. Cet outil aurait donc un impact direct dans la pratique clinique. Des traitements futiles pourraient être éviter et l’indentification de tumeurs ER+ avec peu de chance de répondre à un traitement anti-estrogène amélioré. En conséquence, de la recherche plus appropriée pour les tumeurs résistantes au Tamoxifen, pourront se faire.

Localization and function of the endocannabinoid system throughout the retinogeniculate pathway of vervet monkeys

Le système endocannabinoïde (eCB) est présent dans le système nerveux central (SNC) de mammifères, incluant la rétine, et est responsable de la régulation de nombreux processus physiologiques. Bien que la présence du récepteur cannabinoïde de type 1 (CB1R) a bien été documenté dans la rétine de rongeurs et primates, il y a encore une controverse quant à la présence du récepteur cannabinoïde de type 2 (CB2R) au niveau du SNC. En utilisant la microscopie confocale, nous sommes les premiers à signaler les patrons d’expression du CB2R dans la rétine de singe. Nos résultats démontrent que le CB2R est exprimé exclusivement dans les cellules de Müller de la rétine du singe. En outre, nous avons comparé les différents patrons d’expression du système eCB dans la rétine de la souris, du toupaye, ainsi que du singe vervet et macaque. Nous rapportons que les distributions de CB1R, FAAH (fatty acid amid hydrolase), MAGL (monoacylglycerol lipase) et DAGLα (diacylglycerol lipase alpha) sont hautement conservées parmi ces espèces alors que CB2R et NAPE-PLD (N-acyl phosphatidylethanolamine phospholipase D) présentent différents profils d'expression. CB2R n'a pas été détecté dans les cellules neuronales de la rétine des primates. L’immunoréactivité de NAPE-PLD est présente dans les couches de la rétine de souris et toupayes, mais a été limitée à la couche des photorécepteurs des singes vervet et macaque. Pour étudier les corrélats neuronaux et le rôle de la signalisation du système eCB dans la rétine, nous avons établi un protocole standard pour l'électrorétinographie (ERG), puis enregistré la réponse ERG de la rétine après le blocage des récepteurs avec des antagonistes spécifiques pour CB1R (AM251) et CB2R (AM630). Comparé au témoin, dans des conditions photopiques, et à certaines intensités faibles du stimulus, le blocage de CB1R diminue l'amplitude de l'onde-b, alors qu’à des intensités plus élevées, le blocage de CB2R augmente l'amplitude des deux-ondes a et b. De plus, le blocage des récepteurs cannabinoïdes provoque une augmentation de la latence des deux ondes a et b. Dans des conditions d’adaptation à l'obscurité, le blocage de CB1R et CB2R réduit l’amplitudes de l'onde a seulement à des intensités plus élevées et réduit l’onde b à intensités plus faibles. Des augmentations significatives de latence ont été observées dans les deux cas. Ces résultats indiquent que les récepteurs CB1 et CB2 chez les primates non humains sont impliqués dans la fonction rétinienne conditions photopiques. En outre, nous avons évalué le profil d'expression du CB1R, de FAAH et de NAPE-PLD au-delà de la rétine dans le corps géniculé latéral des singes et nous rapportons pour la première fois que CB1R et FAAH sont exprimés davantage dans les couches magnocellulaires. La NAPE-PLD a été localisée à travers les couches magno- et parvocellulaires. Aucune de ces composantes n’est exprimée dans les couches koniocellulaires. Ces résultats nous aident à mieux comprendre les effets des cannabinoïdes sur le système visuel qui pourraient nous mener à trouver éventuellement de nouvelles cibles thérapeutiques.

Influence of Processing Variables on Protein Quality and Frozen Storage Stability of Two Commercially Important Species of Squid (Loligo duvaucelii and Doryteuthis sibogae )

Cephalopods are utilized as an important food item in various countries because of its delicacy as raw consumed food. Mainly sepia and loligo are consumed raw by Japanese and Russians. The freshness of the products is very important when the product is consumed raw. The major species that dominate our squid catch are Loligo duvaucelii and Doryteuthis sibogae. There is a noticeable difference in the quality of both the species. The needle squid (Doryteuthis sibogae ) contributes about 35% of the total squid landing. Due to the fast deterioration , a major portion of the needle squid, which is caught during the first few hauls, is thrown back to sea. The catch in the last hauls only are taken to the landing centers. At present the needle squid is processed as blanched rings and the desired quality is not obtained if it is processed as whole, whole cleaned or as tubes. In this study an attempt is made to investigate the biochemical characteristics in both the species of squid in relation to their quality and, the process control measures to be adopted. The effect of various treatments on their quality and the changes in proteolytic and lysosomal enzymes under various processing conditions are also studied in detail.Thus this study can provide the seafood industry with relevant suggestions and solutions for effective utilization of both the species of squid with emphasis on needle squid.

Ecotoxic Metal Records and its Degree of Geochemical Symphony in the Niche of Cochin Estuarine System- A Theraptic Perspective

The heavy metal contamination in the environment may lead to circumstances like bioaccumulation and inturn biomagnification. Hence cheaper and effective technologies are needed to protect the precious natural resources and biological lives. A suitable technique is the one which meets the technical and environmental criteria for dealing with a particular remediation problem and should be site-specific due to spatial and climatic variations and it may not economically feasible everywhere. The search for newer technologies for the environmental therapy, involving the removal of toxic metals from wastewaters has directed attention to adsorption, based on metal binding capacities of various adsorbent materials. Therefore, the present study aim to identify and evaluate the most current mathematical formulations describing sorption processes. Although vast amount of research has been carried out in the area of metal removal by adsorption process using activated carbon few specific research data are available in different scientific institutions. The present work highlights the seasonal and spatial variations in the distribution of some selected heavy metals among various geochemical phases of Cochin Estuarine system and also looked into an environmental theraptic/remedial approach by adsorption technique using activated charcoal and chitosan, to reduce and thereby controlling metallic pollution. The thesis has been addressed in seven chapters with further subdivisions. The first chapter is introductory, stating the necessity of reducing or preventing water pollution due to the hazardous impact on environment and health of living organisms and drawing it from a careful review of literature relevant to the present study. It provides a constricted description about the study area, geology, and general hydrology and also bears the major objectives and scope of the present study.

Growth And Characterization Of Te-Se System And Some Tei.I.Urioes

The physical properties of solid matter are basically influenced by the existence of lattice defects; as a result the study of crystal defects has assumed a central position in solid state physics and materials science. The study of dislocations ixa single crystals can yield a great deal of information on the mechanical properties of materials. In order to secure a full understanding of the processes taking place in semiconducting materials, it is important to investigate the microhardness of these materials-—the most reliable method of determining the fine structure of crystals, the revelation of micro—inhomogenities in the distribution of impurities, the effect of dislocation density on the mechanical properties of crystals etc. Basically electrical conductivity in single crystals is a defect controlled phenomenon and hence detailed investigation of the electrical properties of these materials is one of the best available methods for the study of defects in them. In the present thesis a series of detailed studies carried out in Te—Se system, Bi2Te3 and In2Te3 crystals using surface topographical, dislocation and microindentation analysis as well as electrical measurements are presented

Ecotoxicological Assessment of Antifouling Biocides in the Sediments of Cochin Estuarine System

The pollutants discharged into the estuaries are originate from two main sources-industrial and sewage. The former may be toxic which includes heavy metals, residues from antifouling paint particles and pesticides, while large discharges of sewage will contain pathogenic microorganisms. The contamination is enough to destroy the amenities of the waterfront, and the toxic substances may completely destroy the marine life and damage to birds, fishes and other marine organisms. Antifouling biocides are a type of chemical used in marine structure to prevent biofouling. These antifouling biocides gradually leach from the ships and other marine structures into water and finally settled in sediments. Once a saturation adsorption is reached they desorbed into overlying water and causes threat to marine organisms. Previous reports explained the imposex and shell thickening in bivalves owing to the effect of biocides. So bivalves are used as indicator organisms to understand the status of pollution. The nervous system is one of the best body part to understand the effect of toxicant. Acetylcholine esterase enzyme which is the main neurotransmitter in nervous was used to understand the effect of pollutants. Present study uses Acetylcholine esterase enzyme as pollution monitoring indicator

Entropy of a correlated system of nucleons

Realistic nucleon-nucleon interactions induce correlations to the nuclear many-body system, which lead to a fragmentation of the single-particle strength over a wide range of energies and momenta. We address the question of how this fragmentation affects the thermodynamical properties of nuclear matter. In particular, we show that the entropy can be computed with the help of a spectral function, which can be evaluated in terms of the self-energy obtained in the self-consistent Green's function approach. Results for the density and temperature dependences of the entropy per particle for symmetric nuclear matter are presented and compared to the results of lowest order finite-temperature Brueckner-Hartree-Fock calculations. The effects of correlations on the calculated entropy are small, if the appropriate quasiparticle approximation is used. The results demonstrate the thermodynamical consistency of the self-consistent T-matrix approximation for the evaluation of the Green's functions.

Penaeus monodon larvae can be protected from Vibrio harveyi infection by pre-emptive treatment of a rearing system with antagonistic or non-antagonistic bacterial probiotics

This study shows that the disease resistance and survival rate of Penaeus monodon in a larval rearing systems can be enhanced by supplementing with antagonistic or non-antagonistic probiotics. The antagonistic mode of action of Pseudomonas MCCB 102 and MCCB 103 against vibrios was demonstrated in larval mesocosm with cultures having su⁄cient concentration of antagonistic compounds in their culture supernatant. Investigations on the antagonistic properties of Bacillus MCCB 101, Pseudomonas MCCB 102 and MCCB 103 and Arthrobacter MCCB 104 against Vibrio harveyi MCCB111under in vitro conditions revealed that Pseudomonas MCCB 102 and MCCB 103 were inhibitory to the pathogen.These inhibitory propertieswere further con¢rmed in the larval rearing systems of P. monodon. All these four probionts signi¢cantly improved larval survival in long-term treatments as well as when challengedwith a pathogenic strain ofV. harveyiMCCB111. We could demonstrate that Pseudomonas MCCB 102 andMCCB103 accorded disease resistance and a higher survival rate in P. monodon larval rearing systems throughactive antagonism of vibrios,whereas Bacillus MCCB 101 and Arthrobacter MCCB 104 functioned as probiotics through immunostimulatory and digestive enzyme-supporting modes of action.

Significance Of Classification Techniques In Prediction Of Learning Disabilities

The aim of this study is to show the importance of two classification techniques, viz. decision tree and clustering, in prediction of learning disabilities (LD) of school-age children. LDs affect about 10 percent of all children enrolled in schools. The problems of children with specific learning disabilities have been a cause of concern to parents and teachers for some time. Decision trees and clustering are powerful and popular tools used for classification and prediction in Data mining. Different rules extracted from the decision tree are used for prediction of learning disabilities. Clustering is the assignment of a set of observations into subsets, called clusters, which are useful in finding the different signs and symptoms (attributes) present in the LD affected child. In this paper, J48 algorithm is used for constructing the decision tree and K-means algorithm is used for creating the clusters. By applying these classification techniques, LD in any child can be identified

Prediction of Learning Disabilities in School Age Children using SVM and Decision Tree

This paper highlights the prediction of Learning Disabilities (LD) in school-age children using two classification methods, Support Vector Machine (SVM) and Decision Tree (DT), with an emphasis on applications of data mining. About 10% of children enrolled in school have a learning disability. Learning disability prediction in school age children is a very complicated task because it tends to be identified in elementary school where there is no one sign to be identified. By using any of the two classification methods, SVM and DT, we can easily and accurately predict LD in any child. Also, we can determine the merits and demerits of these two classifiers and the best one can be selected for the use in the relevant field. In this study, Sequential Minimal Optimization (SMO) algorithm is used in performing SVM and J48 algorithm is used in constructing decision trees.

Attribute reduction and missing value imputing with ANN: prediction of learning disabilities

Learning disability (LD) is a neurological condition that affects a child’s brain and impairs his ability to carry out one or many specific tasks. LD affects about 10% of children enrolled in schools. There is no cure for learning disabilities and they are lifelong. The problems of children with specific learning disabilities have been a cause of concern to parents and teachers for some time. Just as there are many different types of LDs, there are a variety of tests that may be done to pinpoint the problem The information gained from an evaluation is crucial for finding out how the parents and the school authorities can provide the best possible learning environment for child. This paper proposes a new approach in artificial neural network (ANN) for identifying LD in children at early stages so as to solve the problems faced by them and to get the benefits to the students, their parents and school authorities. In this study, we propose a closest fit algorithm data preprocessing with ANN classification to handle missing attribute values. This algorithm imputes the missing values in the preprocessing stage. Ignoring of missing attribute values is a common trend in all classifying algorithms. But, in this paper, we use an algorithm in a systematic approach for classification, which gives a satisfactory result in the prediction of LD. It acts as a tool for predicting the LD accurately, and good information of the child is made available to the concerned

Using Neural Network Classifier Support Vector Machine Regression for the prediction of Melting Point of Drug – like compounds

In our study we use a kernel based classification technique, Support Vector Machine Regression for predicting the Melting Point of Drug – like compounds in terms of Topological Descriptors, Topological Charge Indices, Connectivity Indices and 2D Auto Correlations. The Machine Learning model was designed, trained and tested using a dataset of 100 compounds and it was found that an SVMReg model with RBF Kernel could predict the Melting Point with a mean absolute error 15.5854 and Root Mean Squared Error 19.7576

Toxic Metal Distribution in the Core Sediment of Cochin Estuarine System (CES)

This article present the result from a study of two sediment cores collected from the environmentally distinct zones of CES. Accumulation status of five toxic metals: Cadmium (Cd), Chromium (Cr), Cobalt (Co), Copper (Cu) and Lead (Pb) were analyzed. Besides texture and CHNS were determined to understand the composition of the sediment. Enrichment Factor (EF) and Anthropogenic Factor (AF) were used to differentiate the typical metal sources. Metal enrichment in the cores revealed heavy load at the northern (NS1 ) region compared with the southern zone (SS1). Elevation of metal content in core NS1 showed the industrial input. Statistical analyses were employed to understand the origin of metals in the sediment samples. Principal Component Analysis (PCA) distinguishes the two zones with different metal accumulation capacity: highest at NS1 and lowest at SS1. Correlation analysis revealed positive significant relation only in core NS1, adhering to the exposition of the intensified industrial pollution

Biennial Metal Discrepancy In The Surface Sediment Of Cochin Estuarine System

This study gave the first report on the biennial metal divergence in the sediments of Cochin Estuarine system (CES). Surface sediments from 6 prominent regions of CES were sampled in 2009 and 2011 for the geochemical and environmental assessment of trace metals (Cd, Co, Cr, Cu, Pb Fe, Mg, Mn, Ni and Zn).Besides texture, total organic carbon (TOC) and CHNS were also done. The contamination and risk assessment were performed by determining geochemical indices. Comparison with sediment quality guidelines were done to assess the probability for ecotoxicological threat to the estuary. Results showed that the measured heavy metals had varied spatial distribution patterns, indicating that they had complex origins and controlling factors