Distinct promoter elements mediate the co-operative effect of Brn-3a and p53 on the p21 promoter and their antagonism on the Bax promoter

Although the promoters of both the Bax and p21 genes are activated by p53, they differ in the effect on this activation of the POU family transcription factor Brn-3a. Thus, Brn-3a inhibits activation of the Bax promoter by p53 but enhances the ability of p53 to activate the p21 promoter. We demonstrate that repression of p53-mediated activation of the Bax promoter involves a complex upstream sequence in which two Brn-3a response elements flank the p53 response element. In contrast, a minimal p21 promoter is activated by Brn-3a and such activation cannot be abolished without abolishing basal promoter activity. Moreover, synergistic activation by Brn-3a and p53 continues to be observed when the p53-binding sites in the p21 promoter are substituted by the Bax p53 site or by the region of the Bax promoter essential for Brn-3a-mediated repression, indicating that the p21 core promoter plays a central role in this response. The significance of these effects is discussed in terms of the different responses of the Bax and p21 promoters and the overlapping but distinct roles of Brn-3a and p53 in neuronal growth arrest and apoptosis

Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease.

Metabolic and cardiovascular diseases are highly prevalent and chronic conditions that are closely linked by complex molecular and pathological changes. Such adverse effects often arise from changes in the expression of genes that control essential cellular functions, but the factors that drive such effects are not fully understood. Since tissue-specific transcription factors control the expression of multiple genes, which affect cell fate under different conditions, then identifying such regulators can provide valuable insight into the molecular basis of such diseases. This review explores emerging evidence that supports novel and important roles for the POU4F2/Brn-3b transcription factor (TF) in controlling cellular genes that regulate cardiometabolic function. Brn-3b is expressed in insulin-responsive metabolic tissues (e.g. skeletal muscle and adipose tissue) and is important for normal function because constitutive Brn-3b-knockout (KO) mice develop profound metabolic dysfunction (hyperglycaemia; insulin resistance). Brn-3b is highly expressed in the developing hearts, with lower levels in adult hearts. However, Brn-3b is re-expressed in adult cardiomyocytes following haemodynamic stress or injury and is necessary for adaptive cardiac responses, particularly in male hearts, because male Brn-3b KO mice develop adverse remodelling and reduced cardiac function. As a TF, Brn-3b regulates the expression of multiple target genes, including GLUT4, GSK3β, sonic hedgehog (SHH), cyclin D1 and CDK4, which have known functions in controlling metabolic processes but also participate in cardiac responses to stress or injury. Therefore, loss of Brn-3b and the resultant alterations in the expression of such genes could potentially provide the link between metabolic dysfunctions with adverse cardiovascular responses, which is seen in Brn-3b KO mutants. Since the loss of Brn-3b is associated with obesity, type II diabetes (T2DM) and altered cardiac responses to stress, this regulator may provide a new and important link for understanding how pathological changes arise in such endemic diseases

A study of the bonding by air-setting refractory mortar at elevated temperatures

The importance of a suitable material for the laying of bricks in furnace and kiln construction has been recognized by the refractory industry for a long time. It is necessary that a strong bond should develop between the bricks to impart strength to the entire construction work. A weak joint would form the weakest link and dangerously weaken the whole structure. Such being the importance of the bond, the refractory industry has made quite an effort to develop jointing materials which would produce strong bonds. During the last two decades, due to intensive research and development work, many good bonding materials have been made available. As a result of such development work it becomes necessary to evaluate the strength of such bonds, and hence test methods were developed to measure the bonding strength of mortars. Adequate specifications and standards of testing methods have been provided both by Federal specifications and by The American Society for Testing Materials. Among several tests recommended by them, the test to determine the strength of the joints is one of the most important. A method has been specified by them by which the strength of joints can be measured at room temperature after air setting or after heat treatment of the joint at several temperatures. According to these methods, a joint after being made, dried at room temperature and at 105⁰ C, is then subjected to the modulus of rupture test. The data indicate the strength of joint which has been attained after air setting. Similarly the strength is determined on the joints which are fired at several temperatures. After firing, the joints are cooled to room temperature, and modulus of rupture is determined as before. Sample results which are recorded as strength of the joints at the specified temperatures are shown in Figure 1 on page 3. This method of measuring bonding strength is now universally practiced by both users and manufacturers of refractory mortars. By careful study of the bonding strength method, it will be realized that the method for measuring strength at various temperatures is an erroneous one. According to this method, information is collected regarding room temperature strength of joints which had been previously subjected to a heat treatment. The strength at higher temperatures as shown in Figure 1 does not indicate the true strength of joints when maintained at these temperatures. Since furnace linings are expected to withstand stresses at operating temperatures, it becomes necessary to have exact knowledge of the true strength of the joints at working temperatures of the furnace and not at room temperatures. The above described test procedure does not provide such information. During the literature review it has been noticed that some attempt has been made to determine strength of joints at a few isolated temperatures. This work, though it adds to present information, does not contribute much to the knowledge or strength of joints through the entire range of temperatures. In view of this, the present investigation was undertaken. This investigation is a study of the behavior of refractory mortars as regards to their bonding strengths at elevated temperatures. During this investigation an attempt has been made to study the strength of joints at elevated temperatures and the effect of various variables of the mortar batch on such strengths. The mortar batches are compounded by varying some of the variables in the batch. These batches are then used to prepare mortar joints. After drying and firing these joints to temperatures ranging from 100⁰ to 1400⁰C, they are then broken at these elevated temperatures to determine the modulus of rupture. Several other tests are also performed to supplement the data. An attempt has been made to determine the factors which caused the change in strength at these temperatures. This was done by petrographic and x-ray methods of investigation. Finally an effort has been made to study the effect of various constituents of the mortar on the strength of the joints at elevated temperatures. The importance of this problem lies in the fact that by this study one can easily evaluate the temperatures to which the refractory mortars can be used. Also one can develop a mortar composition which will give added strength at high temperatures by varying the proportions of various constituents of the mortar batch --The problem, pages 1-4

Input and achievement in an acquisition poor environment: varying levels of l2 proficiency among pre-puberty Mauritian learners of English

The aim of this study is to explore the factors leading to variation in English language proficiency levels in Mauritius, an island situated in the Indian Ocean and where English is the official language spoken along with a French-based Mauritian Creole and another second language, French. The impetus for the study were the increasingly lower scores on exit tests, namely the Certificate of Primary Education (the last examination at the end of the Primary cycle), the Cambridge School Certificate (SC) and the Higher School Certificate (HSC) examination since the introduction of universal secondary education in 1976. The study seeks to characterize and compare learners in rural and urban contexts in Mauritius in terms of the extent to which these settings provide opportunities for English language learning. The chief contention of this study is that there exist different kinds of conditions inside and outside the classroom which make available differential opportunities for English language learning. The central concern of this study is, therefore, to find out to what extent and in what ways the nature of classroom and extra-classroom interaction such as home language use other than English differs in rural and urban classes, and the nature of the conditions for language learning that become available as a result of these differences in classroom and extra-classroom interaction. Taking these exposure factors into account, the study then considers what the variation in achievement actually involves in terms of morpho-syntactic competence. The language sub-systems investigated are pluralization, adverb placement, tense formation, passivization, relativization and WH movement. The informants are French-based Creole speakers at three levels of education from six different English-medium schools in Mauritius. The method of investigation used for this study was observation and analysis (both quantitative and qualitative) of the interaction inside and outside English classes in both rural and urban settings, hi order to develop a framework for observation and analysis of classroom and extra-classroom interaction in terms of the language learning conditions, research literature on first and second language acquisition was examined - this led to a description of the conditions considered necessary for language learning to take place. The investigation into the problem began with the observations in different types of schools in Mauritius, three in a rural setting and three m an urban setting. The home factors, including further exposure to English and the learners' French literacy were also explored. This study led to the hypothesis that the conditions prevailing in the urban classes are more conducive to language learning than the conditions available in the rural classes. The classes in these schools were then compared in terms of the language learning conditions available in each setting. This comparison indicated that there are marked differences between the rural and urban contexts in terms of the nature of the opportunities for exposure to language input, the extent of the opportunities available for learners to participate in interaction in English and the nature of the learning environment available inside and outside the school, at home and in the community. There exist opportunities for acquisition beyond the curriculum for urban learners, while for their rural counterparts, there is not much beyond the learning-based curriculum. These observations led to the hypothesis that the conditions for language learning available in the urban schools are more conducive to language learning than those available in the rural schools. The findings of the study indicate that my morpho- syntactic achievement measurement confirms this hypothesis

RELIABILITY TESTING & BAYESIAN MODELING OF HIGH POWER LEDS FOR USE IN A MEDICAL DIAGNOSTIC APPLICATION

While use of LEDs in fiber optics and lighting applications is common, their use in medical diagnostic applications is rare. Since the precise value of light intensity is used to interpret patient results, understanding failure modes is very important. The contributions of this thesis is that it represents the first measurements of reliability of AlGaInP LEDs for the medical environment of short pulse bursts and hence the uncovering of unique failure mechanisms. Through accelerated life tests (ALT), the reliability degradation model has been developed and other LED failure modes have been compared through a failure modes and effects criticality analysis (FMECA). Appropriate ALTs and accelerated degradation tests (ADT) were designed and carried out for commercially available AlGaInP LEDs. The bias conditions were current pulse magnitude and duration, current density and temperature. The data was fitted to both an Inverse Power Law model with current density J as the accelerating agent and also to an Arrhenius model with T as the accelerating agent. The optical degradation during ALT/ADT was found to be logarithmic with time at each test temperature. Further, the LED bandgap temporarily shifts towards the longer wavelength at high current and high junction temperature. Empirical coefficients for Varshini's equation were determined, and are now available for future reliability tests of LEDs for medical applications. In order to incorporate prior knowledge, the Bayesian analysis was carried out for LEDs. This consisted of identifying pertinent prior data and combining the experimental ALT results into a Weibull probability model for time to failure determination. The Weibull based Bayesian likelihood function was derived. For the 1st Bayesian updating, a uniform distribution function was used as the Prior for Weibull á-â parameters. Prior published data was used as evidence to get the 1st posterior joint á-â distribution. For the 2nd Bayesian updating, ALT data was used as evidence to obtain the 2nd posterior joint á-â distribution. The predictive posterior failure distribution was estimated by averaging over the range of á-â values. This research provides a unique contribution in reliability degradation model development based on physics of failure by modeling the LED output characterization (logarithmic degradation, TTF â<1), temperature dependence and a degree of Relevance parameter `R' in the Bayesian analysis