The role of NOTCH2 gene in human malignant glial brain tumours

Background: Glioblastoma multiforme (GBM), astrocytoma (A) and oligodendroglioma (OG) are the neoplasms of the glial lineage in the Central Nervous System (CNS). Among them, GBM occurs at the highest frequency and shows the shortest patient median survival time of some 10 months as compared for instance to the survival time of OG of about 10 years. Genetically, OG differs from GBM by the frequent combination of loss of heterozygosity (LOH) on chromosomes 1p and 19q, which is associated with more favourable prognosis in OG patients. However, the clinical significance of LOH on 1p in other glioma subtypes remained unknown. Methods and Results: We identified a subgroup of GBM with LOH on centromeric chromosome 1p together with longer survival. The minimally lost area(s) in both GBM and OG converged at the NOTCH2 locus on 1p11 and positively correlated with prognosis in GBM as well as in OG patients. Comparison between gene expression of NOTCH2 and the genetic status at the NOTCH2 locus on chromosome 1p11 supported the hypothesis of a loss of function alteration of NOTCH2 in tumours. However, many GBMs do not display deletions at the NOTCH2 locus on 1p11 and do express the NOTCH2 gene. Abundant expression of components of canonical NOTCH signaling in these tumors and a positive correlation between NOTCH2 transcripts with the target gene HES-1 (P=0.0001) indicated that functional NOTCH signaling in glioma is mainly driven by NOTCH2. In addition, we defined TNC, the gene for the cell migration factor tenascin-C as a novel target gene for NOTCH signaling. We further showed that activation of NOTCH signaling was indeed promoting TNC-dependent glioma cell motility. Thus, together with the ability to increase proliferation, canonical Notch signaling turned out to be critical for glioma progression. We also found that non-canonical Notch signaling was associated with the maintenance of tumorigenic potential of the GBM cells in soft agar culture. In addition, Notch2 had a prosurvival effect on GBM cells by upregulating anti-apoptotic proteins Bcl-2 and Mcl-1, independently of the canonical pathway. Finally, defective degradation pathway of Notch receptors in GBM cells led to slow receptor turnover, thereby providing additional contribution to the oncogenic function of Notch2. Conclusion: This study identified aberrant multi-facetted oncogenic behaviours of Notch proteins, in particular of Notch2, in GBM. This provided a molecular basis for the higher aggressiveness of Notch2-positive GBM compared to Notch2-negative GBM or OG, and suggested Notch2 as a sensible target for new therapeutic approaches against GBM

Effect of Variable Thermal Conductivity on Buoyant Convection in a Cavity with Internal Heat Generation

A numerical study has been made to analyze the effects of variable thermal conductivity on the natural convection of heat generating fluids contained in a square cavity with isothermal walls and the top and bottom perfectly insulated surfaces. The flow is assumed to be two-dimensional. Calculations are carried out by solving governing equations for different parameters. The flow pattern and the heat transfer characteristics inside the cavity are presented in the form of steady-state streamlines, isotherms and velocity profiles. The heat transfer rate is increased by an increase in the thermal conductivity parameter

Antibacterial Activity of Commercially Available Plant Extracts on Selected Campylobacter jejuni Strains

Campylobacter jejuni is recognized as a leading cause of foodborne illness worldwide with approximately 850,000 cases per year in the United Sates. A total of 18 species of Campylobacter have been identified worldwide to date. Foodborne transmission of C. jejuni is mainly through the consumption of unpasteurized milk, contaminated poultry meat and water. C. jejuni can survive in very diverse environments under stressful conditions in human and animals which is different from the specific conditions and media required in laboratory experiments. There has been increased research in recent years to identify naturally occurring antibacterial agents to control and eliminate C. jejuni on poultry. This study involves the evaluation of commercially available plant extracts of oregano, green tea and hawthorn to reduce /eliminate C. jejuni on poultry. Four isolates of C. jejuni, one human and three poultry isolates were used in this study. Research was done in broth culture to determine the effects of these extracts at different concentrations on the 4 isolates using cell counts at regular intervals of 0, 1, 2, 4 and 24 hours post-treatment. Results indicated that oregano and green tea were the most antibacterial and killed all the bacteria in broth culture in 24 hours at all concentrations tested. No significant differences were observed on the action of each of these plant extracts on the different isolates. Hawthorn was not successful in killing any of the strains of C. jejuni in 24 hours and no significant difference in cell counts post-treatment was observed compared to the control. The effects of these plant extracts then were tested as marinades on chicken breast fillets. The results showed that higher concentrations were required in the meat model study as compared to broth studies to completely kill all the bacteria. In the marinade studies, oregano was found to be the most effective, killing all 81176 and PRCC isolates in 2 hours and all the POCC and RECC C. jejuni isolates in 6 hours. The extracts of green tea and hawthorn tested were unsuccessful in killing the C. jejuni isolates within 24 hours at all tested concentrations. The results of this study indicate the potential of using oregano extracts as antimicrobial against C. jejuni on poultry

LOGIC-BASED FORMULA MANAGEMENT STRATEGIES IN AN ACTUARIAL CONSULTING SYSTEM

In many decision support systems, multiple decision methods and models must be combined for solving a complex problem. Expertise is required for selecting, adapting and coordinating appropriate models. This paper describes the design and implementation of a knowledge-based model management system called the Actuarial Consulting System (ACS). The ACS supports actuaries in making pricing decisions in the domain of life insurance. Actuarial knowledge is organized using a graph formalism called Formula Derivation Network (FDN), represented in Prolog as a hierarchy of predicates. On the user level, a Problem Analyzer converts a problem specification by the user into a search problem on the stored collection of FDNs. Using different search strategies, including human expert rules, the Surface Planner generates an efficient solution strategy (sequence of models). At the lowest level, a Plan Executor retrieves or requests model data and issues appropriate function calls to a subroutine library.Information Systems Working Papers Serie

Family Demographics Sway With a Role of Financial Advisor in Risk Tolerance and Investment Decision of Women Working in it Sector, Chennai

Purpose: The purpose of this research is  to analyse the influence of spouse and  family members in addition to the crucial role of financial advisor in risk tolerance and investment decision of women working in IT sector.  This study   is conducted to observe, whether the  women investors  working in IT sector are  reinforced by their family members and  with the effective financial advise given financial advisors in tolerating risk and investment decision.      Theoretical Framework: Savings are the funds set aside to face future contingencies or endowments planned by an individual with a precautionary motive. This habit of savings can be observed in all living creatures in the world and it is high in human beings. The reasons could be to maintain a  luxurious life style and an exponential level of expectations about investments.  Warren Buffet’s, “Save and Spend” principle followers are many in India when compared to the rest of the world. After migration to the urban world, women initiated supporting their family with additional income by starting her career.  The herd behavior is observed among the young couples living in nuclear families towards spending and savings. Also, women started saving and investing  separately and trying to maximize  the returns.   Methodology: Primary data for the study and analysis is collected through a structured questionnaire, prepared based on a review of the literature and tested through a pilot study. The pilot study was conducted by distributing 125 questionnaires to women executives from the IT companies in the sample area. Cronbach Alpha Test was used to determine the degree of consistency among the multiple measurements of each factor and found the overall score of 0.896 as reliable when compared to standard alpha above 0.7 is considered sufficient (George and Mallery, 2001; Pallant, 2005).On completion of the survey and collection of 604 datasheets, it is found that, 162 questionnaires in total found ineffectual due to errors of omission and dual entries, and 442 samples were found suitable for the study. Data analysis is carried out with the same. Three demographics of a family is considered for the study namely marital status, family type and working status of the spouse as close variable to family.  T – test is  conducted with the collected data and p value is observed to test the hypothesis.   Findings: The results show that the role of financial advisors in risk tolerance and investment decisions of women are essential for the reliable and safe investments.  The joint family system is not having a prominent influence in investment decision of working women as the existence of joint family system is in downtrend.  The stimulating effect of spouse is also lesser when compared to financial advisors as the couple hardly find time to discuss exhaustively about the suitable investment strategies.   Research, Practical and Social implications: Robust IT sectors’ 1/3rd of the employees are women with lucrative salaries.  Their huge salaries are channelled properly to an investment mode with an effective guidance of financial advisors.  The women investors are able to get a complete awareness by financial advisors about the current investment scenario and suggested with suitable investment option matches their investment objectives.  A well designed financial literacy is given to the women investors that could help them in mitigating their risks while investing and maximising their returns. Government also systematically monitoring the role of financial advisors to protect the interest of the investors as the investors are primarily depending on them for their investment decisions.   This helps to tap the funds required for industrious activities leading to the development of the economy.   Originality / Value: Financial advisors essentially guide their clients with the adequate financial literacy and awareness.  The financial advisors shall increase trustworthiness among their clients by continuously upgrading and upskilling themselves in the industry.   A cautious approach would help to improve the risk tolerance level of women investors and there by develop a  positive investment decisions in the near future