Telomerase Inhibitors and Activators: Pharmaceutical Importance

Telomeres are specialized functional complexes that protect the ends of eukaryotic chromosomes. The telomeric DNA sequences are tandem repeats of a short hexameric sequence unit. The inability to DNA polymerase to replicate the end of the chromosome during lagging strand synthesis results in the loss of telomeric repeats when cell divides. Telomere shortening provides a barrier to cancer progression and the majority of the cancer cells depend on the activation of telomerase to gain proliferative immortality. Thus, telomerase is a molecular target for diseases since its discovery. Telomerase inhibition enables more specific ground for cancer therapy because the telomerase is not detected in most normal tissues. Some of the synthetic and natural telomerase inhibitors were tried on various cancer cells and there was a decrease in the number of cancer cells. But on the other hand, telomere shortening correlates with cellular aging. Some evidence suggests that the progressive loss of telomeric repeats of chromosomes may function as a molecular clock that triggers senescence. Telomerase-related gene mutations also result in some diseases. Because of this, telomerase activators are important for antiaging and telomerase-dependent disease treatments. This chapter summarizes the pharmaceutical importance of telomeres, telomerase structure, telomerase activators, and inhibitors

A new two-scale model for large eddy simulation of wall-bounded flows

A new hybrid approach to model high Reynolds number wall-bounded turbulent flows is developed based on coupling the two-level simulation (TLS) approach in the inner region with conventional large eddy simulation (LES) away from the wall. This new approach is significantly different from previous near-wall approaches for LES. In this hybrid TLS-LES approach, a very fine small-scale (SS) mesh is embedded inside the coarse LES mesh in the near-wall region. The SS equations capture fine-scale temporal and spatial variations in all three cartesian directions for all three velocity components near the wall. The TLS-LES equations are derived based on defining a new scale separation operator. The TLS-LES equations in the transition region are obtained by blending the TLS large-scale and LES equations. A new incompressible parallel flow solver is developed that accurately and reliably predicts turbulent flows using TLS-LES. The solver uses a primitive variable formulation based on an artificial compressibility approach and a dual time stepping method. The advective terms are discretized using fourth-order energy conservative finite differences. The SS equations are also integrated in parallel, which reduces the overall cost of the TLS-LES approach. The TLS-LES approach is validated and investigated for canonical channel flows, channel flow with adverse pressure gradient and asymmetric plane diffuser flow. The results suggest that the TLS-LES approach yields very reasonable predictions of most of the crucial flow features in spite of using relatively coarse grids.Ph.D.Committee Chair: Menon, Suresh; Committee Member: Ruffin, Stephen; Committee Member: Sankar, Lakshmi; Committee Member: Stoesser, Thorsten; Committee Member: Yeung, Pui-Kue

Preliminary analysis of the effects of confirmation bias on software defect density

In cognitive psychology, confirmation bias is defined as the tendency of people to verify hypotheses rather than refuting them. During unit testing software developers should aim to fail their code. However, due to confirmation bias, most defects might be overlooked leading to an increase in software defect density. In this research, we empirically analyze the effect of confirmation bias of software developers on software defect density

Empirical analyses of the factors affecting confirmation bias and the effects of confirmation bias on software developer/tester performance

Background: During all levels of software testing, the goal should be to fail the code. However, software developers and testers are more likely to choose positive tests rather than negative ones due to the phenomenon called confirmation bias. Confirmation bias is defined as the tendency of people to verify their hypotheses rather than refuting them. In the literature, there are theories about the possible effects of confirmation bias on software development and testing. Due to the tendency towards positive tests, most of the software defects remain undetected, which in turn leads to an increase in software defect density. Aims: In this study, we analyze factors affecting confirmation bias in order to discover methods to circumvent confirmation bias. The factors, we investigate are experience in software development/testing and reasoning skills that can be gained through education. In addition, we analyze the effect of confirmation bias on software developer and tester performance. Method: In order to measure and quantify confirmation bias levels of software developers/testers, we prepared pen-and-paper and interactive tests based on two tasks from cognitive psychology literature. These tests were conducted on the 36 employees of a large scale telecommunication company in Europe as well as 28 graduate computer engineering students of Bogazici University, resulting in a total of 64 subjects. We evaluated the outcomes of these tests using the metrics we proposed in addition to some basic methods which we inherited from the cognitive psychology literature. Results: Results showed that regardless of experience in software development/testing, abilities such as logical reasoning and strategic hypotheses testing are differentiating factors in low confirmation bias levels. Moreover, the results of the analysis to investigate the relationship between code defect density and confirmation bias levels of software developers and testers showed that there is a direct correlation between confirmation bias and defect proneness of the code. Conclusions: Our findings show that having strong logical reasoning and hypothesis testing skills are differentiating factors in the software developer/tester performance in terms of defect rates. We recommend that companies should focus on improving logical reasoning and hypothesis testing skills of their employees by designing training programs. As future work, we plan to replicate this study in other software development companies. Moreover, we will use confirmation bias metrics in addition to product and process metrics in for software defect prediction. We believe that confirmation bias metrics would improve the prediction performance of learning based defect prediction models which we have been building over a decade

An identity-based key infrastructure suitable for messaging applications

Abstract—Identity-based encryption (IBE) systems are relatively recently proposed; yet they are highly popular for messaging applications since they offer new features such as certificateless infrastructure and anonymous communication. In this paper, we intended to propose an IBE infrastructure for messaging applications. The proposed infrastructure requires one registration authority and at least one public key generator and they secret share the master secret key. In addition, the PKG also shares the same master secret with each user in the system in a different way. Therefore, the PKG will never be able to learn the private keys of users under non-collusion assumption. We discuss different aspects of the proposed infrastructure such as security, key revocation, uniqueness of the identities that constitute the main drawbacks of other IBE schemes. We demonstrate that our infrastructure solves many of these drawbacks under certain assumptions

Influence of confirmation biases of developers on software quality: an empirical study

The thought processes of people have a significant impact on software quality, as software is designed, developed and tested by people. Cognitive biases, which are defined as patterned deviations of human thought from the laws of logic and mathematics, are a likely cause of software defects. However, there is little empirical evidence to date to substantiate this assertion. In this research, we focus on a specific cognitive bias, confirmation bias, which is defined as the tendency of people to seek evidence that verifies a hypothesis rather than seeking evidence to falsify a hypothesis. Due to this confirmation bias, developers tend to perform unit tests to make their program work rather than to break their code. Therefore, confirmation bias is believed to be one of the factors that lead to an increased software defect density. In this research, we present a metric scheme that explores the impact of developers’ confirmation bias on software defect density. In order to estimate the effectiveness of our metric scheme in the quantification of confirmation bias within the context of software development, we performed an empirical study that addressed the prediction of the defective parts of software. In our empirical study, we used confirmation bias metrics on five datasets obtained from two companies. Our results provide empirical evidence that human thought processes and cognitive aspects deserve further investigation to improve decision making in software development for effective process management and resource allocation

An alternative account of anti-effeminacy bias: Reputation concerns and lack of coalitional value explain honor-oriented men’s reluctance to befriend feminine men

Anti-effeminacy bias follows a specific pattern with men showing stronger anti-effeminacy bias against male targets than women. Previous explanations focused on men’s higher tendency to stigmatize feminine men as homosexual and motives to maintain a dominant group status. Here, we suggest that certain expressions of anti-effeminacy bias may rather be a manifestation of men’s reputation management motives for coalition formation, and be amplified among high (vs. low) masculine honor-oriented men. In three studies with samples from the UK and Turkey, we showed that men perceived feminine (vs. masculine) male targets as lower on coalitional value and were more reluctant to befriend them, yet this applied only to high (not low) honor-oriented men. Honor-oriented men’s friendship reluctance was mediated by concern with losing reputation by association to targets lacking coalitional value. These findings extend understanding of anti-effeminacy bias by drawing attention to men’s reputation concerns for coalitional reasons and individual differences